Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on ho...Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.展开更多
Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research a...Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research area.However,the transcriptional regulatory mechanisms underlying monoterpenoid synthesis in Z.bungeanum remain unclear,hindering these breeding efforts.In this study,RNA sequencing,gas chromatography–mass spectrometry,and other molecular biology techniques were used to identify the underlying transcriptional regulation mechanisms.Two transcription factors,ZbbHLH2 and ZbERF6,were identified as key regulators of monoterpenoid synthesis in Z.bungeanum that upregulate various monoterpenoid synthesis-associated genes and are novel transcriptional activators of ZbIDI,which encodes the rate-limiting enzyme in plant monoterpenoid synthesis.Functional analysis revealed that the expression of three genes[1]modulates monoterpenoid accumulation in Z.bungeanum peel.These findings provide novel insights into the metabolic regulatory network of monoterpenoid synthesis in Z.bungeanum peel,offer potential strategies for the biofortification of specific monoterpenoids,and will promote the development of Z.bungeanum germplasm for targeted breeding and quality improvement.展开更多
Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antiox...Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antioxidant properties;however,their molecular mechanisms of enzymatic and transcriptional modulation remain unclear.This study aimed to investigate,through an exploratory in silico approach,the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control.Methods:A rational selection of antioxidant,pro-oxidant,and transcriptional targets was performed.Ligands were optimized at the DFT level(M05-2X/6-311+G(d,p))and docked to OS related enzymes.Docking results were analyzed using polygenic antioxidant indices(PAOX)and a similarity interaction index(SSI).Molecular dynamics simulations of selected complexes provided additional insight into potential ligand-protein interaction mechanisms.Results:In silico analyses revealed that N1-acetyl-5-methoxykynuramine(AMK),N1-acetyl-N2-formyl-5-methoxykynuramine(AFMK),and 3-hydroxymelatonin(3OH-M)could partially inhibit pro-oxidant enzymes such as neuronal nitric oxide synthase(nNOS),5-lipoxygenase(5-LOX),thioredoxin reductase(TrxR),and nicotinamide adenine dinucleotide phosphate oxidase(NOX5).The N-(2-(2-acetyl-6,7-dihydroxy-1H-indol-3-yl)ethyl)acetamide(IIcD)and N-(2-(6-hydroxy-7-mercapto-5-methoxy-1H-indol)ethyl)acetamide(dM38)derivatives could potentially stabilize superoxide dismutase(SOD1)and catalase(CAT)enzymes,respectively.Finally,AFMK and dM38 showed consistent interactions with transcriptional regulators,particularly peroxisome proliferator-activated receptor alpha(PPARα)and Kelchlike ECH-associated protein 1(KEAP1).Conclusion:These studies about melatonin-related compounds support a multifactorial profile of redox modulation and provide mechanistic hypotheses for future experimental validation.Among these approaches,the interaction-similarity index is introduced as a novel tool to facilitate the identification of promising redox-active candidates.展开更多
Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and it...Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and its red sport cultivar‘Nanhong'pear.The results showed that‘Nanhong'pear had significantly higher anthocyanin and flavonol contents.Additionally,transcriptomic analysis showed that there were significant differences in the expression of genes involved in phenylpropanoid and flavonoid biosynthesis pathways between the two cultivars,with PuGSTF12 being the most upregulated gene in the‘Nanhong'cultivar.Further analysis identified a novel MYB transcription factor(PuMYB93),and its silencing repressed PuGSTF12 expression and anthocyanin accumulation,suggesting it plays an essential role in the regulation of anthocyanin biosynthesis.Moreover,yeast one-hybrid analysis,electrophoretic mobility shift assay,andβ-glucuronidase assay indicated that PuMYB93 can directly bind to the PuGSTF12 promoter to positively regulate its expression.Additionally,PuGSTF12 silencing suppressed the coloration of PuMYB93-OE peels,suggesting that PuGSTF12 act downstream of PuMYB93.Overall,the findings of this study show that PuMYB93 promotes anthocyanin transport in pears by regulating PuGSTF12 expression to further enhance anthocyanin accumulation.展开更多
Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the reg...Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.展开更多
