Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities...Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities.However,the current challenge lies in the absence of an efficient strategy for systematic screening and identification of NPs that can effectively protect against ZEA-induced toxicity.This study describes a phenotype-based screening strategy for screening NP libraries and discovering more effective compounds to mitigate or counteract the adverse consequences of ZEA exposure in animals.Using this strategy,we initially identified 96 NPs and evaluated the potency and efficacy of two effective candidate compounds,fraxetin,and hydroxytyrosol,based on embryonic phenotype and locomotor activity using a scoring system and the TCMacro method.Furthermore,we performed transcriptome and proteinprotein interaction(PPI)network analyses to extract two mRNA signatures to query the Connectivity Map(CMap)database and predict NPs.The predicted NPs showed the potential to reverse the gene expression profiles associated with ZEA toxicity.Consequently,we further screened these compounds using our model,which indicated that hispidin,daphnetin,and riboflavin exhibit promising in vivo effi-cacy in zebrafish.Notably,throughout the process,fraxetin consistently stood out as the most promising NP.Biological pathway analysis and functional verification revealed that fraxetin completely reversed the toxic effects of ZEA at very low doses.This was achieved by repairing damaged cell apoptosis,modifying the cell cycle pathway,and preventing senescence induction,indicating good application potential.Overall,we demonstrated that this integration strategy can be successfully applied to effectively discover potential antidotes.展开更多
Populus alba‘Berolinensis’is a fast-growing,high-yielding species with strong biotic and abiotic stress resistance,and widely planted for timber,shelter belts and aesthetic purposes.In this study,molecular developme...Populus alba‘Berolinensis’is a fast-growing,high-yielding species with strong biotic and abiotic stress resistance,and widely planted for timber,shelter belts and aesthetic purposes.In this study,molecular development is explored and the important genes regulating xylem forma-tion in P.alba‘Berolinensis’under artificial bending treat-ments was identified.Anatomical investigation indicated that tension wood(TW)was characterized by eccentric growth of xylem and was enriched in cellulose;the degree of ligni-fication was lower than for normal wood(NW)and oppo-site wood(OW).RNA-Seq-based transcriptome analysis was performed using developing xylem from three wood types(TW,OW and NW).A large number of differentially expressed genes(DEGs)were screened and 4889 counted.In GO and KEGG enrichment results,genes involved in plant hormone signal transduction,phenylpropanoid biosynthesis,and cell wall and secondary cell wall biogenesis play major roles in xylem development under artificial bending.Eight expansin(PalEXP)genes were identified from the RNA-seq data;four were differentially expressed during tension wood formation.Phylogenetic analysis indicated that PalEXLB1 belongs to the EXPB subfamily and that the other PalEXPs are members of the EXPA subfamily.A transcriptional regulatory network construction showed 10 transcription factors located in the first and second layers upstream of EXP,including WRKY,ERF and bHLH.RT‒qPCR analy-sis in leaves,stems and roots combined with transcriptome analysis suggests that PalEXPA2,PalEXPA4 and PalEXPA15 play significant regulatory roles in cell wall formation during tension wood development.The candidate genes involved in xylem cell wall development during tension wood formation marks an important step toward identifying the molecular regulatory mechanism of xylem development and wood property improvement in P.alba‘Berolinensis’.展开更多
基金supported by the National Natural Science Foundation of China for Outstanding Youth Science Foundation(31922086)the National Key Research and Development(R&D)Program of China(2018YFD0900400)the Young Top-Notch Talent Support Program and Government Guidance for Local Scientific and Technological Development Projects(23ZYZYTS0513).
文摘Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities.However,the current challenge lies in the absence of an efficient strategy for systematic screening and identification of NPs that can effectively protect against ZEA-induced toxicity.This study describes a phenotype-based screening strategy for screening NP libraries and discovering more effective compounds to mitigate or counteract the adverse consequences of ZEA exposure in animals.Using this strategy,we initially identified 96 NPs and evaluated the potency and efficacy of two effective candidate compounds,fraxetin,and hydroxytyrosol,based on embryonic phenotype and locomotor activity using a scoring system and the TCMacro method.Furthermore,we performed transcriptome and proteinprotein interaction(PPI)network analyses to extract two mRNA signatures to query the Connectivity Map(CMap)database and predict NPs.The predicted NPs showed the potential to reverse the gene expression profiles associated with ZEA toxicity.Consequently,we further screened these compounds using our model,which indicated that hispidin,daphnetin,and riboflavin exhibit promising in vivo effi-cacy in zebrafish.Notably,throughout the process,fraxetin consistently stood out as the most promising NP.Biological pathway analysis and functional verification revealed that fraxetin completely reversed the toxic effects of ZEA at very low doses.This was achieved by repairing damaged cell apoptosis,modifying the cell cycle pathway,and preventing senescence induction,indicating good application potential.Overall,we demonstrated that this integration strategy can be successfully applied to effectively discover potential antidotes.
基金funded by the Fundamental Research Funds for the Central Universities(2572019CT02)Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)The Overseas Expertise Introduction Project for Discipline Innovation(B16010).
文摘Populus alba‘Berolinensis’is a fast-growing,high-yielding species with strong biotic and abiotic stress resistance,and widely planted for timber,shelter belts and aesthetic purposes.In this study,molecular development is explored and the important genes regulating xylem forma-tion in P.alba‘Berolinensis’under artificial bending treat-ments was identified.Anatomical investigation indicated that tension wood(TW)was characterized by eccentric growth of xylem and was enriched in cellulose;the degree of ligni-fication was lower than for normal wood(NW)and oppo-site wood(OW).RNA-Seq-based transcriptome analysis was performed using developing xylem from three wood types(TW,OW and NW).A large number of differentially expressed genes(DEGs)were screened and 4889 counted.In GO and KEGG enrichment results,genes involved in plant hormone signal transduction,phenylpropanoid biosynthesis,and cell wall and secondary cell wall biogenesis play major roles in xylem development under artificial bending.Eight expansin(PalEXP)genes were identified from the RNA-seq data;four were differentially expressed during tension wood formation.Phylogenetic analysis indicated that PalEXLB1 belongs to the EXPB subfamily and that the other PalEXPs are members of the EXPA subfamily.A transcriptional regulatory network construction showed 10 transcription factors located in the first and second layers upstream of EXP,including WRKY,ERF and bHLH.RT‒qPCR analy-sis in leaves,stems and roots combined with transcriptome analysis suggests that PalEXPA2,PalEXPA4 and PalEXPA15 play significant regulatory roles in cell wall formation during tension wood development.The candidate genes involved in xylem cell wall development during tension wood formation marks an important step toward identifying the molecular regulatory mechanism of xylem development and wood property improvement in P.alba‘Berolinensis’.
