Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreati...Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.展开更多
Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive...Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.展开更多
Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The...Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The SGT3 promoter haplotype with(TA)10exhibits signifcantly higher transcriptional activity,correlating with high SGAs content,while the(TA)13haplotype is linked to low SGAs in natural germplasms.展开更多
Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression...Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.展开更多
N^(6)-Methyladenosine(m^(6)A)is the most common modification in the transcriptome of biological RNA and plays roles that include maintaining the stability and transportation of mRNA,mRNA precursor shearing,polyadenyla...N^(6)-Methyladenosine(m^(6)A)is the most common modification in the transcriptome of biological RNA and plays roles that include maintaining the stability and transportation of mRNA,mRNA precursor shearing,polyadenylation,and the initiation of translation.With the improving understanding of RNA methylation,m^(6)A modification is known to play vital roles in plant development and growth.The multi-petalization of flowering plants has high ornamental and research value in horticultural landscapes.However,the mechanism of RNA methylation in flower formation in Magnolia wufengensis,a classical multi-petalizational plant,remains unclear.This study compared and analyzed RNA m^(6)A methylation and the transcriptome in floral buds of two varieties with large differences in tepal number at the early stage of development.It was found that the degree of RNA m^(6)A methylation and relative expression levels of MawuAGL6-2,MawuPI-4,and MawuAGL9 in‘Jiaodan’with 36 tepals were significantly higher than those in‘Jiaohong’with 9 tepals during the development of floral organ primordia.Combined with quantitative real-time PCR,the expression levels of MawuAGL6-2,MawuPI-4,and MawuAGL9were positively correlated with the number of tepals.Transgenic experiments showed that MawuAGL6-1/2,and MawuPI-4 can increase the number of petals in Arabidopsis.Moreover,MawuAGL6-2 and MawuPI-4 can restore the missing petal phenotype of mutant Arabidopsis.Yeast two hybrid and yeast three hybrid indicated that MawuAGL6-2,MawuAP3-1/2,and MawuPI-4 could interact with each other under the mediation of the class E protein MawuAGL9.Based on these results,it is hypothesized that m^(6)A methylation influences the multi-petalization of Magnolia wufengensis by affecting the expression levels of MawuAGL6-2,MawuAP3-1/2,MawuPI-4,and MawuAGL9.These findings provide a better understanding of the molecular mechanisms of epigenetic modifications in flower developmental diversity.展开更多
DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expres...DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.展开更多
Urea is a major end product of nitrogen catabolism,serving as an osmolyte to regulate osmotic stress in fish exposed to varying water environments.It has been well known that urea transporters(UTs)facilitate the rapid...Urea is a major end product of nitrogen catabolism,serving as an osmolyte to regulate osmotic stress in fish exposed to varying water environments.It has been well known that urea transporters(UTs)facilitate the rapid movement of urea across cell membranes.However,researches on ut genes were predominantly focused on elasmobranchs and early developmental stages of fish.In this investigation,a total of three ut genes were identified in spotted sea bass.Phylogenetic,homology,and syntenic analyses were conducted to validate the annotation and assess the evolutionary relationships among ut genes.Both ut-a and ut-b genes have retained their evolutionary stability,demonstrating a significant level of homology between them.To gain deeper insights into the evolution of ut genes in spotted sea bass,we performed selective pressure analysis using site,branch,and branch-site models.The results suggested that positive selection likely played a significant role in shaping the evolution of the ut gene family.Furthermore,tissue-specific expression analyses revealed high expression levels of ut genes in osmoregulatory tissues such as the gill and kidney.Additionally,all three ut genes exhibited salinity-related expression patterns in gill and kidney tissues during both seawater-to-freshwater(SF)and freshwater-to-seawater(FS)adaptation.In situ hybridization results demonstrated the localization of both ut-a and ut-c mRNAs on the gill lamellae and adjacent gill filament epithelium.In summary,our study establishes a solid foundation for future research elucidating the evolutionary relationships and functional significance of ut genes during salinity acclimation in spotted sea bass and other teleost species.展开更多
Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development...Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development.In this study,71 members of the BpGST family were identified from the entire Betula platyphylla Suk.genome.Most of the members encode proteins with amino acid lengths ranging from 101 to 875 and were localized to the cytoplasm by a prediction.BpGSTs can be divided into seven subfamilies,with a majority of birch U and F subfamily members according to gene structure,conserved motifs and evolutionary analysis.GST family genes showed collinearity with 22 genes in Oryza sativa L.,and three genes in Arabidopsis thaliana;promoter cis-acting elements predicted that the GST gene family is functional in growth,hormone regulation,and abiotic stress response.Most members of the F subfamily of GST(BpGSTFs)were expressed in roots,stems,leaves,and petioles,with the most expression observed in leaves.On the basis of the expression profiles of F subfamily genes(BpGSTF1 to BpGSTF13)during salt,mannitol and ABA stress,BpGSTF proteins seem to have multiple functions depending on the type of abiotic stress;for instance,BpGSTs may function at different times during abiotic stress.This study enhances understanding of the GST gene family and provides a basis for further exploration of their function in birch.展开更多
Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyz...Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyzed the global gene expression profile of adipose-derived mesenchymal stem cells(ASCs)using microarray analysis and compared it with stromal vascular fraction(SVF)cells.Results:Microarray analysis revealed that ASCs express elevated levels of genes related to the extracellular matrix(ECM;extracellular matrix)and collagen,which are critical components of tissue remodeling and wound healing.Additionally,genes associated with cell growth,differentiation,motility,and plasticity were highly expressed.When compared to stromal vascular fraction(SVF)cells,ASCs demonstrated enrichment of genes involved in anti-inflammatory responses,immune modulation,tissue repair,cell adhesion,and migration processes.Gene Set Enrichment Analysis(GSEA;Gene Set Enrichment Analysis)showed activation of pathways related to angiogenesis,such as vascular endothelial growth factor(VEGF),Integrin,Wnt signaling pathways,transforming growth factor-beta(TGF-β),extracellular matrix(ECM),and matrix metalloproteinase(MMP),highlighting the significant angiogenic potential of ASCs.Gene Ontology(GO;Gene Ontology)analysis further linked ASCs to biological processes associated with the regulation of cell proliferation and muscle cell differentiation.Conclusion:These findings collectively underscore the suitability of adipose-derived mesenchymal stem cells(ASCs)as a promising candidate for regenerative medicine,particularly in applications involving tissue repair,immune modulation,and promotion of angiogenesis.展开更多
Background Mobile element variants(MEVs)have a significant and complex impact on genomic diversity and phe-notypic traits.However,the quantity,distribution,and relationship with gene expression and complex traits of M...Background Mobile element variants(MEVs)have a significant and complex impact on genomic diversity and phe-notypic traits.However,the quantity,distribution,and relationship with gene expression and complex traits of MEVs in the pig genome remain poorly understood.Results We constructed the most comprehensive porcine MEV library based on high-depth whole genome sequencing(WGS)data from 747 pigs across 59 breeds worldwide.This database identified a total of 147,993 poly-morphic MEVs,including 121,099 short interspersed nuclear elements(SINEs),26,053 long interspersed nuclear elements(LINEs),802 long terminal repeats(LTRs),and 39 other transposons,among which 54%are newly discovered.We found that MEVs are unevenly distributed across the genome and are strongly influenced by negative selec-tion effects.Importantly,we identified 514,530,and 584 candidate MEVs associated with population differentiation,domestication,and breed formation,respectively.For example,a significantly differentiated MEV is located in the ATRX intron between Asian and European pigs,whereas ATRX is also differentially expressed between Asian and European pigs in muscle tissue.In addition,we identified 4,169 expressed MEVs(eMEVs)significantly associated with gene expression and 6,914 splicing MEVs(sMEVs)associated with gene splicing based on RNA-seq data from 266 porcine liver tissues.These eMEVs and sMEVs explain 6.24%and 9.47%,respectively,of the observed cis-heritability and high-light the important role of MEVs in the regulation of gene expression.Finally,we provide a high-quality SNP–MEV reference haplotype panel to impute MEV genotypes from genome-wide SNPs.Notably,we identified a candidate MEV significantly associated with total teat number,demonstrating the functionality of this reference panel.Conclusions The present investigation demonstrated the importance of MEVs in pigs in terms of population diversity,gene expression and phenotypic traits,which may provide useful resources and theoretical support for pig genetics and breeding.展开更多
Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing...Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing two practical models to predict pillar stability status.For this purpose,two robust models were developed using a database including 236 case histories from seven underground hard rock mines,based on gene expression programming(GEP)and decision tree-support vector machine(DT-SVM)hybrid algorithms.The performance of the developed models was evaluated based on four common statistical criteria(sensitivity,specificity,Matthews correlation coefficient,and accuracy),receiver operating characteristic(ROC)curve,and testing data sets.The results showed that the GEP and DT-SVM models performed exceptionally well in assessing pillar stability,showing a high level of accuracy.The DT-SVM model,in particular,outperformed the GEP model(accuracy of 0.914,sensitivity of 0.842,specificity of 0.929,Matthews correlation coefficient of 0.767,and area under the ROC of 0.897 for the test data set).Furthermore,upon comparing the developed models with the previous ones,it was revealed that both models can effectively determine the condition of pillar stability with low uncertainty and acceptable accuracy.This suggests that these models could serve as dependable tools for project managers,aiding in the evaluation of pillar stability during the design and operational phases of mining projects,despite the inherent challenges in this domain.展开更多
It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we p...It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we present an analysis of the evolutionary history of a putative de novo gene,lawc,which overlaps with the conserved Trf2 gene,which encodes a general transcription factor in Drosophila melanogaster.We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region(UTR)of Trf2 and displays an extensive spatiotemporal expression pattern.One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short,highly conserved regions located in Trf2 introns.This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved genes.The observed lawc expression pattern may be due to the overlap of lawc with the 5'-UTR of Trf2.This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.展开更多
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analy...Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analysis of the OsKMP2 gene(LOC_Os02g28850)was performed using online tools such as ExPASy-ProtParam,ProtScale,CD-search,and DNAMAN software.Additionally,qRT-PCR was employed to analyze the tissue expression pattern of OsKMP2.The results showed that the molecular weight of the OsKMP2 is 118.39728 kDa,and it is a hydrophilic and unstable acidic protein.Secondary structure prediction revealed that it primarily consists ofα-helices(69.45%),random coils(25.19%),and extended strands(5.36%).The gene was expressed in various rice tissues,with the highest expression level observed in leaves.These results indicate that the OsKMP2 gene exhibits high evolutionary conservation and functional diversity in rice.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity ...This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.展开更多
Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by ...Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by clinical features like gender,age,and body mass index(BMI),each eliciting distinct biological effects.To assist exercise researchers in understanding these changes from a comprehensive perspective that includes multiple organs,diverse exercise regimens,and a range of clinical features,we developed Exercise Regulated Genes Database(ExerGeneDB),a database of exercise-regulated differential genes.Methods:ExerGeneDB aggregated publicly available exercise-related sequencing datasets and subjected them to uniform quality control and preprocessing.The data,encompassing a variety of types,were organized into a specialized database of exercise-regulated genes.Notably,Exer-GeneDB conducted differential analyses on this collected data,leveraging curated clinical information and accounting for important factors such as gender,age,and BMI.Results:ExerGeneDB has assembled 1692 samples from rats and mice as well as 4492 human samples.It contains data from various tissues and organs,such as skeletal muscle,blood,adipose tissue,intestine,heart,liver,spleen,lungs,kidneys,brain,spinal cord,bone marrow,and bones.ExerGeneDB features bulk ribonucleic acid sequencing(RNA-seq)(including non-coding RNA(ncRNA)and protein-coding RNA),microarray(including ncRNA and protein-coding RNA),and single cell RNA-seq data.Conclusion:ExerGeneDB compiles and re-analyzes exercise-related data with a focus on clinical information.This has culminated in the crea-tion of an interactive database for exercise regulation genes.The website for ExerGeneDB can be found at:https://exergenedb.com.展开更多
Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the...Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the genetic improvement of cotton.There is a strong correlation between SE and zygotic embryogenesis(ZE)in plants.Furthermore,the strategy of ectopic expression of cotton genes into the model plant Arabidopsis has been a widely accepted approach for functional study.Result Based on previous spatial transcriptomics of cotton somatic embryos,two genes,Gh HAT5 and Gh CRK29,were identified.They are highly expressed in cotyledon and epidermal cells of cotton cotyledonary embryos,respectively.In this study,Gh HAT5 and Gh CRK29 were ectopically expressed in Arabidopsis to investigate their functions.The result showed that in Arabidopsis zygotic embryos,the overexpression of Gh HAT5 promoted the development of apical embryonic upper-tier cells and embryonic cotyledon,while the overexpression of Gh CRK29 promoted the development of apical embryonic lower-tier cells and embryonic radicle.Given the similarities between somatic and zygotic embryogenesis,these findings suggest that Gh HAT5 and Gh CRK29 are involved in cotton SE.We also speculate that these genes may promote the expression of the Arabidopsis endogenous gene At SCR,which is crucial for embryonic development.Conclusion These results revealed that Gh HAT5 and Gh CRK29 regulate embryonic development and are essential in advancing our understanding of cotton SE and facilitating targeted genetic manipulation strategies to improve industrial crop traits and agricultural sustainability.展开更多
Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several ...Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.展开更多
基金supported by the Russian Science Foundation(No.22-16-00128),“Investigation of the Toxic Effect of Glyphosates on the Functional State of the Bird Intestinal Microbial Community,Their Growth and Development,and the Development of a Biological Product Based on the Glyphosate Degrading Strain”.
文摘Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.
文摘Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.
基金financially supported by the Guangdong Major Project of Basic and Applied Basic Research,China(2021B0301030004)the National Natural Science Foundation of China(32360757,U2202206 and 32361143517)the Yunnan Fundamental Research Projects,China(202201AT070037,202501AS070012)。
文摘Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The SGT3 promoter haplotype with(TA)10exhibits signifcantly higher transcriptional activity,correlating with high SGAs content,while the(TA)13haplotype is linked to low SGAs in natural germplasms.
基金supported by the National Natural Science Foundation of China(32172010)the Major Program of Guangdong Basic and Applied Basic Research(2019B030302006).
文摘Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.
基金supported by the National Natural Science Foundation of China(Grant No.31570651)。
文摘N^(6)-Methyladenosine(m^(6)A)is the most common modification in the transcriptome of biological RNA and plays roles that include maintaining the stability and transportation of mRNA,mRNA precursor shearing,polyadenylation,and the initiation of translation.With the improving understanding of RNA methylation,m^(6)A modification is known to play vital roles in plant development and growth.The multi-petalization of flowering plants has high ornamental and research value in horticultural landscapes.However,the mechanism of RNA methylation in flower formation in Magnolia wufengensis,a classical multi-petalizational plant,remains unclear.This study compared and analyzed RNA m^(6)A methylation and the transcriptome in floral buds of two varieties with large differences in tepal number at the early stage of development.It was found that the degree of RNA m^(6)A methylation and relative expression levels of MawuAGL6-2,MawuPI-4,and MawuAGL9 in‘Jiaodan’with 36 tepals were significantly higher than those in‘Jiaohong’with 9 tepals during the development of floral organ primordia.Combined with quantitative real-time PCR,the expression levels of MawuAGL6-2,MawuPI-4,and MawuAGL9were positively correlated with the number of tepals.Transgenic experiments showed that MawuAGL6-1/2,and MawuPI-4 can increase the number of petals in Arabidopsis.Moreover,MawuAGL6-2 and MawuPI-4 can restore the missing petal phenotype of mutant Arabidopsis.Yeast two hybrid and yeast three hybrid indicated that MawuAGL6-2,MawuAP3-1/2,and MawuPI-4 could interact with each other under the mediation of the class E protein MawuAGL9.Based on these results,it is hypothesized that m^(6)A methylation influences the multi-petalization of Magnolia wufengensis by affecting the expression levels of MawuAGL6-2,MawuAP3-1/2,MawuPI-4,and MawuAGL9.These findings provide a better understanding of the molecular mechanisms of epigenetic modifications in flower developmental diversity.
