Band 20, Heft 1

This study was to analyze the effect of triptolide (TPL) on proliferation, apoptosis, and the relationship between TPL and the Janus kinase/signal transducer and activator of transcription signaling pathway in hepatoma cells. HepG2 cell line was selected as the experimental object and divided into control, low-dose TPL, medium-dose TPL, and high-dose TPL group. The control group did not receive any drug treatment, while the low, medium, and high-dose groups were treated with TPL at concentrations of 0.02, 0.05, and 0.10 μM, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, flow cytometry, and western blot were used to detach the TPL effect and mechanism. The cell proliferation inhibition rate in each dose group of TPL was lower than that in the control group, and the inhibition rate of cell proliferation increased with the increase of TPL dose ( P < 0.05). The apoptosis rate of TPL in each dose group was higher than that in the control group, and the apoptosis rate increased with the increase of TPL dose ( P < 0.05). The expression of phosphorylated Janus kinase 1 (p-JAK1) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) protein in cells of each dose group of TPL was lower than that in the control group, and the expression of p-JAK1 and p-STAT3 protein decreased with the increase of TPL dose ( P < 0.05). The apoptosis rate of 10 ng/mL transforming growth factor-beta + high-dose group was reduced than that in the high-dose group, and the expression of p-JAK1 and p-STAT3 protein was higher than that in the high-dose group ( P < 0.05). The activity of B-cell lymphoma/leukemia-2-associated X protein (Bax) protein and cysteine aspartic acid protease (Caspase)-3/9 in TPL cells at each dose was raised than that in the control group, and the expression of B-cell lymphoma/leukemia-2 (Bcl-2) protein was decreased than that in the control group. With the increase of TPL dose, the activity of Bax protein and Caspase-3/9 increased, and the Bcl-2 protein decreased ( P < 0.05). As an anti-liver cancer agent, TPL inhibits the proliferation of hepatocellular carcinoma cells and promotes apoptosis. The mechanism may involve inhibiting Janus kinase 1/signal transducer and activator of transcription 3 pathway and activation of apoptosis-related pathways.

Functional dyspepsia (FD) is a chronic disease that occurs in the gastroduodenal region and significantly impacts human health. Maslinic acid (MA), a pentacyclic triterpene acid, is the primary bioactive ingredient in Chinese medicinal herbs such as hawthorn, which exhibits beneficial impacts on the regulation of various disease progressions. However, the specific functions and associated pathways of MA in FD progression remain unclear and require further investigation. In this work, it was demonstrated that MA enhanced the cell viability of human gastric smooth muscle cells (HGSMCs). In addition, the mitochondrial dysfunctions induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) were rescued after MA treatment. Furthermore, autophagy was increased following CCCP treatment, but this phenomenon was counteracted after MA treatment. The oxidative stress, elevated after CCCP treatment, was alleviated following MA addition. Finally, the AMPK/SIRT1 pathway was suppressed after CCCP stimulation but was re-activated after MA treatment. In conclusion, it was uncovered that MA accelerated HGSMC viability and improved mitochondrial function, inhibited autophagy, alleviated oxidative stress, and stimulated the AMPK/SIRT1 pathway. This discovery may offer new insight into the therapeutic effects of MA in FD progression. Graphical abstract

Neonatal sepsis (NS) is highly likely to cause death; however, early diagnosis of NS is still a great challenge. This study aimed to determine the diagnostic values of IL-6, IL-8, and serum amyloid A (SAA) in NS patients. C-Reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-6, IL-8, and SAA were detected in 120 infants with NS (60 premature infants [NS-PIs] and 60 term infants [NS-TIs]). Sixty noninfected premature infants and 60 noninfected term infants composed the control group. Receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of IL-6, IL-8, and SAA alone and in combination with CRP and PCT. The area under the curve (AUC) was calculated to evaluate the diagnostic value. The clinical characteristics of the subjects were recorded. The expression of CRP, PCT, IL-6, IL-8, and SAA was upregulated in patients with NS compared with control subjects. When the SAA cut-off value was 10.18 mg/L, the greatest AUC for the diagnosis of NS-PIs was for SAA (AUC = 0.833, 95% CI 0.762–0.905, P < 0.001). When the CRP cut-off value was 9.562 mg/L, the smallest AUC for the diagnosis of NS-PIs was for CRP (AUC = 0.776, 95% CI 0.684–0.867, P < 0.001). When the IL-8 cut-off value was 52.03 pg/mL, the greatest AUC for the diagnosis of NS-TIs was for IL-8 (0.821). When the IL-8 cut-off value was 52.03 pg/mL, the greatest AUC for the diagnosis of NS-TIs was for IL-8 (AUC = 0.821, 95% CI 0.745–0.898, P < 0.001). When the CRP cut-off value was 13.18 mg/L, the smallest AUC for the diagnosis of NS-TIs was for CRP (AUC = 0.762, 95% CI 0.667–0.857; P < 0.001). Additionally, according to the AUC value, the best combination was SAA and PCT for NS-PI diagnosis, and the best combination was PCT and IL-6 for NS-TI. In conclusion, compared with PCT and CRP, IL-6, IL-8, and SAA are better diagnostic biomarkers. Moreover, PCT combined with SAA is more suitable for diagnosing NS-PIs, and PCT combined with IL-6 is more suitable for diagnosing NS-TIs.

The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection’s inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as “long COVID,” may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19’s impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.

Dental pulp stem cells hold significant prospects for tooth regeneration and repair. However, a comprehensive understanding of the molecular differences between dental pulp stem cells (DPSC, from permanent teeth) and stem cells from human exfoliated deciduous teeth (SHED, from deciduous teeth) remains elusive, which is crucial for optimizing their therapeutic potential. To address this gap, we employed a novel data-independent acquisition (DIA) proteomics approach to compare the protein expression profiles of DPSC and SHED. Based on nano-LC-MS/MS DIA proteomics, we identified over 7,000 proteins in both cell types. By comparing their expression levels, 209 differentially expressed proteins were identified. Subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein–protein interaction network construction, revealed significant metabolic differences and key regulatory nodes. DPSC exhibited significantly higher expression of proteins belonging to the NDUFB family, SMARC family, RPTOR and TLR3. These proteins are known to be involved in critical cellular processes such as mitochondrial energy metabolism, mTOR-related autophagy pathway, and innate immune response. Conversely, SHED displayed elevated expression of AKR1B family, which participated in glycerolipid metabolism and adipogenic differentiation, PRKG1, MGLL and UQCRB proteins associated with thermogenesis. These findings highlight the specific proteomic landscape of DPSC and SHED, suggesting their distinct biological roles and potential applications.

Genomic DNA (gDNA) extraction is an important step in many molecular studies of fungal biology, and it is necessary to evaluate the efficiency, cost-effectiveness, and efficacy of different extraction methods to ensure successful amplification of the target gene and minimize deoxyribonucleic acid (DNA) degradation. The modified cetyltrimethylammonium bromide (CTAB) method was found to be effective in releasing high molecular weight gDNA with minimal protein contamination. Based on anticipated gDNA yield and quality, extraction time, cost effectiveness, successful amplification, and waste management, our findings serve as a guide for selecting techniques of gDNA extraction from fungal species. This study presents a modified CTAB method for extracting DNA from a variety of fungal species including Aspergillus , Penicillium , Alternaria , Dothiorella, and Fusarium . Comparison of three cell crushing methods reveals similar gDNA yields, demonstrating the method’s effectiveness. Furthermore, the modified CTAB method is cost-effective and safe, eliminating the need for grinding with liquid nitrogen or bead beating. The method has a potential use for nucleic-based fungal disease diagnosis such as fish fungal diseases, plant pathogens, fruit rot associated pathogens, and human fungal diseases as we were successful in PCR amplifying several gene loci from varied fungal pathogens.

A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.

Acne is a serious multifactorial inflammatory disease that leads to significant and long-lasting changes. The widespread occurrence of bacterial acne and the excessive use of antibiotics to treat it have increased resistance to antibiotic treatment and led researchers to seek and develop newer antimicrobial agents suitable for various medical purposes. In this study, alginate-coated gold nanoparticles (GANPs), synthesized by the previously reported known method, using sodium alginate and gold salt, investigated the efficacy of the GANPs against various clinical isolates of Staphylococcus , i.e., Staphylococcus aureus , Staphylococcus lentus , Staphylococcus haemolyticus , and Streptococcus thoraltensis , which were all obtained from patients suffering from acne conditions. The results showed that the GANPs had antibacterial efficacy against all the acne-isolated bacteria. The GANP activity against bacterial resistance suggested that metal-based nanoparticulate materials are a promising alternative for treating multidrug-resistant microorganisms. Graphical abstract

The COVID-19 pandemic, an unprecedented global health crisis, has thrust humanity into a relentless battle with a variety of treatments and vaccines against the SARS-CoV-2 virus. Recent developments in nanotechnology have garnered significant interest in the application of metallic nanoparticles (NPs); specifically, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) have demonstrated antimicrobial and antiviral properties. This study investigates the molecular interactions between the receptor binding domains of five SARS-CoV-2 spike protein variants (Alpha, Beta, Delta, Omicron, and Gamma) and the angiotensin-converting enzyme 2 (ACE2) receptor, followed by the docking of AuNPs and AgNPs and the natural compound Beta-escin onto these complexes. As well as the inspection of both NPs against the virus main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). Comprehensive computational simulations utilizing Autodock 4.2 and HDOCK server were employed to evaluate the binding affinities of these NPs toward key viral targets, SARS-CoV-2 Mpro, RdRp, and the spike glycoprotein. The results revealed that both AgNPs and AuNPs exhibited successful binding to the active pockets of SARS-CoV-2 Mpro, with slightly varying binding energies. In contrast, for RdRp, AgNPs demonstrated superior binding affinity compared to AuNPs, with differences in the residues involved in the binding pocket. AuNPs exhibited stronger binding affinities in the spike protein pocket. We also determined robust binding affinities between ACE2 and the spike variants, with the Omicron variant exhibiting the highest affinity. Subsequent docking of AuNPs and AgNPs revealed strong interactions with all ACE2–spike complexes, with AuNPs showing slightly higher affinities. The findings contribute to a deeper understanding of the interactions between NPs and viral proteins, shedding light on their mechanisms of action and their potential to offer innovative solutions for combating infectious diseases, particularly those caused by SARS-CoV-2.

Neuroinflammation represents a critical pathway in the brain for the clearance of foreign bodies and the maintenance of homeostasis. When the neuroinflammatory process is dysregulate, such as the over-activation of microglia, which results in the excessive accumulation of free oxygen and inflammatory factors in the brain, among other factors, it can lead to an imbalance in homeostasis and the development of various diseases. Recent research has indicated that the development of numerous neurodegenerative diseases is closely associated with neuroinflammation. The pathogenesis of neuroinflammation in the brain is intricate, involving alterations in numerous genes and proteins, as well as the activation and inhibition of signaling pathways. Furthermore, excessive inflammation can result in neuronal cell apoptosis, which can further exacerbate the extent of the disease. This article presents a summary of recent studies on the relationship between neuronal apoptosis caused by excessive neuroinflammation and neurodegenerative diseases. The aim is to identify the link between the two and to provide new ideas and targets for exploring the pathogenesis, as well as the prevention and treatment of neurodegenerative diseases. Graphical abstract

Perioperative cognitive dysfunction is a common complication in stroke patients undergoing secondary surgeries. This study investigated the effects of tibial fracture internal fixation (TFIF) surgery on cognitive function and the gut microbiota in mice with a history of stroke. Using the middle cerebral artery occlusion method to induce stroke, we assessed cognitive function via the fear conditioning test and analyzed the gut microbiota through 16S rRNA sequencing. Compared with those in the normal and stroke groups, the cognitive function of the mice in the stroke group that underwent TFIF surgery was significantly impaired. Gut microbiota analysis revealed significant changes in beta diversity, but not in alpha diversity, in these mice. Additionally, TFIF surgery increased microglial activation and IL-1β and lipopolysaccharide (LPS) levels in the brain while reducing α-defensin levels and increasing IL-1β and LPS levels in the colon. These results suggest that TFIF surgery exacerbates cognitive impairment in stroke mice, possibly through alterations in the gut microbiota that impair intestinal defense and promote inflammation. This study highlights the critical role of the gut microbiome in cognitive function and perioperative outcomes, offering insights into potential therapeutic strategies for perioperative cognitive dysfunction in stroke patients. Graphical abstract

Hepatocellular carcinoma (HCC) is a cancer with poor prognosis, underscoring the urgent need for enhanced detection and management. This study aimed to investigate the role of Collectin Subfamily Member 10 (COLEC10) in HCC, which was revealed to be associated with various diseases. Bioinformatics tools, including GEO, cBioPortal, and TCGA, were used to identify differentially expressed genes. The prognostic significance of COLEC10 was assessed in two patient cohorts, and its functional impact on Hep3B and SMMC7721 cells was evaluated through CCK-8 and Transwell assays. The underlying mechanisms of COLEC10 in HCC progression were explored using flow cytometry and western blot. COLEC10 was downregulated in HCC and associated with poorer overall survival and disease progression. The potential interaction of COLEC10, CCBE1, and FCN3 was predicted. COLEC10, CCBE1, and FCN3 were identified as prognostic indicators for HCC. Overexpression of COLEC10 inhibited the proliferation, migration, and invasion of HCC cells. COLEC10 overexpression induced G0/G1 cell cycle arrest and suppressed epithelial–mesenchymal transition (EMT), COLEC10 regulated protein expression in the Hedgehog pathway and phosphorylation of key proteins in the PI3K-AKT pathway. COLEC10 is an independent prognostic factor of HCC. COLEC10 regulates EMT, Hedgehog, and PI3K-AKT pathways, providing new ideas for targeted therapy of HCC.

Traumatic brain injury (TBI) leads to permanent damage, including neurological deficits, cognitive deficits, and cerebral edema. The specific inhibitor of serine protease Omi/high-temperature requirement A2 (Omi/HtrA2), UCF-101, exerts neuroprotective effects, but its role in TBI remains unclear. Eighty-four male Sprague Dawley rats were randomized to control, TBI, UCF-101 of low dose (1.5 μmol/kg), middle dose (3.0 μmol/kg), and high dose (6.0 μmol/kg), Compound C (AMPK inhibitor, 20 mg/kg), and high dose + Compound C groups. TBI rat modeling was operated by the controlled cortical impact method. Modified neurological severity score (mNSS) cognitive function, cerebral edema index, hematoxylin-eosin staining, TUNEL staining for apoptosis, ethidium bromide staining for blood–brain barrier (BBB) permeability, enzyme-linked immunosorbent assay for inflammation response, and Western blot analysis were performed. In TBI rats, UCF-101 caused decreased mNSS score, brain edema, neuronal apoptosis, as well as P-NF-κBp65/NF-κBp65, tumor necrosis factor-α, interleukin (IL)-1β, and IL-8 expression, while P-AMPK/AMPK, zonula occludens protein, Occludin, and Claudin-5 expression increased, accompanied with up-regulated cognitive function. Moreover, Compound C further exacerbated brain tissue lesions, neuronal damage, inflammation response, and neuronal apoptosis, while high-dose UCF-101 offset its effect. UCF-101 may inhibit apoptosis and BBB permeability to exert neuroprotective effects in TBI rats by regulating the AMPK/NF-κB pathway, advancing UCF-101 clinical applications for TBI treatment.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects 70–90% of individuals over the age of 75 and over 100 million people globally. Current treatments primarily offer symptomatic relief and do not effectively halt disease progression, highlighting the need for improved therapeutic strategies. Salt-inducible kinase 1 (SIK1) plays a role in regulating key physiological processes, including gluconeogenesis, glycolysis, and bone metabolism. Despite these insights, the specific role and underlying mechanisms of SIK1 in OA pathogenesis remain inadequately understood. This study aims to elucidate the function of SIK1 in OA cells. We observed that SIK1 was downregulated in a cell model of OA. The overexpression of SIK1 was found to inhibit IL-1β-induced chondrocyte apoptosis and inflammation. Additionally, SIK1 overexpression enhanced the activation of the CRTC2/CREB1 axis, suggesting a protective role for SIK1 in cartilage cells. In summary, SIK1 exerts a protective effect against IL-1β-induced cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling axis.

This study investigated the potential anti-inflammatory and analgesic effects of the rutin–chitooligosaccharide (R-COS) complex both in vitro and in vivo . Initially, the cytotoxicity of R-COS was assessed in RAW 264.7 cells using an MTT assay. Subsequently, an inflammatory study was conducted where R-COS demonstrated a significant reduction in various pro-inflammatory factors (nitric oxide [NO], prostaglandin E2, tumor necrosis factor-α, interleukin-6, interleukin-1, inducible nitric oxide synthase [iNOS], and cyclooxygenase [COX-2]) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells without compromising cell viability. Furthermore, in vivo analysis showcased the protective effect of R-COS on zebrafish embryos exposed to inflammatory stress induced by LPS. R-COS exhibited inhibition against pro-inflammatory factors, specifically COX-2 and iNOS. Notably, R-COS played a modulatory role in calcitonin gene-related peptide and NO levels in zebrafish, reducing the expression of pro-inflammatory factors. Additionally, the study observed analgesic activity in zebrafish treated with R-COS, which mitigated pain-like behavior triggered by acetic acid. Overall, these findings highlight the potential of R-COS, derived from chitosan, as a promising anti-inflammatory agent with broad applications in healthcare and tissue engineering. Graphical abstract

This research investigates how Aurora kinase B (AURKB) functions in trophoblast cells when they are exposed to high levels of glucose during gestational diabetes. The findings from RT-qPCR and western blotting show that when in a high-glucose environment, AURKB expression increases in both the placenta and trophoblast cells of patients with gestational diabetes mellitus. Additionally, when AURKB is silenced in high-glucose conditions, it leads to boosted proliferation of trophoblast cells and reduced inflammation. Knockdown of AURKB inhibits the expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in high glucose (HG) environment. Knockdown of AURKB may ameliorate injury and inflammatory responses in HG-exposed trophoblast cell lines in part by regulating the PI3K/AKT signaling pathway. Graphic abstract

Homer1 interacts with calcium-sensing receptors (CaSRs) in osteoblasts (OBs), with both CaSR and Homer1 playing essential roles in AKT phosphorylation. This study investigated the impact of CaSR on Homer1 expression during the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) at morphological, imaging, and molecular levels, both in vivo and in vitro . A post-oophorectomy osteoporosis model was established in Sprague-Dawley rats, validated through micro-computed tomography, hematoxylin-eosin staining, and biomechanical testing to assess in vivo changes in CaSR expression. BMSCs were isolated from 3 week-old SD rats for in vitro OB differentiation studies, wherein osteogenic differentiation was induced alongside changes in CaSR expression. Morphological alterations were examined using transmission electron microscopy and immunofluorescence staining. Furthermore, the protein and mRNA levels of OB-specific genes were quantified by Western blot and reverse transcription quantitative real-time polymerase chain reaction, with Homer1-related proteins also assessed. Results showed a reduction in CaSR and Homer1 expression in the ovariectomized group. In cellular studies, CaSR activation upregulated AKT, Homer1, and osteogenic markers, promoting cell differentiation. In conclusion, CaSR enhances OB differentiation, likely via Homer1-mediated regulation of AKT signaling, suggesting CaSR as a potential therapeutic target for osteoporosis.

Lung cancer, especially non-small-cell lung cancer (NSCLC), has a poor 5-year survival rate below 20%, with factors like smoking, air pollution, and genetic mutations contributing to its development. ABI3BP, an extracellular matrix protein, inhibits NSCLC progression by regulating key signaling pathways; however, its exact mechanisms remain elusive. This study aimed to explore ABI3BP’s role in NSCLC and its impact on these pathways. We found that ABI3BP expression was significantly reduced in NSCLC cells compared to normal controls. Overexpression of ABI3BP in NSCLC cells resulted in a substantial reduction in cell growth and motility and induced cell cycle arrest. Furthermore, its overexpression suppressed the epithelial–mesenchymal transition (EMT) process in NSCLC cells. In addition, ABI3BP overexpression inhibited the MAPK/ERK pathway in NSCLC cells. Collectively, ABI3BP functions as a tumor suppressor in NSCLC by targeting the MAPK/ERK axis, thereby regulating cell proliferation, motility, and EMT. These findings suggest that ABI3BP represents a potential therapeutic target for NSCLC treatment. Graphical abstract

The aim of this study is to explore the changes in blood uric acid level, blood glucose, and metabolism in hyperuricemia (HUA) mice. The urate oxidase gene of C57BL/6J mouse is knocked out by targeted gene modification technology, and a spontaneous HUA mouse model is established. In the experiment, 20 urate oxidase gene knockout homozygous and wild type C57BL/6J mice are selected to construct the experimental group (EG) and the control group (CG), and the mice in both groups receive multiple intraperitoneal injections of low dose streptozotocin (STZ) solution. The changes in metabolic related indicators such as blood glucose, pancreatic β cell function, water intake, urination, food intake, and body weight are observed and compared between the EG and CG mice. Baseline indicators other than body weight between the two groups of mice before the experiment have no significant difference, P > 0.05. After the injection of STZ solution, body weight between the two groups has significant difference, P < 0.05. Before the experiment and less than 19 days after the start of the experiment, daily water intake and urine output between the two groups of mice have no significant difference, P > 0.05. After the experiment reaches 19 days, two groups’ water intake and urine output have significant difference, P < 0.05. Daily food intake between the two groups of mice has no significant difference, P > 0.05. Before the injection of STZ solution, fasting blood glucose levels between the two groups of mice has no significant difference, P > 0.05. The plasma insulin level of the EG mice was higher than that of the CG mice, with significant difference ( P < 0.05). At the same time, the Homeostasis Model Assessment of Insulin Resistance index and fasting blood uric acid level of the EG mice were overall higher than those of the CG mice, with significant difference ( P < 0.05). From the seventh day after the injection of STZ solution, the random blood glucose level, fasting blood glucose level, fasting insulin level, and blood uric acid level of the EG mice were higher than those of the CG mice, with significant difference ( P < 0.05). For spontaneous HUA mice, the continuous increase in blood uric acid level caused by the disease may cause the increase in blood sugar content, thus promoting the occurrence of diabetes. Second, the content of uric acid in spontaneous HUA mice is maintained at a high level, which will bring or aggravate the damage of pancreatic islet β cells. Graphical Abstract Study investigates the changes in blood uric acid, glucose, and metabolism in HUA mice using a knockout model. Mice with spontaneous HUA show increased blood sugar, insulin resistance, and β-cell damage after STZ injection. Higher uric acid levels may promote diabetes and exacerbate β-cell damage. Significant differences in metabolic indicators were observed between EG and CG.

Hereditary hearing loss, an auditory neuropathy disorder, is characterized by its high prevalence and significant impact on the quality of life of those affected. In Chinese populations, the most prevalent gap junction beta-2 ( GJB2 ) mutation hotspot is c.235delC. Currently available genetic tests require expensive instruments and specialized technicians or have long testing cycles and high costs, and therefore cannot meet point-of-care testing (POCT) requirements. The objective of this study was to evaluate the viability of a POCT kit. In only 42 min, we successfully identified the GJB2 mutation site c.235delC by integrating CRISPR-Cas nucleic acid detection with recombinase-aided amplification (RAA) and a lateral flow dipstick (LFD) method. This method has the capacity to detect low-abundance nucleic acids (as low as 10 2 copies/μL) and low mutation frequency (20%), in addition to accurately distinguishing wild-type, homozygous, and heterozygous mutation. This approach was utilized to assess blood samples from a total of 31 deaf patients and 5 healthy volunteers. All results were subsequently confirmed through the implementation of Sanger sequencing. Our detection results were consistent with Sanger sequencing results. The diagnostic sensitivity and specificity were 100%. The combination of CRISPR-Cas13a and LFD may be a promising method for POCT of deafness genes. Graphical abstract

This study aimed to investigate potential targets for the pathogenesis of atrial fibrillation to facilitate the development of effective treatments. Atrial fibroblasts were isolated and stimulated with 1 μM angiotensin-II (Ang-II) for 24 h. To increase interleukin 11 (IL-11) expression, overexpression plasmids were transfected into atrial fibroblasts. The role and the underlying mechanism of IL-11 in atrial fibrillation were examined by immunofluorescence, measurements of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), and western blotting assays. Results demonstrated that IL-11 was upregulated in Ang-II-elicited atrial fibroblasts. Ang-II treatment increases alpha-smooth muscle actin (α-SMA), ROS and MMP levels, and p62 expression but decreases microtubule-associated protein light chain 3 II/I (LC3 II/I) and Beclin-1 expressions in atrial fibroblasts. These effects were further amplified by IL-11 overexpression. Mechanistically, the mammalian target of rapamycin (mTOR) pathway expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11 upregulation. IL-11 facilitates Ang II-induced differentiation of atrial fibroblasts into myofibroblasts by promoting oxidative stress, mitochondrial dysfunction, and autophagy inhibition through the mTOR pathway. Graphical Abstract

To investigate fecal short-chain fatty acid (SCFA) levels in hematological malignancies (HMs) patient with antibiotic-associated diarrhea (AAD), and explore the impacts of SCFAs on intestinal inflammation and gut microbiota in rats with AAD. Fecal SCFA concentrations were determined by high-performance liquid chromatography. Histologic examination was conducted by hematoxylin–eosin and alcian blue–Periodic acid–Schiff. Interleukin (IL)-10 and IL-18 mRNAs were assessed by quantitative real-time polymerase chain reaction. Claudin3 (CLDN3), Zona Occludens 1 (ZO-1), and plasmalemma vesicle-associated protein (PLVAP) proteins were evaluated by immunofluorescence and western blot. Gut microbiota was assessed by 16S rRNA sequencing. SCFAs are decreased in fecal samples of HM patients with AAD. AAD incidence is correlated with serum albumin level and type/duration of antibiotics administered. SCFAs attenuate colon shortening and intestinal pathology, and reinstate functionality of intestinal barrier by upregulating CLDN3/ZO-1 and downregulating PLVAP. Control (ctrl) group harbors an increased abundance of Lactobacillus , AAD group exhibits an enrichment of Enterorhabdus , AAD + low (L)-SCFAs group displays a predominance of Turicibacter , and AAD + high (H)-SCFAs group exerts an enrichment of Clostridium IV. Altogether, SCFAs alleviate colonic inflammation by regulating gut microbial composition, and provide insight into enhancing intestinal SCFAs content to alleviate AAD-induced symptoms in HM patients by modifying dietary structure. Graphical abstract

To explore the clinical utility and optimal timing of metagenomic next-generation sequencing (mNGS) in diagnosing pathogens in patients with diabetes complicated by community-acquired pneumonia (CAP). The study included 50 hospitalized patients diagnosed with diabetes complicated by CAP who underwent conventional microbiological testing (CMT) and mNGS using bronchoalveolar lavage fluid. Among the 50 cases, 16% presented no respiratory symptoms. There were significant increases in inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, and interleukin-6, with patchy imaging changes being the most prevalent. The positive rates for pathogen detection by mNGS and CMTs were 78 and 21% ( P < 0.05). The mNGS was significantly better than the CMTs in the detection of rare pathogens such as Anaerobes , Chlamydia psittaci, Legionella pneumophila, Mycobacterium bovis, Aspergillus fumigatus , and Pneumocystis japonicus ( P < 0.05). After clinical interpretation, 85% (22/26) of viruses, 24% (9/37) of bacteria, and 25% (2/8) of fungi were non-pathogen organisms by mNGS. There was a significant difference in the rates of adjustment in anti-infection treatment strategies based on the pathogen detection results from CMTs and mNGS, which were 2 and 46%, respectively ( P < 0.05). We found that mNGS was superior to CMTs in terms of the positive rate of pathogen detection, detecting mixed infection incidence, rare pathogen detection rates, and the adjustment of treatment strategies. However, mNGS results need to be interpreted in the context of the clinic. Graphical abstract The use of mNGS to detect pathogens in diabetes mellitus combined with community-acquired pneumonia is described, which can be more advantageous in terms of the positive rate of pathogen detection, mixed infections, and detection of rare pathogens, and can lead to timely adjustments in therapeutic strategies; however, mNGS results need to be interpreted in conjunction with the clinic.