Anthocyanins are the main pigments in ripe strawberry fruits.FaMYB10 and abscisic acid(ABA)are the two major regulators of anthocyanin biosynthesis in the maturation process of strawberry fruits.However,the transcript...Anthocyanins are the main pigments in ripe strawberry fruits.FaMYB10 and abscisic acid(ABA)are the two major regulators of anthocyanin biosynthesis in the maturation process of strawberry fruits.However,the transcriptional regulation of FaMYB10,ABA biosynthesis,and anthocyanin accumulation in strawberry(Fragaria×ananassa)remain largely unknown.Here,a yeast one-hybrid screen using the FaMYB10 promoter identified a class B MADS-domain transcription factor,FaMADS6 in strawberry.FaMADS6 exhibited high expression at the early developmental stage but was hardly detected during maturation of strawberry fruit,a pattern opposite to accumulation of anthocyanins.Transcriptional upregulation of FaMADS6 repressed anthocyanin accumulation and expression of FaMYB10 and the anthocyanin biosynthetic genes,FaCHS,FaCHI,FaF3H,FaANS,and FaUFGT.In contrast,downregulation of FaMADS6 promoted the expression of FaMYB10 and the anthocyanin biosynthetic genes.The promoters of the anthocyanin biosynthetic genes were not directly bound by FaMADS6,in contrast to FaMYB10.Analysis of the DNA binding sequences of FaMADS6 revealed that it also interacted with the promoters of FaNCED2 and FaPYR1,which are involved in the biosynthesis and perception of ABA.Overexpression of FaMADS6 significantly suppressed FaNCED2 and FaPYR1 and ABA synthesis in transgenic strawberry.Together,our findings suggest that FaMADS6 functions as a suppressor of anthocyanin accumulation by directly downregulating FaMYB10 and ABA production during strawberry fruit maturation.展开更多
Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue...Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.展开更多
Flavonoids are crucial secondary metabolites widely distributed in plants,playing vital roles in diverse biological processes.Although the flavonoid biosynthesis pathway has been extensively characterized,the transcri...Flavonoids are crucial secondary metabolites widely distributed in plants,playing vital roles in diverse biological processes.Although the flavonoid biosynthesis pathway has been extensively characterized,the transcriptional regulatory mechanisms remain poorly understood.In this study,we identify the miR166–ATHB14-LIKE module comprising the miR166 and its target gene ATHB14-LIKE as a key regulator of flavonoid biosynthesis in soybean(Glycine max).Knockdown of miR166 or overexpression of ATHB14-LIKE upregulated multiple flavonoid biosynthesis genes,leading to increased flavonoid accumulation.Conversely,miR166 overexpression suppressed these genes and reduced flavonoid levels.We further show that ATHB14-LIKE directly activates specific flavonoid biosynthesis genes by binding to their promoters.Additionally,ATHB14-LIKE forms homodimers and heterodimers with homologous proteins to regulate downstream flavonoid biosynthesis genes.Together,our findings demonstrate that the miR166–ATHB14-LIKE module controls soybean flavonoid content by coordinating the expression of key biosynthetic genes.展开更多
Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promis...Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.展开更多
Anthocyanins play a crucial role in shaping the visual appeal and nutritional quality of fruits.Previous research on anthocyanin biosynthesis in sweet cherry(Prunus avium L.)has primarily relied on single-omics approa...Anthocyanins play a crucial role in shaping the visual appeal and nutritional quality of fruits.Previous research on anthocyanin biosynthesis in sweet cherry(Prunus avium L.)has primarily relied on single-omics approaches or focused on a limited range of metabolites,leaving the regulatory mechanisms and dynamic metabolism of anthocyanins during ripening inadequately characterized.This study integrated anthocyanin-targeted metabolomics and transcriptomics to identify key anthocyanins in sweet cherry and construct a transcriptional regulatory network for anthocyanin biosynthesis.A novel bHLH transcription factor,Prunus avium bHLH transcription factor 102(PavbHLH102),was identified,and its role in regulating cyanidin levels was validated through overexpression and silencing experiments.Both in vitro and in vivo assays demonstrated that PavbHLH102 activates key anthocyanin biosynthetic genes,including PavF3H,PavDFR,and PavUFGT,thereby enhancing fruit coloration.Notably,PavF3′H upregulation significantly increased cyanidin accumulation.This study provides new insights into anthocyanin regulation in sweet cherry and offers valuable resources for improving fruit quality.展开更多
Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and pos...Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and post-transcriptional steps of gene expression.Then,after further analysis of the literature,we report evidence that,not strictly limited to neurodevelopmental effectors,such pleiotropy also applies to other transcription factors,involved in physiology and homeostasis.Furthermore,through the systematic analysis of a major public protein-protein interaction database,we gather strong evidence that the involvement of“canonical”transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon,characterizing hundreds of effectors.Finally,we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario.展开更多
