Glucagon-like peptide-1(GLP-1)reduces postprandial hyperglycaemia,but its short half-life inhibits clinical application.The aim of the current study was to evaluate the treatment efforts of an engineered strain,Lactob...Glucagon-like peptide-1(GLP-1)reduces postprandial hyperglycaemia,but its short half-life inhibits clinical application.The aim of the current study was to evaluate the treatment efforts of an engineered strain,Lactobacillus plantarum-pMG36e-GLP-1(L.plantarum-pMG36e-GLP-1),that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus(T2DM)monkeys.After 7 weeks of oral supplementation with L.plantarum-pMG36e-GLP-1,the fasting blood glucose(FPG)of monkeys was significantly(p<0.05)reduced to a normal level and only a small amount of weight was lost.The results of metagenomic sequencing showed that L.plantarum-pMG36e-GLP-1 caused a substantial(p<0.05)reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera.According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways,19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L.plantarum-pMG36e-GLP-1.LC-MS faecal metabolomics analysis found 41 significant differential metabolites(11 higher and 30 lower)in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant.The present study suggests that L.plantarum-pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment.展开更多
Owing to the lack of physical knowledge of boundary layer transition,the c-Reh transi-tion model introduces closure parameters,which increase the uncertainty of transition prediction.The objective of this work is to q...Owing to the lack of physical knowledge of boundary layer transition,the c-Reh transi-tion model introduces closure parameters,which increase the uncertainty of transition prediction.The objective of this work is to quantify the uncertainties of closure parameters in the quantities of interests and identify the key parameters.The six closure parameters in the uncertainty intervals are used as input variables,and the uncertainties of the output results are propagated by a stochas-tic expansion based on the point-collocation nonintrusive polynomial chaos method.The relative contribution of each parameter to uncertainty is evaluated by the Sobol index.The computational cases include natural and bypass transitional flows on zero-pressure-gradient flat plates,and sub-sonic and transonic flows around airfoils.For most cases,c_(e2),c_(a2),and c_(a1)dominate the uncertainty,and the influence of r ht is also significant when the history effects of flow are evident.The contri-bution of parameters in airfoils is more complex than that in flat plates.The transonic airfoil case shows that flow separation dramatically changes the distribution of Sobol indices,which poses a challenge to the accurate prediction of transition.Generally,c_(e2)and c_(a2)are the key parameters of the c-Reh model.展开更多
基金This study was supported by the National Natural Science Foundation of China(grant no.31760276,31960171,82060638)the Jiangxi Natural Science Foundation(grant no.20171BAB204019,20192ACB20022),and the“double 10-thousand plan”of Jiangxi Province(innovation and technology professionals as the high-end talent).
文摘Glucagon-like peptide-1(GLP-1)reduces postprandial hyperglycaemia,but its short half-life inhibits clinical application.The aim of the current study was to evaluate the treatment efforts of an engineered strain,Lactobacillus plantarum-pMG36e-GLP-1(L.plantarum-pMG36e-GLP-1),that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus(T2DM)monkeys.After 7 weeks of oral supplementation with L.plantarum-pMG36e-GLP-1,the fasting blood glucose(FPG)of monkeys was significantly(p<0.05)reduced to a normal level and only a small amount of weight was lost.The results of metagenomic sequencing showed that L.plantarum-pMG36e-GLP-1 caused a substantial(p<0.05)reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera.According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways,19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L.plantarum-pMG36e-GLP-1.LC-MS faecal metabolomics analysis found 41 significant differential metabolites(11 higher and 30 lower)in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant.The present study suggests that L.plantarum-pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment.
基金supported by the National Numerical Wind Tunnel Project of China(No.NNW2019ZT1-A03)the National Natural Science Foundation of China(No.11721202).
文摘Owing to the lack of physical knowledge of boundary layer transition,the c-Reh transi-tion model introduces closure parameters,which increase the uncertainty of transition prediction.The objective of this work is to quantify the uncertainties of closure parameters in the quantities of interests and identify the key parameters.The six closure parameters in the uncertainty intervals are used as input variables,and the uncertainties of the output results are propagated by a stochas-tic expansion based on the point-collocation nonintrusive polynomial chaos method.The relative contribution of each parameter to uncertainty is evaluated by the Sobol index.The computational cases include natural and bypass transitional flows on zero-pressure-gradient flat plates,and sub-sonic and transonic flows around airfoils.For most cases,c_(e2),c_(a2),and c_(a1)dominate the uncertainty,and the influence of r ht is also significant when the history effects of flow are evident.The contri-bution of parameters in airfoils is more complex than that in flat plates.The transonic airfoil case shows that flow separation dramatically changes the distribution of Sobol indices,which poses a challenge to the accurate prediction of transition.Generally,c_(e2)and c_(a2)are the key parameters of the c-Reh model.
