Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and bioch...Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.展开更多
Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were ava...Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.展开更多
Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Micro...Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between MTLE-HS with and without febrile seizure history were screened by the GEO2R software.Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software.Protein–protein interaction(PPI)networks among DEGs were constructed using the STRING database and analyzed by Cytoscape.Results:A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLEHS samples without febrile seizure,including 25 down-regulated and 490 up-regulated genes.These DEGs were expressed mostly in plasma membrane and synaptic vesicles.The major molecular functions of those genes were voltage-gated ion channel activity,extracellular ligand-gated ion channel activity and calcium ion binding.The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport.Five genes(SNAP25,SLC32A1,SYN1,GRIN1,and GRIA1)were significantly expressed in the MTLE-HS with prolonged febrile seizures.Conclusion:The pathogenesis of MTLE-HS involves multiple genes,and prolonged febrile seizures could cause differential expression of genes.Thus,investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.展开更多
Background:Scutellaria baicalensis Georgi is a medicinal plant prized for its bioactive flavonoid derivatives.Flavonoid O-methyltransferases(OMTs)in this species play a vital role in enhancing these compounds’pharmac...Background:Scutellaria baicalensis Georgi is a medicinal plant prized for its bioactive flavonoid derivatives.Flavonoid O-methyltransferases(OMTs)in this species play a vital role in enhancing these compounds’pharmacological activities,including their antioxidant,anti-inflammatory,and anticancer effects.However,a comprehensive genomic overview of the OMT gene family in S.baicalensis is lacking.Methods:This study conducted a genome-wide identification of the OMT gene family in S.baicalensis using bioinformatics approaches.The identified genes were characterized through phylogenetic,physicochemical,and structural analyses.Furthermore,the response of methoxylated flavonoids and key SbOMT genes to drought stress was investigated.Results:A total of 54 SbOMTs were identified and classified into 9 CCoAOMT and 45 COMT subfamily members.These proteins,with lengths from 129 to 695 amino acids and molecular weights from 14.42 to 76.94 kDa,were predominantly acidic.Subcellular localization predicted 43% to be cytoplasmic.Structurally,the CCoAOMT subfamily was more conserved than the COMT subfamily.Promoter analysis revealed hormone-and stress-responsive cis-elements.Under drought stress,the root content of methoxylated flavonoids(wogonin,wogonoside,and oroxylin A)decreased initially and then increased.The expression of SbOMT06,SbOMT41,SbOMT27,and SbOMT29 was positively correlated with this accumulation,suggesting their involvement in biosynthesis.Conclusion:This study provides foundational insights into the SbOMT gene family,revealing key candidates likely involved in methoxyflavonoid biosynthesis.The findings advance our understanding of the molecular mechanisms in S.baicalensis and offer valuable resources for future metabolic engineering and pathway optimization efforts.展开更多
[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Qu...[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(...Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(HCC).Methods:The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases,validated by immunohistochemistry,and the correlation between G6PD expression and clinical features is analyzed.The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier,Cox regression,and prognostic line graph models.Functional enrichment analysis is performed by protein-protein interaction(PPI)network,GO/KEGG,GSEA and for G6PD-associated differentially expressed genes(DEGs).TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results:Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues(P<0.001).G6PD expression is associated with histological grade,pathological stage,T-stage,vascular infiltration,and AFP level(P<0.05);HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group(P<0.05).The level of G6PD expression affects the levels of macrophages,dendritic cells,B cells,and follicular helper T cells in the tumor microenvironment.Conclusion:High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma,and G6PD may be a target for immunotherapy of HCC.展开更多
Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underp...Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyse...AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.展开更多
The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic ...The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for ...Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis.However,the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear.Herein,we provide evidence that tumor protein 53,a negative regulator of SLC7A11,was significantly upregulated post-spinal cord injury.Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity.We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4,alleviated neuronal ferroptosis,and improved neurological function in a contusion spinal cord injury rat model.The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques.Additionally,Kelch-like protein 4,an E3 ubiquitin ligase adaptor,was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11.In summary,the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury,thereby providing potential targets and insights for clinical translation.展开更多
Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.展开更多
The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for...The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.展开更多
Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe n...Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.展开更多
The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical r...The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical research.The review covers key topics such as computational modelling,bioinformatics,machine learning in medical diagnostics,and the integration of wearable technology for real-time health monitoring.Major findings indicate that computational models have significantly enhanced the understanding of complex biological systems,while machine learning algorithms have improved the accuracy of disease prediction and diagnosis.The synergy between bioinformatics and computational techniques has led to breakthroughs in personalized medicine,enabling more precise treatment strategies.Additionally,the integration of wearable devices with advanced computational methods has opened new avenues for continuous health monitoring and early disease detection.The review emphasizes the need for interdisciplinary collaboration to further advance this field.Future research should focus on developing more robust and scalable computational models,enhancing data integration techniques,and addressing ethical considerations related to data privacy and security.By fostering innovation at the intersection of these disciplines,the potential to revolutionize healthcare delivery and outcomes becomes increasingly attainable.展开更多
Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,w...Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.展开更多
In the year 1971,the world’s biggest structural biology collaboration name—The Research Collaboratory for Structural Bioinformatics(RCSB),was formed to gather all the structural biologists at a single platform and t...In the year 1971,the world’s biggest structural biology collaboration name—The Research Collaboratory for Structural Bioinformatics(RCSB),was formed to gather all the structural biologists at a single platform and then extended out to be the world’s most extensive structural data repository named RCSB-Protein Data Bank(PDB)(https://www.rcsb.org/)that has provided the service for more than 50 years and continues its legacy for the discoveries and repositories for structural data.The RCSB has evolved from being a collaboratory network to a full-fledged database and tool with a huge list of protein structures,nucleic acid-containing structures,ModelArchive,and AlphaFold structures,and the best is that it is expanding day by day with computational advancement with tools and visual experiences.In this review article,we have discussed how RCSB has been a successful collaboratory network,its expansion in each decade,and how it has helped the ground-breaking research.The PDB tools that are helping the researchers,yearly data deposition,validation,processing,and suggestions that can help the developer improve for upcoming years are also discussed.This review will help future researchers understand the complete history of RCSB and its developments in each decade and how various future collaborative networks can be developed in various scientific areas and can be successful by keeping RCSB as a case study.展开更多
Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have groupe...Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.展开更多
基金Supported by National Natural Science Foundation of China(31070361)the Fundamental Research Funds for the Central Universities(0910KYZY43,1112KYQN31)+1 种基金"985 Project"from Minzu University of China(MUC98504-14)Scientific Research Project from State Ethnic Affairs Commission(10ZY01)~~
文摘Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.
基金the National Technical system of Chinese Medicinal Materials Industry(No.CARS-21)the Key Natural Science Projects of West Anhui University in China(No.WXZR201932)+4 种基金the Training Program of Innovate and Entrepreneurship of National College students in China(No.201810376058,201810376061)Anhui Provincial Natural Science Foundation in China(No.2017A030311022)Anhui Provincial University Natural Science Project in China(No.KJ2018A0413,KJ2017a407)Anhui Provincial Quality of Undergraduate project in China(No.2018zygc075,2018jyxm1153,2018jyxm1155)the Teaching and Research Projects of West Anhui University in China(No.wxxy2018026).
文摘Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.
基金the Sanming Project of Medicine in Shenzhen(No.SZSM201911003)National Natural Science Foundation of China(No.81571266,81771405).
文摘Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between MTLE-HS with and without febrile seizure history were screened by the GEO2R software.Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software.Protein–protein interaction(PPI)networks among DEGs were constructed using the STRING database and analyzed by Cytoscape.Results:A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLEHS samples without febrile seizure,including 25 down-regulated and 490 up-regulated genes.These DEGs were expressed mostly in plasma membrane and synaptic vesicles.The major molecular functions of those genes were voltage-gated ion channel activity,extracellular ligand-gated ion channel activity and calcium ion binding.The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport.Five genes(SNAP25,SLC32A1,SYN1,GRIN1,and GRIA1)were significantly expressed in the MTLE-HS with prolonged febrile seizures.Conclusion:The pathogenesis of MTLE-HS involves multiple genes,and prolonged febrile seizures could cause differential expression of genes.Thus,investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.
基金funded by the National Natural Science Foundation of China(82404814,82404863)Start-up Research Fund of Nanjing Agricultural University(130-804141)+1 种基金the National Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project(zyyzdxk-2023293)Scientific research Project of Jiangsu Institute of Product Quality Supervision and Inspection(KJ2025008).
文摘Background:Scutellaria baicalensis Georgi is a medicinal plant prized for its bioactive flavonoid derivatives.Flavonoid O-methyltransferases(OMTs)in this species play a vital role in enhancing these compounds’pharmacological activities,including their antioxidant,anti-inflammatory,and anticancer effects.However,a comprehensive genomic overview of the OMT gene family in S.baicalensis is lacking.Methods:This study conducted a genome-wide identification of the OMT gene family in S.baicalensis using bioinformatics approaches.The identified genes were characterized through phylogenetic,physicochemical,and structural analyses.Furthermore,the response of methoxylated flavonoids and key SbOMT genes to drought stress was investigated.Results:A total of 54 SbOMTs were identified and classified into 9 CCoAOMT and 45 COMT subfamily members.These proteins,with lengths from 129 to 695 amino acids and molecular weights from 14.42 to 76.94 kDa,were predominantly acidic.Subcellular localization predicted 43% to be cytoplasmic.Structurally,the CCoAOMT subfamily was more conserved than the COMT subfamily.Promoter analysis revealed hormone-and stress-responsive cis-elements.Under drought stress,the root content of methoxylated flavonoids(wogonin,wogonoside,and oroxylin A)decreased initially and then increased.The expression of SbOMT06,SbOMT41,SbOMT27,and SbOMT29 was positively correlated with this accumulation,suggesting their involvement in biosynthesis.Conclusion:This study provides foundational insights into the SbOMT gene family,revealing key candidates likely involved in methoxyflavonoid biosynthesis.The findings advance our understanding of the molecular mechanisms in S.baicalensis and offer valuable resources for future metabolic engineering and pathway optimization efforts.
