Cyclic GMP-AMP(cGAMP)synthase(cGAS)plays a pivotal role in the innate immune system.As the primary DNA sensor in cells,cGAS binds to dsDNA in the cytoplasm and forms cGAS-DNA liquid-liquid phase separation(LLPS)and ac...Cyclic GMP-AMP(cGAMP)synthase(cGAS)plays a pivotal role in the innate immune system.As the primary DNA sensor in cells,cGAS binds to dsDNA in the cytoplasm and forms cGAS-DNA liquid-liquid phase separation(LLPS)and activates its catalytic activity.This activation triggers the cGAS-stimulator of interferon genes(STING)signaling pathway,establishing an efficient system for pathogen detection.Beyond pathogen surveillance,cGAS performs a diverse range of roles,involved in inflammatory response,metabolic homeostasis,DNA damage repair,and cell death.These biological functions regulate cellular physiological homeostasis and influence the occurrence and development of diseases.This review provides an overview of the structure,localization,and intracellular biological functions of the cGAS-STING signaling pathway and cGAS-DNA LLPS.Furthermore,we discuss their contribution to the development of tumors,autoimmune diseases,and inflammatory diseases and highlight the innovative strategies in modulating cGAS activity,either through activation or inhibition,as a promising therapeutic approach.展开更多
In regard to erectile function, Yin is flaccidity and Yang erection. In the past decade, research has mostly focused on the Yang aspect of erectile function. However, in recent years, the Yin side is attracting increa...In regard to erectile function, Yin is flaccidity and Yang erection. In the past decade, research has mostly focused on the Yang aspect of erectile function. However, in recent years, the Yin side is attracting increasingly greater attention. This is due to the realization that penile flaccidity is no less important than penile erection and is actively maintained by mechanisms that play critical roles in certain types of erectile dysfunction （ED）; for example, in diabetic patients. In addition, there is evidence that the Yin and Yang signaling pathways interact with each other during the transition from flaccidity to erection, and vice versa. As such, it is important that we view erectile function from not only the Yang but also the Yin side. The purpose of this article is to review recent advances in the understanding of the molecular mechanisms that regulate the Yin and Yang of the penis. Emphasis is given to the Rho kinase signaling pathway that regulates the Yin, and to the cyclic nucleotide signaling pathway that regulates the Yang. Discussion is organized in such a way so as to follow the signaling cascade, that is, beginning with the extracellular signaling molecules （e.g., norepinephrin and nitric oxide） and their receptors, converging onto the intracellular effectors （e.g., Rho kinase and protein kinase G）, branching into secondary effectors, and finishing with contractile molecules and phosphodiesterases. Interactions between the Yin and Yang signaling pathways are discussed as well.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22274166,22021003,22234008,21927807)the Project of the Youth Innovation Promotion Association,Chinese Academy of Sciences(No.2023047).
文摘Cyclic GMP-AMP(cGAMP)synthase(cGAS)plays a pivotal role in the innate immune system.As the primary DNA sensor in cells,cGAS binds to dsDNA in the cytoplasm and forms cGAS-DNA liquid-liquid phase separation(LLPS)and activates its catalytic activity.This activation triggers the cGAS-stimulator of interferon genes(STING)signaling pathway,establishing an efficient system for pathogen detection.Beyond pathogen surveillance,cGAS performs a diverse range of roles,involved in inflammatory response,metabolic homeostasis,DNA damage repair,and cell death.These biological functions regulate cellular physiological homeostasis and influence the occurrence and development of diseases.This review provides an overview of the structure,localization,and intracellular biological functions of the cGAS-STING signaling pathway and cGAS-DNA LLPS.Furthermore,we discuss their contribution to the development of tumors,autoimmune diseases,and inflammatory diseases and highlight the innovative strategies in modulating cGAS activity,either through activation or inhibition,as a promising therapeutic approach.
文摘In regard to erectile function, Yin is flaccidity and Yang erection. In the past decade, research has mostly focused on the Yang aspect of erectile function. However, in recent years, the Yin side is attracting increasingly greater attention. This is due to the realization that penile flaccidity is no less important than penile erection and is actively maintained by mechanisms that play critical roles in certain types of erectile dysfunction （ED）; for example, in diabetic patients. In addition, there is evidence that the Yin and Yang signaling pathways interact with each other during the transition from flaccidity to erection, and vice versa. As such, it is important that we view erectile function from not only the Yang but also the Yin side. The purpose of this article is to review recent advances in the understanding of the molecular mechanisms that regulate the Yin and Yang of the penis. Emphasis is given to the Rho kinase signaling pathway that regulates the Yin, and to the cyclic nucleotide signaling pathway that regulates the Yang. Discussion is organized in such a way so as to follow the signaling cascade, that is, beginning with the extracellular signaling molecules （e.g., norepinephrin and nitric oxide） and their receptors, converging onto the intracellular effectors （e.g., Rho kinase and protein kinase G）, branching into secondary effectors, and finishing with contractile molecules and phosphodiesterases. Interactions between the Yin and Yang signaling pathways are discussed as well.