Flower color is an essential trait in ornamental plant breeding. Lycoris longituba is a popular ornamental plant native to central eastern China. The decrease in anthocyanin accumulation causes L. longituba petal colo...Flower color is an essential trait in ornamental plant breeding. Lycoris longituba is a popular ornamental plant native to central eastern China. The decrease in anthocyanin accumulation causes L. longituba petal color fading during flower development, which considerably affects the ornamental value of L. longituba. However, mechanisms underlying anthocyanin biosynthesis inhibition during L. longituba petal development remain unclear. In this study, three LlDFR genes were confirmed to be involved in anthocyanin biosynthesis and LlDFRc exerted the strongest promoting effect on anthocyanin accumulation. According to the correlation analysis results, LlbHLH12 exhibited the strongest negative correlation with LlDFRc. Quantitative real-time PCR analysis showed that LlbHLH12 was highly expressed during the medium bud and full bloom stages of flower development. LlbHLH12 was identified as a member of subgroup XII of bHLH transcription factor family. Subcellular localization and transcriptional activation ability assay revealed that LlbHLH12 was located in the nucleus without transcriptional activation activity. Overexpression of LlbHLH12 in Nicotiana tabacum and L. longituba inhibited anthocyanin accumulation by suppressing the expression of anthocyanin biosynthetic pathway genes. Furthermore, yeast one-hybrid, dual-luciferase, and β-glucuronidase activity assays showed that LlbHLH12 directly bound to the promoters of LlPAL and LlDFRc and suppressed their expression to inhibit anthocyanin biosynthesis. Overall, our study identified a novel bHLH repressor negatively regulating anthocyanin biosynthesis and provided new insights into the molecular mechanisms underlying color fading in L. longituba petals.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic ...The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.展开更多
After spinal cord injury,programmed cell death is common.In this context,autophagy plays a crucial role in clearing cellular debris,while necroptosis exacerbates neuroinflammation and further damages neural structures...After spinal cord injury,programmed cell death is common.In this context,autophagy plays a crucial role in clearing cellular debris,while necroptosis exacerbates neuroinflammation and further damages neural structures.The neuroprotective drug davunetide has shown substantial therapeutic effects on brain diseases,but its role in treating spinal cord injury remains unclear.Therefore,the aim of this study was to investigate the effects of davunetide on cell death after spinal cord injury.To do this,we established a mouse model of spinal cord contusion and administered davunetide intranasally daily at a dose of 0.5μg/5μL.Mouse locomotor function was assessed using footprint analysis and Basso Mouse Scale scoring,while the extent of spinal cord injury was evaluated using Masson’s trichrome staining.The expression levels of proteins related to locomotor function and spinal cord injury were analyzed by Western blotting and immunofluorescence staining,and protein-protein interactions were evaluated using immunoprecipitation techniques.Our results demonstrated that davunetide not only reduced the size of the injury area but also promoted the recovery of locomotor function after spinal cord injury.Specifically,davunetide exerted its effects by enhancing autophagy and inhibiting necroptosis.Inhibition of autophagy reversed the protective effects of davunetide on necroptosis.Further investigation revealed that davunetide acted through the SIRT1-FOXO1-TFEB signaling pathway,which is key to its therapeutic effects.These findings suggest the potential of davunetide in the treatment of spinal cord injury and provide valuable insights into the underlying mechanisms.This study offers strong scientific evidence to support the development of new therapeutic strategies for spinal cord injury.展开更多
Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,w...Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats,utilizing RNA-seq,ATAC-seq,and H3 K27 ac CUT&Tag.Results A total of 3,143 differentially expressed genes(DEGs)were identified,accompanied by significant alterations in chromatin accessibility and H3 K27 ac modifications between receptive and non-receptive endometria.The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion,immune tolerance,and embryo attachment.Motif enrichment and transcription factor(TF)footprinting analyses identified members of the FOS/JUN,SOX,HNF1,CEBP,and BATF families as candidate regulators,implicating downstream genes involved in ERE establishment,including SPP1,FOXO1,KLF4/6,STAT1,IFI6,ITGB8,PLAC8,DUSP4,NR1D1,ISG15,RUFY4,and PIK3R3.In addition,numerous super-enhancers were identified,indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium.Integration of multi-omics datasets revealed a strong correlation(r>0.7)among chromatin accessibility,H3 K27 ac activation,and the expression of 172 DEGs.Furthermore,a set of hub genes(KLF6,IFI6,MCL1,SDC4,SUSD6,MAFF,and IL6R)that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.Conclusions Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation.These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.展开更多