Radiotherapy (RT) resistance in non-small cell lung cancer (NSCLC) is a significant contributor to tumor recurrence. NAT10, an enzyme that catalyzes ac4C RNA modification, has an unclear role in RT resistance. This study aimed to explore the function of NAT10 in RT resistance in NSCLC. RT-resistant NSCLC cell lines (PC9R and A549R) were established through repeated irradiation. The impact of NAT10 on cellular immunity was evaluated by measuring immune cell populations, cytotoxicity levels, and markers of cell dysfunction. Results demonstrated elevated levels of ac4C and NAT10 in RT-resistant cells. Knockdown of NAT10 suppressed cell proliferation and enhanced immune function in PC9R and A549R cells by upregulating TNF-α and IFN-γ while downregulating PD-1 and TIM-3. Mechanistically, RT resistance in NSCLC was mediated by NAT10-dependent ac4C modification of KPNB1. Furthermore, KPNB1 facilitated PD-L1 nuclear translocation, promoting immune escape in RT-resistant NSCLC cells. Overexpression of KPNB1 enhanced cell proliferation but impaired immune function in RT-resistant NSCLC cells. In conclusion, this study demonstrates that NAT10 upregulates KPNB1 expression through ac4C modification, thereby promoting RT resistance in NSCLC via PD-L1 nuclear translocation. These findings reveal a novel mechanism underlying RT resistance in NSCLC. Graphical abstract

This research investigates the therapeutic efficacy of phytol-mixed micelles in mitigating dexamethasone (Dex)-induced osteoporosis in zebrafish, with a particular focus on scale regeneration. Osteoporosis was induced in zebrafish through exposure to Dex, and the effects of phytol-mixed micelles were evaluated in this model. Following phytol therapy, bone mineralization was assessed using calcium, phosphorus, and alizarin red staining tests. Additionally, commercially available kits quantified the levels of tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HP), and alkaline phosphatase (ALP). The mRNA expression levels of MMP3, osteopontin (OPN), and mitogen-activated protein kinase (MAPK) were examined using reverse transcription polymerase chain reaction (RT-PCR). The findings indicated that phytol significantly increased calcium and phosphorus concentrations. Phytol-mixed micelle therapy led to increased calcium deposition and enhanced bone formation, as evidenced by alizarin red staining. Moreover, phytol administration resulted in increased HP content and upregulated ALP and TRAP activities in zebrafish. RT-PCR tests demonstrated that phytol plays a role in the restoration of the MMP3–OPN–MAPK pathway. In summary, this research highlights the potential of phytol-mixed micelles in ameliorating Dex-induced osteoporosis in zebrafish. Clarifying phytol’s mechanism, particularly its stimulation of the MMP3–OPN–MAPK pathway, provides insight into its role in facilitating bone remodeling. Graphical abstract

The aim of this study is to investigate the mechanism of action and correlation between transforming growth factor beta 1 (TGF-β1) and β-catenin in pelvic organ prolapse (POP). The study compared vaginal wall tissues from two groups: 20 patients with POP (POP group) and 20 who had hysterectomies for benign conditions (control group). Hematoxylin and Eosin and Masson staining visualized collagen, while TUNEL staining detected apoptosis. Protein and mRNA expression levels of TGF-β1, β-catenin, matrix metallopeptidase 2 (MMP2), tissue inhibitor of metalloproteinases 2 (TIMP2), and collagen, type I, alpha 1 (COL1A1) were assessed using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blot techniques. Relationships between the protein expressions of TGF-β1 and β-catenin, β-catenin and COL1A1, and TGF-β1 and COL1A1 were analyzed. In the POP group, vaginal wall collagen fibers were sparse, disorganized, and fragmented, with fewer fibers and more apoptotic cells compared to the control group. Protein and mRNA levels of TGF-β1, β-catenin, TIMP2, and COL1A1 were significantly lower, while MMP2 was higher ( p < 0.05). Positive correlations were found between TGF-β1, β-catenin, and COL1A1. Reduced TGF-β1 and β-catenin levels may trigger POP by affecting pelvic floor collagen metabolism. Graphical abstract

Pleomorphic liposarcomas (PLPSs) commonly occur in the extremities or retroperitoneum. However, cases of primary PLPSs in the female reproductive system are rare, with only one reported case in the ovary. Herein, we describe the case of a patient with primary PLPS involving bilateral ovaries. She presented with a 2-month history of abdominal pain, and underwent total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and excision of surface lesions on the bladder and rectum. Intraoperatively, nitrogen mustard (2%) was used to rinse the abdominal cavity. One week postoperatively, she was administered the first cycle of postoperative cisplatin chemotherapy for intraperitoneal heat infusion chemotherapy plus intravenous liposomal paclitaxel. Postoperative histopathological examination revealed primary PLPS involving both ovaries. Therefore, a doxorubicin liposomal chemotherapy regimen was administered according to the soft tissue sarcoma NCCN guidelines. The patient’s CA-125 levels decreased from 987 to 9.8 U/mL; however, after two chemotherapy sessions, she declined further treatment. The patient was still being followed-up and had no signs of recurrence at the time of writing this report. PLPS tends to be misdiagnosed and underdiagnosed due to its complex pathology and the lack of specific molecular markers. The disease is infrequent in the female reproductive system, and there is no consensus on its diagnostic and therapeutic guidelines. Herein, we summarized the findings of published case reports of PLPSs in organs of the female reproductive system to raise awareness of the disease and discussed its diagnosis, clinical treatment, and prognosis.

This study investigates the role of donor-specific antibodies (DSAs) in liver transplantation outcomes, focusing on their effects on liver damage. Ninety-four patients who underwent liver transplantation between 2019 and 2024 at Atatürk University were included. DSA testing was performed using the Luminex QIAGEN LifeCodes method. Patient demographic data, laboratory results, clinical conditions, and biopsy findings were analyzed. Disease-specific analyses were conducted for Wilson’s disease, autoimmune hepatitis, hepatocellular carcinoma (HCC), and hepatitis B virus (HBV). Due to the limited sample size, larger validation studies are needed, and the impact of the COVID-19 pandemic on the data collection process was considered. At the end of 1 year, persistent DSA had no significant effect on liver damage. However, early DSA positivity, particularly persistence and titration, requires further investigation. In Wilson’s disease, two DSA-positive patients (mean fluorescence intensity [MFI] 1,000–1,500) showed no damage. Among autoimmune hepatitis patients, 5 of 19 were DSA positive (MFI 1,700–5,600), with no detected damage. Four HCC patients were DSA positive (MFI 1,300–2,200). Among HBV patients, 12 of 31 were DSA positive, and 5 experienced liver damage. Tacrolimus levels in the third month were statistically associated with bilirubin levels. Prospective studies are needed to further clarify the clinical significance of DSA.

As sleep appears to be closely related to cognitive status, we aimed to explore the association between the percentage of deep sleep, cognitive state, and the cerebrospinal fluid (CSF) biomarker amyloid-beta 42 in non-demented individuals. In this cross-sectional study, 90 non-demented participants from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration cohort underwent a one-night WatchPAT sleep evaluation. Participants were categorized by cognitive status (patients with mild cognitive impairment [MCI] or cognitively normal [CN] individuals) and CSF Aβ42 status (Aβ42 ≤ 1,030 pg/mL [A+] or Ab42 > 1,030 pg/mL [A−]). After controlling for age, sex, and years of education, a significant inverse association was found between the percentage of deep sleep and the odds of being classified as MCI compared to CN (OR = 0.86, 95% CI [0.76–0.97], p = 0.012). However, a non-significant trend for an inverse association between the percentage of deep sleep and the odds of being classified as A+ was observed (OR = 0.92, 95% CI [0.84–1.01], p = 0.092). This study demonstrates a significant link between deep sleep and MCI. Although more longitudinal studies are needed, deep sleep could potentially serve as a novel biomarker of cognitive decline and an intervention target for dementia prevention. Graphical abstract

The present study introduces an innovative approach to sustainable corrosion inhibition by utilizing the aerial parts of Ephedra fragilis (EF) as a natural inhibitor for steel in hydrochloric acid solutions. Unlike conventional synthetic inhibitors, EF extracts offer an eco-friendly and renewable alternative, emphasizing their potential for industrial applications. Both water and ethanolic extracts were evaluated, and their bioactive compounds were identified using high-performance liquid chromatography. The ethanolic extract was rich in p-coumaric acid , sinapic acid , and hydrated catechin , while the aqueous extract predominantly contained catechin , gallic acid , and 3-hydroxybenzoic acid . Electrochemical techniques, including open circuit potential, electrochemical impedance spectroscopy, and potentiodynamic polarization, demonstrated remarkable corrosion inhibition efficiency, reaching up to 97%. The extracts exhibited mixed-type inhibition behavior, with efficiency improving as the concentration increased. Specifically, inhibition efficiencies of 96.13 and 96.84% were achieved using the Tafel method, highlighting the superior performance of EF extracts compared to many synthetic counterparts. Furthermore, scanning electron microscopy revealed the formation of a dense, protective organic layer on the steel surface, which underpins the high inhibition efficiency. This study not only validates the use of EF as an efficient, sustainable corrosion inhibitor but also opens new avenues for the integration of plant-based inhibitors into industrial practices, providing a long-term, eco-friendly solution to steel corrosion challenges.

Langerhans cell histiocytosis (LCH) is characterized by proliferative histiocyte-like cells. LCH lesions exhibit diverse and nonspecific clinical features, often leading to misdiagnosis and delayed treatment. Primary LCH lesions in the oral cavity remain rare. We report a case of a 27-year-old man with rare adult-onset LCH presenting with progressive mobility of the posterior teeth. The patient experienced increasing tooth mobility and subsequent loss in the upper and lower jaw despite undergoing periodontal treatment. A biopsy of oral mucosal tissue confirmed the Langerhans cell origin. High-resolution computed tomography imaging revealed pulmonary involvement. After undergoing systemic chemotherapy with prednisolone, vinblastine, and etoposide, the patient exhibited favourable follow-up outcomes. This case underscores the value of early diagnosis to prevent disease progression and highlights the need for dentists to be aware of LCH.

Jaranol, a bioactive compound derived from various traditional medicinal herbs, has demonstrated significant anti-inflammatory properties. This study investigates its effects and possible mechanisms underlying its anti-inflammatory role in mast cells, as well as ovalbumin (OVA)-induced allergic rhinitis (AR) mice model. Forty mice were randomly divided into blank, AR, dexamethasone (positive control), and Jaranol groups (10 mg/ml), with 10 mice in each group. Jaranol was found to inhibit nasal mucosal inflammation and reduce mast cell numbers in AR models. It also inhibited the secretion of several inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6, MCP-1, and CXCR10) from mast cells, as well as mast cell proliferation and migration. Interestingly, Pirin was differentially expressed in blank, AR, and Jaranol groups. Further studies indicated that Jaranol inhibited inflammatory cytokine secretion from mast cells by mediating Pirin and also inhibited mast cell proliferation and migration. Moreover, it inhibited mast cell function by suppressing Pirin expression. These findings suggest that Jaranol exerts its therapeutic effects by inhibiting Pirin expression in mast cells, thereby reducing inflammation and histopathological changes associated with AR. Graphical Abstract

Septic arthritis of the hip (SAH) is a prevalent form of infectious arthritis in children that can lead to serious complications if not promptly diagnosed and treated. A 6-year 4-month-old female child with a 1-year history of acute lymphoblastic leukemia chemotherapy was admitted to our hospital due to a 1-day fever. After 1 week, the child experienced right inguinal pain and exhibited severe restriction in the flexion of the right lower limb and hip. Consequently, edema was observed in the right lower extremity and foot. SAH was initially diagnosed using computed tomography and magnetic resonance imaging examinations of both hip joints. Subsequently, incision and irrigation procedure were performed on the hip joint. Following the surgery, pus metagenomic next-generation sequencing (mNGS) were conducted promptly, and the mNGS analysis indicated an Aeromonas veronii infection. The diagnosis of A. veronii SAH was subsequently confirmed through polymerase chain reaction. The child’s condition was successfully treated with a combination of amikacin and imipenem–cilastatin, leading to improvement and subsequent discharge in a satisfactory state. SAH caused by A. veronii is a rare occurrence, and the utilization of mNGS holds significant potential for the early detection of uncommon infections in immunosuppressed children.

High temperature (HT) is a common symptom of infectious myocarditis. This study investigates the effects of HT on the heat shock response (HSR) and apoptosis in cardiomyocytes, with the aim of providing insights into potential treatment strategies for myocarditis. Rat cardiomyocytes (H9c2 cells) were exposed to 42°C for 1 h, followed by a return to 37°C to simulate high fever conditions. The cells were divided into seven groups: control, oe-NC, oe-CLU, HT, HT + oe-NC, HT + oe-CLU, and HT + oe-CLU + LY294002 (PI3K inhibitor). Protein levels of HSP70, HSP90, Bax, Bcl2, CLU, p-PI3K, and p-Akt were measured by Western blot, while mRNA expression of HSP70, HSP90, Bax, Bcl2, and CLU was assessed via reverse transcription quantitative polymerase chain reaction. Cell proliferation (cell counting kit-8 assay), apoptosis (flow cytometry), and reactive oxygen species (ROS) levels (MitoSOX assay) were also evaluated. HT exposure led to decreased cell proliferation, increased apoptosis, and elevated ROS levels ( p < 0.001), while also inducing expression of HSP70 and HSP90 ( p < 0.0001). Overexpression of Clusterin (CLU) enhanced HSP70 and HSP90 levels, reduced apoptosis, improved cell proliferation, and decreased ROS under HT conditions ( p < 0.0001). The PI3K inhibitor reversed these protective effects, confirming the involvement of the PI3K/Akt pathway ( p < 0.05). CLU activates the PI3K/Akt pathway, thereby enhancing the HSR and protecting cardiomyocytes. These findings suggest that CLU could be a potential therapeutic target for myocarditis treatment.

The application of fecal microbiota transplantation (FMT) as a therapeutic strategy to directly modify the makeup of the gut microbiota has made significant progress in the last few decades. The gut microbiota, a sizable microbial community present in the human gut, is essential for digestion, immunomodulation, and nutrition absorption. Alternatively, a growing body of research indicates that gut microbiota is a key contributor to cancer, and intratumoral bacteria are considered to be crucial “accomplices” in the development and metastasis of malignancies. The exceptional clinical effectiveness of FMT in treating melanoma patients has been adequately established in earlier research, which has created new avenues for the diagnosis and treatment of cancer and sparked an increasing interest in the treatment and prevention of other cancers. However, further research on the function and mechanisms of the gut microbiota is required to properly comprehend the impact and role of these organisms in tumor regulation. In this article, we present a detailed account of the influence of FMT on the entire course of cancer patients’ illness and treatment, from tumor development, metastasis, and invasion, to the impact and application of treatment and prognosis, as well as address the associated mechanisms.

High-altitude pulmonary edema (HAPE) is non-cardiogenic pulmonary edema that occurs in healthy individuals who are unable to acclimatize when they ascend above 2,500–3,000 m above sea level in a few days. The pathogenesis of HAPE is complex and it is difficult to explain it by a single mechanism. Currently recognized pathogenesis is related to altered pulmonary hemodynamics, increased pulmonary capillary permeability, inflammatory response, dysregulated sodium–water transport, and impaired alveolar fluid clearance, and it is caused by a combination of causes. A high-altitude environment is both hypobaric and hypoxic, and whether hypobaria contributes to the pathogenesis of HAPE is unknown. We established a model in which 30 Institute of Cancer Research Mice (ICR mice) were divided into normal control (C, n = 6), normobaric hypoxic (CH, n = 8), hypobaric normoxic (HC, n = 8), and hypobaric hypoxic (HH, n = 8) groups. The simulated altitude was 5,000 m above sea level. Lung tissue wet/dry (W/D) ratios were determined, and molecular and histologic examinations were performed on each animal. W/D ratios were increased in the CH, HC, and HH groups compared to controls. ELISA revealed increased IL-1β expression in the HC and HH groups and markedly elevated TNF-α levels in the HH group. Histologic sections disclosed septal thickening and edema with inflammatory cell infiltration in the CH, HC, and HH groups compared with the control group. The HH group exhibited the most severe histopathologic abnormalities that included septal rupture. Electron microscopy demonstrated injury to endothelial and epithelial membranes and disruption of the integrity of the air–blood barrier after hypobaric and/or hypoxic exposures. Our study establishes a direct link between the histologic and physiologic findings of HAPE-like disease and demonstrates that normoxic hypobaria incites HAPE-like pathology. Furthermore, hypoxia and hypobaria act synergistically and stimulate inflammation in ICR mice. Therefore, we suggest that hypobaria plays an important role in the pathogenesis of HAPE.

Intervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strategy for IVDD treatment, while mitophagy prevents degeneration of endplate chondrocytes. Stigmasterol (STM) protects neurons from injuries by triggering mitophagy, yet the effect of STM on the mitophagy of endplate chondrocytes in IVDD has not been reported. In this study, endplate chondrocyte degeneration was induced by interleukin-1β, and the ribonucleic acid (RNA) acetylation level was identified by acetylated RNA immunoprecipitation. Herein, results indicated that STM alleviated endplate chondrocyte degeneration. Besides, STM induced PTEN-induced kinase 1 (PINK1)-mediated mitophagy in degenerated endplate chondrocytes. Moreover, N ‐acetyltransferase 10 (NAT10) increased PINK1 expression by improving PINK1 mRNA acetylation in endplate chondrocytes. In addition, STM regulated NAT10 expression by estrogen receptor 1 (ESR1) in degenerated endplate chondrocytes. In summary, the present study revealed that STM attenuated endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis. These findings would provide novel strategies for the treatment of IVDD.

A-kinase anchor protein 12 (AKAP12) has been reported to be related to lung squamous cell carcinoma (LUSC) progression. However, its role and molecular mechanisms in LUSC have not been revealed. The mRNA and protein levels of AKAP12 and transcription factor 21 (TCF21) were tested by quantitative real-time PCR and western blot. Cell counting kit 8 assay, EdU assay, flow cytometry, wound healing assay, and transwell assay were used to evaluate cell proliferation, apoptosis, migration, and invasion. Cell glycolysis was measured by testing glucose consumption and lactate production. The interaction between AKAP12 and TCF21 was assessed by ChIP assay and dual-luciferase reporter assay. A mice xenograft model was constructed to explore AKAP12 and TCF21 roles in vivo . Our data showed that AKAP12 was underexpressed in LUSC tissues and cells, and its overexpression inhibited LUSC cell growth, metastasis, and glycolysis. TCF21 had decreased expression in LUSC, which facilitated AKAP12 expression through binding to its promoter region to enhance its transcription. Furthermore, TCF21 increased AKAP12 expression to repress LUSC cell growth, metastasis, and glycolysis. In vivo experiments showed that AKAP12 upregulation reduced LUSC tumorigenesis, and TCF21 knockdown reversed this effect. In conclusion, AKAP12 might be a tumor suppressor in LUSC, which was mediated by TCF21 and could inhibit cell growth, metastasis, and glycolysis to restrain LUSC malignant progression. Graphical abstract

Tooth loss represents the most prevalent form of dental agenesis. Anterior tooth loss primarily impacts aesthetics and psychological well-being, whereas posterior tooth loss influences bone growth patterns and masticatory function. Prolonged tooth loss can significantly hinder subsequent restorative procedures. Genetic factors are among the principal contributors to tooth loss, as genes dictate the location, quantity, and morphology of teeth; mutations at specific gene loci may result in underdevelopment or even complete absence of teeth. Investigating the relationship between gene polymorphisms and tooth loss could yield novel insights for future clinical interventions aimed at addressing this issue. Consequently, this study aims to elucidate the correlation between PAX9 and MSX1 gene polymorphisms and instances of tooth loss. We searched Cochrane, PubMed, Web of Science, MEDLINE, EMBASES, and CNKI journal databases for articles up to April 1, 2024 to determine the association of PAX9 and MSX1 genes with the risk of dental development. Used STATA version 11.2 to calculate the odds ratio (OR) and 95% confidence interval (CI). Analyzed meta-regression, sensitivity, and publication bias. Used Bayesian measures of the false positive reporting probability and false discovery probability to examine the reliability of the calculation. Finally, 12 eligible reports were included in this study, including 7 reports on PAX9 rs2073247 , with 873 cases of polymorphism and 812 cases of control; 5 reports on PAX9 rs2073244 , with 668 cases of polymorphism and 668 cases of control; 7 reports on MSX1 rs12532 , with 762 cases of polymorphism and 1,544 cases of control. The ORs and 95% CIs showed a statistically significant relationship between PAX9 rs2073247 or PAX9 rs2073244 polymorphism and tooth agenesis risk. Moreover, there was no association observed for the MSX1 rs12532 polymorphism. In further subgroup analysis of the polymorphisms ( PAX9 rs2073247 , PAX9 rs2073244 ), we found an increased risk of tooth loss in the Caucasian and Hungarian groups. This article concludes that the PAX9 rs2073247 and PAX9 rs2073244 polymorphism might help to increase the risk of tooth agenesis. Understanding the mechanisms of genetic mutations will enable clinical physicians and human geneticists to develop new strategies for future therapeutic research and preventive treatments. Graphical abstract

Neisseria gonorrhoeae is fastidious, visual etiological evidence is extremely difficult to obtain, and positive results from blood cultures are even rarer. A 51-year-old female patient was admitted to our hospital for 3 days with fever, and polyarticular pain was diagnosed as infectious fever by a series of examinations, but the pathogen could not be determined. N. gonorrhoeae was identified by blood culture and mass spectrometry. Combined with the drug sensitivity test results, ceftriaxone was given and she recovered. This case is extremely rare, underlining the importance of standardized timely testing and collaboration between clinical and microbiology laboratories.

Multiple cases of extrapulmonary tuberculosis (TB) combined with pulmonary TB are commonly encountered in clinical practice. Nasopharyngeal TB is often ignored because of its hidden location and nonspecific manifestations. A correlation between cervical lymph node and nasopharyngeal TB has been observed; however, reports of cervical lymph node TB complicated with nasopharyngeal TB are rare, potentially leading to missed diagnosis. Herein, we present a case of nasopharyngeal TB combined with cervical lymph node and pulmonary TB. Radiographic findings consistently suggested TB, although multiple smear tests’ results were negative. After 3 months of diagnostic anti-TB treatment, the nasopharyngeal TB completely disappeared, and the swollen cervical lymph nodes subsided after 1 year of treatment. This case report deepens our understanding of nasopharyngeal TB and emphasizes the need for nasal endoscopy in patients with cervical lymph node TB.

This study evaluated the hepatoprotective potential of p-cymene (p-CYM) against two models of liver damage: ethanol (EtOH)-induced hepatocellular injury and diethylnitrosamine-carbon tetrachloride (DEN-CCl 4 )-induced liver fibrosis (LF). HepG2 cells were treated with p-CYM or silymarin (SIL) before exposure to 10% EtOH in order to induce cellular injury. LF was induced in Sprague–Dawley rats using a single dose of DEN followed by increasing doses of CCl 4 over 60 days. Rats were treated twice weekly with p-CYM or SIL from day 21 to day 60. Results showed that p-CYM effectively mitigated EtOH-induced cell death in HepG2 cells by enhancing the activity of superoxide dismutase and glutathione reductase. In vivo findings revealed that p-CYM attenuated DEN– CCl 4 -induced liver damage by preventing weight loss, improving serum biomarkers (e.g., aspartate transaminase, alanine aminotransferase, alkaline phosphatase, and bilirubin), and reducing liver fibrotic changes. It also decreased the expression of pro-inflammatory and pro-fibrotic markers such as TNF-α, IL-1β, IL-6, TGF-β1, COL1A1 , and TIMP-1 . Molecular docking further supported the experimental findings, showing strong interactions between p-CYM and the target proteins. These results indicate that the hepatoprotective effects of p-CYM are likely due to its combined antioxidant, anti-inflammatory, and anti-fibrotic properties. Graphical abstract

This study investigated the role of glutamine-fructose-6-phosphate transaminase 2 (GFPT2) in the response of epithelial ovarian cancer cells to paclitaxel, a standard chemotherapy drug. We analyzed GFPT2 expression across various EOC cell lines, including SKOV3, HEY, ES-2, A2780, and OVCR3. In HEY cell lines, we performed GFPT2 knockdown, while A2780 cells were engineered for GFPT2 overexpression. Following these manipulations, we assessed the cellular responses to paclitaxel treatment. Results demonstrated a correlation between GFPT2 levels and paclitaxel resistance; those with high GFPT2 (SKOV3 and HEY) expression were less sensitive compared to the cells with low GFPT2 expression (A2780). Downregulating GFPT2 enhanced drug sensitivity in HEY cells, whereas its overexpression impaired drug sensitivity in A2780 cells. Mechanistically, GFPT2’s role in facilitating paclitaxel resistance was linked to the activation of the nuclear factor-κB (NF-κB) signaling pathway, possibly influenced by NK3 Homeobox 2. Our findings suggest that GFPT2 is a critical mediator of paclitaxel resistance through NF-κB pathway activation in EOC, providing potential targets for improving therapeutic efficacy against this challenging malignancy.

Varicose veins are a prevalent vascular disorder affecting millions of individuals worldwide, and we previously reported transfer RNA-derived fragment (tRF) involvement in varicose veins. This study investigated the role of tRF-36 in varicose vein pathogenesis. Varicose veins and adjacent normal vascular tissues were collected to measure the expression of Notch 1, 2, and 3 and the smooth muscle cell (SMC) markers SMA-α, and SM22α. Human vascular SMCs (HVSMCs) were transfected to alter tRF-36 levels and examine the effects on Notch 1–3, tRF-36, SMA-α, and SM22α expression. Notch 1–3 and tRF-36 levels were higher in varicose veins than in adjacent normal vascular tissues. tRF-36 knockdown decreased HVSMC viability, downregulated Notch 1 , 2 , and 3 expression, and upregulated SMC markers ( SMA-α and SM22α ) compared with control HVSMCs. When the Notch pathway was inhibited, the expression of tRF-36 was significantly reduced. Additionally, Notch pathway inhibition showed similar effects to tRF-36 knockdown on HVSMC viability and the expression of SMA-α and SM22α . Furthermore, a Notch pathway inhibitor reversed the effects of the tRF-36 mimic on HVSMCs. Our study suggests a critical role for tRF-36 in varicose veins and demonstrates that tRF-36 knockdown may suppress varicose vein progression by inhibiting the Notch signaling pathway.

