Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the s...Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the so-called type-a waves(large-amplitude rank-ordered wave packets)and type-b waves(isolated wave packets)in the northern South China Sea.At first,we summarized and analyzed the generation and propagation characteristics of these waves.Then,energy budget at the Luzon Strait is calculated.Energy generation has three local maxima every day,of which the largest one corresponds to the emergence of the type-a wave.Energy flux at the west boundary of the Luzon Strait shows two local maxima each day.The larger one is consistent with the generation of the type-a wave and the smaller one is in correspondence with the generation of the type-b wave.Sensitivity experiments are designed to explore the role of the east and west ridge of the Luzon Strait on the generation and propagation of the type-a and type-b waves.It is found that the east ridge is indispensable on the generation of the type-a wave while the west ridge has little contribution.The west ridge diminishes the type-a waves'amplitude but hardly changes their propagation speed.The type-b waves also come from perturbation signals which originate from the east ridge and are enhanced in amplitude and reduced in propagation speed by the west ridge.展开更多
Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specif...Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specific transporters.However,the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.Loss-of-function mutants of OsHKT2;1,which is involved in sodium uptake,exhibit strong salt stress-resistant phenotypes.In this study,OsHKT2;1 was identified as a transcriptional target of the type-B response regulator OsRR22.Loss-of-function osrr22 mutants showed resilience to salt stress,and OsRR22-overexpression plants were sensitive to salt stress.OsRR22 was found to activate the expression of OsHKT2;1 by directly binding to the promoter region of OsHKT2;1 via a consensus cis-element of type-B response regulators.Moreover,rice DELLA protein OsSLR1 directly interacted with OsRR22 and functioned as a transcriptional co-activator.This study has uncovered a novel transcriptional regulatory mechanism by which a type-B response regulator controls sodium transport under salinity stress.展开更多
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金The National Key Research and Development Plan of China under contract No.2016YFC1401300the National Natural Science Foundation of China under contract No.41276008the Taishan Scholars Program
文摘Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the so-called type-a waves(large-amplitude rank-ordered wave packets)and type-b waves(isolated wave packets)in the northern South China Sea.At first,we summarized and analyzed the generation and propagation characteristics of these waves.Then,energy budget at the Luzon Strait is calculated.Energy generation has three local maxima every day,of which the largest one corresponds to the emergence of the type-a wave.Energy flux at the west boundary of the Luzon Strait shows two local maxima each day.The larger one is consistent with the generation of the type-a wave and the smaller one is in correspondence with the generation of the type-b wave.Sensitivity experiments are designed to explore the role of the east and west ridge of the Luzon Strait on the generation and propagation of the type-a and type-b waves.It is found that the east ridge is indispensable on the generation of the type-a wave while the west ridge has little contribution.The west ridge diminishes the type-a waves'amplitude but hardly changes their propagation speed.The type-b waves also come from perturbation signals which originate from the east ridge and are enhanced in amplitude and reduced in propagation speed by the west ridge.
基金supported by the National Natural Science Foundation of China (32001448,32272027)。
文摘Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specific transporters.However,the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.Loss-of-function mutants of OsHKT2;1,which is involved in sodium uptake,exhibit strong salt stress-resistant phenotypes.In this study,OsHKT2;1 was identified as a transcriptional target of the type-B response regulator OsRR22.Loss-of-function osrr22 mutants showed resilience to salt stress,and OsRR22-overexpression plants were sensitive to salt stress.OsRR22 was found to activate the expression of OsHKT2;1 by directly binding to the promoter region of OsHKT2;1 via a consensus cis-element of type-B response regulators.Moreover,rice DELLA protein OsSLR1 directly interacted with OsRR22 and functioned as a transcriptional co-activator.This study has uncovered a novel transcriptional regulatory mechanism by which a type-B response regulator controls sodium transport under salinity stress.
文摘目的分析体质量指数(Body mass index,BMI)与老年慢性心力衰竭(Chronic heart failure,CHF)患者血浆胱抑素C(cystatinC,Cys-C)、N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平相关性,并分析血浆Cys-C、NT-proBNP评估老年CHF患者预后价值。方法选择2021年7月—2022年10月在本院接受治疗的192例老年慢性心力衰竭(CHF)患者作为研究对象,按照BMI指数分为肥胖组(49例)、超重组(68例)和正常组(75例)三组。对比各亚组患者血浆Cys-C、NT-proBNP水平差异,采用Pearson相关性分析的方式探究老年CHF患者BMI指数与血浆Cys-C、NT-proBNP相关性,对入组患者实施12个月随访,将患者按照预后情况区分为死亡组和存活组,对比两亚组患者血浆Cys-C、NT-proBNP水平差异并评估预后评估价值。结果肥胖组患者血浆Cys-C、NT-proBNP水平高于超重组,超重组患者血浆Cys-C、NT-proBNP水平高于正常组,差异具有统计学意义(P<0.05);入组老年CHF患者的BMI指数与其血浆Cys-C、NT-proBN水平均呈现明显的正相关性(r=0.7104,P<0.0001)(r=0.6603,P<0.0001);随访12个月显示,死亡组患者的血浆Cys-C、NT-proBNP水平显著高于存活组患者,差异具有统计学意义(P<0.05);血浆Cys-C、NT-proBNP对老年CHF预后评估曲线下面积(area under curv,AUC)为0.6930(P=0.0009)、0.7982(P<0.0001)。结论老年CHF患者随BMI指数升高,血浆Cys-C、NT-proBNP水平逐渐升高,血浆Cys-C、NT-proBNP对老年CHF临床结局具有一定的预测价值,进一步研究有推广应用于老年CHF预后评估潜力。
