Band 17, Heft 1

The aim of this study was to explore the effects of dabigatran and rivaroxaban on the activities of various coagulation factors. To achieve that, 60 rabbits were randomly divided into experimental groups that received different doses of dabigatran or rivaroxaban. The effects of dabigatran and rivaroxaban on the activities of FII, FV, FVIII, FX, and activated protein C (APC) were analyzed. In the dabigatran groups, activated partial thromboplastin time and thromboplastin time (TT) were prolonged after drug administration, and the activities of FII, FV, FVIII, and FX were inhibited as the drug concentration increased. Low doses of dabigatran inhibited APC activity. In the rivaroxaban groups, APTT and TT were not significantly prolonged after drug administration. In contrast, the high-dose rivaroxaban group exhibited prolonged PT, and the degree of inhibition of the activities of FII, FV, FVIII, and FX increased as the drug concentration increased. Rivaroxaban had no significant effect on APC activity regardless of dosage. As the drug concentration increased, both NOACs had more significant inhibitory effects on the activities of FII, FV, FVIII, and FX. Low concentrations of dabigatran generated an inhibitory effect on APC activity, while high concentrations of dabigatran had no significant effect. Rivaroxaban had no significant effect on APC activity.

The recent SARS-CoV-2 pandemic, which is causing COVID-19 disease, has taught us unexpected lessons about the dangers of human suffering through highly contagious and lethal diseases. As the COVID-19 pandemic is now being partially controlled by various isolation measures, therapeutics, and vaccines, it became clear that our current lifestyle and societal functions may not be sustainable in the long term. We now have to start thinking and planning on how to face the next dangerous pandemic, not just overcoming the one that is upon us now. Is there any evidence that even worse pandemics could strike us in the near future and threaten the existence of the human race? The answer is unequivocally yes. It is not necessary to get infected by viruses found in bats, pangolins, and other exotic animals that live in remote forests to be in danger. Creditable scientific evidence indicates that the human gut microbiota harbor billions of viruses that are capable of affecting the function of vital human organs such as the immune system, lung, brain, liver, kidney, or heart. It is remotely possible that the development of pathogenic variants in the gut can lead to contagious viruses, which can cause pandemics, leading to the destruction of vital organs, causing death or various debilitating diseases such as blindness, respiratory, liver, heart, and kidney failures. These diseases could result in the complete shutdown of our civilization and probably the gradual extinction of the human race. This essay will comment on a few independent pieces of scientific facts, and then combine this information to come up with some (but certainly not all) hypothetical scenarios that could cause human race misery, even extinction, in the hope that these hypothetical scenarios will trigger preventative measures that could reverse or delay the projected adverse outcomes.

Drug resistance contributes to treatment failure and relapse in acute lymphoblastic leukemia (ALL). G1P3 (also known as IFI6, interferon, alpha-inducible protein 6) has been regarded as an antiapoptotic protein in myeloma cells and contributes to chemoresistance in breast cancer. However, the role of G1P3 in the proliferation and chemosensitivity of ALL is largely unknown. Data from colony formation and bromo-deoxyuridine (BrdU) incorporation assays showed that siRNA-mediated downregulation of G1P3 repressed cell proliferation of glucocorticoids-resistant human leukemic cells (CEM-C1), while overexpression of G1P3 promoted the cell proliferation. Cell apoptosis of CEM-C1 was suppressed by G1P3 overexpression accompanied by a decrease in cleaved caspase-3 and caspase-9. Knockdown of G1P3 increased protein expression of cleaved caspase-3 and caspase-9 to promote the cell apoptosis of CEM-C1. Moreover, silencing of G1P3 reduced cell viability and promoted cell apoptosis of CEM-C1 exposed to dexamethasone. The proapoptotic protein B-cell lymphoma 2 interacting mediator of cell death (Bim) was enhanced by the interference of G1P3 in CEM-C1. Silencing of Bim attenuated G1P3 interference-induced decrease in cell viability and increase in cell apoptosis in CEM-C1 exposed to dexamethasone. Conclusively, knockdown of G1P3 inhibited cell proliferation of ALL and sensitized glucocorticoid-resistant ALL cells to dexamethasone through upregulation of Bim-mediated cell apoptosis.

This study aimed to reveal the mechanism by which long noncoding RNAs (lncRNAs) modulate hepatocellular carcinoma (HCC) by regulating mRNA via the N6-methyladenosine (m6A) enzyme. The expression and clinical data of 365 HCC patients and 50 healthy control samples were downloaded from the the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) screened using limma packages from the R. m6A2Target database were used to predict the relationship between m6A enzyme-lncRNA and m6A enzyme-mRNA. The mRNAs in the lncRNA-m6A enzyme-mRNA network were subjected to enrichment analysis. Cox regression analysis was used to screen for RNAs significantly related to HCC prognosis. The expression of differentially expressed RNAs (DERs) was verified using the TCGA dataset and GSE55092. Eighty-five DElncRNAs and 747 DEmRNAs were identified. The mRNAs in the lncRNA-m6A enzyme-mRNA network were primarily involved in mitotic cell division, the p53 signaling pathway, and the cell cycle. Three lncRNAs and 14 mRNAs were significantly associated with HCC prognosis. Furthermore, the expression of 12 DERs differed significantly between patients in the early and advanced stages. LINC00665 was predicted to regulate 11 mRNAs by modulating IGF2BP1, IGF2BP2, and YTHDF1. Thus, this study provides new insights into the roles of lncRNA and m6A enzymes in HCC.

Claudin-14 protein plays an essential role in regulating calcium ions in the kidney and ear. Two phenotypes, hearing loss and kidney stones, were reportedly associated with variations in the CLDN14 gene. This study aimed to understand CLDN14 mutations’ contribution to hearing loss and renal stone formation in a Pakistani cohort. We analyzed CLDN14 sequence variations in 100 patients, along with healthy individuals, to assess whether specific polymorphisms were associated with the disease. Also, we performed an in silico analysis using a mutation database and protein annotation. The rs219779’s genotype CT ( p = 0.0020) and rs219780’s genotype AG ( p = 0.0012) were significantly associated with kidney stones. We also found that a novel haplotype, “TA” associated with kidney stone formation, has moderate linkage disequilibrium. The TA haplotype was significantly correlated with a kidney stone risk formation of 3.76-fold (OR (CI 95%) = 3.76 (1.83–7.72)) and p = 0.0016 compared to other haplotypes. In silico analysis revealed that mutations associated with hearing loss were not correlated with renal stone formation but affected claudin-14 protein stability. We structurally mapped a novel TA haplotype of CLDN14 that, based on our analysis, likely contributes to the pathogenesis of renal stones.

The concanavalin A (Con A)-induced liver injury mouse model is a typical animal model focusing on T cell-dependent hepatic damage in the field of autoimmune hepatitis (AIH). However, the underlying mechanism of hepatic dysfunction due to cell activation or signaling pathways triggered by Con A has not been fully clarified. Therefore, the controversy on this model remains in the academic community. In this article, we first summarized the merit and demerit of this contentious model from the perspectives of cell dysfunction, microcirculation disturbance, involved signaling pathways, as well as the properties of Con A. Then, we summed up the scientific implications of the model in elucidating the pathogenesis of AIH, and the shortcomings of this model were also summarized to elucidate the pathogenesis and application prospect of this classical liver injury mouse model in the study of AIH.

miR-30b, which is encoded by the gene located on chromosome 8q24.22, plays an important role in a variety of diseases. In most types of tumors, miR-30b significantly inhibits the proliferation, migration, and invasion of cancer cells through the regulation of target genes. Moreover, miR-30b can inhibit the PI3K/AKT signaling pathway through the regulation of EGFR, AKT, Derlin-1, GNA13, SIX1, and other target genes, thus inhibiting the EMT process of tumor cells and promoting apoptosis. In addition, miR-30 plays a significant role in alleviating drug resistance in tumor cells. Although the use of miR-30b as a clinical diagnostic indicator or anticancer drug is still facing great difficulties in the short term, with the deepening of research, the potential application of miR-30b is emerging.

This study explored the impact of pulmonary microecological changes on disease progression in non-cystic fibrosis bronchiectasis (nCFB). A careful search of the NCBI BioProject database revealed the 16S rRNA-based microbiological testing results of 441 pulmonary sputum samples from patients in the relatively stable (baseline), acute exacerbation, or recovery stage. After preliminary analysis and screening, we selected 152 samples for further analyses, including determination of the operational taxonomic unit (OTU) distribution at the phylum, class, order, family and genus levels, community structure, alpha diversity, beta diversity, microbial multivariables, correlations, and community structure after the abundances of intragroup samples were averaged. The recovery group showed significant differences in pulmonary microbiological changes ( P < 0.05) compared with the other groups. There were 30 differentially abundant OTUs, with 27 and 7 at the genus and phylum levels, respectively. The Chao1 value of the recovery group was comparable to that of the baseline group, and the Shannon and Simpson values of the recovery group were the highest. Rhodococcus in Actinobacteria was positively correlated with Ochrobactrum in Firmicutes. The differences in pulmonary microecological changes at different nCFB stages may serve as a biologically predictive indicator of nCFB progression.

Low physical activity correlates with increased cancer risk in various cancer types, including colorectal cancer (CRC). However, the ways in which swimming can benefit CRC remain largely unknown. In this study, mice bearing tumors derived from CT-26 cells were randomly divided into the control and swimming groups. Mice in the swimming group were subjected to physical training (swimming) for 3 weeks. Compared with the control group, swimming clearly attenuated tumor volume and tumor weight in CT-26 tumor-bearing mice. RNA sequencing (RNA-seq) identified 715 upregulated and 629 downregulated transcripts (including VEGFA) in tumor tissues of mice in the swimming group. KEGG pathway analysis based on differentially expressed transcripts identified multiple enriched signaling pathways, including angiogenesis, hypoxia, and vascular endothelial growth factor (VEGF) pathways. Consistently, IHC analysis revealed that swimming significantly downregulated CD31, HIF-1α, VEGFA, and VEGFR2 protein expression in tumor tissues. In conclusion, swimming significantly attenuates tumor growth in CT-26 tumor-bearing mice by inhibiting tumor angiogenesis via the suppression of the HIF-1α/VEGFA pathway.

Mild micro-hepatic encephalopathy (MHE) is a severe complication of cirrhosis. At present, there are differences in the consistency of detection strategies and treatment directions for MHE. The characteristic changes in intestinal microbiota and serum metabolites in MHE patients and the possible relevant interaction mechanisms would inevitably affect the developmental direction of MHE. Therefore, the changes in the characteristics of intestinal microbiota and serum metabolites of MHE patients were determined, and the possible interactions between them were analyzed. Stool and serum tests were performed on both the MHE patients and healthy individuals. The 16S rRNA gene high-throughput sequencing and bioinformatics analyses were used to analyze the differences in intestinal microbiota in MHE patients. The serum metabolites were detected using liquid LC-MS/MS (liquid chromatography-mass spectrometry) technology, and the differences in the metabolic networks of blood metabolites in MHE patients were analyzed. A comprehensive bioinformatics analysis approach was adopted to identify the composition and characteristics of microbiota and serum metabolites and the possible correlation between them. The main characteristics of the structural imbalance in the intestinal microbiota of MHE patients included a decrease in the number of beneficial bacteria at the levels of phylum, class, order, family, and genus and an increase in the pathogenic bacteria, resulting in substantial changes in the relative abundances of bacteria in the intestinal microbiota. The main predicted functions that showed significant differences included chromosome, amino acid-related enzymes, methane metabolism, and arginine and proline metabolism. The detection of serum metabolites resulted in 10 different metabolites, including taurocholic acid, citrulline, d -phenyl-lactic acid, l -tyrosine, benzoate, phenylalanine, linoleic acid, eicosapedienic acid, alpha-dimorphecolic acid, and dehydroepiandrosterone. The subsequent metabolite pathways analysis showed differences in the metabolism of linoleic acid, phenyl-propane, caffeine, arginine, proline, glycine, serine, threonine, tyrosine, and pyrimidine compared to the control group. In summary, it seems that the changes in the microbiome that we have identified have resulted in corresponding changes to the serum metabolome. In turn, this may represent changes in the absorption of metabolites from the gut or reflect the changed metabolic capacity of the MHE liver or both. There were characteristic changes in the intestinal microbiota and serum metabolites in the MHE patients. There might be a related interaction mechanism between the two, which would provide evidence and direction for the detection and treatment strategies of MHE.

Unique to plants, growth regulatory factors (GRFs) play important roles in plant growth and reproduction. This study investigated the evolutionary and functional characteristics associated with plant growth. Using genome-wide analysis of 15 plant species, 173 members of the GRF family were identified and phylogenetically categorized into six groups. All members contained WRC and QLQ conserved domains, and the family’s expansion largely depended on segmental duplication. The promoter region of the GRF gene family mainly contained four types of cis -acting elements (light-responsive elements, development-related elements, hormone-responsive elements, and environmental stress-related elements) that are mainly related to gene expression levels. Functional divergence analysis revealed that changes in amino acid site evolution rate played a major role in the differentiation of the GRF gene family, with ten significant sites identified. Six significant sites were identified for positive selection. Moreover, the four groups of coevolutionary sites identified may play a key role in regulating the transcriptional activation of the GRF protein. Expression profiles revealed that GRF genes were generally highly expressed in young plant tissues and had tissue or organ expression specificity, demonstrating their functional conservation with distinct divergence. The results of these sequence and expression analyses are expected to provide molecular evolutionary and functional references for the plant GRF gene family.

In prokaryotes, few studies have applied the flippase ( FLP )/P1-flippase recombination target ( LoxP-FRT ) recombination system to switch gene expression. This study developed a new method for switching gene expression by constructing an FLP / LoxP-FRT site-specific recombination system in Escherichia coli . To this end, we placed the Nos terminator flanked by a pair of LoxP-FRT in front of enhanced green fluorescent protein ( eGFP ). The Nos terminator was used to block the expression of the eGFP . When a plasmid expressing FLP was available, deletion of the Nos terminator would allow expression of eGFP . The regulatory effect was demonstrated by eGFP expression. The efficiency of the gene switch was calculated as high as 89.67%. The results showed that the FLP / LoxP-FRT recombinase system could be used as a gene switch to regulate gene expression in prokaryotes. This new method for switching gene expression could simplify the gene function analysis in E. coli and other prokaryotes, as well as eukaryotes. Graphical abstract

The article presents a study of the antioxidant properties of meat from lambs that received organic forms of iodine and selenium during growth. This meat was included in diets of laboratory animals using a model of acute toxic hepatitis. The experiments resulted in developing and testing a technique that was effective in enriching lamb with bioorganic elements of iodine and selenium and contributed to the activation metabolism in the bodies of animals consuming the meat. The purpose of the presented investigation was to compare the roles of bioorganic iodine and selenium and their combination as antioxidants in rat rations using a model of acute toxic hepatitis induced by carbon tetrachloride. The experimental studies have established a hepatoprotective effect of lamb meat enriched with selenium and iodine on rats suffering from toxic xenobiotic effects. This was confirmed by normalized hematological and biochemical measures in the blood of the experimental rats.

Traumatic brain injury (TBI) is a predominant cause of death and permanent disability globally. In recent years, much emphasis has been laid on treatments for TBI. Increasing evidence suggests that human umbilical cord mesenchymal stem cells (HUCMSCs) can improve neurological repair after TBI. However, the clinical use of HUCMSCs transplantation in TBI has been limited by immunological rejection, ethical issues, and the risk of tumorigenicity. Many studies have shown that HUCMSCs-derived exosomes may be an alternative approach for HUCMSCs transplantation. We hypothesized that exosomes derived from HUCMSCs could inhibit apoptosis after TBI, reduce neuroinflammation, and promote neurogenesis. A rat model of TBI was established to investigate the efficiency of neurological recovery with exosome therapy. We found that exosomes derived from HUCMSCs significantly ameliorated sensorimotor function and spatial learning in rats after TBI. Moreover, HUCMSCs-derived exosomes significantly reduced proinflammatory cytokine expression by suppressing the NF-κB signaling pathway. Furthermore, we found that HUCMSC-derived exosomes inhibited neuronal apoptosis, reduced inflammation, and promoted neuron regeneration in the injured cortex of rats after TBI. These results indicate that HUCMSCs-derived exosomes may be a promising therapeutic strategy for TBI.

Gestational diabetes mellitus (GDM) is a common obstetric disease among pregnant women. This study aimed to explore the effect of dietary pattern management to reduce the incidence of GDM. Here, we, retrospectively, analyzed the influence of dietary patterns on the occurrence of GDM and the correlation between dietary patterns and intestinal microbiome distribution and inflammation in pregnant women. Moreover, patients were assigned to the dietary pattern management group and the nondietary pattern management group, and the effects of dietary patterns on the intestinal microbiome distribution and inflammatory factors were investigated. We found that the intestinal microbiome was changed in GDM patients compared with the healthy controls. The relative abundance of probiotics Lactobacillus and Bifidobacterium significantly decreased in patients with GDM. Moreover, compared with the control group, the expression levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Furthermore, dietary pattern management led to intestinal microbiome changes in patients with GDM. In conclusion, dietary pattern management could alleviate GDM via affecting the intestinal microbiome as well as inflammatory conditions in patients.

The purpose of this study was to explore the regulatory mechanism of Annexin A1 (ANXA1) in glioma cells in the inflammatory microenvironment induced by tumour necrosis factor α (TNF-α) and its effects on glioma cell proliferation. CCK-8 analysis demonstrated that TNF-α stimulation promotes rapid growth in glioma cells. Changes in tumour necrosis factor receptor 1 (TNFR1) and ANXA1 expression in glioma cells stimulated with TNF-α were revealed through western blot analysis and immunofluorescence staining. Coimmunoprecipitation analysis revealed that ANXA1 interacts with TNFR1. Moreover, we found that ANXA1 promotes glioma cell growth by activating the p65 and Akt signalling pathways. Finally, immunohistochemistry analysis showed an obvious correlation between ANXA1 expression and Ki-67 in glioma tissues. In summary, our results indicate that the TNF-α/TNFR1/ANXA1 axis regulates the proliferation of glioma cells and that ANXA1 plays a regulatory role in the inflammatory microenvironment.

We aimed to investigate the effect of the genetic mutant G71R (c. 211G > A) in uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) on the glucuronidation of unconjugated bilirubin. The UGT1A1 wild-type and mutant G71R gene sequences were inserted into the lentiviral vector GV358 plasmid and then transfected into COS-7 cells. Real-time polymerase chain reaction and western blot analyses were used to determine mRNA and protein expression levels of UGT1A1, respectively. High-performance liquid chromatography was used to quantitate the levels of conjugated bilirubin. The results showed no significant difference in the mRNA and protein expression levels between the UGT1A1 wild-type and G71R homozygous and heterozygous mutants. The level of conjugated bilirubin reached a maximum in wild-type UGT1A1-transfected COS-7 cells. However, relative to the UGT1A1 wild-type, conjugated bilirubin concentrations were 71 and 22% with G71R heterozygous- and G71R homozygous-transfected COS-7 cells, respectively. In conclusion, we successfully established in vitro cell models of the UGT1A1 wild-type and the G71R homozygous and heterozygous mutants using a lentiviral vector. Furthermore, the catalytic activity for unconjugated bilirubin was lower in the mutant G71R than the UGT1A1 wild-type enzyme, and a weaker effect was observed in the homozygote.

The accumulation of β-amyloid (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer’s disease (AD). The lack of estrogen is one of the risk factors for AD. Quercetin is a phytoestrogen with a chemical structure similar to that of estrogen. However, the mechanism by which quercetin prevents AD is unclear. PC12 cells were cultured with Aβ 25–35 for 24 h. Then the cells were further treated with 17β-estradiol, genistein, and quercetin for another 24 h, respectively. Next, ICI182780 and U0126 were used to study the mechanisms of estrogen-like neuroprotection. Methyl thiazolyl tetrazolium (MTT) assay was performed to detect cell survival. The protein expression was analyzed by immunofluorescence and western blot. The survival of PC12 cells induced by Aβ 25–35 was increased by quercetin. The levels of estrogen receptor α (ERα) and p-extracellular signal-regulated kinase (ERK)1/2 were improved by quercetin, but not those of ERβ. On the contrary, Bcl-2/Bax was increased and the expression of Caspase-3 was decreased. When the cell was pretreated with ICI182780, the p-ERK1/2 and Bcl-2/Bax ratio was decreased, but Caspase-3 expression was increased. In addition, pretreatment with U0126 would reduce Bcl-2/Bax ratio and increase Caspase-3 protein expression. Conclusively, quercetin plays a neuroprotective role through the ER pathway and the mitogen-activated protein kinase (MAPK) pathway. The MAPK signaling pathways could also be activated by quercetin via the mediation of ERα.

In this study, we explored the effect of nutrition intervention on the management of patients with novel coronavirus pneumonia (NCP). A total of 28 NCP patients receiving therapy in Ningbo First Hospital (China) were enrolled in this study. The nutrition risk was assessed using the Nutritional Risk Screening (NRS)-2002 for the patients subjected to nutrition intervention provided by the Nutritional Department in Ningbo First Hospital, China. Compared to the situation at admission, the body mass index (BMI) and weight of NCP patients were higher at the time of discharge, while no significant difference was observed ( P > 0.05). The serum albumin and hemoglobin levels of NCP patients were significantly increased compared with those at admission and one week after admission ( P < 0.05). The nutrition intervention can improve the nutritional status and prognosis of NCP patients.

Circular RNAs (circRNAs) have previously been confirmed to function as vital regulators in multiple human cancers, including hepatocellular carcinoma (HCC). This study aimed to clarify the role and underlying molecular mechanisms of circ-CFH in HCC. circ-CFH was overexpressed in HCC tissues and cells, and the downregulation of circ-CFH inhibited the development of HCC by repressing cell proliferation, migration, invasion, and glycolysis while enhancing apoptosis in vitro , as well as inhibited tumor growth in vivo . miR-377-3p was negatively regulated by circ-CFH, and silencing of miR-377-3p abolished circ-CFH knockdown-mediated effects on HCC cells. Moreover, overexpression of miR-377-3p could impede the HCC process by targeting RNF38. Mechanistically, the circ-CFH/miR-377-3p/RNF38 axis regulated the progression of HCC cells, which might provide new diagnostic markers for HCC.

