Band 19, Heft 1

In adult olfactory epithelium (OE), ATP plays a role in constant cell turnover and post-injury neuroregeneration. We previously demonstrated that constitutive and ATP-evoked ATP release are present in neonatal mouse OE and underlie continuous cell turn-over and post-injury neuroregeneration, and that activation of purinergic P2X 7 receptors is involved in the evoked release. We hypothesized that both releases are present in adult mouse OE. To study the putative contribution of olfactory sensory neurons to ATP release, we used olfactory sensory neuronal-like OP6 cells derived from the embryonic olfactory placode cells. Calcium imaging showed that OP6 cells and primary adult OE cell cultures express functional purinergic receptors. We monitored ATP release from OP6 cells and whole adult OE turbinates using HEK cells as biosensors and luciferin–luciferase assays. Constitutive ATP release occurs in OP6 cells and whole adult mouse OE turbinates, and P2X 7 receptors mediated evoked ATP release occurs only in turbinates. The mechanisms of ATP release described in the present study might underlie the constant cell turn-over and post-injury neuroregeneration present in adult OE and thus, further studies of these mechanisms are warranted as it will improve our knowledge of OE tissue homeostasis and post-injury regeneration.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

The growing prevalence of hyperuricemia necessitates the urgent development of more potent treatments. This study aimed to develop, optimize, and evaluate the safety and efficacy of porcine–human recombinant uricase (PHRU) both in vitro and in vivo . The study employed gene editing of PHRU through site-directed mutagenesis, with recombinant proteins expressed in vitro utilizing Escherichia coli . The polyethylene glycol (PEG) approach was employed to augment uricase stability and diminish immunogenicity. The pharmacokinetics and pharmacodynamics of PHRU were tested in vitro and in Sprague Dawley rats. Successful expression of the fusion protein in E. coli and the development of the PEGylated drug were achieved. In vitro experiments confirmed the efficacy of PEG-PHRU in degrading uric acid, with PEGylation not markedly affecting the biological activity of PHRU. Animal studies revealed that PEG-PHRU significantly lowered plasma uric acid levels and mitigated hyperuricemia-induced renal damage in rats. Both drug metabolism and pharmacokinetics exhibited favorable characteristics without observable adverse effects in experimental animals. This novel fusion protein shows the potential for ameliorating hyperuricemia and related renal complications, highlighting it as a promising drug candidate with substantial market applications.

The purpose of this study was to explore the related research progress of ocular complications (OCs) caused by type 2 diabetes mellitus (T2DM), tear and tarsal function, and the application of deep learning (DL) in the diagnosis of diabetes and OCs caused by it, to provide reference for the prevention and control of OCs in T2DM patients. This study reviewed the pathogenesis and treatment of diabetes retinopathy, keratopathy, dry eye disease, glaucoma, and cataract, analyzed the relationship between OCs and tear function and tarsal function, and discussed the application value of DL in the diagnosis of diabetes and OCs. Diabetes retinopathy is related to hyperglycemia, angiogenic factors, oxidative stress, hypertension, hyperlipidemia, and other factors. The increase in water content in the corneal stroma leads to corneal relaxation, loss of transparency, and elasticity, and can lead to the occurrence of corneal lesions. Dry eye syndrome is related to abnormal stability of the tear film and imbalance in neural and immune regulation. Elevated intraocular pressure, inflammatory reactions, atrophy of the optic nerve head, and damage to optic nerve fibers are the causes of glaucoma. Cataract is a common eye disease in the elderly, which is a visual disorder caused by lens opacity. Oxidative stress is an important factor in the occurrence of cataracts. In clinical practice, blood sugar control, laser therapy, and drug therapy are used to control the above eye complications. The function of tear and tarsal plate will be affected by eye diseases. Retinopathy and dry eye disease caused by diabetes will cause dysfunction of tear and tarsal plate, which will affect the eye function of patients. Furthermore, DL can automatically diagnose and classify eye diseases, automatically analyze fundus images, and accurately diagnose diabetes retinopathy, macular degeneration, and other diseases by analyzing and processing eye images and data. The treatment of T2DM is difficult and prone to OCs, which seriously threatens the normal life of patients. The occurrence of OCs is closely related to abnormal tear and tarsal function. Based on DL, clinical diagnosis and treatment of diabetes and its OCs can be carried out, which has positive application value.

Remifentanil-induced hyperalgesia (RIH) is a common clinical phenomenon that limits the use of opioids in pain management. Esketamine, a non-competitive N -methyl- d -aspartate (NMDA) receptor antagonist, has been shown to prevent and treat RIH. However, the underlying effect mechanism of esketamine on RIH remains unclear. This study aimed to investigate the role and mechanism of esketamine in preventing and treating RIH based on the NMDA receptor–CaMKIIα pathway. In this study, an experimental animal model was used to determine the therapeutic effect of esketamine on pain elimination. Moreover, the mRNA transcription and protein expression levels of CaMKII and GluN2B were investigated to offer evidence of the protective capability of esketamine in ameliorating RIH. The results demonstrated that esketamine attenuated RIH by inhibiting CaMKII phosphorylation and downstream signaling pathways mediated by the NMDA receptor. Furthermore, ketamine reversed the upregulation of spinal CaMKII induced by remifentanil. These findings suggest that the NMDA receptor–CaMKII pathway plays a critical role in the development of RIH, and ketamine’s effect on this pathway may provide a new therapeutic approach for the prevention and treatment of RIH. Graphical abstract

Human brucellosis is an infectious disease caused by Brucella and is often misdiagnosed for atypical manifestations including fever of unknown origin, headache, weakness, among else. Nocardiosis is a zoonotic disease caused by the genus Nocardia, which usually spreads through the respiratory tract, skin, and digestive tract. Limited research has documented cases of co-infection involving both Brucella and Nocardia pathogens in patients. A 55-year-old male was admitted to our hospital with intermittent high-grade fever. Following sputum and blood cultures, as well as other laboratory examinations, the patient was diagnosed with concurrent brucellosis and nocardiosis. According to recommendations of previous studies and reports, the patient was successively treated with levofloxacin, doxycycline, piperacillin sodium and sulbactam sodium, trimethoprim-sulfamethoxazole, rifampicin, and tigecycline, after which the patient recovered and was discharged. Brucella and Nocardia are both opportunistic pathogens and simultaneous infection of Brucella and Nocardia is relatively rare. If patients continue to experience persistent fever despite receiving empirical antibiotic therapy, it becomes necessary to conduct examinations to identify potential atypical pathogens, including Brucella and Nocardia. Sputum staining, sputum culture, and blood culture are critical auxiliary examinations during clinical practice. The treatment plan should be selected based on guidelines and the individual patient’s condition. Regular reevaluation should be conducted, and antimicrobial agents should be adjusted accordingly.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People’s Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group ( P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission ( P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan–Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Henoch-Schönlein purpura (HSP) and pediatric-onset systemic lupus erythematosus (pSLE) are closely associated with vasculitis and vascular diseases. This study aimed to investigate the clinical diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE. We surveyed 82 HSP patients, 34 pSLE patients, and 10 healthy children. The expression levels of Ang-1, Ang-2, and Tie2 in the serum and urine were assessed using enzyme-linked immunosorbent assay. The diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE were evaluated using receiver operating characteristic curve analysis. The results revealed that the serum and urine expression levels of Ang-2 and Tie2 were significantly elevated in HSP and pSLE patients, whereas the Ang-1/Ang-2 values were reduced. Additionally, Ang-1 was highly expressed in the serum and urine of HSP patients and in the serum of pSLE patients. Ang-1, Ang-2, and Tie2 showed differential expression in various types of HSP and pSLE compared with their expression in healthy controls. In summary, Ang-1, Ang-2, and Tie2 can serve as biomarkers for HSP and pSLE. Moreover, Ang-1/Ang-2 values are reduced in HSP and pSLE patients. Ang-1, Ang-2, and Tie2 can be used as biomarkers for HSP and pSLE. Graphical abstract

This study aimed to clarify the role of pituitary tumor-transforming gene 1 (PTTG1) in proliferation, migration, invasion, and aerobic glycolysis of pancreatic cancer cells, and evaluate the potential of PTTG1 as a therapeutic target. PTTG1 expression in pancreatic cancers was analyzed using the GEPIA databank. In the Panc1 cell with the PTTG1 knockdown or Mia-PaCa2 cells with PTTG1 overexpression, the cell proliferation was evaluated using cell viability curves and colony formation, and wound heal assay and transwell assay were performed to evaluate the migration and invasion, respectively. Furthermore, a western blot was performed to evaluate the expressions of PTTG1, proliferating cell nuclear antigen, E-cadherin, N-cadherin, and c-myc. Meanwhile, the glucose uptake, extracellular acidification rates (ECAR), and oxygen consumption rates (OCR) were analyzed. Our results showed that PTTG1 expression is upregulated in pancreatic cancer, which promoted cell proliferation. Low PTTG1 contributed to higher disease-free survival and overall survival. In Panc1 cell, PTTG1 knockdown resulted in reduced cell viability and colony formation. The migration and invasion abilities of the cells were also reduced in Panc1 with PTTG1 knockdown. Correspondingly, PTTG1 knockdown decreased c-myc expression, glucose uptake, ECAR, and OCR in Panc1 cells. In Mia-PaCa2 cells, PTTG1 overexpression promoted cell proliferation, aerobic glycolysis, and translocation of β-catenin to the nucleus by regulating c-myc. In conclusion, PTTG1 induces proliferation, migration, and invasion, and promotes aerobic glycolysis in pancreatic cancer cells via regulating c-myc, demonstrating the potential of PTTG1 as a therapeutic target.

Interstitial pneumonia with autoimmune features (IPAF) is a type of interstitial lung disease (ILD) with immune features that do not meet the diagnostic criteria for specific connective tissue diseases (CTDs). This retrospective case–control study investigated the role of serum B-cell-activating factor of the tumor necrosis factor family (BAFF) and interleukin (IL)-17 as biomarkers for IPAF. The differences in serum BAFF, IL-17, and IL-10 were compared among patients with idiopathic pulmonary fibrosis (IPF), IPAF, ILD associated with CTD (CTD-ILD), and healthy controls. The patients were treatment naïve. The correlations of BAFF with IL-10, IL-17, and pulmonary function were analyzed. The classifiable value of BAFF for IPAF was examined. The results showed that the serum levels of BAFF and IL-17 in the IPAF and CTD-ILD groups were higher than in the IPF group. High BAFF levels and high predicted diffusion capacity of the lungs for carbon monoxide (DLCO) were independent predictive factors for IPAF vs IPF. In the IPAF and CTD-ILD groups, serum BAFF levels were negatively correlated with predicted values of forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) and positively correlated with serum IL-17 and IL-10 levels. The cutoff value of combined BAFF and IL-17 was 0.704, and the sensitivity and specificity for classifying IPAF were 78.9 and 95.7%, respectively. In conclusion, combining serum BAFF and IL-17 as a biomarker may have classifiable value in differentiating IPAF from other forms of ILD.

Emerging evidence has figured that serum conversion rate of mumps is a crucial link of mumps disease. Nevertheless, a rising number of mumps outbreaks caused our attention and studies examining the serum conversion cases were conducted in small samples previously; this meta-analysis was conducted to assess the immunogenicity and safety of a mumps containing vaccine (MuCV) before 2019. We identified a total of 17 studies from the year of 2002–2017. In the case–control studies, the vaccine effectiveness (VE) of MuCV in preventing laboratory-confirmed mumps was 68% (odds risk: 0.32; 95% confidence interval [CI], 0.14−0.70) while in the cohort studies and randomised control trials, 58% (relative risk [RR]: 0.42; 95% CI, 0.26−0.69). Similar intervals of effectiveness rates were found during non-outbreak periods compared with outbreak periods (VE: 66%; RR: 0.34; 95% CI, 0.18−0.68 versus VE: 49%; RR: 0.51; 95% CI, 0.21−1.27). In addition, the MuCV group with two and three doses did not show enhanced laboratory-confirmed mumps than one dose (VE: 58%; RR: 0.42; 95% CI, 0.20−0.88 versus VE: 65%, RR: 0.35; 95% CI, 0.20−0.61) for the reason of the overlap of 95% CI. MuCV had comparable effectiveness comparing non-outbreak and outbreak period, one dose, and two or three doses. MuCV displayed acceptable adverse event profiles.

Sex hormone-binding globulin (SHBG) is a serum glycoprotein exhibiting the unique feature of binding sex steroids with high affinity and specificity. Over the past few decades, there have been significant breakthroughs in our understanding of the function and regulation of SHBG. The biological role of SHBG has expanded from being considered a simple sex hormone transporter to being associated with several complex physiological and pathological changes in a variety of target tissues. Many factors can affect the plasma SHBG levels, with fluctuations in circulating levels affecting the development of various diseases, such as increasing the risk of developing breast cancer. This article reviews the clinical significance of changes in circulating SHBG levels in the development of breast cancer and the possible influence of these levels on endocrine drug resistance in hormone receptor-positive breast cancer. Higher levels of plasma SHBG significantly reduce the risk of estrogen receptor-positive breast cancer, especially in postmenopausal women. Moreover, the molecular mechanisms by which SHBG affects breast cancer risk are also summarized in detail. Finally, transcriptomics and proteomics data revealed that SHBG expression in breast tissue can effectively distinguish breast cancer from normal tissue. Additionally, the association between SHBG expression levels and various classical tumor-related pathways was investigated.

Trousseau syndrome (TS) is a malignant tumor-mediated complication of the hypercoagulable state with an unknown etiology. Laboratory testing results in patients with TS have indicated elevated D-dimer levels. The imaging analysis in patients who had undergone stroke has shown the presence of several cerebral infarction lesions in multiple regions. Since patients have had malignant tumors for a long time when they suffer from a secondary stroke, the optimum time for radical tumor treatment is usually missed. This study reports a case to improve the early screening and detection of TS and reduce the risk of recurrence of cerebral infarction.

Long-term mechanical ventilation after tracheotomy is a common treatment in intensive care unit patients. This study investigated the differences among the effects of different wetting states on the airway, lung, and serum inflammatory factors. New Zealand rabbits ( n = 36) were selected to construct tracheotomy models and then divided into four groups: Model, Mask, YTH, and Sham groups. Lung tissue dry/wet ratio was used to evaluate the humidification effect; cytokines, including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10, were used to evaluate the inflammatory response; hematoxylin and eosin staining was used to evaluate the histopathology. Post hoc analysis based on the Dunnett t -test was applied. A self-developed integrated wetting device could increase the utilization of wetting solution, enhance the effect of wetting to protect tissue integrity, and suppress airway inflammation, reducing the expression of pro-inflammatory factors while promoting the expression of anti-inflammatory factor IL-10 to inhibit the inflammatory response, compared to other methods. The integrated humidification device provided a new method for clinical nursing practice, improving clinical efficiency and reducing nursing workload. Further clinical trials are required to test its effectiveness and safety in the clinic. Graphical abstract

Because of stress shielding effects, traditional titanium (Ti) alloy scaffolds have a high elastic modulus, which might promote looseness and bone disintegration surrounding the implant, increasing the likelihood of a second surgery. In contrast, 3D-printed porous Ti alloy scaffolds can reduce the scaffold weight while enhancing biocompatibility. Further, these scaffolds’ porous nature allows bone tissue ingrowth as well as strong pore connectivity, which can improve nutrient absorption. Nevertheless, bare Ti alloy implants may fail because of inadequate bone integration; hence, adding a coating on the implant surface is an effective technique for improving implant stability. In this study, a composite coating comprising hydroxyapatite (HAP), chitosan (CS), tannic acid (TA) and copper ions (Cu 2+ ) (Cu 2+ /TA/HAP composite coating) was prepared on the surface of 3D printed porous Ti alloy scaffolds using electrophoretic deposition. Using the standard plate count method, Live/Dead bacteria staining assay, FITC Phalloidin and 4′,6-diamidino-2-phenylindole staining assay, and live/dead staining of cells we determined that the composite coating has better antibacterial properties and cytocompatibility as well as lower cytotoxicity. The Alkaline Phosphatase assay revealed that the coating results showed good osteogenesis potential. Overall, the composite coatings produced in this investigation give new potential for the application of Ti alloys in clinics.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H 2 O 2 ). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H 2 O 2 across biological membranes, in skin cells, and its effects in mitigating H 2 O 2 -induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H 2 O 2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H 2 O 2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H 2 O 2 -treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H 2 O 2 -induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

Stroke is a debilitating condition that often leads to disability and death. The increasing prevalence of stroke has drawn worldwide attention. Extensive evidence indicates a crucial role of genetic determinants in the occurrence and perpetuation of stroke. An Icelandic study identified a significant correlation of the phosphodiesterase 4D ( PDE4D ) single-nucleotide polymorphism (SNP) rs2910829 with stroke susceptibility. However, subsequent studies reported in Chinese populations were contradictory. We implemented a meta-analysis to inspect whether SNP rs2910829 is related to stroke susceptibility in Chinese populations and subsequently performed an in silico analysis to predict its potential functions. Finally, we analysed data from 24 studies comprising 7,484 Chinese stroke patients and 7,962 control individuals. Compared with the CC genotype, the TT genotype was associated with increased susceptibility to stroke (pooled odds ratio [OR] 1.28, 95% confidence interval [CI] 1.13–1.46, P < 0.001), whereas the CT genotype was not. Correspondingly, a significant association was detected under the recessive model (TT vs CT + CC: OR 1.30, 95% CI 1.15–1.47, P < 0.001). Similar results were obtained in large artery atherosclerosis (LAA) stroke but not in small vessel stroke. Bioinformatics analysis also revealed that SNP rs2910829 and its linked SNPs might be implicated in transcriptional regulation. This meta-analysis reveals significant relationships between the PDE4D SNP rs2910829 and susceptibility to stroke and subtype-LAA stroke in Chinese individuals, and further investigations are warranted to evaluate this effect.

The pheochromocytoma is an uncommon endocrine neoplasm that originates from chromaffin cells and causes significant cardiovascular effects through the intermittent or sustained release of catecholamines. In this report, we present a rare case of myocardial infarction (MI) induced by pheochromocytoma. A 53-year-old female presented to the emergency department with a history of intermittent palpitations, back pain, and sweating for over 10 years, which had worsened over the past 2 days. The patient’s cardiac enzymes and troponin levels were significantly elevated, and the electrocardiogram (ECG) showed ST-segment elevation, leading to an initial diagnosis of acute myocardial infarction. Echocardiography revealed apical ballooning, indicative of stress cardiomyopathy. Emergency coronary angiography revealed no significant stenosis, and the patient’s blood pressure was fluctuating. Computerized tomography (CT) scan of the adrenal gland revealed a bilateral adrenal mass, with the left adrenal mass being larger in size after contrast-enhanced CT scan. The patient’s left adrenal gland was successfully removed through laparoscopic adrenalectomy, and histopathology results confirmed the presence of adrenal pheochromocytoma. Follow-up for 3 months after discharge showed the patient had no symptoms and good prognosis. The abnormal findings on echocardiography and ECG resolved. Prompt diagnosis and management of pheochromocytoma are crucial for a favorable prognosis.

Ischemic stroke remains a major cause of disability and death. Kaempferol (Kae) is a neuroprotective flavonoid compound. Thus, this study aimed to explore the impact of Kae on cerebral infarction. We generated the middle cerebral artery occlusion (MCAO) mouse model to study the effects of Kae on infarction volume and neurological function. The oxygen and glucose deprivation (OGD)/reoxygenation (R) model of neural stem cells (NSCs) was established to study the effects of Kae on cell viability, migration, and apoptosis. Cell processes were assessed by cell counting kit-8, Transwell assay, flow cytometry, and TUNEL analysis. The molecular mechanism was assessed using the Western blot. The results indicated that Kae attenuated MCAO-induced cerebral infarction and neurological injury. Besides, Kae promoted cell viability and migration and inhibited apoptosis of OGD/R-treated NSCs. Moreover, OGD/R suppressed total O ‐GlcNAcylation level and O ‐GlcNAcylation of β-catenin, thereby suppressing the Wnt/β-catenin pathway, whereas Kae reversed the suppression. Inactivation of the Wnt/β-catenin pathway abrogated the biological functions of NSCs mediated by Kae. In conclusion, Kae suppressed cerebral infarction by facilitating NSC viability, migration, and inhibiting apoptosis. Mechanically, Kae promoted O ‐GlcNAcylation of β-catenin to activate the Wnt/β-catenin pathway. Kae may have a lessening effect on ischemic stroke. Graphical abstract

Acute myeloid leukemia (AML) is a blood system malignancy where sirtuin 5 (SIRT5) is abnormally expressed in AML cell lines. This study aimed to investigate the SIRT5 effects on the viability and apoptosis of AML cell lines. The mRNA and protein expression levels of succinylation regulatory enzyme in clinical samples and AML cell lines were detected by real-time quantitative polymerase chain reaction and western blotting while cell viability was measured using cell counting kit-8 assay. The apoptosis rate was assessed with flow cytometry. The interaction between SIRT5 and glycine decarboxylase (GLDC) was determined by co-immunoprecipitation and immunofluorescence staining techniques. Results indicated higher mRNA and protein expression levels of SIRT5 in clinical AML samples of AML than in normal subjects. Similarly, cell viability was inhibited, and apoptosis was promoted by downregulating SIRT5, in addition to inhibition of SIRT5-mediated GLDC succinylation. Moreover, rescue experiment results showed that GLDC reversed the effects of SIRT5 knockdown on cell viability and apoptosis. These results, in combination with SIRT5 and GLDC interactions, suggested that SIRT5 was involved in mediating AML development through GLDC succinylation. SIRT5 inhibits GLDC succinylation to promote viability and inhibit apoptosis of AML cells, suggesting that SIRT5 encourages the development of AML. Graphical abstract

Apigenin 7-glucoside (A7G) can suppress cell proliferation and trigger apoptosis in cervical cancer cells. Considering that hypoxia is associated with the malignant phenotypes in cervical cancer, this study aimed to uncover whether A7G exhibits suppressive effects on the hypoxia-induced malignant phenotype of cervical cancer cells (HeLa cells). Compared to normoxia, hypoxia can enhance the malignant phenotypes of HeLa cells, including cell proliferation, reduced sensitivity against chemotherapeutic agents (oxaliplatin and paclitaxel), cancer stemness, migration, and invasion. A7G intervention (20, 40, and 60 μM) could impair these malignant phenotypes of HeLa cells and upregulate the expression level of total and nuclear p16 proteins. Molecular docking analysis showed the interaction between anion exchanger 1 and A7G. In p16-silencing HeLa cells, the anticancer effects of A7G were absent. Therefore, hypoxia derives malignant phenotypes of HeLa cells, which could be impeded by A7G in a p16-dependent manner. Graphical abstract

Endometriosis is increasingly affecting women worldwide and research is focusing on identifying key targets in its pathogenesis. Changes in succinylation genes regulate the function of this protein and further influence the development of the disease. However, the role of succinylation genes in endometriosis is not clear from current studies. The expression of succinylation genes was determined in ectopic endometrium (EC) and ectopic patients with uterine fibroids (EN) by real-time quantitative PCR (qRT-PCR) and Western blot. Cell Counting Kit-8, transwell assays, and flow cytometry were used to assess endometrial stromal cells (ESCs) proliferation, apoptosis, migration, and invasion. KAT2A and ENO1 association was detected by qRT-PCR, immunofluorescence, and CoIP. We found that gene and protein levels of KAT2A were significantly increased in the EC group compared to EN group tissues. KAT2A silencing inhibited cell proliferation, migration, and invasion and promoted apoptosis. Western blot results showed that the expression of ENO1 and its succinylation was significantly upregulated in ECSc after KAT2A overexpression. CoIP results showed that KAT2A is positively bound to ENO1. Immunofluorescence also showed co-localized expression of KAT2A with ENO1. Furthermore, ENO1 overexpression reversed the effects of KAT2A silencing on the malignant behavior of ESCs. In summary, we found that succinylation of ENO1 mediated by KAT2A played a role in promoting the progression of endometriosis. Graphical abstract

Breast cancer, a malignancy originating from the epithelium or ductal epithelium of the breast, is not only highly prevalent in women but is also the leading cause of cancer-related deaths in women worldwide. Research has indicated that breast cancer incidence is increasing in younger women, prompting significant interest from scientists actively researching breast cancer treatment. Copper is highly accumulated in breast cancer cells, leading to the development of copper complexes that cause immunogenic cell death, apoptosis, oxidative stress, redox-mediated cell death, and autophagy by regulating the expression of key cell death proteins or assisting in the onset of cell death. However, they have not yet been applied to clinical therapy due to their solubility in physiological buffers and their different and unpredictable mechanisms of action. Herein, we review existing relevant studies, summarize the detailed mechanisms by which they exert anti-breast cancer effects, and propose a potential mechanism by which copper complexes may exert antitumor effects by causing copper death in breast cancer cells. Since copper death in breast cancer is closely related to prognosis and immune infiltration, further copper complex research may provide an opportunity to mitigate the high incidence and mortality rates associated with breast cancer.

The central nervous system is essential for maintaining homeostasis and controlling the body’s physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3–5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.

Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori ( H. pylori ) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group , Helicobacter , Bacteroides , Klebsiella , and Pseudomonas . In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori -positive (HP_Pos) and H. pylori -negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.

Radiotherapy for treating breast cancer is associated with cardiac damage. This study aimed to investigate the role of the interleukin (IL)-33/soluble receptor ST2 (sST2) axis in radiation-induced cardiac injury. Expressions of IL-33 and sST2 were detected in breast cancer patients following radiotherapy, radiation-induced cardiac damaged mice model, and cardiomyocytes using quantitative real-time PCR (qRT-PCR) and immunohistochemical assay. Cardiac injury was evaluated through an ultrasound imaging system and hematoxylin & eosin staining. The transcriptional factor was assessed using dual-luciferase reporter assay and chromatin immunoprecipitation. The results indicated that IL-33 and sST2 were highly expressed in breast cancer patients, which further elevated post-6 months but reduced after 12 months of radiotherapy. Radiation induces cardiac dysfunction and elevated IL-33 and sST2 levels in a time-dependent manner. However, silencing of IL-33 decreased sST2 expression to alleviate radiation-induced cardiac dysfunction. The IL-33 could be transcriptional activated by TCF7L2 by binding to IL33 promoter sites, which mutation alleviated cardiomyocyte injury caused by radiation. Additionally, radiation treatment resulted in higher levels of TCF7L2, IL-33, and sST2 in cardiomyocytes, and TCF7L2 knockdown reduced IL-33 and sST2 expression. In conclusion, TCF7L2 transcriptional-activated IL-33 mediated sST2 to regulate radiation-induced cardiac damage, providing novel insights into radiotherapy-induced cardiac damage. Graphical abstract

In this research, we delved into the predictive potential of three key markers – the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and Onodera’s prognostic nutritional index (OPNI), in assessing lymph node metastases in breast cancer patients who had internal mammary lymph node involvement following thoracoscopic surgery. Our study revealed notable pathological distinctions between the groups with and without metastases, while age, tumor size, and histological grade exhibited no significant differences. The analysis unveiled statistically significant variances in NLR, SII, and OPNI when comparing these two groups. Multivariate analysis pinpointed NLR (OR = 1.503), SII (OR = 1.987), and OPNI (OR = 0.612) as robust predictors of lymph node metastases. Remarkably, combining these markers (AUC: 0.897) substantially enhanced the precision of predicting lymph node metastases compared to individual measurements (NLR: 0.749, SII: 0.717, and OPNI: 0.787). In conclusion, this study underscores the pivotal role of NLR, SII, and OPNI in predicting lymph node metastasis among breast cancer patients with internal mammary lymph node involvement post-thoracoscopic surgery, affirming our utility as reliable independent predictors of this critical clinical outcome.

Genetic alterations in the TP63 (GenBank: NC_000003.12, ID: 8626) and CCR5 (receptor 5 chemokine co-receptor) (GenBank: NC_000003.12, ID: 1234) genes may increase the risk of developing breast cancer. The aim of this study was to investigate the probable involvement of polymorphisms rs17506395 in the TP63 (tumour protein 63) gene and the CCR5Δ32 mutation in the occurrence of breast cancer in Burkina Faso. This case–control study included 72 patients and 72 controls. Genotyping of SNP rs17506395 (TP63) was performed by polymerase chain reaction–restriction fragment length polymorphism, and genotyping of the CCR5Δ32 mutation was performed by allele-specific oligonucleotide polymerase chain reaction. For SNP rs17506395 (TP63), the genotypic frequencies of wild-type homozygotes (TT) and heterozygotes (TG) were, respectively, 27.72 and 72.22% in cases and 36.11 and 63.89% in controls. No mutated homozygotes (GG) were observed. For the CCR5Δ32 mutation, the genotypic frequencies of wild-type homozygotes (WT/WT) and heterozygotes (WT/Δ32) were 87.5 and 13.5%, respectively, in the cases and 89.29 and 10.71%, respectively, in the controls. No mutated homozygotes (Δ32/Δ32) were observed. None of the polymorphisms rs17506395 of the TP63 gene (OR = 1.47, 95% CI = 0.69–3.17, P = 0.284) and the CCR5Δ32 mutation (OR = 1.32, 95% CI = 0.46–3.77; P = 0.79) were associated with the occurrence of breast cancer in this study.

Sepsis is defined as a dysregulated host response to infection resulting in life-threatening organ dysfunction. Sepsis-associated encephalopathy (SAE) is the main manifestation of sepsis. Inflammation, peroxidation stress injury, and apoptosis are the main factors involved in the pathogenesis of SAE. A growing body of evidence has proved that P2X7 receptor (P2X7R), a cationic channel receptor that is widely distributed in the body, plays a major role in the occurrence and development of inflammatory injury. Therefore, this review mainly describes the activation of P2X7R in sepsis, which leads to the recruitment of inflammatory cells to the cerebral vasculature, the destruction of the blood–brain barrier, the activation of microglial cells in the brain, the apoptosis of brain cells, and other damage processes. This review also illustrates the potential therapeutic value of P2X7R inhibition in SAE.

Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn’s disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

Bortezomib (BTZ), a proteasome inhibitor, is a promising therapeutic option for multiple myeloma (MM) patients. However, drug resistance often occurs, leading to disease relapse and poor prognosis. In this study, we aimed to identify novel genes associated with drug resistance and investigate their roles in BTZ resistance. Through the screening of 26 genes frequently associated with chemosensitivity or drug resistance, we discovered that KDM4C, a histone demethylase, exhibited increased expression in BTZ-resistant MM cells compared to their sensitive counterparts. Overexpression of KDM4C enhanced the tolerance of a MM cell line to the drug, whereas the knockdown of KDM4C , using shRNA, increased the sensitivity of resistant cells to BTZ treatment. This suggests that KDM4C plays a pivotal role in conferring BTZ resistance. Our study offers fresh insights into BTZ resistance in MM and highlights KDM4C as a potential target for overcoming drug resistance.

Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of AD with skin and gut microbiota has been revealed by virtue of the continuous development of sequencing technology and genomics analysis. Also, the gut–brain–skin axis and its mutual crosstalk mechanisms have been gradually verified. Accordingly, the microbiota–skin–gut axis also plays an important role in allergic skin inflammation. Herein, we reviewed the relationship between the microbiota–skin–gut axis and AD, explored the underlying signaling molecules and potential pathways, and focused on the potential mechanisms of probiotics, antimicrobial peptides (AMPs), coagulase-negative staphylococci transplantation, fecal microbiota transplantation, AMPs, and addition of essential fatty acids in alleviating AD, with the aim to provide a new perspective for targeting microbiota in the treatment of allergic skin inflammation.

This study aimed to investigate the efficacy of thymosin α1 combined with XELOX in improving immune function and reducing serum tumor markers in patients with colorectal cancer (CRC) after radical surgery. A total of 180 patients who underwent radical surgery for CRC were divided into two groups: an observation group ( n = 94) receiving thymosin α1 in combination with XELOX and a control group ( n = 86) receiving XELOX alone. Immune function, inflammatory factor levels, serum tumor markers, and quality of life were assessed before and after treatment. Adverse reactions and recurrence rates were compared between the two groups in 1 and 3 years. Following therapy, there was a notable increase in the levels of CD3+, CD4+, and CD4+/CD8+ in all cohorts, particularly in the observation cohort, when compared to pre-therapy levels. Conversely, CD8+ levels decreased across all cohorts, especially in the observation cohort. Additionally, there was an increase in the levels of IL-2 and IFN-γ in the observation cohort, compared to both pre-therapy and control cohort levels, while IL-6 levels decreased. The presence of CEA, CA242, and CA724 reduced significantly across all cohorts following post-therapy, particularly in the observation cohort. Post-therapy, there was a significant increase in the scoring for role, cognitive, social, emotional, and somatic functions in all cohorts, with the most significant improvement observed in the observation cohort. There were no significant differences in the incidence of side effects across cohorts, while neutropenia events were significantly lower in the observation cohort (32.98%) compared to the control cohort (48.84%). The 12-month recurrence rate showed no statistical significance across cohorts, while the observation cohort had a significantly lower three-year recurrence rate (24.47%) compared to the control cohort (59.30%). Thymosin α1 combined with XELOX is effective in improving immune function, reducing serum tumor markers, and minimizing recurrence in CRC patients after radical surgery. This combination therapy may be a promising new direction for the treatment of CRC.

To investigate the vaginal microbiota signature of patients with gynecologic cancer and evaluate its diagnostic biomarker potential. We incorporated vaginal 16S rRNA-seq data from 529 women and utilized VSEARCH to analyze the raw data. α-Diversity was evaluated utilizing the Chao1, Shannon, and Simpson indices, and β-diversity was evaluated through principal component analysis using Bray-Curtis distances. Linear discriminant analysis effect size (LEfSe) was utilized to determine species differences between groups. A bacterial co-abundance network was constructed utilizing Spearman correlation analysis. A random forest model of gynecologic tumor risk based on genus was constructed and validated to test its diagnostic efficacy. In gynecologic cancer patients, vaginal α-diversity was significantly greater than in controls, and vaginal β-diversity was significantly separated from that of controls; there was no correlation between these characteristics and menopause status among the subject women. Women diagnosed with gynecological cancer exhibited a reduction in the abundance of vaginal Firmicutes and Lactobacillus , while an increase was observed in the proportions of Bacteroidetes , Proteobacteria , Prevotella , Streptococcus , and Anaerococcus . A random forest model constructed based on 56 genus achieved high accuracy (area under the curve = 84.96%) in gynecological cancer risk prediction. Furthermore, there were discrepancies observed in the community complexity of co-abundance networks between gynecologic cancer patients and the control group. Our study provides evidence that women with gynecologic cancer have a unique vaginal flora structure and microorganisms may be involved in the gynecologic carcinogenesis process. A gynecological cancer risk prediction model based on characteristic genera has good diagnostic value.

We recruited four aquaporin-4 seropositive optic neuritis patients (five eyes) who received glucocorticoid treatment and underwent optical coherence tomography examination. Baseline medians of the macular ganglion cell layer plus inner plexiform layer (mGCIPL) thickness and volume for the eye of interest were 79.67 µm (73.664 ± 18.497 µm) and 0.58 mm 3 (0.534 ± 0.134 mm 3 ), respectively. At 2 months, the medians of the mGCIPL thickness and volume were 60.00 µm (51.576 ± 12.611 µm) and 0.44 mm 3 (0.376 ± 0.091 mm 3 ), respectively. At 6 months, the medians of the mGCIPL thickness and volume were 59.55 µm (46.288 ± 11.876 µm) and 0.44 mm 3 (0.336 ± 0.084 mm 3 ), respectively. Sample size estimate was achieved using two methods based on the mGCIPL thickness and volume data, with five effect sizes considered. The estimate based on the mGCIPL volume showed that 206 patients were needed at the 6-month follow-up; the power was 80% and effect size was 20%. In conclusion, this study detected retinal damage in aquaporin-4 seropositive optic neuritis patients by optical coherence tomography, and estimated the sample size for two-sample parallel designed clinical trials using two methods.

Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague–Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.

Gold nanoparticles (AuNPs) have unique features that might lead to the development of a new class of diabetic medicines. AuNPs were biosynthesized utilizing sodium-alginate. UV-Vis-spectroscopy, Fourier transforms infrared, field emission scanning electron microscopy (FESEM), and energy dispersive X-ray were used to examine the particles. The potential of AuNPs for improving the diabetes condition was examined along with swimming in rats. FESEM image revealed the spherical morphology with an average particle size of 106.6 ± 20.8 nm. In the diabetic group, serum glucose, blood urea nitrogen (BUN), creatinine, cholesterol, and triglyceride (TG) levels were significantly higher than the control group. Low-density lipoprotein (LDL) was significantly higher and high-density lipoprotein (HDL) was significantly lower in the diabetic group compared to the control group. Malondialdehyde (MDA) levels were also significantly higher in the D group. However, in the groups treated with swimming and gold, these parameters were significantly improved. Specifically, serum-glucose, BUN, creatinine, cholesterol, and TG levels were significantly reduced, while LDL was significantly decreased in the diabetic + swimming + AuNPs group and HDL was significantly increased in the diabetic + AuNPs group. MDA levels were significantly decreased in the treated groups, and other antioxidants were significantly improved in the diabetic + swimming + AuNPs group. Catalase levels were also significantly improved in the D + gold group. It can be concluded that both AuNPs and swimming can decrease diabetic complications. Graphical Abstract

This study explores the effects of the Mediterranean diet, herbal remedies, and their phytochemicals on various gastrointestinal conditions and reviews the global use of medicinal plants for common digestive problems. The review highlights key plants and their mechanisms of action and summarizes the latest findings on how plant-based products influence the digestive system and how they work. We searched various sources of literature and databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus. Our focus was on gathering relevant papers published between 2013 and August 2023. Certain plants exhibit potential in preventing or treating digestive diseases and cancers. Notable examples include Curcuma longa, Zingiber officinale, Aloe vera, Calendula officinalis, Lavandula angustifolia, Thymus vulgaris, Rosmarinus officinalis, Ginkgo biloba, Cynodon dactylon , and Vaccinium myrtillus . The phytochemical analysis of the plants showed that compounds such as quercetin, anthocyanins, curcumin, phenolics, isoflavones glycosides, flavonoids, and saponins constitute the main active substances within these plants. These natural remedies have the potential to enhance the digestive system and alleviate pain and discomfort in patients. However, further research is imperative to comprehensively evaluate the benefits and safety of herbal medicines to use their active ingredients for the development of natural and effective drugs.

The aim of this study was to investigate the frequency distribution of the cytochrome P450 ( CYP450 ) enzymes, CYP2D6 and CYP2C19 , and the form of tamoxifen metab olisat ion in premenopausal patients with breast cancer in the Han and Uygur ethnic groups of Xinjiang to guide rational clinical drug use. A total of 125 Han patients and 121 Uygur patients with premenopausal hormone-receptor-positive breast cancer treated at the Xinjiang Uygur Autonomous Region Cancer Hospital between 1 June 2011 and 1 December 2013 were selected. The common mutation sites in CYP450 were analysed using TaqMan® minor groove binder technology. Genetic testing was performed to determine other metabolic types of tamoxifen, and the genotypes and metabolic types were compared using a Chi-squared test. Between the Han and Uygur groups, there were significant differences in the frequencies of the CYP2D6 (*10/*10) and CYP2C19 (*1/*1) genotypes, with P- values of 0.002 and 0.015, respectively. Genotypes of CYP2D6 (*1/*1), CYP2D6 (*1/*5), CYP2D6 (*5/*5), CYP2D6 (*5/*10) and CYP2C19 (*3/*3) were expressed in the two patient groups, and the difference was not statistically significant ( P > 0.05). In the Han patients, the proportions of extensive, intermediate and poor metabolisers of tamoxifen were 72, 24 and 4%, respectively, whereas those in the Uygur patients were 76.9, 17.4 and 5.7%, respectively, with no significant difference ( P > 0.05). In conclusion, There were partial differences in the CYP2D6 and CYP2C19 gene polymorphisms of CYP450 between the Han and Uygur patients with premenopausal breast cancer, but there was no significant difference between the CYP2D6 and CYP2C19 phenotypes. Further research is needed to determine the relationship between the enzyme genetic differences of CYP450 and the pharmacokinetics and efficacy of tamoxifen. Although there were some differences in genotypes, these did not result in differences in the predicted tamoxifen metabolisation phenotype between the Han and Uygur patients with breast cancer. Therefore, the doses should be adjusted according to the individual genotype data. Graphical abstract

Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1β, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.

This study aimed to investigate spontaneous hypothermia among emergency trauma patients and develop a predictive model. A cohort of 162 emergency trauma patients was categorized into hypothermic ( n = 61) and control ( n = 101) groups, with trauma severity assessed using the modified Glasgow Coma Scale (GCS). Univariate analysis revealed significant differences between the groups in trauma severity, posture, garment wetness, warming measures, pre-hospital fluid resuscitation, and modified GCS scores ( P < 0.05). The hypothermic group exhibited lower prothrombin time compared to the control group ( P < 0.05). A logistic regression model was constructed, expressed as Y = 25.76 − 1.030 X 1 + 0.725 X 2 + 0.922 X 3 − 0.750 X 4 − 0.57 X 6 , and its fit was evaluated using the Hosmer–Lemeshow test. The receiver operating characteristic curve demonstrated an area under the curve of 0.871, with 81.2% sensitivity and 79.5% specificity. The Youden index identified the optimal predictive cut-off at its highest (0.58). Validation results included 86.21% sensitivity, 82.93% specificity, and 84.29% accuracy. Risk factors for spontaneous hypothermia after emergency trauma encompassed trauma severity, posture during consultation, clothing dampness upon admission, warming measures during transfer, pre-hospital fluid resuscitation, and modified GCS scores. The risk prediction model demonstrated high accuracy, enabling effective assessment of spontaneous hypothermia risk in emergency trauma patients and facilitating preventive measures.

We investigated the changes in redox state and protein expression in selected parts of the rat brain induced by a 4 week administration of morphine (10 mg/kg/day). We found a significant reduction in lipid peroxidation that mostly persisted for 1 week after morphine withdrawal. Morphine treatment led to a significant increase in complex II in the cerebral cortex (Crt), which was accompanied by increased protein carbonylation, in contrast to the other brain regions studied. Glutathione levels were altered differently in the different brain regions after morphine treatment. Using label-free quantitative proteomic analysis, we found some specific changes in protein expression profiles in the Crt, hippocampus, striatum, and cerebellum on the day after morphine withdrawal and 1 week later. A common feature was the upregulation of anti-apoptotic proteins and dysregulation of the extracellular matrix. Our results indicate that the tested protocol of morphine administration has no significant toxic effect on the rat brain. On the contrary, it led to a decrease in lipid peroxidation and activation of anti-apoptotic proteins. Furthermore, our data suggest that long-term treatment with morphine acts specifically on different brain regions and that a 1 week drug withdrawal is not sufficient to normalize cellular redox state and protein levels.

Pathogens detected by metagenomic next-generation sequencing (mNGS) and the laboratory blood culture flask method were compared to understand the advantages and clinical significance of mNGS assays in the etiological diagnosis of peritoneal dialysis-associated peritonitis (PDAP). The study involved a total of 37 patients from the hospital’s peritoneal dialysis centre, six of whom were patients with non-peritoneal dialysis-associated peritonitis. Peritoneal dialysis samples were collected from the 37 patients, who were divided into two groups. One group’s samples were cultured using conventional blood culture flasks, and the other samples underwent pathogen testing using mNGS. The results showed that the positive rate of mNGS was 96.77%, while that of the blood culture flask method was 70.97% ( p < 0.05). A total of 29 pathogens were detected by mNGS, namely 24 bacteria, one fungus, and four viruses. A total of 10 pathogens were detected using the bacterial blood culture method, namely nine bacteria and one fungus. The final judgment of the PDAP’s causative pathogenic microorganism was made by combining the clinical condition, response to therapy, and the whole-genome sequencing findings. For mNGS, the sensitivity was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. For the blood culture flask method, the sensitivity was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 0%. In conclusion, mNGS had a shorter detection time for diagnosing peritoneal dialysis-related peritonitis pathogens, with a higher positive rate than traditional bacterial cultures, providing significant advantages in diagnosing rare pathogens.

Against the backdrop of rapid social economy and scientific and technological development, intelligent medical technology expanded based on the Internet plays a crucial role in the innovation and development of the modern medical industry. Intelligent medical technology has completely changed the fixed medical methods of the past, and it can solve the isolated defects between various unit systems, greatly improving the overall informatization level of hospitals. This article analyzed the clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome (NDS) in intelligent medicine. Dyspepsia can cause palpitations, vomiting, abdominal distension, dizziness, and other symptoms so that it can cause discomfort and pain in the middle or around the epigastric region. Therefore, it is necessary to make a correct diagnosis of neurodyspepsia in order to reduce the discomfort of patients. Intelligent medical technology is of great significance in improving patients’ symptoms. This study sets up a control group and an experimental group for the experiment. The control group used conventional medication technology, while the experimental group used intelligent medical technology to analyze the patient samples taken. By comparing the factors that affect patients with NDS, it was found that the physical function score of the experimental group was 6.3% lower than that of the control group. Intelligent medical technology has high diagnostic efficiency and can achieve rapid diagnosis of NDS, meeting the clinical diagnosis and prevention requirements of NDS. Graphical abstract

Endobronchial leiomyomas are rare benign neoplasms of the lungs that arise from the smooth muscle cells of the bronchi and bronchioles. While surgical resection is the mainstay of treatment for these tumors, bronchoscopic interventional therapies are also effective and can help preserve lung function in certain cases. A 40-year-old male patient presented with a persistent cough and sputum production for over 4 months. A chest computed tomography scan revealed nodular lesions in the lower lobe bronchus, later confirmed as an endobronchial leiomyoma. The patient refused surgical intervention and opted for minimally invasive bronchoscopic treatments, including electric snare resection, argon plasma coagulation, and balloon dilation, resulting in a successful outcome with no recurrence during follow-up. Clinicians should consider bronchoscopic interventions as a viable treatment option for endobronchial leiomyomas patients who are either ineligible for surgical resection or opt not to undergo surgery.

A comprehensive survey was carried out to investigate the genetic etiology of short stature in children by whole exon sequencing of a core family cohort to find and study mutations in multiple genes to assess their potential correlations to low height in children. The study included 56 pediatric patients from the Department of Pediatrics at the Zhangzhou Affiliated Hospital of Fujian Medical University. The participants met strict inclusion criteria, including age, Han Chinese ethnicity, low height standard deviation score, and the absence of known causes for short stature. Core pedigrees were identified using exome sequencing. After sequencing, variations were categorized and interpreted according to a variety of factors, including inheritance, location, type, and disease-causing gene databases. Variants were verified by Sanger sequencing. Most of the 97 gene mutations were missense. ACAN, PHEX, and COL2A1 were the most common gene mutations. Copy number variations were identified, particularly associated with the PHEX gene. Protein functional studies revealed that the mutations had a considerable influence on disease-promoting damage. The chromosomal locations with the highest enrichment of these genes were chr12, chr5, and chr2. In conclusion, the study revealed numerous genetic changes that may substantially impact physiological processes and disease. These findings establish the basis for further investigations into their diagnostic and therapeutic capabilities.

Cystic adenomyosis is a rare type of adenomyosis. The main clinical manifestation of uterine cystic adenomyoma is severe dysmenorrhoea, and the condition can be diagnosed by relevant clinical examination. The preferred treatment, with a good prognosis, is lesion resection. The clinical data of a patient with uterine cystic adenomyoma recorded at the Third Hospital of Hebei Medical University are reported herein. A 39-year-old female patient presented with tolerable menstrual pain and aggravated dysmenorrhoea, which she had experienced for 4 years, and menorrhagia, which she had had for approximately 1 year. Ultrasound and tumour marker tests suggested abnormalities, and magnetic resonance imaging confirmed a diagnosis of uterine cystic adenomyoma. A hysteroscopy and intrauterine lesion electrocision were performed, and the results of postoperative pathology tests suggested that the endometriosis cysts had returned to normal after the postoperative intervention. The analysis of the clinical manifestations and diagnosis and treatment of uterine cystic adenomyoma can improve the understanding of the disease and reduce the rates of misdiagnosis and missed diagnoses to ensure early detection with timely diagnosis and treatment.

Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

The aim of this study is to observe the changes in autophagy activities in lung tissues of mice with different degrees of pulmonary fibrosis (PF), and explore the association between PF and autophagy activity. The PF model was established by bleomycin (BLM, 25 and 35 mg/kg) atomization inhalation in C57BL/6 mice, samples were collected on the 7, 14, and 28 days after BLM administration. Hematoxylin–eosin staining was used to observe the pathological changes in lung tissues. Masson staining was utilized to assess areas of blue collagen fiber deposition in lung tissues. Quantitative real time polymerase chain reaction was used to detect the mRNA expressions of autophagy-related genes, including Atg5, Atg7, and Atg10 in lung tissues. Western blot was used to detect the protein expressions of autophagy-related genes, including p62 and LC3II/LC3I in lung tissues. Compared with control group, BLM dose-dependently decreased PaO 2 , mRNA expressions of Atg5, Atg7, Atg10, and LC3II/LC3I, while increased lung wet weight, lung coefficient, PF score, the blue area of collagen fibers, and p62 protein on the 7th, 14th, and 28th days. In conclusion, the more severe the PF induced by BLM, the lower the autophagy activity.

