Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

Effects of freeze-thaw cycle and dry-wet alternation on slope stability

The typical loess on high slopes along the BaoLan High-speed Rail, China, was selected as the research object. The influence of the freeze-thaw cycle and dry-wet alternation on the shear-strength parameters of the unsaturated loess was investigated by laboratory experimental methods. Moreover, the temperature field, seepage field, and stability of slopes with different gradients were simulated under the effect of the freeze-thaw cycle and dry-wet alternation by using the geotechnical analysis software Geo-Studio. The research results showed(1) when the freeze-thaw cycle was repeated on the slope, with the frozen depth increasing, the melted depth did the same; besides, the closed loop of isotherms formed on the slope;(2) under the action of dry-wet circulation, the negative pore-water pressure and volumetric water content showed an upward tendency. However, owing to the different slope gradients, rainfall infiltration was not the same. As time went by, the differences of the negative pore-water pressure and volumetric water content between the slopes of different gradients continued to increase;(3) with the freeze-thaw cycle and dry-wet alternation increasing, the slope-safety factor decreased. Especially in the early period, the slope-safety factor changed remarkably. For slopes undergoing freeze-thaw action, the slope-safety factor was negatively correlated with the gradient. However, with regard to slopes undergoing dry-wet alternation, the result became more complex because the slope-safety factor was related to both seepage strength and slope grade. Accordingly, further research is needed to study the effect of seepage strength and slope grade on the stability of loess slopes.

The Structure and Magnetic Properties of Co₇₇Zr₁₈W₅Melt-Spun Ribbons

Based on X-ray diffraction, microscopic and magnetic analysis, the structure and magnetic properties of Co77Zr18W5 melt-spun ribbons were studied in this paper. A new element to stabilize the metastable Co5Zr phase was found and the coercivity observed in Co-Zr alloys can be obviously enhanced by proper tungsten substitution. The Curie temperature of Co77Zr18W5 ribbons is 475℃ which suggests that W doped Co-Zr alloys may become an attractive candidate perma- nent magnets for practical applications in high temperature. Annealing of the Co77Zr18W5 ribbons results in a decrease of the coercivity which confirmed that the hard magnetic phase is Co5Zr phase in 77Zr18W5 melt-spun ribbons.

妥拉唑啉控制雏鸡实验性近视进展的有效性和安全性

目的::研究肾上腺素α受体阻滞剂妥拉唑啉控制雏鸡实验性近视的有效性和安全性,并探讨其作用机制。方法::实验研究。于2021年3月将61只6日龄白莱航鸡随机分为形觉剥夺对照组(FDM)、形觉剥夺后妥拉唑啉组(FDM+T100)、形觉剥夺后妥拉唑啉联合L-NAME组(FDM+T100+L-NAME)和离焦诱导对照组(LIM)、离焦诱导后妥拉唑啉组(LIM+T100)、离焦诱导后妥拉唑啉联合L-NAME组(LIM+T100+L-NAME)进行有效性研究;空白对照组(Blank)、单纯妥拉唑啉干预组(Blank+T100)进行安全性研究。所有雏鸡均取右眼进行实验干预,妥拉唑啉干预组在造模的同时每天进行玻璃体腔注射12.5μL妥拉唑啉,妥拉唑啉联合L-NAME干预组注射等量妥拉唑啉和L-NAME,对照组注射等体积0.9%氯化钠溶液,持续6 d。记录和统计分析各组处理前后的屈光度和眼球生物参数。安全性研究中,对Blank组和Blank+T100组雏鸡诱导结束后进行视网膜电图检查。雏鸡处死后眼球固定切片进行TUNEL染色观察视网膜功能损害程度。不同近视模型中对照组与T100组、T100组与T100+L-NAME组两两比较,采用独立样本t检验和Mann-Whitney U检验。结果::经过6 d处理后,在形觉剥夺模型中,与FDM组相比,FDM+T100组的屈光度近视化减少(t=-16.16,P<0.001),眼轴增长量减少(t=12.41,P<0.001),脉络膜厚度减薄量减少(t=-2.46,P=0.031);与FDM+T100组相比,FDM+T100+L-NAME组屈光度近视化增加(t=4.20,P=0.001),眼轴增长量增加(t=-2.33,P=0.033)。在离焦诱导模型中,与LIM组相比,LIM+T100组屈光度近视化减少(t=-5.77,P<0.001),眼轴增长量减少(t=4.19,P<0.001);与LIM+T100组相比,LIM+T100联合L-NAME组屈光度近视化增加(t=3.74,P=0.001),眼轴增长量增加(t=-3.20,P=0.005)。安全性研究中,Blank组和Blank+T100组的屈光度及眼球生物参数变化值之间差异均无统计学意义(均P>0.05);ERG结果显示,Blank组和Blank+T100组相比,双眼各检测指标比值之间差异均无统计学意义(均P>0.05)。TUNEL染色显示各组均未见显著凋亡。结论::妥拉唑啉能够有效延缓雏鸡实验性近视的屈光度和眼轴进展,但在应用L-NAME后减弱,提示在妥拉唑啉扩张脉络膜血管时可能也有一氧化氮共同参与发挥作用。

