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Intracellular accumulation of tau inhibits autophagosome formation by activating TIA1-amino acid-mTORC1 signaling

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Military Medical Research 2023年第2期10卷 175-190页

作者： Meng-Zhu Li En-jie liu Qiu-Zhi Zhou shi-Hong Li shi-jie liu Hai-Tao Yu Qi-Hang Pan Fei Sun Ting He Wei-Jin Wang Dan Ke Yu-Qi Feng Jun Li Jian-Zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurosurgery the Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Chemistry Wuhan UniversityWuhan 430072China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226000JiangsuChina.

Background:Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer’s disease(AD).This study aimed to investigate whether and how the accumulating tau may in turn affect ***:The primary hippocampal neurons,N2a and HEK293T cells with tau overexpression were respectively starved and treated with vinblastine to study the effects of tau on the initiating steps of autophagy,which was analysed by Student’s two-tailed *** rapamycin and concanamycin A were employed to inhibit the mammalian target of rapamycin kinase complex 1(mTORC1)activity and the vacuolar H+-ATPase(v-ATPase)activity,respectively,which were analysed by One-way ANOVA with post hoc *** Western blotting,co-immunoprecipitation and immunofuorescence staining were conducted to gain insight into the mechanisms underlying the tau effects of mTORC1 signaling alterations,as analysed by Student’s two-tailed t-test or One-way ANOVA with post hoc *** autophagosome formation was detected by immunofuorescence staining and transmission electron *** amino acids(AA)levels were detected by high performance liquid chromatography(HPLC).Results:We observed that overexpressing human full-length wild-type tau to mimic AD-like tau accumulation induced autophagy *** studies revealed that the increased tau could bind to the prion-related domain of T cell intracellular antigen 1(PRD-TIA1)and this association significantly increased the intercellular level of amino acids(Leucine,P=0.0038;Glutamic acid,P=0.0348;Alanine,P=0.0037;Glycine,P=0.0104),with concordant upregulation of mTORC1 activity[phosphorylated eukaryotic translation initiation factor 4E-binding protein 1(p-4EBP1),P<0.0001;phosphorylated 70 kD ribosomal protein S6 kinase 1(p-p70S6K1),P=0.0001,phosphorylated unc-51-like autophagyactivating kinase 1(p-ULK1),P=0.0015]and inhibition of autophagosome formation[microtubuleassociated protein light chain 3 II(LC3 II),P=0.0073;LC3 pun

关键词： Tau Autophagy Amino acid pathway Mammalian target of rapamycin kinase complex 1(mTORC1) T cell intracellular antigen 1(TIA1)

Effects of the geometrical parameters of the injection nozzle on ethylene-air continuous rotating detonation

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2021年第7期22卷 547-563页

作者： Wei-jie FAN Jin ZHOU shi-jie liu Hao-yang PENG Science and Technology on Scramjet Laboratory College of Aerospace Science and TechnologyNational University of Defense TechnologyChangsha 410073China

Compared with traditional isobaric combustion,continuous rotating detonation(CRD)has been theoretically proved to be a more efficient combustion mode with higher thermal cycle ***,the realization and stable operating of liquid kerosene detonation is still a *** a major component of kerosene pyrolysis products after regenerative cooling,ethylene is a transitional hydrocarbon fuel from kerosene to hydrogen and it is worth *** this paper,a series of 2 D numerical simulations are conducted to investigate the effects of the injection nozzle on the ethylene-air *** geometrical parameters of the nozzle are thoroughly tested including the distance between two neighboring nozzle centers,the nozzle exit width,and the slant angle of the *** results show that an ethylene-air detonation wave is realized and it propagates stably.A small distance between two neighboring nozzle centers is conducive to improving the strength of the CRD wave and leads to greater feedback pressure into the *** the nozzle exit width increases,the strength of the CRD wave and the feedback pressure into the plenum both *** CRD wave propagation velocity is greatly improved and the feedback pressure into the plenum is significantly reduced when the slant angle of the nozzle is *** contrast,a sizeable reduction in velocity is found when the angle is *** co-rotating two-wave propagation mode is observed when the angle is 30°,and the highest CRD propagation velocity and the lowest feedback pressure are both obtained when the angle is 60°.