RTA-408, also referred to as Omaveloxolone, is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and has been demonstrated with protective effects against oxidative stress-induced injury. Oxidative stress is closely associated with the pathogenesis of hepatic ischemia reperfusion injury (HIRI). The aim of this study is to elucidate the impact and underlying mechanisms of RTA-408 in the process of HIRI. In the HIRI mice models, we found that RTA-408 improved liver function of HIRI mice and attenuated the HIRI-induced oxidative stress in vivo . Moreover, the neutrophil infiltration in liver tissues of HIRI mice was alleviated by the administration of RTA-408. RTA-408 treatment also rescued the elevated apoptosis in the liver tissues of HIRI mice. Furthermore, we demonstrated that RTA-408 treatment activated the Nrf2/HO-1 signaling pathway in liver tissues of HIRI mice. Furthermore, the HIRI mice models were developed using Nrf2-deficient mice to explore whether the protective effect of RTA-408 on HIRI was achieved through the activation of Nrf2. The results indicated that RTA-408 did not significantly alleviate the liver injury in Nrf2-deficient mice. Collectively, our results suggest that RTA-408 attenuates HIRI by improving liver function, and attenuating oxidative stress damage, apoptosis and inflammatory response possibly via the Nrf2/HO-1 pathway, which may provide a novel treatment strategy for HIRI patients. Graphical abstract

The current study was designed to explore the clinical significance of serum tissue inhibitor of metalloproteinase 4 (TIMP4) levels in rheumatoid arthritis (RA). The GSE1919 chip was analyzed, differentially expressed genes (DEGs) were identified, and gene ontology as well as Kyoto Encyclopedia of Genes and Genomes analyses of the identified DEGs were conducted. Patients with RA ( n = 96) and healthy individuals ( n = 96) were enrolled in this study. Serum from the participants was collected, and RT-qPCR as well as WB have been conducted to examine TIMP4 levels; additionally, interleukin (IL)-6 and IL-1β levels were determined using the ELISA method. Pearson’s correlation analysis was conducted for evaluating relationships between the expression levels of TIMP4 and those of IL-6 or IL-1β. A receiver operating characteristic (ROC) curve was drawn to determine the potential diagnostic value of serum TIMP4 for RA. TIMP4 was identified as a markedly downregulated gene involved in RA development. TIMP4 levels were significantly decreased in patients with RA, and the results of the ROC analysis showed that TIMP4 may be a potential diagnostic marker. Furthermore, the concentrations of IL-6 and IL-1β were markedly elevated in patients with RA. Finally, TIMP4 levels showed negative correlation with the levels of either IL-6 or IL-1β. TIMP4 is downregulated in RA and is a reliable serum marker for RA diagnosis. Graphical abstract

Lupus nephritis (LN) is the most common and lethal complication of systemic lupus erythematosus. We aimed to explore the protective effect of Sirtuin1 (Sirt1) on LN by regulating the NLRP3 signaling pathway in human glomerular mesangial cells (GMCs). We collected clinical samples from patients with LN, detected Sirt1 protein and mRNA expression using biochemical methods, cultured GMCs in vitro , evaluated levels of oxidative stress, cell apoptosis, and mitochondrial damage, and analyzed the expression of NLRP3 pathway proteins. Our results demonstrated that Sirt1 protein and mRNA were downregulated in the renal tissue of LN patients, and LN serum induced an increase in oxidative stress, cell apoptosis, and mitochondrial damage in GMCs while activating the NLRP3 signaling pathway. Upregulation of Sirt1 inhibited LN serum-induced oxidative stress in GMCs, reduced the number of cell apoptosis, and stabilized mitochondrial structure and function. Moreover, Sirt1 overexpression inhibited the expression of NLRP3 pathway proteins. Our findings suggest that Sirt1 may protect LN by inhibiting the NLRP3 signaling pathway in GMCs. Graphical abstract

The aim of this study is to investigate the effects and mechanism of action of sodium butyrate (SB) on brain injury repair in neonatal rats. 126 neonatal SD rats were randomly allocated to 7 groups, and necrotizing enterocolitis (NEC) and hypoxic–ischemic brain injury (HIBI) rat models were established. Hematoxylin and eosin staining showed that SB intervention alleviated intestinal and brain injuries in the HIBI + SB, NEC + SB, and NEC + HIBI + SB groups. Compared to the NEC and NEC + HIBI groups, the NEC + SB and NEC + HIBI + SB groups had significantly higher interleukin (IL)-10 and lower IL-17 levels ( P < 0.05). Immunohistochemistry revealed increased Bcl-2 expression and decreased Bax expression in the NEC + SB and NEC + HIBI + SB groups compared to the NEC and NEC + HIBI groups in intestinal and brain tissues ( P < 0.05). Compared to the control group (CG), gut microbiota diversity decreased in the HIBI, NEC, and NEC + HIBI groups, and increased significantly in the HIBI + SB, NEC + SB, and NEC + HIBI + SB groups. SB may alleviate brain injury by modulating gut microbiota, affecting IL-10 and IL-17 levels, and regulating Bcl-2 and Bax expression in intestinal and brain tissues. Graphical abstract

We aimed to investigate the roles and interaction effects of high-risk human papillomavirus (HR-HPV) infection, methyltetrahydrofolate reductase (MTHFR) polymorphism, and paired box gene 1 ( PAX1 ) methylation in cervical intraepithelial neoplasia (CIN) and cervical cancer. Polymerase chain reaction was used to detect MTHFR polymorphism and PAX1 methylation; Mantel–Haenszel and Spearman’s rank correlation tests were used to analyze the trends and correlations. Forty cases each of normal control (NC), CIN I, and CIN II/III and 9 squamous cell carcinoma (SCC) cases were enrolled. Increase in age increases the risk of cervical cancer. The HR-HPV infection rate, MTHFR mutation rate, and PAX1 methylation rate in CIN I, CIN II/III, and SCC groups were significantly higher than those in the NC group ( P < 0.05). The above-mentioned rates gradually increased with the degree of cervical lesions. Moreover, HR-HPV infection, MTHFR polymorphism, and PAX1 methylation increased the risk of both CIN and cancer. A positive additive interaction was observed between PAX1 methylation and MTHFR polymorphism across different cervical lesion groups, whereas no interaction was found between HR-HPV infection and PAX1 methylation in lesion progression.

Gliomas can cause nerve cancer-related death, and surgical removal can be challenging. Convallatoxin functioned as anti-proliferation and anti-angiogenesis in cancer cells. However, convallatoxin’s effect on glioma remains unclear. The aim of this study is to investigate the effect of convallatoxin on the proliferation and angiogenesis of glioma cells, and explore the underlying mechanism. Human glioma cell lines U251MG and A172 were treated with 12.5, 25, and 50 nM convallatoxin. Cell proliferation was investigated using the CCK-8 assay and colony formation assay. Migration and invasion were analyzed with transwell assays. Angiogenesis was evaluated using a tube formation assay. The phosphorylation of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3) was measured using Western blots. A xenotransplantation model of nude mice was used to investigate glioma progression. In U251MG and A172 cells, convallatoxin dose-dependently reduced cell viability and colony formation. Convallatoxin suppressed migration and invasion. Similarly, convallatoxin-treated cells had weakened angiogenesis. Convallatoxin downregulated JAK and STAT3 phosphorylation levels. Convallatoxin also inhibited glioma progression in nude mice xenotransplantation models. By inhibiting the JAK/STAT3 signaling pathway, convallatoxin inhibited proliferation, migration, invasion, and angiogenesis of glioma cells, proving to be a promising therapeutic candidate for gliomas. Graphical abstract

Influenza A virus (IAV) is a negative-sense, single-stranded RNA virus, whose genome consists of eight segments encoding multiple structural and non-structural proteins essential for viral replication and host immune evasion. Among these, segment 8 encodes two primary non-structural proteins  NS1, crucial for host immune suppression and virulence and NS2, involved in vRNP export – and their expression is regulated by splicing. Further studies are required to elucidate the role of PKR in IAV mRNA splicing regulation.

With the extensive utilization of antifungal drugs, the drug resistance of Candida albicans is progressively intensifying, and the effect of empirical treatment for C. albicans infection is not evident. There is an urgent need for novel strategies and methods for the treatment of C. albicans infection. Our study utilized the previously constructed C. albicans Ire1 double gene deletion strain to explore the influence of the Ire1 on endoplasmic reticulum (ER) stress and pathogenicity of C. albicans through drug stress phenotype testing, biofilm and hyphomycete formation testing, and mouse systemic infection testing. The results indicate that Ire1 is involved in maintaining the integrity of the C. albicans cell wall and influencing the hyphal formation ability of C. albicans . Concurrently, the deletion of the Ire1 increased the sensitivity of C. albicans to the ER stress agents tunicamycin and dithiothreitol and diminished the biofilm formation ability of C. albicans in vitro , resulting in significant inhibition of the growth of C. albicans . In mouse models, the deletion of Ire1 completely nullified the virulence and pathogenicity of C. albicans in the tail vein infection. In conclusion, Ire1 might be a key target for the potential development of new therapeutic drugs and vaccines.

Patients with small cell lung cancer (SCLC) typically exhibit a poor prognosis, often receiving diagnoses at an advanced stage. Despite recent advances in immunotherapy, the median survival remains approximately one year. Gastrointestinal metastases from lung cancer, based on clinical experience, are exceedingly rare and associated with dire prognoses. This article details the diagnosis and management of an unusual case of SCLC with gastrointestinal metastasis. The patient’s survival was notably prolonged compared to typical SCLC outcomes, providing significant clinical insight. Graphical abstract

Gastric cancer (GC) is a prevalent malignancy with a high incidence rate. Growth factor receptor-bound protein 14 (GRB14) is crucial in cell signal transduction and is associated with tumor growth, invasion, and metastasis. The aim of this study is to investigate the impact of GRB14 on GC growth and metastasis. GRB14 expression and prognosis in GC tissues were analyzed using bioinformatics. The GC cell lines, SGC-7901, MGC-803, BGC-823, and normal gastric epithelial cell line (GES-1) were used in this study. Cell viability, cycle progression, and apoptosis were assessed via CCK-8 and flow cytometry. The colony formation, transwell, and wound-healing assays were conducted to evaluate cell proliferation, invasion, and migration. Protein levels involved in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by Western blot. GRB14 expression was significantly higher in GC tissues than adjacent healthy tissues, correlating with poor prognosis. GRB14 knockdown promoted apoptosis and inhibited cell growth, invasion, and migration, while its overexpression exhibited opposite effects. GRB14 directly interacted with cordon-bleu WH2 repeat protein like 1, facilitating PI3K/AKT signaling in GC cells. This study highlights GRB14’s critical role in GC progression and suggests its potential as a therapeutic target.

15-Lipoxygenase-2 (15-Lox-2) is one of the key enzymes in arachidonic acid (AA) metabolic pathway, which belongs to the unsaturated fatty acid metabolic pathway. This pathway is involved in the foam cell transformation of macrophages during the progression of atherosclerosis (AS). The role of salidroside (SAL) in cardiovascular diseases has been extensively studied, but its impact on macrophage foam cell formation has not yet been clearly clarified. We aimed to determine the effects of 15-Lox-2 deficiency on macrophage (Ana-1 cell) foam cell formation, and those of SAL on 15-Lox-2 -deficient macrophages. 15-Lox-2 -deficient macrophages were generated using short hairpin RNA. Results indicated that 15-Lox-2 expression in the aorta of atherosclerotic patients is lower than that of the normal group. Additionally, 15-Lox-2 deficiency dramatically promoted macrophage uptake of oxidized low-density lipoprotein (ox-LDL) and increased the Cyclin D1 level while dramatically decreasing caspase3 expression. Furthermore, inflammation, complement, and TNF-α signaling pathways, along with IL1α, IL1β, IL18, and Cx3cl1, were activated in 15-Lox-2 -deficient macrophages. These changes were alleviated by SAL through inhibiting AA effects, and the effects of AA on macrophages could be inhibited by SAL. Consistently, phospholipase A2-inhibitor arachidonyl trifluoromethyl ketone (AACOCF3) restored these changes. In summary, SAL reversed the effects of 15-Lox-2 deficiency on macrophages by inhibiting excessive AA and may be a promising therapeutic potential in treating atherosclerosis resulting from 15-Lox-2 deficiency.

Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes. The role of epigenetic regulation in DN has attracted much attention recently. This research was performed to explore the role of FTO in the DN progression. The renal tissues of DN patients were collected and the podocytes were stimulated with high glucose (HG) to establish the DN model in vitro . Western blot along with reverse transcription quantitative polymerase chain reaction assays was performed to analyze the mRNA as well as protein expressions. Immunohistochemistry and immunofluorescence were carried out to measure the FTO and DACT1 levels. The interaction between FTO/IGF2BP1 and DACT1 was verified by double luciferase reports and RNA-binding protein immunoprecipitation assays. FTO was declined, and DACT1 was enhanced in the HG-treated podocytes as well as renal tissues of DN patients. Overexpressed FTO declined the mRNA levels of MCP-1, IL-6, TNF-α, and the apoptosis rate of HG-treated podocytes. The N6-methyladenosine (m6A) levels, mRNA expression, and stability of FTO were depleted after FTO overexpression. DACT1 overexpression reversed the function of oe-FTO in podocytes stimulated with HG. Furthermore, IGF2BP1 knockdown declined the mRNA expression as well as the stability of FTO. In conclusion, FTO-medicated m6A modification of DACT1 was dependent on IGF2BP1 in DN progression. Graphical abstract FTO-medicated m6A modification of DACT1 was dependent on IGF2BP1 in DN progression.

This study aimed to investigate the clinical relevance of inflammatory markers in the severity assessment of ulcerative colitis (UC). The inflammatory markers included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and calcium ion (Ca 2+ ) levels. A retrospective analysis was on 110 patients with UC and 52 patients with irritable bowel syndrome (IBS), admitted to Weifang People’s Hospital between June 2019 and February 2021. UC severity was classified using the modified Mayo score and the Montreal classification system. The study assessed the predictive accuracy and correlation of these inflammatory markers with UC severity and extent. Levels of NLR, PLR, CRP, ESR, and Ca 2+ were significantly elevated in individuals with UC compared to those with IBS. Among patients with UC, significant differences in these markers were observed across varying severity levels as defined by the modified Mayo score. However, aside from ESR, no significant differences were noted in NLR, PLR, CRP, or Ca 2+ levels across groups defined by lesion extent. Receiver operating characteristic curve analysis indicated that NLR exhibited the highest predictive accuracy for UC, with a cut-off value of 2.603 yielding a sensitivity of 0.545, specificity of 0.288, and an area under the curve (AUC) of 0.896. The combined use of NLR, PLR, CRP, ESR, and Ca 2+ demonstrated superior predictive performance, achieving an AUC of 0.972, sensitivity of 0.927, and specificity of 0.923 at a cut-off value of 0.455. NLR, PLR, CRP, ESR, and Ca 2+ exhibit predictive value for UC, with NLR demonstrating the highest individual predictive performance. The combined use of these markers enhances predictive accuracy, highlighting their potential application in clinical practice for the evaluation of severity UC. Due to ethical considerations at our institution, the IBS group was used as a substitute for healthy controls. The IBS group was included solely for the calibration and testing of inflammatory biomarkers, as well as for subsequent analysis of their role in assessing UC severity.

This study explores the potential of zinc valproic acid (Z-VA) complex as a promoter of osteoblast differentiation and a preventive agent against osteoporosis. The concentration of 25 µM Z-VA improved osteoblast differentiation by increasing the expression of Runx2 and type 1 collagen mRNA, alkaline phosphatase activity, and cellular calcium deposition. Dexamethasone-induced osteoporosis models were used in zebrafish and rats. In the zebrafish scale regeneration model, Z-VA decreased the hydroxyproline content and tartrate-resistant acid phosphatase activity while also upregulating the calcium to phosphorus molar ratio, Runx2a MASNA isoform, collagen2α, osteocalcin, and osteonectin. Additionally, Z-VA upregulated osteopontin and mitogen-activated protein kinase expression and downregulated matrix metalloproteinase 3 expression. Z-VA increased calcium deposition, callus formation, and bone growth in a zebrafish fracture model. In the rat model, Z-VA increased the bone transverse diameter, length, weight, mineral content, and mineral density, as well as serum Ca 2+ , inorganic phosphate, interleukin-6, tumor necrosis factor alpha, and alkaline phosphatase. Our results suggest that Z-VA may be an effective anti-osteoporotic agent that stimulates bone growth and prevents bone loss. However, further research is needed to elucidate its mechanisms and enhance its therapeutic application. Graphical abstract

Synovial sarcoma, a mesenchymal spindle cell malignancy commonly seen in young and middle-aged adults, typically occurs in the soft tissues around the major joints of the extremities, with some reports of occurrences outside the joints. However, primary pulmonary cases are rare. This study reports a 52-year-old female patient who was admitted due to coughing and recurrent haemoptysis and was ultimately diagnosed with primary pulmonary synovial sarcoma (PPSS) through surgery and pathology after a series of examinations, including computed tomography scans and bronchoscopy. The tumour was located at the orifice of the dorsal segment of the right lower lobe, and she underwent thoracoscopic right lower lobectomy + lymphadenectomy. After 1 year of follow-up, the patient was in good general condition, without discomfort or signs of tumour recurrence or metastasis. PPSS grows slowly and presents insidiously, with imaging findings lacking specificity, making it easily confused with lung cancer and other pulmonary tumours. In conclusion, this case provides physicians with insights into the clinical presentation, imaging features and necessary pathological and molecular biological tests for PPSS diagnosis, which is essential for improving diagnostic accuracy.

This study evaluated the effectiveness of metagenomic next-generation sequencing (mNGS) in detecting pathogens in patients with pulmonary infections, comparing a low-data-volume, human-depleted quantitative (Q) method and a high-data-volume, non-human-depleted pathogen capture engine (PACE) method. A total of 133 patients were enrolled, comprising 59 in a control group (traditional culture) and 74 in an mNGS group (51 Q and 23 PACE). Bronchoalveolar lavage fluid samples were collected for pathogen detection. Mycobacterium tuberculosis was predominantly detected via general mNGS, whereas Candida albicans and Epstein-Barr virus were more frequently identified by PACE and Q, respectively. Among participants, 22.97% had bacterial mono-infections, and 2.70% had viral mono-infections; the most common co-infection involved bacteria and viruses (25.68%). Patients with fever, abnormal white blood cell, neutrophil percentage, and D-dimer levels exhibited higher detection rates. PACE showed consistently high sensitivity (decreasing from 100 to 92% as thresholds became more stringent) and specificity and accuracy that peaked at 100 and 96%, respectively. The Q method maintained 100% sensitivity at the lowest threshold but showed variable specificity (0.52–0.67) and accuracy (71–75%). These findings highlight the need for caution in clinical applications when using low-data-volume, human-depleted approaches, especially for complex pulmonary infection cases.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare uterine mesenchymal tumor, which is classified as a tumor with uncertain malignant potential. In this case report, we reported a 52-year-old woman who was diagnosed with UTROSCT through pathological examination of uterine intramural nodules. We reported the diagnosis and treatment process, aiming to provide new evidence and insights for the diagnosis and treatment of this rare disease.

Clostridioides difficile is a pathogen that causes pseudomembranous colitis with antibiotic-associated diarrhea. The epidemiology and molecular evolution of C. difficile may differ among different geographic regions, and mining its genomic information can help to understand the epidemiology and molecular evolution of C. difficile and focus on its transmission mode. A C. difficile strain denoted WXL8 was isolated from a human fecal sample from a patient in the intensive care unit, and its physiology and genomic sequence were determined. The total genome size of WXL8 was 4,119,929 bp, and the GC content was 27.97%. The multilocus sequence typing results indicated that WXL8 is strain type 11 (ST11), a genotype widely present in livestock. The WXL8 was located in clade 5 of ST11. The ribotype of WXL8 was a novel ribotype (PR34365). It is the first report of the ST11 (PR34365) strain. Comparative genomic analysis between WXL8 and the other four high-virulence strains (CD630, CDBR81, CDS-0253, and CDR20291) showed differences in gene arrangement, indicating the uniqueness of C. difficile WXL8. In the present study, a novel ribotype (PR34365) ST11 strain of C. difficile was isolated from a patient with diarrhea in Guizhou, China. Our findings suggest that zoonotic CDI should receive more clinical attention.

Coronary heart disease (CHD) is a highly prevalent disease in the elderly population, with atherosclerosis as its pathology, which can also be viewed as a chronic inflammatory response of the organism. Regular moderate-intensity exercise can direct the immune response toward an anti-inflammatory state, which is beneficial for improving the health and exercise tolerance. In cardiac rehabilitation, attention to the management of inflammatory factors as well as the improvement of exercise endurance is beneficial for the rehabilitation of elderly patients with coronary artery disease. This study investigates the impact of tiered cardiac rehabilitation programs on levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and the capacity for physical exertion in older CHD patients. From March 2020 to April 2022, 94 elderly patients with CHD visiting our institution were recruited and randomly allocated into either a control group or an observation group, each comprising 47 participants. The standard care group participated in traditional rehabilitation exercises, whereas the experimental group received customized, tiered, cardiac rehabilitation interventions. We assessed the variations in CRP and tumor necrosis factor alpha (TNF-α) levels, along with exercise capacity, before and after treatment in both groups. The result shows that significant reductions in CRP and TNF-α levels were seen in the experimental group after 4 and 12 weeks, compared to the standard care group. Analysis showed clear trends in CRP and TNF-α changes over the interventions, with the experimental group showing better results. CRP levels decreased consistently, while TNF-α levels stayed stable. The experimental group also showed improvements in physical endurance measures compared to the control group. Interleukin 6 (IL-6) and fibrinogen (Fib) in the observation group decreased compared with the control group ( P < 0.01). After 12 weeks of treatment, CRP and TNF-α showed significant negative correlation with exercise endurance index – 6 min walking test (6 MWT), anaerobic threshold (AT), maximum oxygen consumption (VO 2max ), and exercise duration (ED); significant positive correlation between cardiac rehabilitation grade and exercise endurance index (6 MWT, AT, VO 2max and ED); and both groups experienced cardiovascular adverse events and exercise muscle injury. The analysis shows that the graded nursing of cardiac rehabilitation can effectively reduce the levels of CRP, TNF-α, IL-6, and Fib in elderly patients with CHD and significantly improve the exercise endurance of patients with good safety. Graphical abstract

This study aims to explore changes in peripheral blood T-lymphocyte subsets in colorectal cancer (CRC) patients before and after acupoint catgut embedding (ACE) acupuncture observation. Eighty CRC surgical patients who visited from April 2017 to May 2022 were selected as study samples using the convenience sampling method. Patients were randomly divided into a control group ( n = 40, receiving conventional chemotherapy) and an observation group ( n = 40, receiving 4 weeks of additional ACE acupuncture). The observation group showed higher rates of complete and partial remission compared to the control, though the difference was not statistically significant ( P > 0.05). The observation group experienced less reduction in CD 3+ , CD 4+ T lymphocytes, and natural killer cells during chemotherapy. Compared with the control group, the percentage of CD 3+ and CD 4+ T cells in the observation group significantly increased after the intervention, while CD 8+ T-cell levels decreased. The CD 4+ /CD 8+ ratio was at a higher level, and the discrepancy was statistically obvious ( P < 0.05). Acupuncture therapy can maintain the normal distribution of peripheral blood T-lymphocyte subpopulations during chemotherapy in patients with CRC, thus better maintaining the immune status of patients. Graphical abstract

The holistic approach of traditional Chinese medicine (TCM) has been increasingly being focused on as a potential adjuvant to conventional lung cancer therapies in an attempt at modulating the tumor microenvironment (TME). Covering a diverse range of herbal medicine, acupuncture, and dietary therapy, TCM brings a unique perspective to influencing the TME. Importantly, the study has found the effects of specific TCM compounds, such as cantharidin, boehmenan, shikonin, and salidroside, on lung cancer in the TME. These compounds interact intricately with key apoptotic regulators, oxidative stress pathways, and inflammation-related mechanisms, suggesting their potential role in enhancing conventional therapies. TCM compounds could modulate a variety of cellular and molecular pathways, potentially inhibiting tumor proliferation, invasion, and metastasis. Besides, the practices of TCM alleviate the side effects of conventional treatments and enhance immune function, hence promoting the quality of life among lung cancer patients. In this regard, this review gives a contemporary account of the state of affairs on the part of TCM within the framework of the treatment of lung cancer with reference to its recent developments, and diverse roles.

Co-occurring symptoms such as depression, anxiety, fatigue, and sleep disorders are frequently comorbid with cancer. The causes of these cancer-related symptom clusters are hypothesized sharing a common biological mechanism. This study explored pattern differences of some gut metabolites (glucocorticoids, short-chain fatty acids, gut microbial metabolites from tryptophan) in plasma samples from patients with four types of cancer. Metabolomics analysis was performed to indicate the differences of metabolites. Discrimination model and diagnostic model were constructed using orthogonal partial least squares discriminant analysis, and differential metabolites were screened, then receiver-operating characteristic curve analysis was performed to evaluate the performance of these models. Melatonin (MLT), indole propionic, and skatole were screened as the common differential metabolites shared by four types of cancer, indicating that the intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors. The area under the curve values for the potential candidate biomarker predictors in univariate analysis ranged from 0.771 to 0.989, and in multivariate analysis ranged from 0.985 to 1.00. The sensitivity and specificity of the multivariable model were 94.7–100 and 96.4–100%, respectively. These biomarkers also had good performance in discriminating different pairs of cancer. The analysis of gut microbiota metabolites allows us to characterize the common metabolic characteristics of patients with various cancers. The intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors. Graphical abstract

This study aims to analyze and explore whether tumor biological three-dimensional printing (3DP) models can serve as reliable preclinical model research tools and assist in the personalized treatment of gastrointestinal stromal tumor (GIST) patients. Ten GIST cases admitted to our hospital from May 2024 to September 2024 were included in the personalized treatment group. Patient-derived GIST 3DP models were established, and treatment plans were selected based on the results of drug sensitivity tests. The progression-free survival (PFS) of the personalized treatment group was compared with that of GIST patients who had progressed after first-line treatment and were admitted to our hospital before the study. Treatment safety was also assessed. Immunofluorescence staining technology was used to observe tumor markers in the 3DP tumor models and their corresponding parent tumor tissues, revealing a high degree of consistency, which indicates that the 3DP tumor models highly retain the histological characteristics of the parent tumor tissues. The median PFS of patients in the personalized treatment group was 6.1 months, compared to 5.3 months in the previous treatment group, with a statistically significant difference ( P -value <0.05). The individualized drug sensitivity detection technology based on bio-3D printing technology, used for the personalized treatment of GIST patients who have progressed after first-line treatment, can benefit patients.

Ulcerative colitis-associated colorectal cancer (UCCRC) represents a significant complication of ulcerative colitis. CEBPB has been shown to promote the invasion of colon cancer cells. In this study, we aimed to investigate the role of CEBPB in the progression of cancers associated with colitis. The wild-type (WT) mice, transfected with a vector expressing CEBPB and siRNA targeting CEBPB, along with their littermate controls, were subjected to a challenge using azoxymethane and dextran sodium sulfate to establish a model of UCCRC. Colon tissues and blood samples were collected for analysis through hematoxylin and eosin staining and enzyme linked immunosorbent assay. Immunohistochemical staining was employed to assess protein expression. In the UCCRC model, mice transfected with vectors expressing CEBPB exhibited a reduction in weight loss and colorectal stenosis, as well as disordered colonic gland structure. Additionally, these mice demonstrated an increased number and size of tumors compared to WT controls. Furthermore, transfection with CEBPB resulted in a decrease in both the quantity and dimensions of tumors. NF-κB was found to enhance the phosphorylation level of STAT3 based on Western blot assay. The activation of NF-κB and STAT3 subsequently promoted the proliferation, invasion, and migration of colon cancer cells by clone formation assays, transwell assays, and scratch-wound assays. Moreover, rescue experiments indicated that CEBPB induced UCCRC through the NF-κB/STAT3 signaling pathway. CEBPB mediated colonic injury in UCCRC mice by activating the NF-κB/STAT3 pathway. This finding reveals a previously unrecognized link between CEBPB and colitis-related tumorigenesis and provides new insight into UCCRC pathogenesis.

Cancer is one of the most devastating diseases all over the globe, and it is the second worldwide cause of death, exceeded only by cardiovascular diseases. The therapeutic approach to human cancer has evolved significantly and has varied depending on the type and stage of cancer, as well as the general health status of the patient. Despite the advancements in cancer treatment, various challenges persist in the treatment of cancer, including side effects, drug resistance, and incomplete eradication of tumors. The use of oncolytic bacteria (cancer targeting and destroying bacteria) has been identified to have several advantages over the traditional methods of cancer treatment. Several bacterial species have been identified to be used in the treatment of different types of cancers. Oncolytic therapy can be achieved through the use of a naturally occurring and/or genetically modified bacterial species, including Clostridium , Salmonella, Escherichia coli, and Listeria spp. with their toxins, enzymes, biofilms, and secondary metabolites as well as their spores that leads to direct or indirect killing of cancer cells. This review provides some highlights about the biology and therapeutic potential of oncolytic bacteria individually or in combination with other therapeutic approaches against different types of cancers. Besides, the current challenges and future perspectives will be explored.