Molecular engineering and biomedical applications of ultra-sensitive fluorescent probe for Ag^(+)

A series of probes KJ-x(x=1-3)with carbon chains of different lengths based on the matrix of rhodamine B were engineered to detect Ag^(+)in aqueous solution in this work.Among them,KJ-1 is selected as the best option after in vitro investigation in view of its most sensitive and rapid response to Ag^(+),whose possible sensing mechanism is studied by experimental investigation and theoretical calculation.To identify the practical application of the probe,the detection of Ag^(+)in nonantibiotic fungicide Silver&Health and differentiation between normal hepatocytes and hepatoma cells using confocal imaging was conducted.

Lysosome-targeting red fluorescent probe for broad carboxylesterases detection in breast cancer cells

Available online The abnormal carboxylesterase(CES)expression is closely related to many diseases such as hyperlipidemia,atherosclerosis,obesity,liver cancer,type 2 diabetes mellitus and gastrointestinal stromal tumors.The detection of a single enzyme in practical samples is often constrained by the structural diversity of CESs.Thus,the development of broad-carboxylesterase responsive fluorescent probe,which can detect the presence of wide variety of CESs,may provide overall or category information from another point of view,supplementing the deficiency of single detection for CES subspecies.Organelle lysosome is involved in various cell processes,such as cell signaling,apoptosis,secretion,and energy metabolism.Up to date,lysosome-targeted fluorescent probes,especially those with red emission(over 550 nm,with relatively low biological harmfulness),for CES detection are still rare.A lysosomes-targeted red fluorescent probe CES-Lyso was designed to monitor intracellular a variety of carboxylesterases alteration with wonderful selectivity and sensitivity,which was further applied to distinguish different derived breast cancer cells and monitor carboxylesterase activity in the anticancer drug treatment.

基于RNA-seq技术的雏鸡晚期离焦识别转录组学研究

目的:探讨晚期离焦识别的分子机制。方法:实验研究。将30只7 d龄白来航鸡随机分为负镜组、正镜组和对照组,分别给予雏鸡右眼-10 D/+10 D/0 D透镜诱导,干预时间为6 d。所有动物均在光学干预前后测量屈光度、眼轴和后极部各组织厚度等生物学参数。采用单因素方差分析对数据进行分析。眼球生物学参数测量完毕后分离眼后极部组织,提取RNA,应用RNA-seq技术筛选差异表达基因,并对其进行GO功能注释、KEGG通路分析及PPI网络分析,观察离焦干预对雏鸡后极部各组织转录组的影响。结果:负镜组、正镜组雏鸡的屈光度、眼轴长度以及脉络膜厚度,与对照组相比,差异具有统计学意义(P<0.05);以P<0.05和|log2FC|>1为筛选标准,负镜组与对照组相比,视网膜有203个差异表达基因,脉络膜有757个差异表达基因,巩膜有1509个差异表达基因;正镜组与对照组相比,视网膜有191个差异表达基因,脉络膜有378个差异表达基因,巩膜有1918个差异表达基因。与对照组比,负镜组与正镜组的重叠基因除LOC121112941外均表现出相同的差异表达趋势,GO分析通路存在50%以上重合,KEGG分析视网膜水平的重叠通路是花生四烯酸代谢、酪氨酸代谢和视黄醇代谢;脉络膜水平的重叠通路是内质网中的蛋白质加工,精氨酸和脯氨酸代谢和视黄醇代谢;巩膜水平的重叠通路则为细胞粘附分子、ECM-受体相互作用、粘着斑、细胞因子-细胞因子受体相互作用、硫代谢、糖胺聚糖生物合成-硫酸软骨素/硫酸皮肤素、Toll样受体信号通路、TGF-β信号通路和MAPK信号通路。通过PPI蛋白互作网络分析鉴定出离焦识别过程中各组织的关键基因。结论:本研究在转录组水平上筛选出晚期离焦识别过程的绝大多数重叠基因保持着相同的上调或下调表达趋势,不同方向的离焦信号可能诱导部分通路的相似变化。