关键词： Continuous rotating detonation(CRD) Ethylene-air Injection nozzle Feedback pressure

Numerical study on ethylene-air continuous rotating detonation in annular combustors with different widths

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2022年第5期23卷 388-404页

作者： Wei-jie FAN Wei-dong liu Hao-yang PENG shi-jie liu Jian SUN Science and Technology on Scramjet Laboratory College of Aerospace Science and TechnologyNational University of Defense TechnologyChangsha 410073China State Key Laboratory of Aerospace Dynamic Satellite Control CenterXi’an 710043China

To investigate the impact of combustor width on continuous rotating detonation(CRD)fueled by ethylene and air,a series of 3 D simulations are conducted by changing the inner cylinder radius of an annular combustor while retaining the same outer cylinder *** results show that the CRD wave propagates more steadily and faster as the combustor width *** high-temperature zone at the backward-facing step preheats the propellants and contributes to the steady propagation of the CRD wave in 25-and 30-mm wide *** highest and the lowest velocities are obtained in the30-and 15-mm wide combustors at,respectively,1880.27 and 1681.01 m/*** the other hand,the average thrust decreases as the combustor width *** highest thrust is obtained in the 15-mm wide combustor while the lowest is in the 30-mm wide combustor,at 758.06 and 525.93 N,***,the thrust is much more stable in the 25-and 30-mm wide combustors than in the 15-and 20-mm wide combustors.

关键词： Continuous rotating detonation(CRD) Ethylene-air Combustor width Propagation mode Propulsive performance

Catalytic transfer hydrogenation of biomass-derived furfural to furfuryl alcohol with formic acid as hydrogen donor over CuCs-MCM catalyst

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Chinese Chemical Letters 2021年第3期32卷 1186-1190页

作者： Tao Wang Juan Du Yong Sun Xing Tang Zuo-Jun Wei Xianhai Zeng shi-jie liu Lu Lin Xiamen Key Laboratory of Clean and High-valued Utilization for Biomass College of EnergyXiamen UniversityXiamen 361102China Fujian Engineering and Research Center of Clean and High-valued Technologies for Biomass Xiamen 361102China School of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310058China Department of Paper and Bioprocess Engineering State University of New York College of Environmental Science and ForestrySyracuseNew York 13210United States State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyGuangdong Microbial Culture Collection Center(GDMCC)Guangdong Institute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China

Catalytic transfer hydroge nation(CTH)of furfural(FF)to furfu ryl alcohol(FFA)has received great intere st in recent *** rein,Cu-Cs bimetallic supported catalyst,CuCs(2)-MCM,was developed for the CTH of FF to FFA using formic as hydrogen ***(2)-MCM achieved a 99.6%FFA yield at an optimized reaction conditions of 170℃,1 *** species in CuCs(2)-MCM had dual functions in catalytically decomposing formic acid to generate hydrogen and hydrogenating FF to *** doping of Cs made the size of Cu particles smaller and improved the dispersion of the Cu active *** rtantly,the Cs species played a favorable role in enhancing the hydrogenation activity as a promoter by adjusting the surface acidity of Cu species to an appropriate *** analysis showed that surface acidity is the primary factor to affect the catalytic activity of CuCs(2)-MCM.

关键词： Furfural Furfuryl alcohol CuCs(x)-MCM catalysts Catalytic transfer hydrogenation Formic acid

PTC: Full and Drift Particle Orbit Tracing Code for α Particles in Tokamak Plasmas

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Chinese Physics Letters 2021年第5期38卷 36-40页

作者： Feng Wang Rui Zhao Zheng-Xiong Wang Yue Zhang Zhan-Hong Lin shi-jie liu CFETR Team Key Laboratory of Materials Modification by Laser Ion and Electron Beams(Ministry of Education)School of PhysicsDalian University of TechnologyDalian 116024China

Fusion born α particle confinement is one of the most important issues in burning plasmas,such as ITER and ***,it is extremely complex due to the nonequilibrium characteristics,and multiple temporal and spatial scales coupling with background plasma.A numerical code using particle orbit tracing method(PTC)has been developed to study energetic particle confinement in tokamak *** full orbit and drift orbit solvers are implemented to analyze the Larmor radius effects on α particle *** elastic collisions between alpha particles and thermal plasma are calculated by a Monte Carlo method.A triangle mesh in poloidal section is generated for electromagnetic fields *** between PTC and ORBIT has been accomplished for *** CFETR burning plasmas,PTC code is used for α particle source and slowing down process calculation in 2D *** future work,3D field like toroidal field ripples,Alfven and magnetohydrodynamics instabilities perturbation inducing α particle transport will be analyzed.

关键词： CFETR Full and Drift Particle Orbit Tracing Code for Particles in Tokamak Plasmas PTC Tokamak

Prolonged Alzheimer-like Tau Hyperphosphorylation Induced by Simultaneous Inhibition of Phosphoinositol-3 Kinase and Protein Kinase C in N2a cells

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Acta Biochimica et Biophysica Sinica 2005年第5期37卷 349-354页

作者： Guo-Gang XU Yan-Qiu DENG shi-jie liu Hong-Lian LI Jian-Zhi WANG Department of Pothophysiology,Institute of Neuroscience,Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Department of Pathophysiology Institute of Neuroscience Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030 China

