In order to investigate the protective effects of the overexpression of bcl-xl gene on local cerebral infarction in the transgenic mice subject to permanent occlusion of middle cerebral artery, the models of bcl-xl tr...In order to investigate the protective effects of the overexpression of bcl-xl gene on local cerebral infarction in the transgenic mice subject to permanent occlusion of middle cerebral artery, the models of bcl-xl transgenic mice were established and subjected to cerebral infarction by intraluminal occlusion of the middle cerebral artery. The infarct volume and the neurological scores were observed and comparison between the wild type mice and the transgenic mice was made. It was found that the infarct volume and the neurological scores in the transgenic mice were significantly decreased as compared with those in the wild type mice. It was suggested that the overexpression of bcl-xl gene in transgenic mice could reduce the infarct volume and improve the neurological function of the mice.展开更多
To investigate the expression of Bcl-2 and Bcl-xl gene in sensitive (A2780) and drug-resistance (AD6) human ovarian cancer cell lines and explore the molecular mechanism of multidrug resistance, A2780 and AD6 were det...To investigate the expression of Bcl-2 and Bcl-xl gene in sensitive (A2780) and drug-resistance (AD6) human ovarian cancer cell lines and explore the molecular mechanism of multidrug resistance, A2780 and AD6 were detected by using DNA gel electrophoresis, flow cytometry and RT-PCR. Our results showed that (1)'DNA ladder ' was observed in A2780 and AD6 after cisplatin treatment; (2) after 3.0, 6.0, 9.9 μg/ml of cisplatin treatment, a significant difference was noted in the rate of apoptosis between in A2780 and AD6 (P<0.05); (3) Bcl-2 and Bcl-xl genes were overexpressed in AD6. After cisplatin treatment, the expression of Bcl-2 and Bcl-xl genes was down-regulated in A2780 and AD6. It is concluded that cisplatin could induce the apoptosis of ovarian cancer cells, and the over-expression of Bcl-2 and Bcl-xl genes may contribute to apoptotic inhibition and the development of multidrug-resistance of human ovarian cancer.展开更多
The efficiency and safe range of LipofectamineTM2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using tryp...The efficiency and safe range of LipofectamineTM2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined. The results showed that the survival rate of human keratocytes had no signficant change in the presence of LF2000 (20 μg/ml) or bcl-xl (10 μg/ml) for 24 h. LF2000 could effectively mediate the transfection of exogenous gene bcl-x1 into human keratocytes. The best transfection efficiency could be obtained when the ratio of bcl-xl/LF2000 was 1:8. One day after transfection, the positive cells for bcl-x1 could be detectable, and the positive rate reached the peak on the post-transfection day 3 (48.3 %), then gradually decreased. Fifteen days after transfection, there were few positive cells. It was suggested that LF2000 could effectively transfer the exogenous gene bcl-xl into human keratocytes without obvious toxicity during a concentration range. LF2000/bcl-xl may be likely to play an important role in gene therapy of human keratocytes.展开更多
Grain weight is one of the key components of wheat(Triticum aestivum L.)yield.Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs.A recombinant inbred line(...Grain weight is one of the key components of wheat(Triticum aestivum L.)yield.Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs.A recombinant inbred line(RIL)population derived from a cross between W7268 and Chuanyu 12(CY12)was employed to detect quantitative trait loci(QTLs)for thousand-grain weight(TGW),grain length(GL),grain width(GW),and the ratio of grain length to width(GLW)in six environments.Seven major QTLs,QGl.cib-2D,QGw.cib-2D,QGw.cib-3B,QGw.cib-4B.1,QGlw.cib-2D.1,QTgw.cib-2D.1 and QTgw.cib-3B.1,were consistently identified in at least four environments and the best linear unbiased estimation(BLUE)datasets,and they explained 2.61 to 34.85%of the phenotypic variance.Significant interactions were detected between the two major TGW QTLs and three major GW loci.In addition,QTgw.cib-3B.1 and QGw.cib-3B were co-located,and the improved TGW at this locus was contributed by GW.Unlike other loci,QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike(GNS).They were further validated in advanced lines using Kompetitive Allele Specific PCR(KASP)markers,and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus.Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars.According to gene annotation,spatial expression patterns,ortholog analysis and sequence variation,the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted.Collectively,the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.展开更多
Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(...Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unkn...BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.展开更多
Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported t...Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.展开更多
Root system architecture plays an essential role in water and nutrient acquisition in plants,and it is significantly involved in plant adaptations to various environmental stresses.In this study,a panel of 242 cotton ...Root system architecture plays an essential role in water and nutrient acquisition in plants,and it is significantly involved in plant adaptations to various environmental stresses.In this study,a panel of 242 cotton accessions was collected to investigate six root morphological traits at the seedling stage,including main root length(MRL),root fresh weight(RFW),total root length(TRL),root surface area(RSA),root volume(RV),and root average diameter(AvgD).The correlation analysis of the six root morphological traits revealed strong positive correlations of TRL with RSA,as well as RV with RSA and AvgD,whereas a significant negative correlation was found between TRL and AvgD.Subsequently,a genome-wide association study(GWAS)was performed using the root phenotypic and genotypic data reported previously for the 242 accessions using 56,010 single nucleotide polymorphisms(SNPs)from the CottonSNP80K array.A total of 41 quantitative trait loci(QTLs)were identified,including nine for MRL,six for RFW,nine for TRL,12 for RSA,12 for RV and two for AvgD.Among them,eight QTLs were repeatedly detected in two or more traits.Integrating these results with a transcriptome analysis,we identified 17 candidate genes with high transcript values of transcripts per million(TPM)≥30 in the roots.Furthermore,we functionally verified the candidate gene GH_D05G2106,which encodes a WPP domain protein 2in root development.A virus-induced gene silencing(VIGS)assay showed that knocking down GH_D05G2106significantly inhibited root development in cotton,indicating its positive role in root system architecture formation.Collectively,these results provide a theoretical basis and candidate genes for future studies on cotton root developmental biology and root-related cotton breeding.展开更多
Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinester...Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.展开更多
Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is s...Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).展开更多
●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven fa...●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.展开更多
Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we ...Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.展开更多
Cotton fiber quality is a persistent concern that determines planting benefits and the quality of finished textile products.However,the limitations of measurement instruments have hindered the accurate evaluation of s...Cotton fiber quality is a persistent concern that determines planting benefits and the quality of finished textile products.However,the limitations of measurement instruments have hindered the accurate evaluation of some important fiber characteristics such as fiber maturity,fineness,and neps,which in turn has impeded the genetic improvement and industrial utilization of cotton fiber.Here,12 single fiber quality traits were measured using Advanced Fiber Information System(AFIS)equipment among 383 accessions of upland cotton(Gossypium hirsutum L.).In addition,eight conventional fiber quality traits were assessed by the High Volume Instrument(HVI)System.Genome-wide association study(GWAS),linkage disequilibrium(LD)block genotyping and functional identification were conducted sequentially to uncover the associated elite loci and candidate genes of fiber quality traits.As a result,the previously reported pleiotropic locus FL_D11 regulating fiber length-related traits was identified in this study.More importantly,three novel pleiotropic loci(FM_A03,FF_A05,and FN_A07)regulating fiber maturity,fineness and neps,respectively,were detected based on AFIS traits.Numerous highly promising candidate genes were screened out by integrating RNA-seq and qRT-PCR analyses,including the reported GhKRP6 for fiber length,the newly identified GhMAP8 for maturity and GhDFR for fineness.The origin and evolutionary analysis of pleiotropic loci indicated that the selection pressure on FL_D11,FM_A03 and FF_A05 increased as the breeding period approached the present and the origins of FM_A03 and FF_A05 were traced back to cotton landraces.These findings reveal the genetic basis underlying fiber quality and provide insight into the genetic improvement and textile utilization of fiber in G.hirsutum.展开更多
Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton vari...Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton varieties with heightened resistance to VW stands out as one of the most efficacious protective measures.In this study,we successfully generated two stable transgenic lines of cotton(Gossypium hirsutum L.),VdThitRNAi-1 and VdThit-RNAi-2,using host-induced gene silencing(HIGS)technology to introduce double-stranded RNA(dsRNA)targeting the thiamine transporter protein gene(VdThit).Southern blot analysis confirmed the presence of a single-copy insertion in each line.Microscopic examination showed marked reductions in the colonization and spread of Vd-mCherry in the roots of VdThit-RNAi cotton compared to wild type(WT).The corresponding disease index and fungal biomass of VdThit-RNAi-1/2 also exhibited significant reductions.Real-time quantitative PCR(qRT-PCR)analysis demonstrated a substantial inhibition of VdThit expression following prolonged inoculation of VdThit-RNAi cotton.Small RNA sequencing(sRNA-Seq)analysis revealed the generation of a substantial number of VdThit-specific siRNAs in the VdThit-RNAi transgenic lines.Additionally,the silencing of VdThit by the siVdThit produced by VdThit-RNAi-1/2 resulted in the elevated expression of multiple genes involved in the thiamine biosynthesis pathway in Vd.Under field conditions,VdThit-RNAi transgenic cotton exhibited significantly enhanced disease resistance and yield compared with WT.In summary,our findings underscore the efficacy of HIGS targeting VdThit in restraining the infection and spread of Vd in cotton,thereby potentially enabling the development of cotton breeding as a promising strategy for managing VW.展开更多
Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants...Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants that contain RING-like zinc finger domain and are associated with the regulation of several physiological and biochemical processes.They also play vital roles in plant growth and development such as root formation,leaf development,floral development,hormone biosynthesis,signal transduction,and biotic and abiotic stress responses.Nevertheless,the SRS gene family was not reported in sesame yet.In this study,identification,molecular characterization,phylogenetic relationship,cis-acting regulatory elements,protein-protein interaction,syntenic relationship,duplication events and expression pattern of SRS genes were analyzed in S.indicum.We identified total six SiSRS genes on seven different linkage groups in the S.indicum genome by comparing with the other species,including the model plant Arabidopsis thaliana.The SiSRS genes showed variation in their structure like2–5 exons and 1–4 introns.Like other species,SiSRS proteins also contained‘RING-like zinc finger'and‘LRP1'domains.Then,the SiSRS genes were clustered into subclasses via phylogenetic analysis with proteins of S.indicum,A.thaliana,and some other plant species.The cis-acting regulatory elements analysis revealed that the promoter region of SiSRS4(SIN_1011561)showed the highest 13 and 16 elements for light-and phytohormone-responses whereas,SiSRS1(SIN_1015187)showed the highest 15 elements for stress-response.The ABREs,or ABA-responsive elements,were found in a maximum of 8 copies in the SiSRS3(SIN 1009100).Moreover,the available RNA-seq based expression of SiSRS genes revealed variation in expression patterns between stress-treated and non-treated samples,especially in drought and salinity conditions in.S.indicum.Two SiSRS genes like SiSRS1(SIN_1015187)and SiSRS5(SIN_1021065),also exhibited variable expression patterns between control vs PEG-treated sesame root samples and three SiSRS genes,including SiSRS1(SIN_1015187),SiSRS2(SIN_1003328)and SiSRS5(SIN_1021065)were responsive to salinity treatments.The present outcomes will encourage more research into the gene expression and functionality analysis of SiSRS genes in S.indicum and other related species.展开更多
BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has graduall...BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.展开更多
Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotto...Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses.展开更多
基金a grant from National Natu-ral Sciences Foundation of China (No. 30500167)
文摘In order to investigate the protective effects of the overexpression of bcl-xl gene on local cerebral infarction in the transgenic mice subject to permanent occlusion of middle cerebral artery, the models of bcl-xl transgenic mice were established and subjected to cerebral infarction by intraluminal occlusion of the middle cerebral artery. The infarct volume and the neurological scores were observed and comparison between the wild type mice and the transgenic mice was made. It was found that the infarct volume and the neurological scores in the transgenic mice were significantly decreased as compared with those in the wild type mice. It was suggested that the overexpression of bcl-xl gene in transgenic mice could reduce the infarct volume and improve the neurological function of the mice.
