A variety of endogenous hormone signals,developmental cues,and environmental stressors can trigger and promote leaf lettuce bolting.One such factor is gibberellin(GA),which has been linked to bolting.However,the signa...A variety of endogenous hormone signals,developmental cues,and environmental stressors can trigger and promote leaf lettuce bolting.One such factor is gibberellin(GA),which has been linked to bolting.However,the signaling pathways and the mechanisms that regulate the process have not been discussed in full detail.To clarify the potential role of GAs in leaf lettuce,significant enrichment of GA pathway genes was found by RNA-seq,among which the LsRGL1 gene was considered significant.Upon overexpression of LsRGL1,a noticeable inhibition of leaf lettuce bolting was observed,whereas its knockdown by RNA interference led to an increase in bolting.In situ hybridization analysis indicated a significant accumulation of LsRGL1 in the stem tip cells of overexpressing plants.Leaf lettuce plants stably expressing LsRGL1 were examined concerning differentially expressed genes through RNA-seq analysis,and the data indicated enhanced enrichment of these genes in the‘plant hormone signal transduction’and‘phenylpropanoid biosynthesis’pathways.Additionally,significant changes in LsWRKY70 gene expression were identified in COG(Clusters of Orthologous Groups)functional classification.The results of yeast one-hybrid,β-glucuronidase(GUS),and biolayer interferometry(BLI)experiments showed that LsRGL1 proteins directly bind to the LsWRKY70 promoter.Silencing LsWRKY70 by virus-induced gene silencing(VIGS)can delay bolting,regulate the expression of endogenous hormones,abscisic acid(ABA)-linked genes,and flowering genes,and improve the nutritional quality of leaf lettuce.These results strongly associate the positive regulation of bolting with LsWRKY70 by identifying its vital functions in the GA-mediated signaling pathway.The data obtained in this research are invaluable for further experiments concerning the development and growth of leaf lettuce.展开更多
High temperature stress on different varieties of lettuce seedlings in MDA, proline and soluble sugar content were studied. The results were as follows : With the stress temperature, varieties of leaf lettuce seedling...High temperature stress on different varieties of lettuce seedlings in MDA, proline and soluble sugar content were studied. The results were as follows : With the stress temperature, varieties of leaf lettuce seedlings in the MDA, proline and soluble sugar content gradually increased;Different varieties had the most significant difference in 38/33℃(d/n). The increase of heat-resistant varieties on proline and soluble sugar content was quick and high, while its increase in MDA content was slow and small.展开更多
Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors.Combined immunotherapy and chemotherapy has been explore...Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors.Combined immunotherapy and chemotherapy has been explored against tumor;however,the combination remains controversial.This study aimed to investigate the tumor immune microenvironment(TIME)and the effects of platinum-based neoadjuvant chemotherapy(NACT)in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.Methods Multiplex immunohistochemistry(IHC)with 11 markers(cluster of differentiation[CD]3,CD8,CD4,CD11c,CD68,forkhead box P3[Foxp3],programmed cell death 1[PD-1],programmed cell death 1 ligand 1[PD-L1],indoleamine 2,3-dioxygenase[IDO],cyclin-dependent kinase inhibitor 2A[p16],and cytokeratin[CK])was performed to evaluate TIME from 108 matched pre-and post-NACT cervical cancer samples.The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing(RNA-seq)from four paired samples and subsequently verified in 41 samples using IHC.Results The infiltration rate of the CD8^(+)T cells in treatment-naive cervical cancer was 0.73%,and those of Foxp3^(+)regulatory T cells(Tregs)and IDO^(+)cells were 0.87%and 17.15%,respectively.Moreover,immunoreactive T cells,dendritic cells,and macrophages were more in the stromal than the intratumor region.NACT increased dendritic,CD3^(+)T,CD8^(+)T,and CD4^(+)T cells and decreased Tregs.The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders.Non-responders primarily showed decreased Tregs and no increase in CD8^(+)T or dendritic cell infiltration.Furthermore,dendritic cells interacted more closely with CD3^(+)T cells after NACT,an effect primarily observed in responders.RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex(MHC)I and MHC II after chemotherapy,validated using IHC.Conclusions NACT can reduce Tregs,and when tumor cells are effectively killed,antigen presentation is enhanced,subsequently activating antitumor immunity finitely.Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.展开更多