The objective of this study was to investigate the prevalence of vitamin D deficiency or insufficiency and its association with inflammatory markers and type 2 diabetes. We conducted our research at Qingdao Endocrine and Diabetes Hospital, where serum 25-hydroxyvitamin D3 levels were determined for 2,806 individuals with type 2 diabetes aged 30 and older between January 2018 and December 2019. Medical records were analyzed, and data on health, blood lipids, HbA1c, and inflammation were collected. Our results revealed a high prevalence of vitamin D deficiency in the population. Among male and female patients, median serum 25(OH)D3 levels were 22.46 and 19.00 ng/mL, respectively. More than 60% of female patients had vitamin D deficiency, with over 80% having levels below 30 ng/mL. We observed a favorable connection between high-density lipoprotein cholesterol and 25(OH)D3, while triglycerides and HbA1c showed negative correlations. As 25(OH)D3 levels increased, inflammatory markers such as hypersensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), white blood cell count, neutrophil count, and monocyte count decreased (trend test, p < 0.05), although peripheral blood lymphocytes initially increased and then decreased. After controlling for age and gender, multiple linear regression analysis indicated negative correlations between ESR, hsCRP, and white blood cell count with 25(OH)D3 ( p < 0.05). In conclusion, our study demonstrates that individuals with type 2 diabetes often exhibit vitamin D deficiency or insufficiency, which is associated with elevated levels of inflammatory markers in the blood.

Lung cancer (LC) is regarded as a fatal cancer, and insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) have been found to play a key role in regulating tumor glycolytic metabolism. The aim of this study is to investigate LC proliferation regulated by metabolite-mediated IGF1R lactylation. IGF1R was highly expressed in LC tissues and cells, and the effects of IGF1R on protein stability were inhibited by Lactate dehydrogenase A (LDHA) inhibition. Moreover, the tightness of IGF1R binding to IGF1 was also enhanced by exogenous lactic acid but suppressed by LDHA silencing, while cell viability and proliferation were promoted by over-expression of IGF1R. Exogenous lactic acid further exacerbated the effects of the IGF1R gene, while LDHA knocking down reduced the IGF1R-induced malignant behaviors. The IGF1R and exogenous lactic acid were also found to increase extracellular acidification rate (ECAR) and decrease oxygen consumption rate to regulate glycolysis, which was inhibited by LDHA deficiency in LC cells. The study concluded that IGF1R-mediated aggressive behaviors of LC cells were associated with higher levels of IGF1R lactylation. Moreover, lactic acid can improve the protein stability of the IGF1R oncogene, thus promoting glycolysis and generating lactic acid, forming a closed loop. Therefore, targeting IGF1R is envisaged to provide a novel strategy for developing therapeutic agents against LC.

The goal of the study involved the comparison of clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of malignant lymphoma (ML). The effectiveness of allo-HSCT versus auto-HSCT in the treatment of ML was compared by searching EMBASE, PubMed, Web of Science, and the Cochrane Library for relevant studies. The confidence intervals (CI) and odds ratio (OR) of the article’s outcomes were described by a forest plot. Finally, 972 patients in seven articles were included. Overall survival (OS) did not differ significantly between allo-HSCT and auto-HSCT groups (OR  =  0.87, 95% CI: 0.66–1.14, P  =  0.31). Furthermore, there was no significant difference in adverse reactions (AR) between the two groups (OR  =  1.35, 95% CI: 0.81–2.24, P  =  0.25). We observed a significant difference in progression-free survival (PFS) between the two groups (OR  =  4.14, 95% CI: 2.93–5.35, P < 0.01). There was no evidence of publication bias in this meta-analysis. The incidence of OS and AR differ significantly between allo-HSCT and auto-HSCT, but the PFS was longer in ML patients who received allo-HSCT.

Neuroinflammation is pivotal in the development of neuropathic pain (NeP). While mitochondrial deoxyribonucleic acid (mtDNA) and cyclic GMP-AMP synthase (cGAS) are recognized for inducing inflammation in various neurological disorders, their involvement in NeP remains ambiguous. In this study, we examined: (1) the changes in mtDNA and cGAS in mice with NeP induced by chronic constriction injury (CCI) of the sciatic nerve, whether mtDNA triggers inflammation via the cGAS signaling; (2) the effects of RU.521, a cGAS antagonist, on CCI-induced nociception (allodynia and hyperalgesia) and relative inflammatory protein expression; (3) the activation of microglia and the cGAS-IFN pathway mediated by mtDNA in BV2 cell; (4) the effect of RU.521 on mtDNA-induced inflammatory response in BV2 cells. Results revealed reduced mtDNA levels in the sciatic nerve but increased levels in the spinal cord of CCI mice, along with elevated cGAS expression and inflammatory factors. RU.521 alleviated nociceptive behaviors in CCI mice, possibly by normalizing cGAS levels and suppressing inflammation. Neuron-derived mtDNA provoked cellular activation and upregulated cGAS signaling in BV2 cells. Additionally, RU.521 and DNase I effectively inhibited cGAS-induced inflammation. These findings underscore the critical role of mtDNA accumulation and mtDNA-mediated cGAS signaling in NeP development after peripheral nerve injury. Graphical abstract

The aim of this research is to explore the application value of Deep residual network model (DRN) for deep learning-based multi-sequence magnetic resonance imaging (MRI) in the staging diagnosis of cervical cancer (CC). This research included 90 patients diagnosed with CC between August 2019 and May 2021 at the hospital. After undergoing MRI examination, the clinical staging and surgical pathological staging of patients were conducted. The research then evaluated the results of clinical staging and MRI staging to assess their diagnostic accuracy and correlation. In the staging diagnosis of CC, the feature enhancement layer was added to the DRN model, and the MRI imaging features of CC were used to enhance the image information. The precision, specificity, and sensitivity of the constructed model were analyzed, and then the accuracy of clinical diagnosis staging and MRI staging were compared. As the model constructed DRN in this research was compared with convolutional neural network (CNN) and the classic deep neural network visual geometry group (VGG), the precision was 67.7, 84.9, and 93.6%, respectively. The sensitivity was 70.4, 82.5, and 91.2%, while the specificity was 68.5, 83.8, and 92.2%, respectively. The precision, sensitivity, and specificity of the model were remarkably higher than those of CNN and VGG models ( P < 0.05). As the clinical staging and MRI staging of CC were compared, the diagnostic accuracy of MRI was 100%, while that of clinical diagnosis was 83.7%, showing a significant difference between them ( P < 0.05). Multi-sequence MRI under intelligent algorithm had a high diagnostic rate for CC staging, deserving a good clinical application value.

Drug testing has many test elements. It aims to prevent unqualified drugs from entering the market and ensure drug safety. The existing artificial intelligence (AI) online monitoring system identifies active ingredients in the process of use. Owing to their openness, data are easy to be lost, failing to meet user needs and inducing a specific impact on the use of the monitoring system. With the continuous development of computer and measurement technologies, various biochemical data are increasing at an unprecedented speed, and numerous databases are emerging. Extracting patterns from considerable known data and experimental facts is an essential task for a wide range of biological and chemical workers. Pattern recognition is one of the essential technologies for data mining. It is widely used in industry, agriculture, national defense, biomedicine, meteorology, astronomy, and other fields. To improve the effect of the online drug ingredient recognition system, this study used AI to design an online drug ingredient recognition-embedded monitoring system and applied AI to the teaching field to improve teaching efficiency. First, this study constructed the framework of the AI online drug ingredient recognition-embedded monitoring system and introduced the process of online drug ingredient recognition. Then, it introduced the pattern recognition method, constructed the pattern recognition system, and presented the pattern recognition algorithm and the algorithm evaluation index. Afterward, it used pattern recognition to conduct a qualitative analysis of the infrared spectrum of drug components and introduced the overall process of the qualitative analysis. In addition, this study employed AI to implement changes to the embedded system instruction in colleges and universities, summarizing the current issues. The impact of drug component recognition and the educational impact of embedded systems were investigated in the experimental portion. The experimental findings demonstrated the excellent accuracy, sensitivity, specificity, and Matthew correlation coefficient of the online drug component recognition-integrated monitoring system in this work. Compared with that of other systems, its average drug component recognition accuracy was above 0.85. Students in five majors reported high levels of satisfaction with the embedded system teaching, which is better for delivering college instruction.

To elucidate the molecular genetic mechanisms underpinning feather color in Muscovy ducks. A cohort of 100 Muscovy ducks was meticulously selected for this research. Follicular tissues from ducks exhibiting black and white plumage served as the experimental samples. From these tissues, RNA and proteins were extracted for further analysis. The RNA underwent reverse transcription polymerase chain reaction amplification, followed by validation through western blot assays. The data revealed a significant upregulation in the expression of FN domain-containing protein 1 ( FNDC1 ) and ADAMTS12 genes in Muscovy ducks with white plumage traits as opposed to those with black plumage traits. Specifically, individuals with pure white plumage demonstrated a markedly elevated expression of the FNDC1 gene in comparison to their pure black counterparts. Conversely, expression levels of the ADAMTS12 gene were found to be reduced in ducks with pure black plumage relative to those with pure white plumage. Notably, the expression patterns of FNDC1 and ADAMTS12 genes exhibited inconsistencies between mRNA and protein levels. This study offers significant insights into the molecular genetic mechanisms underlying feather color variation in Muscovy ducks. FNDC1 and ADAMTS12 could be considered potential targets for genetic manipulation or selective breeding strategies aimed at achieving specific feather color phenotypes in Muscovy ducks. Graphical abstract

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats’ growth performance compared to the other diets.

Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL) and is characterized by lymph node enlargement. However, cases involving extra-nodal organ involvement as the first symptom are rare. There are no reports of RT with breast lesions as the first symptom. Nonspecific and atypical clinical manifestations represent key challenges in the accurate diagnosis and appropriate treatment of RT. This case report describes an elderly female patient who presented with breast lesions as the first RT symptom. The patient was admitted with a painless mass in the left breast. Examination revealed multiple lymphadenopathies and abnormally high white blood cell levels. The patient was diagnosed with CLL after hematological tests, assessments of bone marrow morphology, and tissue biopsy. Mammography and B-ultrasonography showed solid space-occupying lesions (BI-RADS category 5) in the left breast. Initially, the patient declined a breast biopsy and was therefore prescribed ibrupotinib treatment, which showed limited efficacy. A needle biopsy of the affected breast indicated the presence of diffuse large B-cell lymphoma. Based on auxiliary and pathological examinations and medical history, the final diagnosis was RT with breast involvement. Zanubrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment provided initial control; however, the treatment strategy required adjustment because of the patient’s fluctuating condition. The current status of the patient is marked as stable, showing an overall achievement of partial alleviation. The patient is in the process of receiving follow-up treatment. We also performed a comprehensive literature review on RT, with particular emphasis on its biological paradigm, prognosis implications, existing therapeutic approaches, and emerging directions in treatment modalities.

Nocardiosis is an infectious disease caused by Nocardia spp., mainly affecting immunocompromised hosts. Nocardia infection is not common; especially Nocardia wallacei infection is even rarer. The patient, female, 61 years old, farmer, has been working in the field for a long time and has normal immune function. Her main clinical manifestation was persistent back pain. Chest-enhanced computed tomography showed pulmonary inflammation. Rare pathogen Nocardia wallac ei was detected in alveolar lavage fluid using matrix-assisted laser destructive ionization time-of-flight mass spectrometry. She received treatment with linezolid and was discharged after her condition improved.

Rhodococcus equi , predominantly recognized as an opportunistic pathogen affecting immunocompromised hosts, and Brucella , a widespread zoonotic bacterium, infrequently co-infect immunocompetent adults, thereby posing a distinctive diagnostic challenge. Here, we describe a case involving a 53-year-old male with a history of goat farming, who presented with persistent chest tightness, cough, and notable weight loss, absent fever. Radiological and bronchoscopic assessments showed a right hilar mass, extensive vertebral destruction, and bronchial lesions, deviating from the typical symptoms associated with either pathogen. Laboratory analyses confirmed a co-infection involving R. equi and Brucella . Initial therapy with levofloxacin and vancomycin proved ineffective; however, a subsequent treatment regimen comprising azithromycin, etimicin, minocycline, and moxifloxacin resulted in substantial clinical improvement. This case accentuates the intricacies involved in diagnosing and managing atypical co-infections in immunocompetent individuals and underscores the importance of careful microbiological testing to inform effective therapeutic strategies.

Adverse cardiac mechanical remodeling is critical for the progression of heart failure following myocardial infarction (MI). We previously demonstrated the involvement of RIP3-mediated necroptosis in the loss of functional cardiomyocytes and cardiac dysfunction post-MI. Herein, we investigated the role of RIP3 in NOD-like receptor protein 3 (NLRP3)-mediated inflammation and evaluated the effects of RIP3 knockdown on myocardial mechanics and functional changes after MI. Our findings revealed that mice with MI for 4 weeks exhibited impaired left ventricular (LV) myocardial mechanics, as evidenced by a significant decrease in strain and strain rate in each segment of the LV wall during both systole and diastole. However, RIP3 knockdown ameliorated cardiac dysfunction by improving LV myocardial mechanics not only in the anterior wall but also in other remote nonischemic segments of the LV wall. Mechanistically, knockdown of RIP3 effectively inhibited the activation of the nuclear factor kappa-B (NF-κB)/NLRP3 pathway, reduced the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the heart tissues, and mitigated adverse cardiac remodeling following MI. These results suggest that downregulation of RIP3 holds promise for preventing myocardial inflammation and cardiac mechanical remodeling following MI by regulating the NF-κB/NLRP3 pathway.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case–control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants – coenzyme Q10 and vitamins E and C – and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20–29, 30–39, and 40–49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

Membrane-associated proteins are important membrane readers that mediate and facilitate the signaling and trafficking pathways in eukaryotic membrane-bound compartments. The protein members in the Phafin family are membrane readers containing two phosphoinositide recognition domains: the Pleckstrin Homology domain and the FYVE (Fab1, YOTB, Vac1, and early endosome antigen 1) domain. Phafin proteins, categorized into two subfamilies, Phafin1 and Phafin2, associate with cellular membranes through interactions involving membrane-embedded phosphoinositides and phosphoinositide-binding domains. These membrane-associated Phafin proteins play pivotal roles by recruiting binding partners and forming complexes, which contribute significantly to apoptotic, autophagic, and macropinocytotic pathways. Elevated expression levels of Phafin1 and Phafin2 are observed in various cancers. A recent study highlights a significant increase in Phafin1 protein levels in the lungs of idiopathic pulmonary fibrosis patients compared to normal subjects, suggesting a crucial role for Phafin1 in the pathogenesis of pulmonary fibrosis. Additionally, phosphatidylinositol-3-phosphate-binding 2 (Pib2), a close relative of the Phafin1 protein, functions as an amino acid sensor activating the TOCR1 pathway in yeasts. This review focuses on delineating the involvement of Phafin proteins in cellular signaling and their implications in diseases and briefly discusses the latest research findings concerning Pib2. Graphical abstract

Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a differential diagnosis when intra-abdominal masses are detected.

A congenital protein anomaly in the erythrocyte membrane skeleton causes a hereditary haemolytic illness known as hereditary spherocytosis (HS). The primary characteristic of HS is an increase in the number of tiny spherical red blood cells in the peripheral blood. The chief clinical features of HS include anaemia, jaundice, splenomegaly, spherical erythrocytosis in the blood, chronic anaemia with haemolysis, and recurrent acute attacks. Most patients have a family history; some have autosomal recessive inheritance, whereas most have autosomal dominant inheritance. In cases of severe hyperbilirubinemia disproportionate to haemolysis, other causes of hyperbilirubinemia should be considered. Gilbert syndrome (GS) is an autosomal dominant illness caused by the reduced activity of uridine diphosphate-glucuronosyl transferase lAl and is characterised by intermittent hyperbilirubinemia without any other signs or symptoms of liver disease. The possibility of the coexistence of HS and GS is very limited. Here we present the case of an elderly man with yellow skin and sclera recurring anaemia, and a final diagnosis of coexisting HS and GS.

This work investigated the high-throughput classification performance of microscopic images of mesenchymal stem cells (MSCs) using a hyperspectral imaging-based separable convolutional neural network (CNN) (H-SCNN) model. Human bone marrow mesenchymal stem cells (hBMSCs) were cultured, and microscopic images were acquired using a fully automated microscope. Flow cytometry (FCT) was employed for functional classification. Subsequently, the H-SCNN model was established. The hyperspectral microscopic (HSM) images were created, and the spatial-spectral combined distance (SSCD) was employed to derive the spatial-spectral neighbors (SSNs) for each pixel in the training set to determine the optimal parameters. Then, a separable CNN (SCNN) was adopted instead of the classic convolutional layer. Additionally, cultured cells were seeded into 96-well plates, and high-functioning hBMSCs were screened using both manual visual inspection (MV group) and the H-SCNN model (H-SCNN group), with each group consisting of 96 samples. FCT served as the benchmark to compare the area under the curve (AUC), F 1 score, accuracy (Acc), sensitivity (Sen), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) between the manual and model groups. The best classification Acc was 0.862 when using window size of 9 and 12 SSNs. The classification Acc of the SCNN model, ResNet model, and VGGNet model gradually increased with the increase in sample size, reaching 89.56 ± 3.09, 80.61 ± 2.83, and 80.06 ± 3.01%, respectively at the sample size of 100. The corresponding training time for the SCNN model was significantly shorter at 21.32 ± 1.09 min compared to ResNet (36.09 ± 3.11 min) and VGGNet models (34.73 ± 3.72 min) ( P < 0.05). Furthermore, the classification AUC, F 1 score, Acc, Sen, Spe, PPV, and NPV were all higher in the H-SCNN group, with significantly less time required ( P < 0.05). Microscopic images based on the H-SCNN model proved to be effective for the classification assessment of hBMSCs, demonstrating excellent performance in classification Acc and efficiency, enabling its potential to be a powerful tool in future MSCs research. Graphical abstract

The corrosion of metals poses a threat to the economy, the environment, and human health due to undesirable reactions and contaminated products. Corrosion inhibitors, including natural products, can play a key role in protecting metallic materials, especially under challenging conditions. In this study, the roots of the Inula viscosa plant were examined for their ability to act as corrosion inhibitors in a 1 M hydrochloric acid (HCl) solution. Different extracts of the plant were evaluated for their corrosion inhibition capacity in a 1 M HCl solution. The effectiveness of different plant extracts was assessed, including an aqueous extract, an ethanolic extract, and a combined water–ethanol extract. Compounds present in the roots of Inula viscosa were identified using high-performance liquid chromatography. The electrochemical properties of the extracts were studied using various techniques such as open circuit potential, electrochemical impedance spectroscopy, and potentiodynamic polarization. Additionally, surface analysis after immersion was performed using scanning electron microscopy. Electrochemical data revealed that Inula viscosa root (IVR) extracts acted as mixed-type corrosion inhibitors with pronounced cathodic characteristics. The inhibitory efficiency was closely related to the concentration of Inula viscosa ( I. viscosa ), showing a significant increase with higher concentrations. This resulted in a decrease in corrosion current and an increase in polarization resistance. Notably, inhibitory efficiency reached high levels, up to 97.7% in mixed extract which represents a mixture between water and ethanol. In our study, it was observed that the mixed extract (water + ethanol) allowed for a greater corrosion inhibition compared to the other solvents studied, 97.7%. Surface analyses confirmed the formation of an organic film layer on the steel surface, attributed to the bonding of functional groups and heteroatoms in I. viscosa components. Therefore, this study paves the way for the potential integration of I. viscosa as a promising corrosion inhibition material, offering durable protection against steel corrosion and opening avenues for various related applications.

Tubular adenomas of the breast are rare benign epithelium-derived tumours, and so few cases have been reported. Most often, the tumours are palpable, well-circumscribed masses in women of childbearing age and are commonly diagnosed as fibroadenomas both clinically and radiographically. We describe the case of a premenopausal patient with tubular adenoma of the breast who presented with small nipple discharge and a palpable breast mass. On imaging, tubular adenomas are practically indistinguishable from fibroadenomas and most commonly present as oval, circumscribed masses that are hypoechoic on ultrasound. On magnetic resonance imaging (MRI), tubular adenomas may present as lobulated or oval masses with a hyperintense signal on T2-weighted imaging and inhomogeneous internal enhancement on dynamic contrast-enhanced MRI. Pathologic findings after resection of the mass confirmed the diagnosis of tubular adenoma.

Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut–brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and vice versa . Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like Lactobacillus and Bifidobacterium , enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.

Delayed or failed bone healing is a significant clinical challenge worldwide. Bone marrow mesenchymal stem cells (BMSCs) offer a promising approach for improving fracture healing. Isomangiferin, a xanthone C-glucoside, is known for its pharmacological activities, but its role in fracture healing remains unclear. In this study, we investigated the effects of isomangiferin on BMSCs under oxidative stress conditions induced by hydrogen peroxide (H 2 O 2 ). Our results showed that isomangiferin promotes osteogenic differentiation and migration of H 2 O 2 -treated BMSCs, reduces apoptosis and reactive oxygen species production, and activates the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway. These findings suggest that isomangiferin may be a potential therapeutic agent for enhancing bone healing by modulating BMSC function.

This study aimed to determine the prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer (HER2 + BC). Transcriptome sequencing and clinicopathological data were downloaded from the Cancer Genome Atlas. The 10X single cell sequencing dataset was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus. Exosomes-Related Genes were extracted from the ExoCarta and Gene Set Enrichment Analysis databases. FGF9, SF3B4, and EPCAM were found and deemed the most accurate predictive signatures. Patients with HER2 + BC were subtyped into three groupings by exosome prognostic gene (EPGs). The expression of SF3B4 was positively linked with the infiltration of macrophages, neutrophils, and CD4 + T cells. The expression characteristics of EPGs were associated with the biological process of “response to xenobiotic stimuli.” Interactions were relatively high between malignant epithelial cells and fibroblasts, endothelial cells, monocytes, and macrophages. Malignant epithelial cells interact more with fibroblasts and endothelial cells. The migration inhibitory factor pathway was the primary outgoing signaling pattern, while the C-C motif chemokine ligand pathway was the primary incoming signaling pattern for communication between malignant epithelial cells and macrophages. This study described the role of exosome signatures in the prognosis and microenvironment of HER2 + BC and provided a basis for future research.

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤−2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL ), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.

Oral squamous cell carcinoma (OSCC) is the most common malignancy among head and neck squamous cell carcinomas. Targeted therapy plays a crucial role in the treatment of OSCC. However, new and more targets are still needed to develop. Stanniocalcin-1 (STC-1) is a glycoprotein hormone that affects the progression of cancers. However, the potential role of STC-1 in OSCC progression remains to be explored. Here, we aimed to elucidate the role of STC-1 in OSCC. We revealed that STC-1 was highly expressed in OSCC tissues and is correlated with poor patient prognosis. Knockdown of STC-1 significantly suppressed the growth of OSCC cells and restrained glycolysis by reducing glucose consumption, ATP production, and lactate levels. Mechanistically, STC-1 ablation inhibited the PI3K/Akt pathway, reducing the phosphorylation levels of PI3K and Akt. In conclusion, STC-1 depletion restrained OSCC cell growth and glycolysis via PI3K/Akt pathway and has the potential to serve as a therapeutic target for OSCC.

The present work focused on investigating the role of the altered expression of complement C1s in proliferation and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and explore its biological functions in ESCC, so as to lay a theoretical foundation and provide certain clinical reference for diagnosing and treating ESCC. Complement C1s expression within ESCC was assessed, and its clinical pathological characteristics in ESCC patients were analyzed. Subsequently, in vitro experiments were performed to further explore the mechanisms by which complement C1s affected ESCC. According to the results, complement C1s expression within ESCC markedly increased relative to adjacent non-cancerous samples. High C1s expression showed positive relation to race, residual lesion, and tumor location of ESCC patients. Complement C1s affected ESCC cell proliferation and apoptosis. Notably, C1s knockdown significantly inhibited ESCC cell proliferation and enhanced their apoptosis. C1s suppressed ESCC cell proliferation via Wnt1/β-catenin pathway and promoted their apoptosis through modulating the expression of Bcl2, Bax, and cleaved-caspase3.

Pseudohypoparathyroidism (PHP) type 1a (PHP 1a) is a rare hereditary disorder characterized by target organ resistance to hormonal signaling and the Albright hereditary osteodystrophy (AHO) phenotype, which features round facial features, short fingers, subcutaneous calcifications, short stature, obesity, and intellectual disability. Progressive osseous heteroplasia (POH) is another rare disorder characterized by heterotopic ossification (HO) that progressively affects skin, subcutaneous tissues, and deep skeletal muscle. PHP 1a is inherited maternally due to a GNAS mutation, while pure POH is inherited paternally. This case study presented a Chinese boy with congenital hypothyroidism, tonic-clonic seizures, hypoparathyroidism, AHO, POH, and joint fixation deformity. Sequencing analysis of GNAS-Gsα revealed a heterozygous C.432+2T>C(P.?) variant (NM_000516.7) affecting the canonical splice donor site of intron 5 in the boy and his mother, indicating maternal inheritance of a GNAS mutation. The patient was diagnosed with POH overlap syndrome (POH/PHP 1a). Following calcium and calcitriol supplementation, he experienced a reduction in seizures, and surgery was performed to correct the joint fixation deformity caused by HO. This case report provided valuable insights into the genotype-phenotype correlations of POH overlap syndrome and underscored the significance of genetic testing in diagnosing rare diseases.

