内源性二氧化硫是心血管系统新的具有治疗前景的气体信号分子

Sulfur dioxide(SO_(2))was previously considered only as air pollutant.In 2008,our group first detected the endogenous SO_(2)gener-ating enzymes as well as its generating pathway in cardiovascular system[1].Our recent studies have shown that endogenous SO_(2)plays important cardiovascular physiologic regulatory roles and has pathophysiological significance.As such,we suggested that it serves as a new gasotransmitter[1-4].

OsHYPK-mediated protein N-terminal acetylation coordinates plant development and abiotic stress responses in rice

N-terminal acetylation is one of the most common protein modifications in eukaryotes,and approximately 40%of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A(NatA)in a co-translational manner.However,the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear.Here,we identify Huntingtin Yeast partner K(HYPK),an evolutionarily conserved chaperone-like protein,as a positive regulator of NatA activity in rice.We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses,attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover.Furthermore,we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation,probably through the Ac/N-degron pathway,which could be induced by abiotic stresses.Taken together,our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover,which are essential for maintaining adaptive phenotypic plasticity in rice.

Macrophage-targeted nanomedicine for chronic diseases immunotherapy

Macrophage is the key innate immune effector in first-line defense against the pathogens, and can be polarized into different phenotypes to regulate a variety of immunological functions. However, the plasticity of macrophage is extraordinarily recruited, activated, and polarized under pathological conditions,playing paramount roles in occurrence, development, and prognosis of various chronic diseases, such as rheumatoid arthritis(RA), atherosclerosis(AS), and cancer. To this end, macrophage has become an important therapeutic target for etiological treatment of these diseases. Meanwhile, with the development of nanotechnology, various nano-drug delivery systems have been explored to target macrophages for disease modulation, displaying unique advantages to address both pharmaceutic and biopharmaceutic limitations of various drugs. This review aims to summarize the recent progress of macrophage-targeted nanomedicine for chronic diseases immunotherapy. First, the origin, polarization and biological functions of macrophages have been introduced, in which macrophages can differentiate into different phenotypes in response to physiological stimuli to play various immunological roles. Then, the macrophage disorder has been reviewed in related with various chronic diseases, and several representative diseases, including AS, RA, obesity, and cancer, have been discussed in detail to elucidate the pathological contributions of macrophages for disease progress. Next, strategies to regulate macrophages for diseases immunotherapy, such as macrophages depletion, macrophage reprograming, inhibition of macrophage recruitment,are summarized, and particular attention has been paid on bio-functional nanomaterials to engineer macrophages via different mechanisms. Further, methods for macrophage-targeting delivery nanosystems are discussed based on both passive and active targeting approaches. Finally, the perspective is speculated for potential clinical translation, and there still has significant room for the development of novel macrophage-targeting nanomedicine for precise, effective, and biosafe therapy.