基金Supported by the Science and Technology Program of Guizhou Provence(Qiankehejichu-ZK[2023]Yiban 271).
文摘[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
文摘Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(HCC).Methods:The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases,validated by immunohistochemistry,and the correlation between G6PD expression and clinical features is analyzed.The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier,Cox regression,and prognostic line graph models.Functional enrichment analysis is performed by protein-protein interaction(PPI)network,GO/KEGG,GSEA and for G6PD-associated differentially expressed genes(DEGs).TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results:Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues(P<0.001).G6PD expression is associated with histological grade,pathological stage,T-stage,vascular infiltration,and AFP level(P<0.05);HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group(P<0.05).The level of G6PD expression affects the levels of macrophages,dendritic cells,B cells,and follicular helper T cells in the tumor microenvironment.Conclusion:High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma,and G6PD may be a target for immunotherapy of HCC.
基金National Natural Science Foundation of China,Grant/Award Number:No.82560858Beijing Science and Technology New Star Program Cross-cooperation Project,Grant/Award Number:No.20240484711Jiangxi Provincial Natural Science Foundation,Grant/Award Number:20252BAC200586。
文摘Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
文摘AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.
基金supported by grants from Shanghai Agriculture Applied Technology Development Program(Grant No.2022-02-08-00-12-F01109)the National Natural Science Foundation of China(Grant No.32272721).
文摘The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.81672161,81871785,82372411(to ZY)the Health Research Project of Health Commission of Anhui Province,No.AHWJ2023A30106(to YX).
文摘Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis.However,the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear.Herein,we provide evidence that tumor protein 53,a negative regulator of SLC7A11,was significantly upregulated post-spinal cord injury.Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity.We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4,alleviated neuronal ferroptosis,and improved neurological function in a contusion spinal cord injury rat model.The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques.Additionally,Kelch-like protein 4,an E3 ubiquitin ligase adaptor,was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11.In summary,the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury,thereby providing potential targets and insights for clinical translation.
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
基金the National Natural Science Foundation of Chinagrant number:81301562 and 81572147。
文摘The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.
基金supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX)the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL)+1 种基金Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY)the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。
文摘Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
文摘The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical research.The review covers key topics such as computational modelling,bioinformatics,machine learning in medical diagnostics,and the integration of wearable technology for real-time health monitoring.Major findings indicate that computational models have significantly enhanced the understanding of complex biological systems,while machine learning algorithms have improved the accuracy of disease prediction and diagnosis.The synergy between bioinformatics and computational techniques has led to breakthroughs in personalized medicine,enabling more precise treatment strategies.Additionally,the integration of wearable devices with advanced computational methods has opened new avenues for continuous health monitoring and early disease detection.The review emphasizes the need for interdisciplinary collaboration to further advance this field.Future research should focus on developing more robust and scalable computational models,enhancing data integration techniques,and addressing ethical considerations related to data privacy and security.By fostering innovation at the intersection of these disciplines,the potential to revolutionize healthcare delivery and outcomes becomes increasingly attainable.
基金supported by the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220003)National Natural Science Foundation of China(32202504)+2 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515030049)Guangdong Rural Revitalization Strategy Special Project(Grant No.2023-NJS-00-003)Special fund for scientific and technological talents introduction of Guangdong Academy of Agricultural Sciences(Grant No.R2021YJ-YB2004)。
文摘Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.
文摘In the year 1971,the world’s biggest structural biology collaboration name—The Research Collaboratory for Structural Bioinformatics(RCSB),was formed to gather all the structural biologists at a single platform and then extended out to be the world’s most extensive structural data repository named RCSB-Protein Data Bank(PDB)(https://www.rcsb.org/)that has provided the service for more than 50 years and continues its legacy for the discoveries and repositories for structural data.The RCSB has evolved from being a collaboratory network to a full-fledged database and tool with a huge list of protein structures,nucleic acid-containing structures,ModelArchive,and AlphaFold structures,and the best is that it is expanding day by day with computational advancement with tools and visual experiences.In this review article,we have discussed how RCSB has been a successful collaboratory network,its expansion in each decade,and how it has helped the ground-breaking research.The PDB tools that are helping the researchers,yearly data deposition,validation,processing,and suggestions that can help the developer improve for upcoming years are also discussed.This review will help future researchers understand the complete history of RCSB and its developments in each decade and how various future collaborative networks can be developed in various scientific areas and can be successful by keeping RCSB as a case study.
文摘Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
