Recent progress in the mouse genome and technology for gene manipulations have led to the generation of a rangeof genetic mouse lines with identified cardiac phenotype. Of these, over 20 mouse lines have been develope...Recent progress in the mouse genome and technology for gene manipulations have led to the generation of a rangeof genetic mouse lines with identified cardiac phenotype. Of these, over 20 mouse lines have been developed with targeted genescoding for β- or α-adrenergic receptors(AR ), components of adrenergic signaling transduction pathways and presynapic factorswhich modulate synthesis and release of catecholamines. Meanwhile there has been significant progress in the mousecardiophysiology and miniaturizaion in methods for in vivo functional assessment. In recent years, there have beencomprehensive resereh, using the gene-based mouse lines, on the adrenergic mechanisms in controlling myocardial functionand development of heart failure. Novel findings have been made on the inhibitory cross-talk between α1B-AR and β-AR,cardiomyopathic phenotype of mice that overexpress β1-AN, β2-AR, Gsa or G qa, and inhibitory effect of an enhanced activityof β-AR kinase-1(β ARK1 ) on β-adrenergic signaling and myocardial contractility. A number of inotropic molecules have beenidentified in vivo and, by the novel crossbrecd strategy for gene complementation, ovempression of β2-AR and adenylylcyclase,or expression of βARK1 inhibitor were success in rescuing cardiorvopathic and heart falure phenotypes in several genetic mouselines. These findings from genetic mouse models provide important information on molecular mechanisms of heart failure anddesign of gene therapy.展开更多
Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response...Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Iuflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction （AMI）, Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes （such as death, recurrent myocardial in- farction, and heart failure） in patients with AMI.展开更多
Due to pollution in second water supply system (SWSS),nine renovation alternative plans were proposed and com-prehensive evaluations of different plan based on Analytical Hierarchy Process (AHP) were presented in this...Due to pollution in second water supply system (SWSS),nine renovation alternative plans were proposed and com-prehensive evaluations of different plan based on Analytical Hierarchy Process (AHP) were presented in this paper. Comparisons of advantages and disadvantages among the plans of SWSS renovations provided solid foundation for selecting the most appro-priate plan for engineering projects. In addition,a mathematical model of the optimal combination of renovation plans has been set up and software Lingo was used to solve the model. As a case study,the paper analyzed 15 buildings in Tianjin City. After simulation of the SWSS renovation system,an optimal scheme was obtained,the result of which indicates that 10 out of those 15 buildings need be renovated in priority. The renovation plans selected for each building are the ones ranked higher in the com-prehensive analysis. The analysis revealed that the optimal scheme,compared with two other randomly calculated ones,increased the percentage of service population by 19.6% and 13.6% respectively,which significantly improved social and economical benefits.展开更多
基金National Health and Medical Research Council funds(APP1004235317808)+2 种基金Australian Research CouncilNational Health and Medical Research Council of AustraliaNational Heart Foundation of Australia
基金澳大利亚National Health and Medical Research Council资助
文摘Recent progress in the mouse genome and technology for gene manipulations have led to the generation of a rangeof genetic mouse lines with identified cardiac phenotype. Of these, over 20 mouse lines have been developed with targeted genescoding for β- or α-adrenergic receptors(AR ), components of adrenergic signaling transduction pathways and presynapic factorswhich modulate synthesis and release of catecholamines. Meanwhile there has been significant progress in the mousecardiophysiology and miniaturizaion in methods for in vivo functional assessment. In recent years, there have beencomprehensive resereh, using the gene-based mouse lines, on the adrenergic mechanisms in controlling myocardial functionand development of heart failure. Novel findings have been made on the inhibitory cross-talk between α1B-AR and β-AR,cardiomyopathic phenotype of mice that overexpress β1-AN, β2-AR, Gsa or G qa, and inhibitory effect of an enhanced activityof β-AR kinase-1(β ARK1 ) on β-adrenergic signaling and myocardial contractility. A number of inotropic molecules have beenidentified in vivo and, by the novel crossbrecd strategy for gene complementation, ovempression of β2-AR and adenylylcyclase,or expression of βARK1 inhibitor were success in rescuing cardiorvopathic and heart falure phenotypes in several genetic mouselines. These findings from genetic mouse models provide important information on molecular mechanisms of heart failure anddesign of gene therapy.
文摘Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Iuflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction （AMI）, Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes （such as death, recurrent myocardial in- farction, and heart failure） in patients with AMI.
基金Project (No.033113111) supported by Tianjin Science Association Key Project,China
文摘Due to pollution in second water supply system (SWSS),nine renovation alternative plans were proposed and com-prehensive evaluations of different plan based on Analytical Hierarchy Process (AHP) were presented in this paper. Comparisons of advantages and disadvantages among the plans of SWSS renovations provided solid foundation for selecting the most appro-priate plan for engineering projects. In addition,a mathematical model of the optimal combination of renovation plans has been set up and software Lingo was used to solve the model. As a case study,the paper analyzed 15 buildings in Tianjin City. After simulation of the SWSS renovation system,an optimal scheme was obtained,the result of which indicates that 10 out of those 15 buildings need be renovated in priority. The renovation plans selected for each building are the ones ranked higher in the com-prehensive analysis. The analysis revealed that the optimal scheme,compared with two other randomly calculated ones,increased the percentage of service population by 19.6% and 13.6% respectively,which significantly improved social and economical benefits.