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

The mortality rate of acute-on-chronic liver failure (ACLF) remains significantly elevated; hence, this study aimed to investigate the impact of heat shock protein family B (small) member 1 (HSPB1) on ACLF in vivo and in vitro and the underlying mechanism. This study used the ACLF mouse model, and liver damage extent was studied employing Masson trichrome, hematoxylin and eosin (H&E), Sirius red staining, and serum biochemical indices. Similarly, hepatocyte injury in lipopolysaccharide (LPS)-induced L02 cells was evaluated using cell counting kit-8 assay, enzymatic activity, flow cytometry, and TUNEL assay, while the underlying mechanism was investigated using western blot. Results showed that the morphology of liver tissue in ACLF mice was changed and was characterized by cirrhosis, fibrosis, collagen fiber deposition, inflammatory cell infiltration, and elevated liver injury indices. Moreover, HSPB1 was upregulated in both ACLF patients and mice, where overexpressing HSPB1 was found to inhibit ACLF-induced liver damage. Similarly, the HSPB1 expression in LPS-treated L02 cell lines was also increased, where overexpressing HSPB1 was found to promote cell viability, inhibit liver injury-related enzyme activity, and suppress apoptosis. Mechanistic investigations revealed that HSPB1 was responsible for inhibiting p-P53 and Bax protein levels, where activated P53 counteracted HSPB1’s effects on cellular behaviors. In conclusion, HSPB1 attenuated ACLF-induced liver injury in vivo and inhibited LPS-induced hepatocyte damage in vitro , suggesting that HSPB1 may be a novel target for ACLF therapy.

IgG4-related tubulointerstitial nephritis (IgG4-related TIN) is the prevalent clinical manifestation of IgG4-related diseases (IgG4-RD). However, there are limited cases of IgG4-RD occurring with membranous nephropathy (MN) in the absence of phospholipase A2 receptor (PLA2R). There have been no indications of treatment using Tripterygium wilfordii . This study reported a rare case of IgG4-RD with PLA2R-associated MN without any of the distinct IgG4-related TIN. The patient was treated effectively with T. wilfordii . A 71-year-old patient was admitted to the medical facility after presenting with a 1 month history of edema and 8 months of albuminuria. The renal biopsy tissue examination confirmed the presence of MN (phase II) in the absence of pathological manifestations of IgG4-related TIN. Immunohistochemistry identified PLA2R++ (granular capillaries). The serum PLA2R antibody titer was 1:180 (1:20). The patient met the diagnosis with IgG4-RD. Over 8 years of follow-up, the patient was effectively treated with low-dose hormones and T. wilfordii , without any adverse effects. This MN is considered a unique form of IgG4-RD, regardless of whether PLA2R antibodies are present or not. Research suggests that T. wilfordii could be a promising option for elderly people with IgG4-related MN, as it has been found to have fewer adverse effects.

Hepatocellular carcinoma (HCC) is a highly vascularized carcinoma, and targeting its neovascularization represents an effective therapeutic approach. Our previous study demonstrated that the baculovirus-mediated endostatin and angiostatin fusion protein (BDS-hEA) effectively inhibits the angiogenesis of vascular endothelial cells and the growth of HCC tumors. However, the mechanism underlying its anti-angiogenic effect remains unclear. Increasing evidence suggests that autophagy has a significant impact on the function of vascular endothelial cells and response to cancer therapy. Hence, the objective of this research was to investigate the correlation between BDS-hEA-induced angiogenesis inhibition and autophagy, along with potential regulatory mechanisms. Our results demonstrated that BDS-hEA induced autophagy in EA.hy926 cells, as evidenced by the increasing number of autophagosomes and reactive oxygen species, accompanied by an upregulation of Beclin-1, LC3-II/LC3-I, and p62 protein expression. Suppression of autophagy using 3-methyladenine attenuated the functions of BDS-hEA-induced EA.hy926 cells, including the viability, proliferation, invasion, migration, and angiogenesis. Moreover, BDS-hEA induced autophagy by downregulating the expression of CD31, VEGF, and VEGFR2, as well as phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR), while concurrently upregulating phosphorylated AMP-activated protein kinase (p-AMPK). The in vivo results further indicated that inhibition of autophagy by chloroquine significantly impeded the ability of BDS-hEA to suppress HCC tumor growth in mice. Mechanistically, BDS-hEA prominently facilitated autophagic apoptosis in tumor tissues and decreased the levels of ki67, CD31, VEGF, MMP-9, p-AKT, and p-mTOR while simultaneously enhancing the p-AMPK expression. In conclusion, our findings suggest that BDS-hEA induces autophagy as a cytotoxic response by modulating the AMPK/AKT/mTOR signaling pathway, thereby exerting anti-angiogenic effects against HCC.

Osteoarthritis (OA) is a chronic degenerative disease characterized by overall joint tissue damage. Metformin (Met) has been shown to inhibit inflammatory reactions, though its potential protective mechanism on cartilage remains unclear. This study investigated Met’s potential to protect cartilage in an OA rat model. Various morphological experiments were conducted to assess changes in cartilage tissue morphology before and after Met treatment. Protein and mRNA levels of cartilage-specific genes were measured using western blot, immunohistochemical staining, and RT-qPCR. Additionally, protein levels of autophagy-related and mTOR pathway-related proteins were measured. The results indicate an imbalance in the synthesis and degradation metabolism of chondrocytes, downregulation of cellular autophagy, and activation of the PI3K/Akt/mTOR pathway after surgery. However, treatment with Met could upregulate the expression of synthetic metabolic factors, indicating its contribution to cartilage repair. Furthermore, analysis of autophagy and pathway protein levels indicated that Met effectively attenuated autophagic damage to osteoarthritic cartilage cells and abnormal activation of the PI3K/Akt/mTOR pathway. In conclusion, Met can inhibit the abnormal activation of the PI3K/AKT/mTOR signaling pathway in cartilage tissue, promote the restoration of cartilage cell autophagic function, improve the balance of cartilage cell synthesis and degradation metabolism, and thus exert a protective effect on rat joint cartilage. Graphical abstract

New drugs for the treatment of bacterial vaginosis (BV) are yet to be developed due to concerns that they may contribute to the increase in antibiotic resistance in BV. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, we investigated the bacteriostatic activity of the AMPs Pexiganan, plectasin, melittin, and cathelicidin-DM against Gram-negative and Gram-positive bacteria both in vitro and in a mouse model of BV infection. The results showed that Pexiganan, melittin, and cathelicidin-DM had significant antibacterial activity against both Gram-negative and Gram-positive bacteria. AMPs have great potential for clinical application in the treatment of vaginitis, and this study provides an experimental basis for their use in the active immunoprophylaxis of BV.

Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2−, CD5 dim , CD4−, CD8+, CD56−, and CD30−. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.

Diabetic kidney disease (DKD) is one of the main microvascular complications of diabetes mellitus, as well as the leading cause of end-stage renal disease. Intestinal microbiota has emerged as a crucial regulator of its occurrence and development. Dysbiosis of the intestinal microbiota can disrupt the intestinal mucosal barrier, abnormal immunological response, reduction in short-chain fatty acid metabolites, and elevation of uremic toxins, all closely related to the occurrence and development of DKD. However, the underlying mechanisms of how intestinal microbiota and its metabolites influence the onset and progression of DKD has not been fully elucidated. In the current review, we will try to summarize the microecological mechanism of DKD by focusing on three aspects: the intestinal microbiota and its associated metabolites, and the “gut–kidney axis,” and try to summarize therapies targeted at managing the intestinal microbiota, expecting to provide theoretical basis for the subsequent study of the relationship between intestinal homeostasis and DKD, and will open an emerging perspective and orientation for DKD treatment.

The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted β-oxidation and reduced hepatocyte lipid synthesis ( P < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis ( P < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs ( P < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization ( P < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM. Graphical abstract

Hypertension is commonly classified into essential hypertension and secondary hypertension, although definitive classification can be challenging in some cases. Here, we discussed a patient who admitted for refractory hypertension, exhibiting various clinical manifestations including inadequate estrogen secretion, underdeveloped secondary sexual characteristics, primary amenorrhea, short stature, multiple moles, and somatic abnormalities. The patient was finally diagnosed with Turner syndrome (TS) based on clinical findings and chromosomal analysis. The genetic karyotype identified was 46,X,i(X)(q10).

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.

The objective of this study was to investigate the relationship between low attenuation area (LAA) scores, pulmonary function parameters, and clinical prognosis in patients with chronic obstructive pulmonary disease (COPD). COPD patients were divided into four LAA-based grades. Various lung function parameters were measured and correlated with LAA scores. Patient symptoms were examined using the St. George’s Respiratory Questionnaire (SGRQ) and exercise capacity using the 6-min walk test (6MWT). Statistical analysis determined the significance of differences. Higher levels of LAA were associated with decreased lung function and airflow limitations, suggesting a positive relationship between the two. Clinical symptom scores increased as COPD severity based on LAA stratification worsened. Reduced exercise capacity was shown by a substantial decline in 6MWT scores as COPD severity increased. As LAA scores increased, SGRQ scores increased, indicating a decreased quality of life (QOL). The study demonstrated a relationship between LAA scores and COPD severity. High LAA scores were associated with poor lung function, worse clinical symptoms, limited exercise capacity, and lower QOL. These findings show that LAA scores are clinically relevant for disease severity assessment and COPD management. Further research is required to determine LAA scores’ prognostic significance in disease progression and treatment response to enhance COPD therapy.

Recent scientific investigations have revealed the intricate mechanisms underlying bone formation, emphasizing the essential role of long non-coding RNAs (lncRNAs) as critical regulators. This process, essential for skeletal strength and functionality, involves the transformation of mesenchymal stem cells into osteoblasts and subsequent deposition of bone matrix. lncRNAs, including HOX transcript antisense RNA (HOTAIR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), differentiation antagonizing non-coding RNA (DANCR), and maternally expressed gene 3 (MEG3), have emerged as prominent players in this regulatory network. HOTAIR modulates osteoblast differentiation by interacting with chromatin-modifying enzymes, while MALAT1 regulates osteogenic differentiation through microRNA interactions. DANCR collaborates with Runx2 to fine-tune osteoblast differentiation, and MEG3 orchestrates multiple signaling pathways crucial for bone formation. Moreover, other lncRNAs such as H19, lncRNA for enhancing osteogenesis 3, rhabdomyosarcoma 2-associated transcript, urothelial cancer associated 1, taurine up-regulated gene 1, and nuclear enriched abundant transcript 1 contribute to the complex regulatory network governing osteoblast activities. Understanding the precise roles of these lncRNAs offers promising avenues for developing innovative therapeutic strategies targeting bone-related disorders like osteoporosis. Overall, this review summarizes the pivotal role of lncRNAs in bone formation, highlighting their potential as targets for future research endeavors aimed at advancing therapeutic interventions in bone diseases.

Many cancers exhibit resistance to chemotherapy, resulting in a poor prognosis. The transcription factor NRF2, activated in response to cellular antioxidants, plays a crucial role in cell survival, proliferation, and resistance to chemotherapy. This factor may serve as a promising target for therapeutic interventions in esophageal carcinoma. Recent research suggests that NRF2 activity is modulated by ubiquitination mediated by the KEAP1-CUL3 E3 ligase complex, highlighting the importance of deubiquitination. However, the specific deubiquitinase responsible for regulating NRF2 in esophageal cancer remains unknown. In this study, a novel regulator of the NRF2 protein, Ubiquitin-Specific Protease 35 (USP35), has been identified. Mechanistically, USP35 modulates NRF2 stability through enzymatic deubiquitination. USP35 interacts with NRF2 and facilitates its deubiquitination. Knockdown of USP35 leads to a notable increase in NRF2 levels and enhances the sensitivity of cells to chemotherapy. These findings suggest that the USP35-NRF2 axis is a key player in the regulation of therapeutic strategies for esophageal cancer.

The aim of the present study is to explore the potential prediction value of neutrophil-to-lymphocyte ratio (NLR) or peripheral blood platelet-to-lymphocyte ratio (PLR) for rebleeding in patients with esophagogastric variceal bleeding (EVB). We have enrolled 80 rebleeding patients with EVB and 113 EVB patients without rebleeding in the present study. The lymphocyte, platelet counts, the PLR, and the NLR of the candidates were calculated, and receiver-operating characteristic curve was drawn to examine whether NLR or PLR is a sensitive biomarker for distinguishing rebleeding patients from the EVB patients. We observed that NLR and PLR were all significantly increased in rebleeding patients with EVB compared with the non-rebleeding patients ( p < 0.01); moreover, the area under the curve of NLR and PLR was 0.7037 (95% confidence interval [CI], 0.6281–0.7792) and 0.7468 (95% CI, 0.6793–0.8144), respectively, suggesting that NLR or PLR is a sensitive biomarker for distinguishing non-rebleeding patients from the rebleeding patients. We reported that NLR and PLR were significantly increased in the peripheral blood of patient with esophagogastric variceal rebleeding, suggesting that NLR and PLR may be potential early diagnostic and prognostic markers for the rebleeding among patients with EVB.

Gestational diabetes mellitus (GDM) is a metabolic disease that occurs during pregnancy. Herein, we investigate G protein-coupled receptor 1 (GPR1) in mediating GDM through the phosphorylation of serine/threonine kinase (AKT) pathway. Thirty pregnant SD rats were grouped into: normal pregnancy control group (NC), GDM model group, and GDM model + high-dose GPR1 antagonist treatment (GDM + Ari) group. GDM model was established, and the GDM + Ari group adopted GPR1 antagonist aripiprazole. The blood glucose level, insulin level, and insulin resistance (IR) were detected. The expression and phosphorylation of GPR1, AKT, and extracellular signal-regulated kinase (ERK) in placental tissue were detected using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB). The serum insulin concentration, glucose concentration, and glycated hemoglobin concentration during pregnancy in GDM group SD rats were significantly higher than those in the NC group ( P < 0.05). The expression and phosphorylation levels of GPR1, AKT, and ERK in the placental tissue of SD pregnant rats in the GDM group were significantly lower than those in the NC group. Furthermore, compared with the GDM group, the expression of GPR1, AKT, and ERK in placental tissue was significantly reduced in the GDM + Ari group, while simultaneously enhancing the blood glucose level and IR level. In addition, the survival number, body weight, and malformation rate of the offspring of the GDM + Ari group were significantly improved, and there was no significant effect on the number of offspring. The expressions of GPR1, AKT, and ERK in placental tissue exhibited a significant decrease, while the glucose level and IR were observed to increase in the GDM + Ari group. Enhancing the expression of GPR1 may activate AKT phosphorylation to alleviate GDM. GPR1 could potentially serve as a novel target for diabetes treatment, offering new insights into managing GDM. Graphical abstract

Sepsis-induced acute lung injury is associated with lung epithelial cell injury. This study analyzed the role of the antimicrobial peptide LL37 with mitochondrial DNA (LL37–mtDNA) and its potential mechanism of action in lipopolysaccharide (LPS)-treated rat type II alveolar epithelial cells (RLE-6TN cells). RLE-6TN cells were treated with LPS alone or with LL37–mtDNA, followed by transcriptome sequencing. Differentially expressed and pivotal genes were screened using bioinformatics tools. The effects of LL37–mtDNA on cell viability, inflammation, apoptosis, reactive oxygen species (ROS) production, and autophagy-related hallmark expression were evaluated in LPS-treated RLE-6TN cells. Additionally, the effects of Hsp90aa1 silencing following LL37–mtDNA treatment were investigated in vitro. LL37–mtDNA further suppressed cell viability, augmented apoptosis, promoted the release of inflammatory cytokines, increased ROS production, and elevated LC3B expression in LPS-treated RLE-6TN cells. Using transcriptome sequencing and bioinformatics, ten candidate genes were identified, of which three core genes were verified to be upregulated in the LPS + LL37–mtDNA group. Additionally, Hsp90aa1 downregulation attenuated the effects of LL37–mtDNA on LPS-treated RLE-6TN cells. Hsp90aa1 silencing possibly acted as a crucial target to counteract the effects of LL37–mtDNA on viability, apoptosis, inflammation, and autophagy activation in LPS-treated RLE-6TN cells.

Pain has been a prominent medical concern since ancient times. Despite significant advances in the diagnosis and treatment of pain in contemporary medicine, there is no a therapeutic cure for chronic pain. Chinese herbaceous peony, a traditional Chinese analgesic herb has been in clinical use for millennia, with widespread application and substantial efficacy. Paeoniflorin (PF), the main active ingredient of Chinese herbaceous peony, has antioxidant, anti-inflammatory, anticancer, analgesic, and antispasmodic properties, among others. The analgesic effect of PF, involving multiple critical targets and pain regulatory pathways, has been a hot spot for current research. This article reviews the literature related to the analgesic effect of PF in the past decade and discusses the molecular mechanism of the analgesic effect of PF, including the protective effects of nerve cells, inhibition of inflammatory reactions, antioxidant effects, reduction of excitability in nociceptor, inhibition of the nociceptive excitatory neuroreceptor system, activation of the nociceptive inhibitory neuroreceptor system and regulation of other receptors involved in nociceptive sensitization. Thus, providing a theoretical basis for pain prevention and treatment research. Furthermore, the prospect of PF-based drug development is presented to propose new ideas for clinical analgesic therapy.

Oxidative stress has been widely believed to be the mechanism responsible for developing diseases such as arthritis, asthma, dementia, and aging. Solanum nigrum Linn. is a common edible medicinal herb that belongs to the family Solanaceae which has more than 180 chemical components that have so far been discovered. The main bioactive components of these are steroidal saponins, alkaloids, phenols, and polysaccharides. This article presents comparative phytochemical profiling including total phenolic, total flavonoid, alkaloid, proanthocyanidins, tannin, and vitamin C contents of three Algerian S. nigrum samples collected from three different locations in the Algerian desert. Additionally, the potential antioxidant activity of the three samples was assessed by 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and oxidative hemolysis inhibition assay. Moreover, the correlation between the major phenolic phytoconstituents previously reported and isolated from the plant and antioxidant activity has also been done by in silico molecular docking. Ten bioactive compounds were docked with selected proteins, arachidonate-5-lipoxygenase (PDB: 6n2w) and cytochrome c peroxidase (PDB: 2x08), to check their affinity with binding sites of these proteins for the possible mechanism of action. The docking scores suggest that S. nigrum ’s quercetin and kaempferol may play a significant role in its antioxidant action. Graphical abstract

Diabetic retinopathy (DR), a major complication of diabetes causing blindness, is characterized by retinal damage due to capillary degeneration and vascular leakage. Current treatments are not fully effective, highlighting the need for searching new therapeutic targets. Hematopoietic cell kinase (HCK), a protein involved in various diseases, has been identified as a potential biomarker in DR, but its role in disease progression requires further investigation. Here we investigated the role of HCK in DR and its potential mechanism. We found the expression of HCK increased under the stimulation of high glucose (HG) in human retinal capillary endothelial cells (HRECs). Knockdown of HCK can improve HREC cell viability and the integrity of the internal blood–retinal barrier. HCK depletion suppressed the AMPK pathway in HG-induced HRECs. In summary, HCK may be a potential target for the treatment of DR, which provides a theoretical basis for the development of new treatment strategies.

This study aimed to clarify the role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes and the role of voltage-dependent anion channel 1 (VDAC1) in the PINK1/Parkin signaling pathway in mouse glomerular podocytes. For this purpose, podocytes were cultured with rapamycin and observed using microscopy. The apoptosis rate of podocytes was detected by flow cytometry. Changes in the mitochondrial membrane potential were measured. The autophagy-related proteins VDAC1, PINK1, Parkin, and LC3 were detected, and mitochondrial autophagosomes were observed via transmission electron microscopy. In the present study, we demonstrated that the number of podocytes treated with rapamycin was significantly reduced. Compared with those in the control group, the apoptosis rate of podocytes and the degree of mitochondrial membrane potential depolarization were significantly higher. We also found the expression levels of VDAC1, PINK1, Parkin, and LC3 were significantly increased. In the rapamycin-treated group, the numbers of swollen mitochondria and mitochondrial autophagosomes were significantly higher. Finally, we showed that rapamycin can upregulate the expression of VDAC1, PINK1, Parkin, and LC3 in glomerular podocytes, which is correlated with mitophagy. VDAC1 is involved in mitophagy and is related to the PINK1/Parkin signaling pathway, serving as an indicator of mitophagy in podocytes.

Non-Hodgkin lymphoma (NHL) limited to the larynx is very rare. The authors present the clinical diagnosis and treatment of four patients with laryngeal NHL. Case 1 was diagnosed with glottic, subglottic, and tracheal mucosa-associated lymphoid tissue (MALT) lymphoma, and was treated with radiotherapy and chemotherapy after surgery. Case 2 was diagnosed with laryngeal MALT lymphoma and underwent radiotherapy. Case 3 was diagnosed with angioimmunoblastic T-cell lymphoma, and was treated with radiotherapy and chemotherapy. Case 4 had MALT lymphoma in the glottic area with a malignant thyroid tumor, and was treated with radiotherapy and chemotherapy after surgery. More reports and research on this disease are needed.

Intracranial infection (ICI) is a frequent and serious complication after neurosurgery. Macrogenome next-generation sequencing (mNGS) technology can provide reference for clinical diagnosis and treatment of ICI. This work aimed to explore the application value of mNGS technology in analyzing the clinical characteristics of human immunodeficiency virus (HIV) infection and ICI after neurosurgery. A total of 60 patients with ICI were enrolled as the research objects, all patients underwent routine cerebrospinal fluid analysis and traditional pathogen detection, followed by mNGS genome analysis. Using clinical diagnosis of ICI as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for both detection methods were calculated. Receiver operating characteristic curves were constructed to assess the area under the curve (AUC) for evaluating the clinical value of mNGS in suspected intracranial infectious pathogen diagnosis. Results showed a positivity rate of 71.67% (43 cases) with mNGS compared to 28.33% (17 cases) with traditional pathogen detection methods, demonstrating a significant difference ( P < 0.05). The sensitivity of mNGS for detecting ICIs was 83.7%, significantly higher than the 34.88% observed with traditional methods ( P < 0.05). The pathogen detection rate of mNGS was higher than traditional methods ( P = 0.002), with an AUC of 0.856 (95% CI: 0.638–0.967), significantly greater than the AUC of 0.572 (95% CI: 0.350–0.792) for traditional methods ( P < 0.05). mNGS successfully identified microorganisms such as Cryptococcus , Propionibacterium , Staphylococcus , Corynebacterium , Micrococcus , and Candida associated with ICIs. These findings underscore the clinical applicability of mNGS technology in analyzing the characteristics of HIV infection and ICI post-neurosurgical procedures. This technology enables more accurate diagnosis and treatment of ICIs, providing valuable insights for developing effective therapeutic strategies. Graphical abstract

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immune responses. They are widely distributed in various tissues and organs, including the eyes. In the ocular context, permanent DCs are present at the peripheral edge of the retina and the peripapillary area in an immature state. However, during the inflammatory process, DCs become activated and contribute to the development of uveitis. This review focuses on introducing the characteristics and status of DC-induced uveitis, exploring factors that can influence the status of DCs, and discussing feasible methods for treating DCs in both experimental autoimmune uveitis animal models and humans. It emphasizes the importance of further research on molecular pathways and signaling pathways that regulate the function of DCs. For example, investigating molecules such as cytotoxic T-lymphocyte-associated protein 4, which inhibits the B7-CD28 co-stimulatory interaction, can help improve immune homeostasis. The aim is to identify new therapeutic targets and develop targeted strategies for DCs, such as DC vaccine therapy or the use of immune modulators. These approaches can be tailored to the immune characteristics and disease manifestations of individual patients, enabling personalized treatment strategies. This may include the personalized design and precise medication of DC therapy, with the ultimate goal of improving treatment efficacy while minimizing adverse reactions.

Diabetic cardiomyopathy (DCM) is identified as a progressive disease that may lead to irreparable heart failure. Toll-like receptor (TLR) signaling is believed to be implicated in the pathogenesis of DCM. This study intended to explore the potential impact of Toll-like receptor 4 (TLR4) on DCM in vitro and in vivo . Streptozotocin and HG medium were utilized to induce diabetes in animal and cell models, respectively. Selective TLR4 inhibitor TAK-242 and calcium/calmodulin-dependent protein kinase-II (CaMKII) inhibitor KN-93 were employed to explore the involvement of TLR4/CaMKII in DCM. TLR4 expression was increased in DCM hearts, while inhibition of TLR4 activation by TAK-242 improved cardiac function, attenuated heart hypertrophy, and fibrosis, as well as reduced oxidative stress and proinflammatory cytokine levels in rats, which were confirmed by Doppler echocardiography, hematoxylin and eosin staining, and Masson Trichome staining and specific enzyme-linked immunosorbent assay kits. Besides, the expression of hypertrophy-related molecules and oxidative stress damage were also inhibited by TAK-242. Furthermore, TAK-242 treatment reduced CaMKII phosphorylation accompanied by decreased expression of NOD-like pyrin domain-containing protein 3, gasdermin D (GSDMD), The N-terminal domain of Gasdermin D (GSDMD-N), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 both in vivo and in vitro. Similar positive impacts on HG-induced pyroptosis were also observed with KN-93 treatment, and this was achieved without affecting TLR4 expression. Collectively, our work suggested that TAK-242 demonstrated substantial benefits against DCM both in vivo and in vitro , potentially attributed to the suppression of the TLR4-mediated CaMKII/NLRP3 pathway activity.