This study aimed to investigate whether and how Moloney murine leukemia virus integration site 1 (Bmi-1) plays a role in the regulation of glucose transporter 1 (GLUT1) in gastric adenocarcinoma (GAC). GAC and matched noncancerous tissues were obtained from GAC patients who underwent surgical treatment at the China-Japan Union Hospital, Jilin University (Changchun, Jilin, China). The human GAC cell line AGS and the gastric epithelial cell line GES-1 were used for in vitro studies. BALB/c nude mice were used for in vivo studies. The Bmi-1 and GLUT1 protein levels were significantly greater in human tissues from GAC patients and AGS cells in comparison with controls. Silencing of Bmi-1 resulted in significant decrease in glucose uptake, lactate levels, and GLUT1 expression. In vivo 18 F-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) imaging studies indicated that the nude mice bearing xenografts of AGS cells treated with Bmi-1-specific small interfering RNA (siRNA) had a significantly lower maximum standardized uptake value (SUV max ) in comparison with the control mice. Thus, Bmi-1 directly upregulates GLUT1 gene expression, through which it is involved in enhancing glucose uptake in GAC. The results also provide scientific evidence for 18 F-FDG PET/CT imaging to evaluate Bmi-1 and glucose uptake in GAC.

Cerebral white matter lesion (WML) and lacunar infarction (LI) were primary causes of cognitive deficit. Our study aimed to investigate the correlation between LI and cognitive deficit in the elderly with WML. A total of 118 participants (96 WML patients and 22 controls) were consecutively enrolled according to neuroimaging diagnosis of magnetic resonance imaging for this retrospective study. Neuroimaging evaluation and cognitive function assessment were analyzed. Compared with the controls, moderate and severe WML groups had significantly lower scores of Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). Most cognitive domains of MOCA scores decreased, corresponding to the severity of WMLs. While there was no significant difference in score of MMSE between deep WML (DWML) and periventricular WML (PVL) groups, the scores of visuospatial/executive and naming function domains of MOCA appeared to be low in the DWML group. The scores of MMSE and MOCA were higher in only WMLs (WML−) group than WMLs combined with LIs (WML+) group, except for the naming cognitive domain. Moreover, LIs were independently correlated with the cognitive deficit in the elderly with WMLs. In the elderly with WMLs, the presence of LIs is associated with further aggravation of cognitive deficit.

The aim of the study was to investigate the inhibitory effect of hydroxysaff yellow A (HSYA) on diabetic retinopathy (DR). For this, a total of 27 rats were randomly divided into normal control, model, and HSYA groups. The body weight, blood glucose, and blood–retinal barrier damage of the rats were observed and compared. The pathological change of retinal tissue were measured using H&E staining. The apoptosis of retinal tissue ganglion cells was detected by TUNEL. The interleukin (IL)-1β and tumor necrosis fator (TNF)-α levels were detected using enzyme-linked immunosorbent assay. The level of malondialdehyde (MDA) was detected using thiobarbituric acid method. Superoxide dismutase levels were detected using xanthine oxidase method; Nrf2 and total HO-1 protein expressions were detected using western blot assay; Bcl-2 and P53 protein expression was measured using immunohistochemical staining. The body weight and retinal damage of the HYSA group were significantly improved ( p < 0.01, respectively). The apoptosis index of the HYSA group was lower than the model group ( p < 0.001). The IL-1β, TNF-α, and MDA levels of the HYSA group were significantly improved in comparison with those of the model group ( p < 0.01, respectively). The Nrf-2, HO-1, Bcl-2, and P53 protein expression of HYSA group was significantly improved ( p < 0.001, respectively). In conclusion, HYSA can effectively alleviate the apoptosis of retinal ganglion cells in type 2 diabetic rats and improve the progression of DR.

Three-dimensional (3D) printers mainly create 3D objects by stacking thin layers of material. The effect of the tools created using the fused deposition modeling (FDM) 3D printer on nerve cells remains unclear. In this study, the effects of polytetrafluoroethylene (PTFE) models and two different types of polylactic acid (PLA) models (white or natural), were created using the FDM 3D printer on axon extension were compared using the Campenot chamber. Neurons were isolated from the dorsal root ganglia and added to the central compartment of the Campenot chambers after isolation, processing, and culturing. On day 7, after the initiation of the culture, the difference of the axon extensions to the side compartments of each group was confirmed. We also compared the pH and the amount of leakage when each of these chambers was used. The PLA was associated with a shorter axon extension than the PTFE (white p = 0.0078, natural p = 0.00391). No difference in the pH was observed ( p = 0.347), but there was a significant difference on multiple group comparison ( p = 0.0231) in the amount of leakage of the medium. PTFE was found to be a more suitable material for culturing attachments.

This study aimed to investigate the relationship between interleukin (IL)-35 level and IL-35-producing regulatory T cells (iTr35 subset) in Mycobacterium tuberculosis (Mtb)-infected mice. After the mice were injected with Mtb strain H37R via tail vein, the bacterial burden, lung lesions, and the impact of immune suppression on the infected mice were respectively assessed. The results, when compared with the control mice, showed that the mRNA expression levels of the p35 and Epstein-Barr virus-induced gene 3 of IL-35 were significantly increased in the Mtb-infected mouse spleen at 4 or 8 weeks post-infection and their protein expression levels were concurrently increased in the lungs of the mice, especially in 8 week infected mice. In addition, the levels of serum IL-35 and the iTr35 subset in the spleen of mice were also increased in 4 or 8 weeks post-infection compared with the control mice. Importantly, the high bacterial burden and lung lesions and the low mouse weight were found at 8 week post-infection. Therefore, the mice infected with Mtb resulted in elevating IL-35 level and iTr35 subset and increasing bacterial burden and lung lesions. The findings from the study suggest IL-35 and iTr35 cells may exert an immune suppression role in chronic Mtb-infected mice.

Complex forms of diabetes are the ultimate common pathway involving multiple genetic variations and multiple environmental factors. Type 2 diabetes (T2DM) is classified as complex diabetes. Varying degrees of insulin deficiency and tissue insulin resistance are two key links to T2DM. The islet β cell dysfunction plays a crucial role in the pathogenesis of T2DM. The decompensation of the islet β cell to insulin resistance is a common mechanism leading to the pathogenesis of T2DM. Available data show that genetic factors mainly affect cell function. At present, a number of susceptibility genes related to T2DM have been reported at home and abroad. In this study, the diabetes-related genes in the case of early-onset diabetes with a significant family history were examined, and our results showed the presence of the intron mutations of catalase ( CAT ) gene and hepatocyte nuclear factor 1β ( HNF1β ) gene. The patient enrolled in this study was observed and analyzed, thus, increasing further understanding of the genes associated with diabetes and exploring the pathogenesis of diabetes from the molecular level. This is significant for guiding the prevention, treatment, and prognosis evaluation of diabetes.

Penicillium expansum is the main cause of apple rot. Besides, it can also produce mycotoxin patulin (PAT). Therefore, the search for substances that can inhibit the activity and toxigenicity of P. expansum has become a hot research topic. This study investigates the inhibitory effects of fengycin on patulin production in P. expansum. P. expansum was cultured under different environments with different concentrations of fengycin. The patulin content produced per unit weight of P. expansum mycelium was detected and determined by high pressure liquid chromatography (HPLC). Synergy brands (SYBR) GreenI Real-time PCR was used to detect the expression levels of 6-methylsalicylic acid synthase (6-MSAS) and isoepoxydon dehydrogenase (IDH), which were the key genes of producing patulin of P. expansum mycelium, in the conditions treated by fengycin and untreated. After fengycin treatments, not only the patulin content in every unit weight of P. expansum mycelium but also the expression level of 6-MSAS decreased significantly. The expression level of 6-MSAS of treatment was 0.11 folds of control. However, the expression level of IDH treated by fengycin decreased slightly. Fengycin could inhibit the P. expansum from producing patulin by downregulating the expression of key synthetic genes 6-MSAS.

Diabetic retinopathy (DR) is a type of main microvascular complication of diabetes mellitus (DM) and an important factor that causes blindness in adults. SOX4 is a transcription factor expressed in the pancreas and is essential for normal endocrine pancreatic development. However, the effect and the regulatory mechanism of SOX4 on DR have not been reported. In the present study, upregulation of SOX4 was found in DM patients, particularly in DR patients and mice models. The in vitro experiments showed that SOX4 depletion increased the viability and inhibited the inflammation level of human retinal endothelial cells (HRCECs) induced by high glucose. Besides, SOX4 knockdown inhibited the migration and angiogenesis of HRCECs upon high glucose treatment. Mechanically, depletion of SOX4 inhibited the NF-κB pathway. Therefore, SOX4 could serve as a promising target for DR treatment.

SARS-CoV-2 pandemic is one of the most critical pandemics during human civilization. Several therapeutic strategies for COVID-19 management have been offered; nonetheless, none of them seems to be sufficiently beneficial. In effect, vaccines have been proffered as a viable option. The critical issue now is to concentrate on protecting individuals against illness through immunization. One of the causes for concern among the researchers, physicians, and generally the whole community from the onset of vaccination has been the adverse effects (specifically blood clots) that may be observed after the injection of the COVID-19 vaccine. In some countries, such concerns have even resulted in the temporary or permanent discontinuation or abandonment of the application of some vaccines (especially AstraZeneca and Janssen). By evaluating rigorous studies published on this subject, the present article is aimed at identifying the association between blood clot incidence and COVID-19 vaccination. Various methods for producing the COVID-19 vaccines are analyzed, along with their possible pros and cons as well as common and rare side effects, especially VITT and blood clots. Finally, the differences of various vaccines on thrombotic events, WHO recommendations for VITT treatment, and blood clots statics are discussed.

Chromosomal abnormality is one of the important causes of dysplasia in children. However, due to regional and ethnic differences, the reported rates of chromosomal abnormalities in patients with dysplasia vary greatly. Moreover, the clinical manifestations in children with rare chromosomal diseases were heterogeneous. So, we retrospectively analyzed the karyotype results of 436 children with dysplasia and conducted a detailed analysis of rare chromosomal diseases. The results showed that chromosomal abnormalities were present in 181 of 436 cases. Intellectual disability, dysmorphology, congenital malformations, the disorder of sexual development, and short stature were the main five clinical symptoms in children with chromosomal abnormalities. Moreover, 136 cases of Trisomy 21 (Tri21) were detected, of which 130 were standard Tri21, 5 were robertsonian Tri21, and 1 was chimera type. In addition, 16 cases of rare abnormal karyotype, including complex Tri21, complex Turner syndrome, 4p-syndrome, 18q-syndrome, and 5p-syndrome, were also detected. In summary, chromosome abnormality is one of the important causes of dysplasia in children. Furthermore, prenatal screening and diagnosis could play a great significance in preventing dysplasia in children. In addition, the retrospective analysis of rare cases is valuable for clinical diagnosis and risk assessment of recurrence.

Growth differentiation factor 11 (GDF11) has been implicated in rejuvenating functions in age-related diseases. The molecular mechanisms connecting GDF11 with these anti-aging phenomena, including reverse age-related cardiac hypertrophy and vascular and neurogenic rejuvenation, remain unclear. In this study, we sought to uncover the molecular functions of GDF11 using bioinformatics and network-driven analyses at the human gene and transcription levels using the gene co-expression network analysis, the protein–protein interaction network analysis, and the transcription factor network analysis. Our findings suggested that GDF11 is involved in a variety of functions, such as apoptosis, DNA repair, telomere maintenance, and interaction with key transcription factors, such as MYC proto-oncogene, specificity protein 1, and ETS proto-oncogene 2. The human skin fibroblast premature senescence model was established by UVB. The treatment with 10 ng/mL GDF11 in this cell model could reduce cell damage, reduce the apoptosis rate and the expression of caspase-3, and increase the length of telomeres. Therefore, our findings shed light on the functions of GDF11 and provide insights into the roles of GDF11 in aging.

This study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) group, and the NR4A1 activation group (Cytosporone B; 1 μM). The expression levels of the epithelial marker E-cadherin, the mesenchymal markers fibronectin (FN), vimentin, smooth muscle alpha-actin (α-SMA), and fibroblast-specific protein 1 (FSP-1), and the components of the transforming growth factor (TGF)-β pathway were detected by real-time polymerase chain reaction and western blotting. Compared with the control group, E-cadherin in the acetaldehyde group was downregulated, whereas FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 were upregulated ( P < 0.05). Compared with the acetaldehyde group, NR4A1 agonist upregulated E-cadherin and downregulated FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 ( P < 0.05). After acetaldehyde stimulation, TGF-β, Smad2/3/4, and zinc finger E-box-binding homeobox (ZEB) were upregulated, while Smad7 mRNA levels were downregulated (all P < 0.05). Compared with acetaldehyde alone, NR4A1 agonist increased Smad7 mRNA levels and reduced TGF-β, Smad2/3/4, and ZEB mRNA levels (all P < 0.05). NR4A1 activation suppresses acetaldehyde-induced EMT, as shown by epithelial and mesenchymal marker expression. The inhibition of the TGF-β–Smad2/3/4–ZEB signaling during HSC activation might be involved.

Embryonic stem cells (ESCs) differentiation is a process of replication and refinement, and the directional lineage differentiation of ESCs involves the epithelial-mesenchymal transition (EMT)- mesenchymal-epithelial transition (MET) process. A previous study revealed that Zinc finger E-box-binding homeobox 1 (Zeb1) plays a vital role in EMT, which could repress E-cadherin promoter and induce an EMT in cells. To verify the expression of Zeb1 and its correlation with Lin28a in mouse ESCs differentiation, we performed qRT-PCR and western blots to detect the expression of Lin28a mRNA and protein after Zeb1 knockdown. The expression of Zeb1 decreased over time of mouse ESCs differentiation but significantly increased in mouse embryonal carcinoma cells. After knockdown of Zeb1, Lin28a and Vimentin expression were decreased, while E-cadherin expression increased both in mouse ESCs, EBs, GC1, and P19 cells. We found that Zeb1 promoted the invasive ability of mouse embryonal carcinoma cells. These results revealed that expression of Zeb1 decreased during the differentiation of ESCs, and Lin28a and EMT processes can be regulated by Zeb1, which need to be verified in the future studies.

Cadmium sulfide quantum dots (CdS QDs) are being developed for sensors, fluorescent probes, and other platforms and are attracting increasing attention. Given the growing demand for QDs, it is clear that there is a need to understand their potential toxicity to organisms. However, little is known regarding the genotoxicity of CdS QDs to humans. Therefore, this study used CdS QDs as the research object, cultured human peripheral blood lymphocytes, and randomly divided them into a control group, CdS I group (CdS QDs), and CdS II group (CdS QDs coated with thioglycolic acid). After cultivation, we measured the olive tail distance, tail length, tail DNA%, lymphocyte micronucleus rate, and aneuploid rate. The comet test results indicated that the indices of the QD group were significantly larger than those of the control group ( P < 0.05). The results of the micronucleus and chromosome aberration tests showed that the lymphocyte micronucleus rate and chromosome aneuploid rate in the QD group were significantly increased ( P < 0.05) compared with those in the control group. In conclusion, CdS QDs have certain genotoxicity to human peripheral blood lymphocytes, and the DNA damage caused by CdS QDs encapsulated with thioglycolic acid is less severe than that caused by nonencapsulated CdS QDs.

NKX2.5 is a transcription factor that plays a key role in cardiovascular growth and development. Several independent studies have been previously conducted to investigate the association between the single-nucleotide polymorphism (SNP) 606G >C (rs3729753) in the coding region of NKX2.5 and congenital heart disease (CHD). However, the results of these studies have been inconsistent. Therefore, the present study aimed to reveal the relationship between NKX2.5 SNP 606G >C and the risk of CHD as possible in the Chinese population through meta-analysis. After retrieving related articles in PubMed, MEDLINE, EMBASE, Web of science, Cochrane, China National Knowledge Infrastructure, Wanfang DATA, and VIP database until August 2021, a total of eight studies were included in the present meta-analysis. The qualified research data were then merged into allele, dominant, recessive, heterozygous, homozygous, and additive models. Overall results of the current meta-analysis showed that 606G >C was not associated with CHD of the Chinese population in any model. In addition, subgroup analysis based on CHD type gave the same negative result. Results of sensitivity analysis showed that there was no significant correlation after the deletion of each study. Furthermore, it was noted that the results were negative and the heterogeneity was not significant. In conclusion, it was evident that NKX2-5 SNP 606G >C may not lead to the risk of CHD in Chinese population.

Clinically, pentothal sodium has been widely used for primary and general anesthesia induction. Also, it has been used to effectively inhibit convulsion. Pentothal sodium has a strong inhibitory effect on the respiratory center, excessive drug administration, and rapid dose rate that cause death of experimental animals on the respiratory depression. This study used a modified pentothal sodium solution to investigate its anesthetic effect. The pentothal sodium solution was modified based on pentothal sodium upon additions of magnesium sulfate, propylene glycol, and pure ethanol. The anesthetic effect of the modified pentothal sodium on Sprague–Dawley (SD) rats was investigated by comparing traditional pentothal sodium and ketamine; 60 SD rats were randomly divided into three groups. Each group was treated with traditional pentothal sodium, modified pentothal sodium, or ketamine, respectively, via intraperitoneal injection. The symptoms of experimental rats were observed, and onset time and anesthetic time were both recorded. The data were analyzed using statistical software. There were no significant differences in onset time and anesthetic time between the three groups. The variation of onset time and anesthetic time of the group treated with modified pentothal sodium was shorter than that of the other two groups. Furthermore, the number of anesthetic rats after the first injection was significantly higher than that of the other two groups. The modified pentothal sodium is capable of providing a stable anesthetic effect. The function and effect are much better than traditional pentothal sodium and ketamine.

High myopia is a common ocular genetic disease in the world. The study sought to investigate the effect of the Insulin-like growth factor-1 (IGF-1) and Matrix metalloproteinase-9 (MMP-9) genes polymorphisms on high myopia in a Han population of China. This study recruited 216 unrelated Han Chinese subjects, including 103 cases with high myopia and 113 controls. Four tagging single nucleotide polymorphisms (SNPs) of IGF-1 and MMP-9 genes were genotyped using the Sequenom MassARRAY method. The chi-square test showed that the family history was significantly correlated with myopia. The SNP genotypes were all in Hardy–Weinberg equilibrium ( P > 0.05). Among the four SNPs, there were statistically significant differences in the genotype and allele frequencies of rs2236416 between the groups ( P = 0.024). The significant associations of rs2236416 between cases and controls also appeared after Bonferroni multiple correction ( P = 0.024). Then, there were significant differences in the genotypes dominant model and codominant model of rs2236416 between groups ( P = 0.007 and P = 0.004, respectively). rs5742632 showed a significant difference between the cases and the controls in the recessive model ( P = 0.037). Our findings indicated that rs2236416 of MMP-9 was associated with myopia in the population. The result suggested MMP-9 gene locus may play a role in myopia.

This study aimed to explore potential biomarkers and molecular mechanisms in preeclampsia (PE) progression. Gene expression profiles of GSE147776 and GSE96984 were downloaded, followed by the identification of common differentially expressed genes (co-DEGs) and common differentially expressed lncRNAs (co-DElncRNAs) in PE patients between the two datasets. Key genes were identified using gene set enrichment analysis (GSEA), followed by functional enrichment analyses. Subsequently, the miRNAs of key genes and miRNA-related lncRNAs were predicted, followed by the construction of the lncRNA–miRNA–gene ceRNA network. Furthermore, the key genes associated with different gestational stages were identified. As a result, 192 co-DEGs and 16 co-DElncRNAs were revealed from the two datasets. Based on two outstanding PE-associated pathways, including glaucoma and PE, identified by GSEA, ten key genes, including IGFBP1 , CORIN , and C3 , were revealed. Key genes, including IL1A and IL1B , were enriched in the developmental process involved in reproduction. Furthermore, ceRNAs, such as LINC00473-miR-4476-IL1A, LINC00473-miR-1291-IL1B, and NAV2-AS4-miR-6131-REN, were identified. Moreover, REN expression was significantly upregulated in the first- and second-trimester placentae compared to C-section-term placentae. In conclusion, these key genes may serve as novel biomarkers for PE. The detection of REN expression may help in the early prediction of PE and the initiation of prophylactic medical treatment.

Circular-RNA friend leukemia virus integration 1 (circ-FLI1; hsa_circ_0000370) is a noninvasive biomarker for the diagnosis of colon carcinoma (CC). Herein, we intended to investigate its functions and competing endogenous RNA (ceRNA) mechanisms in CC cells. In terms of expression status, circ-FLI1 was abnormally upregulated in CC patients’ tumors and cells, paralleled with DKC1 upregulation and miR-197-3p downregulation. Most strikingly, there was a direct target relationship between miR-197-3p and circ-FLI1 or DKC1 based on the starbase database, dual-luciferase reporter assay, and RNA immunoprecipitation. Functionally, the colony formation assay, MTS method, fluorescence-activated cell sorting method, cell cycle and apoptosis assays, and transwell assays were performed, and the results revealed that interfering circ-FLI1 and re-expressing miR-197-3p could restrict colony formation, cell viability, cell cycle progression, and migration/invasion of CC cells with apoptosis rate elevation; besides, they promoted oxaliplatin (L-OHP)-induced cell viability inhibition. Furthermore, there were counteractive effects between circ-FLI1 silencing and miR-197-3p depletion, miR-197-3p overexpression and DKC1 restoration on regulating CC cell functions and L-OHP resistance. With a xenograft tumor model, the anti-growth role of circ-FLI1 silencing was also found in vivo with or without L-OHP treatment. Collectively, we demonstrated that circ-FLI1 might confer L-OHP resistance and malignant progression of CC presumably through the circ-FLI1/miR-197-3p/DKC1 ceRNA axis.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive cancer with a very poor prognosis. The proper treatment decision and possible prognosis outcome for advanced LCNEC is always an enormous challenge due to its scarcity. Here, we presented a 59-year-old male patient with advanced LCNEC with a non-neuroendocrine immunophenotype who received endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime as a first-line treatment. At present, the patient’s condition is well controlled by medication only and has a progression-free survival of more than 2 years. Adverse effects recorded for this patient during treatment courses include nausea, vomiting, II–III quality bone marrow toxicity, and PD-1 blockage-related hypothyroidism. This case report discussed the feasibility of immunotherapy, anti-angiogenesis agents, and chemotherapy as a first-line therapy in advanced LCNEC.

