Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin ...Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood.Here,we performed a comprehensive analysis of genome resequencing,metabolome,and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN.Metabolites analysis revealed that 72.18%of sesquiterpenes was highly accumulated in HAN compared to JL.Integrated omics analysis found a DBR2-Like(DBR2L)gene may be involved in artemisinin biosynthesis.DBR2L was highly homologous with DBR2,belonged to ORR3 family,and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde.Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A.annua and were clustered into three variation types.The promoter activity of diverse variant types showed obvious differences.Furthermore,the core region(-625 to 0)of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened.Thus,the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis.The promoter variation in DBR2L affects its expression level,and thereby may result in the different yield of artemisinin in varieties of A.annua.It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A.annua,and will assist in a high yield of artemisinin in A.annua.展开更多
Erratum to:J Zhejiang Univ-Sci B(Biomed&Biotechnol)202122(9):718-732 https:/doi.org/10.1631/jzus.B2000544.The original version of this article(Liu et al.,2021)unfortunately contained a mistake:statement of equal c...Erratum to:J Zhejiang Univ-Sci B(Biomed&Biotechnol)202122(9):718-732 https:/doi.org/10.1631/jzus.B2000544.The original version of this article(Liu et al.,2021)unfortunately contained a mistake:statement of equal contribution is missing.This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work.The original article has been corrected.展开更多
This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure(HF)-related stroke.HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expr...This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure(HF)-related stroke.HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus(GEO)database.Weighted gene co-expression network analysis(WGCNA)was conducted to identify key modules and hub genes.Gene Ontology(GO)and pathway enrichment analyses were performed on genes in the key modules.Genes in HF-and stroke-related key modules were intersected to obtain common genes for HF-related stroke,which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke.Key genes were functionally annotated through GO in the Reactome and Cytoscape databases.Finally,key genes were validated in these two datasets and other datasets.HF-and stroke-related datasets each identified two key modules.Functional enrichment analysis indicated that protein ubiquitination,Wnt signaling,and exosomes were involved in both HF-and stroke-related key modules.Additionally,ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke.OTU deubiquitinase with linear linkage specificity(OTULIN)and nuclear factor interleukin 3-regulated(NFIL3)were determined to be the key genes in HF-related stroke.Through functional annotation,OTULIN was involved in protein ubiquitination and Wnt signaling,and NFIL3 was involved in DNA binding and transcription.Importantly,OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups.Protein ubiquitination,Wnt signaling,and exosomes were involved in HF-related stroke.OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes,and thus serve as promising intervention targets.展开更多
基金supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ13-YQ-101,ZZ16-ND-10-09,ZZ16-ND-10-28)the CACMS Innovation Fund(CI2021A04107),the National Natural Science Foundation of China(U1812403-1)+1 种基金the National Key Research and Development Project(2019YFE0108700,China)the Fundamental Research Funds for the Central Universities(3332022051).
文摘Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood.Here,we performed a comprehensive analysis of genome resequencing,metabolome,and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN.Metabolites analysis revealed that 72.18%of sesquiterpenes was highly accumulated in HAN compared to JL.Integrated omics analysis found a DBR2-Like(DBR2L)gene may be involved in artemisinin biosynthesis.DBR2L was highly homologous with DBR2,belonged to ORR3 family,and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde.Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A.annua and were clustered into three variation types.The promoter activity of diverse variant types showed obvious differences.Furthermore,the core region(-625 to 0)of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened.Thus,the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis.The promoter variation in DBR2L affects its expression level,and thereby may result in the different yield of artemisinin in varieties of A.annua.It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A.annua,and will assist in a high yield of artemisinin in A.annua.
文摘Erratum to:J Zhejiang Univ-Sci B(Biomed&Biotechnol)202122(9):718-732 https:/doi.org/10.1631/jzus.B2000544.The original version of this article(Liu et al.,2021)unfortunately contained a mistake:statement of equal contribution is missing.This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work.The original article has been corrected.
基金supported by the National Natural Science Foundation of China(No.81900387)the Guangdong Basic and Applied Basic Research Fund(No.2019A1515011806)+1 种基金the Fundamental Research Funds for the Central Universities(No.19ykpy97)the Science and Technology Program of Guangzhou City of China(No.201803040010)。
文摘This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure(HF)-related stroke.HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus(GEO)database.Weighted gene co-expression network analysis(WGCNA)was conducted to identify key modules and hub genes.Gene Ontology(GO)and pathway enrichment analyses were performed on genes in the key modules.Genes in HF-and stroke-related key modules were intersected to obtain common genes for HF-related stroke,which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke.Key genes were functionally annotated through GO in the Reactome and Cytoscape databases.Finally,key genes were validated in these two datasets and other datasets.HF-and stroke-related datasets each identified two key modules.Functional enrichment analysis indicated that protein ubiquitination,Wnt signaling,and exosomes were involved in both HF-and stroke-related key modules.Additionally,ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke.OTU deubiquitinase with linear linkage specificity(OTULIN)and nuclear factor interleukin 3-regulated(NFIL3)were determined to be the key genes in HF-related stroke.Through functional annotation,OTULIN was involved in protein ubiquitination and Wnt signaling,and NFIL3 was involved in DNA binding and transcription.Importantly,OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups.Protein ubiquitination,Wnt signaling,and exosomes were involved in HF-related stroke.OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes,and thus serve as promising intervention targets.