Exercise training can significantly improve skeletal muscle mitochondrial function and has been proven to be highly relevant to alterations in skeletal muscle DNA methylation. However, it remains unclear whether late-in-life exercise has an effect on promoter methylation of PGC-1α, a key regulator of mitochondrial biogenesis. Here we employed two distinct exercise modalities, constant medium intensity exercise training (CMIT) and high-intensity interval exercise training (HIIT), to investigate their impacts on PGC-1α expression and methylation regulation in skeletal muscle of aged mice. The results revealed a notable decrease in PGC-1α expression in skeletal muscle of aged mice, accompanied by elevated methylation levels of the PGC-1α promoter, and increased DNA methyltransferase (DNMT) protein expressions. However, both forms of exercise training significantly corrected PGC-1α epigenetic changes, increased PGC-1α expression, and ameliorated skeletal muscle reduction. Furthermore, exercise training led to elevated expression of proteins related to mitochondrial biogenesis and energy metabolism in skeletal muscle, improving mitochondrial structure and function. In conclusion, late-in-life exercise improved skeletal muscle function, morphology, and mitochondria biogenesis, which may be associated with hypomethylation in promoters of PGC-1α and increased content of skeletal muscle PGC-1α. Notably, there was no clear difference between HIIT and CMIT in PGC-1α expression and skeletal muscle function. Graphical abstract

This study aimed to investigate the presence of antibiotic susceptibility patterns and bacterial profiles of some multi-drug-resistant bacteria isolated from the effluents of Kolladiba and Debark Hospitals. Sixteen samples were collected from Kolladiba and Debark Hospitals in North Gondar, Ethiopia, to investigate the presence of multi-drug-resistant bacteria. To assess susceptibility patterns, well-isolated bacterial colonies were subjected to seven antibiotics. The selected resistant isolates were characterized using morphological and biochemical tests. Plasmid DNA analysis of the isolates was also performed. Out of a total of 28 bacterial isolates, 12 were found to be multi-drug resistant. Among the tested antibiotics, erythromycin was the most resistant antibiotic, while novobiocin was the most effective antibiotic. A plasmid profile study of the isolates revealed both the presence and absence of plasmids. The number of plasmids ranged from zero to four, with plasmid sizes of 100, 900, 1,000, 1,400, 1,500, and 1,800 base pairs. This study concluded that effluents from both hospitals have high number of multi-drug-resistant isolates. The genes responsible for multi-drug resistance in bacterial isolates under this study could be either plasmid-mediated or chromosomal DNA-mediated. The presence of multi-drug-resistant bacteria in these effluents should not be overlooked.

This study aimed to investigate the expression and clinical significance of syncytin-1 in the serum exosomes of hepatocellular carcinoma (HCC) patients. Serum samples were collected from 61 patients with newly diagnosed HCC and 61 healthy individuals. Exosomes were extracted from serum samples and identified using transmission electron microscopy and Western blot. The relative expression levels of syncytin-1 in exosomes were determined by real-time quantitative PCR. The protein expression levels of alpha-fetoprotein and syncytin-1 in HCC patients were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to evaluate the sensitivity and specificity of serum exosomal syncytin-1 in diagnosing HCC. The relationships between syncytin-1 expression and clinical pathological features were analyzed using receiver operating characteristic curve analysis. The results showed that the expression level of syncytin-1 in the serum of patients with newly diagnosed HCC was significantly higher than that in the normal control group ( P < 0.0001). Using pathological diagnosis as the gold standard, the sensitivity and specificity of syncytin-1 for the auxiliary diagnosis of HCC were 91.3% and 75.5%, respectively, which were significantly higher than those of alpha-fetoprotein (P < 0.0001). The relative expression level of serum exosomal syncytin-1 was significantly associated with lymph node metastasis, degree of differentiation, and CNLC staging of HCC patients (P < 0.05). In conclusion, syncytin-1 in serum exosomes has high sensitivity and specificity for diagnosing HCC and can serve as a novel tumor marker for early screening, detection, and staging of HCC.

The study aimed to verify the pathogenic malarial kidney infections and histopathological pictures in mice infected with Plasmodium chabaudi using Indigofera oblongifolia leaf extract silver nanoparticles (IOLEAgNPs). Fifty healthy adult female mice C57BL/6 were used. Animals were divided into five groups, with each group of ten mice. The first control non-infected group was given distilled water for 7 days. The second group was orally given 50 mg/kg of IOLEAgNPs. The third, fourth, and fifth groups were injected intraperitoneally with 10 5 parasitized erythrocytes of P. chabaudi . After 1 h, the fourth group received 50 mg/kg of IOLEAgNPs, while the fifth group orally received 10 mg/kg chloroquine phosphate. The histopathology of the kidney was studied by routine histology method with hematoxylin–eosin staining. The kidney revealed cerebral microvessel congestion, hemorrhages, and necrosis. Cast formation, glomerulonephritis, tubular necrosis, and congestion were observed in the kidney cortex. Consequently, the targeted medical IOLEAgNPs reduced this degeneration impact on renal tissue. Proven that plant-source synthesized IOLEAgNPs play a preventive role as antimalarial agents in female mice infected with P. chabaudi.

The heterogeneity of ovarian cancer (OC) has made developing effective treatments difficult. Nowadays, hormone therapy plays a growing role in the treatment of OC; however, hormone modulators have had only limited success so far. To provide a more rigorous foundation for hormonal therapy for different OC subtypes, the current study used a series of bioinformatics approaches to analyse the expression profiles of genes encoding membrane progesterone (PGRMC1, progestins and the adipoQ receptor [PAQR] family), and androgen (zinc transporter member 9 [ZIP9], OXER1) receptors. Our work investigated also their prognostic value in the context of OC. We found differences in expression of ZIP9 and OXER1 between different OC subtypes, as well as between patient tumour and normal tissues. Expression of mRNA encoding PAQR7 and PAQR8 in a panel of OC cell lines was below the qPCR detection limit and was downregulated in tumour tissue samples, whereas high expression of PGRMC1 and PAQR4 mRNA was observed in rare subtypes of OC cell lines. In addition, chemical inhibition of PGRMC1 reduced the viability of rare OCs represented by COV434 cells. In conclusion, PGRMC1 and PAQR4 are promising targets for anticancer therapy, particularly for rare subtypes of OC. These findings may reflect differences in the observed responses of various OC subtypes to hormone therapy.

To explore the impact of score in patients with diabetes peripheral neuropathy (DPN) treated with traditional Chinese medicine package (TCMP) plus red light therapy and lipoic acid on malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), total antioxidant capacity (TAOC), motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Toronto Clinical Scoring System (TSS). A total of 108 patients with DPN hospitalized in the hospital were chosen and divided into groups with the random number table. In the control group (CG) 54 patients were treated with conventional lipoic acid, and 54 patients in the experimental group (EG) accepted TCMP plus red light on the basis of the CG. The MDA, SOD, TAOC, MNCV, SNCV, and TSS scores before treatment and after treatment were compared between the two groups. Before treatment, there was no statistically significant difference in the levels of oxidation indicators, nerve conduction velocity, and symptom scores between the two groups ( P > 0.05). After treatment, the MDA in the EG was lower than that in the CG, with a statistical significance difference ( P < 0.05). The SOD and TAOC in the EG were higher than those in the CG, and the difference was statistically significant ( P < 0.05). The MNCV and SNCV of median nerve, common peroneal nerve, and tibial nerve in the EG were significantly higher than those in the CG ( P < 0.05). The TSS score of the EG was lower than that of the CG, and the difference was statistically significant ( P < 0.05). The treatment of patients with DPN with lipoic acid plus TCMP and red light therapy can improve the symptoms and signs of disease, promote the recovery of motor and sensory conduction velocity, and optimize the body oxidation indicators. Graphical abstract

In our prior research, it was noted that slit guidance ligand 3 (SLIT3), a member of the SLIT-secreted protein family, may play a potential role in tumorigenesis. In addition, our prior work has found that the SLIT3 gene is highly methylated, especially in advanced-stage lung cancer tissues. Herein, we propose the hypothesis that abnormal SLIT3 expression may be linked to lung cancer development. In this study, decreased SLIT3 at the transcriptome and proteome levels was observed in lung cancer tissues. Furthermore, the downregulation of SLIT3 was related to a higher tumor stage and poorer prognosis. Silencing SLIT3 expression enhanced cell proliferation and migration, indicating potential characteristics of a tumor suppressor gene of SLIT3 in non–small-cell lung cancer (NSCLC). Furthermore, SLIT3 deficiency stimulates UBE2C upregulation and regulates NSCLC progression through Wnt3A/β-catenin signaling. The activation of the WNT signaling pathway was highly correlated with chemoresistance development in lung cancer. In conclusion, SLIT3 deficiency promotes lung cancer onset and progression by modulating UBE2C/WNT signaling. SLIT3/UBE2C/WNT may serve as novel biomarkers and therapeutic targets in NSCLC. Graphical abstract

Calcium homeostasis is correlated closely with the occurrence and development of various cancers. The role of calcium homeostasis in prostate cancer has remained unclear. The present study aimed to investigate the relationship between transmembrane and crimp-crimp domain 1 (TMCO1) and calreticulin (CALR) in the pathological characteristics of prostate cancer and the mechanism of action on prostate cancer metastasis. Effects of CALR recombinant protein and TMCO1 knockdown on prostate cancer cells were investigated using following methods: cell cloning, Transwell, wound scratch assay, JC-1 assay, Fluo-4 Assay, endoplasmic reticulum (ER) fluorescent probe, mitochondrial fluorescence probe, Western blot and Immunofluorescence. TMCO1 and CALR are overexpressed in prostate cancer and knockdown of TMCO1 significantly inhibited the invasion, migration and cell proliferation. Furthermore, knocking down TMCO1 modulated the intensity of ER probes and mitochondrial fluorescence probes, and affected the levels of intracellular calcium ion and mitochondrial membrane potential. In addition, CALR recombinant protein upregulated the expression of epithelial-mesenchymal transition marker, Vimentin, Conversely, knockout of TMCO1 significantly reduced the expression of CALR and Vimentin. Knockout of TMCO1 can reverse the effect of CALR recombinant protein, elucidating the pivotal roles of TMCO1 and CALR in the regulation of prostate cancer metastasis through modulation of calcium homeostasis.

The resistance of tumor cells to chemotherapy drugs is a critical determinant in the recurrence and metastasis of nasopharyngeal carcinoma (NPC). Therefore, it is crucial to identify effective biotargets that can enhance the sensitivity of NPC cells to chemotherapy drugs. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a central role in regulating chemotherapy resistance across various tumor types. However, its specific function in NPC cells remains unclear. This study reveals that hnRNPK is overexpressed in NPC tissues while weakly expressed in normal nasopharyngeal tissues. The expression level of hnRNPK is negatively associated with NPC patient survival. Importantly, hnRNPK is a key inducer of chemotherapy resistance in NPC, as evidenced by the significant increase in NPC cell sensitivity to cisplatin following hnRNPK knockdown. Mechanistically, hnRNPK induces chemotherapy resistance in NPC cells by suppressing the activation of the Akt/caspase 3 pathway. In NPC tumor-bearing mice, hnRNPK knockdown enhances the efficacy of cisplatin chemotherapy. Consequently, this work identifies a potential target for enhancing the sensitivity of NPC cells to chemotherapy. Graphical abstract

Fibrosis is the primary cause of retinal detachment and visual decline. Here, we investigated the role of Prohibitin 2 (PHB2) in modulating fibrosis in ARPE-19 cells stimulated by transforming growth factor (TGF)-β2. The proliferation, migration, and apoptosis of ARPE-19 cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and flow cytometry assays, and levels of fibrosis-associated and pathway-related proteins were determined by performing western blotting. To examine the mechanisms underlying ARPE-19 cell fibrosis, we performed RNA sequencing, protein–protein interaction network, and enrichment analyses. We detected increases in the expression of the fibrosis-related proteins fibronectin and collagen I in response to TGF-β2 treatment, whereas the expression of PHB2 was downregulated. PHB2 overexpression suppressed the proliferation and migration of TGF-β2-stimulated ARPE-19 cells, promoted apoptosis, and inhibited fibrosis and Smad and non-Smad pathways. PHB2 overexpression inhibited the advanced glycation end-product (AGE)–receptor of advanced glycation end-product (RAGE) pathway activated by TGF-β2 treatment, which contributed to enhancing the effects of PHB2 on cellular processes, fibrosis, and Smad and non-Smad pathways. Conversely, exogenous application of AGE counteracted the effects of PHB2 overexpression. We conclude that by suppressing the AGE–RAGE pathway, PHB2 exerts an inhibitory effect on TGF-β2-induced fibrosis in ARPE-19 cells.

Autoimmune encephalitis (AE) associated with autoantibodies against γ-aminobutyric acid-B receptor (GABA B R-AE) is frequently identified in middle-aged and elderly males. The disease is characterized by seizures, mental, and behavioral abnormalities, as well as recent memory decline. Anti-GABA B R antibody-associated encephalitis, presenting with syncope as the first symptom is rare. Here we report a case of AE with syncope as the first symptom. A 55-year-old male presented to the emergency department with transient loss of consciousness, initially diagnosed as syncope. As the disease progressed, the patient exhibited seizures, abnormal mental behavior, and cognitive impairment. Ultimately, the patient was diagnosed with right lung small cell lung cancer. The initial atypical symptoms and the lack of clear imaging features of GABA B R encephalitis hinder early diagnosis. This case highlights the importance of screening for the underlying etiology of syncope in middle-aged and elderly patients.

Lonicera japonica is a well-known medicinal plant, and the Damaohua cultivar is one of the oldest known honeysuckle cultivars in China. The 155,151 bp chloroplast genome of this cultivar was obtained through Illumina sequencing. The genome includes a pair of inverted repeats (IRa and IRb; 23,789 bp each), a large single-copy region (88,924 bp), and a small single-copy (SSC) region (18,649 bp). In total, 127 unique genes were identified: 80 protein-coding, 39 tRNA, and 8 rRNA genes. Only ycf3 contained two introns. Eighty-nine large repetitive sequences and 54 simple sequence repeats were detected. Fifty potential RNA editing sites were predicted. Adaptive evolution analysis revealed that infA, matK, petB, petD, rbcL, rpl16, rpl2, rps3, ycf1, and ycf2 were positively selected, possibly reflecting the specific environmental adaptations of this cultivar. Sequence alignment and analysis revealed several candidate fragments for Lonicera species identification, such as the intergenic regions rpoB-petN, rbcL-accD, and psaA-ycf3. The IR region boundary and phylogenetic analysis revealed that the L. japonica cv. Damaohua chloroplast genome was most closely related to the L. japonica genome, but there were five distinct differences between the two. There are four sites with high variability between L. japonica and L. japonica cv. Damaohua with nucleotide variability (Pi) greater than 0.002, including rps2-rpoC2, atpB-rbcL, ycf1, and ycf1-trnN GUU. The differences between L. japonica and L. japonica cv. Damaohua were further confirmed by the single nucleotide polymorphism sites between these two species. Therefore, this study revealed that the chloroplast genome can serve as a universal super barcode for plant identification, which can identify differences and help distinguish Lonicera japonica from related species. An understanding of Lonicera japonica cv. Damaohua chloroplast genomics and a comparative analysis of Lonicera species will provide a scientific basis for breeding, species identification, systematic evolution analysis, and chloroplast genetic engineering research on medicinal honeysuckle plants. Graphical abstract

The aim of this study was to study the effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on glutathione (GSH) metabolism in human ovarian cancer cells induced by phosphoramide mustard (PM). The experiment was divided into five groups, namely, the blank group (ovarian cancer cells), the control group (ovarian cancer cells + HUC-MSCs), the model group (ovarian cancer cells + PM), the treatment group (ovarian cancer cells + PM + HUC-MSCs), and the inhibitor group (ovarian cancer cells + PM + HUC-MSCs + extracellular signal-regulated protein kinase inhibitor PD98059). The apoptosis rate of ovarian cancer cells was detected by flow cytometry. Intracellular levels of oxidized glutathione (GSSG), GSH, γ-glutamyl cysteine synthetase (γ-GCS), and intracellular reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay. Protein imprinting and real-time fluorescence quantitative PCR were used to detect extracellular regulated protein kinase (ERK), p-ERK heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) protein levels. First, the apoptosis rate in the model group was increased compared with that of the blank group. The levels of γ-GCS, p-ERK, HO-1, and Nrf-2 decreased, while the levels of malondialdehyde, GSSG, and ROS increased. Second, compared with the model group, the apoptosis rate in the treatment group decreased. GSH, γ-GCS, p-ERK, HO-1, and Nrf2 levels increased. Malondialdehyde, GSSG, and ROS levels decreased. Third, after the administration of ERK inhibitor, the apoptosis rate of cells increased. GSH, p-ERK, and HO-1 levels decreased. GSSG and ROS levels increased ( P < 0.05), and γ-GCS level had a downward trend compared with the treatment group. To conclude, HUC-MSCs may regulate the ERK–Nrf2–HO-1 pathway to increase γ-GCS expression and GSH production, reduce ROS level and apoptosis of ovarian cancer cells, and improve antioxidant capacity.

Recent studies have reported that electroacupuncture (EA) can treat osteoporosis, but most of which were based on the “kidney governing bones” theory. However, the ancient Chinese medical textbook Huangdi Neijing pointed out that “Gallbladder Meridian of Foot Shaoyang” correlates with bone diseases, including osteoporosis, although the therapeutic regimens were lost after the Tang Dynasty. Here, we explored whether EA at GB points improves osteoporosis and its underlying mechanism. We constructed ovariectomized mice and treated them with EA at GB30 ( Huantiao ), GB34 ( Yanglingquan ), and GB39 ( Xuanzhong ) acupoints. EA treatment significantly improved bone parameters in osteoporotic mice, as evidenced by micro-computed tomography and histological assessment. Additionally, EA treatment elevated the serum levels of estradiol and SOD that were downregulated in osteoporotic mice. Transcriptome and qPCR results verified that EA treatment upregulated the expression of genes associated with bone formation. Moreover, transcriptome analysis revealed differential enrichment of the PI3K–Akt pathway. Furthermore, Western blot analysis demonstrated that estradiol partially counteracted a reduction in p-AKT expression induced by hydrogen peroxide. These findings indicate that EA treatment increases serum estradiol levels in mice, thus inhibiting osteoporosis induced by oxidative stress. This effect is achieved by activating the PI3K–Akt signaling pathway.

Diabetic nephropathy (DN) presents a significant public health challenge due to its high rate of incidence and severe health consequences. Renalase has been identified as having renal-protective properties. A key contributor to albuminuria in DN patients is podocyte loss. The function of Renalase in DN in relation to podocyte activity needs to be explored further. In this study, we assessed the therapeutic efficacy of Renalase by monitoring changes in urine protein levels and podocyte health in db/db mice. We also induced hyperglycemia (HG) to stimulate podocyte clone 5 (MPC5) cells to create a model of podocyte loss in DN. Through co-culturing these cells with Renalase or H 2 O 2 , we investigated the process by which Renalase prevents podocyte loss in vitro . In db/db mice, Renalase expression was significantly reduced, and adenoviral-mediated Renalase expression markedly alleviated DN symptoms and proteinuria. Furthermore, podocytopathy in db/db mice was significantly mitigated. In vitro , Renalase improved the expression of podocyte marker proteins, podocin, and nephrin, which are reduced by HG, as well as decreased oxidative stress and restrained apoptosis. Our findings suggest that Renalase can mitigate DN by reducing proteinuria through podocyte protection, potentially by inhibiting oxidative stress and apoptosis. These data suggest that Renalase may serve as a novel therapeutic agent in suppressing DN. Graphical abstract Annotation: The red line represents inhibition; Blue represents improvement

Dicranostigma leptopodum ( Maxim .) Fedde, an intriguing plant of the Papaveraceae family, exhibits numerous physiological activities, including antitumor, cytotoxic, immune-boosting, antibacterial, antioxidant, insecticidal, smooth muscle modulation, antiarrhythmic, fluorescent probe capabilities, as well as hypolipidemic and hypoglycemic effects. The plant’s diverse pharmacological actions are believed to be attributed to its rich reservoir of alkaloids distributed throughout the entire plant. This review encompasses an exploration of the chemical constituents, pharmacological activities, species distribution, extraction and separation methodologies, and content determination of D. leptopodum , aiming to contribute to its further advancement in medicinal development. Graphical abstract

Lung cancer is considered the most ubiquitous malignant form of cancer, and the current treatment strategies do not offer effective outcomes to the patients. The present study examined the effectiveness of natural drugs delphinidin (DN) and oroxylin A (OA) in inhibiting the development of lung cancer cells (A549) through the blocking of the Signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) intervene signaling pathways. These included cytotoxicity assessments, reactive oxygen species (ROS) levels, apoptotic morphological features, mitochondrial membrane potential (ΔΨm), nuclear fragmentation, and cell cycle analysis. Furthermore, the combination of DN and OA treatments on the expression of STAT-3, FAK, and various proliferation and apoptotic proteins was studied using western blotting. The results we have obtained are that the combination of DN and OA causes significant cytotoxicity, ROS, alteration of ΔΨm, and nuclear fragmentation, resulting in apoptosis of A549 cells. Furthermore, A549 cells treated with DN and OA concurrently displayed increased cell cycle arrest at the G2/M phase. Additionally, the combined DN and OA treatment inhibited the expression of STAT3 and FAK, suppressing proliferation and the induction of pro-apoptotic protein expressions in A549 cells. Thus, a combination of DN and OA could be used as a therapeutical approach to malignant forms of lung cancer.

A 60-year-old woman with bilateral lower extremity oedema for several days was admitted to the hospital on 21 November 2023. Previously, after receiving rectal cancer resection in February 2023, she had been receiving drug chemotherapy, during which she had normal urinalysis and renal function. However, 10 days before admission, after the drug regimen was adjusted to tislelizumab + fruquintinib, she developed bilateral lower extremity oedema with foamy urine; this was later extended to facial oedema. After a histologic examination of renal biopsy, it was judged as drug-induced glomerular microangiopathy (GMA) with focal segmental glomerulosclerosis-like lesions accompanied by immune complex-mediated glomerulonephritis. The condition was controlled by stopping the anti-tumour drug, lowering glucose with linagliptin, and providing renal protection with Nephritis Rehabilitation Tablets, and the patient recovered well at the follow-up visit after 6 months. This case may be GMA induced by tislelizumab or fruquintinib and was examined in this study.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as “cardiorenal syndrome,” where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure–chronic heart failure (CRF–CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a “two-step surgical method”), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF–CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF–CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF–CHF groups showed significant increases in LVEDP and LVW/BW ( P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels ( P < 0.05). Compared to the CRF and CHF groups, the CRF–CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels ( P < 0.05). Rats with CRF–CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

This study evaluated the therapeutic efficacy of the gastrointestinal health anti-diarrheal mixture (GHAM) on diarrhea induced by spleen deficiency, focusing on its modulation of gut microbiota. Using specific pathogen-free Wistar rats, a spleen deficiency model was created through senna leaf gavage. Rats were divided into control, model, positive control, and GHAM treatment groups. After a 14-day treatment, fecal samples were analyzed via 16S rDNA sequencing to assess microbiota alterations. GHAM significantly mitigated diarrhea and enhanced food intake and fecal quality. It increased the abundance of beneficial bacteria, such as Romboutsia and Clostridium_sensu_stricto_1 , and decreased the levels of diarrhea-associated bacteria, such as Prevotellaceae and Bacillus , thereby improving microbiota functionality. GHAM’s modulation of gut microbiota structure and function effectively alleviated spleen deficiency-induced diarrhea, positioning it as a potential natural herbal treatment for gastrointestinal ailments. This study lays the groundwork for further exploration of GHAM’s regulatory impact on gut health.

Radiotherapy is a cornerstone in the treatment of various tumors, yet radioresistance often leads to treatment failure and tumor recurrence. Several factors contribute to this resistance, including hypoxia, DNA repair mechanisms, and cancer stem cells. This review explores the diverse elements that drive tumor radiotherapy resistance. Historically, resistance has been attributed to cellular repair and tumor repopulation, but recent research has expanded this understanding. The tumor microenvironment – characterized by hypoxia, immune evasion, and stromal interactions – further complicates treatment. Additionally, molecular mechanisms such as aberrant signaling pathways, epigenetic modifications, and non-B-DNA structures play significant roles in mediating resistance. This review synthesizes current knowledge, highlighting the interplay of these factors and their clinical implications. Understanding these mechanisms is crucial for developing strategies to overcome resistance and improve therapeutic outcomes in cancer patients.