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism...Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.展开更多
The significant variation in plant regeneration efficiency between indica and japonica rice poses a major challenge for crop improvement.However,the molecular basis for this divergence remains largely unclear.In this ...The significant variation in plant regeneration efficiency between indica and japonica rice poses a major challenge for crop improvement.However,the molecular basis for this divergence remains largely unclear.In this study,we investigated the role of Oryza sativa AUXIN RESPONSE FACTOR 13(OsARF13),a transcription factor involved in callus-related processes.We observed that OsARF13 expression is significantly higher in japonica rice callus than in indica rice callus.This differential expression might be associated with an allelic variation in the promoter region of OsARF13,where a deletion commonly found in indica rice corresponds to the loss of a conserved auxin-responsive element(AuxRE)motif.To functionally characterize OsARF13,we generated CRISPR/Cas9-mediated knockout mutants.These mutants exhibited a substantial reduction in callus fresh weight,demonstrating that OsARF13 is required for efficient callus induction.Transcriptome analysis of the osarf13 mutant further showed that OsARF13 influences the expression of genes involved in hormone signal transduction and stress responses.Our findings suggest that OsARF13 is a key component of the regulatory network governing callus induction and that natural variation in its promoter might provide a potential explanation for the differential regenerative capacity between japonica and indica rice subspecies.展开更多
Heat stress reduces theanine content in tea plants,but the underlying molecular mechanism remains unclear.In this study,a temperature gradient treatment(20℃,25℃,30℃,and 35℃)was performed to unveil the effect of he...Heat stress reduces theanine content in tea plants,but the underlying molecular mechanism remains unclear.In this study,a temperature gradient treatment(20℃,25℃,30℃,and 35℃)was performed to unveil the effect of heat stress on biosynthesis and accumulation of theanine.We found that heat stress induced metabolic changes,characterized by decreased theanine content and increased catechin levels.In addition,heat stress up-regulated the expression of the class B heat shock transcription factor gene CsHSFB2c,while significantly suppressing the transcription of key theanine biosynthetic genes CsTS1 and CsGS1.Functional studies showed that silencing CsHSFB2c increased theanine content,while its overexpression significantly decreased theanine levels.Consistent with these changes,silencing CsHSFB2c upregulated the expression of CsTS1 and CsGS1,while overexpression of CsHSFB2c downregulated their expression.Yeast one-hybrid(Y1H)and dual-luciferase reporter gene(Dual-LUC)assays showed that CsHSFB2c directly binds to the promoters of CsTS1 and CsGS1 and inhibits their expression.These results demonstrate that CsHSFB2c mediates heat-induced suppression of theanine biosynthesis by directly inhibiting the expression of CsTS1 and CsGS1.This study provides a theoretical basis for improving the heat resistance and quality of tea plants via molecular breeding.展开更多
Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimeriz...Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).展开更多
基金supported by the National Natural Science Foundation of China (81672028 and 81371788)。
文摘Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.
基金supported by the National Natural Science Foundation of China(31872706)the National Key Research and Development Program of China(2019 YFD1000603).
文摘Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research area.However,the transcriptional regulatory mechanisms underlying monoterpenoid synthesis in Z.bungeanum remain unclear,hindering these breeding efforts.In this study,RNA sequencing,gas chromatography–mass spectrometry,and other molecular biology techniques were used to identify the underlying transcriptional regulation mechanisms.Two transcription factors,ZbbHLH2 and ZbERF6,were identified as key regulators of monoterpenoid synthesis in Z.bungeanum that upregulate various monoterpenoid synthesis-associated genes and are novel transcriptional activators of ZbIDI,which encodes the rate-limiting enzyme in plant monoterpenoid synthesis.Functional analysis revealed that the expression of three genes[1]modulates monoterpenoid accumulation in Z.bungeanum peel.These findings provide novel insights into the metabolic regulatory network of monoterpenoid synthesis in Z.bungeanum peel,offer potential strategies for the biofortification of specific monoterpenoids,and will promote the development of Z.bungeanum germplasm for targeted breeding and quality improvement.
基金supported by the SECIHTI project Ciencia Basica y de Frontera(No.CBF2023-2024-1141)https://secihti.mx/(accessed on 01 August 2025).
