The amino-functionalization of TS-1 zeolite followed by immobilization of phosphotungstic acid(HPW)was presented to prepare a strong solid acid catalyst for the synthesis of bio-based tributyl citrate from the esterif...The amino-functionalization of TS-1 zeolite followed by immobilization of phosphotungstic acid(HPW)was presented to prepare a strong solid acid catalyst for the synthesis of bio-based tributyl citrate from the esterification of citric acid and n-butanol.γ-Aminopropyltriethoxysilane(APTES)was first grafted on the TS-1 zeolite via the condensation reactions with surface hydroxyl groups,and subsequently the HPW was immobilized via the reaction between the amino groups and the protons from HPW-forming strong ionic bonding.The Keggin structure of HPW and MFI topology of TS-1 zeolite were well maintained after the modifications.The amino-functionalization generated abundant uniformly distributed active sites on TS-1 for HPW immobilization,which promoted the dispersity,abundance,as well as the stability of the acid sites.The tetrahedrally coordinated framework titanium and non-framework titania behaved as weak Lewis acid sites,and the protons from the immobilized HPW acted as the moderate or strong Brønsted acid sites.An optimized TBC yield of 96.2%(mol)with a conversion of-COOH of 98.1%(mol)was achieved at 150℃for 6 h over the HPW immobilized on amino-functionalized TS-1.The catalyst exhibited good stability after four consecutive reaction runs,where the activity leveled off at still a relatively high level after somewhat deactivation possibly caused by the leaching of a small portion of weakly anchored APTES or HPW.展开更多
The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabol...The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.展开更多
Strawberry is a major fruit crop worldwide because its nutritional and health benefits to human health,but its productivity is limited by Botrytis cinerea.Sucrose nonfermentation 1-related protein kinase 1(SnRK1)has a...Strawberry is a major fruit crop worldwide because its nutritional and health benefits to human health,but its productivity is limited by Botrytis cinerea.Sucrose nonfermentation 1-related protein kinase 1(SnRK1)has a defense function against pathogens,but the function of SnRK1 in the defense response to B.cinerea in plants is still unclear.In this study,FaSnRK1a-OE and RNAi fruits were constructed and then inoculated with B.cinerea.The result reveals a positive role of Fa SnRK1a in the regulation of resistance to gray mold.FaSnRK1a affects SA content by regulating FaPAL1 and FaPAL2 expressions.The genes related to the SA signaling pathway(FaTGA1 and FaTGA2.1)were significantly increased/decreased in FaSnRK1a-OE or FaSnRK1a-RNAi fruit,respectively.FaSnRK1a interacted with the FaWRKY33.2 protein and negatively regulated FaWRKY33.2 expression,and FaWRKY33.2 acts as a repressor of disease resistance to B.cinerea.Finally,FaSnRK1a regulates the expression of six PR genes and the activities of antioxidant enzymes to boost defense response after B.cinerea inoculation.Our findings showed that FaSnRK1a increases the resistance of strawberry fruit to B.cinerea via SA signaling pathway and interaction with the FaWRKY33.2 transcription factor.展开更多
Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM ...Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.展开更多
Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluor...Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.展开更多
BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against...BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.展开更多
Omega-3(linolenic acid(ALA),docosapentaenoic acid,eicosapentaenoic acid)and omega-6(linoleic acid(LA),arachidonic acid)polyunsaturated fatty acids are essential for health and normal physiological functioning in human...Omega-3(linolenic acid(ALA),docosapentaenoic acid,eicosapentaenoic acid)and omega-6(linoleic acid(LA),arachidonic acid)polyunsaturated fatty acids are essential for health and normal physiological functioning in humans.Here we report a genome-wide association study(GWAS)on LA content in chicken meat.The 19 significant single nucleotide polymorphisms(SNPs)identified by the GWAS approach were annotated in VILL,PLCD1 and OXSR1 genes with