Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wid...Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.展开更多
Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes fro...Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes from erythromycin-treated rats were exposed to PQT in the presence of potassium ferricyanide which broke down the cytochrome P-450 Fe(Ⅱ)-metabolite complexes and restored the functional cytochrome P-450,PQT metabolism was further increased. Acetylspiramycin did not form the complexes, so potassium ferricyanide showed no effect on the PQT metabolism in microsomes from acetylspiramycin-treated rats. Triacetyloleandomycin,a specific inhibitor of cytochrome P-450ⅢAI, inhibited PQT metabolism by 53% in liver microsomes from dexamethasone-treated rats.These results indicate the cytochrome P-450ⅢA seems to be involved in metabolism of PQT in rat liver microsomes.展开更多
The key to studying urban sustainable development depends on quantifying stores, efficiencies of urban metabolisms and capturing urban metabolisms′ mechanisms. This paper builds up the metabolic emergy account and qu...The key to studying urban sustainable development depends on quantifying stores, efficiencies of urban metabolisms and capturing urban metabolisms′ mechanisms. This paper builds up the metabolic emergy account and quantifies some important concepts of emergy stores. Emphasis is placed on the urban metabolic model based on the slack based model(SBM) method to measure urban metabolic efficiencies. Urban metabolic mechanisms are discussed by using the regression method. By integrating these models, this paper analyzes the urban metabolic development in Beijing from 2001 to 2010. We conclude that the metabolic emergy stores of Beijing increased significantly from 2001 to 2010, with the emergy imported accounting for most of the increase. The metabolic efficiencies in Beijing have improved since the 2008 Olympic Games. The population, economic growth, industrial structures, and environmental governance positively affect the overall urban metabolism, while the land expansion, urbanization and environmentally technical levels hinder the improving of urban metabolic efficiencies. The SBM metabolic method and the regression model based on the emergy analysis provide insights into the urban metabolic efficiencies and the mechanism. They can promote to integrate such concepts into their sustainability analyses and policy decisions.展开更多
We consider the process of hemodialysis performed by means of a hollow fiber dialyzer with a special focus on the dynamics of the light solutes （including metabolic waste products） through the porous fibers membrane...We consider the process of hemodialysis performed by means of a hollow fiber dialyzer with a special focus on the dynamics of the light solutes （including metabolic waste products） through the porous fibers membrane. The model we illustrate here completes the one formulated in a previous paper in which solutes concentrations in the dialyzate were neglected. Exploiting the large difference between the characteristic time of the processes in the machine and the relaxation time to equilibrium in the body, we confine our study to the case of constant input data in order to emphasize the role of the solute transport mechanisms. Numerical solutions show that diffusion is dominant at the early stage of filtration.展开更多
文摘Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.
文摘Our results show that in liver microsomes from erythromycin,acetylspiramycin and dexamethsone pretreated rats,the rate of praziquantel( PQT)disappearence was increased as compared with control rat When microsomes from erythromycin-treated rats were exposed to PQT in the presence of potassium ferricyanide which broke down the cytochrome P-450 Fe(Ⅱ)-metabolite complexes and restored the functional cytochrome P-450,PQT metabolism was further increased. Acetylspiramycin did not form the complexes, so potassium ferricyanide showed no effect on the PQT metabolism in microsomes from acetylspiramycin-treated rats. Triacetyloleandomycin,a specific inhibitor of cytochrome P-450ⅢAI, inhibited PQT metabolism by 53% in liver microsomes from dexamethasone-treated rats.These results indicate the cytochrome P-450ⅢA seems to be involved in metabolism of PQT in rat liver microsomes.
基金Under the auspices of National Natural Science Foundation of China(No.41371008,41101119)New Start Academic Research Projects of Beijing Union University(No.ZK201201)
文摘The key to studying urban sustainable development depends on quantifying stores, efficiencies of urban metabolisms and capturing urban metabolisms′ mechanisms. This paper builds up the metabolic emergy account and quantifies some important concepts of emergy stores. Emphasis is placed on the urban metabolic model based on the slack based model(SBM) method to measure urban metabolic efficiencies. Urban metabolic mechanisms are discussed by using the regression method. By integrating these models, this paper analyzes the urban metabolic development in Beijing from 2001 to 2010. We conclude that the metabolic emergy stores of Beijing increased significantly from 2001 to 2010, with the emergy imported accounting for most of the increase. The metabolic efficiencies in Beijing have improved since the 2008 Olympic Games. The population, economic growth, industrial structures, and environmental governance positively affect the overall urban metabolism, while the land expansion, urbanization and environmentally technical levels hinder the improving of urban metabolic efficiencies. The SBM metabolic method and the regression model based on the emergy analysis provide insights into the urban metabolic efficiencies and the mechanism. They can promote to integrate such concepts into their sustainability analyses and policy decisions.
文摘We consider the process of hemodialysis performed by means of a hollow fiber dialyzer with a special focus on the dynamics of the light solutes （including metabolic waste products） through the porous fibers membrane. The model we illustrate here completes the one formulated in a previous paper in which solutes concentrations in the dialyzate were neglected. Exploiting the large difference between the characteristic time of the processes in the machine and the relaxation time to equilibrium in the body, we confine our study to the case of constant input data in order to emphasize the role of the solute transport mechanisms. Numerical solutions show that diffusion is dominant at the early stage of filtration.