文摘Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antioxidant properties;however,their molecular mechanisms of enzymatic and transcriptional modulation remain unclear.This study aimed to investigate,through an exploratory in silico approach,the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control.Methods:A rational selection of antioxidant,pro-oxidant,and transcriptional targets was performed.Ligands were optimized at the DFT level(M05-2X/6-311+G(d,p))and docked to OS related enzymes.Docking results were analyzed using polygenic antioxidant indices(PAOX)and a similarity interaction index(SSI).Molecular dynamics simulations of selected complexes provided additional insight into potential ligand-protein interaction mechanisms.Results:In silico analyses revealed that N1-acetyl-5-methoxykynuramine(AMK),N1-acetyl-N2-formyl-5-methoxykynuramine(AFMK),and 3-hydroxymelatonin(3OH-M)could partially inhibit pro-oxidant enzymes such as neuronal nitric oxide synthase(nNOS),5-lipoxygenase(5-LOX),thioredoxin reductase(TrxR),and nicotinamide adenine dinucleotide phosphate oxidase(NOX5).The N-(2-(2-acetyl-6,7-dihydroxy-1H-indol-3-yl)ethyl)acetamide(IIcD)and N-(2-(6-hydroxy-7-mercapto-5-methoxy-1H-indol)ethyl)acetamide(dM38)derivatives could potentially stabilize superoxide dismutase(SOD1)and catalase(CAT)enzymes,respectively.Finally,AFMK and dM38 showed consistent interactions with transcriptional regulators,particularly peroxisome proliferator-activated receptor alpha(PPARα)and Kelchlike ECH-associated protein 1(KEAP1).Conclusion:These studies about melatonin-related compounds support a multifactorial profile of redox modulation and provide mechanistic hypotheses for future experimental validation.Among these approaches,the interaction-similarity index is introduced as a novel tool to facilitate the identification of promising redox-active candidates.
基金supported by the National Natural Science Foundation of China(32372641)the Shandong Provincial Natural Science Foundation,China(ZR2024QC143)the Liaoning Provincial Natural Science Foundation,China(2022-MS-258)。
文摘Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and its red sport cultivar‘Nanhong'pear.The results showed that‘Nanhong'pear had significantly higher anthocyanin and flavonol contents.Additionally,transcriptomic analysis showed that there were significant differences in the expression of genes involved in phenylpropanoid and flavonoid biosynthesis pathways between the two cultivars,with PuGSTF12 being the most upregulated gene in the‘Nanhong'cultivar.Further analysis identified a novel MYB transcription factor(PuMYB93),and its silencing repressed PuGSTF12 expression and anthocyanin accumulation,suggesting it plays an essential role in the regulation of anthocyanin biosynthesis.Moreover,yeast one-hybrid analysis,electrophoretic mobility shift assay,andβ-glucuronidase assay indicated that PuMYB93 can directly bind to the PuGSTF12 promoter to positively regulate its expression.Additionally,PuGSTF12 silencing suppressed the coloration of PuMYB93-OE peels,suggesting that PuGSTF12 act downstream of PuMYB93.Overall,the findings of this study show that PuMYB93 promotes anthocyanin transport in pears by regulating PuGSTF12 expression to further enhance anthocyanin accumulation.
基金supported by the China Agricultural Research System(Grant No.CARS-09)the Central Government Guiding Local Science and Technology Development Project(Grant No.YDZX2023029)the Gansu Planning Projects on Science and Technology(Grant No.23CXNJ0013).
文摘Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.
基金supported by the National Key R&D Program of China(Grant No.2022YFD1600700)Natural Science Foundation of China(Grant Nos.32372644,32472661)+1 种基金Natural Science Foundation of Universities in Anhui Province,China(Grant Nos.2022AH050931,2023AH051043)Anhui Provincial Natural Science Foundation,China(Grant No.2108085MC105).