highly polymorphic linkage blocks,and explained 4.5%of the phenotypic variation in the LA content.Specifically,the PLCD1 mRNA expression level was negatively correlated with the LA content,and significantly higher in chickens with low LA content than in those with high LA content.In addition,PLCD1 was found to be involved in metabolic pathways,etc.Furthermore,the LA content was correlated with volatile organic compounds(e.g.,octanal,etc.),but no relationship was found with intramuscular fat and triglycerides in chicken meat.The results indicated that there are key SNPs in PLCD1 that regulate the content of LA,and it has no significant effect on fat deposition,but may affect the content of volatile organic compounds(VOCs).展开更多
Sugarcane smut caused by Sporisorium scitamineum is a destructive disease responsible for significant losses in sugarcane production worldwide.However,the mechanisms underlying the pathogenicity of this fungus remain ...Sugarcane smut caused by Sporisorium scitamineum is a destructive disease responsible for significant losses in sugarcane production worldwide.However,the mechanisms underlying the pathogenicity of this fungus remain largely unknown.In this study,we found that the disruption of the SsRSS1 gene,which encodes a salicylic acid(SA)sensing regulator,does not affect phenotypic traits such as the morphology,growth rate,and sexual mating ability of haploid basidiospores,but rather reduces the tolerance of basidiospores to SA stress by blocking the induction of SsSRG1,a gene encoding a SA response protein in S.scitamineum.SsRSS1 deletion resulted in the attenuation of the virulence of the fungus.In addition to a significant reduction in whip formation,a portion of plantlets(18.3%)inoculated with theΔSsRSS1 strains were found to be infected but failed to produce whips for up to 90 days post-inoculation.However,the development of hyphae and teliospore from theΔSsRSS1-infected plants that formed whips seemed indistinguishable from that in the wild-type-infected plants.Combined,our findings suggested that SsRss1 is required for maintaining fungal fitness in planta by counteracting SA stress.展开更多
It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effect...It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.展开更多
基金supported by the National Natural Science Foundation of China(21978089)the Program of Shanghai Academic/Technology Research Leader(21XD1433000)Key Research and Development Program of Xinjiang Uygur Autonomous Region(2022B01032-1).
文摘The amino-functionalization of TS-1 zeolite followed by immobilization of phosphotungstic acid(HPW)was presented to prepare a strong solid acid catalyst for the synthesis of bio-based tributyl citrate from the esterification of citric acid and n-butanol.γ-Aminopropyltriethoxysilane(APTES)was first grafted on the TS-1 zeolite via the condensation reactions with surface hydroxyl groups,and subsequently the HPW was immobilized via the reaction between the amino groups and the protons from HPW-forming strong ionic bonding.The Keggin structure of HPW and MFI topology of TS-1 zeolite were well maintained after the modifications.The amino-functionalization generated abundant uniformly distributed active sites on TS-1 for HPW immobilization,which promoted the dispersity,abundance,as well as the stability of the acid sites.The tetrahedrally coordinated framework titanium and non-framework titania behaved as weak Lewis acid sites,and the protons from the immobilized HPW acted as the moderate or strong Brønsted acid sites.An optimized TBC yield of 96.2%(mol)with a conversion of-COOH of 98.1%(mol)was achieved at 150℃for 6 h over the HPW immobilized on amino-functionalized TS-1.The catalyst exhibited good stability after four consecutive reaction runs,where the activity leveled off at still a relatively high level after somewhat deactivation possibly caused by the leaching of a small portion of weakly anchored APTES or HPW.
基金supported by the National Natural Science Foundation of China,Nos.81974134(to XX)and 82000895(to HL)National Key Research and Development Program of China,Nos.2021YFA1101200&2021YFA1101202National Natural Science Foundation of Hunan Province,China,No.2022JJ30071(to HL)。
文摘The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.
