In today's world, the innovation of science and technology has become the key support for improving comprehensive national strength and changing the mode of social production and lifestyle. The country that posses...In today's world, the innovation of science and technology has become the key support for improving comprehensive national strength and changing the mode of social production and lifestyle. The country that possesses world-class scientific and technological innovation cities maximizes the attraction of global innovation factors and wins a strategic initiative in international competition. Based on the urban zip code geodatabase, an evaluation system of urban innovation with the perspective of innovation outputs, and the spatial evolutionary mode, concerning the structure of innovation space of Shanghai and Beijing from 1991 to 2014, was developed. The results of the research indicated that the zip code geodatabase provided a new perspective for studying the evolving spatial structure of urban innovation. The resulting evaluation of the spatial structure of urban innovation using the urban zip code geodatabase established by connecting random edge points, was relatively effective. The study illustrates the value of this methodology. During the study period, the spatial structure of innovation of Shanghai and Beijing demonstrated many common features: with the increase in urban space units participating in innovation year by year, the overall gap of regional innovation outputs has narrowed, and the trend towards spatial agglomeration has strengthened. The evolving spatial structure of innovation of Shanghai and Beijing demonstrated differences between the common features during the 25 years as well: in the trend towards the suburbanization of innovation resources, the spatial structure of innovation of Shanghai evolved from a single-core to a multi-core structure. A radiation effect related to traffic arteries as spatial diffusion corridors was prominent. Accordingly, a spatial correlation effect of its innovation outputs also indicated a hollowness in the city center; the spatial structure of innovation of Beijing had a single-core oriented structure all the way. Together with the tendency for innovation resources to be agglomerated in the city center, the spatial correlation effect of innovation outputs reflected the characteristics of the evolutionary feature where "rural area encircles cities". The innovation spatial structure of Shanghai and Beijing have intrinsic consistency with the spatial structure of their respective regions(Yangtze River Delta urban agglomeration and Beijing-Tianjin-Hebei metropolitan region), which suggested that the principle of proportional and disproportional distribution of a city-scale pattern of technological and innovational activities is closely related to its regional innovation pattern.展开更多
In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma H...In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.展开更多
Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mas...Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mass is found world-wide as more cultures acquire a Western lifestyle.In the United States,life expectancy declines by 3 years for those with a body mass index over 30 and by 10 years for those with a body mass index over 40 due,in large part,to the increased prevalence of cardiovascular disease.Over the past decade we have come to appreciate that adipose tissue functions as an endocrine organ,and that obesity contributes to cardiovascular and metabolic disorders through cytokine imbalances that promote the development of a chronic,low grade inflammatory state.Bioactive proteins secreted from fat are generally referred to as adipokines.Under conditions of obesity,adipose tissue expresses higher levels of pro-inflammatory adipokines,such as TNF- and IL- 6,and lower levels of anti-inflammatory cytokines. Adiponectin in the prototypical anti-inflammatory adipokine,and its expression is down-regulated in obese individuals.Low adiponectin levels have shown to be an independent risk factor for developing type 2 diabetes,myocardial infarction and hypertension. Studies with genetically manipulated mice have shown that adiponectin protects against the development of a number of diseases that are prevalent in obese individuals including insulin re- sistance,atherosclerosis,LV hypertrophy,and a peripheral artery disease.However,no adiponectin-based therapies have been successfully launched in the clinic due,in large part,to difficulties associated with the high natural abundance of adiponectin (0.01%of the serum protein) and its complex structure.My laboratory performs genetic screens to identify novel adiponectin-like factors involved in metabolic and cardiovascular regulation.One of these newly discovered factors,referred to as Sfrp5, is a secreted protein that is largely produced by adipocytes.Sfrp5 functions by binding to and inhibiting the actions on non-canonical,pro-inflammatory Wnt proteins.We have shown that Sfrp5 and Wnt5a function as a molecular rheostat to control the inflammatory state of the fat pad microenvironment. It is likely that this system also functions to control inflammatory processes that occur in cardio-vascular diseases.展开更多