As a globally popular leafy vegetable and a representative plant of the Asteraceae family,lettuce has great economic and academic significance.In the last decade,high-throughput sequencing,phenotyping,and other multi-...As a globally popular leafy vegetable and a representative plant of the Asteraceae family,lettuce has great economic and academic significance.In the last decade,high-throughput sequencing,phenotyping,and other multi-omics data in lettuce have accumulated on a large scale,thus increasing the demand for an integrative lettuce database.Here,we report the establishment of a comprehensive lettuce database,LettuceGDB(https://www.lettucegdb.com/).As an omics data hub,the current LettuceGDB includes two reference genomes with detailed annotations;re-sequencing data from over 1000 lettuce varieties;a collection of more than 1300 worldwide germplasms and millions of accompanying phenotypic records obtained with manual and cutting-edge phenomics technologies;re-analyses of 256 RNA sequencing datasets;a complete miRNAome;extensive metabolite information for representative varieties and wild relatives;epigenetic data on the genome-wide chromatin accessibility landscape;and various lettuce research papers published in the last decade.Five hierarchically accessible functions(Genome,Genotype,Germplasm,Phenotype,and O-Omics)have been developed with a user-friendly interface to enable convenient data access.Eight built-in tools(Assembly Converter,Search Gene,BLAST,JBrowse,Primer Design,Gene Annotation,Tissue Expression,Literature,and Data)are available for data downloading and browsing,functional gene exploration,and experimental practice.A community forum is also available for information sharing,and a summary of current research progress on different aspects of lettuce is included.We believe that LettuceGDB can be a comprehensive functional database amenable to data mining and database-driven exploration,useful for both scientific research and lettuce breeding.展开更多
基金The Beijing Joint Research Program for Germplasm Innovation and NewVariety Breeding(G20220628003)The Beijing Natural Science Foundation Program(22JF0014)The National Natural Science Foundation of China(3177110780)all contributed financially to the present project.
文摘A variety of endogenous hormone signals,developmental cues,and environmental stressors can trigger and promote leaf lettuce bolting.One such factor is gibberellin(GA),which has been linked to bolting.However,the signaling pathways and the mechanisms that regulate the process have not been discussed in full detail.To clarify the potential role of GAs in leaf lettuce,significant enrichment of GA pathway genes was found by RNA-seq,among which the LsRGL1 gene was considered significant.Upon overexpression of LsRGL1,a noticeable inhibition of leaf lettuce bolting was observed,whereas its knockdown by RNA interference led to an increase in bolting.In situ hybridization analysis indicated a significant accumulation of LsRGL1 in the stem tip cells of overexpressing plants.Leaf lettuce plants stably expressing LsRGL1 were examined concerning differentially expressed genes through RNA-seq analysis,and the data indicated enhanced enrichment of these genes in the‘plant hormone signal transduction’and‘phenylpropanoid biosynthesis’pathways.Additionally,significant changes in LsWRKY70 gene expression were identified in COG(Clusters of Orthologous Groups)functional classification.The results of yeast one-hybrid,β-glucuronidase(GUS),and biolayer interferometry(BLI)experiments showed that LsRGL1 proteins directly bind to the LsWRKY70 promoter.Silencing LsWRKY70 by virus-induced gene silencing(VIGS)can delay bolting,regulate the expression of endogenous hormones,abscisic acid(ABA)-linked genes,and flowering genes,and improve the nutritional quality of leaf lettuce.These results strongly associate the positive regulation of bolting with LsWRKY70 by identifying its vital functions in the GA-mediated signaling pathway.The data obtained in this research are invaluable for further experiments concerning the development and growth of leaf lettuce.
文摘High temperature stress on different varieties of lettuce seedlings in MDA, proline and soluble sugar content were studied. The results were as follows : With the stress temperature, varieties of leaf lettuce seedlings in the MDA, proline and soluble sugar content gradually increased;Different varieties had the most significant difference in 38/33℃(d/n). The increase of heat-resistant varieties on proline and soluble sugar content was quick and high, while its increase in MDA content was slow and small.