Meningiomas, accounting for approximately 33% of primary central nervous system tumors, are the most prevalent type in this category. Advanced age is frequently viewed as a barrier to surgical intervention, yet recent cases have challenged this perception by demonstrating successful outcomes in elderly patients. This case report aims to illustrate the feasibility and benefits of surgical treatment in older individuals. An 84-year-old patient presented with a newly diagnosed meningioma and underwent surgical tumor removal at age 88. Following a comprehensive preoperative evaluation that excluded significant comorbidities, the procedure utilized advanced surgical techniques and optimized postoperative care to ensure safety and recovery. Pathology revealed a World Health Organization grade 1 fibrous meningioma, confirming its benign nature. The patient tolerated the surgery well and recovered successfully, marking her as the oldest reported individual to undergo such treatment. This case demonstrates that advanced age does not inherently limit tumor growth or preclude surgical intervention. Through meticulous patient assessment and personalized treatment strategies, elderly patients can achieve positive outcomes. It highlights the value of a tailored approach, prioritizing overall health and specific medical needs, and supports proactive surgical management to enhance quality of life and clinical results. This challenges traditional assumptions about age-related restrictions on surgical feasibility.

In recent years, there has been a notable increase in the prevalence of tumors and tuberculosis (TB), particularly among elderly and immunocompromised populations. Early diagnosis and treatment are crucial for significantly improving patient outcomes. However, traditional diagnostic methods exhibit certain limitations. The rapid advancement of metagenomic next-generation sequencing (mNGS) has shown promising applications in the field of infectious diseases. We describe an 88-year-old male with multiple comorbidities, including newly diagnosed localized prostate cancer, who presented asymptomatically. Routine mNGS screening unexpectedly identified Mycobacterium tuberculosis , suggesting that malignancy may foster immune conditions favoring latent TB reactivation. This case emphasizes mNGS’s role as a rapid, sensitive diagnostic adjunct for occult infections in high-risk populations.

This investigation explores the impact of hesperidin and its zinc( ii ) complex on osteoblast differentiation and subsequent bone formation. The biocompatibility of synthesized complexes (0–20 μg/mL) was assessed in vitro using mouse mesenchymal stem cells, while in vivo toxicity was evaluated using a chick embryo model. Both hesperidin and its zinc( ii ) complex were found to be non-toxic at a concentration of 10 μg/mL. Notably, these compounds significantly increased alkaline phosphatase activity and enhanced calcium deposition. Molecular analyses revealed upregulation of Runx2 and type 1 collagen mRNA expression, along with increased levels of osteonectin and osteocalcin proteins, while negative regulators of osteoblast differentiation (Smad7, Smurf1, HDAC7) were downregulated. A new aspect of this study is demonstrating that the zinc( ii ) complex of hesperidin uniquely enhances osteogenic activity compared to hesperidin alone, highlighting its potential to improve bone formation significantly. Additionally, we elucidated the role of miR-143-3p in mediating these effects, achieved through HDAC7 suppression and enhanced Runx2 expression, assessed using the pmirGLO dual luciferase reporter system. Zebrafish studies further demonstrated the complexes’ effects on bone formation, revealing increased osteoblastic activity and improved calcium-to-phosphorus ratios in regenerated scales. These findings underscore the potential of hesperidin–Zn( ii ) as a promising therapeutic agent for bone tissue engineering.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Chemokines are a class of proteins that possess characteristics of both chemoattractants and cytokines. They play a pivotal role in CVD by regulating the recruitment of immune cells and suppressing inflammatory responses. These proteins are crucial for maintaining cardiac function and for managing myocardial cell damage under various stress conditions. Autophagy, a vital intracellular degradation mechanism, is essential for clearing misfolded proteins and damaged organelles, thus promoting cell survival during starvation and other stress conditions. A substantial body of research indicates that chemokines can modulate the development of CVD by influencing the autophagy process. Research has shown that targeting pathways such as CXCR4 and CXCL12, defective CXCL16/CXCR6, and inhibiting CX3CL1 can regulate autophagy and impact CVD. The protective role of chemokines in CVD through the modulation of autophagy may offer new perspectives for treatment.

Rheumatoid arthritis (RA) is an autoimmune disease causing joint inflammation, deformity, cartilage deterioration, and pain. Benzimidazole derivatives exhibit various pharmacological properties. This study evaluated the antiarthritic, immunomodulatory, and anti-inflammatory potential of a benzimidazole derivative 2-(2-(benzylthio)-1 H -benzo[ d ]imidazol-1-yl)- N ′-(4-nitrobenzylidiene) acetohydrazide (BMZ-AD) in a Freund’s complete adjuvant (FCA)-induced arthritic rat model. FCA was administered on day 0, and treatment with BMZ-AD (25 mg/kg, 50 mg/kg, and 75 mg/kg) and piroxicam (10 mg/kg) began on day 7 and continued up to 28 days. Rats were sacrificed on day 28. Arthritis was assessed using an arthritic scoring index, and paw edema was measured with a digital water plethysmometer. Biochemical and hematological parameters were analyzed, reverse transcription polymerase chain reaction measured the mRNA expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and molecular docking evaluated BMZ-AD interactions with these proteins. Enzyme-linked immunosorbent assay determined prostaglandin E2 levels. BMZ-AD treatment reduced inflammation, pannus formation, and pro-inflammatory cytokines (TNF-α and IL-6) and decreased PGE2 levels, comparable to piroxicam. Blood profiles improved with significant reductions in white blood cells and platelets in treatment groups. BMZ-AD demonstrated antiarthritic, anti-inflammatory, and immunomodulatory properties, suggesting that it could be a potential drug for RA treatment with fewer side effects.

Alzheimer’s disease (AD) is characterized by amyloid-beta plaques and tau tangles in the brain, but these markers alone do not predict disease progression. The intersection of these pathologies with other processes including metabolic changes may contribute to disease progression. Brain glucose metabolism changes are among the earliest detectable events in AD. Pyruvate kinase (PKM) has been implicated as a potential biomarker to track these metabolic changes. We have developed an enzyme-linked immunosorbent assay (ELISA) to assess PKM levels in cerebrospinal fluid (CSF). First, we verified the relationship of CSF PKM levels with cognitive decline, revealing a correlation between elevated CSF PKM levels and accelerated cognitive decline in preclinical AD patients in a tau-dependent manner. We developed the ELISA using two PKM-specific antibodies and validated it through quality control steps, indicating robust quantification of PKM. We showed that ELISA measurements of PKM correlate with mass spectrometry values in matching samples. When tested on an independent cohort, the assay confirmed elevation of PKM in AD. These findings support the use of PKM as a potential biomarker for tracking early metabolic changes in AD, offering a novel tool for investigating metabolic alterations and their intersection with other underlying pathologies in AD progression.

This study focuses on the critical role of HDAC11 in age-related hearing loss and its underlying mechanisms. Through cellular experiments, we deeply explored the effects of HDAC11 on the proliferation and senescence of HEI-OC1 cells. The results showed that HDAC11 overexpression significantly reduced the acetylation level of α-microtubule protein, which in turn affected the stability of microtubule structure and accelerated the apoptosis and senescence process of HEI-OC1 cells. In addition, the overexpression of HDAC11 inhibited the Pink1/Parkin signaling pathway, which impeded the mitochondrial autophagy process and ultimately led to mitochondrial dysfunction. In animal experiments, we further verified the ameliorative effect of HDAC11 overexpression on hearing loss in aged mice. The experimental results showed that HDAC11 overexpression not only attenuated the histopathological damage of the cochlea in aged mice but also effectively improved their hearing function. Notably, HDAC11 overexpression suppressed the expression of cellular autophagy-related proteins and Pink1 and Parkin proteins. In summary, the present study preliminarily revealed that HDAC11 may regulate mitochondrial autophagy by inhibiting the Pink1/Parkin pathway, thus providing a new theoretical basis for improving hearing loss in the elderly.

The aim of this study is to systematically retrieve, synthesize, and assess methodologies employed in the development of paclitaxel-induced peripheral neuropathic pain (PIPNP) animal models, with the objective of optimizing protocols for model construction and evaluation. A structured search strategy was implemented using the terms “Paclitaxel-induced peripheral neuropathic pain” OR “Chemotherapy-induced peripheral neuropathic pain” AND “animal models” OR “rats” OR “mice” OR “experimental animals” across the China National Knowledge Infrastructure, Wanfang, and VIP databases. Identical search criteria were applied to the PubMed and Web of Science platforms. The literature search covered publications from database inception through December 31, 2024. A total of 128 articles were reviewed, including 18 in Chinese and 110 in English. All studies employed rodent models, including 16 strains and including both sexes, with ages ranging from 5 weeks to 10 months. In rats, 28 distinct modeling protocols were identified: 4 involving continuous paclitaxel injections, 23 employing alternate-day injections, and 1 using a single administration. For mice, 21 methods were recorded, comprising 6 continuous, 13 alternate-day, and 2 single-injection protocols. Upon successful model induction, six behavioral pain alterations were consistently documented, evaluated using 16 different assessment techniques. Current PIPNP models predominantly utilize 6- to 8-week-old male Sprague-Dawley (SD) rats, with paclitaxel administered at 2 mg/kg on either days 0, 2, 4, and 6 or days 1, 3, 5, and 7. Based on data mining and comparative evaluation of modeling approaches, the use of 6- to 8-week-old male SD rats or 8- to 10-week-old male C57BL/6J mice with paclitaxel administered at 2 mg/kg on days 1, 3, 5, and 7 is recommended for establishing PIPNP models. The translational alignment between PIPNP models and clinical phenotypes remains insufficient and requires further refinement.

Long-term repeated exposure to various stimuli leads to chronic liver damage, inflammation, fibrosis, and eventually cirrhosis. Pyroptosis, a mode of inflammatory programed cell death, affects the progression of liver fibrosis/cirrhosis. However, current research on drugs targeting the pyroptosis pathway as a therapeutic strategy in liver fibrosis and cirrhosis remains limited. This review aims to explain the relationship between pyroptosis and liver cirrhosis and focuses on methods for the treatment of liver cirrhosis based on targeted pyroptosis. Here, 31 inhibitor drugs that target inflammasomes, gasdermin D, or caspases are discussed. Although the inhibitory effect of these drugs on pyroptosis is indisputable, their efficacy on cirrhosis needs a thorough investigation. Seventeen natural plant compounds that improve liver fibrosis/cirrhosis in cellular and animal models through targeting pyroptosis are also reviewed. In addition, stem cell replacement therapy and exosomes have broad application prospects in liver cirrhosis from the perspective of pyroptosis. In the future, the primary challenges will involve validating the efficacy of the aforementioned drugs in targeting pyroptosis for cirrhosis treatment using human liver organoids as well as determining their potential clinical application.

The use of plant-based medicines for the production of green nanomaterials represents a viable route for cancer treatment. In this study, we report a novel method for the biosynthesis of zinc oxide nanoparticles (ZnO NPs) using the leaf extract of Ruellia tuberosa L. a medicinal plant known for its therapeutic properties. The study aims to test and investigate the ability of these R. tuberosa -derived ZnO NPs (RT-ZnO NPs) to cause apoptosis in human prostate cancer (PC) cells and clarify their fundamental molecular pathways. The developed RT-ZnO NPs were analysed employing field emission scanning electron microscopy, which exhibited a spherical shape with a median particle size of 156.7 nm. The methylthiazolyldiphenyl-tetrazolium bromide experiment showed that RT-ZnO NPs demonstrated considerable cytotoxicity toward DU 145 PC cells, with an IC₅₀ value of 26.82 µg/mL, while demonstrating low toxicity against normal HPE-15 prostate epithelial cells. Furthermore, the molecular analysis demonstrated that the NPs boosted p53 expression while suppressing both total and phosphorylated STAT3, indicating that anticancer activity is mediated by the p53 and STAT3 signalling pathways. This study focuses on a green and cost-effective method for creating anticancer nanomaterials, with RT-ZnO NPs emerging as a potential alternative for PC therapy. Graphical abstract

Severe aplastic anemia (SAA) and nasopharyngeal carcinoma (NPC) are two different diseases and are life-threatening if left untreated. The co-occurrence of SAA and NPC is rare and presents a complex therapeutic paradox. This study reports a unique case of a patient diagnosed with both SAA and NPC. The patient initially underwent haploidentical hematopoietic stem cell transplantation (HSCT) to achieve rapid hematologic recovery, followed by nimotuzumab + radiotherapy for carcinoma treatment. This case suggests that sequential haploidentical HSCT and radiotherapy may represent a promising therapeutic strategy for patients with coexisting SAA and NPC.

Psoriasis is a chronic, immune-mediated skin condition marked by excessive cell growth and inflammation. Current therapies frequently have limitations, such as side effects and insufficient efficacy, emphasizing the need for safer, more effective options. Erianin (ERN), a naturally occurring bioactive molecule produced from Dendrobium chrysotoxum , has anti-inflammatory and antioxidant characteristics, although its therapeutic potential in psoriasis has not been fully investigated. The purpose of this investigation was to look into the protective benefits of ERN against psoriasis-like skin inflammation utilizing laboratory-based cell models and an imiquimod-induced psoriasis animal model. Human keratinocytes were subjected to pro-inflammatory cytokines in vitro to simulate psoriasis disease, and cell survival and proliferation were measured. In vivo , mice given ERN for 6 days demonstrated a significant decrease in skin thickness, inflammatory cell infiltration, and overall histopathological alterations. ERN reduced pro-inflammatory substances (IL-6, IL-17, IL-23, IL-1β), TNF-α, COX-2, and inducible nitric oxide synthase, while increasing anti-inflammatory cytokine IL-10 and antioxidant-related molecules. Additionally, ERN stimulated the Kelch-like ECH-associated protein 1- nuclear factor erythroid 2-related factor 2 signaling pathway, which is essential for cellular antioxidant defense. The results presented here demonstrate that ERN reduces psoriasis-like inflammation by modifying immunological responses and increasing antioxidant protection, pointing to its potential as a viable therapeutic agent for psoriasis treatment. Graphical abstract

Breast cancer (BC) is a common malignant tumor with a frequent occurrence in women, and its occurrence and progression are influenced by various factors. This work aimed to investigate the expression of human epidermal growth factor receptor-2 (HER-2) in BC and its relationship with tumor-infiltrating lymphocytes (TILs) and the clinical pathological features of BC patients. Data from 470 BC patients were collected, and TIL levels were assessed. Immunohistochemistry (IHC) was performed to further analyze the relationship between TILs and clinical pathological parameters, as well as the expression of CD8 and HER-2. Immunohistochemical results revealed that the HER-2-positive expression rate was 28.72% (135/470), and its expression intensity significantly increased with higher histological grades (low grade: 15.2%, moderate grade: 28.5%, high grade: 42.6%, P < 0.05). CD8-positive cells were predominantly located in the tumor stroma, with a positive rate of 56.38% (265/470). Moreover, the positive expression intensity in the high TIL level group was significantly higher than in the low TIL level group (high TIL group: 78.9%, low TIL group: 35.4%, P < 0.05). The statistical results indicated that 37.45% (176/470) of cases exhibited no or low TIL levels, 42.34% (199/470) showed moderate TIL levels, and 20.21% (95/470) presented high TIL levels. TIL levels were significantly associated with histological grade of BC (percentage of high-grade cases in the high TIL group: 65.3%, in the low TIL group: 22.1%, P < 0.05), Ki-67 index (high TIL group: 45.2% ± 12.3%, low TIL group: 25.6% ± 10.8%, P < 0.05), vascular tumor embolism (VTE) (VTE-positive rate in the high TIL group: 38.9%, in the low TIL group: 12.4%, P < 0.05), lymph node metastasis (LNM) (LNM-positive rate in the high TIL group: 52.6%, in the low TIL group: 28.4%, P < 0.05), and estrogen receptor (ER) expression (ER-negative rate in the high TIL group: 68.4%, in the low TIL group: 32.1%, P < 0.05). Spearman correlation analysis revealed a positive correlation between TILs and HER-2 ( r = 0.149, P = 0.002), as well as CD8 ( r = 0.593, P = 0.001). Analysis of the GEPIA database showed that patients with high HER-2 expression had significantly lower disease-free survival (DFS) compared to those with low expression (hazard ratio [HR] = 1.45, P = 0.003), while patients with high CD8 expression exhibited significantly higher DFS than those with low expression (HR = 0.72, P = 0.001). In HER-2-positive BC patients, TIL levels were positively correlated with HER-2 and CD8 expression (high HER-2 expression group: TIL high expression rate 48.6%, low HER-2 expression group: TIL high expression rate 15.2%, P < 0.05). TIL levels in HER-2-positive BC patients were positively correlated with both HER-2 and CD8 expression. TIL levels were closely related to the prognosis of BC patients, which may provide a theoretical basis for precision treatment in BC. Graphical abstract This study focused on breast cancer (BC) and explored the relationship between the expression of human epidermal growth factor receptor-2 (HER-2) and tumor-infiltrating lymphocyte (TIL) and its clinicopathological features. It was found that TIL was positively correlated with HER-2, and TIL level was closely related to various clinicopathological features. At the same time, the high expression of CD8A was related to the better overall survival of patients, and the intensity of HER-2 expression increased with the increase of histological grade. These results provide a theoretical basis for the accurate treatment of BC. Overview of the relationship between HER-2 expression, tumor infiltrating lymphocytes, and clinicopathological characteristics in BC.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a robust analytical technology that has become integral to biomolecular research. Since its introduction into microbiology in the early 2000s, its versatility has enabled a wide spectrum of applications extending from routine microbial identification to advanced proteomic profiling, antimicrobial resistance testing, biomarker discovery, and even historical disease investigation. In proteomics, MALDI-TOF MS has proven valuable for identifying disease-associated proteins, with applications in oncology, metabolic disorders such as diabetes and dyslipidemia, neurodegenerative diseases, hemoglobinopathies, and neonatal screening. Additionally, it has facilitated pharmacokinetic studies by enabling detailed analysis of drug distribution and metabolism. Despite limitations such as dependency on reference databases and challenges in distinguishing closely related species, ongoing advancements continue to enhance its accuracy and range. The integration of MALDI-TOF MS with molecular methods like polymerase chain reaction further strengthens its diagnostic utility. This review aims to present recent technological progress while highlighting the expanding interdisciplinary utility of MALDI-TOF MS. Emphasis is placed on emerging fields, including paleopathology, where its potential remains underexploited. By outlining its evolving capabilities, we propose a conceptual framework that positions MALDI-TOF MS as a unifying platform capable of driving innovation across diverse scientific and biomedical disciplines.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. A few genes, such as BAP1 , are associated with the tumorigenesis of ccRCC. Mutations in BAP1 are related to a proportion of ccRCCs. In this study, to explore the functional role of BAP1 in ccRCC, the potential interacting proteins with BAP1 in ccRCC cells are to be identified, and the gene expression profiles of BAP1 knockdown 786-O cells are to be analyzed.

In some cases, higher IgG4 levels are accompanied by increased circulating IgE, higher eosinophil counts, and various autoantibodies. Among these cases, IgG4-related disease (IgG4-RD) is one of the most frequently diagnosed conditions. This study reported two particularly complex and rare cases of hypereosinophilic syndrome (HES) associated with elevated IgG4 and T-cell clonality. The first case involved T-cell clonality complicated by HES and IgG4-RD, presenting with clinical features resembling eosinophilic granulomatosis with polyangiitis (EGPA). Laboratory findings showed a serum IgG4 concentration of 8.74 g/L, an IgG4/IgG ratio of 40.58%, and positive results for P-anti-neutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Renal biopsy findings were consistent with IgG4-related interstitial nephritis. However, routine hematological testing revealed a markedly elevated eosinophil count of 14.75 × 10 9 /L and eosinophilic infiltration in both lymph nodes and kidney tissue. Furthermore, monoclonal rearrangements of the T-cell receptor gamma and delta genes were identified. The second patient was ultimately diagnosed with HES with elevated IgG4 and T-cell clonality, with an elevated IgG4 concentration of 2.458 g/L and an eosinophil count of 14.75 × 10 9 /L. In conclusion, in cases presenting with elevated IgG4 levels and hypereosinophilia, further pathological and genetic evaluations may be essential to guide appropriate and timely treatment, improving patient prognosis.

The aim of this study is to investigate the role of electroacupuncture in alleviating sciatic nerve injury. A rat model for sciatic nerve crush injury was established using clamping forceps, and then electroacupuncture at the “Zusanli” (ST36) and Huantiao” (GB30) acupoints was performed. The values of sciatic functional index (SFI), paw withdrawal latency (PWL), and paw withdrawal threshold (PWT) were evaluated. The mRNA expression of neurotrophic factors in nerve tissues was examined by RT-qPCR analysis. Morphometric analyses of transverse sections at the sciatic nerve distal to injury were performed 8 weeks post-injury. Immunofluorescence staining of sciatic nerve and western blotting were performed to measure the expression of myelin protein zero (MPZ) and autophagy markers. The experimental results displayed that the motor and sensory functions of sciatic nerve crush injury rats were restricted by pressure application. Electroacupuncture ameliorated sciatic nerve injury by increasing SFI, PWT, and PWL values in model rats during the recovery period. Electroacupuncture upregulated the mRNA expression of neurotrophic factors (brain-derived neurotrophic factor and nerve growth factor), increased the diameter of fibers and axon, and increased the thickness of myelin sheath after electroacupuncture. Electroacupuncture reduced MPZ and p62 expression while increasing LC3B and beclin-1 expression. In conclusion, electroacupuncture alleviates sciatic nerve injury by promoting nerve regeneration and autophagy. Graphical abstract

Polydatin is a stilbene that has been demonstrated to regulate lipid, cholesterol, and glucose metabolism in humans. However, its potential role in cholesterol gallstone formation remains uncertain. C57BL/6 mice were fed a lithogenic diet (LD) and administered polydatin via intragastric administration. At the end of the 8-week study period, the animals were euthanized in order to collect bile/serum samples and gallbladder/liver tissues for subsequent analysis. In vitro studies were conducted in which human intrahepatic biliary epithelial cells (HIBECs) were exposed to lipopolysaccharide (LPS) for a period of 24 h. Subsequently, the culture supernatant and cells were harvested for further analysis. The results demonstrated that polydatin markedly reduced cholesterol gallstone formation, attenuated pathological alterations in the gallbladder and liver tissues, and improved lipid profiles in serum and bile samples. Moreover, polydatin exhibited anti-inflammatory properties, regulated cholesterol metabolism-related genes, and activated the PPAR-γ signaling pathway in mice fed an LD diet. In HIBECs, polydatin treatment prevented LPS-induced inflammatory cytokine release, dysregulation of cholesterol metabolism-related genes, and inactivation of the PPAR-γ pathway. This study is the first to demonstrate that polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via the PPAR-γ signaling pathway. Graphical abstract

RNF144 family proteins, including RNF144A and RNF144B, members of the RING-between-RING domain-containing ubiquitin E3 ligase family, serve as critical regulators of protein ubiquitination. Despite increasing research attention in recent years, particularly regarding their distinct functional roles in pathophysiological processes, a comprehensive synthesis of existing findings remains absent. To address this knowledge gap, we conducted a systematic literature search in PubMed using the following query terms: “RNF144,” “RNF144A,” “RNF144B,” “PIR2,” “IBRDC2,” and “P53RFP.” This review systematically examines current evidence regarding the molecular mechanisms and pathophysiological significance of RNF144A/B across various disease systems. Through critical analysis of structural characteristics, substrate interactions, and signaling pathways, we aim to clarify their dual roles in cellular homeostasis and disease pathogenesis. This synthesis not only consolidates current understanding but also identifies key knowledge gaps requiring further investigation, particularly regarding isoform-specific functions and therapeutic targeting potential. Graphical abstract

In a cross-sectional analysis of 14,973 adults from North China, thyroid nodules (TNs) were detected via high-resolution ultrasonography in 8,104 participants (54.1%), with a higher prevalence among women. The mean age of those with TNs was significantly higher (51.39 ± 15.41 vs 41.83 ± 12.43 years, p < 0.001). Univariate analyses indicated that female sex (OR ≈ 2.0), older age (OR ≈ 1.03 per year), elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and higher BMI were significantly linked to TNs. In contrast, total cholesterol and uric acid did not reach significance in the final model. A nomogram incorporating these risk factors demonstrated moderate predictive performance (AUC = 0.84 in the training set; 0.78 in the validation set). While the study’s large sample size is a strength, its cross-sectional design limits conclusions about causality, and potential overfitting cannot be excluded. Future research should include thyroid hormone measurements, external validation of the nomogram, and longitudinal follow-up to clarify the role of metabolic factors. These findings highlight the importance of age, sex, and metabolic profiles – particularly dyslipidemia and obesity – in screening for TNs during routine health examinations.

Metastasis remains a major challenge to improve the survival of patients with hepatocellular carcinoma (HCC). Artesunate is an antimalarial drug that also has anti-cancer properties. Additionally, O -GlcNAcylation has been implicated in cancer progression. In this study, we investigated whether artesunate regulated HCC cell migration and invasion and explored its impact on protein O -GlcNAcylation. Cellular functions, including viability, migration, and invasion, were evaluated using the cell counting kit-8, scratch assay, and Transwell analysis. Molecular docking and biolayer interferometry were employed to assess the binding interaction between artesunate and OGA. Furthermore, the O -GlcNAcylation of ZEB1 was examined using immunoprecipitation, cycloheximide chase assay, and immunoblotting. Our results demonstrated that artesunate significantly inhibited HCC cell viability, migration, and invasion. OGA expression was increased in HCC cells after artesunate treatment. Artesunate directly bound to OGA, and OGA knockdown reversed the inhibition of malignant behaviors induced by artesunate. Additionally, OGA suppressed the O -GlcNAcylation of ZEB1 at the Ser670 site, decreasing protein stability. Knockdown of ZEB1 inhibited HCC cellular behaviors. In conclusion, artesunate inhibits HCC cell migration and invasion by binding to OGA, which removes the O -GlcNAcylation of ZEB1 at the Ser670 site. These findings provide a new action mechanism for artesunate to treat HCC. Graphical abstract Artesunate combines with OGA, which promotes O -GlcNAcylation of ZEB1 and thus reduces the protein stability of ZEB1, further inhibiting migration and invasion of hepatocellular carcinoma cells.

Pancreaticoduodenectomy is the standard surgical treatment for a range of malignant and some benign diseases. The mortality rate associated with this procedure has decreased to less than 3% in recent years, although the morbidity remains high at 6–40%. Common complications may include delayed gastric emptying, pancreatic fistula, intra-abdominal abscess, and gastrointestinal or intra-abdominal bleeding, among others. Bleeding and pseudoaneurysm formation are likely to be the most significant complications. This is a case report about gastrointestinal bleeding following a Whipple procedure from an aberrant hepatic artery originating from the superior mesenteric artery (SMA), treated by endovascular means. The SMA was cannulated under local anesthesia and direct puncture of the common femoral artery. Catheterization and angiogram of the aberrant right hepatic artery identified the pseudoaneurysm and bleeding site at its bifurcation. Coil embolization resulted in pseudoaneurysm occlusion and bleeding management. Hepatic perfusion was not affected as the main vasculature of the liver, namely the common hepatic artery, remained intact. The management of hemorrhage following pancreatectomy represents a significant challenge, particularly given the vulnerability of the patient cohort and the necessity for re-operation in an anatomically challenging environment. Endovascular intervention is the preferred method of treatment when applicable, as it can be performed under local anesthesia and is associated with less morbidity.