Nakaseomyces glabratus , previously known as Candida glabrata , has the great potential to cause systemic fungal infections despite its similarity to baker’s yeast. Its pathogenicity is attributed to the production of numerous virulence factors, among which the YPS genes ( YPS1 – YPS11 ) encoding aspartyl proteases have yet to be sufficiently characterized, and limited studies suggest their involvement in cellular homeostasis. The study’s novelty is an investigation of the role of YPS in N. glabratus’s ability to adapt to different host environments. For this purpose, we isolated RNA from N. glabratus cells grown in both host niche-mimicking culture media, such as artificial saliva (AS) and vagina-simulating media (VS), as well as standard yeast media (RPMI 1640 and YPDA). We then performed quantitative real-time PCR to evaluate YPS gene expression at different growth phases. At the early logarithmic phase, we observed a general increase in the expression levels of YPS genes; however, at the stationary phase, high expression levels were maintained for YPS7 in RPMI 1640 and YPDA media and YPS6 in RPMI 1640 and AS media. In addition, although the VS medium does not promote the proliferation of N. glabratus , the yeast can survive in an acidic environment, and the significantly overexpressed gene is YPS7 . These findings underscore the significant modulation of N. glabratus YPS gene expression in response to external environmental conditions. This research provides insights into the molecular basis of N. glabratus pathogenicity and highlights new potential targets for antifungal therapy. Graphical abstract

Peripheral blood samples from 15 septic patients admitted within 24 h and 8 healthy volunteers were used to conduct RNA-seq. Quantitative PCR of THP1 cells was performed to investigate the expression levels of the selected key genes. A total of 1,128 differential genes were identified, 721 of which were upregulated and 407 were downregulated. These genes are mainly involved in neutrophil activation, T cell regulation, immune effector process regulation, cytokine receptor activity, and cytokine binding. The six target genes were ELANE, IL1R2, RAB13, RNASE3, FCGR1A, and TLR5. In the sepsis group, FCGR1A and TLR5 were positively associated with survival compared to ELANE, IL1R2, RAB13, and RNASE3, which were adversely associated with survival. Furthermore, a meta-analysis based on public databases revealed an increased expression of these six target genes in the peripheral blood of patients with sepsis. In addition, we discovered that monocytes primarily express these genes. Using qPCR, we confirmed that these six important genes were highly expressed in lipopolysaccharide-treated THP1 cells. In summary, these findings suggest that ELANE, IL1R2, RAB13, RNASE3, FCGR1A, and TLR5 may influence the prognosis of patients with sepsis and provide novel insights and potential avenues for the treatment of sepsis.

This study aims to comprehensively investigate the role of coagulation factor II thrombin receptor (F2R) in breast cancer (BC) and to evaluate its potential as a biomarker in this context. Data on female BC were retrieved from the TCGA database. Comparative analyses were performed, including enrichment analysis, tumor immune microenvironment analysis, drug sensitivity testing, molecular docking, and cell-based experiments, to assess the expression and function of F2R in BC. Statistical analyses and graphical representations were conducted using R software. The study confirmed a significant upregulation of F2R in BC, which was associated with a more favorable prognosis. Clinical correlation analysis revealed a strong association between F2R expression and key clinical parameters, such as estrogen receptor and progesterone receptor status. Additionally, genes co-expressed with F2R were significantly linked to various biological processes, including cell cycle regulation, oxidative phosphorylation, ribosomal function, and extracellular matrix interactions. F2R also showed associations with immune modulators, particularly CD200 and NRP1. Drug sensitivity analysis, molecular docking, and cell experiments consistently demonstrated positive correlations between F2R expression and sensitivity to dasatinib. This study underscores the potential of F2R as a valuable biomarker in BC, providing insights into the molecular mechanisms underlying tumorigenesis. Graphical abstract

Mucinous carcinoma is a rare clinical disease. Although well described in the literature, a mucinous carcinoma diagnosis is often difficult due to its atypical clinical presentation. We report a female patient with a right inguinal mass and ileocecal myxo carcinoma who was misdiagnosed as having a right incarcerated inguinal hernia invading the peritoneum incarcerated inguinal hernia and ileocecal myxo carcinoma. Intraoperative exploration of the mucous material occupying the patient’s right lower abdominal cavity and exclusion of right inguinal incarcerated hernia revealed the misdiagnosis. The first clinical manifestations of ileocecal mucinous carcinoma are often not readily apparent and may be misdiagnosed as an incarcerated inguinal hernia. When a color ultrasonography suggests an incarcerated inguinal hernia, an abdominal CT should be considered, and an enhanced CT should be performed as needed to observe the abdominal cavity. Ileocecal mucinous carcinoma should also be distinguished from other diseases with similar clinical manifestations. The patient had received conservative treatment for acute appendicitis, and it is recommended to conduct a B-ultrasound, CT, and other reviews after surgery. Clinicians should be aware of missed surgical opportunities following appendicitis caused by mucinous adenoma.

Bladder cancer (BC) is the tenth most common tumor worldwide, characterized by high incidence rates and mortality. This study aimed to explore the role of Methyltransferase like 13 (METTL13) in BC cells. J82 and T24 cells were cultured for in vitro experiments. Cell viability, migration, and invasion were assessed using CCK-8 and transwell assays. Senescence-associated beta-galactosidase (SA-β-gal) levels were detected using a β-galactosidase staining kit. METTL13 and cell cycle-related protein levels were quantified using RT-qPCR and Western blotting. The results showed that METTL13 was upregulated in BC cells. Silencing METTL13 decreased cell viability, migration, and invasion in BC cells, whereas METTL13 overexpression increased these parameters. Additionally, METTL13 knockdown inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Inhibition of the PI3K/AKT pathway reversed the effects of METTL13 on cell viability, migration, invasion, and cell cycle-related proteins in BC cells. In vivo experiments showed that METTL13 knockdown inhibited tumor growth and development. In conclusion, this study demonstrated that METTL13 promoted the malignant behaviors of BC cells through activation of the PI3K/AKT signaling pathway. METTL13 may be a promising therapeutic target for BC in the future. Graphical abstract

Both irreversible electroporation (IRE) and radiofrequency ablation (RFA) are viable ablation methods for localized treatment of liver tumors. We conducted a meta-analysis to access the efficacy and safety of IRE and RFA in liver cancer treatment. Clinical studies on IRE and RFA for the treatment of liver cancer were collected from PubMed and CNKI until June 2023. We screened the literature for ablation success rates at 1 month post-operation, extracting keywords such as “ablation success rate,” “technical success rate,” “recurrence rate,” and “complication” for meta-analysis. A total of 37 articles were included: 24 related to RFA involving 1,685 cases and 13 related to IRE involving 524 cases. The results demonstrate that ablation success rates at post-operative 1 month for IRE and RFA were 86% (95% CI: 82–89%) and 87% (95% CI: 81–92%), respectively. Technical success rates were 96% (95% CI: 88–100%) and 99% (95% CI: 96–100%). In addition, the recurrence rate was 16% (95% CI: 12–22%) in RFA group and 16% (95% CI: 9–23%) in IRE group. In terms of safety, the RFA had a complication rate of 28% (95% CI: 10–50%) and the IRE had a rate of 26% (95% CI: 13–43%). In conclusion, IRE and RFA exhibit similar ablation success rates at 1 month post-operation and comparable complication rates, making them both safe and effective treatment options.

Colorectal cancer (CRC) is a common malignant tumor characterized by a high degree of invasiveness, and since zinc-α2 glycoprotein (ZAG) has been implicated in the progression of several malignancies, this study was designed to investigate the role of ZAG in CRC. Its expression was assessed using the GEPIA database, and short hairpin RNA (shRNA) interference was conducted to create ZAG knockdown in CRC cell lines. We also conducted lipid synthesis, cell proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) experiments to elucidate the effects of ZAG expression on CRC, as well as explored the potential underlying mechanistic pathways. Our findings reveal that ZAG is overexpressed in CRC. In vitro , ZAG knockdown resulted in the suppression of lipid production, cell division, and EMT while concurrently promoting apoptosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway was found to mediate the effects of ZAG on CRC cells. In conclusion, the downregulation of ZAG can inhibit CRC cell survival, EMT, and lipid production via the PI3K/AKT/mTOR signaling pathway. Graphical Abstract

Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy characterized by glucose intolerance, which poses risks to both maternal and fetal health. Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, exhibits various biological functions and has been implicated in the modulation of several diseases. However, the regulatory effects and underlying mechanisms of Baicalein in GDM progression remain unclear. In this study, we found that Baicalein ameliorates metabolic disturbances in GDM mice by improving glucose tolerance, insulin sensitivity, fasting blood glucose levels, and plasma insulin levels. Additionally, Baicalein treatment positively impacted litter size and birth weight. GDM mice exhibited increased inflammation and oxidative stress, which were mitigated following Baicalein administration (40 mg/kg). Furthermore, elevated protein levels of NLRP3, IL-1β, and IL-18 observed in GDM mice were reduced by Baicalein treatment. In conclusion, Baicalein inhibits the NLRP3 inflammasome and alleviates placental inflammation and oxidative stress associated with GDM. These findings provide valuable insights into the potential therapeutic role of Baicalein in managing GDM.

Breast cancer (BC) has a prevalence rate of 21.8% among Saudi women and ranks as the third leading cause of death in Western nations. Nanotechnology offers innovative methods for targeted BC therapy, and this study explores the use of single-walled carbon nanotubes (SWCNTs) for delivering the senna leaf extract. The study evaluated the effects of increasing dosages of senna leaf extract conjugated to SWCNTs on MCF-7 cells. Cell viability was assessed using the MTT assay, while Giemsa staining revealed morphological changes. Additionally, the comet assay and agarose gel electrophoresis were employed to evaluate the pro-apoptotic potential. The potential of mitochondrial membrane and the production of reactive oxygen species (ROS) were investigated using the JC-1 dye. The results indicated that treated cells exhibited apoptotic characteristics, including elevated ROS levels and decreased mitochondrial membrane potential. In summary, the application of nanotechnology to deliver the senna leaf extract shows promise as a herbal treatment for BC, suggesting a potential breakthrough in combating this widespread and deadly disease.

To investigate the biological role of MFAP5 in endometrial cancer (EC). HEC-1-A and Ishikawa cells overexpressing MFAP5 were created. Cell proliferation, apoptosis, migration, and invasion were evaluated using CCK8, colony formation, flow cytometry, and transwell assays. A western blot was used to analyze the expression of markers affiliated with the epithelial–mesenchymal transition process and AKT/mTOR pathway. As a result, MFAP5 was found to be down-regulated in EC. Overexpression of MFAP5 suppressed proliferation and promoted apoptosis of HEC-1-A and Ishikawa cells, as evidenced by the inhibition of cell viability and colony formation, and the increase in cell apoptosis rate. Besides, overexpression of MFAP5 attenuated the abilities of cell migration and invasion, as well as reduced MMP2 and MMP9 protein expression. Furthermore, E-cadherin protein level was elevated, while N-cadherin and α-SMA protein levels were decreased, and the phosphorylation of AKT and mTOR was reduced in cells overexpressing MFAP5. Our findings indicate that MFAP5 overexpression inhibits the malignant behaviors of EC cells, possibly by blocking the AKT/mTOR pathway, suggesting that MFAP5 may be a new therapeutic target for EC.

This study sought to explore the value of major ozonated autohemotherapy (MOA) as a treatment for spinal cord injury (SCI) in a rat model system. In total, 54 female Sprague-Dawley rats were randomized into sham-operated, SCI model, and MOA treatment groups. We found that relative to the SCI model group, rats that underwent MOA treatment exhibited improved locomotor scores on days 14, 21, and 28 after injury ( p < 0.05) together with reduced residual urine on days 5, 7, 14, and 21 after injury ( p < 0.05). MOA treatment also lowered proinflammatory TNF-α, IL-1α, and C1q levels on day 3 post-injury ( p < 0.05), decreased malondialdehyde levels, and enhanced superoxide dismutase activity ( p < 0.001). Activated astrocytes in MOA-treated rats exhibited larger soma and higher levels of extracellular matrix secretion, whereas reactive microglia in the MOA group presented with a ramified morphology in contrast to the amoeboid morphology exhibited by these cells in SCI model rats. MOA offers potential value as a means of protecting spinal cord integrity, potentially through anti-inflammatory, antioxidant, and regulatory effects that shape the polarization of astrocytes and microglia.

Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g., MAP2 for dendrites and TAU for axons, while the scaffolding proteins AnkG and TRIM46 mark the axon-initial-segment. In tauopathies, such as Alzheimer’s disease (AD), TAU sorting, and neuronal polarity are disrupted, leading to MT loss. However, modeling and studying MTs in human neuronal cells relevant to the study of AD and TAU-related neurodegenerative diseases (NDD) is challenging. To study MT dynamics in human neurons, we compared two cell culture systems: SH-SY5Y-derived neurons (SHN) and induced pluripotent stem cell-derived neurons (iN). Using immunostaining and EB3-tdTomato time-lapse imaging, we found AnkG absent in SHN but present in iN, while TRIM46 was present in both. TAU and MAP2 showed axonal and dendritic enrichment, respectively, similar to mouse primary neurons. Both neuron types exhibited polarized MT structures, with unidirectional MTs in axons and bidirectional MTs in dendrites. Polymerization speeds were similar; however, iNs had more retrograde MT growth events, while SHN showed a higher overall number of growth events. Thus, SHN and iN are both suitable for studying neuronal cell polarity, with SHN being particularly suitable if the focus is not the AIS.

This study aimed to investigate the differential expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in relation to the Toll-like receptor (TLR)/nuclear factor κB (NF-κB) signaling pathway in an obese rat model. A total of 200 8-week-old male Wistar rats were randomly assigned to a control group (Ctrl, n = 40) and an observation group (Obs, n = 160), with obesity induced through a high-fat diet. Following modeling, the Obs group was further divided into a model group, a PI3K/AKT inhibition group, a TLR/NF-κB inhibition group, and a combined PI3K/AKT + TLR/NF-κB inhibition group, with 40 rats in each. Metabolic changes were assessed by monitoring the glucose infusion rate (GIR), as well as conducting an intraperitoneal glucose tolerance test (IPGTT) and an intraperitoneal insulin tolerance test (IPITT). Hematoxylin and eosin staining was utilized to observe morphological changes in adipose tissue, while Western blotting was employed to detect the expression levels of proteins associated with the PI3K/AKT and TLR/NF-κB signaling pathways in adipose tissue. The results indicated that the Obs group exhibited significantly higher blood glucose and insulin levels during the IPGTT and IPITT experiments compared to the Ctrl group ( P < 0.05). Additionally, the GIR, as well as the expression levels of p-PI3K and p-AKT proteins in the Obs group, were significantly lower than those in the Ctrl group ( P < 0.05). In both the PI3K/AKT inhibition group and the combined PI3K/AKT + TLR/NF-κB inhibition group, the expression of relevant proteins further declined ( P < 0.05). These findings suggest that while a high-fat diet decreases the activity of the PI3K/AKT signaling pathway, it concurrently promotes inflammatory responses by upregulating the TLR-4 and NF-κB signaling pathways, indicating a critical role for these pathways in obesity-related metabolic abnormalities. Graphical abstract This study investigated the effects of activation and inhibition of the PI3K/AKT and TLR-4/NF-κB signaling pathways on insulin resistance in a high-fat diet-induced obese rat model. The results indicate that a high-fat diet can activate these signaling pathways by regulating the expression of related proteins, affecting metabolic health. Rat PI3K/AKT pathway protein.

Retinal diseases, which can lead to significant vision loss, are complex conditions involving various cellular and molecular mechanisms. The interleukin-6 (IL-6) family, particularly Oncostatin M (OSM), has garnered attention for their roles in retinal inflammation, angiogenesis, and neuroprotection. This comprehensive review explores the dual nature of OSM and other IL-6 family members in retinal pathophysiology, highlighting their contribution to both degenerative and regenerative processes. The review also examines current research on OSM’s interaction with key signaling pathways and discusses the potential of OSM and the IL-6 family as potential therapeutic targets. Understanding these mechanisms could lead to innovative treatments that modulate OSM activity, offering new avenues for managing retinal diseases and contributing to the development of more effective interventions.

Otitis media (OM) is a prevalent childhood ear disease characterized by inflammation of the middle ear cavity, which can lead to ear pain, fever, and hearing loss. The pathogenesis of OM is multifaceted, encompassing a variety of factors including bacterial or viral infections, host immune responses, and the function of middle ear epithelial cells. Boswellic acid (BA), a natural triterpene compound extracted from frankincense resin, has been proven to possess significant anti-inflammatory and immunomodulatory effects. This study aims to investigate the effects of BA on lipopolysaccharide (LPS)-stimulated inflammatory responses and apoptosis in human middle ear epithelial cells (HMEECs) and its potential mechanisms. Our findings demonstrated that BA enhances the proliferation of LPS-stimulated HMEECs and concurrently inhibits their apoptosis. In addition, BA blocked LPS-stimulated HMEEC inflammation. Mechanistically, BA suppressed the NF-κB/IκBα axis in LPS-stimulated HMEECs. In conclusion, BA effectively inhibits LPS-stimulated inflammation and apoptosis by mediating the NF-κB/IκBα axis, highlighting its potential as a therapeutic agent for OM.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death and disability worldwide, and circRNA dysregulation is functionally associated with COPD. This study explored the potential of circRMRP and circRPL27 as biomarkers of COPD. Blood samples from COPD patients and healthy controls were collected. COPD patients were divided into mild, moderate, and severe groups according to lung function. Quantitative real-time polymerase chain reaction technology was used to determine the expression of circRPL27 and circRMRP in COPD. Receiver operating characteristic curve was drawn to explore the value of circRMRP and circRPL27 in diagnosing COPD. circRMRP and circRPL27 levels were elevated in serum of COPD patients and increased with the severity of COPD. CircRMRP and circRPL27 were associated with smoking history, WBC, and FEV1/FVC, and were positively correlated with smoking history and WBC, and negatively correlated with FEV1/FVC. In COPD, both circRMRP and circRPL27 had diagnostic values, but circRPL27 was better. circRMRP and circRPL27 may be useful non-invasive biomarkers for COPD diagnosis.

We investigated the protective effect of the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) on cardiomyocyte injury induced by HCN1 channel overexpression, and explored the underlying mechanisms. An HCN1 overexpression vector was constructed and transfected into H9C2 cells, followed by PDTC treatment. The experiments comprised the following groups: control, control + PDTC, overexpression negative control, HCN1 overexpression (HCN1-OE), and combined HCN1-OE + PDTC groups. Cell proliferation was assessed using the CCK8 assay, while apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. ELISA kits were used to determine the levels of malondialdehyde, superoxide dismutase, and interleukin-1 beta. The HCN1-OE group exhibited increased apoptosis, elevated ROS, and decreased survival. Western blot (WB) analysis revealed increased levels of p65, p-IκB, IKKβ, NLRP3, Beclin-1, and LC3 II/I proteins in the HCN1-OE group. PDTC treatment for 48 h post-HCN1-OE resulted in improved cell viability, reduced apoptosis, and decreased ROS in the HCN1-OE + PDTC group. Immunofluorescence and WB analysis indicated a reduction in HCN1 and NF-κB pathway protein levels in the HCN1-OE + PDTC group. In conclusion, PDTC provided protection against HCN1-induced cardiomyocyte injury, potentially by modulating inflammatory cytokines and regulating the IKKβ/IκB/NF-κB signaling pathway.

Moroccan Cannabis sativa L. seeds were investigated for their phenolic profile and antidiabetic potential. Ultra-high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry analysis revealed a rich phenolic composition, including benzoic acid, cannabisin B, genistein, and epicatechin. In vitro , the seed extract exhibited potent α-amylase inhibitory activity (half-maximal inhibitory concentration = 25.02 ± 4.03 μg/mL). In vivo studies in diabetic rats demonstrated significant hypoglycemic, hypolipidemic, hepatoprotective, and nephroprotective effects. Molecular docking studies further supported these findings, revealing strong interactions between identified phenolic and the α-amylase enzyme. These results highlight the potential of C. sativa seeds as a natural source of bioactive compounds for diabetes management.

Breast cancer is a common malignant tumor of women. Ki67 is an important biomarker of cell proliferation. With the quantitative analysis, it is an important indicator of malignancy for breast cancer diagnosis. However, it is difficult to accurately and quantitatively evaluate the count of positive nucleus during the diagnosis process of pathologists, and the process is time-consuming and labor-intensive. In this work, we employed a quantitative analysis method of Ki67 in breast cancer based on deep learning approach. For the diagnosis of breast cancer, according to breast cancer diagnosis guideline, we first identified the tumor region of Ki67 pathological image, neglecting the non-tumor region in the image. Then, we detect the nucleus in the tumor region to determine the nucleus location information. After that, we classify the detected nucleuses as positive and negative according to the expression level of Ki67. According to the results of quantitative analysis, the proportion of positive cells is counted. Combining the above process, we design a breast Ki67 quantitative analysis pipeline. The Ki67 quantitative analysis system was assessed on the validation set. The Dice coefficient of the tumor region segmentation model was 0.848, the Average Precision index of the nucleus detection model was 0.817, and the accuracy of the nucleus classification model was 96.66%. Besides, in clinical independent sample experiment, the results show that the proposed breast Ki67 quantitative analysis system achieve excellent correlation with the diagnosis efficiency of doctors improved more than ten times and the overall consistency of diagnosis is intra-group correlation coefficient: 0.964. The research indicates that our quantitative analysis method of Ki67 in breast cancer has high clinical application value.

Bacteriocins produced by Bacillus subtilis have gained recognition for their safe use in humans. In this study, we aimed to assess the inhibitory activity of an antimicrobial peptide synthesized by the wild-type strain of B. subtilis against the notorious pathogen Pseudomonas aeruginosa . Our investigation employed the broth microdilution method to evaluate the inhibitory potential of this peptide. Among the four different pathogen strains tested, P. aeruginosa exhibited the highest susceptibility, with an inhibition rate of 29.62%. In parallel, we explored the cultivation conditions of B. subtilis , recognizing the potential of this versatile bacterium for applications beyond antimicrobial production. The highest inhibitory activity was achieved at pH 8, with an inhibition rate of 20.18%, indicating the potential for optimizing pH conditions for enhanced antimicrobial peptide production. For the kinetics of peptide production, the study explored different incubation periods and agitation levels. Remarkably, the highest activity of B. subtilis was observed at 24 h of incubation, with an inhibition rate of 44.93%. Finally, the study focused on the isolation of the antimicrobial peptide from the cell-free supernatant of B. subtilis using ammonium sulfate precipitation at various concentrations. The highest recorded activity was an impressive 89.72% achieved at an 80% concentration. Graphical abstract

The study focused on the contribution of effective microorganisms (EM) and their consortia, used in commercial biological preparations and formulations for soil revitalization, to the degradation of a mixture of 13 polycyclic aromatic hydrocarbons (PAHs) commonly found in the soil environment. PAHs, diverse forms of which are present in the environment, never occur individually but always as a part of a chemical mixture. Therefore, the research presented in this article, focusing on the EM impact on the mixture of PAHs, reflects the conditions most similar to natural ones. On Day 35 of the experiment, PAH levels decreased by 75.5–95.5%. The highest PAHs degradation efficiency was achieved for fluorene, with a preparation containing eight bacteria strains from the Bacillus genus: B. coagulans, B. amyloliquefaciens, B. laterosporus, B. licheniformis, B. mucilaginosus, B. megaterium, B. polymyxa, and B. pumilus . All tested preparations containing bacterial consortia and a preparation with the yeast S. cerevisiae intensified the PAHs degradation more effectively than formulations including only the yeast Yarrowia lipolytica or a mixture of Debaryomyces hansenii and Bacillus . The designed and proposed research will contribute to the development of biotechnological methods – bioremediation by microorganisms that are safe for the human and environment health.

The abundance of Panonychus citri McGregor 1916 (Acari: Tetranychidae) and its associated enemies ( Euseius stipulatus Athias-Henriot, 1960; Typhlodromus sp.; Phytoseiulus persimilis Athias-Henriot, 1957) was studied on two 12-year-old citrus cultivars, specifically Clementine “Nules” ( Citrus Clementina ) and Valencia ( Citrus sinensis ), in the Gharb region of Morocco. Throughout the entire monitoring period in the Valencia late cultivar, the density of the spider mite P. citri on leaves was notably higher at 38.0% ( n = 1,212 mobile forms). Predator P. persimilis exhibited a leaf occupancy of 25.0% ( n = 812), followed by Typhlodromus sp. at 20.0% ( n = 643). Conversely, the abundance of E. stipulatus was lower at 17.0% ( n = 538). In the Nules variety, P. citri abundance recorded a higher percentage at 48.0% ( n = 1,922). E. stipulatus emerged as the most abundant predator at 23.0% ( n = 898), followed by P. persimilis with 16.0% ( n = 639). Meanwhile, the population of Typlodromus sp. remained notably low at 13.0% ( n = 498). Regarding the fluctuation of the different mites studied on the two cultivars across monitoring dates, the period from May 4 to June 1 was characterized by low temperatures and a diminished presence of mite populations ( P. citri, E. stipulatus, Typhlodromus sp., and P. persimilis ). However, from June 7 to June 19, characterized by high temperatures, a notable increase in the presence of mite populations was observed. As regards the effect of the variety on the different mites studied, the varietal impact was significant.