文摘Anthocyanins are the main pigments in ripe strawberry fruits.FaMYB10 and abscisic acid(ABA)are the two major regulators of anthocyanin biosynthesis in the maturation process of strawberry fruits.However,the transcriptional regulation of FaMYB10,ABA biosynthesis,and anthocyanin accumulation in strawberry(Fragaria×ananassa)remain largely unknown.Here,a yeast one-hybrid screen using the FaMYB10 promoter identified a class B MADS-domain transcription factor,FaMADS6 in strawberry.FaMADS6 exhibited high expression at the early developmental stage but was hardly detected during maturation of strawberry fruit,a pattern opposite to accumulation of anthocyanins.Transcriptional upregulation of FaMADS6 repressed anthocyanin accumulation and expression of FaMYB10 and the anthocyanin biosynthetic genes,FaCHS,FaCHI,FaF3H,FaANS,and FaUFGT.In contrast,downregulation of FaMADS6 promoted the expression of FaMYB10 and the anthocyanin biosynthetic genes.The promoters of the anthocyanin biosynthetic genes were not directly bound by FaMADS6,in contrast to FaMYB10.Analysis of the DNA binding sequences of FaMADS6 revealed that it also interacted with the promoters of FaNCED2 and FaPYR1,which are involved in the biosynthesis and perception of ABA.Overexpression of FaMADS6 significantly suppressed FaNCED2 and FaPYR1 and ABA synthesis in transgenic strawberry.Together,our findings suggest that FaMADS6 functions as a suppressor of anthocyanin accumulation by directly downregulating FaMYB10 and ABA production during strawberry fruit maturation.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)[(2024)648]the Program of China National Tobacco Corporation(110202101032(JY-09),110202201003(JY-03))+2 种基金the Program of Guizhou Branch of China National Tobacco Corporation(2023XM02,2022XM05 and 2024XM01)the Qiankehe Platform Project(ZSYS[2025]028)the Program of China National Tobacco Corporation(110202102034).
文摘Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.
基金the Projects of Science and Technology of Shanghai(22N11900400)Key Projects of Beijing Institute of Life Science and Technology(2024400CB0050)+1 种基金National Natural Science Foundation of China(32488102)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24030303)。
文摘Flavonoids are crucial secondary metabolites widely distributed in plants,playing vital roles in diverse biological processes.Although the flavonoid biosynthesis pathway has been extensively characterized,the transcriptional regulatory mechanisms remain poorly understood.In this study,we identify the miR166–ATHB14-LIKE module comprising the miR166 and its target gene ATHB14-LIKE as a key regulator of flavonoid biosynthesis in soybean(Glycine max).Knockdown of miR166 or overexpression of ATHB14-LIKE upregulated multiple flavonoid biosynthesis genes,leading to increased flavonoid accumulation.Conversely,miR166 overexpression suppressed these genes and reduced flavonoid levels.We further show that ATHB14-LIKE directly activates specific flavonoid biosynthesis genes by binding to their promoters.Additionally,ATHB14-LIKE forms homodimers and heterodimers with homologous proteins to regulate downstream flavonoid biosynthesis genes.Together,our findings demonstrate that the miR166–ATHB14-LIKE module controls soybean flavonoid content by coordinating the expression of key biosynthetic genes.
基金supported by the National Natural Science Foundation of China(Grant Nos.32102311 and 32102338)the China Postdoctoral Science Foundation(Grant No.2021M690129).
文摘Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.
基金funding from the Natural Science Foundation of Sichuan Province,China(Grant Nos.2025ZNSFSC1100,2024NSFSC0324)the National Key Research and Development Project(Grant No.2017YFC0505104)+2 种基金the Sichuan Agricultural University Dual Support Plan Special Project(Grant No.2024ZYTS020)the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(Grant No.GZB20250863)the China Postdoctoral Science Foundation(Grant No.2025M773740).
文摘Anthocyanins play a crucial role in shaping the visual appeal and nutritional quality of fruits.Previous research on anthocyanin biosynthesis in sweet cherry(Prunus avium L.)has primarily relied on single-omics approaches or focused on a limited range of metabolites,leaving the regulatory mechanisms and dynamic metabolism of anthocyanins during ripening inadequately characterized.This study integrated anthocyanin-targeted metabolomics and transcriptomics to identify key anthocyanins in sweet cherry and construct a transcriptional regulatory network for anthocyanin biosynthesis.A novel bHLH transcription factor,Prunus avium bHLH transcription factor 102(PavbHLH102),was identified,and its role in regulating cyanidin levels was validated through overexpression and silencing experiments.Both in vitro and in vivo assays demonstrated that PavbHLH102 activates key anthocyanin biosynthetic genes,including PavF3H,PavDFR,and PavUFGT,thereby enhancing fruit coloration.Notably,PavF3′H upregulation significantly increased cyanidin accumulation.This study provides new insights into anthocyanin regulation in sweet cherry and offers valuable resources for improving fruit quality.
基金supported by SISSA(intramural funding to AM)International FOXG1 Research Foundation(Grant to AM)+1 种基金Italian Ministery of University and Research(Grant PRIN222022M95RC7 to AM)Fondazione Telethon(Grant GMR22T2018 to AM).