基金National Natural Science Foundation of China,No.41471108,No.41501141
文摘In today's world, the innovation of science and technology has become the key support for improving comprehensive national strength and changing the mode of social production and lifestyle. The country that possesses world-class scientific and technological innovation cities maximizes the attraction of global innovation factors and wins a strategic initiative in international competition. Based on the urban zip code geodatabase, an evaluation system of urban innovation with the perspective of innovation outputs, and the spatial evolutionary mode, concerning the structure of innovation space of Shanghai and Beijing from 1991 to 2014, was developed. The results of the research indicated that the zip code geodatabase provided a new perspective for studying the evolving spatial structure of urban innovation. The resulting evaluation of the spatial structure of urban innovation using the urban zip code geodatabase established by connecting random edge points, was relatively effective. The study illustrates the value of this methodology. During the study period, the spatial structure of innovation of Shanghai and Beijing demonstrated many common features: with the increase in urban space units participating in innovation year by year, the overall gap of regional innovation outputs has narrowed, and the trend towards spatial agglomeration has strengthened. The evolving spatial structure of innovation of Shanghai and Beijing demonstrated differences between the common features during the 25 years as well: in the trend towards the suburbanization of innovation resources, the spatial structure of innovation of Shanghai evolved from a single-core to a multi-core structure. A radiation effect related to traffic arteries as spatial diffusion corridors was prominent. Accordingly, a spatial correlation effect of its innovation outputs also indicated a hollowness in the city center; the spatial structure of innovation of Beijing had a single-core oriented structure all the way. Together with the tendency for innovation resources to be agglomerated in the city center, the spatial correlation effect of innovation outputs reflected the characteristics of the evolutionary feature where "rural area encircles cities". The innovation spatial structure of Shanghai and Beijing have intrinsic consistency with the spatial structure of their respective regions(Yangtze River Delta urban agglomeration and Beijing-Tianjin-Hebei metropolitan region), which suggested that the principle of proportional and disproportional distribution of a city-scale pattern of technological and innovational activities is closely related to its regional innovation pattern.
基金supported by National Institute of Health Grant HL-48739 and HL-68216
文摘In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.
文摘Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mass is found world-wide as more cultures acquire a Western lifestyle.In the United States,life expectancy declines by 3 years for those with a body mass index over 30 and by 10 years for those with a body mass index over 40 due,in large part,to the increased prevalence of cardiovascular disease.Over the past decade we have come to appreciate that adipose tissue functions as an endocrine organ,and that obesity contributes to cardiovascular and metabolic disorders through cytokine imbalances that promote the development of a chronic,low grade inflammatory state.Bioactive proteins secreted from fat are generally referred to as adipokines.Under conditions of obesity,adipose tissue expresses higher levels of pro-inflammatory adipokines,such as TNF- and IL- 6,and lower levels of anti-inflammatory cytokines. Adiponectin in the prototypical anti-inflammatory adipokine,and its expression is down-regulated in obese individuals.Low adiponectin levels have shown to be an independent risk factor for developing type 2 diabetes,myocardial infarction and hypertension. Studies with genetically manipulated mice have shown that adiponectin protects against the development of a number of diseases that are prevalent in obese individuals including insulin re- sistance,atherosclerosis,LV hypertrophy,and a peripheral artery disease.However,no adiponectin-based therapies have been successfully launched in the clinic due,in large part,to difficulties associated with the high natural abundance of adiponectin (0.01%of the serum protein) and its complex structure.My laboratory performs genetic screens to identify novel adiponectin-like factors involved in metabolic and cardiovascular regulation.One of these newly discovered factors,referred to as Sfrp5, is a secreted protein that is largely produced by adipocytes.Sfrp5 functions by binding to and inhibiting the actions on non-canonical,pro-inflammatory Wnt proteins.We have shown that Sfrp5 and Wnt5a function as a molecular rheostat to control the inflammatory state of the fat pad microenvironment. It is likely that this system also functions to control inflammatory processes that occur in cardio-vascular diseases.