Ethnobotanical studies revealed the experience and knowledge of people who learned the therapeutic virtues of plants through trials and errors and transferred their knowledge to the next generations. This study determined the ethnobotanical use of Juniperus drupacea (Andiz) in the Antalya province and the current and future potential distribution areas of J. drupacea in Türkiye during 2041–2060 and 2081–2100 according to the SSP2-4.5 and SSP5-8.5 scenarios and based on the IPSL-CM6A-LR climate change model. The very suitable areas encompassed 22379.7 km 2 . However, when the SSP2-4.5 scenario was considered, the areas most suitable for J. drupacea comprised 6215.892 km 2 for 2041–2060 and 378.318 km 2 for 2081–2100. Based on the SSP5-8.5 scenario, the area most suitable for J. drupacea was 979.082 km 2 for 2041–2060. However, no suitable areas were identified with the SSP5-8.5 scenario for 2081–2100. Considering the models for the future estimated distribution areas of J. drupacea , serious contractions endangering the species are predicted in its distribution areas. Therefore, scientific research should focus on identifying J. drupacea populations and genotypes that demonstrate resilience to future drought conditions resulting from climate change. This endeavor is crucial as it holds significant ecological and economic values.

The common squid, Todarodes pacificus , is an important commercial species that inhabits the northwest Pacific Ocean, particularly the East Japan Sea, the Pacific coast of Japan, and the East China Sea. In this study, we chose 29 individuals from three areas: one type from the Sea of Japan and two types from the East China Sea. A total of 43,529 SNPs were obtained using genotyping-by-sequencing (GBS). Our analyses revealed low genetic diversity and genetic differentiation in each type. Heterozygote deficiency and inbreeding have caused this low level of genetic diversity. Population structure analysis indicated that the three types were genetically similar, which may be attributed to strong gene flow combined with the demographic history events during the last 2 million years. This new GBS application technique provides valuable information for the conservation of marine species genetics and could be useful for the effective management of this resource.

The genus Pistacia , with its species having notable ecological, economic, and medicinal implications, demonstrates remarkable environmental adaptability. The central objective of the study is to analyze interspecific variations between Pistacia atlantica subsp. atlantica and Pistacia terebinthus across three distinct bioclimatic zones in the Middle Atlas region of Morocco. The methodology includes collecting dendrometric measurements and conducting macromorphological examinations on these two taxa, with a detailed analysis of 27 qualitative and quantitative variables. A micro-morphological analysis of leaves, using scanning electron microscopy (SEM), is employed to explore specific features such as size and stomatal density, as well as qualitative aspects like epidermal cell shape and trichomes. Dendrometric measurements have revealed that the canopy surface and the number of trunks per tree can serve as distinctive features between the two species. Regarding the sex ratio of Pistacia atlantica subsp. atlantica , 59% of the examined trees are males, primarily associated with the jujube tree in arid zones and the dwarf palm in humid areas. In contrast, female Pistacia terebinthus exhibit a similar percentage, predominantly associated with oak groves and cade juniper in their distribution areas. Principal component analysis of biometric measurements emphasized a significant disparity between the two species, representing 60.25% of the total variance. The use of SEM unveiled new features facilitating the identification of the two species. By leveraging the macromorphological and micromorphological variability of pistachio trees, we can qualify those best suited to diverse bioclimates. In this regard, we suggest incorporating them into reforestation and rehabilitation programs aimed at restoring our declining ecosystems.

The lichen-rich pine forests of Cladonio-Pinetum represent special habitats protected under the Natura 2000 scheme. A rapid decline in their density has been observed in recent years. Macrofungi are an important component of the community and sensitive bioindicators; therefore, observations of the response of their sporocarps can be used to draw conclusions about changes induced in habitats. In our study, we tried to detect differences in species richness, composition, and biomass of the ectomycorrhizal fungal communities in areas rich in lichens indicating the good state of the community, and rich in bryophytes signaling its progressive degradation. The influence of precipitation and temperature on species richness and biomass was checked, and the possibility of using the sporocarps-based method to assess the effectiveness of active protection treatments, which are a form of partial protection carried out to maintain specific natural habitats. For detailed studies, six plots were selected from which sporocarps were collected, dried and weighed. A total of 1,575 sporocarps, representing 49 taxa were collected. A higher number of taxa (39) in lichen-rich plots were found. In bryophyte-rich areas, 27 taxa were recorded. The total yield was 13,151 g dry weight ha −1 . In lichen-rich plots, the biomass was almost half lower. Graphical abstract

Plant diversity in southern Yemen is crucial for maintaining rangeland ecosystem functions. This diversity contributes to the resilience of local pastoral communities, by providing essential forage and resources. However, high stocking density has led to the overuse of palatable species, resulting in increased competition for forage. This study evaluates the nutritional value of 25 indigenous forage species from the natural rangelands of Lahij Governorate. Significant variations were observed among the Forage species, with moisture content ranging from 4 to 39.6%, crude protein from 5.5 to 21.4%, non-fiber carbohydrates from 31.8 to 66.4%, crude fiber from 8.3 to 42.65%, and ash content from 9.2 to 34.6%. Clitoria ternatea , Lycium barbarum , Senegalia mellifera , Vigna sinensis , Albizia lebbeck , and Acacia trees with crude protein content higher than 16% showed substantial potential as livestock feed due to their favorable proximate compositions. Incorporating these high-potential species into regular livestock diets could significantly enhance the sustainability and productivity of pastoral systems in southern Yemen, addressing the current fodder shortage.

Low-carbohydrate diets (LCDs) are frequently recommended for alleviating obesity, and the gut microbiota plays key roles in energy metabolism and weight loss. However, there is limited in-human research on how LCD changes gut microbiota. In this before–after study, 43 participants were assigned to the LCD intervention for 4 weeks. The main objective was to investigate the specific changes that occur in the participants’ microbiome in response to the LCD. Changes in gut microbiota were analyzed using 16s rRNA sequencing. Body composition was measured using InBody 770. Remarkably, 35 participants (79.07%) lost more than 5% of their body weight; levels of BMI, body fat, and total cholesterol were significantly decreased, indicating the effectiveness of the LCD intervention. The richness of microbiota significantly increased after the intervention. By taking the intersection of ANOVA and linear discriminant analysis effect size (LEfSe) analysis results, we identified three phyla, three classes, four orders, five families, and six genera that were differentially enriched between baseline and week-4 time points. Among the three phyla, relative abundances of Firmicutes and Actinobacteriota decreased significantly, while Bacteroidetes increased significantly. At the genus level, Ruminococcus , Agathobacter , Streptococcus , and Bifidobacterium showed a significant reduction in relative abundances, whereas Parabacteroides and Bacteroides increased steadily. Our results demonstrate that LCD can effectively alleviate obesity and modify certain taxa of gut microbiota, providing potential insights for personalized dietary interventions against obesity. Graphical abstract

To enhance our understanding of Aspergillus cristatus , an important functional microorganism, the characteristics of its mitochondrial genome were analyzed and compared with related species. The mitochondrial genome of A. cristatus was determined to be 77,649 bp in length, with 15 protein-coding regions. Notably, its length surpassed that of the other species, primarily attributable to the intron length. Gene order exhibited significant variations, with greater conservation observed in the genus Penicillium compared to Aspergillus . Phylogenetic tree analyses indicated that the genera Aspergillus and Penicillium are closely related but monophyletic. Furthermore, the phylogenetic tree constructed based on protein-coding genes effectively distinguished all strains with high branching confidence. This approach provides a robust reflection of the evolutionary relationship between A. cristatus and its related species, offering potential for the development of molecular markers suitable for Aspergillus and Penicillium .

Mulberry is a common crop rich in flavonoids, and its leaves (ML), fruits (M), and branches (Ramulus Mori, RM) have medicinal value. In the present study, a total of 118 flavonoid metabolites (47 flavone, 23 flavonol, 16 flavonoid, 8 anthocyanins, 8 isoflavone, 14 flavanone, and 2 proanthocyanidins) and 12 polyphenols were identified by ultra-performance liquid chromatography–electrospray ionization-tandem mass spectrometry. The most abundant in ML were 8- C -hexosyl-hesperetin O -hexoside and astragalin, the most abundant in M were 8- C -hexosyl-hesperetin O -hexoside and naringenin, and the most abundant in RM were cyanidin 3- O -galactoside and gallocatechin–gallocatechin. The total flavonoid compositions of ML and RM were essentially the same, but the contents of flavonoid metabolite in more than half of them were higher than those in M. Compared with ML, the contents of flavone and flavonoid in RM and M were generally down-regulated. Each tissue part had a unique flavonoid, which could be used as a marker to distinguish different tissue parts. In this study, the differences between flavonoid metabolite among RM, ML, and M were studied, which provided a theoretical basis for making full use of mulberry resources.

Catfish ( Clarias magur ) is a popular freshwater fish food worldwide. The processing of this fish generates a significant amount of waste, mainly in the form of viscera, which constitutes around 10–12% of the fish’s total weight. This study was focused on extracting polyunsaturated fatty acid (PUFA)-rich oil from catfish viscera, aiming to enhance the extraction process and make the production of oil and handling of fish byproducts more cost-effective. The wet reduction method, a solvent-free approach, was used for extraction, with yield optimization done via the Box–Behnken design. The resulting oil was evaluated for its oxidative quality and chemical characteristics. The optimal conditions for the wet rendering process were as follows: viscera to water ratio, 1:0.5 (w/v); temperature, 90℃; and time, 20 min, yielding 12.40 g/100 g of oil. The oil extracted under optimal wet rendering conditions had quality and oxidative stability comparable to solvent extraction and fewer secondary oxidation compounds. This oil had a higher PUFA content, specifically a 4:1 ratio of omega 6 to omega 3. Such oil, derived from catfish viscera, is suitable for the food industry due to its solvent-free extraction method.

The cardiometabolic index (CMI) is an emerging and effective indicator for predicting the presence of metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the relationship between CMI and MAFLD using data from NHANES 2017–2020. In this cross-sectional study, a total of 3,749 subjects were included. The study conducted a thorough analysis of CMI with three multivariate logistic regression models, subgroup analyses, and restricted cubic splines (RCS) were utilized. Using multifactorial logistic regression as the primary method of analysis, we found that a higher CMI was also significantly associated with an increased risk of MAFLD (OR = 1.45, 95% CI (1.05–2.01)). This result was further visualized by the RCS curve: There was a non-linear positive correlation between CMI and MAFLD incidence (the turning point is CMI = 0.4554). These findings were strongly reinforced by subsequent subgroup and sensitivity analyses. There is a robust positive relationship between the CMI and the risk of MAFLD, providing valuable clinical benefits for early detection and screening of MAFLD. It is important to highlight the presence of a non-linear association between CMI and MAFLD, with an inflection point identified at CMI = 0.4554.

Atherosclerosis (AS) is a chronic vascular disease associated with lipid accumulation. Understanding the molecular mechanisms of AS is essential. Ubiquitin-specific protease 7 (USP7) is a deubiquitination enzyme involved in various cellular processes, including lipid metabolism. In this study, we aimed to elucidate the role of USP7 in AS progression and its underlying mechanism using ApoE-deficient mice. We found that USP7 ablation improved the morphological characteristics of AS in these mice. USP7 knockdown reduced inflammation, evidenced by decreases in inflammatory markers IL-6, TNF-α, and IL-1β by 35, 40, and 38%, respectively ( p < 0.01). Additionally, USP7 depletion reduced oxidative stress, indicated by a 30% reduction in malondialdehyde levels and increases in superoxide dismutase and glutathione peroxidase levels by 25 and 28%, respectively ( p < 0.01). Moreover, USP7 knockdown blocked lipid accumulation in aortic tissue cells. Mechanistically, USP7 knockdown inhibited enhancer of Zeste Homolog 2 (EZH2) expression, thereby suppressing AS progression. In conclusion, USP7 depletion alleviated AS progression in ApoE-deficient mice by targeting EZH2 expression. USP7 may serve as a therapeutic target for AS.

Milk microbiome contributes substantially to the formation of specific organoleptic and physicochemical characteristics of dairy products. The assessment of the composition and abundance of milk microbiota is a challenging task strongly influenced by many environmental factors. Specific dairy products may be designated by the Protected Designation of Origin (PDO) and Protected Geographical Indication (PGI) labeling, which however, occasionally fail to differentiate them according to specific quality characteristics, which are defined by different microbiota-driven reactions. Combining the above limitations, the scope of the present study, was to summarize the existing information toward three main issues. First, to assess the influence level of the diet type and grazing to rumen–GI tract, mammary gland, and udder microbiome formation in ruminants. Second, to discuss the factors affecting milk microbiota, as well as the effect of the endo-mammary route on milk microbial taxa. Lastly, to evaluate “milk microbiome” as a tool for product differentiation, according to origin, which will contribute to a more robust PDO and PGI labeling. Although the limitations are still a matter of fact (especially considering the sample collection, process, evaluation, and avoidance of its contamination), significant progress has been made, regarding the identification of the factors affecting dairy products’ microbiota and its core composition. In conclusion, although so far not totally efficient in dairy products molecular identification, with the progress in soil, water, plant, and animal host’s microbiota assembly’s characterization, microbiomics could provide a powerful tool for authentication and traceability of dairy products.

The aim of this study is to establish area-specific NPSB (18.9% N, 37.7% P 2 O 5 , 6.95% S, and 0.1% B) fertilizer rate recommendations for the optimal grain yield of faba bean. The field experiment was conducted in two locations in the 2021 and 2022 cropping seasons using a randomized complete block design with three replications. The nine treatments included 0, 25, 50, 75, 100, 125, 150, 175, and 200 kg ha −1 NPSB fertilizer rates. An economic analysis was conducted for grain yield using the International Maize and Wheat Improvement Center procedure. The analysis of variance results showed that blended fertilizer significantly ( p < 0.01) affected plant height, number of pods per plant, number of seeds per plant, hundred seeds weight, biomass yield, grain yield (GY), and harvest index. The combined location mean result showed that applying a 125 kg ha −1 NPSB rate produced the highest GY (4857.2 kg ha −1 ). The result of economic analysis demonstrated that applying a 125 kg ha −1 NPSB rate earned the highest net benefits (212824.0 ETB ha −1 ) and marginal rate of return (3653.43%). Therefore, a 125 kg ha −1 NPSB fertilizer rate is recommended for high yield and profitability of faba bean production in the study area and other similar soil types. Graphical abstract

Delayed sowing of winter cereals or unfavorable weather conditions in autumn may make it impossible to carry out herbicide treatment in autumn. In such cases, weed control should be started in the spring. During this time, the plantation should be protected as effectively as possible because the weeds are at an advanced stage of growth. Therefore, they are less sensitive to applied herbicides. In the treatment, it is worth using a mixture of different mechanisms of action. Studies were conducted to evaluate the effectiveness of a band of tribenuron-methyl, and MCPA applied as soluble granules in spring control of dicotyledonous in winter cereals. The biological efficacy of herbicides was estimated in the 25 field experiments on winter cereals in Poland. Postemergence, a spring application of tribenuron-methyl + MCPA, effectively controls the majority of weed species present in spring: Anthemis arvensis , Brassica napus , Capsella bursa-pastoris , Centaurea cyanus , Lamium purpureum , Matricaria chamomilla , Tripleurospermum inodorum , Stellaria media and Thlaspi arvense . Satisfactory control was confirmed for Veronica persica , Viola arvensis, and Galium aparine . Tribenuron-methyl with MCPA is recommended for application to winter cereals in spring. To prevent the development of resistance in weeds, it is advantageous to combine two active substances.

The microbiome is the synchronised congregation of millions of microbial cells in a particular ecosystem. The rhizospheric, phyllospheric, and endospheric microbial diversity of lower groups of plants like pteridophytes, which includes the Ferns and Fern Allies, have also given numerous alternative opportunities to achieve greener and sustainable agriculture. The broad-spectrum bioactivities of these microorganisms, including bioremediation of heavy metals (HMs) in contaminated soil, have been drawing the attention of agricultural researchers for the preparation of bioformulations for applications in climate-resilient and versatile agricultural production systems. Pteridophytes have an enormous capacity to absorb HMs from the soil. However, their direct application in the agricultural field for HM absorption seems infeasible. At the same time, utilisation of Pteridophyte-associated microbes having the capacity for bioremediation have been evaluated and can revolutionise agriculture in mining and mineral-rich areas. In spite of the great potential, this group of microbiomes has been less studied. Under these facts, this prospective review was carried out to summarise the basic and applied research on the potential of Pteridophyte microbiomes for soil bioremediation and other agricultural applications globally. Gaps have also been indicated to present scopes for future research programmes.

Scientific fertilization is an important technical means of achieving high and stable peanut yields. Using soil testing and formula fertilization, the “3414” optimal regression design was used and included 14 nitrogen (N), phosphorus (P), and potassium (K) fertilization treatments. Ternary quadratic functions of the fertilizer effect were established according to three-season field experiments and the regression analysis of fertilizer–yield function was performed to explore the optimal fertilizer application mode and ratio for peanuts under mulched drip irrigation (MDI), and a suitable fertilizer application system was established. The ternary quadratic equation relating peanut yield ( y ) and the fertilizer application rates of N (N), P (P 2 O 5 ), and K (K 2 O) was obtained after fitting, i.e., y = 2912.528 + 21.432N + 16.324P + 6.181K − 0.051N 2 − 0.109P 2 − 0.061K 2 + 0.017NP + 0.023NK + 0.086PK, and significance analysis and typicality assessment were performed. The model R 2 was 0.9709, both values are extremely significant ( p < 0.01), which indicates that the obtained ternary quadratic fertilizer effect function is typical and could be used for statistical purposes and fertilization recommendations. Three quadratic fertilizer effect functions were obtained. Among them, the equation for K is extremely significant, and the equations of N and P are significant. According to the assumption that the marginal yield is zero and the marginal profit is zero, the fertilizer application rate with the maximum yield, the fertilizer application rate with the best economic benefits, and the corresponding yields were obtained. The optimal fertilizer application rate predicted by the ternary quadratic fertilizer effect function was relatively high, so the three quadratic fertilizer effect functions were used for prediction. Under the test conditions, the recommended fertilizer application rates for peanuts under MDI are 256.6 kg N per ha, 164.2 kg P 2 O 5 per ha, and 213.2 kg K 2 O per ha, the recommended fertilization ratio is 1:0.64:0.83, and the recommended ratio under formula fertilization is 23:15:19. The study has developed a data-based decision support system for Xinjiang drip-irrigated peanut, which assists farmers and agricultural managers in making more scientific and precise fertilization decisions based on the specific growth requirements of the crops and soil conditions. This evidence-based methodology enhances the precision of agricultural management, which is conducive to increasing crop yields while reducing resource wastage and environmental impact. However, multipoint and multiyear experiments are still needed to ensure that the findings are adaptable to the diverse soil conditions and fluctuating climate patterns that may be encountered in practice.

There is limited information on the best NPSB rate for maize production. Thus, the study aimed to determine the optimal NPSB fertilizer dose for maximizing maize yield and profitability. The nine treatments that included 0, 25, 50, 75, 100, 125, 150, 175, and 200 NPSB kg ha −1 were tested using a randomized complete block design with three replications. The results showed that increasing NPSB application significantly influenced maize plant height, ear height, hundred-seed weight, aboveground biomass yield, and grain yield. Specifically, the application of 150 kg ha⁻¹ NPSB consistently produced the tallest plants, highest ear heights, heaviest hundred-seed weights, and maximum aboveground biomass and grain yields across both sites. Economic analysis revealed that the 150 kg ha⁻¹ NPSB earned the highest net benefits and marginal rates of return, indicating its economic viability for smallholder farmers. Beyond 150 kg ha⁻¹, further increases in NPSB did not enhance yield or economic returns significantly. These findings underscore the importance of balanced fertilization for maximizing maize productivity and profitability while ensuring efficient resource use and environmental sustainability. Implementing optimized fertilizer practices with 150 kg ha⁻¹ NPSB can empower farmers in the study area and similar agroecological zones to achieve sustainable maize production and economic success.

Multispectral devices have a huge potential to be utilized in biological, ecological, and agricultural studies, providing valuable information on plant structure and chemical composition. The aim of the study was to assess the reliability and sensitivity of the affordable leaf spectrometer PolyPen (PP) in comparison with the highly sensitive analytical device FieldSpec-4. Measurements at the leaf level were realized on a collection of 24 diverse field-grown wheat ( Triticum sp. L.) genotypes in several growth phases during the regular growing season, focusing on whole spectral curves and a set of 41 spectral reflectance indices. As expected, the sensitive analytical device showed a higher capacity to capture genotypic variability and the ability to distinguish seasonal changes compared to a low-cost multispectral device. Nevertheless, the analysis of the data provided by low-cost sensors provided a group of parameters with good sensitivity, including reasonable correlations between the records of the two devices ( r > 0.80). Based on the large obtained datasets, we can conclude that the application of a low-cost PP leaf spectrometer in plant and crop studies can be efficient, but the selection of parameters is crucial. Thus, the present study provides valuable information for users of affordable leaf spectrometers in fundamental and applied plant science.

Colorectal cancer (CRC) is the third most common tumor, with an increasing number of deaths worldwide each year. Tremendous advances in the diagnosis and treatment of CRC have significantly improved the outcomes for CRC patients. Additionally, accumulating evidence has hinted the relationship between acidic nuclear phosphoprotein 32 family member E (ANP32E) and cancer progression. But the role of ANP32E in CRC remains unclear. In our study, through TCGA database, it was demonstrated that the expression of ANP32E was enhanced in COAD tissues ( n = 286). In addition, the mRNA and protein expression of ANP32E was also confirmed to be upregulated in CRC cell lines. Further investigation uncovered that knockdown of ANP32E suppressed cell proliferation and glycolysis, and facilitated cell apoptosis in CRC. Moreover, inhibition of ANP32E inhibited the AKT/mTOR pathway. Through rescue assays, we discovered that the reduced cell proliferation, glycolysis and the enhanced cell apoptosis mediated by ANP32E repression was reversed by SC79 treatment. In summary, ANP32E aggravated the growth and glycolysis of CRC cells by stimulating the AKT/mTOR pathway. This finding suggested that the ANP32E has the potential to be explored as a novel biomarker for CRC treatment.

Bovine respiratory disease (BRD) is a significant veterinary challenge, often exacerbated by pathogen resistance, hindering effective treatment. Traditional testing methods for primary pathogens –  Mycoplasma bovis , Pasteurella multocida , and Mannheimia haemolytica  – are notably time-consuming and lack the rapidity required for effective clinical decision-making. This study introduces a TaqMan MGB probe detection chip, utilizing fluorescent quantitative PCR, targeting key BRD pathogens and associated drug-resistant genes and sites. We developed 94 specific probes and primers, embedded into a detection chip, demonstrating notable specificity, repeatability, and sensitivity, reducing testing time to under 1 h. Additionally, we formulated probes to detect mutations in the quinolone resistance-determining region, associated with fluoroquinolone resistance in BRD pathogens. The chip exhibited robust sensitivity and specificity, enabling rapid detection of drug-resistant mutations in clinical samples. This methodology significantly expedites the diagnostic process for BRD and sensitive drug screening, presenting a practical advancement in the field.

Plumage color, a pivotal attribute delineating diverse Muscovy duck strains, assumes considerable significance within the field of Muscovy duck breeding research. This study extends the existing research by delving into the hereditary aspects of genes associated with plumage coloration in Muscovy ducks. The principal objective is to discern marker genes conducive to targeted breeding strategies based on plumage color, thereby furnishing indispensable technical foundations for the development of novel Muscovy duck varieties. Our investigation focused on scrutinizing the impact of MYOT and MB genes on the genetic expression of plumage color at both the RNA and protein levels in Muscovy ducks. The results elucidate that black Muscovy ducks manifest markedly elevated mRNA and protein expression levels of MYOT and MB genes in comparison to their white counterparts, indicating that both genes may play a constructive regulatory role in the context of plumage coloration in Muscovy ducks. The outcomes of this study delineate a discernible correlation between MYOT and MB genes and the plumage coloration in Muscovy ducks. Employing gene expression analysis, we successfully identified candidate genes that may be intricately linked to the determination of plumage color in these ducks.

The taste and tenderness of meat are the main determinants of carcass quality in many countries. This study aimed to discuss the mechanisms of intramuscular fat deposition in grazing and house-breeding cattle. We performed transcriptome analysis to characterize messenger RNA and microRNA (miRNA) expression profiles. A total of 456 and 66 differentially expressed genes (DEGs) and differentially expressed (DE) miRNAs were identified in the adipose tissue of grazing and house-breeding cattle. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the association of DEGs with fatty acid metabolism, fatty acid degradation, peroxisome proliferator-activated receptors signaling pathway, adenosine monophosphate-activated protein kinase signaling pathway, adipocytokine signaling pathway, and the association of DE miRNAs with mitogen-activated protein kinase signaling pathway. Apolipoprotein L domain containing 1, pyruvate dehydrogenase kinase 4, and sphingosine-1-phosphate lyase 1 genes may be the key regulators of fat metabolism in grazing cattle. Finally, we found that miR-211 and miR-331-5p were negatively correlated with the elongation of very long-chain fatty acids protein 6 (ELOVL6 ), and miR-331-5p might be the new regulator involved in fat metabolism. The results indicated that ELOVL6 participated in various functions and pathways related to fat metabolism. Meanwhile, miR-331-5p, as a new regulator, might play an essential role in this process. Our findings laid a more in-depth and systematic research foundation for the formation mechanism and characteristics of adipose tissue in grazing cattle.