P21-activated protein kinases (PAKs) are thought to be at the center of tumor signaling pathways. As a representative member of the group II PAK family, P21-activated protein kinase 4 (PAK4) plays an important role in the development of tumors, with several biological functions such as participating in oncogenic transformation, promoting cell division, resisting aging and apoptosis, regulating cytoskeleton and adhesion, as well as suppressing antitumor immune responses. PAK4 is also crucial in biological processes, including the occurrence, proliferation, survival, migration, invasion, drug resistance, and immune escape of tumor cells. It is closely related to poor prognosis and tumor-related pathological indicators, which have significant clinical and pathological significance. Therefore, this article offers a review of the structure, activation, and biological functions of PAK4 and its clinical and pathological importance. This overview should be of assistance for future research on PAK4 and tumors and provide new ideas for tumor treatment and prognostic evaluation of patients.

Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-β1 (10 ng/mL), sorafenib (10 µM) + TGF-β1 (10 ng/mL), and TGF-β1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-β1 treatment enhanced ovarian cancer cell epithelial–mesenchymal transition (EMT), whereas sorafenib and a selective TGF-β1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-β1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-β1 inhibitors in ovarian cancer in vivo .

Nanobodies (Nbs) are recombinant single-domain fragments derived from camelids’ heavy-chain antibodies (HCAbs). Nanobodies are increasingly used in numerous biotechnological and medical applications because of their high stability, solubility, and yield. However, one major obstacle prohibiting Nb expansion is the affordability of specific detector antibodies for their final revelation. In this work, the production of a specific anti-Nb antibody as a general detector for camel antibodies, conventional cIgG, and HCAb, and their derived Nbs was sought. Thus, a T7 promoter plasmid was constructed and used to highly express six different Nbs that were used in a successful rabbit immunization. Affinity-purified rabbit anti-Nb rIgG was able to detect immobilized or antigen-bound Nbs via enzyme-linked immunosorbent assay, and its performance was comparable to that of a commercial anti-6× His antibody. Its capacities in dosing impure Nbs, detecting Nbs displayed on M13 phages, and revealing denatured Nbs in immune blotting were all proven. As expected, and because of shared epitopes, rabbit anti-Nb cross-reacted with cIgG, HCAbs, and 6× His-tagged proteins, and the percentage of each fraction within anti-Nb rIgG was determined. Anti-Nb is a promising tool for the checkpoints throughout the recombinant Nb technology.

Neuroblastoma (NB) is a commonly occurring malignancy in children. Epithelial-mesenchymal transition (EMT) is an adaptive change in promoting tumor metastasis. As an important factor in regulating tumor metastasis, whether legumain could promote metastasis of NB by EMT is still unexplored. Legumain is the active form of prolegumain, abundant in tumor plasma. So in the current study, different forms of legumain were identified in NB. Second, correlation analysis of N-cadherin and active legumain was identified by western blot analysis. Third, legumain gene amplification or gene knockdown were proceeded to examine the effect of legumain on EMT by scratch and transwell assay; meanwhile, active mature legumain or its asparagine endopeptidase (AEP) inhibitor was also added in. Finally, legumain can be detected differently in NB cells. Changes in legumain could influence NB metastasis by regulating EMT markers (e.g., N-cadherin, vimentin, and slug). Besides, the effect of legumain on EMT by its AEP activity was proved by intervention experiment of AEP gene transfection and gene knockdown experiments or adding recombinant human legumain suspension or specific inhibitor of AEP in NB cells ( p < 0.05). These results suggest that legumain can promote invasion and migration of NB by regulating EMT, and EMT of NB is regulated by AEP activity of legumain, which can be inhibited by a specific AEP inhibitor.

Osteoarthritis (OA) is a chronic arthritic disease characterized by cartilage degradation, synovial inflammation, and subchondral bone lesions. The studies on the pathogenesis of OA are complex and diverse. The roles of receptors signaling in chondrocyte anabolism, inflammatory factors expression of synovial fibroblast, and angiogenesis in subchondral bone are particularly important for exploring the pathological mechanism of OA and clinical diagnosis and treatment. By reviewing the relevant literature, this article elaborates on the abnormal expression of receptors and the signaling transduction pathways from different pathological changes of OA anatomical components, aiming to provide new research ideas and clinical therapeutic value for OA pathogenesis.

Bladder cancer (BC) is one of the most common malignancies involving the urinary system. Our previous study demonstrated that cobra venom membrane toxin 12 (MT-12) could effectively inhibit BC cell growth and metastasis and induce apoptosis. However, the specific molecular mechanism remains unknown. In this study, we explored whether MT-12 inhibits BC cell proliferation by inducing autophagy cell death through mitochondrial dysfunction. As a result, MT-12 inhibited proliferation and colony formation in RT4 and T24 cells. In the BC xenograft mouse model, autophagy inhibitor 3-MA alleviated the inhibitory effect of MT-12 on tumor growth. In addition, immunostaining revealed downregulated autophagy in MT-12-treated RT4 and T24 cells. We also found that MT-12 led to dysfunctional mitochondria with decreased mitochondrial membrane potential, mtDNA abundance, and increased ROS production, ultimately inducing autophagic apoptosis via the ROS/JNK/P53 pathway. MT-12 inhibits BC proliferation in vitro and in vivo by enhancing autophagy. MT-12 induces mitochondrial dysfunction and decreases autophagy, leading to increased ROS production, which in turn activates the JNK/p53 pathway, leading to BC apoptosis.

We detected the expressions of hsa_circRNA_000121 and hsa_circRNA_ 004183 in papillary thyroid microcarcinoma (PTMC) and explored their relationship with the invasiveness of PTMC. PTMC patients with ( n = 30; metastasis group) and without lymph node metastasis ( n = 30; nonmetastasis group) were included. The levels of hsa_circRNA_000121, hsa_circRNA_004183, hsa-miR-4763, hsa-miR-6775, sarcoma gene ( SRC ), and MMP-14 were detected with real-time polymerase chain reaction. Receiver-operating characteristic (ROC) analyzed the diagnostic value of hsa_circRNA_000121 and hsa_circRNA_004183. Binary logistic regression analysis evaluated the relationship of gene expression with PTMC invasiveness. In PTMC tissue samples, compared with the metastasis group, the expression of hsa_circRNA_000121, hsa_circRNA_004183, SRC , and MMP-14 in the nonmetastasis group decreased, while the expression of hsa-miR-4763 and hsa-miR-6775 increased. In peripheral blood, compared with the metastasis group, the expression of hsa_circ_000121 and hsa_circRNA_004183 in the nonmetastasis group decreased. Both hsa_circRNA_000121 and hsa_circRNA_004183 had good sensitivity and specificity for diagnosing PTMC lymph node metastasis, with a cut-off value of 0.796 and 0.938, respectively. However, the gene expressions were not significantly associated with PTMC lymph node metastasis. Hsa_circRNA_000121 may upregulate SRC expression through hsa-miR-4763, while hsa_circRNA 000121 may upregulate MMP-14 expression through hsa-miR-6775, thereby promoting the aggressiveness of PTMC and ultimately leading to cervical lymph node metastasis. hsa_circRNA_000121 and hsa_circRNA_004183 may become potential biomarkers of PTMC aggressiveness.

The ancient Chinese remedy BuyangHuanwu Decoction (BHD) is used to treat qi deficit and blood stasis conditions. This work investigated the effect of BHD on cerebral vasospasm (CVS) caused by subarachnoid hemorrhage (SAH). Rats were randomly assigned into four groups: control group, SAH group, SAH + BHD [13 g/(kg day)] group, and SAH + BHD [26 g/(kg day)] group. The Garcia neurological scoring scale was used to assess neurological dysfunction. Hematoxylin and eosin stains were used to determine the extent of vasospasm by measuring the diameter of the basilar artery. Western blot was used to measure the concentrations of phosphoinositide 3-kinase (PI3K), AKT, and phospho-AKT expression levels. RT-PCR was used to determine PI3K and AKT RNA expressions. Immunohistochemistry and enzyme-linked immunosorbent assay were used to measure levels of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO), respectively, in cerebrospinal fluid. BHD treatment ameliorated CVS and mitigated neurological dysfunction after SAH. Furthermore, the findings suggest that NO concentration was increased through the activation of classical PI3K/AKT signaling and the eNOS pathway. Thus, BHD showed multifaceted roles in preventing damage via decreasing vasospasm and improving neurological impairments caused by CVS after SAH.

We investigated the role of the interaction between the Notch and Toll-like receptor 4 (TLR4) pathways in septic myocardial injury. The sepsis model was induced in rats with lipopolysaccharide (LPS). Rats were divided into control, LPS, LPS + TAK242 ((6 R )-6-[ N -(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate) and LPS + DAPT ( N -[ N -(3,5-difluorophenacetyl)- l -alanyl]- s -phenylglycinetbutylester) groups. Heart function was evaluated with a Cardiac Doppler ultrasound. Myocardial morphological changes were detected by hematoxylin-eosin staining (H&E). Apoptosis was assessed by a TUNEL assay. The mRNA and protein levels were detected with real-time PCR, Western blot, and immunohistochemistry analysis. We found that heart function in the LPS + TAK242 group was significantly improved, but not in the LPS + DAPT group. LPS + TAK242 had a lower level of degeneration and necrosis of cardiomyocytes and inflammatory cell infiltration, as well as lower apoptosis and caspase-3 expression than the LPS group. Compared with the LPS group, the inflammatory cell infiltration was reduced in the LPS + DAPT group, while the degeneration and necrosis of cardiomyocytes were not obviously improved. Additionally, the expression levels of tumor necrosis factor-α and Interleukin-6, the protein contents of Notch intracellular domain and Hes1, and the P65 nuclear factor kappa-B (NF-κB) to P-P65 NF-κB ratio in LPS + TAK242 group and LPS + DAPT group were significantly lower than those in LPS group. Conclusively, the interaction between TLR4 and Notch signaling pathways enhances the inflammatory response in the septic heart by activating NF-κB. Blocking the TLR4 pathway with TAK242 can improve heart dysfunction and myocardial damage in sepsis, while blocking the Notch pathway with DAPT cannot effectively prevent heart dysfunction and myocardial damage in sepsis.

The monosodium iodoacetate (MIA)-induced osteoarthritis (OA) may lead to cartilage degeneration and histopathological lesions. However, the correlation between inflammatory reaction and subchondral bone remodeling in a rodent osteoarthritic model is ambiguous. In this study, intra-articular injection of MIA was performed in 36 four-week-old specific pathogen-free male Wistar rats to induce OA. After 4 weeks of intervention, changes in intrinsic structural properties of the subchondral bones were measured, and the histological evaluation, as well as biochemical analysis, was conducted. We found that intra-articular injection of MIA increased chondrocyte apoptosis and promoted cartilage matrix degradation, such as cartilage surface defects and shallow or disappearing staining. MIA also induced inflammation, improved the expression of IL-1β, TNF-α, and matrix metalloproteinase, and decreased the expression of cartilage-specific proteins with the extension of modeling time. Meanwhile, the MIA also significantly accelerated the subchondral bone remodeling, as shown by the decreased subchondral bone density, thinning of trabeculae, disordered cartilage structure, and morphology. In conclusion, we have shown that MIA-induced rodent osteoarthritic model would cause decreased subchondral bone density, sparse trabecular bone, and other manifestations of osteoporosis accompanied by an inflammatory response, which would worsen with the progression of modeling time. Our results suggest that different phases of MIA-induced OA are associated with the changes in subchondral bone microstructure and the progression of local inflammation.

Type II Abernethy malformation is an extremely reported congenital extrahepatic portosystemic shunt in complication with nephrotic syndrome. We present the case of an 8-year-old boy who presented with symptoms of type II Abernethy malformation and nephrotic syndrome. This diagnosis of this type II Abernethy malformation was based on physical examination, blood tests, urinalysis, nephrotic and hepatic function tests, routine clinical lipid measurements, abdominal ultrasonography, and computed tomographic angiography. A kidney biopsy revealed the pathological features of nephrotic syndrome. This is the second reported patient diagnosed with type II Abernethy malformation and nephrotic syndrome. Captopril treatment was effective in improving the symptoms of this case. A patient with type II Abernethy malformation related to immune complex-mediated glomerular injury was effectively improved with medication. Type II Abernethy malformation is a causative factor of immune complex-mediated glomerular injury in nephrotic syndrome. Captopril treatment significantly improved the symptoms in this case.

A 49-year-old woman was admitted to our hospital because of haemoptysis for 6 days. This patient claimed no medical history except high blood sugar. Chest computed tomography (CT) showed infection and multiple nodules on both sides of the lung. Blood tests showed no obvious abnormalities. Tracheoscopy showed haemorrhagic discharge in the left upper lobe and an old thrombus obstructing the lumen in the anterior basal segment of the right lower lobe. Then, CT-guided percutaneous lung biopsy was performed. The pathological results suggested multiple nodular-like lesions in the submitted tissues, and tumour cells were round or short fusiform, forming a solid nest structure, visible mitosis, and a vascular cavity-like structure containing red blood cells. Immunohistochemistry revealed positive staining for Vimentin, Bcl-2, CD31, and CD34; negative staining for CD68, SMA, CR, and D2-40; and 40% Ki67+ positivity. Based on the earlier data, the patient was diagnosed with pulmonary epithelioid haemangioendothelioma. This patient did not receive any treatment for several reasons. Unfortunately, the patient died 8 weeks after diagnosis. In conclusion, we present a case featuring the rapid death due to PEH.

Transcatheter arterial embolization (TAE) is a widely used technique in treating hepatic carcinoma but may cause liver injury in some cases. This study investigated the hepatoprotective effect of the preprocessed peroxisome proliferator-activated receptor-α (PPAR-α) agonist-WY-14643 following TAE. A total of 60 rabbit liver cancer models were developed and divided into a combined treatment (WY-14643 and TAE), TAE, and control groups. After TAE, we examined the histopathological picture and liver functions. Further, the expression of antioxidant enzymes, tumor necrosis factor-α (TNF-α), nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB), PPAR-α, and B-cell lymphoma-2 (Bcl-2) was analyzed. Liver function tests, pathology score, and apoptosis index significantly worsened in the TAE group but were normalized in the combined treatment group. In addition, ELISA results showed that antioxidant enzyme activity significantly increased, while the malondialdehyde content and level of inflammatory cytokines were significantly reduced in the combined treatment group. Furthermore, compared to the TAE group, the expressions of PPAR-α, antioxidant enzymes superoxide dismutase1 (SOD1) and SOD2, and Bcl-2 were significantly elevated, while NF-κB was significantly reduced in the combined treatment group. On the other hand, the expression of NF-κB in tumor tissues was significantly reduced by pretreatment with WY-14643. Therefore, PPAR-α can ameliorate liver injury by exerting its anti-oxidative, anti-inflammatory, and anti-apoptotic functions.

This study explored the correlation between peripheral blood CD3 ＋ , CD3 ＋ /CD4 ＋ , CD3 + /CD8 + , CD4 ＋ /CD8 ＋ , CD3 − /CD16 + CD56 + , and CD3 − CD19 + and disease activity of different subtypes of systemic lupus erythematosus (SLE). The percentages of CD3 + , CD3 + /CD4 + , CD3 + /CD8 + , CD4 + /CD8 + , CD3 − /CD16 + CD56 + , and CD3 − CD19 + in the peripheral blood of patients ( n = 80) classified into lupus nephritis, blood involvement, and joint involvement and SLE in different active stages were detected by flow cytometry. Their correlations with baseline clinical experimental indicators of SLE patients’ SLE disease activity index score (SLEDAI) and complement C3 were analyzed. The results showed that CD3 + , CD3 + /CD4 + , and CD3 + /CD8 + at baseline level were negatively correlated with SLEDAI scores. These were positively correlated with C3. In conclusion, T-lymphocyte subpopulations are closely related to SLE activity and can be used as reference indicators to evaluate the SLE activity.

ALK fusion genes are diverse. Approximately 30 different ALK fusion protein partners have been described previously, and some of these fusion proteins have been reported to be effective against ALK -tyrosine kinase inhibitor (TKI). ALK rearrangements often occur at a common breakpoint in exon 20 of the genome. SLC8A1-ALK , a novel fusion protein partner, comes from exon 2 of the SLC8A1 gene rearranged with exon 20 of the ALK gene. Here, we reported a patient with advanced lung adenocarcinoma harboring a SLC8A1-ALK fusion who benefited from first-line treatment with alectinib. After 2 months of taking alectinib, the targeted lung lesions and intrahepatic metastases regressed significantly. To date, the patient has achieved nearly 1 year of progression-free survival while taking the drug. Given the diversity of ALK fusion genes and the different efficacy of ALK-TKIs, we believe that this case report has an important clinical reference.

Fibroblast growth factor 21 (FGF21) is secreted by hepatocytes as a peptide hormone to regulate glucose and lipid metabolism. FGF21 promotes hepatic ketogenesis and increases ketone body utilization in starvation. Histones are the target molecules of nutrients in regulating hepatic metabolic homeostasis. However, the effect of ketone bodies on FGF21 expression and the involvement of histones in it is not clear yet. The present study observed the effects of β-hydroxybutyrate (β-OHB), the main physiological ketone body, on FGF21 expression in human hepatoma HepG2 cells in vitro and in mice in vivo , and the role of histone deacetylases (HDACs) in β-OHB-regulated FGF21 expression was investigated. The results showed that β-OHB significantly upregulated FGF21 gene expression and increased FGF21 protein levels while it inhibited HDACs’ activity in HepG2 cells. HDACs’ inhibition by entinostat upregulated FGF21 expression and eliminated β-OHB-stimulated FGF21 expression in HepG2 cells. Intraperitoneal injections of β-OHB in mice resulted in the elevation of serum β-OHB and the inhibition of hepatic HDACs’ activity. Meanwhile, hepatic FGF21 expression and serum FGF21 levels were significantly increased in β-OHB-treated mice compared with the control. It is suggested that β-OHB upregulates FGF21 expression through inhibition of HDACs’ activity in hepatocytes.

Early-stage non-small cell lung cancer (NSCLC) patients are at substantial risk of poor prognosis. We attempted to develop a reliable metabolic gene-set-based signature that can predict prognosis accurately for early-stage patients. Least absolute shrinkage and selection operator method Cox regression models were performed to filter the most useful prognostic genes, and a metabolic gene-set-based signature was constructed. Forty-two metabolism-related genes were finally identified, and with specific risk score formula, patients were classified into high-risk and low-risk groups. Overall survival was significantly different between the two groups in discovery (HR: 5.050, 95% CI: 3.368–7.574, P < 0.001), internal validation series (HR: 6.044, 95% CI: 3.918–9.322, P < 0.001), GSE30219 (HR: 2.059, 95% CI: 1.510–2.808, P < 0.001), and GSE68456 (HR: 2.448, 95% CI: 1.723–3.477, P < 0.001). Survival receiver operating characteristic curve at the 5 years suggested that the metabolic signature (area under the curve [AUC] = 0.805) had better prognostic accuracy than any other clinicopathological factors. Further analysis revealed the distinct differences in immune cell infiltration and tumor purity reflected by an immune and stromal score between high- and low-risk patients. In conclusion, the novel metabolic signature developed in our study shows robust prognostic accuracy in predicting prognosis for early-stage NSCLC patients and may function as a reliable marker for guiding more effective immunotherapy strategies.

The aim of this study was to investigate the role of BTBD10 in glioma tumorigenesis. The mRNA and protein levels of BTBD10 in 52 glioma tissues and eight normal brain tissues were determined using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. U251 human glioblastoma cells were infected with BTBD10-expressing or control lentiviruses. Cell growth was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis and cell cycle distribution were analyzed using flow cytometry. Cyclin D1 and p-Akt levels were determined using western blot analysis. The results showed that BTBD10 mRNA and protein levels were significantly lower in glioma tissues than in normal brain tissues. Additionally, BTBD10 levels were significantly lower in high-grade gliomas than in low-grade tumors. Compared with control cells, U251 cells overexpressing BTBD10 exhibited decreased cell proliferation, increased cell accumulation at the G0/G1 phase, increased cell apoptosis, and decreased levels of cyclin D1 and p-Akt. These findings show that BTBD10 is downregulated in human glioma tissue and that BTBD10 expression negatively correlates with the pathological grade of the tumor. Furthermore, BTBD10 overexpression inhibits proliferation, induces G0/G1 arrest, and promotes apoptosis in human glioblastoma cells by downregulating cyclin D1- and Akt-dependent signaling pathways.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients’ co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

It remains a huge challenge for clinicians to diagnose Pneumocystis jirovecii pneumonia (PJP) by a conventional method, which leads to delay in diagnosing PJP, accounting for higher mortality in patients with rheumatoid arthritis (RA). A 69-year-old woman, who suffered from RA for years, developed acute respiratory failure. The computed tomography scan showed diffused effusion and ground glass opacity in both lungs, which could not be differentiated from interstitial pneumonia. Metagenomic next-generation sequencing (mNGS) revealed P. jirovecii in both serum and bronchoalveolar lavage fluid with reads per million (RPM) of 17 and 437, while other diagnostic tests did not detect any pathogenic microorganism. The results were verified by quantitative polymerase chain reaction (mtSSU region) against the same samples. The DNA RPM of P. jirovecii declined notably after treatment with trimethoprim/sulfamethoxazole. The patient was discharged without treatment and finally passed away. This case fully highlights the sensitivity of mNGS in early diagnosis of PJP, which is of great significance for prognosis and treatment. Nonetheless, the clinical application of mNGS is worth further standardization and normalization.