文摘Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and post-transcriptional steps of gene expression.Then,after further analysis of the literature,we report evidence that,not strictly limited to neurodevelopmental effectors,such pleiotropy also applies to other transcription factors,involved in physiology and homeostasis.Furthermore,through the systematic analysis of a major public protein-protein interaction database,we gather strong evidence that the involvement of“canonical”transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon,characterizing hundreds of effectors.Finally,we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario.
基金supported by the National Natural Science Foundation of China(Grant Nos.31870695,32071828)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Flower color is an essential trait in ornamental plant breeding. Lycoris longituba is a popular ornamental plant native to central eastern China. The decrease in anthocyanin accumulation causes L. longituba petal color fading during flower development, which considerably affects the ornamental value of L. longituba. However, mechanisms underlying anthocyanin biosynthesis inhibition during L. longituba petal development remain unclear. In this study, three LlDFR genes were confirmed to be involved in anthocyanin biosynthesis and LlDFRc exerted the strongest promoting effect on anthocyanin accumulation. According to the correlation analysis results, LlbHLH12 exhibited the strongest negative correlation with LlDFRc. Quantitative real-time PCR analysis showed that LlbHLH12 was highly expressed during the medium bud and full bloom stages of flower development. LlbHLH12 was identified as a member of subgroup XII of bHLH transcription factor family. Subcellular localization and transcriptional activation ability assay revealed that LlbHLH12 was located in the nucleus without transcriptional activation activity. Overexpression of LlbHLH12 in Nicotiana tabacum and L. longituba inhibited anthocyanin accumulation by suppressing the expression of anthocyanin biosynthetic pathway genes. Furthermore, yeast one-hybrid, dual-luciferase, and β-glucuronidase activity assays showed that LlbHLH12 directly bound to the promoters of LlPAL and LlDFRc and suppressed their expression to inhibit anthocyanin biosynthesis. Overall, our study identified a novel bHLH repressor negatively regulating anthocyanin biosynthesis and provided new insights into the molecular mechanisms underlying color fading in L. longituba petals.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
基金supported by grants from Shanghai Agriculture Applied Technology Development Program(Grant No.2022-02-08-00-12-F01109)the National Natural Science Foundation of China(Grant No.32272721).
文摘The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.
基金supported by the Natural Science Foundation of Zhejiang Province,No.LY21H060009(to WN)National Natural Science Foundation of China,Nos.82072192 and 82372540(to KZ)+2 种基金Medical and Health Technology Plan Project of Zhejiang Province,No.2024KY155(to KZ)Natural Science Foundation of Ningbo,No.2023J256(to KZ)Science and Technology Bureau Foundation of Wenzhou,No.Y20220211(to CW).
文摘After spinal cord injury,programmed cell death is common.In this context,autophagy plays a crucial role in clearing cellular debris,while necroptosis exacerbates neuroinflammation and further damages neural structures.The neuroprotective drug davunetide has shown substantial therapeutic effects on brain diseases,but its role in treating spinal cord injury remains unclear.Therefore,the aim of this study was to investigate the effects of davunetide on cell death after spinal cord injury.To do this,we established a mouse model of spinal cord contusion and administered davunetide intranasally daily at a dose of 0.5μg/5μL.Mouse locomotor function was assessed using footprint analysis and Basso Mouse Scale scoring,while the extent of spinal cord injury was evaluated using Masson’s trichrome staining.The expression levels of proteins related to locomotor function and spinal cord injury were analyzed by Western blotting and immunofluorescence staining,and protein-protein interactions were evaluated using immunoprecipitation techniques.Our results demonstrated that davunetide not only reduced the size of the injury area but also promoted the recovery of locomotor function after spinal cord injury.Specifically,davunetide exerted its effects by enhancing autophagy and inhibiting necroptosis.Inhibition of autophagy reversed the protective effects of davunetide on necroptosis.Further investigation revealed that davunetide acted through the SIRT1-FOXO1-TFEB signaling pathway,which is key to its therapeutic effects.These findings suggest the potential of davunetide in the treatment of spinal cord injury and provide valuable insights into the underlying mechanisms.This study offers strong scientific evidence to support the development of new therapeutic strategies for spinal cord injury.