文摘DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.
基金supported by the National Natural Science Foundation of China(No.32072947)the China Agriculture Research System(No.CARS-47)。
文摘Urea is a major end product of nitrogen catabolism,serving as an osmolyte to regulate osmotic stress in fish exposed to varying water environments.It has been well known that urea transporters(UTs)facilitate the rapid movement of urea across cell membranes.However,researches on ut genes were predominantly focused on elasmobranchs and early developmental stages of fish.In this investigation,a total of three ut genes were identified in spotted sea bass.Phylogenetic,homology,and syntenic analyses were conducted to validate the annotation and assess the evolutionary relationships among ut genes.Both ut-a and ut-b genes have retained their evolutionary stability,demonstrating a significant level of homology between them.To gain deeper insights into the evolution of ut genes in spotted sea bass,we performed selective pressure analysis using site,branch,and branch-site models.The results suggested that positive selection likely played a significant role in shaping the evolution of the ut gene family.Furthermore,tissue-specific expression analyses revealed high expression levels of ut genes in osmoregulatory tissues such as the gill and kidney.Additionally,all three ut genes exhibited salinity-related expression patterns in gill and kidney tissues during both seawater-to-freshwater(SF)and freshwater-to-seawater(FS)adaptation.In situ hybridization results demonstrated the localization of both ut-a and ut-c mRNAs on the gill lamellae and adjacent gill filament epithelium.In summary,our study establishes a solid foundation for future research elucidating the evolutionary relationships and functional significance of ut genes during salinity acclimation in spotted sea bass and other teleost species.
基金supported by the National Key Research and Development Program of China(No.2021YFD2200304)FundamentalResearch Funds for the Central Universities(2572022DQ08)the National Natural Science Foundation of China(No32171738).
文摘Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development.In this study,71 members of the BpGST family were identified from the entire Betula platyphylla Suk.genome.Most of the members encode proteins with amino acid lengths ranging from 101 to 875 and were localized to the cytoplasm by a prediction.BpGSTs can be divided into seven subfamilies,with a majority of birch U and F subfamily members according to gene structure,conserved motifs and evolutionary analysis.GST family genes showed collinearity with 22 genes in Oryza sativa L.,and three genes in Arabidopsis thaliana;promoter cis-acting elements predicted that the GST gene family is functional in growth,hormone regulation,and abiotic stress response.Most members of the F subfamily of GST(BpGSTFs)were expressed in roots,stems,leaves,and petioles,with the most expression observed in leaves.On the basis of the expression profiles of F subfamily genes(BpGSTF1 to BpGSTF13)during salt,mannitol and ABA stress,BpGSTF proteins seem to have multiple functions depending on the type of abiotic stress;for instance,BpGSTs may function at different times during abiotic stress.This study enhances understanding of the GST gene family and provides a basis for further exploration of their function in birch.
基金supported through National Research Foundation(NRF)of Korea grants funded by the Korean Government(No.NRF-2022R1F1A1064405)the research fund of Catholic Kwandong University and Catholic Kwandong University International St.Mary’s Hospital for S.-W Kim.
文摘Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyzed the global gene expression profile of adipose-derived mesenchymal stem cells(ASCs)using microarray analysis and compared it with stromal vascular fraction(SVF)cells.Results:Microarray analysis revealed that ASCs express elevated levels of genes related to the extracellular matrix(ECM;extracellular matrix)and collagen,which are critical components of tissue remodeling and wound healing.Additionally,genes associated with cell growth,differentiation,motility,and plasticity were highly expressed.When compared to stromal vascular fraction(SVF)cells,ASCs demonstrated enrichment of genes involved in anti-inflammatory responses,immune modulation,tissue repair,cell adhesion,and migration processes.Gene Set Enrichment Analysis(GSEA;Gene Set Enrichment Analysis)showed activation of pathways related to angiogenesis,such as vascular endothelial growth factor(VEGF),Integrin,Wnt signaling pathways,transforming growth factor-beta(TGF-β),extracellular matrix(ECM),and matrix metalloproteinase(MMP),highlighting the significant angiogenic potential of ASCs.Gene Ontology(GO;Gene Ontology)analysis further linked ASCs to biological processes associated with the regulation of cell proliferation and muscle cell differentiation.Conclusion:These findings collectively underscore the suitability of adipose-derived mesenchymal stem cells(ASCs)as a promising candidate for regenerative medicine,particularly in applications involving tissue repair,immune modulation,and promotion of angiogenesis.
