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Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-lnduced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells

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Chinese Medical Journal 2018年第8期131卷 950-955页

作者： Guo-Qiang Zhang Yong-Kang Tao Yong-ping Bai Sheng-Tao Yan shui-ping zhao Department of Emergency China-Japan Friendship Hospital Beijing 100029 China Department of Geriatric Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Cardiology The Second Xiangya Hospital Central South University Changsha Hunan 410011 China

Background：Oxidized low-density lipoprotein （ox-LDL）-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic translation initiation factor 2α-subunit （eIF2α）/CCAAT/enhancer-binding protein homologous protein （CHOP） endoplasmic reticulum （ER） stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial ***：Human umbilical vein endothelial cells （HUVECs） were treated with simvastatin （0.1, 0.5, or 2.5 μmol/L） or DEVD-CHO （selective inhibitor of caspase-3, 100 μmol/L） for 1 h before the addition of ox-LDL （100 μg/ml） and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance （ANOVA） followed by post hoc pairwise comparisons using Tukey’s tests. A value of P 〈 0.05 was considered statistically ***：Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis （31.9% vs. 4.9%, P 〈 0.05）. Simvastatin （0.1, 0.5, and 2.5 μmol/L） led to a suppression of ox-LDL-induced apoptosis （28.0%, 24.7%, and 13.8%, F = 15.039, all P 〈 0.05, compared with control group）. Ox-LDL significantly increased the expression of PERK （499.5%, P 〈 0.05） and phosphorylation of eIF2α （451.6%, P 〈 0.05）, if both of which in the control groups were considered as 100%. Simvastatin treatment （0.1, 0.5, and 2.5 μmol/L） blunted ox-LDL-induced expression of PERK （407.8%, 339.1%, and 187.5%, F = 10.121, all P 〈 0.05, compared with control group） and phosphorylation of eIF2α （407.8%, 339.

关键词： Apoptosis Endoplasmic Reticulum Stress Endothelial Cells Oxidized Low-Density Lipoprotein Simvastatin

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2016 Chinese guidelines for the management of dyslipidemia in adults

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Journal of Geriatric Cardiology 2018年第1期15卷 1-29页

作者： Jun-Ren ZHU Run-Lin GAO shui-ping zhao Guo-ping LU Dong zhao Jian-Jun LI Joint committee for guideline revision

Abbreviations ACS： acute coronary syndrome ALT： alanine aminotransferase Apo： apolipoprotein ASCVD： atherosclerotic cardiovascular disease AST： aspartate aminotransferase

关键词： Adults Chinese guidelines Dyslipidemia

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L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

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Chinese Medical Journal 2016年第9期129卷 1108-1112页

作者： Xiang-Zhu Xie Xin Huang shui-ping zhao Bi-Lian Yu Qiao-Qing Zhong Jian Cao Department of Geriatric Cardiology Chinese PLA General Hospital Beijing 100853 China Postgraduate Department Chinese PLA Medical School Beijing 100853 China Department of Cardiology The Second XiangYa Hospital of Central South Univeisit-y Changsha Hunan 410011 China

Background： Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein- 1 （MCP- 1）. Oxidized low-density lipoprotein （oxLDL） participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinftammatory function of αLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L 1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods： Fully differentiated 3T3-L 1 adipocytes were incubated in the medium containing various concentration of L-4F （0-50 gg/ml） with oxLDL （50 Lag/ml） stimulated, with/without protein kinase A （PKA） inhibitor H-89 （10 gmol/L） preincubated. The concentrations of MCP- 1 in the supematant, the mRNA expression of MCP- 1, the levels of CCAAT/enhancer binding protein α （C/EBPα）, and CCAAT/ enhancer binding protein 13 （C/EBPβ） were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results： OxLDL stimulation induced a significant increase ofMCP-1 expression and secretion in 3T3-L 1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F （50 μg/ml）（P 〉 0.05）. OxLDL stimulation showed no significant effect on C/EBPa protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPI3 protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions： OxLDL induces C/EBPI3 protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L 1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBP-β signaling pat