Long non-coding RNAs (lncRNAs) are broadly transcribed in the genome of human and play critical roles in the progression of multiple diseases. Long non-coding HOXB cluster antisense RNA 1 (HOXB-AS1) is a tumor exciter in various cancers. This study aimed to investigate the involvement of HOXB-AS1 in hepatocellular carcinoma (HCC). In the following study, HOXB-AS1 was unveiled to be highly expressed in HCC tissues as opposed to normal tissues. Silencing of HOXB-AS1 led to the loss of proliferation, migration, and invasiveness of HCC cells, namely Hep3B and Huh7. Moreover, the data showed that expression levels of HOXB-AS1 contribute significantly to the patient’s survival rates. Otherwise, HOXB-AS1 levels in the serum of patients proved HOXB-AS1 as a biomarker for analysis and treatment of HCC. In summary, this study highlights HOXB-AS1 as key upregulated lncRNA in HCC which being an oncogene can cause proliferation and metastasis of HCC cells. The results also highlighted HOXB-AS1 as a promising biomarker for early diagnosis and prognosis of patients with HCC.

This study aims to synthesize a magnetic resonance imaging (MRI) contrast agent that can specifically target the asialoglycoprotein receptor of liver cancer cells and evaluate its ability as a targeted MRI contrast agent. Lactobionic acid (LA) and polyethylene glycol (PEG) were used to modify superparamagnetic iron oxide nanoparticles (SPION) to obtain LA-PEG-SPION. LA-PEG-SPION was uniformly spherical under the electron microscope, with regular morphology and good dispersion. The particle size of LA-PEG-SPION was about 30 ± 4.5 nm, and its surface potential was about 31 ± 1.5 mV. LA-PEG-SPION had no toxicity or low toxicity to HepG2 cells and HeLa cells, even at 400 μg/mL. The uptake of LA-PEG-SPION by HepG2 cells was higher than that of SPION, with increased blue-stained particles. The fluorescent labeling rate of HepG2 cells reached 68.8%, which was higher than that of the control group. In vitro, MRI showed that the T2-weighted signal intensity of HepG2 cells was lower than that of the control group. Conclusively, LA-PEG-SPION nanoparticles are synthesized in a simple and efficient way. They are successfully applied to the T2-weighted contrast-enhanced MRI in liver cancer in vitro , and they have the potential to be used for in vivo research and clinical studies.

In this study, we aimed to characterize the liver protein profile of Chaohu ducks using two-dimensional electrophoresis and proteomics. The livers were quickly collected from 120 healthy, 84-day-old Chaohu ducks. The intramuscular fat (IMF) content of the left pectoralis muscle was determined using the Soxhlet extraction method. The total protein of liver tissues from the high and low IMF groups was extracted for proteomics. Functional enrichment analysis of the differentially expressed proteins (DEPs) was conducted using gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). In total, 43 DEPs were identified. Functional enrichment analysis indicated that these DEPs were significantly related to four lipid metabolic processes: carboxylic acid metabolic process, ATP metabolic process, oxoacid metabolic process, and organic acid metabolic process. Three pathways correlated with lipid metabolism were identified using KEGG analysis: glycolysis/gluconeogenesis, pentose phosphate pathway, fructose, and mannose metabolism. Eight key proteins associated with lipid metabolism were identified: ALDOB, GAPDH, ENO1, RGN, TPI1, HSPA9, PRDX1, and GPX1. Protein–protein interaction analysis revealed that the glycolysis/gluconeogenesis pathway mediated the interaction relationship. Key proteins and metabolic pathways were closely related to lipid metabolism and showed a strong interaction in Chaohu ducks.

Nasopharyngeal tuberculosis is a rare disease. Even in areas where tuberculosis is endemic, its incidence is also extremely low. Here, we will report a rare case of nasopharyngeal tuberculosis. A 29-year-old male patient presented with a 2-month history of sore throat, nasal congestion, dysphagia, and low-grade fever. Thickened mucosa in the posterior wall of the nasopharynx was shown from nasopharyngoscopy, covered with a thick, yellowish, purulent secretion that was not easily removed. Computed tomography of the nasopharynx showed thickening of the mucosa in the right and left bilateral walls and the posterior wall with indistinct margins. Histopathological examination diagnosed nasopharyngeal tuberculosis granuloma. Nasopharyngeal tuberculosis is rare and has atypical symptoms. When a new organism appears in the nasopharynx, it should be differentiated from tuberculosis, autoimmune diseases, and tumors, and a tissue biopsy of the new organism should be performed to make a final diagnosis based on histopathology.

Lactobacilli ( n = 24), isolated from human infants and yogurt, showed variable in vitro activity against Salmonella enteritidis (8.0 ± 1.0 to 16.6 ± 0.5 mm) and other gut pathogens (9.0 ± 1.0 to 15.3 ± 0.5 mm), as determined by a well diffusion assay. The isolates were identified as Limosilactobacillus fermentum (FY1, FY3, FY4, IL2, and IL5), Lactobacillus delbrueckii (FY6 and FY7), Lactobacillus sp. (IL7), and Lactobacillus gasseri (IL12). All isolates showed variable in vitro tolerance to acidic pH for 3 h and visible growth at pH 4 and in the presence of 0.3% ox-bile. The antibiotic susceptibility profile of Lactobacillus isolates indicated resistance against vancomycin, ciprofloxacin, streptomycin, and lincomycin. Isolates had variable auto-aggregation and showed variable capabilities to co-aggregate with S. enteritidis . Based on all tested parameters, L. fermentum IL2, L. fermentum IL5, and L. gasseri IL12 were selected for co-culture experiments, followed by in vivo evaluation in Balb/c mice. All the selected isolates resulted in a 100% reduction in S. enteritidis in broth. Lactobacillus isolates efficiently colonized mouse guts and inhibited S. enteritidis colonization. Overall, there was ≥99.06% and ≤4.32 Mean log 10 reduction in Salmonella counts in mice feces within 7 days. The study, thus, provided characterized lactobacilli that could be considered as potential ingredients for probiotic formulations intended to prevent S. enteritidis infection in humans.

Obesity and periodontitis constitute mutual risk factors in respiratory disorders; this study aimed to explore the pulmonary immune response to periodontal infection using combined animal models with diet-induced obesity (DIO). Thirty-two C57 BL/6J mice were randomly divided into low-fat (LF) or high-fat (HF) diet groups and fed an LF diet as a control or an HF diet to induce obesity. The 30-week mice in the diet group were divided into periodontal ligation group (10 days using Porphyromonas gingivalis ATCC 33277) or sham-ligation group. The expressions of the macrophage-specific maker (F4/80), macrophage chemotactic protein1 (MCP1), and inflammatory cytokines in lung tissues were analyzed. The mRNA and protein levels of F4/80, MCP1, interleukin (IL)-1β, and IL-6 expressions were significantly upregulated by obesity in lung tissues. However, the mRNA and protein levels of F4/80, MCP1, and IL-6 were downregulated by periodontitis in DIO mice relative to that of the HF control group. Periodontitis increased tumor necrosis factor-α level of lung tissues under LF, while IL-10 was not affected by obesity regardless of periodontitis. Periodontitis may aggravate pulmonary immune response in obese rodents. This may relate to the imbalance of the pro- and anti-inflammatory cytokine status of lung lesions, which tends to attenuate the infiltration of alveolar macrophages.

Bacterial colonization of male reproductive tissues, cells, and fluids, and the subsequent impact of bacteria on the sperm architecture, activity, and fertilizing potential, has recently gained increased attention from the medical and scientific community. Current evidence strongly emphasizes the fact that the presence of bacteria in semen may have dire consequences on the resulting male fertility. Nevertheless, the molecular basis underlying bacteriospermia-associated suboptimal semen quality is sophisticated, multifactorial, and still needs further understanding. Bacterial adhesion and subsequent sperm agglutination and immobilization represent the most direct pathway of sperm–bacterial interactions. Furthermore, the release of bacterial toxins and leukocytic infiltration, associated with a massive outburst of reactive oxygen species, have been repeatedly associated with sperm dysfunction in bacteria-infested semen. This review serves as a summary of the present knowledge on bacteriospermia-associated male subfertility. Furthermore, we strived to outline the currently available methods for assessing bacterial profiles in semen and to outline the most promising strategies for the prevention and/or management of bacteriospermia in practice.

TIPE1 is a gene in the TNFAIP8 family involved in immune regulation and tumorigenesis. Although previous studies demonstrated that TIPE1 might play different roles in different tumors, its expression and role in lymphoma are unclear. Here we observed TIPE1 expression in diffuse large B cell lymphoma (DLBCL). Two microarrays containing 96 tumor tissue specimens were obtained from the Affiliated Hospital of Nantong University biobank. All specimens came from patients with a clear pathological diagnosis of lymphoma, lymphadenitis, breast cancer, or bladder cancer, and we performed immunohistochemical experiments on these tissue specimens. GEPIA and TIMER platforms were used for bioinformatic analyses. We found higher TIPE1 expression in tumor tissues from patients with lymphoma compared with those with lymphadenitis, breast cancer, or bladder cancer. The GEPIA and TIMER analyses revealed that TIPE1 was upregulated in DLBCL tissues but not in invasive breast carcinoma, urothelial bladder carcinoma, or liver hepatocellular carcinoma tissues. TIPE1 expression was irrelevant for pathological stage, overall survival, or DLBCL immune infiltration levels. However, TIPE1 expression was correlated with MKI67 expression in DLBCL. Overall, TIPE1’s high expression levels in DLBCL may contribute to tumor growth in DLBCL.

The Ca 2+ -activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation ( n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

Interleukin (IL)-17A plays a role in the development of atherosclerotic plaques; however, the mechanism remains unclear. In this study, apolipoprotein E-deficient (ApoE –/– ) mice were fed a high-fat diet to induce atherosclerosis, followed by the treatment with exogenous recombinant IL-17A or the neutralizing antibody to confirm the impact of IL-17A on the established atherosclerotic plaques. We found that both the stimulation of IL-17A and blockage of endogenous IL-17 via antibody did not affect the size of the established plaques. However, IL-17A significantly increased the vulnerability of plaques characterized by the accumulation of lipids and T cells with a concurrent decrease in the number of smooth muscle cells. In addition, the blockage by IL-17 neutralizing antibody attenuated plaque vulnerability. Furthermore, we found that although IL-17A did not affect the efferocytosis of macrophages to apoptotic cells, it promoted the apoptosis of macrophages in the presence of oxidized low-density lipoprotein in vitro . Also, IL-17A upregulated chemokines MCP-1 and CXCL-10 expression in the plaques. Our data indicated that IL-17A controlled both SMC and macrophage accumulation and the apoptosis within the plaque, which may further weaken the aorta wall. This study suggests that IL-17A may be a potential therapeutic target for cardiovascular diseases.

Suppurative arthritis has an acute onset and mostly affects old people and children. Recently, the incidence of adult suppurative hip arthritis, as well as its serious consequences, has increased. The deep hip joint and surrounding hypertrophic muscle tissue limit physical examination. Furthermore, they may cause variable and atypical symptoms of suppurative hip arthritis, possibly inducing delayed diagnosis and treatment. This atypical presentation is uncommon, causing delayed diagnosis and treatment, thus worsening the outcomes. We herein report the case of a 58-year-old man with Staphylococcus aureus ( S. aureus ) septicemia and multiple organ failure due to left pyogenic arthritis of the hip. The patient’s early symptoms were extremely atypical given that he only presented hip pain. Moreover, there was no obvious history of trauma or inflammatory manifestations, such as fever or local swelling, and laboratory examination results and imaging findings were atypical. However, the disease progressed rapidly, developing into systemic sepsis within a short period of time followed by multiple organ failure and death. Early diagnosis and effective treatment of S. aureus hip arthritis are essential to avoid poor outcomes.

Oral squamous cell carcinoma (OSCC) prognosis remains poor. Here we aimed to identify an effective prognostic signature for predicting the survival of patients with OSCC. Gene-expression and clinical data were obtained from the Cancer Genome Atlas database. Immune microenvironment-associated genes were identified using bioinformatics. Subtype and risk-score analyses were performed for these genes. Kaplan–Meier analysis and immune cell infiltration level were explored in different subtypes and risk-score groups. The prognostic ability, independent prognosis, and clinical features of the risk score were assessed. Furthermore, immunotherapy response based on the risk score was explored. Finally, a conjoint analysis of the subtype and risk-score groups was performed to determine the best prognostic combination. We found 11 potential prognostic genes and constructed a risk-score model. The subtype cluster 2 and a high-risk group showed the worst overall survival; differences in survival status might be due to the different immune cell infiltration levels. The risk score showed good performance, independent prognostic value, and valuable clinical application. Higher risk scores showed higher Tumor Immune Dysfunction and Exclusion scores, indicating that patients with a high-risk score were less likely to benefit from immunotherapy. Finally, conjoint analysis for the subgroups and risk groups showed the best predictive ability.

This study reports two cases of squamous cell carcinoma of the thyroid (SCCT) presenting as the thyroid goiter, involving one case of primary squamous cell carcinoma originating from the thyroid (PSCCT) and the other case of secondary SCCT of the thyroid. A retrospective analysis of the clinical and pathological findings was done in this study report. In case 1, the thyroid ultrasound showed multi-hypoechoic well-defined nodules, labeled as 3 using Thyroid Imaging Reporting and Data System, measuring 34.1 mm × 28.9 mm × 30.3 mm and 26.5 mm × 22.2 mm × 23.9 mm in the left in the right lobar thyroid, respectively. The patient underwent surgery and was histologically diagnosed with PSCCT. In case 2, the thyroid ultrasound showed a 25.2 mm × 22.2 mm × 18.8 mm hypoechoic nodule in the right lobar thyroid. The patient underwent a frozen biopsy, the results of which increased suspicion of squamous cell carcinoma. A frozen biopsy was followed by an endoscopic evaluation that detected an ulcerative mass measuring 3.0 cm within the mucosa of esophagus. Due to a scarcity of cases, SCCT is a great challenge for the pathologists and the managing team to come up with the best treatment strategy for the patients.

Paraquat (PQ) is a nonselective herbicide that induces oxidative reactions and multiple-organ failure on exposure. Crocin, a carotenoid obtained from saffron, has demonstrated many therapeutic effects against neural conditions because of its antioxidant properties. In this study, 30 male Wistar rats were divided into 6 groups to evaluate the protective effects of crocin and crocin-loaded niosomes (NC) against PQ in the brain. The levels of total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), superoxide dismutase (SOD), and catalase (CAT) activity were measured as the markers of redox status. Histopathological changes in the CA1 region of the hippocampus were evaluated by cresyl violet staining. Results indicated that both crocin and NC were able to attenuate the adverse effects of PQ at the histopathological level, which was following the changes in LPO ( P < 0.0001), TAC ( P < 0.01), and TTG ( P < 0.05) level. The activity of CAT ( P < 0.01) and SOD ( P < 0.01) could be restored either by crocin or NC. Also, results indicated that nanoformulation of crocin in niosomes appears to be more promising. In conclusion, both crocin and NC showed favourable effects of PQ in the brain of rats, and were determined to be excellent agents to prevent acute toxicities of PQ. Furthermore, these two compounds can be known to provide neuroprotection.

Matrix metalloproteinase-2 (MMP-2) and cluster of differentiation 147 (CD147) both play important roles in the development of kidney fibrosis, and CD147 can induce the production and activation of MMP-2. In the early stage of kidney fibrosis, MMP-2 promotes extracellular matrix (ECM) production and accelerates the development of kidney fibrosis, while in the advanced stage, MMP-2 activity decreases, leading to reduced ECM degradation and making it difficult to alleviate kidney fibrosis. The reason for the decrease in MMP-2 activity in the advanced stage is still unclear. On the one hand, it may be related to hypoxia and endocytosis, which lead to changes in the expression of MMP-2-related active regulatory molecules; on the other hand, it may be related to insufficient CD147 function. At present, the specific process by which CD147 is involved in the regulation of MMP-2 activity is not completely clear, and further in-depth studies are needed to clarify the roles of both factors in the pathophysiology of kidney fibrosis.

Although we know something about single-cell neuromuscular junctions, it is still unclear how multiple skeletal muscle cells coordinate to complete intricate spatial curve movement. Here, we hypothesize that skeletal muscle cell populations with action potentials are aligned according to curved manifolds in space (a curved shape in space). When a specific motor nerve impulse is transmitted, the skeletal muscle also moves according to the corresponding shape (manifolds). The action potential of motor nerve fibers has the characteristics of a time curve manifold, and this time-manifold curve of motor nerve fibers comes from the visual cortex in which spatial geometric manifolds are formed within the synaptic connection of neurons. This spatial geometric manifold of the synaptic connection of neurons originates from spatial geometric manifolds outside nature that are transmitted to the brain through the cone cells and ganglion cells of the retina. The essence of life is that life is an object that can move autonomously, and the essence of life’s autonomous movement is the movement of proteins. Theoretically, because of the infinite diversity of geometric manifold shapes in nature, the arrangement and combination of 20 amino acids should have infinite diversity, and the geometric manifold formed by the protein three-dimensional spatial structure should also have infinite diversity.

Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is the most prevalent adult B-cell malignancy, and a small percentage of CLL transforms into aggressive lymphomas. CLL also causes immune dysfunction due to the over-expansion of immature and ineffective B-cells. When our patient with indolent CLL presented with anemia, pancytopenia, and splenomegaly, all his healthcare providers presumptively assumed a malignant transformation of CLL. However, these are also the signs and symptoms of babesiosis. Herein, we report a case where B. microti infection was presumed as a malignant transformation of CLL and narrowly avoided a devastating outcome. Although the patient developed fulminant sepsis, he finally received the correct diagnosis and treatment. Unfortunately, the disease recrudesced twice. Each time, it became more difficult to control the infection. We describe the clinical course of the case and discuss the case-specific literature review. This report highlights the importance of differential diagnoses ruling out infections which include babesiosis, prior to initiating the treatment of B-cell malignancy.

Time-related cognitive function refers to the capacity of the brain to store, extract, and process specific information. Previous studies demonstrated that the cerebellar cortex participates in advanced cognitive functions, but the role of the cerebellar cortex in cognitive functions is unclear. We established a behavioral model using classical eyeblink conditioning to study the role of the cerebellar cortex in associative learning and memory and the underlying mechanisms. We performed an investigation to determine whether eyeblink conditioning could be established by placing the stimulating electrode in the middle cerebellar peduncle. Behavior training was performed using a microcurrent pulse as a conditioned stimulus to stimulate the middle cerebellar peduncle and corneal blow as an unconditioned stimulus. After 10 consecutive days of training, a conditioned response was successfully achieved in the Delay, Trace-200-ms, and Trace-300-ms groups of guinea pigs, with acquisition rates of >60%, but the Trace-400-ms and control groups did not achieve a conditioned stimulus-related blink conditioned response. It could be a good model for studying the function of the cerebellum during the establishment of eyeblink conditioning.

Reactivation of latent human herpesvirus 2 (HHV-2) can cause spontaneous recovering aseptic meningitis and recurrent meningitis in adults, but it rarely affects the brain parenchyma to cause encephalitis. Here, we report the case of a 37-year-old male patient admitted to our hospital due to fever with a progressive headache for 3 days and paroxysmal episodes of unconsciousness for 1 day. Brain magnetic resonance imaging (MRI) revealed viral meningoencephalitis. Then, metagenomics next-generation sequencing (mNGS) was applied, which detected 12,024 unique sequences of HHV-2 in cerebrospinal fluid (2022), indicating HHV-2 encephalitis. After antiviral treatment, the patient’s symptoms improved, and he was discharged. During the 1-month follow-up, the patient recovered without any new symptoms, but a brain MRI revealed significant atrophy of the original foci. The patient was finally diagnosed with HHV-2 necrotizing meningoencephalitis, which is extremely rare. mNGS helped with the clinical diagnosis and strengthened our understanding of HHV-2 infections in the central nervous system.

Multiple primary malignant neoplasms (MPMNs) are defined as multiple tumors with different pathogenic origins. MPMNs are rare, but the morbidity rate is on the rise. With the development of anti-tumor treatments, such as targeted therapy and immunotherapy, the overall survival of cancer patients has been significantly prolonged, leading to an increased number of patients with MPMNs. A crucial aspect of MPMNs management is deciding how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. Herein we report a 60-year-old male who developed four different malignancies, including esophageal squamous cell carcinoma, upper urinary tract urothelial carcinoma, mediastinal small cell lung cancer, and left lung squamous cell carcinoma over 20 years and received appropriate treatment of each cancer with long survival.

The study’s purpose was to investigate the biological function of long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) in hepatoma carcinoma (HCC). HCC tissues and cells exhibited increased levels of NEAT1 and decreased levels of miR-125a-5p. Reduction in the expression of NEAT suppressed HepG2 cell proliferation and increased apoptosis. This was accompanied by suppression of the AKT/mTOR and ERK pathways, while the opposite was observed for miR-125a-5p. Angiogenesis assay results indicated that NEAT was proangiogenic. A dual-luciferase reporter assay indicated that NEAT1 was bound to miR-125a-5p and miR-125a-5p was bound to vascular endothelial growth factor (VEGF). The proangiogenic effects of NEAT and its stimulation of AKT/mTOR and ERK were reversed by miR-125a-5p. The anti-angiogenic effects of miR-125a-5p and its inhibitory effect on AKT/mTOR and ERK pathways were reversed by co-incubation with VEGF. The conclusion was that NEAT1 enhances angiogenesis in HCC by VEGF via a competing endogenous RNA (ceRNA) of miR-125a-5p that regulates AKT/mTOR and ERK pathways.