基金National Key Research and Development Program of China(2022YFF1000103)Postdoctoral Fellowship Program of CPSF under Grant Number GZC20240620.
文摘Background Mobile element variants(MEVs)have a significant and complex impact on genomic diversity and phe-notypic traits.However,the quantity,distribution,and relationship with gene expression and complex traits of MEVs in the pig genome remain poorly understood.Results We constructed the most comprehensive porcine MEV library based on high-depth whole genome sequencing(WGS)data from 747 pigs across 59 breeds worldwide.This database identified a total of 147,993 poly-morphic MEVs,including 121,099 short interspersed nuclear elements(SINEs),26,053 long interspersed nuclear elements(LINEs),802 long terminal repeats(LTRs),and 39 other transposons,among which 54%are newly discovered.We found that MEVs are unevenly distributed across the genome and are strongly influenced by negative selec-tion effects.Importantly,we identified 514,530,and 584 candidate MEVs associated with population differentiation,domestication,and breed formation,respectively.For example,a significantly differentiated MEV is located in the ATRX intron between Asian and European pigs,whereas ATRX is also differentially expressed between Asian and European pigs in muscle tissue.In addition,we identified 4,169 expressed MEVs(eMEVs)significantly associated with gene expression and 6,914 splicing MEVs(sMEVs)associated with gene splicing based on RNA-seq data from 266 porcine liver tissues.These eMEVs and sMEVs explain 6.24%and 9.47%,respectively,of the observed cis-heritability and high-light the important role of MEVs in the regulation of gene expression.Finally,we provide a high-quality SNP–MEV reference haplotype panel to impute MEV genotypes from genome-wide SNPs.Notably,we identified a candidate MEV significantly associated with total teat number,demonstrating the functionality of this reference panel.Conclusions The present investigation demonstrated the importance of MEVs in pigs in terms of population diversity,gene expression and phenotypic traits,which may provide useful resources and theoretical support for pig genetics and breeding.
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
文摘Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing two practical models to predict pillar stability status.For this purpose,two robust models were developed using a database including 236 case histories from seven underground hard rock mines,based on gene expression programming(GEP)and decision tree-support vector machine(DT-SVM)hybrid algorithms.The performance of the developed models was evaluated based on four common statistical criteria(sensitivity,specificity,Matthews correlation coefficient,and accuracy),receiver operating characteristic(ROC)curve,and testing data sets.The results showed that the GEP and DT-SVM models performed exceptionally well in assessing pillar stability,showing a high level of accuracy.The DT-SVM model,in particular,outperformed the GEP model(accuracy of 0.914,sensitivity of 0.842,specificity of 0.929,Matthews correlation coefficient of 0.767,and area under the ROC of 0.897 for the test data set).Furthermore,upon comparing the developed models with the previous ones,it was revealed that both models can effectively determine the condition of pillar stability with low uncertainty and acceptable accuracy.This suggests that these models could serve as dependable tools for project managers,aiding in the evaluation of pillar stability during the design and operational phases of mining projects,despite the inherent challenges in this domain.
基金funded by a grant from the Russian Science Foundation № 24-24-00354
文摘It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we present an analysis of the evolutionary history of a putative de novo gene,lawc,which overlaps with the conserved Trf2 gene,which encodes a general transcription factor in Drosophila melanogaster.We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region(UTR)of Trf2 and displays an extensive spatiotemporal expression pattern.One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short,highly conserved regions located in Trf2 introns.This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved genes.The observed lawc expression pattern may be due to the overlap of lawc with the 5'-UTR of Trf2.This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
基金Supported by College Student Innovation and Entrepreneurship Training Program(S202210553003)Hunan Provincial Education Department Outstanding Youth Research Project(23B0820).