This article conducts a meta-analysis to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). A total of 63 papers were initially retrieved, and eight clinical studies were collected. The estimated effect of ORR was [OR = 0.40, 95% CI 0.29–0.51; p = 0.08], the estimated effect of complete response rate was [OR = 0.21, 95% CI 0.14–0.31; p < 0.001], while the estimated effect of 1-year progression-free survival was [OR = 0.33, 95% CI 0.22–0.47; p = 0.01]. The estimated effect of 1-year OS was [OR = 0.67, 95% CI 0.55–0.77; p = 0.05]. In addition, the estimated effect of grade 3 adverse events was [OR = 0.33, 95% CI 0.22–0.46; p = 0.01]. Overall, PD-1/PD-L1 inhibitors demonstrated suboptimal therapeutic efficacy in the selected trials for R/R DLBCL. However, combining PD-1/PD-L1 inhibitors with CAR-T showed potential for improved treatment outcomes. Additionally, PD-1/PD-L1 inhibitors were found to be safe and well-tolerated in patients with R/R DLBCL.

The purpose of this study was to explore the potential mechanism of SATB2 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway promoting fracture healing in vivo . An SD model of humeral fracture in rats was established and treated. Following a 6-week treatment period, the morphology of the fracture was assessed. Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), osteocalcin, C-telopeptide of type I collagen (CTX-I), and bone morphogenetic protein 2 (BMP-2) were determined. Alkaline phosphatase (ALP), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and other relevant molecules such as PI3K and p-AKT were measured. The results showed that SATB2 overexpression repaired humeral fracture and bone continuity. SATB2 overexpression resulted in a significant reduction in RANKL, IL-6, TNF-α, and CTX-I expression, while simultaneously increasing OPG, ALP, osteocalcin, and BMP-2. This indicates that SATB2 inhibits osteoclast activity and promotes osteoblast function. Additionally, SATB2 overexpression increased PI3K and p-AKT protein expression in humerus. Furthermore, the inhibitory effect of the PI3K/AKT inhibitor on PI3K and p-AKT protein expression was counterbalanced by upregulating SATB2. In conclusion, SATB2 promotes fracture healing in humeral fracture rats by stimulating the proliferation and differentiation of osteoblasts, which is related to the activation of PI3K/AKT signaling pathway.

The current work has further elucidated the expression and functional implication of cysteine desulfurase (NFS1) in gastric cancer (GC), the prognostic value, and therapeutic target because of the interaction with tumor immune infiltration and ferroptosis. Transcriptomic data from TCGA and GTEX were analyzed to assess mRNA expression and survival correlation with NFS1 among GC patients. A total of 152 GC cases were retrospectively analyzed. The level of NFS1 expression was upregulated in GC tissues compared to non-tumor gastric tissues, which was related to clinical characteristics and poor prognosis. Downregulation of the NFS1 protein in the GC cell line had an adverse effect on the migration, invasion, and proliferation of cells. In addition, NFS1 and immune correlation analysis showed that the level of NFS1 expression was related to a variety of immune cells and characteristics of the immune microenvironment. Based on functional enrichment analysis, NFS1 may have a role in ferroptosis and the tumor microenvironment (TME), such as epithelial–mesenchymal transition control, and the stromal and immunologic responses. NFS1 is a potential diagnostic and prognostic biomarker linked to ferroptosis and the TME, and provides a novel target for cancer treatment and immunotherapy.

Diabetic foot ulcer (DFU) is a severe and prevalent complication of diabetes mellitus, posing substantial risks to patient health and increasing healthcare burdens globally. These chronic wounds often result from a complex interplay of factors, including neuropathy, ischemia, infection, immune dysregulation, and vascular dysfunction, leading to significant morbidity and, in severe cases, amputation. Effective management of DFUs necessitates a comprehensive understanding of their risk factors and prognostic indicators. This review provides an in-depth examination of the various risk factors and prognostic markers associated with DFUs, integrating insights from cellular mechanisms, emerging biomarkers, omics-based research, serological studies, and clinical assessments. We explore the underlying biological processes, such as the impact of chronic hyperglycemia, oxidative stress, inflammation, impaired angiogenesis, and the role of the microbiome in DFU development. The role of serological markers, including inflammatory and glycemic indicators, in predicting DFU risk and progression is discussed. Additionally, clinical markers and advanced assessment tools, such as ulcer grading systems and imaging technologies, used to evaluate DFU severity and healing are reviewed. By synthesizing these diverse perspectives, this review aims to offer a holistic view of DFU management, highlighting how understanding the interplay of risk factors and prognostic markers can lead to improved prevention strategies and personalized therapeutic interventions.

Allergic rhinitis (AR) is a frequent respiratory condition characterized by elevated immunoglobulin E (IgE) levels and nasal mucosal inflammation. Atractylenolide I (ATL-I), a bioactive ingredient in medicinal plants, is known for its ability to alleviate tissue damage by inhibiting inflammatory and oxidative stress responses. In this study, we aimed to investigate the protective roles of ATL-I in AR and reveal the potential mechanism involved. The AR model was developed in mice by intraperitoneal sensitization followed by intranasal exposure to ovalbumin. The effects of ATL-I on allergic responses were evaluated by recording sneezing and rubbing frequencies and measuring the serum concentrations of Th1 and Th2 cytokines following the intragastric administration of ATL-I. The activation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) pathway and the NOD-like receptor 3 (NLRP3) inflammasome was assessed via Western blotting and immunohistochemistry. The results showed that ATL-I administration alleviated allergic responses in AR mice, as evidenced by significant decreases in the frequencies of sneezing and rubbing and in the serum concentrations of histamine and IgE. Compared with control mice, AR mice presented downregulated Th1 cytokines and upregulated Th2 cytokines, whereas the Th1/Th2 imbalance was improved by ATL-I. ATL-I reduced the mucosal layer thickness and alleviated goblet cell hyperplasia in AR mice. Furthermore, ATL-I inhibited TLR4/NF-κB pathway activation in mucosal tissues, which resulted in the inactivation of the downstream NLRP3 inflammasome. In summary, our results indicate that ATL-I alleviates allergic responses by inhibiting the TLR4/NF-κB/NLRP3 pathway, providing a promising therapeutic strategy for AR. Graphical abstract

Determining the critical elements in melanoma stem cell growth could aid in preventing the development of malignant cancer. The purpose of this study was to illustrate how FBXO31 affects the stemness, invasion, and migratory properties of melanoma stem cells. Side population (SP) cells with tumor stem cell characteristics were sorted from A375 melanoma cells. The mRNA and protein expression levels of FBXO31 in SP cells were detected using molecular techniques. FBXO31 was then transfected into SP cells, and the proportion of CD147 (+) cells in SP cells was detected by flow cytometry. FBXO31 was also transfected into CD147 (+) cells, and their spheroid formation, migration, and invasion ability were measured. Additionally, CD147 (−) and CD147 (+) cells were inoculated into nude mice to assess the effect of FBXO31 on tumor growth and metastasis. The findings demonstrate that FBXO31 is downregulated in SP cells. Upon FBXO31 transfection, the proportion of CD147 (+) cells sorted from SP cells decreased. CD147 (+) cells exhibit higher stemness characteristics, migration, and invasion abilities than CD147 (−) cells. However, these characteristics were markedly suppressed following FBXO31 transfection in CD147 (+) cells. In vivo experiment further showed that CD147 (+) cells promoted tumor growth and metastasis, while after transfection with FBXO31, tumor proliferation and metastatic abilities were inhibited. Overall, FBXO31 inhibits the migration, invasion, and stemness characteristics of CD147 (+) melanoma stem cells. Graphical abstract

Traditional serrated adenomas (TSAs) and sessile serrated adenomas (SSAs) are known precursors to colorectal cancer (CRC), but differentiating between them morphologically can be challenging. This study developed an immune molecule-based model to distinguish TSA from SSA using RNA sequencing data from the GEO datasets (GSE117606, GSE45270, GSE117607). Gene expression profiling was conducted with the R package GEOquery, and immune cell infiltration was assessed using CIBERSORTx. Differential expression analysis of immune-related genes was performed with the “limma” package. Enrichment analysis of differentially expressed genes (DEGs) was conducted using “clusterProfiler” for Gene Ontology and kyoto encyclopedia of genes and genomes pathways, identifying protein-protein interaction networks to find core hub genes. Notable differences in immune cell infiltration were observed among SSA, TSA, CRC, and healthy tissues, involving various immune cell types. A total of 45 DEGs (34 upregulated, 11 downregulated) were identified, with CCL2 and CXCL11 emerging as key hub genes. Their diagnostic potential was validated through receiver operating characteristic analysis in GEO datasets and clinical samples, while immunohistochemistry revealed decreased expression of CCL2 and CXCL11 in SSA compared to TSA and normal tissues, indicating their role in SSA pathogenesis and potential as molecular diagnostic markers. The diagnostic value of CCL2 is superior to that of CXCL11, while the diagnostic value of CXCL11 requires further experimental verification.

This study investigates the previously unexplored role of CXC chemokine receptor 6 (CXCR6) in hepatic fibrosis, where excessive extracellular matrix deposition by activated hepatic stellate cells (aHSCs) drives disease progression. Through analysis of gene expression omnibus datasets and human fibrotic liver samples, we identified significant CXCR6 upregulation, subsequently validated in murine fibrosis models. Using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry, we demonstrated that CXCR6 silencing in vitro promoted aHSC senescence – as confirmed by senescence-associated β-galactosidase staining and Cell Counting Kit-8 assays – while simultaneously restricting the pro-inflammatory senescence-associated secretory phenotype (SASP). Mechanistically, the enzyme-linked immunosorbent assay revealed this process involves modulation of the interleukin-1 alpha/nuclear factor-kappa beta feedback loop. Our findings position CXCR6 inhibition as a promising therapeutic strategy that uniquely targets both fibrogenesis (through hepatic stellate cell senescence induction) and inflammation (via SASP regulation) in hepatic fibrosis.

Cadmium induces toxicity to both flora and fauna, even when it is present in trace amounts. Electroplating, pigments, smelting, mining, alloy production, plastic, cadmium–nickel batteries, fertilizers, pesticides, paint, synthesis of dye, textile operations, and refining sectors all release cadmium into the aquatic environment. “Solvent extraction, adsorption, ion exchange, and precipitation” are a few strategies for removing cadmium. Biochar is an inexpensive and sustainable adsorbent that has proven to be an efficacious adsorbent for the recovery of Cd( ii ) from water. This study discusses the toxicity of cadmium as well as some recent developments of pristine biochar and modified biochar for the elimination of cadmium (Cd) from aqueous solution. Graphical abstract

Pulmonary cryptococcosis (PC) is an invasive fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii . Its clinical presentation and radiological findings are often non-specific, making early diagnosis challenging. Herein, the case of a 44-year-old male who presented with dizziness and headache is reported. Initial cranial magnetic resonance imaging and chest computed tomography (plain and contrast-enhanced) suggested lung cancer with brain metastasis. A definitive diagnosis was established only after a lung mass biopsy, followed by a cytological smear and histopathological analysis, confirmed PC. The patient was treated with antifungal therapy postoperatively and responded well. This case underscores the importance of considering PC in differential diagnoses to enable prompt diagnosis and treatment, potentially reducing associated mortality.

This report presents a case of solitary pulmonary metastasis from colon cancer, characterized by cystic airspaces, which can mimic a second primary lung cancer (LC). Preoperative contrast-enhanced computed tomography in a patient with colon cancer revealed a pulmonary micronodule with a cystic cavity in the right upper lobe. The patient subsequently underwent left-sided hemicolectomy followed by six cycles of chemotherapy. During follow-up, computed tomography demonstrated resolution of the right upper lobe nodule. However, 36 months after chemotherapy, a solid nodule with cystic airspaces appeared in the right upper lobe, exhibiting marginal spiculation, traversing vessels, and enhancement, suggestive of cystic LC. Intraoperative frozen section analysis indicated features of intestinal adenocarcinoma. A right upper lobe wedge resection was performed, and postoperative histopathology confirmed the lesion as metastatic colon adenocarcinoma with cystic airspaces. Solitary pulmonary metastasis from colon cancer is relatively uncommon, particularly with cystic presentation. Clinicians and radiologists should maintain heightened suspicion in such atypical cases to avoid missed or delayed diagnoses.

Peripheral nerve injury-induced muscle atrophy is characterized by chronic inflammation and dysregulated macrophage polarization. RUNX1, a transcription factor upregulated in denervated muscle, has been implicated in linking muscle degeneration to inflammatory processes, but its downstream targets and mechanisms remain unclear. The aim of this study is to delineate the RUNX1-JUNB-NF-κB axis in driving inflammation-mediated muscle atrophy. The GSE183802 single-nucleus RNA sequencing dataset was analyzed to identify RUNX1-associated pathways. A sciatic nerve transection model in mice was established to validate RUNX1 expression dynamics. Chromatin immunoprecipitation, dual-luciferase reporter assays, and siRNA-mediated knockdown were used to confirm RUNX1’s transcriptional regulation of JUNB . In vitro models (C2C12 myotubes, RAW 264.7 macrophages) assessed RUNX1-driven inflammatory responses, NF-κB activation, and extracellular matrix remodeling. RUNX1 was significantly upregulated in denervated muscle, particularly in myonuclei and macrophage subclusters, correlating with elevated atrophy markers (MuRF1, Atrogin-1). RUNX1 overexpression directly activated JUNB transcription via promoter binding, leading to NF-κB pathway activation (increased p65 phosphorylation) and M1 macrophage polarization (enhanced IL-1β/TNF-α secretion). JUNB knockdown reversed RUNX1-induced pro-inflammatory cytokine release, NF-κB signaling, and muscle atrophy markers. This study identifies the RUNX1-JUNB-NF-κB axis as a central regulator of inflammation-driven muscle atrophy following denervation. Targeting this pathway may offer therapeutic potential to mitigate neurogenic muscle degeneration and immune-mediated damage in conditions such as peripheral nerve injuries or motor neuron diseases. Graphical abstract

The present study aimed to evaluate the therapeutic potential of Indigofera oblongifolia with silver nanoparticles (AgNPs) and chloroquine (CQ) 10 mg/kg in treating lung inflammation caused by Plasmodium chabaudi infection in a mouse model. Fifty female C57BL/6 mice were divided into five groups: control, Indigofera oblongifolia leaf extract (IOLE) AgNPs treated, P. chabaudi infected, infected and IOLE AgNPs treated, infected and CQ 10 mg/kg treated. Lung histopathology was assessed using microscopic analysis and immunohistochemistry investigation for TNF-α and IL-6. The results showed that the positive control of AgNPs slightly triggered proinflammatory cytokines and created an oxidative stress status in lung tissue. The group IOLE AgNPs treatment significantly restored the normal organization of the control lung tissue. It reduced alveolar and septal congestion, edema, and necrosis compared to the infected lung. Therefore I. oblongifolia as a natural medical plant displayed significant antimalarial and anti-oxidant properties effectively, reducing inflammatory signs and cytokine levels in P. chabaudi -infected lungs and treating the harmful impact of AgNPs in P. chabaudi -infected + I. oblongifolia with AgNPs lung. While CQ shows limited efficiency, it showed moderate improvement in the histological architecture such as thicker alveolar and bronchiolar walls and restricted expansion. However, the septal and alveolar congestion, hemosiderin concentration, edema, and necrotic cells were still present. Also, immunohistochemistry expression of proinflammatory cytokines is still expressed. In conclusion, this study highlights the therapeutic potential of I. oblongifolia for malaria management. Also, this study uniquely explored the combined influences of I. oblongifolia leaf extract and AgNPs on lung inflammation caused by P. chabaudi infection. Previous studies may have explored these components separately, but the current study examines their synergistic potential in treating malaria-related lung pathology. Consequently, the study compared the efficacy of I. oblongifolia with that of CQ, revealing that the latter exhibited limited efficiency due to drug resistance and its inability to restore the normal features of its histology. This comparison highlights the potential impact of I. oblongifolia as a more effective alternative in malaria treatment, particularly in cases where conventional drugs fail. Graphical abstract

Gene regulation is important during tissue formation, but redundant systems make it difficult to study in vivo. The protein Jazf-1 is a member of the NuA4/TIP60 histone-modifying complex, and a transcriptional repressor has been suggested to be important for Drosophila melanogaster eye development. We used the GAL4-UAS system to determine the impact of altering gene expression. GAL4-UAS manipulations of Jazf-1 in the eye caused variable and not fully penetrant phenotypes. Increased expression of Jazf-1 has been shown to suppress a Lobe 2 small eye phenotype. We found that Lobe 2 produces a sensitive background for an in vivo assay to monitor gene regulatory complexes. Depleting Jazf-1 and other NuA4/TIP60 complex members significantly enhanced the eye phenotype. We also tested Hr78, which directly interacts with Jazf-1, and found it inversely modifies the Lobe 2 phenotype. An Hr78 mutation predicted to uncouple the Jazf-1 interaction but still capable of interactions with transcriptional activators further enhanced the Lobe 2 mutant phenotype, suggesting the loss of a repressing complex. We believe that Hr78 is acting as an anchor for repressing and activating complexes and the NuA4/TIP60 complex helps repress genes that can negatively impact eye formation in the context of Lobe 2 .

This article aims to explore the effects of salmon demineralized bone matrix (DBM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone formation. Salmon DBM, with its high water absorption capacity, was used to construct a composite material with rhBMP-2 under pH 7.0 and optimal temperature conditions. The compound effects of the composite material were evaluated by measuring its mechanical strength, microstructure, and biocompatibility through scanning electron microscopy and cell culture experiments. The effect of rhBMP-2 within the composite was assessed by in vivo fluorescence imaging. rhBMP-2 was successfully loaded onto salmon DBM and released slowly. The composite material’s structure, strength, and cell compatibility were unaffected. The compressive strength was 2.87 MPa, slightly higher than DBM alone (2.27 MPa). In vivo imaging showed slow release of rhBMP-2, with more than 50% fluorescence intensity remaining after 3 days. Cytotoxicity tests showed no harmful effects, with over 95% cell growth. Rats with rhBMP-2-loaded DBM had higher serum calcium (1,569 ± 114 mg/L) than those with DBM alone (1,349 ± 110 mg/L, p < 0.05). Histology showed more bone growth and calcium deposition around rhBMP-2-loaded DBM. Loading rhBMP-2 onto DBM does not alter its physical, chemical, or biological properties; it enhances the osteogenic potential of DBM.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease in China; there is an urgent need to identify more effective treatments for IgAN. A 34-year-old woman presented with proteinuria of >2 years’ duration. She was diagnosed with IgA nephropathy and was treated with a combination of telitacicept and half-dose glucocorticoids. At the time of writing, the patient’s urinary protein concentration and renal function were normal. A combination of telitacicept and half-dose glucocorticoids is an effective way to treat IgAN.

The legalization of cannabis for industrial and medicinal purposes has significantly expanded worldwide. This study delves into the analgesic potential toxicity study of chloroformic extract from the Moroccan Cannabis sativa L. ( C. sativa ) cultivar, Khardala (KH extract). Our findings reveal that the lethal dose of KH extract is ≥5,000 mg/kg, with mice given 2,000 mg/kg exhibiting neurotoxic symptoms, including piloerection, aggressiveness, and fear, along with marked hepato-renal toxicity indicated by elevated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine in both male and female subjects. Importantly, no toxicity was observed at 250 mg/kg and 500 mg/kg doses. Remarkably, at a dose of 500 mg/kg, the KH extract demonstrated a potent analgesic effect superior to cannabidiol (CBD), suggesting a synergistic interaction among the extract’s bioactive compounds, such as CBD, cannabidivarin (CBDV), Delta 9 tetrahydrocannabinol (THC), cannabigerol (CBG), Delta 9 tetrahydrocannabivarin (THCV), and β-caryophyllene. In silico analysis supports these findings, showing the strong binding potential of THC, THCV, CBG, and CBDV to delta opioid receptors, with G -scores >−5.0 kcal/mol, highlighting the promising analgesic efficacy of this cannabis cultivar extract. This study underscores the therapeutic potential of the KH cultivar, positioning it as a promising candidate for pain management therapies. Graphical abstract

Wound healing is a precisely regulated dynamic process in which signaling pathways play a central role. This article provides a comprehensive review of the signaling pathways involved in wound healing, emphasizing their roles in inflammation, vascular regeneration, cell proliferation, and extracellular matrix remodeling. We further discuss the crosstalk between these pathways and their contributions to wound healing dysregulation. Finally, we explore emerging therapeutic strategies targeting these pathways, including small-molecule inhibitors, gene therapy, and biologics, summarizing their preclinical and clinical efficacy. By elucidating the molecular mechanisms underlying wound healing and potential interventions, this review aims to provide valuable insights for future research and translational applications in wound healing.

Brain metastases (BMs) usually occur in the advanced stage of cancers with a poor prognosis. This study aimed to compare the clinical efficacy and effects on cognitive function of immunotherapy combined with whole brain radiotherapy (WBRT) and immunotherapy combined with WBRT plus sequential integrated boost (SEB) in the treatment of multiple BMs. A total of 57 patients diagnosed with BMs were included in Kezhou People’s Hospital Affiliated to Nanjing Medical University between 2021 and 2023. Patients were allocated into the WBRT group ( n = 27) and the WBRT + SEB group ( n = 30) based on whether to receive a boost. The WBRT + SEB group showed a higher complete response rate and objective response rate compared to the WBRT group (26.7 vs 14.8%, 90.0 vs 66.7%) (all P < 0.05). The two groups had a median overall survival (OS) time of 11.2 months (95% confidence interval [CI]: 9.3–13.1) and 9.4 months (95% CI: 6.2–12.6), respectively, with no statistically significant difference ( P = 0.176). There was no difference in the levels of mini-mental state examination score at 1, 3, and 6 months, as well as the risk of adverse events, after WBRT between the two groups. In conclusion, SEB may improve the remission rate of lesions but not prolong the OS time. The boost would neither increase serious side effects nor would it aggravate cognitive impairment caused by WBRT.

The aim of this study is to investigate the characteristics and etiology of endometrial hyperemia in patients with polycystic ovary syndrome (PCOS) through two complementary approaches: clinical data analysis to characterize endometrial hyperemia and clinical trials to elucidate its underlying causes. ELISA was employed to quantify inflammatory mediators in endometrial tissue, while reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were conducted to assess the expression levels of molecules associated with endoplasmic reticulum stress (ERS). Additionally, RT-qPCR was used to determine the mRNA expression levels of HIF-1α, VEGF, and EPO. Compared with non-PCOS patients, those with PCOS exhibited a significantly higher prevalence of chronic endometritis (CE) ( P < 0.05) along with increased levels of inflammatory factors ( P < 0.05). Furthermore, the mRNA expression levels of HIF-1α, VEGF, and EPO, as well as ERS-related molecules, were significantly elevated in PCOS patients ( P < 0.05). These findings indicate that women with PCOS are more likely to suffer from CE and that endometrial hyperemia is the primary manifestation of CE in these patients. The results further suggest that endometrial hypoxia-induced ERS may contribute to the development of endometrial hyperemia in PCOS patients.

The Latin scientific name of turmeric is Curcuma longa L., and it belongs to the Zingiberaceae plant family. Curcumin is a yellow compound extracted from the rhizomes of turmeric, known for its various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. This study presents a comprehensive review of the relationship between curcumin and the immune response in breast cancer (BC). Specific therapeutic approaches of curcumin for BC treatment are summarized. The anti-tumor activity of curcumin has garnered significant attention, with unique immunomodulatory effects on inhibiting cancer cell proliferation, inducing autophagy, affecting the cell cycle, and regulating cell apoptosis. Curcumin enhances immune cell-mediated actions against cancer cells through modulation of immune response pathways, alteration of the tumor microenvironment, and influencing immune cell function. Curcumin, via multiple pathways such as anti-inflammatory, antioxidant, apoptosis-inducing, and immunomodulatory effects, holds important clinical value in BC therapy. Graphical abstract

Descurainia sophia (L.) Webb ex Pran known as Flixweed is recognized as an ethnomedicinal plant in Chinese traditional medicine, offering numerous therapeutic benefits. Antioxidant chemicals found in this medicinal plant protect cellular integrity from various sources of damage and may help prevent cancer. In this study, we investigated copper/nickel nanoparticles (Cu/NiBMNPs@Flixweed) that were green-mediated following principles of green chemistry, utilizing the aqueous extract of D. sophia seeds for the treatment of lung carcinoma. The effectiveness of these Cu/Ni nanoparticles’ effectiveness was tested against three common human lung cancer cell lines. Methods such as X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), Fourier transform-infrared spectroscopy, and energy dispersive X-ray were used to analyze the Cu/Ni nanoparticles produced through environmentally friendly methods. The XRD pattern revealed that the crystalline structure of the generated NPs is seen in the XRD pattern. According to the FE-SEM results, the nanoparticles had an average size of 68.52 nm and a semi-spherical shape. The IC 50 values of Cu/NiBMNPs@Flixweed against HLC-1, LC-2/ad, and PC-14 cells were found to be 170, 98, and 57 μg/mL, respectively. The IC 50 values of Cu/NiBMNPs@Flixweed against 2,2-diphenyl-1-picrylhydrazyl free radicals was 30 μg/mL. Recent research indicates that Cu/NiBMNPs@Flixweed may be a promising option to assist in the treatment various types of lung cancer. Graphical abstract

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. A key pathological feature of AF is atrial fibrosis, which promotes arrhythmogenic remodeling. While myocardial fibrosis has been widely observed in AF models, the underlying molecular mechanisms driving fibrotic progression remain incompletely understood. AF rats were modeled using acetylcholine, followed by treatment with different concentrations of dapagliflozin (DAPA) or positive control amiodarone. To elucidate the role of the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) pathway in AF, lipopolysaccharide (LPS; an HMGB1/RAGE pathway activator) and FPS-ZM1 (a RAGE inhibitor) were employed. Cardiac function, myocardial fibrosis, and inflammation-related proteins were assessed using echocardiography, enzyme-linked immunosorbent assay, histological staining, Western blotting, and reverse transcription quantitative polymerase chain reaction. AF rats exhibited marked cardiac dysfunction, fibrosis, and increased expression of inflammatory markers. DAPA restored cardiac function, attenuating fibrosis and inflammation. LPS aggravated cardiac injury, while DAPA attenuated the damage, with the greatest protective effects observed in the LPS + DAPA + FPS-ZM1 group. DAPA attenuates atrial fibrosis and cardiac dysfunction in AF rats by inhibiting the HMGB1/RAGE pathway. This study suggests the potential of DAPA as a therapeutic option for AF.