基金ThisprojectwassupportedbytheNationalNaturalScienceFoun dationofChina (No .30 0 70 786 )andagrantfromtheScientificandTechnologicalDevelopmentPlanofHubeiProvince (No .2 0 0 0 1P15 0 5 )
文摘To investigate the expression of Bcl-2 and Bcl-xl gene in sensitive (A2780) and drug-resistance (AD6) human ovarian cancer cell lines and explore the molecular mechanism of multidrug resistance, A2780 and AD6 were detected by using DNA gel electrophoresis, flow cytometry and RT-PCR. Our results showed that (1)'DNA ladder ' was observed in A2780 and AD6 after cisplatin treatment; (2) after 3.0, 6.0, 9.9 μg/ml of cisplatin treatment, a significant difference was noted in the rate of apoptosis between in A2780 and AD6 (P<0.05); (3) Bcl-2 and Bcl-xl genes were overexpressed in AD6. After cisplatin treatment, the expression of Bcl-2 and Bcl-xl genes was down-regulated in A2780 and AD6. It is concluded that cisplatin could induce the apoptosis of ovarian cancer cells, and the over-expression of Bcl-2 and Bcl-xl genes may contribute to apoptotic inhibition and the development of multidrug-resistance of human ovarian cancer.
文摘The efficiency and safe range of LipofectamineTM2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined. The results showed that the survival rate of human keratocytes had no signficant change in the presence of LF2000 (20 μg/ml) or bcl-xl (10 μg/ml) for 24 h. LF2000 could effectively mediate the transfection of exogenous gene bcl-x1 into human keratocytes. The best transfection efficiency could be obtained when the ratio of bcl-xl/LF2000 was 1:8. One day after transfection, the positive cells for bcl-x1 could be detectable, and the positive rate reached the peak on the post-transfection day 3 (48.3 %), then gradually decreased. Fifteen days after transfection, there were few positive cells. It was suggested that LF2000 could effectively transfer the exogenous gene bcl-xl into human keratocytes without obvious toxicity during a concentration range. LF2000/bcl-xl may be likely to play an important role in gene therapy of human keratocytes.
基金supported by the Major Program of National Agricultural Science and Technology of China(NK20220607)the West Light Foundation of the Chinese Academy of Sciences(2022XBZG_XBQNXZ_A_001)the Sichuan Science and Technology Program,China(2022ZDZX0014)。
文摘Grain weight is one of the key components of wheat(Triticum aestivum L.)yield.Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs.A recombinant inbred line(RIL)population derived from a cross between W7268 and Chuanyu 12(CY12)was employed to detect quantitative trait loci(QTLs)for thousand-grain weight(TGW),grain length(GL),grain width(GW),and the ratio of grain length to width(GLW)in six environments.Seven major QTLs,QGl.cib-2D,QGw.cib-2D,QGw.cib-3B,QGw.cib-4B.1,QGlw.cib-2D.1,QTgw.cib-2D.1 and QTgw.cib-3B.1,were consistently identified in at least four environments and the best linear unbiased estimation(BLUE)datasets,and they explained 2.61 to 34.85%of the phenotypic variance.Significant interactions were detected between the two major TGW QTLs and three major GW loci.In addition,QTgw.cib-3B.1 and QGw.cib-3B were co-located,and the improved TGW at this locus was contributed by GW.Unlike other loci,QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike(GNS).They were further validated in advanced lines using Kompetitive Allele Specific PCR(KASP)markers,and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus.Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars.According to gene annotation,spatial expression patterns,ortholog analysis and sequence variation,the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted.Collectively,the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (81873736,31872779,81830032)+2 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001,2021A1515012526)Natural Science Foundation of Guangdong Province (2021A1515012526,2022A1515012651)。
文摘Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.
基金Supported by National Natural Science Foundation of China,No.82100594.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.
基金supported by the National Natural Science Foundation of China,No.81870975(to SZ)。
文摘Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.