Periodontitis is a common disease that is difficult to treat, and if not controlled in time, it causes severe conditions, such as alveolar bone resorption and tooth loosening and loss. Periodontal ligament stem cells constitute a promising cell source for regenerative treatment of periodontitis due to their high osteogenic differentiation capacity. PDLSC osteogenesis plays a central role in periodontal regeneration through successive cytokine-mediated signaling pathways and various biochemical and physicochemical factors. However, this process is inhibited in the inflammatory periodontitis environment due to high concentrations of lipopolysaccharide. Here, we review the mechanisms that influence the osteogenic differentiation of periodontal stem cells in this inflammatory microenvironment.

Gastric cancer (GC) is one of the most common malignant tumors. The mechanism of GC radioresistance and new radiosensitizers must be revealed and developed to treat GC. Serine hydroxymethyltransferase 2 (SHMT2) is responsible for encoding the mitochondrial form of the pyridoxal phosphate-dependent enzyme. SHMT2 plays a critical role in several types of cancers, while its possible effect on the radiological resistance in GC is still unclear. In this study, we investigated the role of SHMT2 in the radiological resistance of GC. Our data confirmed that SHMT2 was highly expressed in radiation-resistant GC cells. SHMT2 reduced the radiosensitivity of GC cells. In addition, SHMT2 is involved in radiation-induced GC cell apoptosis. Further, SHMT2 regulated the Wnt/β-catenin pathway, therefore reducing the radiosensitivity of GC cells in vivo . In conclusion, we revealed that depletion of SHMT2 enhanced the sensitivity of GC cells to interventional radiotherapy through the Wnt/β-catenin pathway.

There are few reports available on the combination therapy of continuous renal replacement therapy (CRRT) and double filtration plasmapheresis (DFPP) in patients with systemic lupus erythematosus (SLE) complicated by severe bacterial infections, especially in children. A 14-year-old female child with recurrent SLE complicated by severe sepsis-induced multiple organ dysfunction syndrome was administered CRRT combined with DFPP for blood purification in addition to routine immunosuppressant therapy. The changes in autoantibodies, cytokines, and coagulation function indexes of the patient before and after treatment were compared to explore the effect of such therapy on progression and prognosis. After DFPP therapy, significant decreases in the levels of double-stranded DNA antibody, cytokines interleukin (IL)-6, IL-10, and procalcitonin (PCT) were observed. Fibrinogen (Fib) decreased and needed to be replenished following DFPP. After CRRT combined with DFPP, the patient began to urinate sparingly (urine volume was < 50 mL/day) at the seventh week, the urine volume was > 400 mL/day (up to 560 mL/day) at the ninth week (63 days), and the urine volume was >1,000 mL/day at the tenth week, at which time the renal function had fully recovered. DFPP may reduce the plasma Fib concentration, which needs to be replenished in a timely manner. CRRT combined with DFPP shows efficacy in patients with SLE, but the coagulation function requires close monitoring.

Multiple primary malignancies (MPMs) are defined as the coexistence of at least two unrelated primary malignancies in a single patient, with the tumors differing in their histology. MPMs in the same patient, when present within 6 months of the primary tumor diagnosis, are considered a synchronous occurrence. In this case report, we describe a 61-year-old man who presented with three distinct tumors concurrently in 2021: noninvasive urothelial carcinoma of the bladder, diffuse large B-cell lymphoma, and squamous cell carcinoma of the lung. We discuss the process of therapy and briefly review the literature. MPMs are increasing in incidence, requiring an interdisciplinary approach to diagnosis and treatment.

In influenza vaccine development, Madin–Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer associated with a poor prognosis. ICC accounts for about 10% of primary liver malignancies but with increasing incidence in recent years. Recently, some studies suggested that minimally interventional therapy can be used in the treatment of ICC. However, there are few references on interventional therapy for the clinical treatment of ICC. Herein we reported a case of a 48-year-old man who suffered from ICC. The patient was diagnosed with ICC by computerized tomography scan and pathological biopsy. The patient was completely cured by minimally interventional therapy with iodine-125 seed implantation. These results provide an important reference for the treatment option of ICC.

Corneal disease was the most critical cause of vision loss. This study aimed to research a new method and provide a theoretical basis for treating corneal injury. A mice corneal epithelial injury model was constructed by the method of mechanical curettage. Models were treated with sphingosine 1-phosphate (S1P) and si-Spns2. An immunofluorescence assay was used to detect βIII-tubulin. The expressions of neurotrophic factor, S1P transporter, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway-related proteins were detected by western blot. Hematoxylin–eosin staining was processed to detect the effect of SIP on corneal repair in mice. si-Spns2 inhibited the effect of S1P. S1P significantly repaired the corneal injury, while si-Spns2 treatment made it more severe. Moreover, S1P could significantly increase the levels of NGF, BDNF, GDNF, Spns2, and p-ERK1/2. si-Spns2 inhibits the effect of S1P in the expression of these proteins. S1P significantly increased axonal differentiation of trigeminal ganglion neurons, which was inhibited after si-Spns2 treatment. S1P promoted corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model. Treatment of corneal injury by S1P may be an effective approach.

The role of the calcifying nanoparticles (CNPs) in the calcification process of the outer cyst wall in hepatic cystic echinococcosis (HCE) remains unknown. CNPs were isolated from the tissues of the patients with HCE. Western blotting, alkaline phosphatase staining, and alizarin staining were performed to detect the cellular calcium ion deposition induced by the CNPs. CCK-8 and flow cytometry assays were conducted to determine the effect of CNPs on the apoptosis of mesenchymal stem cells (MSCs). Western blot experiments were performed to examine the expression levels of apoptosis-related factors and TGF-β1/Smad signaling pathway constituents. Treatment with CNPs induced the differentiation of MSCs. Calcium-related proteins, including OPN, BMP-2, and RUNX2, were upregulated after the CNP treatment. Similarly, CNP exposure increased the cellular calcium ion deposition in MSCs. In addition, the expression of Bax and Caspase-8 was elevated by the CNPs in MSCs. Treatment with CNPs promoted MSC apoptosis and inhibited the MSC growth. The TGF-β1/Smad signaling pathway was also activated after the CNP treatment. This study indicated that CNPs may play a critical role in initiating calcification of the outer cyst wall of HCE and promote the decay of echinococcosis, providing a new strategy for the treatment of hepatic echinococcosis.

Prognostic markers are the biomarkers used to measure the disease progression and patient outcome regardless of treatment in coronavirus disease 2019 (COVID-19). This study aimed to analyze laboratory parameters as prognostic markers for the early identification of disease severity. In this study, 165 patients attending Sukraraj Tropical and Infectious Disease Hospital with COVID-19 were enrolled and divided into severe and non-severe groups. The demographic data, underlying co-morbidities, and laboratory findings were analyzed and compared between severe and non-severe cases. The correlation between the disease criticality and laboratory parameters was analyzed. Cut-off values of parameters for severe patients were speculated through the receiver operating characteristics (ROC) curve, and regression analysis was performed to determine the risk factors. Patients with severe COVID-19 infection had significantly higher absolute neutrophil count, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), ferritin, positive carbohydrate reactive protein (CRP), glucose, urea, creatinine, and aspartate aminotransferase, while lower absolute lymphocyte count, absolute eosinophil count (AEC), and red blood cell count in comparison to non-severe infection. ROC analysis gave a cut-off value (sensitivity, specificity) of age, AEC, NLR, PLR, and ferritin as 47.5 years (70.2, 64.7%), 335 cells/mm 3 (74, 67%) 3.3 (68.4, 63.7%), 129 (77.2, 51%), and 241 ng/mL (74.0%, 65.0%) respectively. Risk factor analysis showed higher age, low AEC, high ferritin, and positive CRP as independent risk factors associated with severe COVID-19 infection. Hematological and inflammatory markers, including novel NLR and PLR, should be assessed to aid clinicians in the early identification of severe cases, prioritization of cases, and effective management to decrease the mortality of COVID-19 patients.

This study investigated the role of N 6-methyladenosine (m6A) and alternative splicing (AS) in bladder cancer (BLCA). The BLCA-related RNA expression profiles and AS events were downloaded from the UCSC Xena and SpliceSeq databases, respectively. Differentially expressed AS (DEAS) was screened, and prognostic-related DEAS events were used to construct prognostic risk models based on Cox proportional hazards regression analysis. Receiver operating characteristic curves and multivariate Cox analysis were used to evaluate the predictive efficiency and independence of these models. We also constructed a protein-to-protein interaction (PPI) network and a regulation network of splicing factors (SFs) and DEAS events. In total, 225 m6A-related prognostic-related DEAS events were identified. The predictive ability of each prognostic model was good, and the alternate terminator model showed the best performance when the area under the curve was 0.793. The risk score of the model was an independent prognostic factor for BLCA. The PPI network revealed that AKT serine/threonine kinase 1, serine- and arginine-rich SF6, and serine- and arginine-rich SF2 had higher-node degrees. A complex regulator correlation was shown in the SF and DEAS networks. This study provides insights for the subsequent understanding of the role of AS events in BLCA.

The purpose of this study was to characterize the testicular profile of Zucker diabetic fatty (ZDF) rats presenting with type 2 diabetes mellitus (DM2) in the absence or presence of obesity. To achieve this, testes were collected from 270-day-old male Wistar ( n = 15), ZDF nonobese ( n = 15), and ZDF obese rats ( n = 16). Changes to the testicular structure were quantified morphometrically, while immunocytochemistry was employed to assess caspase-3 activity. Reactive oxygen species (ROS) production, fluctuations of major antioxidant molecules, and the extent of damage to the proteins and lipids were assessed in tissue lysates. Levels of selected interleukins (ILs) were determined by enzyme-linked immunosorbent assay. The results reveal significant alterations to the testicular structure accompanied by caspase-3 overexpression, particularly in ZDF obese rats. The most notable disruption of the oxidative balance, characterized by ROS overproduction, antioxidant deficiency, protein, and lipid deterioration was recorded in ZDF rats suffering from both DM2 and obesity. Accordingly, the highest concentrations of pro-inflammatory IL-1, IL-6, and IL-18 accompanied by reduced levels of the anti-inflammatory IL-10 were found in testicular tissue collected from ZDF obese rats. This study highlights the vulnerability of male gonads to pathophysiological changes caused by hyperglycemia, which are further exacerbated by excessive adipose tissue.

This study investigated the effects of glucose and osmotic pressure on the proliferation and cell cycle of trophoblast cells. HTR8/SVneo cells were treated with 0 (no glucose), 1 (low glucose), 5 (normal), and 25 mmol/L (high glucose) glucose. In addition, the cells were treated with 5 mmol/L glucose (normal) and 5 mmol/L glucose + 20 mmol/L mannitol (mannitol). The cell morphology and proliferation were determined by microscopy and a cell counting kit-8 assay. The cell cycle and apoptosis were examined by flow cytometry. The cell number was relatively decreased and morphological changes were intermediate in the high-glucose group compared with the low-glucose groups. The proportion of cells in the G2/M phase was higher in the low-glucose group than in the other groups, and it was lower in the G1 phase and higher in the S phase in the high-glucose group than in the other groups. Compared with 24 h, cell proliferative activity was restored to a certain extent after 48 h in the high-glucose group. In summary, the blood glucose concentration might influence the proliferation of trophoblast cells. A high-glucose environment inhibited initial cell proliferation, which could be moderately restored after self-regulation. Furthermore, the proliferation of trophoblasts was not affected by the osmotic pressure.

Norovirus is a prominent enteric virus responsible for severe acute gastroenteritis disease burden worldwide. In our current study, we analyzed 7,804 norovirus sequences of human and animals in China which were detected from 1980 to 2020 from GenBank. The GenBank database was searched up to May 2021 with the following search terms: “norovirus” or “norwalk virus” and “China.” The 7,804 norovirus sequences were collected and evaluated by phylogenetic analysis using MEGA X software package. The online typing tool (https://www.rivm.nl/mpf/typingtool/norovirus/) was used to confirm the genotypes. There were 36 norovirus genotypes prevailing in China. GII.4 was the most prevalent genotype, and GII.2, GII.3 and GII.17 also emerged during different time periods. Most sequences were detected in East China (41.72%, 3,256/7,804), but different norovirus genotypes were distributed widely across the country. A variety of norovirus genotypes, including GI, GII, GIII, GIV, GV, GVI, GVII and GX, were reported in different animals. Furthermore, a GI.3 sequence detected from animal had high identity with norovirus detected in human from the same region, indicating the potential norovirus zoonotic transmission in China. In conclusion, these results indicated that norovirus sequences with considerable genetic diversity distributed widely in China, with potential reverse zoonotic transmission from human to animals.

Turner syndrome (TS) is a congenital chromosomal abnormality that affects approximately 1 in 2,500 people. Both in China and abroad, few studies exist on the incidence of tumors in patients with TS. Most reported cases are complicated with gonadal germ cell tumors, and extragonadal tumors are rare, with the latter not yet being reported in China. Through chromosome karyotype analysis and surgical exploration, a pediatric patent was diagnosed with TS complicated with gonadoblastoma and adrenal neuroblastoma. The patient was short in stature and had a facial deformity. After admission, adrenal computed tomography was conducted, and a right adrenal mass was identified as a neurogenic tumor. After surgical resection and gonadal exploration, the pathological results revealed left gonadoblastoma, right gonadal stromal cell hyperplasia, and ganglion neuroblastoma (mixed type) in the right adrenal gland. Pediatric patients with TS have an increased likelihood of developing neuroblastoma and adrenal-related tumors, and changes in adrenal hormone levels and clinical manifestations are often not obvious when combined with adrenal-related tumors. To avoid missed diagnosis and delayed treatment, screening for adrenal tumors is therefore recommended for patients with TS before the initiation of growth hormone treatment.

Diabetic kidney dysfunction is closely associated with renal fibrosis. Although the suppression of fibrosis is crucial to attenuate kidney damage, the underlying mechanisms remain poorly understood. In this study, renal injury in diabetic mice was induced by the intraperitoneal injection of streptozotocin (100 or 150 mg/kg) for 2 consecutive days. In the model mice, remarkable renal injury was observed, manifested by albuminuria, swelling of kidneys, and histopathological characteristics. The renal fibrosis was obviously displayed with high-intensity staining of fibrin, type IV collagen (Col IV), and fibronectin. The levels of Col IV and transforming growth factor-β1 were significantly increased in diabetic mice kidneys. The aggravated fibrotic process was associated with the overexpression of HMGB1, TLR2/4, and p-NF-κB. Furthermore, a high expression of F4/80 and CD14 indicated that macrophage infiltration was involved in perpetuating inflammation and subsequent fibrosis in the kidneys of diabetic mice. The results demonstrate that the severity of renal fibrosis is positively associated with the activation of HMGB1/TLR2/4 signaling in diabetes.

There have been several false-positive results in the antibody detection of COVID-19. This study aimed to analyze the distribution characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M (IgM) and immunoglobulin G (IgG) in false-positive results using chemiluminescent immunoassay. The characteristics of false-positive results in SARS-CoV-2 IgM and IgG tests were analyzed. The false-positive proportion of single SARS-CoV-2 IgM-positive results was 95.88%, which was higher than those of single SARS-CoV-2 IgG-positive results (71.05%; p < 0.001) and SARS-CoV-2 IgM- and IgG-positive results (39.39%; p < 0.001). The S/CO ratios of SARS-CoV-2 IgM and IgG in false-positive results ranged from 1.0 to 50.0. The false-positive probability of SARS-CoV-2 IgM in the ratios of specimen signals to the cutoff value (S/CO) range (1.0–3.0) was 95.06% (77/81), and the probability of false-positive results of SARS-CoV-2 IgG in the S/CO range (1.0–2.0) was 85.71% (24/28). Dynamic monitoring showed that the S/CO values of IgM in false-positive results decreased or remained unchanged, whereas the S/CO values of IgG in false-positive results decreased. The possibility of false-positive single SARS-CoV-2 IgM-positive and single SARS-CoV-2 IgG-positive results was high. As the value of S/CO ratios decreased, the probability of false-positives consequently increased, especially among the single SARS-CoV-2 IgM-positive results.

Myocardial infraction (MI) is the leading cause of high morbidity and mortality worldwide. It was still urgently needed to find new and effective drugs for MI treatment by the use of myocardial ischemia/reperfusion (I/R) model. Sushi repeats contain the protein X-Linked 2 (SRPX2), which regulates a variety of important cell functions. However, its possible role in myocardial I/R and the progression of MI is still unclear. In this study, we investigated the role of SRPX2 in myocardial I/R. SRPX2 showed low expression in IR rats and H9C2 cells induced by oxygen–glucose deprivation/reperfusion (OGD/R). SRPX2 could increase OGD/R-induced H9C2 cell survival. In addition, SRPX2 suppressed the apoptosis of OGD/R-induced H9C2 cells. Furthermore, we found that SRPX2 could inhibit ER stress induced by OGD/R in H9C2 cells. Mechanically, we found that SRPX2 suppressed the PI3K/Akt/mTOR pathway, thus attenuating OGD/R -induced injury in H9C2 cells. Therefore, SRPX2 has the potential to serve as a target for MI treatment.

To study the role and mechanism of aquaporin-8 (AQP8) in placental vascular development in gestational diabetes mellitus (GDM), hematoxylin–eosin staining and immunohistochemistry were utilized to analyze the histopathological changes in placentas in GDM patients. Transwell, CCK-8, and tube formation assays were performed to examine cell migration, proliferation, and tube formation. AQP8, vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor alpha (TNF)-α, and vascular endothelial growth factor (VEGF)-A expression levels were investigated. Relative to the control group, the placentas in the GDM group showed morphological changes, the number of microvessels in the placental villi arterioles was significantly higher, and the area of microvessels in the arterioles of placental villi was significantly lower. The expression levels of VCAM-1, TNF-α, VEGF-A, and AQP8 in the GDM placentas and human umbilical vein endothelial cells (HUVECs) stimulated by high glucose were significantly higher than those in the control group, and AQP8 was located in placental endothelial cells. Overexpression of glucose and AQP8 inhibited tube formation, migration, and proliferation in HUVECs. High glucose levels can induce dysfunction in vascular endothelial cells and lead to pathological changes in the placental vascular structure in GDM. AQP8 overexpression in placental GDM can inhibit endothelial cell behavior, cause endothelial cell dysfunction, and further participate in the occurrence and development of GDM placental vascular lesions.

Ischemic stroke (IS), usually caused due to an abrupt blockage of an artery, is the leading cause of disability and the second leading cause of death worldwide. The association of the C-reactive protein (CRP) gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS susceptibility has been widely studied, but the results remain inconsistent. Our study aimed to assess the association between CRP gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS risk. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang databases were searched up to April 2022 to identify eligible studies. The Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. The odd ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between CRP gene (rs3093059 T/C and rs1205 C/T) polymorphisms and IS risk. Eighteen case–control studies with 6339 cases and 29580 controls were identified. We found that CRP (s3093059 T/C and rs1205 C/T) polymorphism was not significantly associated with the risk of IS in any genetic model (recessive model: OR 1.00, 95% CI 0.79–1.26; OR 1.06, 95% CI 0.90–1.25). When stratified analysis by country, genotype method, source of controls, and NOS score, still no statistically significant association was found. Our study indicated that the CRP (rs3093059 T/C and rs1205 C/T) polymorphisms were not associated with the susceptibility to IS.

To investigate the effects of growth hormone (GH) on pubertal obese male rats, a rat model of high-fat diet-induced obesity was established in juvenile male rats. The model rats were divided into the treatment group (GH) and the non-treatment group (physiological saline). After 4 weeks, we measured the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), estrogen (E2), testosterone (T), and insulin-like growth factor (IGF-1). The morphological changes of the liver and testis were assessed, and the expression of aromatase was detected. The levels of ALT, AST, TC, TG, LDL-C, E2, and IGF-1 in the treatment group were significantly lower than in the non-treated model rats ( P < 0.001). The levels of HDL-C and T of GH-treated rats were significantly higher than those of the non-treatment group ( P < 0.001). Compared with non-treated model rats, GH-treated model rats showed reduced liver steatosis, improved morphological structure of the testicular seminiferous tubules, and an increased number of spermatogenic cells. The treatment group also showed lower expression of aromatase in the liver and testis compared with the non-treatment group. GH partially protected pubertal male rats from obesity-induced lipid metabolic disorder and sexual retardation.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an important surface molecule of activated T cells that has a strong affinity with the B7 molecule on the surface of antigen-presenting cells. Among these molecules, the CTLA-4 extracellular region (CTLA-4 IgV) may be used as a novel immune adjuvant molecule for delivering antigens and inducing strong humoral and cellular immune responses. In this study, bioinformatics analysis was performed to determine and clone the extracellular region of Xinjiang sheep CTLA-4 (NM_001009214). The CTLA-4 IgV gene was amplified and ligated into the pMD19-T vector, and the positive bacteria were screened by blue-white spots for sequencing and comparison. The correctly sequenced CTLA-4 IgV was digested and then ligated into the prokaryotic expression vector pET-30a(+). The plasmid pET30a–CTLA-4 IgV was constructed to induce the expression of the recombinant protein CTLA-4 IgV. Thereafter, CTLA-4 IgV was identified. Clustal X multiple sequence alignment revealed that the protein sequence of Xinjiang sheep CTLA-4 IgV was different from that of the known CTLA-4 extracellular region. The 3D protein structure of Xinjiang sheep CTLA-4 IgV was constructed via the bioinformatics method. Subsequently, molecular docking between the Xinjiang sheep CTLA-4 IgV protein and the B7 molecule was conducted. Results revealed multiple binding sites in the extracellular region of Xinjiang sheep CTLA-4, and two multiple interactions ensured stable binding after docking. The functionality of the Xinjiang sheep CTLA-4 IgV protein was further verified by fusing the CTLA-4 extracellular V region with EgG1Y162, a protective protein from Echinococcus granulosa , and the purified recombinant protein CTLA-4 IgV–EgG1Y162 was expressed with the mouse bone marrow-derived. The addition of the Xinjiang sheep CTLA-4 IgV protein at the amino terminus promoted the binding of EgG1Y162 to dendritic cells (DCs) and increased the maturation rate of these cells, further indicating that the protein could effectively improve the antigen presentation ability of DCs. The CTLA-4 extracellular domain protein of Xinjiang sheep is unique and has the potential to promote the presentation of the fusion protein by DCs as an adjuvant. The cloning and expression of this gene provide new measures and ideas for the preparation of the Xinjiang sheep vaccine to prevent zoonotic diseases. Graphical abstract

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial–mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3 ; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo . RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

Osteoporosis is a progressive bone disorder with a higher incidence in the elderly and has become a major public health concern all over the world. Therefore, it is urgent to investigate the mechanisms underlying the pathogenesis of osteoporosis. In this study, the osteoporosis animal model was established, and then rat bone marrow mesenchymal stem cells (rBMSCs) were cultured. The results showed that PHF8 expression was decreased in osteoporosis rats compared to controls. Overexpression of PHF8 promoted BMSC osteogenic differentiation and the expression of osteogenesis-related genes. In addition, the Wnt/β-catenin signaling pathway in BMSCs was inhibited in osteoporosis rats, which was rescued by overexpression of PHF8. After treatment with the Wnt pathway antagonist, the improved osteogenic differentiation of BMSCs induced by overexpression of PHF8 was blocked. Collectively, our data revealed that the decreased expression of PHF8 in osteoporosis rats suppressed the osteogenic differentiation of BMSCs, which was then restored by PHF8 overexpression. Furthermore, the inhibition of the Wnt/β-catenin signaling pathway in BMSCs suppressed osteogenic differentiation. Thus, these findings indicated that PHF8 plays a role in osteogenic differentiation through the Wnt/β-catenin signaling pathway. Graphical abstract

Breast cancer is one of the most common cancers affecting females worldwide. Early detection and diagnosis of breast cancer may aid in timely treatment, reducing the mortality rate to a great extent. To diagnose breast cancer, computer-aided diagnosis (CAD) systems employ a variety of imaging modalities such as mammography, computerized tomography, magnetic resonance imaging, ultrasound, and histological imaging. CAD and breast-imaging specialists are in high demand for early detection and diagnosis. This system has the potential to enhance the partiality of traditional histopathological image analysis. This review aims to highlight the recent advancements and the current state of CAD systems for breast cancer detection using different modalities.