A chronic inflammatory skin disorder, psoriasis, affects 2–3% of people worldwide. A bioactive substance, glycitein (GCN), has several pharmacological characteristics. This work aims to evaluate the effects of GCN on the in vitro proliferation and death of human HaCaT keratinocytes. An in vitro model was created to simulate psoriatic features utilizing HaCaT keratinocytes activated by M5 cytokines. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test was used to quantify cell viability, whereas the BrdU assay was used to assess the proliferation rate. Using a DCFH-DA probe and an Annexin V-FITC/propidium iodide detection kit, flow cytometry was used to examine the generation of reactive oxygen species (ROS) and apoptosis, respectively. Western blot and quantitative polymerase chain reaction were employed to determine the amounts of phosphorylated Akt (p-Akt) and Akt proteins. GCN dramatically decreased the inflammation and hyperproliferation that cytokines caused in HaCaT keratinocytes. The alteration of mitochondrial membrane potential promoted apoptosis and caused cell cycle arrest at the sub-G1 phase, which indicates apoptotic DNA fragmentation. The suppression of the PI3K/Akt signalling pathway was linked to increased intracellular ROS levels brought on by GCN therapy. These results imply that GCN reduces inflammation and keratinocyte hyperproliferation by controlling cell cycle progression and apoptosis via ROS-associated inhibition of the PI3K/Akt pathway. Graphical abstract

Cell proliferation and epithelial–mesenchymal transition (EMT) are two common tumor phenotypes closely linked to malignant tumor progression. Genes regulating tumor progression often exhibit consistent regulatory trends in these phenotypes; however, certain genes may display inconsistent regulatory patterns in tumor proliferation and EMT. In this investigation, initial transcriptomic and tumor database analyses revealed that alcohol dehydrogenase 5 (ADH5) is downregulated in non-small cell lung cancer (NSCLC) tissues and correlates negatively with NSCLC prognosis. Subsequent experimental manipulation of ADH5 levels in tumor cells demonstrated that ADH5 overexpression decreased proliferation while enhancing migration and invasion capacities in NSCLC cells. Moreover, ADH5 overexpression hindered xenograft tumor growth in nude mice. However, ADH5 knockdown yielded contrasting outcomes by stimulating NSCLC cell proliferation while impeding migration and invasion abilities. Notably, ADH5 overexpression triggered EMT through Smad2/Smad3 activation, leading to the upregulation of SRY-Box Transcription Factor 9. TGFbetaR1/ALK5 inhibitor SB431542 was able to alleviate the effects of ADH5 overexpression on NSCLC cells. This study indicates a critical role of ADH5 in tumors associated with cancer cell growth inhibition but EMT activation. These findings underscore ADH5 as a potential regulator of NSCLC cell plasticity, emphasizing its promise as a therapeutic target for NSCLC management.

Clove, Syzygium aromaticum , is a medicinal plant from the Myrtaceae family with various applications in traditional medicine. The plant has been studied for its analgesic, anti-inflammatory, antiviral, and anticancer properties. This study focuses on the green synthesis of silver nanoparticles using clove leaf extract. The synthesized NPs were characterized using chemical methods and their anticancer activity was tested against a leukemia cell line, along with the signaling pathway that followed. The AgNPs were synthesized in a spherical shape and were less than 50 nm in size. The cytotoxic effects of the AgNPs on PCS-800-011 primary peripheral blood mononuclear cells and 32D-FLT3-ITD leukemia cells were evaluated over 48 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer cells showed reduced viability with an IC 50 value of 162 µg/mL after exposure to the AgNPs. Through a detailed examination of the mTOR pathway, it was observed that AgNPs can alter the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting 32D-FLT3-ITD cell growth and death. This pathway may contribute to the inhibition of the cell cycle and induction of apoptosis by AgNPs. For this reason, AgNPs may be used as a natural anti-cancer treatment for leukemia. Graphical abstract

Excessive intracellular copper accumulation triggers cuproptosis, a novel regulated cell death process with therapeutic potential. Analyzing 566 The Cancer Genome Atlas samples alongside lung adenocarcinoma (LUAD)-specific microarray and single-cell sequencing data, we identified 109 cuproptosis-associated genes, of which C1QBP and PFKP emerged as key prognostic markers. Four-gene risk model stratified patients into high- and low-risk groups with distinct survival outcomes, where high-risk scores correlated with advanced TNM stages. Clinical validation confirmed that elevated C1QBP / PFKP expression in LUAD tissues predicted shorter progression-free survival. Functional assays demonstrated that silencing C1QBP or PFKP increased intracellular copper concentration, suppressed proliferation, and inhibited invasion, mechanistically linking these genes to cuproptosis dysregulation. Our findings nominate C1QBP / PFKP as actionable targets for LUAD therapy, offering both prognostic biomarkers and copper-metabolism-directed treatment strategies.

Exosomes are important mediators of intercellular communication, primarily through the transfer of miRNAs. However, the mechanisms regulating exosome secretion and miRNA cargo loading in T cells remain incompletely understood. In this study, we investigated the effects of bee venom (BV), a natural compound with known immunomodulatory activity, on the exosomal miRNA profile in human Jurkat T cells. The non-cytotoxic concentration of BV (2 μg/mL) was identified using the CCK-8 assay. Exosomes were isolated from BV-treated and control cells and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis (NTA), with NTA also used to quantify particle concentration for assessing changes in secretion levels. High-throughput sequencing identified 74 differentially expressed miRNAs (44 upregulated, 30 downregulated), which were validated by quantitative real-time PCR. Functional enrichment analyses (gene ontology, kyoto encyclopedia of genes and genomes, disease ontology, Reactome) revealed associations with pathways related to neural development, cell cycle regulation, and tumorigenesis. BV treatment significantly promoted exosome release and selectively altered miRNA cargo. These findings suggest that BV modulates T cell–derived exosome output and composition, providing mechanistic insights into how it may influence immune-related signaling pathways.

Pure red cell aplasia (PRCA) is a rare blood disorder that is characterized by severe hypo-erythroid bone marrow hypoplasia leading to severe anemia that usually does not respond to standard treatment. In patients with chronic kidney disease (CKD), especially in those patients who are erythropoiesis-stimulating agent (ESA) resistant, management can be quite difficult. In this case report, we will present a 67-year-old woman with CKD (not on dialysis) who presented with refractory anemia (hemoglobin 45–65 g/L) and was ultimately diagnosed with PRCA after bone marrow aspirate. This patient had previously received treatment (ESAs, iron supplementation, and multiple blood transfusions) without improvement in her blood counts. After initiation of oral Roxadustat 100 mg t.i.w., her hemoglobin increased gradually and stabilized between 100 and 106 g/L, and she no longer required blood transfusions. This case report highlights the potential role of Roxadustat as a new therapeutic option for PRCA and ESA-resistant CKD. While these data are encouraging, larger controlled studies are going to be required to evaluate measures of efficacy, dosing, and long-term safety in this population.

Breast cancer (BC) is a major global health concern, ranking among the most common neoplasms and representing one of the leading causes of cancer-related deaths worldwide. Early recognition and classification of BC subtypes are crucial for improving patient outcomes. Therefore, identifying novel biomarkers with diagnostic and prognostic significance is of great importance. The Wnt signaling pathway plays a significant role in BC by influencing various cell cycle regulation processes and stem cell renewal. This study aims to identify novel Wnt-associated biomarker panels for BC patients, composed of multiple molecular factors. A series of bioinformatical analyses have been employed, including weighted gene co-expression network analysis, differential expression analysis, Kaplan–Meier survival analysis, logistic regression model evaluation, and receiver operating characteristic construction. Thus, this study revealed potential diagnostic and prognostic signatures based on comprehensive analyses of BC patient data sourced from The Cancer Genome Atlas database. Consequently, four gene signatures were constructed: two differentiate ER+ from ER-BC: TTC8, SLC5A7, and PLCH1 for overall survival (OS); ZNF695, SLC7A5, and PLCH1 for disease free survival (DFS), while the other two effectively distinguish tumor from normal samples: SPC25, ANLN, KPNA2, SLC7A5 for OS; SPC25, KIF20A, SKA3, DTL, CDCA3, ANLN, TTK, RAD54L, MYBL2, ZNF695, and SLC7A5 for DFS. Graphical abstract

Renal cell carcinoma (RCC) is an aggressive malignancy with a poor prognosis influenced by pyroptosis in tumor-associated M2 macrophages. This study investigated how kynurenine modulates pyroptosis in M2 macrophages and promotes RCC progression. M2 macrophages were treated with pyroptosis inhibitor VX-765 or kynurenine to evaluate their effects on cell viability and pyroptosis. Transwell co-culture systems were employed to assess the impact of M2 macrophages on RCC cell proliferation, colony formation, and viability. The interaction between kynurenine and CASP1 (caspase-1), a key executor of pyroptosis that cleaves gasdermin D (GSDMD) to trigger inflammatory cell death, was analyzed using surface plasmon resonance. The results demonstrated that VX-765 treatment significantly enhanced M2 macrophage viability while reducing pyroptosis, thereby promoting RCC cell proliferation in co-culture systems. Kynurenine significantly enhanced M2 macrophage viability while suppressing pyroptosis. Mechanistically, kynurenine reduced the cleavage of CASP1 (caspase-1) by directly binding to it. Overexpression of CASP1 reversed kynurenine-induced suppression of pyroptosis in M2 macrophages. Furthermore, CASP1 overexpression abolished kynurenine-mediated enhancement of RCC cell viability, colony formation, and proliferation. This study revealed that kynurenine inhibits pyroptosis in M2 macrophages via direct targeting of CASP1, creating a tumor-supportive microenvironment that accelerates RCC progression. These findings establish the kynurenine–CASP1 axis as a critical regulator of M2 macrophage pyroptosis and demonstrate its role in promoting RCC progression, identifying a potential therapeutic target for RCC treatment. Graphical abstract

Gastric cancer is among the most common gastrointestinal malignancies with high morbidity and mortality rates, highlighting the need to further elucidate its pathogenesis and identify effective therapeutic targets. The regulatory factor X (RFX) gene family encodes transcription factors implicated in the development and progression of several cancers. Although RFX5 has been reported to influence tumor progression in various malignancies, its specific role in gastric adenocarcinoma remains unclear. In this study, we investigated the functional effects of RFX5 in gastric adenocarcinoma. Our findings revealed that RFX5 is highly expressed in gastric adenocarcinoma tissues. Silencing of RFX5 significantly inhibited cell proliferation and migration, while promoting apoptosis in gastric adenocarcinoma cells. Mechanistically, RFX5 knockdown activated the silent information regulator transcript 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling axis. These results suggest that RFX5 facilitates the growth and motility of gastric adenocarcinoma cells and suppresses apoptosis, at least in part, through modulation of the SIRT1/AMPK pathway.

Radiotherapy is an important cancer treatment for breast cancer patients, improving overall survival; however, it can lead to a common complication, radiation-induced heart disease (RIHD). N6-methyladenosine (m6A) RNA modification plays a critical role in the regulation of myocardial function. The aim of this study is to investigate the effect of m6A modification on cardiac injury following radiotherapy for breast cancer. Cardiac dysfunction was assessed by echocardiography and hematoxylin and eosin staining. The expression of ALKBH5 was analyzed by quantitative real-time PCR, western blot, and immunohistochemistry. The underlying mechanism was investigated using methylated RNA immunoprecipitation (MeRIP), RIP, and dual-luciferase reporter assays. The results showed that in RIHD, ALKBH5 expression was upregulated in breast cancer patients after radiotherapy and in RIHD mouse models. ALKBH5 downregulated the m6A modification level of Toll-like receptor 4 (TLR4). Overexpression of TLR4 abolished the inhibitory effect of ALKBH5 silencing on RIHD in mice. In summary, this study revealed a novel regulatory mechanism of ALKBH5-mediated m6A demethylation in RIHD, which could provide a promising therapeutic strategy for cardiac dysfunction following radiotherapy in breast cancer patients. Graphical abstract

The large demand for Roman chamomile essential oil leads to nonnegligible residues in the process of steam distillation. It is an urgent problem to recycle these residues to solve the pollution in the ecological environment and enhance the industrial value. In this study, the components of different fractions extracted from the Roman chamomile residue were analyzed, and their antioxidant, whitening, and anti-aging activities were evaluated. It was found that the crude extract (CE) contained large amounts of polyphenols and flavonoids and displayed obvious antioxidant, whitening, anti-aging activities, and extremely low cytotoxicity. After fractional extraction, polyphenols and flavonoids were largely enriched in the ethyl acetate fraction (EaF), and total polyphenols and total flavonoids increased three- and fourfold, respectively, compared with CE. Especially, the rutin content increased 5.18-fold, quercetin increased 7.29-fold, and luteolin increased 10.58-fold. While chlorogenic acid and p -coumaric acid were mainly enriched in n -butanol fraction (NbF), and increased 2.1- and 2.75-fold than that in CE, respectively. The antioxidant, whitening and anti-aging activities of EaF are significantly higher than those of CE, especially the inhibition for hyaluronidase, elastase were greater than those of epigallocatechin gallate (EGCG), and its inhibitory effects on the tyrosinase and melanin content in B16F10 cells were stronger than those of kojic acid. NbF also showed lower IC 50 values than EGCG against hyaluronidase and elastase. These results indicated that the Roman chamomile residue, especially the CE, EaF, and NbF, had excellent antioxidant, whitening, and anti-aging activities and could be a new natural raw material for use in functional cosmetic formulations. Graphical abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and emerging evidence implicates circadian rhythm disruption in its pathogenesis. Here, we identified the core circadian gene Cryptochrome1 ( Cry1 ) as a potential tumor suppressor in HCC. Clinical analysis revealed that low Cry1 expression correlated with poor prognosis, showing a median survival of 36 vs 47 months, and Cry1 expression was significantly reduced in HCC cell lines (0.6-fold in SMMC-7721 vs LO2). Functional studies demonstrated that Cry1 overexpression reduced proliferation by 30% with more cells in the G1 phase, as well as inhibited migration/invasion, while Cry1 knockdown increased proliferation by 50% with less cells in the G1 phase and increased migration/invasion. Finally, we found Cry1 depletion downregulated pro-apoptotic BAX and upregulated anti-apoptotic BCL2, while Cry1 overexpression produced the opposite effects, suggesting its role in apoptosis via the BCL2/BAX-mediated apoptosis pathway. These findings indicate that Cry1 acts as a tumor suppressor in HCC, providing insights into the circadian dysfunction-cancer pathogenesis connection and its potential as a diagnostic biomarker and therapeutic target requires further verification through preclinical and clinical investigations in the future.

Lanthanum (La) accumulates resulted in detrimental alterations in the morphology and structure of hippocampal neurons, but the specific mechanism remains unclear. At 49 days after the birth of LaCl 3 -exposed offspring rats, number of Nissl bodies and the neural cell structure in hippocampal tissue was evaluated by Nissl and HE staining; the ultrastructure of hippocampal CA1 zone was observed by electron microscopy. Learning and memory ability of the offspring decreased after LaCl 3 exposure. Nissl staining showed that in the La-exposed rats, Nissl body number in the hippocampus was significantly decreased, and the cell arrangement was disordered. The ultramicroscopic structure of hippocampal neurons in La-exposed rats showed that the mitochondrial volume was increased; ridges were shorter, decreased in number, and marginally shifted; and the matrix electron density was also decreased. The contents of TNFR1, P-RIPK1, P-RIPK3, and P-MLKL in hippocampal neurons increased significantly as the LaCl 3 dose increased. La exposure retarded the growth and development of offspring rat, resulted hippocampal nerve cell necroptosis, and impaired spatial learning and memory, which related to abnormal expression of TNFR-RIPK1/RIPK3 pathway. Graphical abstract

Lung cancer is one of the most common and deadly malignancies worldwide, underscoring the need for reliable biomarkers that can inform prognosis and guide postoperative surveillance. This prospective study examined longitudinal changes in 10 tumor-associated autoantibodies in 71 patients with early-stage non-small-cell lung cancer (NSCLC) who underwent surgical resection. Blood samples were collected preoperatively and at 3-, 6-, and 12-month post-surgery. Enzyme-linked immunosorbent assays were used to measure serum autoantibodies against p53, MUC1, NY-ESO-1, APE1, PGP9.5, SOX2, GBU4-5, GAGE7, CAGE, and MAGE1. Logistic regression models assessed associations with 1-year recurrence, while Cox proportional hazards models evaluated overall survival. Substantial reductions in p53, GBU4-5, and CAGE autoantibodies correlated with lower recurrence risk and improved 1-year survival, even after false discovery rate adjustment ( p < 0.05). NY-ESO-1 showed borderline significance for recurrence, and SOX2 was borderline for survival but did not remain significant after correction. These findings suggest that monitoring dynamic declines in certain autoantibodies (most notably CAGE) may offer clinically meaningful prognostic information following surgical resection. While further validation in larger, independent cohorts is required, our results highlight the potential of serial autoantibody profiling as a noninvasive tool for personalized postoperative management in early-stage NSCLC patients.

Cancer treatment continues to face challenges due to adverse effects, drug resistance linked with conventional therapies, and high costs. As increasing interest in safer and cost-effective alternatives drugs, natural products such as flavonoids have been explored for treating cancer. Rutin, a dietary flavonoid, exhibits diverse pharmacological activities that may contribute to cancer prevention and treatment. It interferes with cancer progression by inducing apoptosis and autophagy, promoting cell cycle arrest, regulating oxidative stress, activating tumor suppressor gene, and modulating various signaling cascades. Recent studies also suggest that combining rutin with other therapeutic agents or employing nanoformulations may enhance its bioavailability and anticancer efficacy. This review critically examines anticancer mechanisms across various cancer types and highlights novel strategies to explored their therapeutic potential. The comprehensive clinical trials and mechanistic studies are needed to validate its safety, bioavailability, and efficacy in cancer management.

Pectin has bad effects on the sensory quality of cigarettes. In order to reduce the pectin content in tobacco leaves, polygalacturonase (PG) gene was extracted from Aspergillus niger sw06, and recombinant plasmid pPICZαA was constructed and transformed into Pichia pastoris X33 to build an engineered strain X33/pPICZαA-PG. Transformant genomic fragment was 1,608 bp. The genomic fragment was amplified and recovered, and sequencing indicated that PG gene expression have been successfully inserted into P. pastoris expression vector. Positive clones were detected by SDS protein with a molecular weight of about 60 kDa. The enzyme production cycle of the recombinant strain was 36 h, and crude enzyme activity was 2872.91 U/mL. The fusion protein was purified by nickel Sepharose affinity chromatography. A clear band was detected and the concentration of recombinant protein was 8.1 μg/μL. It showed a good effect on degrading pectin after addition of the PG crude enzyme produced by recombinant yeast on the tobacco pulp. The optimized addition amount on process product line was 0.8%, which could reduce tobacco pulp pectin from 3.65 to 3.01% and achieve a degradation rate of 17.53%. Sensory evaluation showed that the effect was better when the addition amount of pulping was 0.4%.

The development of lung squamous cell carcinoma (LUSC) is associated with the intratumoral microbiota. To facilitate faster clinical decisions and predict patient prognosis, we constructed an intratumoral microbial abundance prognostic scoring (MAPS) model for LUSC and analyzed its prognostic performance. Data on the LUSC tumor microbiome, patient survival, and clinical information were downloaded from The Cancer Microbiome Atlas and The Cancer Genome Atlas databases. Differentially abundant microbial genera in LUSC tumors were analyzed, and their prognostic value was evaluated. The differential abundance of key genera in the MAPS model was validated using lung adenocarcinoma (LUAD) tumors and normal tissues. Of 52 microbial genera with increased abundance and 437 with decreased abundance in LUSC tumors, 462 were highly related to the disease. Seven of 13 genera that were significantly related to prognosis were selected to construct the MAPS model. The MAPS risk grouping was identified as a prognostic risk factor for LUSC. Among the seven genera in the MAPS model, Indibacter , Oceanospirillum , Thalassomonas , and Thermopetrobacter differed in abundance between LUAD tumors and normal tissues and may be the key intratumoral microorganisms involved in LUSC and LUAD development. In conclusion, our MAPS model may be a powerful prognostic biomarker for LUSC.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. A rare but severe complication is haemophagocytic lymphohistiocytosis (HLH), an aggressive syndrome of excessive immune activation. Managing both conditions is particularly challenging in patients with multiple comorbidities. A 78-year-old male with a complex history, including myasthenia gravis and chronic kidney disease, was admitted with sepsis. Investigations confirmed infection with methicillin-resistant Staphylococcus aureus and human herpesvirus 8. He was subsequently diagnosed with HLH based on bone marrow findings of haemophagocytosis and elevated soluble CD25 levels. He was treated with a combination of antibiotics, immunomodulatory agents, and supportive care. After 21 days of treatment, the patient’s condition improved significantly. This case highlights the importance of early recognition and timely intervention in the management of sepsis and HLH in patients with multiple comorbidities. A multidisciplinary approach and individualised treatment strategies are crucial for improving patient outcomes.

The long-term survival and quality of life of liver transplantation (LT) recipients has emerged as a critical focus, where managing sarcopenia (a syndrome of diminished muscle mass and strength) and perioperative nutrition is paramount. This study aimed to delineate the knowledge landscape and identify key research trends and potential molecular mechanisms linking LT and sarcopenia through bibliometric and bioinformatics analyses. This study employs bibliometric and bioinformatics analyses to evaluate research trends and molecular mechanisms linking LT and sarcopenia. Data were retrieved from Web of Science database, and tools such as CiteSpace, VOSviewer, and R were used for data analysis and visualization. A total of 448 studies published over the past two decades were analyzed. Our bibliometric analysis revealed geographical distribution patterns, authorship networks, journal contributions, and thematic trends related to both LT and sarcopenia. Bioinformatics analysis identified 78 biphenotypic target genes shared by LT and sarcopenia, with hub genes including IL1B, ADIPOQ, and TNF showing strong associations. Enrichment analyses further highlighted significant biological processes, such as “response to peptide hormone” and “regulation of glucose transmembrane transport,” suggesting potential molecular mechanisms underlying the interaction between LT and sarcopenia. This study highlights the importance of incorporating routine sarcopenia assessments into the clinical management of LT candidates to optimize treatment strategies. Future research should focus on elucidating the molecular pathways connecting these conditions and developing targeted interventions to improve LT patients’ outcomes and quality of life. Graphical abstract

Cancer immunotherapy has revolutionized oncologic treatment by harnessing and reprogramming the immune system to target malignant cells. This review provides a comprehensive picture of modern approaches to immunotherapy-based treatment strategies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells, mRNA vaccines, and biomaterials-based platforms, with a focus on their translational value and application to precision medicine. Emerging insights into the tumor microenvironment, immune resistance mechanisms, and T-cell subpopulation dynamics (e.g., γδ T cells, exhausted CD8⁺ T cells) are analyzed to elucidate immunotherapy response variability. Biomaterials such as injectable scaffolds, nanogels, and artificial antigen-presenting cells enable localized and sustained immune modulation, improving delivery precision and therapeutic efficacy. Personalized approaches, including neoantigen vaccine development and artificial intelligence (AI)-assisted biomarker prediction, are rapidly advancing individualized treatment regimens. Clinical trials illustrate how combination strategies with ICIs, chemotherapy, and nanomedicine enhance patient survival. Despite challenges including immune-related adverse events, manufacturing complexity, and global access disparities, integration of AI and multi-omics platforms promises to optimize patient stratification and therapeutic outcomes. This evolving paradigm positions personalized immunotherapy at the forefront of future oncologic care. Graphical abstract

To investigate the causal relationship between two adverse reproductive outcomes (male infertility and spontaneous abortion) and COVID-19 infection using Mendelian randomization (MR) analysis. A two-sample MR study was conducted to examine potential causal links between COVID-19 infection severity and reproductive outcomes, using large-scale genome-wide association study (GWAS) summary statistics from European-ancestry populations. GWAS summary statistics were analyzed for COVID-19 phenotypes (infection: n = 1,683,769; hospitalized: n = 1,557,411; very severe respiratory-confirmed: n = 1,388,342; critical illness: n = 10,056) and reproductive outcomes (spontaneous abortion: n = 98,453; male infertility: n = 73,479). Causal estimates were calculated using inverse variance weighted (IVW), weighted median, MR-Egger regression, and weighted mode methods. IVW analysis revealed no significant association between genetic susceptibility to COVID-19 infection and male infertility (odds ratio [OR] = 0.7668; 95% confidence interval [CI]: 0.3798–1.5484; p = 0.4590) or spontaneous abortion (OR = 0.9936; 95% CI: 0.8066–1.2241; p = 0.8518). Similar null associations between COVID-19 severity phenotypes (hospitalized, very severe respiratory-confirmed, and critical illness) and male infertility or spontaneous abortion were observed. Sensitivity analyses using alternative methods confirmed the absence of pleiotropy and heterogeneity. This two-sample MR analysis provides robust evidence against a causal relationship between COVID-19 and increased risks of male infertility or spontaneous abortion. Graphical abstract Mendelian randomization (MR) analysis reveals no causal effect of COVID-19 infection on male infertility or spontaneous abortion.

Stüve–Wiedemann syndrome (SWS) is a rare autosomal recessive genetic disorder characterised by skeletal dysplasia, dysautonomia, and multi-system abnormalities. It is typically caused by variants in the leukaemia inhibitory factor receptor (LIFR) gene. This case report presents a novel and complex heterozygous variant in the LIFR gene in a 2-month-old Chinese infant, which contributes to the limited literature on SWS in the Chinese population and underscores the importance of early identification and intervention. The infant was born at 38 weeks of gestation via caesarean section due to breech presentation. He presented with multiple symptoms, including persistent pulmonary hypertension of the newborn, recurrent hyperthermia, and joint deformities. Whole exome sequencing identified a novel compound heterozygous variant in the LIFR gene. The infant underwent various interventions, including mechanical ventilation, inhaled nitric oxide, and nasogastric feeding. Despite these measures, the infant experienced recurrent hyperthermia episodes leading to multi-organ dysfunction. The infant was eventually stabilised, but follow-up revealed global developmental delay and persistent skeletal abnormalities. Early identification of the LIFR gene variant is crucial for timely intervention and management of multi-system complications. Further research is warranted to explore targeted therapies and improve outcomes for patients with this rare disorder.

The immunoproteasome regulatory component proteasome activator subunit beta (PSME2) plays a crucial role in immune regulation, yet its impact on intestinal barrier integrity in ulcerative colitis (UC) remains unclear. This study aimed to elucidate the involvement of PSME2 in UC pathogenesis. Clinical samples from UC patients and healthy controls were analyzed to assess PSME2 expression. A dextran sulfate sodium-induced colitis mouse model was employed to evaluate disease progression, colon histology, and PSME2 levels. In vitro , colonic cells were treated with lipopolysaccharide (LPS) to examine tight junction protein (claudin-1) expression and inflammatory mediators (IL-6, IL-10, TNF-α). Autophagy modulation was investigated using PSME2 silencing and chloroquine (CQ) treatment. PSME2 upregulation in UC and colitis mice correlated with disease severity. In vitro , LPS suppressed claudin-1 expression, while PSME2 knockdown restored claudin-1 levels and reduced inflammatory cytokines. PSME2 depletion enhanced autophagy, as indicated by an increased LC3-II/LC3-I ratio, reduced p62, and elevated LC3B puncta. CQ treatment reversed the protective effects of PSME2 silencing, confirming autophagy’s role in barrier integrity. PSME2 exacerbates intestinal inflammation by promoting cytokine release and disrupting epithelial barrier function through autophagy dysregulation. Suggesting its potential as a therapeutic target.

Diabetes insipidus is characterized by polyuria and polydipsia, often resulting from central or nephrogenic causes. In diabetic emergencies, hyperosmolar hyperglycemic state (HHS), severe hypernatremia, and ventricular fibrillation are life-threatening conditions that require prompt intervention. This report describes a 47-year-old male with poorly controlled diabetes mellitus, who developed coma, excessive thirst, polyuria, hyperglycemia (47.29 mmol/L), hypernatremia (195.6 mmol/L), and plasma hyperosmolality (385 mOsm/kg). Despite fluid resuscitation and insulin therapy, refractory hypernatremia persisted, leading to a diagnosis of central diabetes insipidus (CDI). The patient also developed ventricular fibrillation, which was managed with defibrillation. Concurrently, desmopressin and blood purification were administered to address CDI and severe hypernatremia. This case emphasizes the importance of considering CDI when polyuria persists despite glucose control. The occurrence of ventricular fibrillation underscores the necessity of continuous cardiac monitoring in the context of hypovolemia and severe electrolyte imbalance. We propose that diabetes mellitus-related vascular injury impairs blood flow in the hypothalamus–pituitary tract, disrupting arginine vasopressin synthesis and secretion, contributing to CDI in poorly controlled diabetes mellitus. Graphical abstract

Escin, a natural medicinal saponin, has garnered significant attention in recent years for its pharmacological effects in various diseases. Though the structure and pharmacodynamic targets of escin are documented, reviews on its efficacy and mechanisms were still mainly from the clinical application perspective at the organ level or animal models. Deeper discussion at the tissue microenvironment level remains sparse, as the sophisticated cell and molecular technique is required. Contradictory conclusion might occur if such experiment setups are not carefully distinguished. This article reviews and analyzes literature to discuss escin’s ability to improve the tissue microenvironment of blood vessel walls and elucidates the underlying mechanisms. Escin demonstrates significant anti-inflammatory properties and neutralizes free radicals, thereby protecting vascular endothelial cells from oxidative stress. Additionally, escin’s anticoagulant properties reduce blood viscosity, preventing clot formation and maintaining vessel patency. These mechanisms collectively enhance the tissue microenvironment of blood vessel walls and promote cardiovascular health, which provides a multi-target therapeutic strategy for cardiovascular diseases (CVD), integrating anti-inflammatory, antioxidant, endothelial repair, and microcirulation-enhancing mechanisms, consistent with current pathophysiological insights. The article also addresses the current research status, challenges, and future potential of escin in vascular protection, offering new perspectives and strategies for CVD treatment and prevention.