基金supported by the Jiangsu Natural Science Foundation,China(BK20231468)the Fundamental Research Funds for the Central Universities,China(ZJ24195012)+3 种基金the National Natural Science Foundation in China(31871668)the Jiangsu Key R&D Program,China(BE2022384)the Xinjiang Uygur Autonomous Region Science and Technology Support Program,China(2021E02003)the Jiangsu Collaborative Innovation Center for Modern Crop Production Project,China(No.10)。
文摘Root system architecture plays an essential role in water and nutrient acquisition in plants,and it is significantly involved in plant adaptations to various environmental stresses.In this study,a panel of 242 cotton accessions was collected to investigate six root morphological traits at the seedling stage,including main root length(MRL),root fresh weight(RFW),total root length(TRL),root surface area(RSA),root volume(RV),and root average diameter(AvgD).The correlation analysis of the six root morphological traits revealed strong positive correlations of TRL with RSA,as well as RV with RSA and AvgD,whereas a significant negative correlation was found between TRL and AvgD.Subsequently,a genome-wide association study(GWAS)was performed using the root phenotypic and genotypic data reported previously for the 242 accessions using 56,010 single nucleotide polymorphisms(SNPs)from the CottonSNP80K array.A total of 41 quantitative trait loci(QTLs)were identified,including nine for MRL,six for RFW,nine for TRL,12 for RSA,12 for RV and two for AvgD.Among them,eight QTLs were repeatedly detected in two or more traits.Integrating these results with a transcriptome analysis,we identified 17 candidate genes with high transcript values of transcripts per million(TPM)≥30 in the roots.Furthermore,we functionally verified the candidate gene GH_D05G2106,which encodes a WPP domain protein 2in root development.A virus-induced gene silencing(VIGS)assay showed that knocking down GH_D05G2106significantly inhibited root development in cotton,indicating its positive role in root system architecture formation.Collectively,these results provide a theoretical basis and candidate genes for future studies on cotton root developmental biology and root-related cotton breeding.
文摘Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.
基金supported by the Notional Natural Science Foundation of China,No.81960417 (to JX)Guangxi Key Research and Development Program,No.GuiKeA B20159027 (to JX)the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2022GXNSFBA035545 (to YG)。
文摘Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).
文摘●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.
基金supported by grants from the Major Program of National Agricultural Science and Technology of China(NK20220607)the National Natural Science Foundation of China(32272059 and 31971883)the Science and Technology Department of Sichuan Province(2021YFYZ0002,2022ZDZX0014,and 2023NSFSC1995)。
文摘Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.
基金supported by the National Key Research and Development Program of China(2022YFD1200300)the Central Plain Scholar Program,China(234000510004)the National Supercomputing Center in Zhengzhou,China。
文摘Cotton fiber quality is a persistent concern that determines planting benefits and the quality of finished textile products.However,the limitations of measurement instruments have hindered the accurate evaluation of some important fiber characteristics such as fiber maturity,fineness,and neps,which in turn has impeded the genetic improvement and industrial utilization of cotton fiber.Here,12 single fiber quality traits were measured using Advanced Fiber Information System(AFIS)equipment among 383 accessions of upland cotton(Gossypium hirsutum L.).In addition,eight conventional fiber quality traits were assessed by the High Volume Instrument(HVI)System.Genome-wide association study(GWAS),linkage disequilibrium(LD)block genotyping and functional identification were conducted sequentially to uncover the associated elite loci and candidate genes of fiber quality traits.As a result,the previously reported pleiotropic locus FL_D11 regulating fiber length-related traits was identified in this study.More importantly,three novel pleiotropic loci(FM_A03,FF_A05,and FN_A07)regulating fiber maturity,fineness and neps,respectively,were detected based on AFIS traits.Numerous highly promising candidate genes were screened out by integrating RNA-seq and qRT-PCR analyses,including the reported GhKRP6 for fiber length,the newly identified GhMAP8 for maturity and GhDFR for fineness.The origin and evolutionary analysis of pleiotropic loci indicated that the selection pressure on FL_D11,FM_A03 and FF_A05 increased as the breeding period approached the present and the origins of FM_A03 and FF_A05 were traced back to cotton landraces.These findings reveal the genetic basis underlying fiber quality and provide insight into the genetic improvement and textile utilization of fiber in G.hirsutum.