关键词： Adipocytes CCAAT/Enhancer-Binding Proteins L-4F Monocyte Chemoattractant Protein-1 Oxidized low-densityLipoprotein Protein Kinase A

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Amendment of the low-density lipoprotein cholesterol target in the‘Chinese Guidelines for the Prevention and Treatment of Adult Dyslipidemia’:Opinion

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Chronic Diseases and Translational Medicine 2016年第1期2卷 -页

作者： shui-ping zhao The Second Xiangya Hospital of Central South University 86 Mid-Renmin Road Changsha Hunan 410399 China

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2023 China Guidelines for Lipid Management

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老年心脏病学杂志:英文版 2023年第9期20卷 621-663页

作者： Jian-Jun LI shui-ping zhao Dong zhao Guo-ping LU Dao-Quan PENG Jing LIU Zhen-Yue CHEN Yuan-Lin GUO Na-Qiong WU Sheng-Kai YAN Zeng-Wu WANG Run-Lin GAO National Center for Cardiovascular Diseases Fuwai HospitalChinese Academy of Medical SciencesBeijingChina The Second Xiangya Hospital of Central South University ChangshaHunanChina Beijing Anzhen Hospital Capital Medical UniversityBeijingChina Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina Affiliated Hospital of Zunyi Medical University School of Laboratory Medicine of Zunyi Medical UniversityZunyiGuizhouChina

Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of death among urban and rural residents in China,and elevated low-density lipoprotein cholesterol(LDL-C)is a risk factor for *** the increasing burden of ASCVD,lipid management is of the utmost *** recent years,research on blood lipids has made breakthroughs around the world,hence a revision of China guidelines for lipid management is imperative,especially since the target lipid levels in the general population vary in respect to the risk of *** level of LDL-C,which can be regarded as appropriate in a population without frisk factors,can be considered abnormal in people at high risk of developing *** a result,the“Guidelines for the prevention and treatment of dyslipidemia”were adapted into the“China Guidelines for Lipid Management”(henceforth referred to as the new guidelines)by an Experts’committee after careful *** new guidelines still recommend LDL-C as the primary target for lipid control,with CVD risk stratification to determine its target *** guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle,be used as an initial line of treatment,followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors,as *** new guidelines provide guidance for lipid management across various age groups,from children to the *** aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

关键词： Lipid prevention hence

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Understanding Human and Machine Interaction from Decision Perspective: An Empirical Study Based on the Game of Go

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Journal of Systems Science & Complexity 2024年第2期37卷 647-667页

作者： zhao ping LI Xuerong WANG Shouyang Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100190China

The authors aim to interpret human and AI interactions from the decision *** authors decompose the interaction analysis into the following main components in the context of interactions:Individual behavior patterns,interaction relationships,and comprehensive *** authors interpret intertemporal decisions from a physical perspective and employ cross-discipline concepts and methodologies to extract the behavior characteristics of players in the empirical case *** the individual behavior patterns,the authors find that human players prefer short-term periods to AI in *** interaction relationship analysis reveals a dynamic relationship between possible short-term co-movement and nearly counter-movement in the long *** authors apply principal component analysis to descriptive indicators and discover a regular decision *** main behavior pattern of players in the game of Go is switching between careful and daring *** differences in the decision hierarchies imply a discrepancy of patience between humans and AI.

关键词： Coherence analysis decision hierarchy machine behaviour multitaper spectral analysis

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Superior and safer lithium sulfur batteries realized by robust polysulfides-retarding dam with high flame retardance

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Journal of Energy Chemistry 2024年第2期89卷 471-486,I0011页

作者： Junling Wang Yanfang Cao Zhirong Wang Yinquan zhao Chuang He Fudong zhao Chaoling Han shui Yu Jiangsu Key Laboratory of Hazardous Chemicals Safety and Control College of Safety Science and EngineeringNanjing Tech UniversityNanjing 211816JiangsuChina Department of Architecture and Civil Engineering City University of Hong KongHong Kong 999077China School of Mechanical and Power Engineering Nanjing Tech UniversityNanjing 211816JiangsuChina