We present an unusual case of bilateral dacryoadenitis in a middle-aged patient with adult-onset Still’s disease (AOSD). We reviewed relevant clinical studies addressing the association between lacrimal lesions and AOSD. A 50-year-old Chinese woman with a 4 year history of recurrent fever and rashes was admitted to the hospital. She had also developed nodules on both eyelids 10 months before admission. After undergoing resection of the left lacrimal gland, the patient received steroids and immunosuppressive therapy. The patient showed good postoperative recovery during the 20 month follow-up. In this case, the pathological examination conducted after orbital surgery helped clinicians differentiate between dacryoadenitis and other orbital lesions. In a review of the literature, dacryoadenitis occurred after the onset of AOSD, and all cases showed non-granulomatous chronic inflammation by histopathology, which indicated that the lacrimal gland may be an inflammatory target and is affected by systemic inflammation in AOSD.

This study aimed to examine B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) in gastric adenocarcinoma (GAC) and its association with the maximal standard uptake value (SUVmax) of preoperative fluorine-18-fludeoosyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). Clinicopathological data were retrospectively collected from 60 primary GAC patients. The Bmi-1 protein expression in GAC and adjacent noncancerous tissues was examined by immunohistochemistry and western blot analysis. Pearson’s correlation analysis was conducted to assess the correlation between Bmi-1 expression and the SUVmax. The Bmi-1 protein levels were significantly greater in GAC versus noncancerous tissues, and higher Bmi-1 was significantly correlated with a lower degree of tumor differentiation, higher tumor stages, more lymph node metastasis, and depth of invasion. The SUVmax value was significantly correlated with the T stage, N stage, and clinical stage, but not with age, gender, tumor size, histological differentiation degree, or Lauren classification. Moreover, a significant positive correlation between Bmi-1 and SUVmax was observed in GAC tissues. In conclusion, our findings demonstrate a novel correlation between Bmi-1 and preoperative SUVmax in GAC patients who did not receive radiotherapy, chemotherapy, or targeted treatment before surgery, and both are positively correlated with unfavorable prognostic factors and a higher grade of malignancy.

In the current research context of precision treatment of malignant tumors, the advantages of immunotherapy are unmatched by conventional antitumor therapy, which can prolong progression-free survival and overall survival. The search for new targets and novel combination therapies can improve the efficacy of immunotherapy and reduce adverse effects. Since current research targets for immunotherapy mainly focus on lymphocytes, little research has been done on erythrocytes. Nucleated erythroid precursor stem cells have been discovered to play an essential role in tumor progression. Researchers are exploring new targets and therapeutic approaches for immunotherapy from the perspective of erythroid progenitor cells (EPCs). Recent studies have shown that different subtypes of EPCs have specific surface markers and distinct biological roles in tumor immunity. CD45 + EPCs are potent myeloid-derived suppressor cell-like immunosuppressants that reduce the patient’s antitumor immune response. CD45 − EPCs promote tumor invasion and metastasis by secreting artemin. A specific type of EPC also promotes angiogenesis and provides radiation protection. Therefore, EPCs may be involved in tumor growth, infiltration, and metastasis. It may also be an important cause of anti-angiogenesis and immunotherapy resistance. This review summarizes recent research advances in erythropoiesis, EPC features, and their impacts and processes on tumors.

Numerous studies have indicated that mean platelet volume (MPV) and platelet distribution width (PDW) were correlated with spontaneous abortion (SAB), but the results were contradictory. Hence, we performed a meta-analysis to assess the association of MPV and PDW with SAB. We systematically searched on China National Knowledge Internet, PubMed, and Embase up to May 2022 to retrieve eligible studies. The synthesized standard mean difference (SMD) with a 95% confidence interval (CI) was used to evaluate the correlation of MPV and PDW with SAB. A total of 20 studies were finally included in this meta-analysis. The pooled analysis results showed that PDW was markedly increased in patients with SAB versus women with a healthy pregnancy (SMD = 1.03; 95% CI: 0.51–1.54; p = 0.0001), while there were no significant differences in MPV between women with SAB and those with healthy pregnancy (SMD = 0.19; 95% CI: −0.26 to 0.65; p = 0.40). Therefore, PDW may serve as a potential marker for predicting SAB. However, homogeneous and multiethnic studies with larger sample sizes are warranted to validate our findings due to several limitations in this meta-analysis. Graphical abstract

Neural tube closure disorders, including anencephaly, spina bifida, and encephalocele, cause neural tube defects (NTDs). This congenital disability remained not only a major contributor to the prevalence of stillbirths and neonatal deaths but also a significant cause of lifelong physical disability in surviving infants. NTDs are complex diseases caused by multiple etiologies, levels, and mechanisms. Currently, the pathogenesis of NTDs is considered to be associated with both genetic and environmental factors. Here, we aimed to review the research progress on the etiology and mechanism of NTDs induced by methylation modification caused by folic acid deficiency. Folic acid supplementation in the diet is reported to be beneficial in preventing NTDs. Methylation modification is one of the most important epigenetic modifications crucial for brain neurodevelopment. Disturbances in folic acid metabolism and decreased S -adenosylmethionine levels lead to reduced methyl donors and methylation modification disorders. In this review, we summarized the relationship between NTDs, folic acid metabolism, and related methylation of DNA, imprinted genes, cytoskeletal protein, histone, RNA, and non-coding RNA, so as to clarify the role of folic acid and methylation in NTDs and to better understand the various pathogenesis mechanisms of NTDs and the effective prevention.

The toll-like receptor 4 (TLR4) pathway is involved in seizures. We investigated whether ultrasound-targeted microbubble destruction (UTMD)-mediated delivery of short hairpin RNA (shRNA) targeting the TLR4 gene (shRNA-TLR4) can reduce ischemia-induced seizures in rats with hyperglycemia. A total of 100 male Wistar rats were randomly assigned to five groups: (1) Sham; (2) normal saline (NS); (3) shRNA-TLR4, where rats were injected with shRNA-TLR4; (4) shRNA-TLR4 + US, where rats were injected with shRNA-TLR4 followed by ultrasound (US) irradiation; and (5) shRNA-TLR4 + microbubbles (MBs) + US, where rats were injected with shRNA-TLR4 mixed with MBs followed by US irradiation. Western blot and immunohistochemical staining were used to measure TLR4-positive cells. Half of the rats in the NS group developed tonic-clonic seizures, and TLR4 expression in the CA3 region of the hippocampus was increased in these rats. In addition, the NS group showed an increased number of TLR4-positive cells compared with the Sham group, while there was a decreased number of TLR4-positive cells in the shRNA, shRNA + US, and shRNA + MBs + US groups. Our findings indicate that the TLR4 pathway is involved in the pathogenesis of ischemia-induced seizures in hyperglycemic rats and that UTMD technology may be a promising strategy to treat brain diseases.

An increasing number of microorganisms are being identified as pathogens for diseases in macroalgae, but the species composition of bacteria related to Caulerpa lentillifera , fresh edible green macroalgae worldwide, remains largely unclear. The bacterial communities associated with C. lentillifera were investigated by high-throughput 16S rDNA sequencing, and the bacterial diversities in washed and control groups were compared in this study. A total of 4,388 operational taxonomic units were obtained from all the samples, and the predominant prokaryotic phyla were Proteobacteria , Bacteroidetes , Planctomycetes , Cyanobacteria , Actinobacteria , Verrucomicrobia , Chloroflexi , and Acidobacteria in C. lentillifera . The bacterial diversity changed with seasons and showed an increasing trend of diversity with the rising temperature in C. lentillifera . There were slight reductions in the abundance and diversity of bacteria after washing with tap water for 2 h, indicating that only parts of the bacterial groups could be washed out, and hidden dangers in C. lentillifera still exist. Although the reduction in the abundance of some bacteria revealed a positive significance of washing C. lentillifera with tap water on food safety, more effective cleaning methods still need to be explored.

Caragana intermedia ( C. intermedia ) is a kind of drought-tolerant leguminous shrub. WRKY transcription factors are one of the largest family of transcription factors in plants and play critical regulatory roles in stress tolerance and the development of plants. In our study, CiWRKY48 was cloned from C. intermedia , analyzed using bioinformatics software, and expressed with a prokaryotic expression system. The results showed that the open reading frame (ORF) of CiWRKY48 was 1158bp, the molecular weight (MW) was 42 kDa, and its subcellular localization was in the nucleus. Additionally, fusion protein was obtained, and confirmed by western blotting. The stress resistance of the pET30a-His-MBP-CiWRKY48 transformed Escherichia coli expression strain was reduced under mannitol and salt treatment, compared with the control. Overall, our findings provided a foundation for uncovering the function of CiWRKY48.

Hybridization of Brassica napus with various Brassicaceae species can result in obtaining new forms with increased resistance to blackleg, a dangerous disease caused mainly by Leptosphaeria maculans . In this study, we aimed to correlate the field resistance of selected Brassica hybrids to blackleg with chromosomal structure revealed by Fluorescence in situ hybridization. Tested genotypes varied in the number of chromosomes and rDNA signals. The greatest variation was observed for A1-type chromosomes. Field evaluation also revealed significant differences in L. maculans resistance. Performed analyses allowed to distinguish three B. napus × Brassica fruticulosa genotypes in which variable patterns of chromosomal structure might be connected to field resistance. However, a more thorough study, including the detection of all A-genome chromosomes, is required.

Plant bolting is regulated and controlled by various internal and external factors. We aimed to provide an improved method for breeding to determine whether there is a synergism between hormones and to explore the regulatory effect of plant hormones on the bolting of leaf lettuce. Lettuce plants were sprayed with exogenous auxin and gibberellin separately or in combination. The specific bolting period was determined by the change in stem length and cytological observation. The dynamic changes in endogenous hormones and genes closely related to bolting were analyzed. Treatment with gibberellin alone and the combined application of auxin and gibberellin induced bolting on the fourth day, and treatment with auxin alone resulted in bolting on the eighth day. In the early bolting stage, the auxin contents in the stems of the treatment groups, especially the combined gibberellin and auxin group, were higher than those of the control group. After the application of exogenous auxin and gibberellin, we found that the expression of the ARF8 and GID1 genes was upregulated. Based on the results of our study, combined treatment with exogenous gibberellin and auxin was the best method to promote the bolting of leaf lettuce, and the ARF8 and GID1 genes are closely related to this process.

As there is a global water crisis facing the whole world, it is important to find alternative solutions to treat wastewater for reuse. Hence, plants have an effective role in removing pollutants from wastewater, which has been emphasized in this review article. Biological treatment of wastewater can be considered an eco-friendly and cost-effective process that depends on in the future. Living organisms, including plants, can remediate pollutants in wastewater, especially in agricultural fields, such as dyes, heavy metals, hydrocarbons, pharmaceuticals, and pesticides. This review discusses the different activities of plants in pollutant elimination from wastewater and sheds light on the utilization of plants in this scope. This review focuses on the remediation of the most common contaminants present in wastewater, which are difficult to the removal with microorganisms, such as bacteria, fungi, and algae. Moreover, it covers the major role of plants in wastewater treatment and the potential of phytoremediation as a possible solution for the global water crisis. Graphical abstract

The most predominant type of resistance (R) genes contain nucleotide-binding sites and leucine-rich repeat (NBS-LRR) domains, characterization of which is helpful for plant resistance improvement. However, the NBS genes of Ipomoea trifida (H.B.K.) remain insufficient to date. In this study, a genome-wide analysis of the NBS-encoding gene in I. trifida (H.B.K.) was carried out. A total of 442 NBS encoding genes were identified, amounting to 1.37% of the total genes of I. trifida (H.B.K.). Based on the analysis of the domains, the identified ItfNBS genes were further classified into seven groups: CNL, NL, CN, N, TNL, TN, and RNL. Phylogenetic analysis showed that the I. trifida NBS genes clustered into three independent clades: RNL, TNL, and CNL. Chromosome location analysis revealed that the distribution of ItfNBS genes in chromosomes was uneven, with a number ranging from 3 to 45. Multiple stress-related regulatory elements were detected in the promoters of the NBS-encoding genes, and their expression profiles were obtained. The qRT-PCR analysis revealed that IbNBS10 , IbNBS20 , IbNBS258 , and IbNBS 88 responded to stem nematode infection. These results provide critical proof for further characterization and analysis of NBS-encoding genes with important functions.

In the present study, we explored whether magnetic iron oxide nanoparticles (MNPs-Fe 3 O 4 ) can be used to alleviate the toxicity of 3-nitrophenol (3-NP) to rice ( Oryza sativa L.) seedlings grown under hydroponic conditions. The results showed that 3-NP from 7 to 560 μM decreased the growth, photochemical activity of the photosystem II (PS II), and chlorophyll content of the seedlings in a concentration-dependent manner. In the presence of 3-NP, 2,000 mg L −1 MNPs-Fe 3 O 4 were added to the growth medium as the absorbents of 3-NP and then were separated with a magnet. The emergence of MNPs-Fe 3 O 4 effectively alleviated the negative effects of 3-NP on rice seedlings. In addition, the long-term presence of MNPs-Fe 3 O 4 (from 100 to 2,000 mg L −1 ) in the growth medium enhanced the growth, production of reactive oxygen species (ROS), activities of antioxidant enzymes, photochemical activity of PS II, and chlorophyll content of the rice seedlings. These results suggest that MNPs-Fe 3 O 4 could be used as potential additives to relieve the physiological toxicity of 3-NP to rice seedlings.

In plants, Dof transcription factors are involved in regulating the expression of a series of genes related to N uptake and utilization. Therefore, the present study investigated how DNA-binding with one finger (Dof) genes are expressed in response to nitrogen (N) form and concentration to clarify the role of Dof genes and their functions in promoting N assimilation and utilization in poplar. The basic characteristics and expression patterns of Dof genes in poplar were analyzed by the use of bioinformatics methods. Dof genes expressed in response to N were screened, after which the related genes were cloned and transformed into Arabidopsis thaliana ; the physiological indexes and the expression of related genes were subsequently determined. The function of Dof genes was then verified in Arabidopsis thaliana plants grown in the presence of different N forms and concentrations. Forty-four Dof genes were identified, most of which were expressed in the roots and young leaves, and some of the Dof genes were expressed under ammonia- and nitrate-N treatments. Three genes related to N induction were cloned, their proteins were found to localize in the nucleus, and PnDof30 was successfully transformed into Arabidopsis thaliana for functional verification. On comparing Arabidopsis thaliana with WT Arabidopsis thaliana plants, Arabidopsis thaliana plants overexpressing the Dof gene grew better under low N levels; the contents of soluble proteins and chlorophyll significantly increased, while the soluble sugar content significantly decreased. The expressions of several AMT, NRT, and GS genes were upregulated, while the expressions of several others were downregulated, and the expression of PEPC and PK genes significantly increased. In addition, the activity of PEPC, PK, GS, and NR enzymes significantly increased. The results showed that overexpression of PnDof30 significantly increased the level of carbon and N metabolism and improved the growth of transgenic Arabidopsis thaliana plants under low-N conditions. The study revealed the biological significance of poplar Dof transcription factors in N response and regulation of related downstream gene expression and provided some meaningful clues to explain the huge difference between poplar and Arabidopsis thaliana transformed by exogenous Dof gene, which could promote the comprehensive understanding of the molecular mechanism of efficient N uptake and utilization in trees.

Nondeep physiological dormancy exists in freshly harvested pecan ( Carya illinoinensis ) seed, and the endocarp inhibits the seed germination. New methods were tried to detect if “chemical dormancy” or “mechanical dormancy” was caused by the endocarp. The germination of freshly harvested pecan seed with the removal of different parts of the endocarp and the fracture pressure of the endocarp of pecan seed soaked in water at different temperatures were tested. The results showed that (1) there was no significant difference in germination rate between the pecan kernel keeping in touch and out of touch with the same part of the endocarp, (2) whether a part of endocarp was removed to expose the radicle, preventing endocarp from splitting by glue inhibited the radicle elongation significantly, (3) the fracture pressure of the endocarp decreased significantly over water uptake time, and (4) little difference in the fracture pressure of the endocarp between different soaking temperatures. In conclusion, it suggested that (1) the endocarp caused “mechanical dormancy” but “chemical dormancy,” (2) the prevention of radicle elongation was due to the endocarp pressuring the cotyledon rather than the direct physical restriction on the radicle, and (3) the radicle elongation seemed to be able to respond to the suture split and the pressure on the cotyledon.

Ophiopogonis Radix, also known as Maidong in Chinese, is largely produced in the Sichuan and Zhejiang provinces: “Chuan-maidong (CMD)” and “Zhe-maidong (ZMD),” respectively. This study aimed to distinguish and evaluate the quality of CMD and ZMD. In this study, the tubers of CMD and ZMD were investigated using UPLC-Q/TOF-MS, GC-MS, and LC-MS methods, respectively. Overall, steroidal saponins, homoisoflavonoids, amino acids, and nucleosides were quickly identified. Furthermore, multivariate statistical analysis revealed that CMD and ZMD could be separated. Moreover, CMD showed higher levels of 4-aminobutanoic acid, glycine, l -proline, monoethanolamine, and serine than ZMD. Besides, the levels of chlorogenic acid, traumatic acid, cytidine, cadaverine, pyridoxine 5-phosphate, glutinone, and pelargonidin 3- O -(6- O -malonyl-β- d -glucoside) were remarkably higher in ZMD than in CMD. Furthermore, these different constituents were mainly associated with galactose metabolism; starch and sucrose metabolism; cysteine and methionine metabolism; valine, leucine, and isoleucine biosynthesis; and glycerophospholipid metabolism. In general, these results showed many differences between the bioactive chemical constituents of Ophiopogon japonicus from different production areas, where ZMD performed better in the quality assessment than CMD, and that UPLC-Q/TOF-MS, GC-MS, and LC-MS are effective methods to discriminate medicinal herbs from different production areas. Graphical abstract

Asparagus cochinchinensis is a traditional Chinese medicinal plant. The chloroplast (cp) genome study on A. cochinchinensis is poorly understood. In this research, we collected the data from the cp genome assembly and gene annotation of A. cochinchinensis , followed by further comparative analysis with six species in the genus Asparagus . The cp genome of A. cochinchinensis showed a circular quadripartite structure in the size of 157,095 bp, comprising a large single-copy (LSC), a small single-copy (SSC), and two inverted repeat (IR) regions. A total of 137 genes were annotated, consisting of 86 protein-coding genes, 8 ribosomal RNAs, 38 transfer RNAs, and 5 pseudo-genes. Forty scattered repetitive sequences and 247 simple sequence repeats loci were marked out. In addition, A/T-ending codons were shown to have a basis in the codon analysis. A cp genome comparative analysis revealed that a similar gene composition was detected in the IR and LSC/SSC regions with Asparagus species. Based on the complete cp genome sequence in Asparagaceae, the result showed that A. cochinchinensis was closely related to A. racemosus by phylogenetic analysis. Therefore, our study providing A. cochinchinensis genomic resources could effectively contribute to the phylogenetic analysis and molecular identification of the genus Asparagus .

Mitogen-activated protein kinase (MAPK) cascades are conserved and universal signal transduction modules that play important roles in regulating stress responses in plants. Although MAP3K, MP2K, and MPK family in tea plant ( Camellia sinensis ) have been investigated, little is known about MPK family genes responding to various abiotic stresses in tea plant. In this study, we performed a comprehensive genome-wide analysis of the tea plant MAPKs ( CsMPKs ) family gene based on the genomic data of tea plants by bioinformatics-based methods. Here, 21 putative CsMPK genes were identified in the tea plant and divided into 4 subfamilies according to the homologous to Arabidopsis and their phylogenetic relationships. The gene structure and conserved motifs of these CsMPKs in the same group showed high similarity, suggesting that they were highly conserved and might have a similar function. The expression profiles of the CsMPK genes were further investigated by quantitative real-time reverse transcription PCR, indicating that many CsMPK genes were involved in response to cold, drought, heat, or heat combined with drought treatment, suggesting their potential roles in abiotic stress responses in tea plant. These results would provide valuable information for further exploring the functional characterization of CsMPK genes in tea plants.

Reverse transcription quantitative PCR (RT-qPCR) is a technique widely used to investigate the expression of genes. An appropriate reference gene (RG) is essential for RT-qPCR analysis to obtain accurate and reliable results. Caragana intermedia plays an important role in afforestation as a bush. However, due to the lack of appropriate RGs, the research on development-related genes is limited. In this study, the selection for suitable RGs of different organs at various development stages to normalize the results of RT-qPCR about development-related genes was performed. To test the expression stability across all samples, we used the software algorithms such as geNorm, NormFinder, BestKeeper, and RefFinder to evaluate all the candidate RGs. Our results showed that CiEF1α was the most stable RG with little fluctuation among all samples. In addition, CiGAPDH in roots, CiSKIP1 in stems and leaves, and CiEF1α in different organs were selected as the most stable RGs. To confirm the applicability of the most stable RGs, the relative expression of CiWRKY17 was normalized using different candidate RGs. Taken together, our research laid a foundation for the study of development-related genes in C. intermedia .

Somatic embryogenesis receptor-like kinases ( SERKs ), a subfamily of receptor-like kinases, play important roles in response to abiotic stresses in addition to apomictic reproductive development in numerous plant species. The purpose of the present work was to determine if an ortholog of the SERK gene is present in the Diospyros lotus genome, isolate it and analyze its expression during embryogeny and abiotic stress. An ortholog of the SERK gene was isolated from the D. lotus genome, and designated as DlSERK1 . The physical and chemical properties, protein structure, and evolutionary relationship of the DlSERK 1 protein were analyzed by bioinformatics methods, and the expression of DlSERK1 gene during embryonic development and under low-temperature, salt, and drought stresses was examined through real-time quantitative PCR analysis. DlSERK1 contained 1,881 bp open reading frame encoding 626 amino acids, with a molecular mass of 69.18 kDa and pI of 5.34. DlSERK1 had strong hydrophilic property, signal peptide cleavage sites, and two transmembrane regions, indicating that DlSERK1 is a secretory protein. The secondary structure of DlSERK1 was consistent with the tertiary structure, both of which were dominated by random curls and alpha-helices. DlSERK1 had the typical structure of SERK proteins, and harbored multiple phosphorylation and glycosylation sites. Quantitative analysis showed that DlSERK1 was expressed during the embryonic development period, and the highest expression level was at 10 days post-flowering. The DlSERK1 expression level was down-regulated under low-temperature stress and up-regulated under drought and salt stresses. Our study showed that DlSERK1 was expressed in embryo development and could respond to low-temperature, drought, and salt stresses, which lays a foundation for further research on the function of SERK1 in the apomixis growth and development of environmental adaptation in D. lotus.

Rapidly increasing cadmium (Cd) pollution led to the increase in contamination in farmland. The study explained the Cd resistance mechanisms of Plantago asiatica L. via physiological, metabolomic, and transcriptomic analyses. The results showed that as soil Cd level increased, proline content declined and then increased significantly. In contrast to the H 2 O 2 content change trend, contents of soluble protein and malondialdehyde (MDA) first decreased, then increased, and finally, declined. Leaf Cd concentration was positively related to soluble protein content and negatively to both MDA content and activities of superoxide dismutase (SOD) and catalase (CAT). Most of the top 50 differential metabolites belonged to organic acids and sugars. Besides combining metabolome and transcriptome data, in the metabolic network involving the target metabolic pathways (e.g., ascorbate and aldarate metabolism, glutathione metabolism, galactose metabolism, and glyoxylate and dicarboxylate metabolism), dehydroascorbate (DHA), regulated by l -ascorbate peroxidase (APX) and l -gulonolactone oxidase (GULO), was significantly up-regulated. This illuminated that, in P. asiatica , CAT and SOD played vital roles in Cd resistance, and soluble protein and MDA acted as the main indexes to characterize Cd damage. It also suggested that DHA functioned effectively in Cd resistance, and the function was regulated by APX and GULO. Graphical abstract

Unexplained recurrent spontaneous abortion (URSA) is a major concern in reproductive medicine. Neutrophil cytosolic factor 1 ( NCF1 ) polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases. We investigated the association of the missense single nucleotide polymorphism (SNP) rs201802880 (NCF1-339) in NCF1 with URSA and explored its function. We performed NCF1-339 SNP genotyping of samples from 152 Chinese patients with URSA and 72 healthy controls using nested PCR and TaqMan assays. ROS production and RELA (NF-κB subunit) expression in the blood of participants with different NCF1-339 genotypes were determined. The frequencies of the wild-type (GG) and mutant (GA) genotypes remarkably differed between the URSA and control groups. The mutant genotype was associated with an increased risk of recurrent abortion. Furthermore, ROS levels in the URSA group with the GG genotype were significantly higher than those in the group with the GA genotype ( p < 0.05). RELA expression in URSA patients with the GA genotype was considerably higher than that in control individuals with the GG genotype. These findings indicate that mutations in NCF1 may increase the risk of URSA via the NADP/ROS/NF-κB signaling pathway, which has implications for the diagnosis and treatment of URSA.

Drought stress has devastating impacts on faba bean production, particularly with the current abrupt climate changes in arid environments. Hence, it is essential to identify drought-tolerant genotypes. The present study aimed at assessing six faba bean genotypes under three irrigation levels during two winter successive growing seasons (2018/2019 and 2019/2020). The applied irrigation levels were well-watered (every 4 days (D1), moderate drought every 8 days (D2), and severe drought 12 days (D3)) regimes. The analysis of variance exhibited highly significant differences among genotypes, irrigation treatments, and their interactions for all studied traits, except the number of pods plant −1 in the first season. Yield traits of all assessed genotypes decreased significantly with increasing drought stress. Otherwise, proline content (Pro) increased significantly with increasing drought stress. The genotypes Giza.843, Nubaria.2, and Nubaria.3 recorded the highest values of plant height, number of branches/plant, pods/plant, pods weight/plant, 100 seed weight, seed yield/plant, and seed yield/kg under drought stress. Similarly, the highest Pro was displayed by Giza.843 and Nubaria.3 under drought stress in both seasons. Furthermore, Giza.843, Nubaria.2, and Nubaria.3 genotypes had the highest values for most tolerant indices. Accordingly, these genotypes could be exploited in developing drought-tolerant and high-yielding faba bean genotypes in arid environments through breeding programs.

Asparagus setaceus (Kunth) Jessop is a horticultural plant of the genus Asparagus . Herein, the whole chloroplast (cp) genome of A. setaceus was sequenced with PacBio and Illumina sequencing systems. The cp genome shows a characteristic quadripartite structure with 158,076 bp. In total, 135 genes were annotated, containing 89 protein-coding, 38 tRNA, and 8 rRNA genes. Contrast with the previous cp genome of A. setaceus registered in NCBI, we identified 7 single-nucleotide polymorphisms and 15 indels, mostly situated in noncoding areas. Meanwhile, 36 repeat structures and 260 simple sequence repeats were marked out. A bias for A/T-ending codons was shown in this cp genome. Furthermore, we predicted 78 RNA-editing sites in 29 genes, which were all for C-to-U transitions. And it was also proven that positive selection was exerted on the rpoC1 gene of A. setaceus with the K a / K s data. Meanwhile, a conservative gene order and highly similar sequences of protein-coding genes were revealed within Asparagus species. Phylogenetic tree analysis indicated that A. setaceus was a sister to Asparagus cochinchinensis . Taken together, our released genome provided valuable information for the gene composition, genetics comparison, and the phylogeny studies of A. setaceus .

Globally, the trend of using food additives and eating ready-made fast food has led to a deleterious impact on immune organs. Monosodium glutamate (MSG), as a food additive in a high-lipid diet (HLD), acts as a silent killer of immune cells. Hence, the present study aimed to evaluate the role of MSG in HLD on spleen injury in rats. Results showed that a 2.52-fold and 1.91-fold increase in spleen index in MSG and MSG + HLD group indicates splenomegaly, whereas a 1.36-fold and 1.29-fold increase in pro-inflammatory cytokines in MSG and MSG + HLD-fed rats, respectively, promote the inflammatory response. Additionally, MSG and MSG + HLD induce oxidative stress by 1.81-fold and 1.1-fold increased generation of reactive oxygen species (ROS) in macrophage population, and 1.38-fold and 1.36-fold increased generation of ROS in lymphocytes population, respectively. Furthermore, mitochondrial membrane potential was significantly reduced by 1.43-fold and 1.18-fold in MSG and MSG + HLD groups. Therefore, the current study argues that MSG has more detrimental effects on the spleen than MSG + HLD due to the presence of antioxidants in HLD, which suppresses the deleterious impact of MSG. Hence, it can be inferred that MSG induces spleen injury via targeting redox-guided cellular signaling with inflammatory response, leading to severe immune system anomalies. Graphical abstract

With the onset of coronavirus disease in December 2019, the normal routine and lifestyle of the humans has adversely affected all over the world. This change in lifestyle not only increased the level of stress and anxiety, but also badly modified the eating habits during the lockdown period. This increased the rate of binge eating disorder in people who were already immune-compromised. This rapid communication aims to develop awareness among people to stay calm during this pandemic and eat healthy.

Honey has been used as a traditional remedy for various health benefits. This study investigated the potential of honey against the onset of autoimmune diabetes and its associated secondary complications in type 1 diabetic (T1D) experimental animals. Autoimmune diabetes was induced in Sprague Dawley rats, and at the same time, the rats were treated with honey or metformin. Sandwich ELISAs were used to estimate blood glucose, hemoglobin A1C (HbA1c), total cholesterol, and triglycerides. Histopathological examinations determined the T1D-induced lesions on kidneys, pancreas, cornea, and retina. Treatment of rats with honey during the course of T1D induction showed a significant reduction in fasting-blood-glucose and HbA1c ( p < 0.01), and total lipid profile was also improved ( p < 0.05). Not only these, but honey also reduced the T1D-induced lesions in the kidney, pancreas, and cornea/retina ( p < 0.05). Metformin showed similar effects and was used as a positive control. In conclusion, honey showed therapeutic potential against the onset of autoimmune diabetes, as it reduces blood glucose/HbA1c and improves the lipid profile by reducing the plasma levels of total cholesterol, low-density lipoproteins (LDL), very low-density lipoprotein (VLDL), and triglycerides. Moreover, it also showed protective potential against the development of diabetic nephropathy, pancreatitis, and retinopathy.

The Fat Mass and Obesity-associated (FTO) gene has been shown to play an important role in developing obesity, manifesting in traits such as increased body mass index, increased waist-to-hip ratio, and the distribution of adipose tissues, which increases the susceptibility to various metabolic syndromes. In this study, we evaluated the impact of fruit-based diets of Solanum melongena (SMF) and Solanum aethiopicum fruits (SAF) on the FTO gene expression levels in a high-fat diet (HFD)-induced obese animals. Our results showed that the mRNA level of the FTO gene was downregulated in the hypothalamus, and white and brown adipose tissue following three and six weeks of treatment with SMF- and SAF-based diets in the HFD-induced obese animals. Additionally, the Solanum fruit supplementation exhibited a curative effect on obesity-associated abrasions on the white adipose tissue (WAT), hypothalamus, and liver. Our findings collectively suggest the anti-obesity potential of SMF and SAF via the downregulation of the FTO gene.

Overweight and obesity have been linked with increased intake of sugar-sweetened beverages. On the other hand, physical activity has been known to lead to weight loss. Therefore, we hypothesized that exercise might influence the Lactobacillus population in fecal microbiota as their changed abundance is often associated with shifts in the physical activity and diet. In our experiment, Wistar rats were allocated into groups with normal feed or added sugar-sweetened beverages with or without access to a running wheel. Interestingly, only a combination of physical activity and sweetened beverage intake was associated with a significant increase in fecal lactobacilli abundance, suggesting a connection between exercise and a rise in lactobacilli abundance. Moreover, physical activity has improved weight-related parameters and led to increased plasma and mRNA adiponectin levels. Ghrelin and leptin plasma levels were unaltered. Taken together, our results demonstrate that effect of physical activity on adiposity even during unhealthy feeding patterns is accompanied by increased lactobacilli abundance in the fecal microbiota population.

Coreopsis tinctoria Nutt. was used to extract oleoresin through supercritical CO 2 extraction technology. The extraction conditions were optimized using response surface methodology, and the chemical composition of C. tinctoria Nutt. oleoresin (CTO) was analyzed. Under the optimal conditions, the antioxidant activity of oleoresin was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH˙) and 2,2′-azino-bis-(3-ethylbenzo-thiazoline-6-sulphonic acid)diammonium salt (ABTS˙ + ) free radical scavenging assays. The optimal extraction conditions were a 27.5 MPa extraction pressure, a 45°C extraction temperature, and a 3 h extraction time. Under these extraction conditions, oleoresin yield was up to 3.163%. Compared to steam distillation extraction, the CTO extracted using supercritical CO 2 had more abundant components. The EC 50 of CTO for DPPH˙ and ABTS˙ + free radical scavengers was 1.54 and 1.07 mg/mL, respectively.

Plant-based foods are becoming an increasingly frequent topic of discussion, both scientific and social, due to the dissemination of information and exchange of experiences in the media. Plant-based diets are considered beneficial for human health due to the supply of many valuable nutrients, including health-promoting compounds. Replacing meat-based foods with plant-based products will provide many valuable compounds, including antioxidants, phenolic compounds, fibers, vitamins, minerals, and some ω3 fatty acids. Due to their high nutritional and functional composition, plant-based foods are beneficial in acute and chronic diseases. This article attempts to review the literature to present the most important data on nutrients of plant-based foods that can then help in the prevention of many diseases, such as different infections, such as coronavirus disease, pneumonia, common cold and flu, asthma, and bacterial diseases, such as bronchitis. A properly structured plant-based diet not only provides the necessary nutrients but also can help in the prevention of many diseases.

Selenium may influence the biosynthesis of individual proteins in the yeast cell cytosol. In this study, we used two-dimensional (2D) electrophoresis to identify proteins that are differentially expressed by the enrichment of selenium in Saccharomyces cerevisiae yeast cells. We chose eight protein fractions for further proteomic analysis. A detailed analysis was performed using the Ultraflextreme matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight mass spectrometer, which enables fast and accurate measurement of the molecular weight of the analysed proteins. This study, for the first time, provides evidence that selenium-enriched yeast contains higher levels of mitochondria malate dehydrogenase, adenosine-5′-triphosphate (ATP)-dependent RNA helicase dbp3, and tryptophan dimethylallyltransferase, and alanyl-tRNA editing protein AlaX than yeast without the addition of selenium. It should be emphasised that the proteomic variability obtained reflects the high biological and complexity of yeast metabolism under control and selenium-enriched conditions and can be properly used in the future as a model for further research aimed at determining the expression of appropriate metabolic genes.

Ghee is a traditional Tibetan dairy product with high-fat content, low yield, plasticity, caseation, and rich nutrition. In this study, we analyzed the diversity of microbial communities in yak milk and ghee samples at high and low altitudes, especially the Lactobacillus genus, and further used metabolomic techniques to compare the differences in metabolites in yak ghee at different altitudes. The results showed that the increase in altitude had a significant and generally inhibitory effect on the microbial community diversity in milk ghee, and yak milk at high altitude was abundant in nutrients, which could antagonize the negative impact of increased altitude. Using non-targeted metabolomics, we infer the composition of flavor compounds in ghee: nine kinds of carboxylic acids, 11 kinds of esters, six kinds of ketones, two kinds of alcohols, and four kinds of alkene compounds, among which the key flavor compounds are dl -2-(acetylamino)-3-phenylephrine acid, 1-(4-methoxyphenyl)-2-propanone, sebacic acid, Lysope 18:1, and uracil 1-beta- d -arabinofuranoside. These flavor substances are found in Lactococcus , Lactobacillus , and Streptococcus . With the participation of Lactobacillus , it is synthesized through biosynthesis of alkaloids derived from ornithine, lysine, and nicotine acid and glyoxylate and decarboxylate metabolism, among which Lactococcus plays a key role. In this study, a variety of lactic acid bacteria related to ghee fermentation were screened out, revealing the composition of volatile flavor compounds in Gannan yak milk ghee in the Qinghai–Tibet Plateau and providing a reference for further key volatile flavor compounds and the formation mechanism of flavor compounds.

Heavy metal (HM) pollution is a severe and common environmental problem in mining area soil. It is imperative to understand the micro ecological characteristics of mining area soil for HM contaminated soil remediation. This study described the effects of HM pollution level and soil physical and chemical parameters on microbial diversity. In this study, high-throughput sequencing technology was used to study the effects of HM pollution on the diversity and composition of the soil microbial community. The soil groups were barren, exhibiting alkaline pH, low total nitrogen (TN), and total potassium (TK) according to soil fertility standard. Compared with the control group, there was severe multiple HM pollution in the other five groups, including lead (Pb), cadmium (Cd), zinc (Zn), and copper (Cu). The dominant phyla accounting for more than 1% of the overall community in all soil groups were Proteobacteria (34.432 ± 7.478%), Actinobacteria (22.947 ± 4.297%), Acidobacteria (10.47 ± 2.439%), Chloroflexi (7.89 ± 2.980%), Planctomycetota (5.993 ± 1.558%), Bacteroidota (4.275 ± 1.980%), Cyanobacteria (3.478 ± 2.196%), Myxococcus (2.888 ± 0.822%), Gemmatimonadota (2.448 ± 0.447%), Firmicutes (1.193 ± 0.634%), Patescibacteria (0.435 ± 0.813%), and Nitrospirota (0.612 ± 0.468%). Proteobacteria and Actinobacteria were predominant at the phylum level, which showed a certain tolerance to HMs. In addition, redundancy analysis (RDA) results showed that Pb, Cu, Zn, and Cd were strongly correlated with each other ( P < 0.01). Other nutrient elements (except for TK) were significantly positively correlated with each other. Cu and nutrient element TK had an important impact on bacterial community structure. Therefore, bacteria with the function of HM tolerance and bioremediation in extreme environments should be researched, which provides a foundation for future ecological remediation of contaminated soil by using microbial remediation technology. Graphical abstract

Nitrification in agricultural soil is an important process for food production. In acidic soil, nitrification is however also considered to be a major source of N 2 O production. The nitrification rate largely depends on the community composition of ammonia-oxidizing organisms. To obtain a view of the nitrification rates and N 2 O emission situations in low pH soils in Southern China and understand their relations with the microbial community composition, here we conducted 15 N tracer experiments and microorganism community composition analysis using four acidic agricultural soil samples collected in Southern China. A single dominant community (relative abundance >68%) of the ammonia-oxidizing bacteria and ammonia-oxidizing archaea was observed in the soils with pH = 4.81–6.02. A low amount of NO 3 – {\text{NO}}_{3}^{\mbox{--}} was produced from the nitrification in the strongly acidic soil (pH = 4.03), and the calculated nitrification rate in this soil was significantly lower than those of other soils with pH = 4.81–6.02. High N 2 O emissions but low 15 N–N 2 O emissions were observed in the soil with pH = 4.03. Our results suggest that, under aerobic conditions, soil pH is an important factor affecting nitrification through modifying the microorganism composition.

Cinnamomum balansae Lecomte (Lauraceae), an economically important forest tree, is distributed in the tropical forests of central and northern Vietnam, which has been threatened in recent decades due to the destruction of its habitat and over-exploitation. The genetic diversity and population structure of the species have not been fully evaluated. We used a set of 15 microsatellites to analyze 161 adult trees from 9 different populations, representing the geographical distribution of C. balansae . Ninety-two different alleles were identified. Here our results showed a low genetic diversity level with an average H o = 0.246 and H e = 0.262, and a high level of genetic differentiation ( F ST = 0.601). The bottleneck tests indicated evidence of a reduction in the population size of the two populations (TC and CP). Additionally, all three clustering methods (Bayesian analysis, principal coordinate analysis, and Neighbor-joining tree) were identified in the two genetic groups. The Mantel test showed a significant positive correlation between genetic distance and geographic distance ( R 2 = 0.7331). This study will provide a platform for the conservation of C. balansae both in ex-situ and in-situ plans.

Microplastics (MPs), as a physical anthropogenic contaminant, represent a serious, human health concern due to their toxicity and ability to act as vectors for other pollutants and pathogens. This study aimed to screen for MP contamination in marine fish in Taif market, Saudi Arabia. A total of 22 fish species were used according to their different marine habitats and feedings. We have focused on extracting MPs from gills and muscles using KOH digestion. Nile red dye was used for the MP identification under fluorescence microscopy followed by the Fourier-transform infrared spectroscopy analysis. This study has reported MP contamination in gills and muscles of all the studied fish, in which poly(vinyl butyral) (PVB) was present in epipelagic species, poly(vinylidene fluoride) (PVDF) and poly(2,4,6,-tribromostyrene) (PtBS) were present in pelagic species, and PtBS and chlorosulfonated polyethylene were present in demersal/benthopelagic species. Moreover, benthic fish samples contain PtBS particles; reef-associated species have three different MP particles/fiber PtBS, PVDF, and poly(vinyl formal) and the rest of the studied species samples contain PtBS. The results highlight that the MP pollution increased to reach different species from the pelagic species to the benthic ones. PtBS as a type of polystyrene was the most dominant MP found in most species.