文摘Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analysis of the OsKMP2 gene(LOC_Os02g28850)was performed using online tools such as ExPASy-ProtParam,ProtScale,CD-search,and DNAMAN software.Additionally,qRT-PCR was employed to analyze the tissue expression pattern of OsKMP2.The results showed that the molecular weight of the OsKMP2 is 118.39728 kDa,and it is a hydrophilic and unstable acidic protein.Secondary structure prediction revealed that it primarily consists ofα-helices(69.45%),random coils(25.19%),and extended strands(5.36%).The gene was expressed in various rice tissues,with the highest expression level observed in leaves.These results indicate that the OsKMP2 gene exhibits high evolutionary conservation and functional diversity in rice.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
文摘This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.
基金supported by grants from the National Natural Science Foundation of China(82225005, 82020108002 to JX,82200321 to QZ)Science and Technology Commission of ShanghaiMunicipality(23410750100,20DZ2255400,, 21XD1421300 to JX)+1 种基金the“Dawn”Program of Shanghai Educa-tion Commission(19SG34 to JX)Shanghai Sailing Program(21YF1413200 to QZ).
文摘Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by clinical features like gender,age,and body mass index(BMI),each eliciting distinct biological effects.To assist exercise researchers in understanding these changes from a comprehensive perspective that includes multiple organs,diverse exercise regimens,and a range of clinical features,we developed Exercise Regulated Genes Database(ExerGeneDB),a database of exercise-regulated differential genes.Methods:ExerGeneDB aggregated publicly available exercise-related sequencing datasets and subjected them to uniform quality control and preprocessing.The data,encompassing a variety of types,were organized into a specialized database of exercise-regulated genes.Notably,Exer-GeneDB conducted differential analyses on this collected data,leveraging curated clinical information and accounting for important factors such as gender,age,and BMI.Results:ExerGeneDB has assembled 1692 samples from rats and mice as well as 4492 human samples.It contains data from various tissues and organs,such as skeletal muscle,blood,adipose tissue,intestine,heart,liver,spleen,lungs,kidneys,brain,spinal cord,bone marrow,and bones.ExerGeneDB features bulk ribonucleic acid sequencing(RNA-seq)(including non-coding RNA(ncRNA)and protein-coding RNA),microarray(including ncRNA and protein-coding RNA),and single cell RNA-seq data.Conclusion:ExerGeneDB compiles and re-analyzes exercise-related data with a focus on clinical information.This has culminated in the crea-tion of an interactive database for exercise regulation genes.The website for ExerGeneDB can be found at:https://exergenedb.com.
基金supported by the National Key Research and Development Program of China(No.2022YFD1200300)。
文摘Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the genetic improvement of cotton.There is a strong correlation between SE and zygotic embryogenesis(ZE)in plants.Furthermore,the strategy of ectopic expression of cotton genes into the model plant Arabidopsis has been a widely accepted approach for functional study.Result Based on previous spatial transcriptomics of cotton somatic embryos,two genes,Gh HAT5 and Gh CRK29,were identified.They are highly expressed in cotyledon and epidermal cells of cotton cotyledonary embryos,respectively.In this study,Gh HAT5 and Gh CRK29 were ectopically expressed in Arabidopsis to investigate their functions.The result showed that in Arabidopsis zygotic embryos,the overexpression of Gh HAT5 promoted the development of apical embryonic upper-tier cells and embryonic cotyledon,while the overexpression of Gh CRK29 promoted the development of apical embryonic lower-tier cells and embryonic radicle.Given the similarities between somatic and zygotic embryogenesis,these findings suggest that Gh HAT5 and Gh CRK29 are involved in cotton SE.We also speculate that these genes may promote the expression of the Arabidopsis endogenous gene At SCR,which is crucial for embryonic development.Conclusion These results revealed that Gh HAT5 and Gh CRK29 regulate embryonic development and are essential in advancing our understanding of cotton SE and facilitating targeted genetic manipulation strategies to improve industrial crop traits and agricultural sustainability.
基金supported by the National Natural Science Foundation of China(Grant Nos.81872686 and 82173611)the National Key Research and Development Program of China(Grant No.2018YFC2000703)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)。
文摘Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.