To investigate the clinicopathological features of three patients with Merkel cell carcinoma (MCC). The clinicopathological features, immunophenotypes, diagnosis and differential diagnosis, treatment, and prognosis of the three patients with MCC were analyzed retrospectively. Among the three patients, two were male and one was female. The age range of the patients was 55–79 years, while their mean age was 66.6 years. The maximum and mean tumor diameters were 1.8–2.5 cm and 2.1 cm, respectively. The tumors were located in surface areas such as the face and forearm. The tumor masses were mostly round, with a gray, solid appearance and qualitative sections. Microscopic examination revealed that the MCCs of the three patients had roughly the same morphology. Light microscopy indicated that the MCCs appeared as an intradermal mass with a narrow “Grenz band” separated from the epidermis, often accompanied by necrosis (apoptotic bodies) and patchy lymphocyte infiltration. Histological assessment of the MCCs showed monomorphic cell hyperplasia with cables, trabeculae, or sheet formation, hyperchromatic nuclei, vacuoles, cytoplasm with a “salt and pepper” appearance, and nuclear division. Immunophenotyping found tumor cells that were CK (+), CD56 (+), Syn (+), EMA (+), β-catenin (membrane +), LCA (−), CD99 (−), S100 (−), HMB-45 (−), SOX-10 (−), TTF-1 (−), CDX-2 (−), and CD34 (−), along with a Ki-67 proliferation index of 60–70%. Of the three patients with MCC, two were immunophenotypic CgA negative and one was positive. Additionally, two immunophenotypes exhibited CK20 negativity, and one showed paranuclear punctate positivity for CK20. MCC is a highly malignant cutaneous neuroendocrine carcinoma, requiring the combination of pathological morphology examination and immunophenotyping to confirm the diagnosis. Moreover, the primary MCC treatment of surgical treatment should be supplemented with chemotherapy and/or local radiotherapy to alleviate its poor prognosis, easy recurrence or metastasis, and high mortality.

Lignocellulosic biomass, owing to its recalcitrant nature, requires a consortium of enzymes for its breakdown. The present study deals with the isolation of cellulolytic bacterial strains from landfill leachate collected from the Pulau Burung landfill site of Penang, Malaysia, and consortia were constructed to test their cellulolytic efficiency. The dinitro salicylate method was used for the estimation of enzyme activity, and consortia were compared with promising bacterial strains. The combined potential of promising bacterial strains was optimized at varying experimental conditions to detect their maximum cellulolytic activity. The results showed that eight bacterial strains reflected hydrolytic activities, and these were identified by 16S rDNA sequence as Bacillus subtilis, Bacillus pumilus, Bacillus proteolyticus, Bacillus paramycoides, Bacillus cereus, Bacillus altitudinis, Bacillus niacin, and Bacillus thuringiensis. Consortia A included Bacillus proteolyticus, Bacillus subtilis, Bacillus pumilus, and Bacillus paramycoides and reflected high thermophilic inclination as the optimal temperature was 45°C at pH 6 with the highest cellulase activity of 0.90 U/ml. Consortia B included Bacillus cereus, Bacillus altitudinis, Bacillus niacin, and Bacillus thuringiensis and showed a cellulase activity of 0.78 U/ml at 38°C and pH 6. The results reflected the significant potential of these Bacillus strains and consortia in the breakdown of cellulose into useful end products. The consortia further proved that a synergistic relationship was more favourable for bioconversion processes.

In order to study the sequence characteristics, gene order, and codon usage of the mitochondrial genome of Haemaphysalis hystricis , and to explore its phylogenetic relationship, a total of 36 H. hystricis isolated from dogs were used as sample in this study. The mitochondrial genome of a H. hystricis was amplified with several pairs of specific primers by PCR, and was sequenced by first generation sequencing. The mitochondrial genome of H. hystricis was 14,719 bp in size, and it contained 37 genes including 13 protein coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and AT-rich region. Each PCG sequence had different lengths, the sequence longest and shortest gene were nad 5 (1,652 bp) and atp 8 (155 bp), respectively, among the 13 PCGs. All PCGs used ATN as their initiation codon, 10 of 13 PCGs used TAN as their termination codon, and 3 of which had incomplete termination codon (TA/T). Most of the 22 tRNAs with different sizes could form the classical cloverleaf structures expect for tRNA - Ala , tRNA - Ser1 , tRNA - Ser2 , and tRNA - Glu , and there were base mismatch (U-U and U-G) in all the 22 tRNAs sequences. Two rRNAs, namely rrnL and rrnS , had different lengths, rrnL located between tRNA - Leu1 and tRNA - Val , and rrnS located between tRNA - Val and tRNA - Ile , respectively. Two AT (D-loop) control areas with different lengths were in the mitochondrial genome, the NCRL was located between tRNA - Leu2 and tRNA - Cys , and the NCRS was located between rrnS and tRNA - Ile . The complete mitochondrial genome sequence of H. hystricis was AT preferences, and the gene order is the same as that of other Haemaphysalis family ticks. However, phylogenetic analysis showed that H. hystricis was most closely related to Haemaphysalis longicornis among the selected ticks. The mitochondrial genome not only enriches the genome database, provides more novel genetic markers for identifying tick species, and studying its molecular epidemiology, population genetics, systematics, but also have implications for the diagnosis, prevention, and control of ticks and tick-borne diseases in animals and humans.

The aim of this study was to examine the prevalence of multidrug-resistant tuberculosis (MDR-TB) within the tuberculosis (TB) population in Huzhou City, identify associated risk factors, furnish reference values for clinical practice, and establish standardized anti-TB treatment regimens. Retrospectively analyzing data from TB patients in Huzhou City encompassed 2,261 cases with sputum smear positive and 1,754 cases with sputum smear negative from January 2016 to December 2022. There were 3.66%(147/4,015) TB patients identified as MDR-TB. Multivariate logistic regression analysis showed that the risk of developing MDR-TB in individuals with comorbidities was 9.17 times higher than in individuals without comorbidities (odds ratio [OR] = 9.17, 95% confidence interval [CI]: 6.5–12.93, P < 0.001). The risk of progressing to MDR-TB with a positive sputum smear was 1.93 times higher than with a negative one (OR = 1.93, 95% CI: 1.35–2.77, P < 0.001). The risk of developing MDR-TB was 1.69 times higher in patients had smoking history than in those without (OR = 1.69, 95% CI: 1.11–2.56, P = 0.014). The main risk factors for developing MDR-TB were male patients, smoking history, sputum smear positive, farmer, body mass index ≤18.5, retreated cases, and those combination of diabetes or pneumoconiosis.

Human activities significantly influence landscapes, altering natural habitats and ecosystem services. This study examines the relationship between human impacts, measured by the hemeroby index and coefficient of anthropogenic impact (CAI´), and the presence of natural habitats in the Czech Republic. Using CORINE land cover data and natural habitat mapping, we analysed national and regional scales to assess the effectiveness of these indicators in reflecting environmental changes. Compared with the simple anthropogenic impact coefficient (CAI´), the hemeroby index, which accounts for both the quantity and quality of ecosystems, provides more detailed insights. At the national level, both indices had an equally close relationship with the proportion of natural habitats, but at the regional level, the results for the hemeroby index were better. Our findings indicate a strong negative correlation between human impacts and the proportion of natural habitats, emphasizing the importance of refined indicators for environmental monitoring and policy-making. The advantage of both indices is that they could be easily calculated from satellite images and/or land cover data. Therefore, they could be used worldwide.

The Siberian flying squirrel ( Pteromys volans ) is an arboreal, nocturnal, and gliding rodent. It is crucial for maintaining ecosystem balance and the dispersal of forest seeds. In Northeast China, the number of Siberian flying squirrels is decreasing and their habitats are shrinking due to logging and habitat loss. To make more targeted and effective measures to protect and manage the population, there is an urgent need to study the genetic changes in the population, particularly looking at genetic diversity and gene flow. In this study, we collected hair samples from 91 Siberian flying squirrels in a way that did not harm them. Then, we analyzed the DNA in these samples, specifically using cytochrome b and microsatellite loci, and examined the genetic diversity and population structure of flying squirrels living in the northern Changbai Mountains of Northeast China. The results indicated that the genetic diversity in the populations was high. However, a high proportion of rare haplotypes and a low frequency of alleles indicated that the genetic diversity might decline in the future. There were significantly low to moderate levels of genetic differentiation among the four populations. According to our STRUCTURE analysis, the four geographical populations belonged to three genetic clusters (Fangzheng, Bin County, and Weihe–Muling). The isolation by distance model could not effectively explain the current pattern of the population genetic structure. The haplotype network showed no clear phylogeographic pattern among the four geographic populations, indicating that the geographic barriers between the flying squirrels might have formed only recently. To better protect the Siberian flying squirrels, conservation methods should be further improved. For example, habitat restoration and ecological corridor construction should be carried out to increase gene exchange and help the population recover and grow faster. Graphical Abstract

This study investigates the diversity and distribution of Suillus fungi in Pinus sylvestris var. mongolica (PSM) forests across Inner Mongolia, with a focus on understanding the environmental factors influencing fungal communities. High-throughput sequencing was utilized to analyze soil fungal communities across 12 PSM forest sites, alongside assessments of meteorological variables and soil enzyme activities. Thirteen Suillus species were identified, with S. clintonianus being the dominant species. The diversity of Suillus fungi exhibited significant geographical variation, with diversity decreasing from east to west. Precipitation and leucine aminopeptidase activity were identified as key drivers of fungal distribution. The soil fungal community was predominantly saprotrophic, playing a crucial role in nutrient cycling and ecosystem stability. The findings provide a deeper understanding of the role of ectomycorrhizal fungi in sustaining forest health and offer valuable insights for sustainable forest management and restoration efforts in semi-arid regions.

Atmospheric nitrogen (N) deposition is recognized as a pivotal nutrient input in forest ecosystems. However, significant gaps persist in our comprehension of the global-scale fate of N in forest ecosystems. In a pioneering effort, this study analyzed the fluxes and determinants of deposited N by 234 observations from 52 published articles. Our findings indicated that plant uptake, soil retention, and N losses, respectively, accounted for 27.4, 57.9, and 14.6% of the total deposited N. The fate of deposited N was significantly influenced by a suite of factors, including forest type, climatic parameters such as mean annual temperature (MAT) and precipitation (MAP), edaphic characteristics such as soil pH and the carbon to nitrogen ratio (C/N), and experimental factors like nitrogen addition rate (NR), nitrogen forms (NF), plot size (PS) for 15 N studies, and the duration of study. For the uptake of deposited N, MAP emerged as the predominant positive factors, whereas NR was the dominant negative factors; for deposited N soil retention, NR was the key positive factors, while MAT was the key negative factors; for N losses, MAP was the predominant positive factors, with the C/N ratio serving as a significant negative factor. Thus, for a given forest ecosystem with relatively stable climate and soil conditions, NR, NF, and the soil C/N were the main controlling factors regulating the fate of deposited N. These insights significantly advance our grasp of the N cycle in forest ecosystems. Consecutive monitoring of the impact of deposited N on soil N transformations and carbon sequestration is needed in future studies.

Pathogenic co-infections in plants significantly impact microbial diversity and disease outcomes, yet their effects on microbial community structure and ecological processes remain unclear. Tobacco plants were co-infected with Ralstonia solanacearum and Neocosmospora falciformis . 16S ribosomal RNA and internal transcribed spacer amplicon sequencing were used to assess bacterial and fungal communities, respectively, in infected tobacco stems. The results were compared between co-infected and healthy control tobacco plants to assess the effects of infection. Co-infection reduced microbial diversity and shifted community structure, promoting ecological specialization. Network analysis revealed synergistic interactions between the pathogens, enhancing virulence through positive correlations with certain microbial taxa. Conversely, some taxa exhibited antagonistic effects, potentially limiting pathogen proliferation. Deterministic processes were found to dominate microbial community assembly under infection conditions, significantly reshaping the microbial landscape compared to healthy control plants. This study highlights the profound effects of co-infection on microbial diversity, community composition, microbial interactions, and community assembly processes in tobacco plants. These findings provide valuable insights for developing more targeted plant disease management strategies by manipulating microbial communities. Graphical abstract

To investigate the effect of coal industry-related airborne particulate matter (PM) on ocular surface tear film injury and inflammatory factor expression. Male Sprague-Dawley (SD) rats were randomly divided into the treatment group and the normal control group, with five rats in each group. A dust chamber was used to simulate the air contamination conditions associated with the coal industry. Tear secretion, tear-film breakup time (BUT), conjunctival congestion score, and relative expression levels of tear inflammatory factors, including interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α, were compared between the treatment group and the normal control group. After 4 weeks’ exposure, tear secretion (2.64 ± 0.57 mm vs 5.42 ± 0.28 mm), BUT (4.23 ± 0.47 s vs 6.15 ± 0.36 s), and conjunctival congestion score [2 (2, 3) vs 0 (0, 1)] were significantly different between the treatment group and the control group (all P < 0.05), and hematoxylin-eosin stain showed that the number of goblet cells decreased in the treatment group. In addition, the relative expression levels of IL-6, IL-17, and TNF-α in tears of the treatment group were significantly different from those of the normal control group (all P < 0.05). Coal industry-related airborne PM exposure can damage tear film function and increase relative expression levels of tear inflammatory factors in SD rats.

Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) is an important predator of Myzus persicae (Sulzer) (Homoptera: Aphididae). In this study, the morphological characteristics and living habits of S. macrogaster were observed and recorded. It evaluated the variations in developmental rate and predatory capacity of S. macrogaster when preying on M. persicae under five constant temperature regimes (16–32°C). Regression analyses assessing the relationship between temperature and the developmental rates of the egg, first, second, and third larval instars, and pupa of S. macrogaster were performed. In addition, the life table of hoverflies with M. persicae as prey at 28°C was determined. The results demonstrated that development rates at the egg, larval, and pupal stages gradually increased as the temperature increased from 16 to 32°C. The highest threshold temperature occurred at 7.93°C, in the egg stage. The threshold temperature and effective accumulated temperature of the whole generation of S. macrogaster were 5.56°C and 312.50° days, respectively. The larvae consumed more prey at 20°C than at other temperatures; however, the maximum value of the larva predation was 28.3 M. persicae per larva at 28°C, and the average duration of S. macrogaster development was 14.3 days from egg to adult emergence. The mortality of the egg stage of S. macrogaster was 18.0%, and the survival rate from the egg hatch to the adult stage was 58% at 28°C. These results provide valuable information for the release of S. macrogaster into managed systems to reduce M. persicae infestations under a wide range of temperature conditions.

Eleonora’s falcon ( Falco eleonorae ) has a unique ecology that makes it ideal for studying predator–prey dynamics. Its diet shifts seasonally, with insects dominating the non-breeding and pre-laying periods, and birds becoming the main prey during chick-rearing. This systematic review explores the falcon’s foraging behavior during the pre-breeding and breeding phases within its global breeding range, emphasizing insect prey. Following PRISMA guidelines, the review includes studies from ten Mediterranean countries and the Canary Islands. Literature was sourced from Web of Science, Google Scholar, PubMed, and Scopus, covering both peer-reviewed and grey literature up to 2024. From 18 scientific publications and personal observations, 120 insect species and morphospecies from 47 families were recorded as prey. Coleoptera, Hymenoptera, and Hemiptera were the most frequent insect orders. Migratory species such as Acherontia atropos , Anax parthenope , and Anax ephippiger were also documented. This review contributes valuable knowledge for future studies on the dietary ecology of Eleonora’s falcon and similar raptors.

Drought is a major abiotic stress in restricting the growth, development, and yield of maize. As a significant epigenetic regulator, small RNA also functions in connecting the transcriptional and post-transcriptional regulatory network. Further to help comprehending the molecular mechanisms underlying drought adaptability and tolerance of maize, an integrated multi-omics analysis of transcriptome, sRNAome, and degradome was performed on the seedling roots of an elite hybrid Zhengdan958 under drought stress. In this study, 2,911 genes, 32 conserved miRNAs, and 12 novel miRNAs showed a significantly differential expression under drought stress. Moreover, 6,340 target genes of 445 miRNAs were validated using degradome sequencing, forming 281 miRNA–mRNA pairs in control (CK) and drought-stressed (DS) library. These target genes were mainly involved in the plant hormone signal transduction and phenylpropanoid biosynthesis pathways. The integrated multi-omics analysis revealed that five DEmiRNA–mRNA pairs displayed negatively correlated expression patterns, which were also verified by qRT-PCR. Tissue-specific expression profile and regulatory network analysis revealed that miR528a/b- Zm00001d021850 , miR408a/b- Zm00001d020794 , and miR164e- Zm00001d003414 might be essential in root-specific drought stress response of maize Zhengdan958 seedlings. These worthwhile will promote the functional characterization of miRNA–mRNA modules response to drought stress, and potentially contribute to drought-resistance breeding of maize.

This study evaluated frost tolerance in flowers of seven major apple cultivars grown in Korea to develop frost-resistant varieties for sustainable apple production under climate change. Flowers at full bloom were exposed to simulated frost conditions at −2°C, and frost damage was assessed using the total flower frost damage rate and King flower frost damage rate. Over 3 years, “Arisoo” consistently exhibited strong frost tolerance, whereas ‘Fuji’ was frost-sensitive. Transcriptomic analysis revealed significant differences in gene expression both within cultivars under different treatments and between cultivars under identical conditions. A higher number of differentially expressed genes were upregulated under frost stress in both cultivars, indicating key regulatory mechanisms involved in frost adaptation. Functional annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis identified plant hormone signaling, mitogen-activated protein kinase signaling, and starch and sucrose metabolism can contribute to frost tolerance. Our findings offer critical insights into the genetic and molecular mechanisms of frost tolerance, contributing to the development of resilient apple varieties and sustainable production systems under climate change.

Wheat yellow (stripe) rust is one of the most destructive diseases worldwide. Growing resistant cultivars is the most economical and eco-friendly method to control the disease. To determine heritability and gene number of durable resistance to stripe rust, four Egyptian wheat cultivars were crossed to four genotypes; Jupateco 73R, Opata 85, Anza, and Pavon 76 carrying the durable resistant genes were studied to enhance wheat yellow rust durable resistance. The genetic analysis has been done based on F 1 , and F 2 of crosses, and our findings confirmed the di-genic and tri-genic control to this disease. The result from the F 2 population showed that Misr2/Opata and Giza168/Anza were segregated fitting the expected ratios of 57 resistant: 7 susceptible. The segregation ratios of resistance and susceptibility of F 2 plants showed tri-genic hereditary of yellow rust resistance, permitting the following conclusions about the genes expressed in adult plants suggesting a difference of three dominant genes between the parental cultivars. The cross Giza168/Pavon76 was showed phenotypic ratios fitted the theoretical ratios, 63 resistant: 1 susceptible, suggesting difference of two dominant and one recessive gene for resistance. These genotypes are very important for wheat breeding to stripe rust resistance in Egypt. Graphical abstract

Water metabolism is fundamental to sustaining physiological functions in living organisms and plays a particularly vital role in poultry, especially laying hens. It directly influences their health status and production performance. Follicular development, a crucial phase in the reproductive cycle of laying hens, is highly sensitive to water availability. Insufficient hydration can lead to increased stress, reduced synthesis of ovarian hormones, and impaired follicular maturation, while excessive hydration may disturb osmotic balance and interfere with normal follicle growth. Although existing studies have preliminarily demonstrated a link between water metabolism and follicular function, the molecular mechanisms – particularly those involving aquaporins, hormonal receptors, and intracellular signaling pathways – have not been comprehensively elucidated. By integrating molecular biology techniques, physiological indicators, and imaging analysis, this study reveals how water status regulates follicular development through the modulation of AQP1 and AQP3 expression, activity of follicle-stimulating hormone and luteinizing hormone receptors, and the MAPK/ERK and PI3K/Akt signaling pathways. It was found that water restriction significantly downregulated AQP1 and AQP3 expression and reduced FSH receptor and LH receptor activities. These molecular adjustments likely serve as adaptive responses to minimize water loss and preserve the stability of the follicular microenvironment. Meanwhile, water-restricted conditions enhanced MAPK/ERK activation and attenuated PI3K/Akt signaling, further influencing follicular growth. These findings contribute to a more refined understanding of the role of water metabolism in reproductive regulation and provide theoretical support for optimizing breeding strategies under hydration-related stress conditions. Graphical abstract The graphical abstract above outlines the research plan of the study, summarizing the key stages involved in investigating the molecular mechanisms of water metabolism in laying hens and their effect on follicular development. The flowchart begins with identifying the research question, which focuses on understanding how water metabolism influences follicular growth at a molecular level. This leads to the methods stage, where molecular biology techniques, physiological assessments, and imaging analysis are employed. Data collection follows, involving tracking water intake, analyzing biochemical markers, and monitoring follicular development through ultrasound and molecular assays. Finally, the analysis stage integrates the data to identify correlations between water metabolism and follicular development, focusing on gene expression, protein levels, and signaling pathways. This visual representation efficiently summarizes the study's progression from hypothesis formulation to data-driven insights, illustrating the dynamic interplay between water status and reproductive physiology in laying hens.

The fall armyworm (FAW), Spodoptera frugiperda , is a dangerous migratory pest. Evaluating the effect of sex ratio on the FAW offspring population is particularly important for field control. In this study, five different sex ratio treatments (female/male = 3:1, 2:1, 1:1, 1:2, and 1:3) were conducted to investigate the effects of sex ratio on the life history traits of FAW. The results showed that sex ratio significantly affected lifetime fecundity, developmental duration of the preadult stage, hatch rate, and emergence rate but had no effect on longevity of parental and offspring adults, larval duration, pupation rate, or number of eggs/moth of offspring. The lifetime fecundity and hatch rate of parental adults and the number of adult offspring/moth were the lowest when the sex ratio was 3:1, while the lifetime fecundity and number of adult offspring/moth were the highest and pupation duration was the shortest when the sex ratio was 1:1. The number of eggs/moth of parental adults and total adults in the F1 generation were higher in male-biased groups than in female-biased groups, and male annihilation appears to be a more effective control strategy. These findings have implications for improving laboratory rearing, population forecasting, and control of FAW in the field.

Rafflesiaceae is a family of endangered plants whose members are solely parasitic to the tropical grape vine Tetrastigma (Vitaceae). Currently, the genetics of their crosstalk with the host remains unexplored. In this study, we use homology-based in silico approaches to characterize micro-RNAs (miRNAs) expressed by Sapria himalayana and Rafflesia cantleyi from published omics data. Derived from secondary structures or hairpins, miRNAs are small regulators of gene expression. We found that some plant-conserved miRNA still exists in Rafflesiaceae. Out of 9 highly conserved miRNA families in plants, 7 families (156/157, 159/319, 160, 165/166, 171, 172, 390) were identified with a total of 22 variants across Rafflesiaceae. Some miRNAs were missing endogenous targets and may have evolved to target host miRNA, though this requires experimental verification. Rafflesiaceae miRNA promoters are mostly inducible by ethylene that mediates stress response in the host but could be perceived by the parasites as a signal for growth. This study provides evidence that certain miRNAs with ancient origins in land plants still exist in Rafflesiaceae, though some may have been coopted by parasites to target host genes.

Rubus corchorifolius , a medicinal plant of the Rosaceae family, is known for its diverse bioactive compounds. This study employs widely targeted metabolomics to investigate the metabolic profiles of leaf, stem, and flower tissue from R. corchorifolius . Using ultra-performance liquid chromatography coupled with tandem mass spectrometry, we identified 1,946 metabolites across the three tissue types. Multivariate statistical analyses revealed distinct metabolic signatures for each tissue, with flowers showing the most distinctive profile. Differential accumulation of flavonoids, phenolic acids, and primary metabolites reflected the specialised functions of each tissue type. Pathway enrichment analysis highlighted tissue-specific metabolic activities, including flavonoid biosynthesis in flowers and chlorophyll metabolism in leaves. This comprehensive metabolic characterisation provides a foundation for further investigations into the biosynthetic pathways and physiological functions of bioactive compounds in R. corchorifolius , potentially guiding future applications in medicine and agriculture.

Gerbera piloselloides (L.) Cass., 1820 of the genus Gerbera is of importance in Chinese ethnic medicine. In this research, the whole genome DNA of G. piloselloides was extracted and sequenced using the Illumina NovaSeq platform, its chloroplast genome was assembled and annotated, and its sequence characteristics were analyzed using bioinformatic methods. The results showed that its chloroplast genome has a length of 151,871 bp and contains 133 annotated genes, consisting of 88 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. In total, 202 simple sequence repeat sites and 43 long repeats were detected in G. piloselloides , mainly consisting of mono-nucleotide and tri-nucleotide repeats, with A/T as the major base composition. The chloroplast genome of G. piloselloides contains 22,772 codons, with leucine-coding codons being the most abundant. Comparative genomics showed that the genome structure, composition and variation were basically the same in the Asteraceae family. The phylogenetic tree analysis indicated a close relationship between the genus Atractylodes and Gerbera, consistent with the morphological classification. The research of the G. piloselloides chloroplast genome will lay a foundation for species discrimination, genetic evolution analysis, and DNA barcode construction in Gerbera plants.

The excessive use of phosphorus (P) fertilizers increases crop production but can lead to P-induced zinc (Zn) deficiencies, making both nutrients unavailable to plants. Plant–microbe interactions, such as with Pseudomonas aeruginosa , can alleviate these constraints by solubilizing Zn and P in soil. A soil incubation study revealed that applying P. aeruginosa with farmyard manure (FYM) significantly increased Zn and P solubilization (6.86 mg/l; 14.83 mg/l) compared to control (3.15 mg/l; 13.67 mg/l). A field experiment evaluated the effects of P. aeruginosa on the biochemical composition of groundnut plants under five treatments. The T2, T3, and T4 treatments had the highest protein, carbohydrate, and chlorophyll levels, likely due to the heterogeneous activity of FYM and the mineral solubilizing ability of P. aeruginosa . Groundnut seeds from T3 (combined liquid inoculant and FYM) had the highest iodine (88.47 mg KOH/g), saponification value (195.56 mg KOH/g), and free fatty acid content (2.23 g oleic acid). The pH of the T3 soil decreased from 8.3 to 7.5, and significant increases were observed in electrical conductivity (from 2.88 to 0.30 dS/m), calcium carbonate (2.53–1.7%), organic carbon (0.39–1.91%), nitrogen (273.75–788.25 kg/ha), P (20.1–59.65 kg/ha), potassium (182.25–346.5 kg/ha), and Zn (1.53–7.24 mg/kg). The study suggests that the combined application of liquid formulants of P. aeruginosa with FYM is advantageous, as FYM supports microbial growth by providing essential nutrients for mineralization. Moreover, liquid inoculants formulated with polyvinylpyrrolidone as an osmo protectant demonstrated enhanced shelf-life and mineral solubilization, contributing to improved biochemical properties in groundnut plants.

