卧床休息与长期制动是重症监护室(intensive care unit,ICU)患者普遍存在的现象,这增加了ICU获得性衰弱及其他并发症的发生风险。早期康复有助于改善ICU患者身体功能,减少谵妄等问题的发生,提高其生存质量和生活质量,对促进其早日回归...卧床休息与长期制动是重症监护室(intensive care unit,ICU)患者普遍存在的现象,这增加了ICU获得性衰弱及其他并发症的发生风险。早期康复有助于改善ICU患者身体功能,减少谵妄等问题的发生,提高其生存质量和生活质量,对促进其早日回归家庭或社会具有重要意义。该文就ICU环境中患者早期康复实践现况及其影响因素进行综述。展开更多
Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function.Although it is well establis...Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function.Although it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals,little was known about the transportation mechanism and substrate specificity of spinster.Here,we report a crystal structure of spinster homolog from Hyphomonas neptunium,HnSPNS,in its inward-facing conformation with and without substrate bound.HnSPNS is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices.A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue,R42,which is locked in position by the interactions with conserved residues E129 and R122.Our results suggest that human spinster serves as a transporter translocating negativelycharged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.展开更多
The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the bloo...The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progre展开更多
文摘卧床休息与长期制动是重症监护室(intensive care unit,ICU)患者普遍存在的现象,这增加了ICU获得性衰弱及其他并发症的发生风险。早期康复有助于改善ICU患者身体功能,减少谵妄等问题的发生,提高其生存质量和生活质量,对促进其早日回归家庭或社会具有重要意义。该文就ICU环境中患者早期康复实践现况及其影响因素进行综述。
基金supported by the National Key Research and Development Program of China (2017YFC1001303 and 2018YFC1004704)NSFC-CAS Joint Fund for Research Based on Large-Scale Scientific Facilities (U1632132)+1 种基金NSFC General Program (31670849)SHIPM-pi fund (JY201804) from Shanghai Institute of Precision Medicine, Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine
文摘Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function.Although it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals,little was known about the transportation mechanism and substrate specificity of spinster.Here,we report a crystal structure of spinster homolog from Hyphomonas neptunium,HnSPNS,in its inward-facing conformation with and without substrate bound.HnSPNS is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices.A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue,R42,which is locked in position by the interactions with conserved residues E129 and R122.Our results suggest that human spinster serves as a transporter translocating negativelycharged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.
基金supported by the National Natural Science Foundation of China,No.82104412(to TD)Shaanxi Provincial Key R&D Program,No.2023-YBSF-165(to TD)+1 种基金the Natural Science Foundation of Shaanxi Department of Science and Technology,No.2018JM7022(to FM)Shaanxi Provincial Key Industry Chain Project,No.2021ZDLSF04-11(to PW)。
文摘The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progre