基金supported by National Natural Science Foundation of China(Grant Nos.31672099,31801812)the National Modern Agroindustry Technology Research System Fund(Grant No.CARS-30-2-02)。
文摘Strawberry is a major fruit crop worldwide because its nutritional and health benefits to human health,but its productivity is limited by Botrytis cinerea.Sucrose nonfermentation 1-related protein kinase 1(SnRK1)has a defense function against pathogens,but the function of SnRK1 in the defense response to B.cinerea in plants is still unclear.In this study,FaSnRK1a-OE and RNAi fruits were constructed and then inoculated with B.cinerea.The result reveals a positive role of Fa SnRK1a in the regulation of resistance to gray mold.FaSnRK1a affects SA content by regulating FaPAL1 and FaPAL2 expressions.The genes related to the SA signaling pathway(FaTGA1 and FaTGA2.1)were significantly increased/decreased in FaSnRK1a-OE or FaSnRK1a-RNAi fruit,respectively.FaSnRK1a interacted with the FaWRKY33.2 protein and negatively regulated FaWRKY33.2 expression,and FaWRKY33.2 acts as a repressor of disease resistance to B.cinerea.Finally,FaSnRK1a regulates the expression of six PR genes and the activities of antioxidant enzymes to boost defense response after B.cinerea inoculation.Our findings showed that FaSnRK1a increases the resistance of strawberry fruit to B.cinerea via SA signaling pathway and interaction with the FaWRKY33.2 transcription factor.
基金support from the Ningxia Hui Autonomous Region Key Research and Development Program(Project No.2021BEG03041).
文摘Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.
基金supported by the Zhejiang Province Traditional Chinese Medicine Health Science and Technology Program(2023ZL570).
文摘Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.
文摘BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.
基金the National Natural Science Foundation of China(31872340)the State Key Laboratory of Animal Nutrition(2004DA125184G2109)+2 种基金the Basic Research from Chinese Academy of Agricultural Sciences(Y2019XK06)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(ASTIP-IAS04)the earmarked fund for China Agriculture Research System(CARS-41).
文摘Omega-3(linolenic acid(ALA),docosapentaenoic acid,eicosapentaenoic acid)and omega-6(linoleic acid(LA),arachidonic acid)polyunsaturated fatty acids are essential for health and normal physiological functioning in humans.Here we report a genome-wide association study(GWAS)on LA content in chicken meat.The 19 significant single nucleotide polymorphisms(SNPs)identified by the GWAS approach were annotated in VILL,PLCD1 and OXSR1 genes with highly polymorphic linkage blocks,and explained 4.5%of the phenotypic variation in the LA content.Specifically,the PLCD1 mRNA expression level was negatively correlated with the LA content,and significantly higher in chickens with low LA content than in those with high LA content.In addition,PLCD1 was found to be involved in metabolic pathways,etc.Furthermore,the LA content was correlated with volatile organic compounds(e.g.,octanal,etc.),but no relationship was found with intramuscular fat and triglycerides in chicken meat.The results indicated that there are key SNPs in PLCD1 that regulate the content of LA,and it has no significant effect on fat deposition,but may affect the content of volatile organic compounds(VOCs).
基金supported by the grants from the National Natural Science Foundation of China(31872635)the Guangxi Key Laboratory of Sugarcane Biology,China(2018-266-Z01)the Department of Science and Technology of Guangxi Zhuang Autonomous Region,China(AD17129002).
文摘Sugarcane smut caused by Sporisorium scitamineum is a destructive disease responsible for significant losses in sugarcane production worldwide.However,the mechanisms underlying the pathogenicity of this fungus remain largely unknown.In this study,we found that the disruption of the SsRSS1 gene,which encodes a salicylic acid(SA)sensing regulator,does not affect phenotypic traits such as the morphology,growth rate,and sexual mating ability of haploid basidiospores,but rather reduces the tolerance of basidiospores to SA stress by blocking the induction of SsSRG1,a gene encoding a SA response protein in S.scitamineum.SsRSS1 deletion resulted in the attenuation of the virulence of the fungus.In addition to a significant reduction in whip formation,a portion of plantlets(18.3%)inoculated with theΔSsRSS1 strains were found to be infected but failed to produce whips for up to 90 days post-inoculation.However,the development of hyphae and teliospore from theΔSsRSS1-infected plants that formed whips seemed indistinguishable from that in the wild-type-infected plants.Combined,our findings suggested that SsRss1 is required for maintaining fungal fitness in planta by counteracting SA stress.
基金funding from the Spring City Plan:The High-Level Talent Promotion and Training Project of Kunming and the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory(Grant No.:2022YKZY001).
文摘It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.