基金This study was supported by the National Clinical Research Center for Obstetrics and Gynecology(No.2015BAI13B05)the National Key Technology Research and Development Program of China(Nos.2022YFC2704400,2022YFC2704403)the National Natural Science Foundation of China(No.81802896).
文摘Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors.Combined immunotherapy and chemotherapy has been explored against tumor;however,the combination remains controversial.This study aimed to investigate the tumor immune microenvironment(TIME)and the effects of platinum-based neoadjuvant chemotherapy(NACT)in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.Methods Multiplex immunohistochemistry(IHC)with 11 markers(cluster of differentiation[CD]3,CD8,CD4,CD11c,CD68,forkhead box P3[Foxp3],programmed cell death 1[PD-1],programmed cell death 1 ligand 1[PD-L1],indoleamine 2,3-dioxygenase[IDO],cyclin-dependent kinase inhibitor 2A[p16],and cytokeratin[CK])was performed to evaluate TIME from 108 matched pre-and post-NACT cervical cancer samples.The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing(RNA-seq)from four paired samples and subsequently verified in 41 samples using IHC.Results The infiltration rate of the CD8^(+)T cells in treatment-naive cervical cancer was 0.73%,and those of Foxp3^(+)regulatory T cells(Tregs)and IDO^(+)cells were 0.87%and 17.15%,respectively.Moreover,immunoreactive T cells,dendritic cells,and macrophages were more in the stromal than the intratumor region.NACT increased dendritic,CD3^(+)T,CD8^(+)T,and CD4^(+)T cells and decreased Tregs.The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders.Non-responders primarily showed decreased Tregs and no increase in CD8^(+)T or dendritic cell infiltration.Furthermore,dendritic cells interacted more closely with CD3^(+)T cells after NACT,an effect primarily observed in responders.RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex(MHC)I and MHC II after chemotherapy,validated using IHC.Conclusions NACT can reduce Tregs,and when tumor cells are effectively killed,antigen presentation is enhanced,subsequently activating antitumor immunity finitely.Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.
基金supported by the Beijing Academy of Agriculture and Forestry Sciences(KJCX201907-2 to J.W.,KJCX201917 to C.Z.,and KJCX20200204 and KJCX20220105 to X.Y.)the Beijing Postdoctoral Research Foundation(2021-ZZ-133 to B.L.)the National Natural Science Foundation of China(31621001 to X.Y.).
文摘As a globally popular leafy vegetable and a representative plant of the Asteraceae family,lettuce has great economic and academic significance.In the last decade,high-throughput sequencing,phenotyping,and other multi-omics data in lettuce have accumulated on a large scale,thus increasing the demand for an integrative lettuce database.Here,we report the establishment of a comprehensive lettuce database,LettuceGDB(https://www.lettucegdb.com/).As an omics data hub,the current LettuceGDB includes two reference genomes with detailed annotations;re-sequencing data from over 1000 lettuce varieties;a collection of more than 1300 worldwide germplasms and millions of accompanying phenotypic records obtained with manual and cutting-edge phenomics technologies;re-analyses of 256 RNA sequencing datasets;a complete miRNAome;extensive metabolite information for representative varieties and wild relatives;epigenetic data on the genome-wide chromatin accessibility landscape;and various lettuce research papers published in the last decade.Five hierarchically accessible functions(Genome,Genotype,Germplasm,Phenotype,and O-Omics)have been developed with a user-friendly interface to enable convenient data access.Eight built-in tools(Assembly Converter,Search Gene,BLAST,JBrowse,Primer Design,Gene Annotation,Tissue Expression,Literature,and Data)are available for data downloading and browsing,functional gene exploration,and experimental practice.A community forum is also available for information sharing,and a summary of current research progress on different aspects of lettuce is included.We believe that LettuceGDB can be a comprehensive functional database amenable to data mining and database-driven exploration,useful for both scientific research and lettuce breeding.