基金financially supported by the National Natural Science Foundation of China(No.32502862)the Collection,Utilization and Innovation of Animal Resources by Research Institutes and Enterprises of Chongqing(No.Cqnyncwkqlhtxm)+1 种基金the Chongqing Modern Agricultural Industry Technology System(CQMAITS202513)the Key Project of Chongqing Technology Innovation and Application Development Special Program(CTSB2025TIAD-KPX0079)。
文摘Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats,utilizing RNA-seq,ATAC-seq,and H3 K27 ac CUT&Tag.Results A total of 3,143 differentially expressed genes(DEGs)were identified,accompanied by significant alterations in chromatin accessibility and H3 K27 ac modifications between receptive and non-receptive endometria.The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion,immune tolerance,and embryo attachment.Motif enrichment and transcription factor(TF)footprinting analyses identified members of the FOS/JUN,SOX,HNF1,CEBP,and BATF families as candidate regulators,implicating downstream genes involved in ERE establishment,including SPP1,FOXO1,KLF4/6,STAT1,IFI6,ITGB8,PLAC8,DUSP4,NR1D1,ISG15,RUFY4,and PIK3R3.In addition,numerous super-enhancers were identified,indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium.Integration of multi-omics datasets revealed a strong correlation(r>0.7)among chromatin accessibility,H3 K27 ac activation,and the expression of 172 DEGs.Furthermore,a set of hub genes(KLF6,IFI6,MCL1,SDC4,SUSD6,MAFF,and IL6R)that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.Conclusions Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation.These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.
基金supported by Hebei Natural Science Foundation(H2024206476)Medical Science Research Project of Hebei(20240101).
文摘Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.
基金supported by the National Natural Science Foundation of China(Grant Nos.32201834 and 32201814)the Hainan Provincial Natural Science Foundation of China(Grant No.324RC530)+1 种基金the Hainan Provincial‘Nanhai NewStar’Science and Technology Innovation Platform Project,China(Grant No.NHXXRCXM-202362)the Research Startup Funding from Hainan Institute of Zhejiang University,China(Grant No.0201-6602-A12202).
文摘The significant variation in plant regeneration efficiency between indica and japonica rice poses a major challenge for crop improvement.However,the molecular basis for this divergence remains largely unclear.In this study,we investigated the role of Oryza sativa AUXIN RESPONSE FACTOR 13(OsARF13),a transcription factor involved in callus-related processes.We observed that OsARF13 expression is significantly higher in japonica rice callus than in indica rice callus.This differential expression might be associated with an allelic variation in the promoter region of OsARF13,where a deletion commonly found in indica rice corresponds to the loss of a conserved auxin-responsive element(AuxRE)motif.To functionally characterize OsARF13,we generated CRISPR/Cas9-mediated knockout mutants.These mutants exhibited a substantial reduction in callus fresh weight,demonstrating that OsARF13 is required for efficient callus induction.Transcriptome analysis of the osarf13 mutant further showed that OsARF13 influences the expression of genes involved in hormone signal transduction and stress responses.Our findings suggest that OsARF13 is a key component of the regulatory network governing callus induction and that natural variation in its promoter might provide a potential explanation for the differential regenerative capacity between japonica and indica rice subspecies.
基金supported by the Major Project of Guizhou Provincial Science and Technology Program,China([2024]027)the High-Level Innovative Talents Project of Guizhou Province,China(GCC[2023]014)+1 种基金the Guizhou Provincial Tea Industry Technology System,China(GZCYCYJSTX-03)the Science and Technology Project of China Huaneng Group(HNKJ2022-H135)。
文摘Heat stress reduces theanine content in tea plants,but the underlying molecular mechanism remains unclear.In this study,a temperature gradient treatment(20℃,25℃,30℃,and 35℃)was performed to unveil the effect of heat stress on biosynthesis and accumulation of theanine.We found that heat stress induced metabolic changes,characterized by decreased theanine content and increased catechin levels.In addition,heat stress up-regulated the expression of the class B heat shock transcription factor gene CsHSFB2c,while significantly suppressing the transcription of key theanine biosynthetic genes CsTS1 and CsGS1.Functional studies showed that silencing CsHSFB2c increased theanine content,while its overexpression significantly decreased theanine levels.Consistent with these changes,silencing CsHSFB2c upregulated the expression of CsTS1 and CsGS1,while overexpression of CsHSFB2c downregulated their expression.Yeast one-hybrid(Y1H)and dual-luciferase reporter gene(Dual-LUC)assays showed that CsHSFB2c directly binds to the promoters of CsTS1 and CsGS1 and inhibits their expression.These results demonstrate that CsHSFB2c mediates heat-induced suppression of theanine biosynthesis by directly inhibiting the expression of CsTS1 and CsGS1.This study provides a theoretical basis for improving the heat resistance and quality of tea plants via molecular breeding.
文摘Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).