基金supported by the National Key Research and Development Program of China(2022YFD1200300)the National Natural Science Foundation of China(32072376 and 32372515)+3 种基金Winall Hi-tech Seed Co.,Ltd.,China(GMLM2023)the Nanfan Special Project of Chinese Academy of Agricultural Sciences(CAAS)(ZDXM2303 and YBXM2415)the Natural Science Foundation of Hebei Province,China(C2022204205)the Agricultural Science and Technology Innovation Program of CAAS。
文摘Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton varieties with heightened resistance to VW stands out as one of the most efficacious protective measures.In this study,we successfully generated two stable transgenic lines of cotton(Gossypium hirsutum L.),VdThitRNAi-1 and VdThit-RNAi-2,using host-induced gene silencing(HIGS)technology to introduce double-stranded RNA(dsRNA)targeting the thiamine transporter protein gene(VdThit).Southern blot analysis confirmed the presence of a single-copy insertion in each line.Microscopic examination showed marked reductions in the colonization and spread of Vd-mCherry in the roots of VdThit-RNAi cotton compared to wild type(WT).The corresponding disease index and fungal biomass of VdThit-RNAi-1/2 also exhibited significant reductions.Real-time quantitative PCR(qRT-PCR)analysis demonstrated a substantial inhibition of VdThit expression following prolonged inoculation of VdThit-RNAi cotton.Small RNA sequencing(sRNA-Seq)analysis revealed the generation of a substantial number of VdThit-specific siRNAs in the VdThit-RNAi transgenic lines.Additionally,the silencing of VdThit by the siVdThit produced by VdThit-RNAi-1/2 resulted in the elevated expression of multiple genes involved in the thiamine biosynthesis pathway in Vd.Under field conditions,VdThit-RNAi transgenic cotton exhibited significantly enhanced disease resistance and yield compared with WT.In summary,our findings underscore the efficacy of HIGS targeting VdThit in restraining the infection and spread of Vd in cotton,thereby potentially enabling the development of cotton breeding as a promising strategy for managing VW.
文摘Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants that contain RING-like zinc finger domain and are associated with the regulation of several physiological and biochemical processes.They also play vital roles in plant growth and development such as root formation,leaf development,floral development,hormone biosynthesis,signal transduction,and biotic and abiotic stress responses.Nevertheless,the SRS gene family was not reported in sesame yet.In this study,identification,molecular characterization,phylogenetic relationship,cis-acting regulatory elements,protein-protein interaction,syntenic relationship,duplication events and expression pattern of SRS genes were analyzed in S.indicum.We identified total six SiSRS genes on seven different linkage groups in the S.indicum genome by comparing with the other species,including the model plant Arabidopsis thaliana.The SiSRS genes showed variation in their structure like2–5 exons and 1–4 introns.Like other species,SiSRS proteins also contained‘RING-like zinc finger'and‘LRP1'domains.Then,the SiSRS genes were clustered into subclasses via phylogenetic analysis with proteins of S.indicum,A.thaliana,and some other plant species.The cis-acting regulatory elements analysis revealed that the promoter region of SiSRS4(SIN_1011561)showed the highest 13 and 16 elements for light-and phytohormone-responses whereas,SiSRS1(SIN_1015187)showed the highest 15 elements for stress-response.The ABREs,or ABA-responsive elements,were found in a maximum of 8 copies in the SiSRS3(SIN 1009100).Moreover,the available RNA-seq based expression of SiSRS genes revealed variation in expression patterns between stress-treated and non-treated samples,especially in drought and salinity conditions in.S.indicum.Two SiSRS genes like SiSRS1(SIN_1015187)and SiSRS5(SIN_1021065),also exhibited variable expression patterns between control vs PEG-treated sesame root samples and three SiSRS genes,including SiSRS1(SIN_1015187),SiSRS2(SIN_1003328)and SiSRS5(SIN_1021065)were responsive to salinity treatments.The present outcomes will encourage more research into the gene expression and functionality analysis of SiSRS genes in S.indicum and other related species.
基金Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0308.
文摘BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.
基金supported by the State Key Laboratory of Aridland Crop Science,Gansu Agricultural University,China(GSCS-2019-10)the National Natural Science Foundation of China(31801414 and 32260478)+2 种基金the Gansu Province Science and Technology Program,China(20JR10RA531)the Natural Science Foundation of Xinjiang Uygur Autonomous Region,China(2022D01E103)the Education Technology Innovation Project of Gansu Province,China(2022QB-076)。
文摘Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses.