Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in ...Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.展开更多
Based on the retrospection of researches on carrying capacity, this article reviewed systematically the research progresses on carrying capacity of relative resources (CCRR). Then the viewpoint was put forward that CC...Based on the retrospection of researches on carrying capacity, this article reviewed systematically the research progresses on carrying capacity of relative resources (CCRR). Then the viewpoint was put forward that CCRR is not an appropriate method of appraising the regional sustainability, but a sound way to obtain cognition for coordinating spatial location and flow of population and economy. However, as the most popular computing method of CCRR, the Weighting Linear Sum Model is defective in the random of weight choice and the neglect of matching among different resources. Therefore, this article established the Geometric Model on CCRR based on modifying Weighting Linear Sum Model, which can be used to appraise regions where resources are close matching. Employing the Geometric Model, the article empirically analyzed the population and economic CCRR in Hubei Province from 1978 to 2006. The result indicates that the population in Hubei Province is overloading while the economic carrying capacity is abundant compared to the whole country, and the economic insufficiency restricts the population carrying capacity. In the future, Hubei Province will become one of the core developing zones which are characterized by economic conglomeration.展开更多
基金supported by the National Natural Science Foundation of China(81970202,81903609,U21A20339)the Natural Science Foundation of Heilongjiang Province,China(LH2022H002)+1 种基金the Outstanding Young Talent Research Fund of College of Pharmacy,Harbin Medical University(2019-JQ-02)2021(the second batch)Research Funds for affiliated research institutes in Heilongjiang Province(CZKYF2021-2-C013).
文摘Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.
基金National Natural Science Fundation of China (Grant No:40671062)
文摘Based on the retrospection of researches on carrying capacity, this article reviewed systematically the research progresses on carrying capacity of relative resources (CCRR). Then the viewpoint was put forward that CCRR is not an appropriate method of appraising the regional sustainability, but a sound way to obtain cognition for coordinating spatial location and flow of population and economy. However, as the most popular computing method of CCRR, the Weighting Linear Sum Model is defective in the random of weight choice and the neglect of matching among different resources. Therefore, this article established the Geometric Model on CCRR based on modifying Weighting Linear Sum Model, which can be used to appraise regions where resources are close matching. Employing the Geometric Model, the article empirically analyzed the population and economic CCRR in Hubei Province from 1978 to 2006. The result indicates that the population in Hubei Province is overloading while the economic carrying capacity is abundant compared to the whole country, and the economic insufficiency restricts the population carrying capacity. In the future, Hubei Province will become one of the core developing zones which are characterized by economic conglomeration.
