As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great ...As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great threat to human health.In this study,we constructed a novel fungal pathogen-responsive assembly of cuprous oxide(Cu_(2)O)nanoparticles(NPs)for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen,Candida albicans(C.albicans).This assembly was formed by coating the initial Cu_(2)O NPs with both phosphatidylethanolamine(PE)and bovine serum albumin(BSA),followed by hydrophobic/electrostatic interaction-driven formation of the Cu_(2)O-PE-BSA microaggregates.The formed microaggregates could be induced for disassembly by the fungal pathogen C.albicans,leading to close binding of the NPs to the cell wall of the pathogen.Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen,but had extreme low toxicity to mammalian cells.In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues.This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.展开更多
Nonalcoholic fatty liver disease(NAFLD)encompasses a spectrum of pathologies,ranging from steatosis to nonalcoholic steatohepatitis(NASH).The factors promoting the progression of steatosis to NASH are still unclear.Re...Nonalcoholic fatty liver disease(NAFLD)encompasses a spectrum of pathologies,ranging from steatosis to nonalcoholic steatohepatitis(NASH).The factors promoting the progression of steatosis to NASH are still unclear.Recent studies suggest that mitochondrial lipid composition is critical in NASH develop-ment.Here,we showed that CDP-DAG synthase 2(Cds2)was downregulated in genetic or diet-induced NAFLD mouse models.Liver-specific deficiency of Cds2 provoked hepatic steatosis,inflammation and fibrosis in five-week-old mice.CDS2 is enriched in mitochondria-associated membranes(MAMs),and hepatic Cds2 deficiency impaired mitochondrial function and decreased mitochondrial PE levels.Overexpression of phosphatidylserine decarboxylase(PISD)alleviated the NASH-like phenotype in Cds2^(f/f);AlbCre mice and abnormal mitochondrial morphology and function caused by CDS2 deficiency in hepatocytes.Additionally,dietary supplementation with an agonist of peroxisome proliferator-activated receptor alpha(PPARa)attenuated mitochondrial defects and ameliorated the NASH-like phe-notype in Cds2^(f/f);AlbCre mice.Finally,Cds2 overexpression protected against high-fat diet-induced hepatic steatosis and obesity.Thus,Cds2 modulates mitochondrial function and NASH development.展开更多
基金the National Natural Science Foundation of China(31870139 and 81873961)the Natural Science Foundation of Tianjin(19JCZDJC33800)+1 种基金the National Training Program of Innovation and Entrepreneurship for Undergraduates(201810055105)the Fundamental Research for the Central Universities。
文摘As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great threat to human health.In this study,we constructed a novel fungal pathogen-responsive assembly of cuprous oxide(Cu_(2)O)nanoparticles(NPs)for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen,Candida albicans(C.albicans).This assembly was formed by coating the initial Cu_(2)O NPs with both phosphatidylethanolamine(PE)and bovine serum albumin(BSA),followed by hydrophobic/electrostatic interaction-driven formation of the Cu_(2)O-PE-BSA microaggregates.The formed microaggregates could be induced for disassembly by the fungal pathogen C.albicans,leading to close binding of the NPs to the cell wall of the pathogen.Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen,but had extreme low toxicity to mammalian cells.In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues.This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.
基金the Ministry of Science and Technology of China(2018YFA0506902,2016YFA0500100,and 2018YFA081104)the National Natural Science Foundation of China(9195420001,31771305,and 31630019)Chinese Academy of Sciences(XDPB17)。
文摘Nonalcoholic fatty liver disease(NAFLD)encompasses a spectrum of pathologies,ranging from steatosis to nonalcoholic steatohepatitis(NASH).The factors promoting the progression of steatosis to NASH are still unclear.Recent studies suggest that mitochondrial lipid composition is critical in NASH develop-ment.Here,we showed that CDP-DAG synthase 2(Cds2)was downregulated in genetic or diet-induced NAFLD mouse models.Liver-specific deficiency of Cds2 provoked hepatic steatosis,inflammation and fibrosis in five-week-old mice.CDS2 is enriched in mitochondria-associated membranes(MAMs),and hepatic Cds2 deficiency impaired mitochondrial function and decreased mitochondrial PE levels.Overexpression of phosphatidylserine decarboxylase(PISD)alleviated the NASH-like phenotype in Cds2^(f/f);AlbCre mice and abnormal mitochondrial morphology and function caused by CDS2 deficiency in hepatocytes.Additionally,dietary supplementation with an agonist of peroxisome proliferator-activated receptor alpha(PPARa)attenuated mitochondrial defects and ameliorated the NASH-like phe-notype in Cds2^(f/f);AlbCre mice.Finally,Cds2 overexpression protected against high-fat diet-induced hepatic steatosis and obesity.Thus,Cds2 modulates mitochondrial function and NASH development.