Lygus pratensis , an important agricultural pest, is seriously detrimental to cotton in China. For the research and development of attractants, the present study screened and identified plant volatiles with activity against the pest. Out of the total 20 volatiles identified from seven hosts, 16 volatiles were selected and evaluated. Electrophysiological test results revealed the highest electroantennogram values of heptacosane, heptadecane, decanal, ( E )-4-hexen-1-ol, dodecane, β-pinene, and cis -3-hexenyl isovalerate on adult insects. A significant difference in the behavior of female adults ( P < 0.01) was noted in the trend behavioral tests when the concentration of heptacosane, nonadecane, heptadecane, decanal, 3-hexen-1-ol, and dodecane was 10 −3 (V/V), and that of β-pinene was 10 −4 (V/V). The field trapping test confirmed a significant difference in the trapping effect of heptadecane at 10 −2 (V/V) and 10 −3 (V/V), decanal at 10 −1 (V/V) and 10 −3 (V/V), β-pinene at 10 −2 (V/V), and dodecane at 10 −4 (V/V) compared to that of other volatiles ( P < 0.05). These findings suggested the strong attractant effect of heptadecane, dodecane, decanal, and β-pinene on adults, indicating their potential application as effective attractants for the ecological control of L. pratensis .

Long-term fertilization will affect the above-ground vegetation, but we have little understanding of soil bacterial community structure and diversity so far. This study aims to study the effect of organic fertilization on the soil bacterial community structure and diversity of protected long-term continuous tomato cropping by using high-throughput sequencing technology. Results show that (1) fertilization application (chemical fertilizer [CF] and vermicompost [VM]) significantly changed the soil physico-chemistry properties, such as soil pH decreased compared with control treatment and increased the soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents; (2) VM increased the Shannon index of soil bacteria but decreased the soil Chao1 index; and (3) soil Proteobacteria and Actinomycetes were dominant taxa and the relative abundance of Actinobacteria increased by 36.40–44.27 and 25.80–29.35%, with CF and VM, respectively, compared with the control. Pearson correlation analysis showed that soil pH, SOC, TN, TP, and TK were the main environmental factors that affected the diversity and richness of soil bacterial communities. Redundancy analysis (RDA) showed that the SOC and TN play important roles in the composition of soil bacterial communities. In summary, the effect of VM on the soil bacterial community structure of continuous tomato cropping is better than that of CF, which should be used in the sustainable production of facility tomatoes.

Fluopimomide is a novel acid amide fungicide registered for the control of many plant pathogens. In the present study, the effects of soil-treated fluopimomide on soil micro biomass, disease incidence, plant growth, soil enzyme activity, and marketable yield of tomato ( Solanum lycopersicum L.) were investigated via field trial. In addition, the application prospect in China was also evaluated. In the experiment, five treatments with three replications and a randomized complete block design were followed. The treatments were: furrow application of fluopimomide (25% suspension concentrate, SC) at the dosage of 375, 750, and 1,500 g ha −1 , which was recommended, double recommended, and quadruple recommended dosages, respectively. Besides, common control fungicide fluopicolide (5% SC) furrow was applied at recommended application dosages of 750 mL ha −1 , and a non-treated control was also undertaken. Results indicated that fluopimomide exhibited no effects on the amount of soil bacteria and actinomycetes, and its inhibition effect on fungi amount could be recovered at 60 days after treatment (DAT). With the recommended application dosage, fluopimomide could efficiently reduce the number of plant pathogens in soil by 79.56–85.80%, significantly reduce the disease incidences in tomato plants by 80.00–88.24%, and improve plant height by 13.25–24.05% and marketable yield by 16.88%. Furthermore, soil enzymes exhibited a complex response to fluopimomide, and AOB and nifH gene copy numbers were increased by the double and quadruple recommended dosage of fluopimomide. Based on the above results, fluopimomide could be recommended as an efficient fungicide for the tomato field.

This study assessed the prevalence of plague bacterium ( Yersinia pestis ) among rodents captured in Umzingwane and Nkayi districts, south-western Zimbabwe. A total of 44 rodents were captured on three consecutive days per trapping session in the study sites using a removal trapping method in April 2018. Captured rodents were euthanized, and blood samples were collected. The Giemsa stain method was used to detect plague bacteria. The trapping success was not significantly different ( χ ² = 1.50, df = 1, P = 0.221), 8.5% for the Nkayi district, while in the Umzingwane district, it was 8%. Overall, only one rodent species, i.e., Mastomys natalensis , tested positive for Y. pestis in the Umzingwane district, thus yielding a prevalence rate of 2.3% for the entire study area. This was the most important finding of a Y. pestis -positive rodent in a non-endemic wild area in the Umzingwane district. These results point to a low prevalence of Y. pestis in the study area and the importance of an active plague disease surveillance and monitoring system.

This study investigated the effects of irrigation and nitrogen (N) fertilization on mitigating salt-induced Na + toxicity and sustaining sea rice growth for perfecting irrigation and fertilization of sea rice. Three irrigation methods (submerged irrigation, intermittent irrigation, and controlled irrigation), three kinds of N fertilizers (urea, controlled release urea, and mixed N fertilizer), and control treatment without NaCl were set up in a pot experiment of sea rice with NaCl stress. The electrical conductivity in root layer soil of treatment with mixed N fertilizer and intermittent irrigation decreased slowly with the growth of rice and was significantly smaller than that of other treatments with NaCl. The Na + content in sea rice of intermittent irrigation was the least, and that of submerged irrigation was significantly smaller than that of controlled irrigation, but the K + and Ca 2+ contents of three irrigation treatments were opposite to the Na + content. The Na + content of treatment with mixed N fertilizer and intermittent irrigation was the lowest, while the K + , Ca 2+ , and Mg 2+ contents of mixed N fertilizer and intermittent irrigation were the highest in treatments with NaCl. The cell membrane permeability and malondialdehyde contents of rice leaves of mixed N fertilizer and intermittent irrigation were significantly smaller than those of other treatments with NaCl. The rice yield of mixed N fertilizer was significantly greater than that of urea and controlled release urea, and that of mixed N fertilizer and intermittent irrigation was increased by 104, 108, 277, 300, and 334% compared with mixed N fertilizer and submerged irrigation, urea and intermittent irrigation, urea and submerged irrigation, controlled release urea and intermittent irrigation, and controlled release urea and submerged irrigation, respectively. Therefore, the treatment of mixed N fertilizer and intermittent irrigation is worth recommending for being used for planting sea rice on coastal saline-sodic soil.

Pyroptosis is a kind of cell necrosis mediated by inflammasomes. The caspase 1-induced cleavage of gasdermin D (GSDMD) is a canonical pathway to cause membrane pores and eventually cell pyroptosis. Poly- l -lysine (PLL) is widely used to enhance cell adhesion during experiments. Human THP-1 cells are a typical cell line used to study pyroptosis due to their monocytic and macrophage-like characteristics. However, it was found that THP-1 cells seeded on the PLL-coated slides died. To figure out the reason, we observed the morphology of THP-1 cells on PLL-coated slides, which showed obvious pore forming on the cell membranes and cell swelling. The indicated pyroptosis-related protein expression was evaluated and it showed that the conventional caspase-1 pathway of pyroptosis was activated through the NLRP3 inflammasome in THP-1 monocytes on the PLL-coated slides. Hence, PLL-guided cell adhesion induces cell pyroptosis in THP-1 monocytes, which calls for THP-1 dominant studies of pyroptosis to avoid the use of PLL-coated slides or PLL-related drugs.

A histidine (His)-tag is composed of six His residues and typically exerts little influence on the structure and solubility of expressed recombinant fusion proteins. Purification methods for recombinant proteins containing His-tags are relatively well-established, thus His-tags are widely used in protein recombination technology. We established a one-step enzyme-linked immunosorbent assay (ELISA) for His-tagged recombinant proteins. We analyzed variable heavy and light chains of the anti-His-tag monoclonal antibody 4C9 and used BLAST analyses to determine variable zones in light (VL) and heavy chains (VH). VH, VL, and alkaline phosphatase (ALP) regions were connected via a linker sequence and ligated into the pGEX-4T-1 expression vector. Different recombinant proteins with His tags were used to evaluate and detect ALP-scFv activity. Antigen and anti-His-scFv-ALP concentrations for direct ELISA were optimized using the checkerboard method. ZIKV-NS1, CHIKV-E2, SCRV-N, and other His-tag fusion proteins demonstrated specific reactions with anti-His-scFv-ALP, which were accurate and reproducible when the antigen concentration was 50 µg mL −1 and the antibody concentration was 6.25 µg mL −1 . For competitive ELISA, we observed a good linear relationship when coating concentrations of recombinant human anti-Müllerian hormone (hAMH) were between 0.78 and 12.5 µg mL −1 . Our direct ELISA method is simple, rapid, and accurate. The scFv antibody can be purified using a prokaryotic expression system, which provides uniform product quality and reduces variations between batches.

The present study involved building a model of immune-related genes (IRGs) that can predict the survival outcomes of tongue squamous cell carcinoma (TSCC). Using the TCGA database, we collected the gene expression profiles of patients with TSCC and analyzed the differences in IRGs obtained from the ImmPort database. Subsequently, we constructed a predictive model. Transcription factors and differentially expressed IRGs can be used to construct TSCC regulatory network. CIBERSORT tool was used to analyze the relative proportion of 22 tumor-infiltrating immune cells in TSCC samples. Finally, a prognostic model is constructed. We established an IRG model formed by seven genes. The receiver operating characteristic value of the prognostic model based on IRGs is 0.739. After the analysis of the correlation between IRGs and clinical and pathological conditions, we found that Gast was related to grade, IRF9, LTB, and T stage. Among the 22 tumor-infiltrating immune cells, the resting natural killer (NK) cells were found to be related to the 5-year survival rate. This study constructed a prognostic model formed by seven IRGs and discussed the tumor-infiltrating immune cells, which are related to the survival outcome, reflecting the potential regulatory role of TSCC tumor immune microenvironment that could potentially promote individualized treatment.

Biochar-based fertilizers are used to improve soil’s physiochemical and biological properties and increase fertilizer utilization rate. Therefore, a technological model of biochar-based fertilizers is essential for the reduced application. This study was conducted to determine the effects of the different levels of biochar-based fertilizer applications on soil and plant nutrient content, as well as maize yield. Biochar-based fertilizer increased the total N content of maize stem and kernel and the total P content of maize axis and kernel. Biochar-based fertilizer increased the total P but decreased the total K of maize plants while increasing the fertilizer’s partial productivity. Treatment B1 (600.00 kg hm −2 of biochar-based fertilizer) increased the dry-matter weight of the maize at silking and filling stages by 1.60 and 15.83%. Treatment B1 increased the ear length, diameter, and plant height. Compared with BCK (600.00 kg hm −2 of conventional fertilizer), the yield of B1 was increased by 9.23%, and the difference was significant ( p < 0.05). Biochar-based fertilizer treatments B2–B5 (biochar-based fertilizer reduced by 5–20%) reduced maize yield, but there was no significant difference between their yield and BCK. This study aimed to provide a basic understanding and reference for maize fertilizer reduction with good application prospects.

The CPP -like plant‐specific transcription factor has a prominent role in plant development and growth through cell division and differential activities. However, little information is available about the CPP gene family in Triticum aestivum L. Herein, we identified 37 and 11 CPP genes in the wheat and rice genome databases, respectively. The phylogeny of the CPP protein-like family members was further divided into five subfamilies based on structural similarities and phenotypic functional diversities. The in silico expression analysis showed that CPP genes are highly expressed in some tissues, such as shoot apex, shoot, leaf, leaf sheath, and microspore. Furthermore, the qRT-PCR found higher expression for TaCPP gene family members in leaf, leaf blade, young spike, mature spike, and differential expression patterns under abiotic stresses, including heat, drought, salt, and hormonal treatment, such as indole acetic acid and 1-aminocyclopropane-1 carboxylic acid. We found that CPP gene family members are mostly located in the nucleus after infiltrating the CPP5-1B-GFP and TaCPP11-3B-GFP into tobacco leaves. The overexpression of the TaCPP5-1D gene revealed that the CPP gene positively regulates the germanium, shoot, and root activities in Arabidopsis . The TaCPP5-1D -overexpressed plants showed less anti-oxidative sensitivity under drought stress conditions. These results demonstrated that TaCPP5-1D protein has a crucial contribution by interacting with TaCPP11-3B protein in maintaining stress homeostasis under the natural and unfavorable environmental conditions for growth, development, and stress resistance activities. Therefore, this study could be used as pioneer knowledge to further investigate the function of CPP genes in plant growth and development.

Mung bean is one of Ethiopia’s most important pulse crops in the lowlands. The main constraints to mung bean productivity in Ethiopia are low soil fertility and improved varieties. During the 2018 cropping season, a field experiment was conducted in Kindo Koysha woreda with the objective of evaluating the effects of NPS fertilizer rates on yield and yield attributing traits of four mung bean varieties. Treatments consisted of factorial combinations of four mung bean varieties (N26, Shewarobit, NVL-1, and Chinese) with four NPS fertilizer rates (0, 50, 100, and 150 kg ha −1 ) laid out in randomized complete block design with three replications. The combination of the N26 variety with 150 kg NPS produced the highest number of pods per plant (15.46), seeds per pod (10.93), grain yield (1240.70 kg ha −1 ), and biomass (3177.40 kg ha −1 ). Moreover, the combination of 100 kg NPS ha −1 with the variety N26 also generated the highest net return (31,734.30 Birr ha −1 ) with a marginal rate of return of 771.71%. Thus, it may be tentatively stated that the usage of 100 kg NPS ha −1 with the variety N26 was determined to be optimum for the development of mung bean in the study region.

Irrigation regimes should be chosen to maximize crop yield and water use efficiency. To realize high yield and efficient water use with the appropriate furrow irrigation regime, the effects of two regimes (alternate furrow irrigation and conventional furrow irrigation) and three lower soil moisture limits (60, 70, and 80%) were studied on winter wheat yield and water consumption using a multi-level fuzzy comprehensive evaluation method. The results show that under the two regimes, alternate furrow irrigation and conventional furrow irrigation, when the lower limit of the soil moisture is 70%, the harvest index (0.45 and 0.39, respectively) and crop water productivity of winter wheat (1.86 and 1.90 kg m −3 , respectively) are highest. The comprehensive fuzzy evaluation model considers multiple measures, including yield, harvest indices, irrigation volume, total water consumption, and crop water productivity – the index values are highest at the 70% condition, which are 0.3468 and 0.3432, respectively. Therefore, it can be concluded that a moderate water deficit is conducive to saving water resources and improving water use efficiency. In conclusion, a multi-level and multi-factor indices system of furrow irrigation regime was constructed based on ensuring winter wheat production. Conventional furrow irrigation is recommended in areas with sufficient irrigation water, while alternating furrow irrigation, which can reduce the total amount of irrigation required, is suitable for areas with water shortages.

The Mongolian horses have excellent endurance and stress resistance to adapt to the cold and harsh plateau conditions. Intraspecific genetic diversity is mainly embodied in various genetic advantages of different branches of the Mongolian horse. Since people pay progressive attention to the athletic performance of horse, we expect to guide the exercise-oriented breeding of horses through genomics research. We obtained the clean data of 630,535,376,400 bp through the entire genome second-generation sequencing for the whole blood of four Abaga horses and ten Wushen horses. Based on the data analysis of single nucleotide polymorphism, we severally detected that 479 and 943 positively selected genes, particularly exercise related, were mainly enriched on equine chromosome 4 in Abaga horses and Wushen horses, which implied that chromosome 4 may be associated with the evolution of the Mongolian horse and athletic performance. Four hundred and forty genes of positive selection were enriched in 12 exercise-related pathways and narrowed in 21 exercise-related genes in Abaga horse, which were distinguished from Wushen horse. So, we speculated that the Abaga horse may have oriented genes for the motorial mechanism and 21 exercise-related genes also provided a molecular genetic basis for exercise-directed breeding of the Mongolian horse.

Seasonal forecasts coupled with crop models can potentially enhance decision-making in smallholder farming in Africa. The study sought to inform future research through identifying and critiquing crop and climate models, and techniques for integrating seasonal forecast information and crop models. Peer-reviewed articles related to crop modelling and seasonal forecasting were sourced from Google Scholar, Web of Science, AGRIS, and JSTOR. Nineteen articles were selected from a search outcome of 530. About 74% of the studies used mechanistic models, which are favored for climate risk management research as they account for crop management practices. European Centre for Medium-Range Weather Forecasts and European Centre for Medium-Range Weather Forecasts, Hamburg, are the predominant global climate models (GCMs) used across Africa. A range of approaches have been assessed to improve the effectiveness of the connection between seasonal forecast information and mechanistic crop models, which include GCMs, analogue, stochastic disaggregation, and statistical prediction through converting seasonal weather summaries into the daily weather. GCM outputs are produced in a format compatible with mechanistic crop models. Such outputs are critical for researchers to have information on the merits and demerits of tools and approaches on integrating seasonal forecast and crop models. There is however need to widen such research to other regions in Africa, crop, farming systems, and policy.

In this study, the data of fertility indicators of soil samples (0–20 cm) in 1980s, 2000 and 2015 in Chenzhou city were used, and the soil integrated fertility index (IFI) was calculated. The results showed that the soil pH was decreased, total nitrogen (TN), organic matter (OM), available phosphorus (AP) and potassium (AK), exchangeable calcium (Ca 2+ ), magnesium (Mg 2+ ) and available copper (Cu) contents were increased, total phosphorus (TP), available sulfur (S) and water-soluble chlorine (Cl − ) contents were decreased, total potassium (TK), available boron (B), iron (Fe), manganese (Mn) and zinc (Zn) were decreased first and then increased. In 2015, most of the fields were higher in pH, OM, TN, AN, AK, Ca 2+ , Mg 2+ , S, Fe, Mn, Cu and Zn, suitable in B, but lower in TP, AP, TK, available molybdenum (Mo) and Cl − . Most of the fields were in the middle grade of IFI in 2000 and 2015, and the mean IFI increased from 0.492 to 0.556 from 2000 to 2015. Thus, for soil improvement, more attention should be paid to adjust soil pH, reduce the application of organic, nitrogen and calcium fertilizers, while increase the fertilizer application of other nutrients.

Genus Tatera is comprised of 12 species, but only one species, Tatera indica , exists in Asia. T. indica is considered an agricultural pest and host of a few zoonotic diseases. However, the data on morphological characteristics are published, but the aspect of molecular characterization is lacking to confirm the status of subspecies in most of the Asian countries including Pakistan. Therefore, the present study is the first study on morphological and molecular characterization of T. indica to get a phylogenetic relationship with the population of T. indica in Pakistan. Almost all the morphometric, cranial, and dental values of T. indica were lower in the present study as compared to the specimen from Iran, Syria, and Turkey. The molecular analysis indicated the presence of sub-species of T. indica . Interestingly, the cytochrome b gene sequence showed more resemblance to the Iranian rat than the previously reported sequence of a Pakistani T. indica. Iran shares a border with Pakistan, and migration between the two countries could be a possible reason. The resembling morphometric data on Iranian rats also explain this phenomenon. The present study found, although minor, evidence of the presence of sub-species even within Pakistan. Unfortunately, the previously submitted sequence from Pakistan was not supplemented with morphometric data and the exact capturing site of the rat. Therefore, further molecular and morphometric data from other regions are required to confirm the presence of sub-species.

In this study, we analyzed the meat quality of Qianhua Mutton Merino sheep (QHMM). QHMM and Small-tail Han sheep (STH) were selected as the test animals. After slaughtering, the longissimus dorsi muscles were tested to determine the nutrient composition, content of amino acid, fatty acid, and muscle fiber diameter. According to the nutrient test result, the protein content of QHMM was higher than that of STH. However, the fat content was significantly lower ( P < 0.05) than STH. Additionally, total amino acid content, total essential amino acid content, total half-essential amino acid content, total non-essential amino acid content, and flavor amino acid content of QHMM were significantly higher ( P < 0.05) than those of STH. Moreover, the contents of C22:1 n9, C18:2 n6, C18:3 n6, C22:6 n6, and C10:0 of the muscle in QHMM were significantly higher ( P < 0.05) than those of STH. Furthermore, the essential amino acid score, the total unsaturated-to-saturated fatty acid ratio, and the polyunsaturated-to-saturated fatty acid ratio of QHMM were greater than those of STH. Additionally, the muscle fiber diameter of QHMM was considerably lower ( P < 0.01) than that of STH. In conclusion, the meat quality of QHMM was better than that of STH.

This commentary is about running an academic research laboratory group, including some reflections, memories, and tips on effectively managing such a group of scientists focused on one’s research. The author’s academic career has spanned from 1982 to 2022, including postdoctoral research associate through the rank of professor with tenure. Currently, the author is in the final year of 3 years of phased retirement. One must be willing to work hard at running a research laboratory. Also, stay focused on funding the laboratory tasks and publishing one’s work. Recruit the best people possible with advice from the collective laboratory group. Laboratory group members felt more like they were a part of a collective family than simply employees; however, what works best for the researcher is what matters. Several other points to discuss will include managing university roles, recruiting laboratory personnel, getting recognition, dealing with intellectual property rights, and publishing work. In closing, there are many more positives than negatives to leading a research laboratory group. Finally, one cannot replace the unforgettable memories and the legacy of a research laboratory group.

There is a saying that as people get older, they prefer to speak more about the past and less about the future. As I go through the last chapter of my scientific career, which spans from 1988–2022, I traced my scientific genealogy and the most important scientific achievements of my laboratory. By examining close to 1,000 PubMed-indexed papers published, I found out that none of them describes best our most important contributions. Also, by realizing that our contributions in science would have likely been discovered by others shortly afterwards, I focused my attention to other metrics. I suggest here that the best metric of success is the number of people that have been trained in my lab, and found their own way in their professional and other endeavors. Over the years, I trained over 250 individuals, of which 49 obtained a PhD, 19 an MSc, 37 were post-doctoral fellows, 5 were clinical fellows and about 150 were co-op/undergraduates and summer students. Many of these individuals now hold important positions in Academia, Government and Industry. My graduates, who have now created their own genealogy and many more individuals with roots to my laboratory, are now serving the society. In conclusion, I consider the development of young trainees as my most important career contribution.