Co-injection of wortmannin（inhibitor of phosphatidylinositol-3 kinase,PI3K）and GF109203X（inhibitor of protein kinase C,PKC）into the rat brain was found to induce spatial memory deficiency andenhance tau hyperphosphorylation in the hippocampus of rat *** establish a cell model with durativeAlzheimer-like tau hyperphosphorylation in this study,we treated N2a neuroblastoma cells with wortmanninand GF109203X separately and simultaneously,and measured the glycogen synthase kinase 3（GSK-3）activity by γ-（32）P-labeling and the level of tau phosphorylation by Western *** was found that theapplication of wortmannin alone only transitorily increased the activity of GSK-3（about 1 h）and the level oftau hyperphosphorylation at Ser396/Ser404 and Ser199/Ser202 sites（no longer than 3 h）;however,a prolongedand intense activation of GSK-3（over 12 h）and enhanced tan hyperphosphorylation（about 24 h）wereobserved when these two selective kinase inhibitors were applied *** conclude that the simultaneousinhibition of PI3K and PKC can induce GSK-3 overactivation,and further strengthen and prolong the Alzheimer-like tau hyperphosphorylation in N2a cells,suggesting the establishment of a cell model with early pathologicalevents of Alzheimer’s disease.

关键词： Alzheimer’s disease(AD) tau glycogen synthase kinase 3(GSK-3) protein kinase C(PKC) phosphatidylinositol-3 kinase(PI3K) N2a cells

Spatially resolved transcriptomic profiling of placental development in dairy cow

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Zoological Research 2024年第3期45卷 586-600页

作者： Guang-Hui Tan shi-jie liu Ming-Le Dou De-Feng Zhao Ao Zhang Heng-Kuan Li Fu-Nong Luo Tao shi Hao-Ping Wang Jing-Yuan Lei Yong Zhang Yu Jiang Yi Zheng Fei Wang Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYanglingShaanxi 712100China Key Laboratory of Livestock Biology Northwest A&F UniversityYanglingShaanxi 712100China Key Laboratory of Animal Biotechnology of the Ministry of Agriculture Northwest A&F UniversityYanglingShaanxi 712100China College of Information Engineering Northwest A&F UniversityYanglingShaanxi 712100China

The placenta plays a crucial role in successful mammalian *** animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons,essential for full-term fetal *** cow placenta harbors at least two trophoblast cell populations:uninucleate(UNC)and binucleate(BNC)***,the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches,and the molecular mechanisms governing trophoblast differentiation and *** fill this knowledge gap,we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation,attaining high-resolution,spatially resolved gene expression *** on clustering and cell marker gene expression analyses,key transcription factors,including YBX1 and NPAS2,were shown to regulate the heterogeneity of trophoblast cell *** communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental *** analysis of cell trajectories identified a set of genes involved in regulation of trophoblast ***,spatial modules and co-variant genes that help shape specific tissue structures were ***,these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

关键词： Spatial transcriptomics Dairy cow Placenta Gestation

Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions

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Acta Pharmacologica Sinica 2004年第3期25卷 22-26页

作者： Yi-peng WANG,Xian-tao LI,shi-jie liu,Xin-wen ZHOU,Xiao-chuan WANG,Jian-zhi WANG2 TongjiMedical College,Huazhong University of Science and Technology,Wuhan 430030,China Tongji Medical College Huazhong University of Science and Technology Wuhan 430030

AIM: To explore the protective effects of melatonin (Mel) on the abnormal phosphorylation of neuronal cytoskeletal proteins. METHODS: We generated a neuroblastoma (SH-SY5Y) cell system in which cytoskeletal proteins are abnormally phosphorylated resulting in microtubule disruption due to the marked inhibition of protein phosphatase activities by okadaic acid (OA). RESULTS: OA-induced declines in cell viability and mitochondrial metabolic activity were remarkably prevented by Mel. In addition, the hyperphosphorylation/accumulation of neurofilament- (NF-) H/M subunits and the disruption of microtubules, induced by OA, were significantly inhibited by Mel. CONCLUSION: Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.

关键词： Alzheimer disease protein phosphatase okadaic acid neurofilament proteins melatonin

Research progress of renal interstitial fibrosis

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TMR Integrative Medicine 2017年第3期1卷 109-123页

作者： shi-jie liu Xi Zhao Yao-Guang Wang Man Li Tianjin University of Traditional Chinese Medicine Tianjin China The First Teaching Hospital of TianjinUniversity of Traditional Chinese Medicine Tianjin China Tianjin Beichen District Chinese Medicine Hospital Tianjin China

Renal interstitial fibrosis （RIF） is a common pathological process of chronic kidney disease that progresses toend-stage renal failure. The degree of RIF is closely related to renal function. The study of the pathogenesis of renalinterstitial fibrosis, exploration of effective prevention measures to delay the progress of end stage renal disease andprolong the life of patients is significant. The pathology of RIF has complicated extracellular and intercellularmechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of thedisease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because currentmedical approaches do not reliably slow or reverse RIF. The research progress of RIF in recent years issummarized as follows.

关键词： Renal interstitial fibrosis Research process Mechanism