Environmental pollution and overfishing of wild spiny loach have led to the increased demand for breeding the fish. However, the nutritional value between the wild and cultivated spiny loaches was unknown. Therefore, this study aimed to evaluate the nutritional components among the wild and cultivated spiny loaches at different growth stages by analyzing and comparing the proximate compositions, fatty acids, amino acids and volatile compounds. Results showed that the cultivated ones had significantly higher energy and fat contents than the wild. Particularly, the cultivated second-age spiny loach contained the highest contents of polyunsaturated fatty acids (4.83 ± 0.01%) and EPA + DHA (0.85 ± 0.02%). Besides, the total essential amino acid content of cultivated second-age spiny loach was 2201.28, exceeding that recommended in the FAO/WTO scoring pattern (2,190). And it had the highest flavor amino acid (6.24 ± 0.04 g/100 g), essential amino acid index value (71.82) and higher contents of volatile compounds. Overall, the cultivated spiny loach, especially that at the second growth stage, displayed the highest nutritional value. The findings of this study would help farmers to harvest the suitable breeding stage of spiny loaches from the perspective of nutritional value, which is beneficial to the sustainable fish farming. Graphical abstract

The expansion of Chinese spiny frog ( Quasipaa spinosa ) aquaculture has increased the prevalence and severity of diseases such as “skin rot” disease, which is triggered by harmful bacteria. Previous studies have mainly focused on pathogen identification and vaccine development. However, frog immune responses following pathogenic bacterial infection have hardly been investigated. We thus examined the immune response of Chinese spiny frog to skin rot disease caused by Proteus mirabilis . The liver transcriptomes of Chinese spiny frog infected with P. mirabilis were sequenced using the MGISEQ-2000 platform. We identified a total of 138,936 unigenes, of which 32.35% were known genes. After infection with P. mirabilis , 801 genes showed differential expression, with 507 upregulated and 294 downregulated genes. These differentially expressed genes were enriched in pathways related to cytokine–cytokine receptor interaction, TNF signaling, and toll-like receptor signaling, according to Kyoto Encyclopedia of Genes and Genomes analysis. Following P. mirabilis infection, immune genes, including H2-Aa , hamp1 , LYZ , CXCL10 , and IRAK3 , were significantly upregulated, while NLRP3 , ADAM19 , TYK2 , FETUB , and MSR1 were significantly downregulated. The results provide important information on how the immune system of Chinese spiny frog responds to P. mirabilis infection and help understand the development of skin rot in cultured frog species. Graphical abstract

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM.

Branches covering (BC) is a way to reuse the pruned branches and save the cost of ground cloth. This study investigated the effects of BC and ground-cloth covering on the soil microcosm environment by measuring the chemical properties and microbial communities at different soil depths for 6 years. The results revealed that BC significantly improved soil chemical properties, increased the abundance of bacterial microbial communities and the diversity and homogeneity of bacteria and fungi, while decreased the abundance of fungal microbial communities. There was a threshold value for the regulation of microbial communities by BC, which decreased the high-abundance communities ( Proteobacteria , Ascomycota , etc.) and increased the low-abundance communities ( Acidobacteriota , Basidiomycota , etc.). Fungi were more sensitive to BC than bacteria. The stability and homogeneity of microorganisms were stronger in the 15–25 cm soil layer. The bacterial phyla were dominated by Proteobacteria , with the top 10 phyla accounting for more than 80% of the relative abundance; the genera were dominated by MND1 , with the top 10 genera accounting for about 10%. The fungal phyla were dominated by Ascomycota , with the top 10 phyla accounting for 50–90%; the genera were dominated by unidentified Pyronemataceae sp., with the top 10 genera accounting for 30–60%. The phyla that differed significantly between treatments were mainly Proteobacteria , Ascomycota , Acidobacteriota , and Basidiomycota . In addition, metabolism was the predominant function in bacteria, while Saprotroph was the predominant function in fungi. Bacteroidota correlated strongly with soil chemical properties and bacterial functions, while Chytridiomycota correlated strongly with soil chemical properties and Pathogen-Saprotroph-Symbiotroph. In conclusion, BC can improve soil nutrient content and optimize microbial community structure and function. Through initially assessing the effects of BC on soil nutrients and microorganisms in pear orchard rows, this study provides a reference for excavating key microorganisms and updating the soil row management model.

We grew three yellow Camellia species (the calcifuge C. nitidissima and C. tunghinensis , and the calcicole C. pubipetala ) in acidic and calcareous soils for 7 months and assessed their photosynthetic physiological characteristics, growth performance, and element concentrations in this developmental context. The calcifuge C. nitidissima and C. tunghinensis species exhibited poor growth with leaf chlorosis, growth stagnation, and root disintegration in calcareous soils, and with their P n , G s , T r , F v / F m , ΦPSII, ETR, qP, leaf Chla, Chlb, and Chl(a + b) concentrations, and root, stem, leaf, and total biomass being significantly lower when grown in calcareous soils relative to in acidic soils. In contrast, the calcicole C. pubipetala grew well in both acidic and calcareous soils, with few differences in the above parameters between these two soil substrates. The absorption and/or transportation of nutrient elements such as N, K, Ca, Mg, and Fe by the two calcifuge Camellia species plants grown in calcareous soils were restrained. Soil type plays a major role in the failure of the two calcifuge Camellia species to establish themselves in calcareous soils, whereas other factors such as competition and human activity are likely more important limiting factors in the reverse case. This study furthers our understanding of the factors influencing the distribution of these rare and endangered yellow Camellia species, allowing for improved management of these species in conservation projects and horticultural production.

NaHCO 3 accelerates the aging of tobacco leaves; however, the underlying molecular mechanisms have not been elucidated. This study aimed to explore the mechanism of NaHCO 3 in the promotion of tobacco leaf maturation using transcriptome analysis. Leaves on plants or detached leaves of the tobacco variety, Honghua Dajinyuan, were sprayed with or without 1% NaHCO 3 . The leaf yellowing was observed, the pigment content and enzyme activities were determined and RNA sequencing (RNA-seq) was performed. Spraying NaHCO 3 onto detached leaves was found to promote leaf yellowing. Pigment content, catalase activity, and superoxide dismutase activity significantly decreased, whereas peroxidase activity and malondialdehyde content significantly increased. RNA-seq demonstrated that spraying with NaHCO 3 upregulated genes associated with cysteine and methionine metabolism; alpha-linolenic acid metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis and downregulated genes related to photosynthesis and carotenoid biosynthesis. Genes correlated with autophagy-other, valine, leucine, and isoleucine degradation, and the MAPK signaling pathway were upregulated while those correlated with DNA replication, phenylalanine, and tyrosine and tryptophan biosynthesis were downregulated in detached leaves sprayed with NaHCO 3 compared with the plant leaves sprayed with NaHCO 3 . Overall, this study is the first to elucidate the molecular and metabolic mechanisms of NaHCO 3 in the promotion of tobacco leaf maturation.

Allene oxide synthase (AOS) is a key enzyme involved in the jasmonic acid (JA) synthesis pathway in plants. To explore its function on the regulatory mechanism of JA synthesis, we screened and identified two AOS genes HvnAOS1 and HvnAOS2 in qingke. Both HvnAOS1 and HvnAOS2 contained conserved heme-binding motif, which is most closely related to AtsAOS2, indicating controlled dehydration of fatty acid hydroperoxides to allene oxides. Molecular docking simulations identified the key amino acid sites that were important for heme binding and interaction with 13( S )-HPOT, respectively. The expression pattern also indicated that HvnAOS1 and HvnAOS2 were highly induced by JA, abscisic acid, and salicylic acid. Subcellular localization of HvnAOS1 and HvnAOS2 using transient expression of Agrobacterium tumefaciens showed the green fluorescent protein signal in the cell cytoplasm of the N . benthamiana leaves. Overexpression of HvnAOS1 and HvnAOS2 in Arabidopsis aos mutant restored male fertility and plant resistance to Botrytis cinerea , indicating that HvnAOS1 and HvnAOS2 can restore the functions of AOS in Arabidopsis aos mutant.

Irrigation and fertilization are indispensable links in the jujube planting industry in southern Xinjiang, China. Regulating the relationship between fertilization and irrigation can effectively reduce costs and improve economic efficiency. A 2-year water and fertilizer optimization coupling test was conducted to determine the optimal water and nutrient supply scheme. The three-factor randomized block experiment included water (W), nitrogen (N), and phosphorus (P). According to the principal component analysis of each index, each treatment’s comprehensive score was obtained. Using yield and economic regression models, the theoretical value and yield value of the optimal economic benefit are inferred. When W, N, and P were applied together, the fruit quality and yield of each treatment significantly differed, and the vitamin C, soluble sugar, and sugar-acid ratio increased significantly with an increase in N fertilizer. However, the titratable acid decreased. An increase in irrigation and nitrogen application significantly increased fruit yield. The comprehensive score was the highest in the N4P3W2 treatment, which improved fruit quality, and the lowest in the N3P3W2 treatment. When the amounts of N, P, and W were 275.56 kg hm −2 , 413. 66 kg hm −2 , and 7278.19 m 3 hm −2 , respectively, the theoretical economic benefit was the best. The N4P3W2 treatment is the optimal treatment.

The application of fertilizers and soil quality are crucial for grape fruit quality. However, the molecular data linking different fertilizer (or soil conditioner [SC]) treatments with grape fruit quality is still lacking. In this study, we investigated three soil treatments, namely inorganic fertilizer (NPK, 343.5 kg/hm 2 urea [N ≥ 46%]; 166.5 kg/hm 2 P 2 O 5 [P 2 O 5 ≥ 64%]; 318 kg/hm 2 K 2 O [K 2 O ≥ 50%]), organic fertilizer (Org, 9 t/hm 2 [organic matter content ≥ 35%, N + P 2 O 5 + K 2 O ≥ 13%]), and SC (SC, 3 t/hm 2 [humic acid ≥ 38.5%; C, 56.1%; H, 3.7%; N, 1.5%; O, 38%; S, 0.6%]), on 4-year-old Cabernet Sauvignon grapevines. Compared with the NPK- and Org-treated groups, the SC significantly improved the levels of soluble solids, tannins, anthocyanins, and total phenols in the grape berries, which are important biochemical indicators that affect wine quality. Furthermore, we conducted RNA-seq analysis on the grapevine roots from each of the three treatments and used weighted gene co-expression network analysis to identify five hub genes that were associated with the biochemical indicators of the grape berries. Furthermore, we validated the expression levels of three hub genes ( ERF , JP , and SF3B ) and five selected genes related to anthocyanin biosynthesis ( UFGT1 , UFGT2 , UFGT3 , GST , and AT ) by using quantitative reverse transcription-polymerase chain reaction. Compared to the NPK and Org treatment groups, the SC treatment resulted in a significant increase in the transcription levels of three hub genes as well as VvUFGT1 , VvUFGT3 , VvGST , and VvAT . These results suggest that the SC can improve grape fruit quality by altering gene transcription patterns in grapevine roots and further influence the biochemical indices of grape fruits, particularly anthocyanin content. This study reveals that the application of SC can serve as an important measure for enhancing vineyard SC and elevating grape quality.

Reabsorption of the nucleus pulposus (NP) in lumbar disc herniation (LDH) refers to the natural absorption or even complete disappearance of LDH. In order to better treat LDH, it is necessary to further study its mechanism and develop new therapeutic drugs. Clematidis Radix Et Rhizoma is a ranunculus family plant which has multiple biological activities, and Embinin is one of its bioactive ingredients. However, its effects on LDH were unclear. In this study, the role of Embinin was investigated in LDH rat models. LDH model was established by lumbar epidural insertion of tail disc. Our results showed that Embinin promoted lumbar disc neovascularization, induced apoptosis of NP cells in LDH rats, and promoted lumbar disc resorption. Furthermore, mechanistic study showed that Embinin activated the cAMP pathway in the rat models. In conclusion, Embinin has the potential to serve as a drug for the treatment of LDH. Graphical abstract

Salinity accumulation poses a threat to the production and productivity of economically important crops such as tomatoes ( Solanum lycopersicum L.). Currently, salt tolerance breeding programs have been limited by insufficient genetic and physiological knowledge of tolerance-related traits and a lack of an efficient selection domain. For that purpose, we aimed to determine the ability of tomato cultivars to tolerate salt based on seed traits by multiple biochemical pathways. First, we tested three tomato cultivars according to their response to different sodium chloride (NaCl) concentrations (0, 6.3, 9.8, 13.0, and 15.8 dS m −1 ) and then we analysed their amino acids, organic acids, and phytohormones. Considering the results of germination traits, it is possible to conclude that cultivar H-2274 was more tolerant to salt stress than others. As a result, multivariate discriminant analysis including principal component analysis and two-way hierarchical clustering analyses were constructed and demonstrated that tomato cultivars were separated from each other by the amino acid, organic acid, and phytohormone contents. Considering germination traits of tomato seeds, cv. ‘H-2274’ was more tolerant to salinity than others depending on high proline (29 pmol µl −1 ) and citric acid (568 ng µl −1 ) assays. Biochemical variability offers a valuable tool for investigating salt tolerance mechanisms in tomatoes, and it will be appreciated to find high-tolerant tomato cultivar(s) to saline conditions. Also, the findings of this study have significant potential for practical applications in agriculture, particularly in developing salt-tolerant tomato cultivars to enhance productivity in saline environments and address socio-economic challenges.

A pot experiment was conducted to investigate the combined effects of different nitrogen fertilizer levels (5, 25, and 45 kg of pure nitrogen per 667 m²) and biochar concentrations (0, 0.7, 1.4, and 2.1%) on the growth, yield, and fruit quality of pepper. The findings indicated that a combination of 25 kg/667 m 2 of nitrogen and either 0.7% or 1.4% biochar significantly enhanced plant growth, yield, and fruit quality. Specifically, the N2 treatment (25 kg of pure nitrogen per 667 m²) increased substrate porosity, alkali-hydrolyzed nitrogen content, and available phosphorus content. It also boosted root activity and superoxide dismutase activity in pepper leaves, resulting in increased yield and better fruit quality. Furthermore, the proper addition of biochar (0.7–1.4% by weight) enhanced the physical and chemical properties of the substrate, including increased chlorophyll content and enzyme activity in plants, thereby leading to improved overall plant growth, yield, and fruit quality.

Chenopodium ambrosioides aerial parts have been historically employed in traditional medicine for addressing various ailments such as headaches, abdominal discomfort, joint issues, and respiratory disorders, alongside treatments for lice and warts. This study aimed to conduct a comprehensive phytochemical analysis of C. ambrosioides and assess the acute and subacute toxicity of oral treatments using fractions in preclinical trials. Spectrophotometric analysis via LC–MS/MS was used to characterize the plant’s chemical composition. Acute toxicity evaluation followed Organisation for Economic Co-operation and Development code 42 guidelines, conducted on adult male and female Wistar strain mice. Subsequently, Swiss mice were divided into six groups for the subacute toxicity study, receiving oral doses of 200 mg/kg extracts and fractions for 28 days. Daily observations and biochemical analyses were performed, with LC–MS/MS revealing a diverse array of compounds including organic acids, flavonoids, phenolic acids, rutin, hesperidin, nicotiflorine, and fumaric acid. Results indicated no lethality or alterations in body weight in treated groups, though some organ weight changes were noted. Biochemical analyses demonstrated values within the normal range for all groups, suggesting that the treatments did not induce adverse effects. Acute and subacute treatments with fractions did not result in lethality or toxic alterations at therapeutic doses, implying the safety of the product at appropriate levels. This study underscores the potential of C. ambrosioides as a safe therapeutic option warranting further exploration.

This study aimed to explore the effects of different nitrogen, phosphorus, and potassium ratios on the yield and nutritional quality of greenhouse tomatoes under a water and fertilizer integration model. Greenhouse tomatoes were used as the research object, and the “3414” fertilizer trial design was employed to assess tomato growth, yield, quality, and soil indicators across various treatment combinations. The goal was to determine the optimal fertilization scheme and recommend appropriate fertilizer quantities for tomato cultivation and production. The results revealed that different fertilizer ratios significantly affected both the quality and yield of tomatoes. Overall, the tomato yield tended to increase with higher fertilization amounts, with potassium exhibiting the most pronounced effect on yield increase, followed by phosphorus and nitrogen. The comprehensive analysis of principal components indicated that the N 2 P 2 K 1 treatment yielded the highest nutritional quality and yield. Therefore, the best fertilization combination identified in this study consisted of nitrogen fertilizer at 197.28 kg hm −2 , phosphorus fertilizer at 88.75 kg hm −2 , and potassium fertilizer at 229.80 kg hm −2 . These findings provided the scientific basis for optimizing fertilization practices in greenhouse tomato cultivation and production in the Jilin Province.

Considering the pear in the arid region as the research object, single-factor testing and water–fertilizer coupling testing were conducted. The response of pear tree growth to water, nitrogen, and phosphorus was explored and provided a theoretical basis for efficient water and fertilizer management. Among them, the single-factor test set water, nitrogen, and phosphorus as the three factors, and five levels were set. Screening out W3, W4, N3, N4, P3, and P4 promoted plant nutrient uptake and fruit quality. Eight treatments were set up in the water and fertilizer coupling test: Treatment 1 (T1, W3N3P3), Treatment 2 (T2, W3N3P4), Treatment 3 (T3, W3N4P3), Treatment 4 (T4, W3N4P4), Treatment 5 (T5, W4N3P3), Treatment 6 (T6, W4N3P4), Treatment 7 (T7, W4N4P3), and Treatment 8 (T8, W4N4P4). The results showed that the leaf area index of the T1, T2, T3, and T4 treatments was significantly higher than that of the other treatments at maturity. The yield, single fruit weight, and primary fruit rate were the highest under T3 treatment. The gray correlation degree analysis of fruit quality showed that the T3 treatment had the highest degree of correlation and ranking of each fruit quality index, indicating that the T3 treatment had the highest fruit quality. The yield model showed that irrigation with 6510.06 m 3 hm −2 , nitrogen fertilizer with 337.5 kg N hm −2 , and phosphate fertilizer with 262.5 kg P hm −2 had the best yield. A detailed investigation of pear tree growth and fruit quality showed that the T3 treatment had the best fruit growth and development performance, and the pear fruit quality was the best.

To date, the association of potato tuber microbiota is poorly understood. In this study, the endophytic bacterial flora of seed potato tubers was identified and the diversity of healthy and unhealthy tubers was compared. Metagenomic DNA extracted from healthy and unhealthy samples of seed potato tubers was used for the analysis of microbial communities. Next generation sequencing of the ∼460 bp v3–v4 region of the 16S rRNA gene was carried out using the Illumina Miseq platform. The data were analysed using the Divisive Amplicon Denoising Algorithm 2 pipeline. Sequence analysis of the potato metagenome identified amplicon sequence variants (ASVs) assigned to 745 different taxa belonging to eight Phyla: Firmicutes (46.2%), Proteobacteria (36.9%), Bacteroidetes (1.8%), Actinobacteria (0.1%), Tenericutes (0.005%), Saccharibacteria (0.003%), Verrucomicrobiota (0.003%), and Acidobacteria (0.001%). In healthy seed potato tubers, 55–99% of ASVs belonged to Firmicutes, including Bacillus, Salinibacillus, Staphylococcus, Lysinibacillus, Paenibacillus , and Brevibacillus genera within the taxonomic order Bacillales. However, in the visually unhealthy tubers, only 0.5–3.9% of ASVs belonged to Firmicutes while 84.1–97% of ASVs belonged to Proteobacteria. This study highlights that diverse bacterial communities colonize potato tubers, which contributes to the understanding of plant–microbe interactions and underscores the significance of metagenomic approaches in agricultural research.

The research into the use of plants as plentiful reservoirs of bioactive chemicals shows significant potential for agricultural uses. This study focused on analyzing the chemical composition and potency of an ethanolic extract obtained from the aerial parts (leaves and stems) of Salsola kali against potato pathogenic fungal and bacterial pathogens. The isolated fungal isolates were unequivocally identified as Fusarium oxysporum and Rhizoctonia solani based on morphological characteristics and internal transcribed spacer genetic sequencing data. The antifungal activity of the extract revealed good inhibition efficacy against R. solani (60.4%) and weak activity against F. oxysporum (11.1%) at a concentration of 5,000 µg/mL. The S. kali extract exhibited strong antibacterial activity, as evidenced by the significant inhibition zone diameter (mm) observed in all three strains of bacteria that were tested: Pectobacterium carotovorum (13.33), Pectobacterium atrosepticum (9.00), and Ralstonia solanacearum (9.33), at a concentration of 10,000 µg/mL. High-performance liquid chromatography analysis revealed the presence of several polyphenolic compounds (μg/g), with gallic acid (2942.8), caffeic acid (2110.2), cinnamic acid (1943.1), and chlorogenic acid (858.4) being the predominant ones. Quercetin and hesperetin were the predominant flavonoid components, with concentrations of 1110.3 and 1059.3 μg/g, respectively. Gas chromatography-mass spectrometry analysis revealed the presence of many bioactive compounds, such as saturated and unsaturated fatty acids, diterpenes, and phytosterols. The most abundant compound detected was n -hexadecanoic acid, which accounted for 28.1%. The results emphasize the potential of S. kali extract as a valuable source of bioactive substances that possess good antifungal and antibacterial effects, which highlights its potential for many agricultural uses.

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-β1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects.

This study investigates the osmotic dehydration process of watermelon rind using a solution composed of honey and sucrose. The impact of the ratio of rind-to-solution and temperature on the process is illustrated. Pre-treatments such as blanching, microwaves, and ultrasonication were utilized. Ultrasonication reduces the time needed for osmosis in a sample, resulting in increased fluid loss and solute uptake; therefore, it was selected as the method to investigate the kinetics and modelling of mass transfer. The effective diffusivities for water loss (ranging from 3.02 × 10 −5 to 4.21 × 10 −4 m 2 s −1 ) and solid gain (ranging from 1.94 × 10 −6 to 3.21 × 10 −6 m 2 s −1 ) were shown to increase with process variables such as temperature and the rind-to-solution ratio. The activation energy decreased as the process temperature increased, ranging from 3.723 to 0.928 kJ mol −1 for water loss and from 1.733 to 0.903 kJ mol −1 for solid gain, respectively. The sample treated with microwaves exhibited the maximum dehydration coefficient, rendering it appropriate for producing dehydrated products. Five empirical models were utilized, with the power law model ( R 2 = 0.983) and the Magee model ( R 2 = 0.950) being the most suitable for water loss data and solid gain, respectively.

This study examined the effects of exogenous 2,4-epibrassinolide (EBR) on photosynthetic traits of 53 cowpea varieties under NaCl stress. The results of different analysis and correlation analysis showed that these 53 germplasm resources had rich genetic diversity, and significant correlations existed among various photosynthetic traits. Under NaCl stress, Pn was highly significantly positively correlated with Gs and Tr and extremely significantly negatively correlated with Ci. Under EBR treatment, Pn was extremely significantly positively correlated with Gs, Ci, Tr and it was significantly negatively correlated with Chla, Chlb, Chl(a + b), and Y(II). Under EBR treatment and NaCl stress, Pn was extremely significantly positively correlated with Tr, and significantly positively correlated with Gs and carotenoid reflectance index. Principal component analysis shows that in CK group and EBR treatment group, cowpea photosynthesis traits can be summarized as six principal components, contributing 82.298 and 83.046%, respectively, can replace 19 photosynthetic traits to evaluate 53 cowpea varieties; under NaCl stress group and EBR + NaCl stress group, photosynthesis traits can be summarized as seven principal components, with cumulative contribution rate of 84.564 and 85.742%, respectively. In the untreated case, the cluster analysis was used to screen 32 cowpea varieties exhibiting the strongest photosynthetic capacity. Under salt stress, six of these varieties were classified as salt-tolerant. Under EBR spraying + salt stress, all four varieties showed strong photosynthetic capacity, and EBR showed the best relief of salt stress. The results of this study will provide a theoretical basis for the application of exogenous EBR to alleviate cowpea salt stress damage.

Copper (Cu) is considered one of the major heavy metal pollutants in agriculture, leading to reductions in crop yield. To reveal the molecular mechanisms of resistance to copper stress in maize ( Zea mays L.) seedlings, transcriptome analysis was conducted on the hybrid variety Zhengdan 958 exposed to 0 (control), 5, and 10 mM Cu stress using RNA-seq. In total, 619, 2,685, and 1,790 differentially expressed genes (DEGs) were identified compared to 5 mM versus 0 mM Cu, 10 mM versus 0 mM Cu, and 10 mM versus 5 mM Cu, respectively. Functional categorization of DEGs according to Gene Ontology revealed that heme binding, defense response, and multiorganism processes were significantly enriched under copper stress. Additionally, Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the copper stress response is mediated by pathways involving phenylpropanoid biosynthesis, flavonoid biosynthesis, and glutathione metabolism, among others. The transcriptome data demonstrated that metabolite biosynthesis and glutathione metabolism play key roles in the response of maize seedlings to copper stress, and these findings provide valuable information for enhancing copper resistance in maize.