This research investigated the correlation between routine semen parameters and the sperm DNA fragmentation index (DFI) in infertile males with non-liquefying semen, aiming to provide insights for infertility management. We conducted a retrospective analysis of 152 infertile males at our Andrology Department from March 2023 to March 2024, assessing differences in semen parameters and DFI based on liquefaction times and identifying influential factors on DFI. Participants were divided into two groups based on their semen liquefaction times: less than 60 min (111 patients) and 60 min or more (41 patients). The group with normal liquefaction times demonstrated significantly better forward and total sperm motility, and lower sperm morphology indices and DFI values. A positive correlation was found between DFI and liquefaction time, while a negative correlation was observed with motility and normal sperm ratio. Specifically, each additional minute of liquefaction time increased DFI by 0.13, and a 1% decrease in normal sperm ratio increased DFI by 0.73. The findings indicate that delayed semen liquefaction correlates with poorer sperm motility and morphology and higher DFI, underscoring the importance of comprehensive semen assessment in evaluating male fertility.

There is a variety of Rhododendron plants in the Tibetan plateau; yet, little is known about their variations in leaf anatomical traits and the implications for environmental adaptation. In this study, we investigated the anatomical traits of leaves in five Rhododendron L. species from Shergyla Mountain on the Tibetan plateau. The results showed that the five species have notable intraspecific and interspecific differences in the thickness of leaves, cuticle thickness, adaxial epidermis thickness, palisade parenchyma thickness, spongy parenchyma thickness, and tightness of leaf palisade parenchyma ( P < 0.05). There are autocorrelations among these anatomical traits of the leaves, indicating the existence of synergistic changes. The interspecific variations in leaves’ anatomical structures illustrated their spectrum of plasticity to habitat heterogeneity. Our findings demonstrated that Rhododendron plants have developed typical ectopic leaves to adapt to harsh conditions of the Tibetan plateau.

Moringa is a perennial tree with high nutritional value, and it is drought tolerant and barren but has poor cold resistance during the seedling stage. This study selected Piriformospora indica (PI) and arbuscular mycorrhizal fungus (AM) as inoculants, Moringa seedlings were inoculated, and their growth and physiological responses were evaluated under different low-temperature stress times. The research results show that PI and AM can symbiotically associate with Moringa successfully and promote their nutritional growth. At low temperature, Moringa inoculated with PI and AM exhibited better physiological resistance. However, the effect of mixed inoculation of PI and AM is not as significant as that of single inoculation of any strain. Inoculating plant growth-promoting rhizobia (PGPR) reduced the richness of fungal communities and the number of unique operational taxonomic units (OTUs), with PI being the most prominent. Vaccination with PGPR also increased bacterial diversity, richness, and the number of unique OTUs, with AM inoculation showing the most prominent performance. This suggests that Moringa seedling growth and responsiveness to low-temperature stress are significantly influenced by PGPR, and there may be interactions between different bacterial strains. The results suggest that PGPR can improve the yield and quality of Moringa by promoting growth and regulating stress resistance.

Potassium plays an important role in improving crop growth, yield, and quality; however, choosing the right potassium fertiliser remains challenging. To determine the optimal potassium fertiliser for kiwifruit, this study investigated the effects of different potassium sources on kiwifruit yield and postharvest quality as well as plant and soil nutrient contents in an orchard in Shaanxi Province, Northwest China. Two types of potassium fertiliser were examined (K 2 SO 4 and KCl; total K 2 O = 584 kg ha −1 ) at two different application stages (basal and topdressing) under the following four treatments: basal K 2 SO 4 + KCl topdressing, basal K 2 SO 4 + K 2 SO 4 topdressing, basal KCl + K 2 SO 4 topdressing, and basal KCl + KCl topdressing. The different potassium sources had no significant effect on kiwifruit yield; however, a slight increase in yield and economic gain was observed under combined treatment with K 2 SO 4 and KCl compared to single fertiliser treatment. Meanwhile, the single fruit weight and vitamin C content of the fruit were 7.0 and 4.6% higher under treatment with basal K 2 SO 4 + KCl topdressing compared with K 2 SO 4 treatment alone, and 3.1 and 14.9% higher compared with KCl treatment alone. Moreover, application of KCl promoted potassium and chlorine absorption by both the leaves and fruit. However, no significant differences in the content of sulphate or chloride ions in the surface soil (0–40 cm) were observed between potassium sources. In contrast, in deeper soil, the content of chloride ions was highest after KCl treatment, while that of sulphate ions was highest after K 2 SO 4 topdressing. Overall, these findings suggest that the most appropriate potassium source for kiwifruit production is basal application of K 2 SO 4 followed by KCl as topdressing in the study region.

Powdery mildew ( Erysiphe necator Schw.) fungal disease in vineyards is becoming an increasingly important concern due to climate change and the emergence of resistant populations after heavy spraying. Recently, new disease control methods based on phenological development, disease development, and meteorological data have been established in Türkiye. These models can provide sufficient protection with minimal fungicide use and minimize residue problems due to excessive fungicide use. In this study, the activities of the UC Davis risk index model, decision support strategy (DSS) models, and classical model, based on plant phenological development stages suggested by the Turkish Ministry of Agriculture and Forestry, were used to protect against powdery mildew. Three alternative control strategies were investigated for 2 years using two grape varieties. In addition, the amount of pesticide residue in the final product by the spraying models was also evaluated. The UC Davis risk index model was applicable in places with similar climatic conditions, such as Bursa Province, and showed better results than other spraying programs. Although the classical model proposed by the Ministry of Agriculture and Forestry is generally less effective than the UC Davis risk index model, once less spraying achieved high effectiveness rates each season. The UC Davis risk index model considerably lowered the disease incidence rate in clusters below the 5% limit. The DSS model provided poorer protection than the other two models evaluated in this study. Among the fungicides with active ingredients, thiophanate-methyl, kresoxim-methyl, and penconazole, only thiophanate-methyl exceeded the 0.1 ppm (mg/kg) limit specified in the European Union Pesticide Maximum Residue Limits and Turkish Food Codex Pesticide Maximum Residue Limits for both grape varieties. Alternating fungicides with different active ingredients instead of a single fungicide at regular intervals throughout the season can reduce residue problems of grapes and the risk of pathogen resistance to fungicides.

DREB7 in Glycine max (L) is a novel trans-acting transcription factor (TF) that binds to the cis -acting sequences of promoters to activate the expression of downstream genes in response to abiotic factors. This study presents the experimental results and analyzes the relationship between the overexpression of the GmDREB7 and GmP5CS , as well as the proline content, in transgenic soybean lines. The results of qRT-PCR analysis of four TG1 transgenic soybean lines (TG1-2, TG1-5, TG1-7, and TG1-10) showed that the GmDREB7 gene had significantly higher transcriptional expression under untreated and salt stress conditions. Under salt stress conditions, the two transgenic lines, TG1-5 and TG1-10, had the most significant increase in GmDREB7 and GmP5CS gene expression levels, as well as the highest proline accumulation ( P < 0.05). The in silico molecular docking analysis confirmed a specific interaction between the DREB7 protein and GmP5CS promoter. These findings demonstrate that overexpression of the gene encoding the TF DREB7 enhanced the transcription of the GmP5CS gene and increased proline accumulation in soybean plants under salt stress conditions. The GmDREB7 gene can be a promising candidate for enhancing salt tolerance in soybeans. Graphical abstract

Aquatic plants, such as water hyacinths, Eichhornia crassipes , are indicators of environmental changes. This study explores the response of water hyacinths to wastewater exposure by analyzing their bioelectrical signals. The analysis includes time, frequency, and joint time-frequency domains, evaluating the plant’s response to water quality variation. In the time domain, the Lempel-Ziv complexity analysis was used to demonstrate how the plant’s response evolves over time, while spectral entropy was used for frequency domain analysis. By using adaptive Gabor representation, the joint time-frequency behavior of the signal was evaluated. All these advanced digital signal processing techniques were used to evaluate the plant’s ability to detect and adapt to the presence of pollutants. The results show that water hyacinths can serve as part of a reliable instrumentation system for real-time aquatic ecosystem monitoring, as the plant’s bioelectrical signals changed both in the time domain and frequency domain. Graphical abstract

The Lamiaceae family is one of the widest plant families among Greek flora, consisting of a great variety of species, with the genus Stachys being one of its largest representatives, spread to most continents. The genus Stachys is also known for its beneficial properties and has been used for years as a traditional remedy for healing various health conditions. Stachys iva , an endemic plant in the Kozani Regional unit, has also been consumed as an infusion by locals and is reported to relieve common cold symptoms, have antimicrobial properties, and contribute to normalizing blood glucose levels. The present study aimed to identify the chemical compounds (such as phenolic acids, flavonoids, and phenylethanoid glycosides) responsible for the herb’s pharmacological properties and determine the optimal extraction conditions to gather an extract with high therapeutic value without solvent and energy waste. Experiments conducted proved that extracting by simple stirring with deionized water for 75 min at 80°C is the best option. In contrast, the extract’s total polyphenol content was determined, and the compounds were identified by high-performance liquid chromatography analysis. In addition, other methods were utilized (e.g., ferric-reducing antioxidant power assay and 2,2-diphenyl-1-picrylhydrazyl antiradical activity assay) to reveal potent antioxidant, anti-hydrogen peroxide, and anti-inflammatory activity, while the correlation between these properties and extraction conditions was also examined. Graphical Abstract

Honey has been used for centuries due to its health-promoting properties. Honey and its bioactive compounds regulate oxidative stress, inflammation, and other biological activities, making it a promising natural remedy. Its role as anti-diabetic, wound healing, cardioprotective, anti-microbial, and hepatoprotective potential has been proven through in vitro and in vivo studies. Moreover, its role in disease management has been reported through the inhibition of pro-inflammatory enzymes and downregulation of pro-inflammatory cytokine expression and secretion. Besides, it exerts modulatory actions on various signaling pathways such as nuclear factor-κB, tumor suppressor genes, apoptosis, angiogenesis, and MAPK pathway. The main aim of this review is to present a wide-ranging overview of the current evidence regarding the impact of honey on the management of various pathogenic conditions. However, further research based on animal models and clinical trials is required to fully understand the mechanisms of action and safety in the management of various diseases. There is limited clinical data on honey and its mechanisms of action. However, comprehensive clinical studies are needed to fully investigate the potential health benefits of honey, including its efficacies, safety, bioavailability, and underlying mechanisms of action.

The metabolism of maltose and maltotriose, the primary sugars in brewing wort, depends on an efficient transport system. However, most Saccharomyces cerevisiae strains transport maltotriose inefficiently, leaving residual α-glucosides in the final product. Proteins involved in maltotriose transport exhibit diverse polymorphic sequences linked to sugar transport efficiency. In this study, a wild S. cerevisiae strain was placed under adaptive selection, resulting in a strain with a 65 and 44% increase in maltose and maltotriose transport rates, respectively. Genes encoding maltose and maltotriose transporters, including MAL x1, MPH x, and AGT 1, were detected in both the native and adapted strains. One variant of Mal31p, carrying a polymorphism at position 371 in transmembrane helix 7, was identified. This helix has been reported to have a high likelihood of undergoing polymorphisms. Bioinformatics analysis revealed structural changes affecting substrate interactions and channel dynamics, with the polymorphism conferring greater protein flexibility and reducing electrostatic interactions. These results suggest that the residue at position 371 in maltose and maltotriose transporters is a key element distinct from those previously reported. Additionally, we propose a significant set of polymorphic residues within these transporters potentially resulting from the evolution of these proteins. Graphical abstract

The valorization of agricultural by-products is a key strategy for environmental sustainability. This study focuses on optimizing the extraction of phenolic compounds from by-products (peels, fibrous strands, and seeds) of two Tunisian squash landraces (e.g. Bejaoui and Karkoubi) using the response surface methodology to enhance their antioxidant and antibacterial properties. Ethanol concentration, extraction time, and temperature were the key parameters evaluated for their impact on phenolic compounds yield and bioactivity. High-performance liquid chromatography identified the major bioactive phenolic compounds, including vanillic acid, catechin gallate, hydroxytyrosol, and chlorogenic acid. The optimal extraction conditions for each by-product were defined as follows: Bejaoui peels (51.5% ethanol, 40.8°C, 50.5 min), fibrous strands (50.4% ethanol, 37.1°C, 36.3 min), and seeds (30% ethanol, 36.4°C, 8 min); Karkoubi peels (13.2% ethanol, 43.4°C, 47.2 min), fibrous strands (33.4% ethanol, 46.6°C, 10.8 min), and seeds (10.65% ethanol, 55.34°C, 23.16 min). The results demonstrated that optimizing extraction conditions may lead to significant enhancement of the total phenolic content and antiradical activity, with experimental values closely matching predictive models. Furthermore, the bioactive properties of these by-products, particularly their antibacterial activity, highlight their potential application as novel eco-friendly matrices for natural antioxidant and antimicrobial agents. This study underscores the importance of optimizing sustainable extraction techniques to maximize the valorization of agricultural waste, contributing to both environmental protection and the development of innovative natural products within the circular economy concept. Graphical abstract

Liupao tea is known for its anti-inflammatory antioxidant and regulation of gut microecological balance properties. This study aims to investigate the therapeutic effects of Liupao tea aqueous extract (LPTAE) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The rats were randomly divided into five groups: the Normal group, the DSS group, the LPTL group, the LPTM group, and the LPTH group. Throughout the experiment, the rats’ activity levels, stool consistency, and body weights were observed and recorded daily. After the experiment, colon length was measured, and colon tissues were collected for pathological analysis. Additionally, the colon contents were analyzed for gut microbiota composition and short-chain fatty acid (SCFA) level, while serum samples were collected to determine inflammatory and oxidative factors. The results indicated that treatment with low, medium, and high doses of LPTAE significantly inhibited weight loss, alleviated rectal bleeding, and reduced colon shortening compared to the DSS group. It also decreased the disease activity index and histopathological activity index scores in the rats. Furthermore, LPTAE reduced the levels of inflammatory cytokines such as IL-1 β , IL-6, TNF- α , and malondialdehyde, while simultaneously increasing the levels of superoxide dismutase and SCFAs, including acetic acid, propionic acid, and butyric acid. 16S rDNA gene sequencing of the gut microbiota revealed that all doses of LPTAE reversed the decrease in both α and β diversities caused by UC, increased the relative abundance of beneficial bacteria such as Lactobacillus , Muribaculaceae, Alloprevotella , and Blautia , and decreased the levels of harmful bacteria such as Prevotella , Romboutsia , and Bacteroides . In summary, within the tested doses (100, 150, 250 mg/kg), LPTAE alleviated DSS-induced colitis by modulating the gut microbiota and correcting the metabolic imbalance of SCFAs.

The abundant and renewable resources from fruit by-products are getting emphasis on their valorization. These by-products may contain toxic substances due to factors such as cultivation, harvesting, transportation, preservation, or processing. Hence, presenting scientific overviews of the toxicological qualities and detoxification trends of these by-products are critical for implicating their possible valorization. The present demand for valorization of fruit by-products requires emphasis and methodologies for the detoxification of any toxicants to develop healthier products. This review emphasized the toxicological qualities of by-products from fruits for which the maximum global production occurred in 2022. In this review, heavy metals (arsenic, cadmium, cobalt, chromium, nickel, lead, and mercury), mycotoxins, toxicant organic compounds, anti-nutritional factors, and pesticide/fungicide residues of the selected fruit byproducts were discussed. Current trends to reduce possible toxicants of these by-products during their valorization were emphasized. Novel functional foods valorized from these fruit by-products and future perspectives of detoxification were also focused on in this review. Graphical abstract

Although cornelian cherry is an underutilized fruit species, its fruits have a high biological value due to valuable biologically active substances, especially polyphenols. The total content of polyphenols accounts for 37% of all the bioactive substances examined. Flavonols, anthocyanins, flavan-3-ols, and phenolic acids represent the main groups of phenolic compounds present and thanks to these compounds, cornelian cherry fruits possess mainly antioxidant, anti-inflammatory, antimicrobial, metabolic, antidiabetic, cardioprotective, and anticancer effects. This review summarizes new research aimed at popularizing this lesser-known species not only for direct consumption but also for further processing.

Encapsulation of the refined extract from squash fruit peels was evaluated for the design of functional foods with beneficial effects on human health. The percentage of maltodextrin and gum Arabic in the wall material as well as the concentration of the refined extract were the independent variables for the Box Behnken design, and their impact on response variables (total phenolic compound [TPC] content, DPPH activity, the size of particles, and polydispersity index [Pdi]) was evaluated. The obtained emulsions were compared based on their TPC content, as well as their antioxidant activities. Optimum conditions were as follows: maltodextrin percentage of 23.8%, gum Arabic percentage of 27.7%, and phenolic extract percentage of 48.5%. Under these conditions, the response variables were the following: TPC content of 46.01 mg of gallic acid equivalent per gram of extract (mg GAE/g of E); DPPH inhibition percentage of 64.85% at 1 mg/mL, particle size of 571.22 nm, and Pdi of 0.46. Once the emulsion was optimized, we tried to define the combination of variables that produced microcapsules with the highest TPC content and the highest antioxidant activity. Physicochemical parameters and biological activities were also assessed. Microcapsule parameters were a pH of 4.2, a viscosity of 17 mPa/s, and a turbidity of 0.412 NTU (Nephelometric Turbidity Units), and color measurements were L = 102.4, a = 3.5, and b = 7.8. Indeed, the TPC content was 37.2 mg GAE/g dried residue and antiradical activity against DPPH was 44.2%. The inhibitory effects of the optimized emulsion on Enterococcus faecalis , Pseudomonas aeruginosa , Salmonella typhimurium , and Staphylococcus aureus were investigated, and the results indicated the highest sensitivity (89% inhibition) for S. typhimurium . Our results indicate the efficiency of the optimized emulsification process for developing microcapsules of high quality as well as the potential of using them in the development of novel food and pharmaceutical products. Graphical abstract

Here, we provide a current review of strategies aimed at improving the bioavailability of curcuminoids, a group of compounds with therapeutic potential. This review discusses formulations from the traditional supplementation approaches to the innovative methods to enhance solubility and bioavailability, including cyclodextrins and hydrophilic carriers. Additionally, colloidal delivery strategies, such as micelles, liposomes, solid lipid particles, and emulsions, are examined as promising vehicles for curcuminoid delivery. The review underscores the importance of clinical trials in assessing the efficacy of these formulations and highlights a pivotal yet frequently neglected factor in curcuminoid research: the differentiation between total and free curcuminoid quantification. In summary, this concise review evaluates existing curcuminoid formulations and explores innovative approaches to improve their bioavailability.

The consumption of chia seeds has surged in recent years, primarily due to their beneficial chemical composition and health effects. Sprouting chia seeds can enhance the content of essential nutrients, including antioxidants and vitamins. The study investigates the impact of sprouting on the bioactive compounds and antioxidant activity of chia seeds under both favorable and stressful conditions. Chia seeds were sprouted in tap water, distilled water, and varying concentrations of seawater. The parameters analyzed included antioxidant activity, the reducing capacity of antioxidants, total polyphenol content, flavonoid content, and phenolic profile. Results indicated that sprouting significantly influences antioxidant activity in seeds sprouted in tap and distilled water, with a decrease observed only in the 2,2′-azinobis(3-ethyl-2,3-dihydrobenzothiazol-6-sulfonate) method for distilled water. Additionally, sprouting in both water types led to a statistically significant increase ( p < 0.05) in reducing capacity and total polyphenol content. Under high salinity conditions, sprouting in 100% seawater resulted in a significant increase ( p < 0.05) in antioxidant activity, reducing capacity, and total polyphenol content. These findings suggest that sprouting chia seeds, particularly under saline conditions, could enhance their nutritional profile, presenting potential applications in the food and nutrition industry and indicating possibilities for ecological cultivation.

The advancement of genetic techniques in food production offers significant potential for improving crop quality, yield, and sustainability. However, these innovations present a complex set of dilemmas concerning nutritional quality, food authenticity, socioeconomic implications, regulatory challenges, and human health. This article explores contemporary genetic methods such as marker-assisted selection, genome editing (CRISPR-Cas9), and tissue culture, highlighting their applications and limitations. Additionally, transgenic approaches and biofortification strategies are examined for their role in enhancing nutritional value. It examines the trade-offs between organoleptic properties and nutritional integrity, revealing a concerning trend toward prioritizing sensory attributes over health benefits. Furthermore, the potential health implications of genetic manipulation, including links to autoimmune and hormonal disorders, are critically analyzed with a focus on allergenicity concerns and long-term safety assessments. The discussion underscores the urgent need for sustainable practices in food genetics that align with environmental goals and public health priorities. Finally, a call to action is made for collaborative dialogue among scientists, policymakers, and consumers to prioritize health, sustainability, and transparency in food production, ensuring that agricultural advancements benefit all stakeholders while preserving the ecological balance for future generations. Graphical abstract

Rhynchophylline (Rhy) is an attractive candidate, harboring ameliorative effects on Alzheimer’s disease (AD). Nevertheless, its application is impeded by its low water solubility and poor bioavailability. Here we synthesized and characterized the Rhy-loaded hyaluronic acid-modified hafnium metal-organic frameworks (HA@Rhy@Hf-MOF). The drug release profiles of free Rhy from HA@Rhy@Hf-MOF were evaluated, and the cellular toxicity was assessed through Cell Counting Kit-8 (CCK-8) assay. In vivo experiments included behavioral experiments of various murine capabilities, with neuronal damage appraised through Hematoxylin and Eosin staining and Nissl staining. Subsequently, the formation of AD-related amyloid beta (Aβ) plaques formation and Tau phosphorylation were measured. The HA@Rhy@Hf-MOF with spherical shape were presented as uniformly dispersed and with a negative charge, exhibiting a pronounced pharmacological sustained-release effect and minimal cellular toxicity. Findings from the Morris water maze test, novel object recognition test, and elevated plus maze test substantiated that HA@Rhy@Hf-MOF effectively mitigated cognitive deficiency and anxiety, and enhanced spatial learning in AD mice. Immunofluorescence staining and Western blot both illustrated that HA@Rhy@Hf-MOF could attenuate hippocampal Aβ formation and deposition, as well as tau hyperphosphorylation. In conclusion, HA@Rhy@Hf-MOF exerts its therapeutic efficacy against AD by targeting the deposition of Aβ plaques and inhibiting site-specific phosphorylation of Tau.

The aim of this study is to analyze scientific literature to investigate the current research status, focus areas, and developmental trends in nanoparticle systems for rheumatoid arthritis (RA) therapy. To do that, Research articles published from 2003 to 2023 were retrieved from the Web of Science database, and analysis included quantitative output, distribution by country/region, collaborative publishing data, influential authors, high-yield institutions, keywords, hotspots, and development trends. Visual knowledge maps were generated using VOSviewer and Citespace. Findings reveal a steady increase in publications related to nanoparticle systems for RA therapy, indicating growing global interest. China leads with 487 papers (37.433%), followed by the United States (233, 17.909%), India (179, 13.759%), South Korea (89, 6.841%), and Egypt (50, 3.843%). Active collaboration is observed, particularly between the United States and countries such as China, Germany, Saudi Arabia, India, England, and Pakistan. The Chinese Academy of Sciences ranks first in total articles published (55), with Liu Y from China being the most prolific author. The Journal of Controlled Release emerges as a primary outlet in this field. Primary keyword clusters include “Drug delivery systems,” “Gold nanoparticles,” “Transdermal delivery,” “Angiogenesis,” “Collagen-induced arthritis,” “Rheumatoid arthritis,” “Oxidant stress,” “Dendritic cells,” and “pH sensitive.” Research hotspots with great development potential include “Immunopathological Mechanisms,” “Novel drugs,” and “Smart delivery system.” In conclusion, research on nanoparticle systems for RA therapy has significantly expanded over the past two decades, with a focus on elucidating pathogenetic mechanisms and advancing novel drug delivery strategies anticipated to be prominent in the foreseeable future.

The poultry industry faces multifaceted challenges, including escalating demand for poultry products, climate change impacting feed availability, emergence of novel avian pathogens, and antimicrobial resistance. Traditional disease control measures are costly and not always effective, prompting the need for complementary methods. Gene editing (GE, also called genome editing) technologies, particularly CRISPR/Cas9, offer promising solutions. This article summarizes recent advancements in utilizing CRISPR/Cas GE to enhance infectious disease control in poultry. It begins with an overview of modern GE techniques, highlighting CRISPR/Cas9’s advantages over other methods. The potential applications of CRISPR/Cas in poultry infectious disease prevention and control are explored, including the engineering of innovative vaccines, the generation of disease-resilient birds, and in vivo pathogen targeting. Additionally, insights are provided regarding regulatory frameworks and future perspectives in this rapidly evolving field.

Hafnium nitride (HfN) coatings with different thicknesses and various composition ratios were successfully fabricated on the surface of titanium alloys by magnetron sputtering, and their antibacterial properties and biocompatibility were evaluated. The structures of the coatings were characterized by X-ray diffraction (XRD; DX-2700BH diffractometer) in symmetric θ –2 θ scanning mode. The surface morphologies of the coatings were characterized by scanning electron microscopy (SEM; Nova NanoSEM450). The surface element distribution of the film was characterized by the energy-dispersive spectrometer (EDAX ELECT PLUS). The antibacterial properties of different materials against Staphylococcus aureus (ATCC 25923) were evaluated by plate colony counting, crystal violet staining, SEM, and SYTO-9/PI live/dead bacterial staining. The proliferation of bone marrow mesenchymal stem cells was detected by CCK-8 assays, and the biocompatibilities of different materials were evaluated by calcein-acetoxymethyl/propidium iodide (PI) live/dead cell staining. The surface morphology and element analyses revealed that the HfN coatings and titanium substrates did not contain other substances, and their surfaces were relatively uniform. After 24 h incubated with Staphylococcus aureus , sample 2 (50 nm thick, N 2 flow rate of 2.5 sccm) displayed the best antibacterial performance. CCK-8 cell proliferation and calcein-AM/PI live/dead cell staining assays indicated that sample 2 had the best biocompatibility. The modified titanium implants had good biocompatibility and antibacterial properties. The results presented here can potentially guide and inspire additional ideas to alter the surfaces of titanium implants. Graphical abstract

Although citrus essential oils, including lemongrass essential oil, have antibacterial, anti-biofilm, and antioxidant properties, their biological instability and poor water solubility render them unsuitable for industrial usage. Thus, this study aimed to prepare both lemongrass essential oil emulsion (LEO-E) and lemongrass essential oil nanoemulsion (LEO-NE), and evaluate their different bioactivities. Characterization by gas chromatography–mass spectroscopy (GC–MS) and evaluation of antimicrobial, antibiofilm, antioxidant, and anticancer activities were carried out. GC–MS results illustrated that D -limonene compound is the dominant among other compounds in LEO. According to transmission electron microscopy and dynamic light scattering, LEO-NE appeared as spherical-shaped droplets with a constant size spanning from 29.1 to 37.4 nm with a polydispersity index value of 0.163. Antimicrobial results showed that LEO-NE exhibited promising antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans , and Austromerope brasiliensis with inhibition zones of 25.33 ± 1.1, 26.5 ± 0.5, 22 ± 1, 24.33 ± 0.5, 28.6 ± 1, and 27.97 ± 0.9 mm, respectively. Moreover, LEO-NE showed considerable antiـbiofilm efficacy toward S. aureus and P. aeruginosa with inhibition percentages at 1/2 of MIC of 98.92 and 92.62%, respectively. Furthermore, LEO-NE exhibited antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl method with 88.5% at 100 µg/mL concentration. In addition, LEO-NE displayed potential anticancer activity toward the human prostate cancer cell line (PC3) and human liver cancer cell line (Hep-G2), where IC 50 values were 170.09 and 105.06%, respectively. In conclusion, the prepared LEO-NE in the current study had antimicrobial, antibiofilm, antioxidant, and anticancer activities, which can be used in the medical and pharmaceutical fields. Graphical abstract