The unparalleled energy density has granted lithium-sulfur batteries(LSBs)with attractive ***,LSBs still face some unsurpassed challenges in industrialization,with polysulfides shuttling,dendrite growth and thermal hazard as the major problems triggering the cycling instability and low *** the merit of convenience,the method of designing functional separator has been ***,the carbon aerogel confined with CoS_(2)(CoS_(2)-NCA)is constructed and coated on Celgard separator surface,acquiring CoS_(2)-NCA modified separator(CoS_(2)-NCA@C),which holds the promoted electrolyte affinity and flame *** revealed,CoS_(2)-NCA@C cell gives a high discharge capacity 1536.9 mAh/g at 1st cycle,much higher than that of Celgard cell(987.1 mAh/g).Moreover,the thermal runaway triggering time is dramatically prolonged by 777.4 min,corroborating the promoted thermal safety of ***,the higher coulombic efficiency stability and lower overpotential jointly confirm the efficacy of CoS_(2)-NCA@C in suppressing the lithium dendrite ***,this work can provide useful inspirations for designing functional separator,coping with the vexing issues of LSBs.

关键词： Lithium-sulfur batteries Thermal safety Flame retardancy Separator

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Modeling the Interaction between Vacancies and Grain Boundaries during Ductile Fracture

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 2019-2034页

作者： Mingjian Li ping Yang Pengyang zhao Department of Engineering Mechanics School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China

The experimental results in previous studies have indicated that during the ductile fracture of pure metals,vacancies aggregate and form voids at grain ***,the physical mechanism underlying this phenomenon remains not fully *** study derives the equilibrium distribution of vacancies analytically by following thermodynamics and the micromechanics of crystal *** derivation suggests that vacancies cluster in regions under hydrostatic compression to minimize the elastic strain ***,a finite element model is developed for examining more general scenarios of interaction between vacancies and grain *** model is first verified and validated through comparison with some available analytical solutions,demonstrating consistency between finite element simulation results and analytical solutions within a specified numerical accuracy.A systematic numerical study is then conducted to investigate the mechanism that might govern the micromechanical interaction between grain boundaries and the profuse vacancies typically generated during plastic *** simulation results indicate that the reduction in total elastic strain energy can indeed drive vacancies toward grain boundaries,potentially facilitating void nucleation in ductile fracture.

关键词： Ductile fracture vacancy grain boundary micromechanical finite element method

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Targeting CD47-SIRPα axis for Hodgkin and non-Hodgkin lymphoma immunotherapy

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Genes & Diseases 2024年第1期11卷 205-217页

作者： Pengcheng zhao Longyan Xie Lei Yu ping Wang School of Life Sciences and Medicine Shandong University of TechnologyZiboShandong 255000China Tongji University Cancer Center Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200092China

The interaction between cluster of differentiation 47(CD47)and signal regulatory proteinα(SiRPa)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune *** of CD47 occurs widely across various tumor cell types and transmits the"don't eat me"signal to macrophages to avoid phagocytosis through binding to *** of the CD47-SIRPa axis is therefore a promising approach for cancer *** is the most common hematological malignancy and is an area of unmet clin-ical *** review mainly described the current strategies targeting the CD47-SIRPa axis,including antibodies,SiRPaFc fusion proteins,small molecule inhibitors,and peptides both in preclinical studies and clinical trials with Hodgkin lymphoma and non-Hodgkin lymphoma.

关键词： Cancer treatment CD47-SIRPαaxis Hodgkin lymphoma Immunotherapy Non-Hodgkin lymphoma

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Encouraging Solution to the Problem of Synthesizing Protein α-Thioester

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Chinese Journal of Chemistry 2024年第10期42卷 1114-1120页

作者： Xinliang Liu Zijun Gao Jie zhao Farong Ye ping Huang ping Wang Center for Chemical Glycobiology Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsFrontiers Science Center for Transformative MoleculesSchool of Chemistry and Chemical EngineeringZhangjiang Institute for Advanced StudyShanghai JiaoTongUniversityShanghai 200240China Shenzhen Research Institute of Shanghai Jiao Tong University ShenzhenGuangdong 518057China

Expressed protein ligation(EPL)provides a powerful tool to access large-size proteins with precise *** methods for constructing the critical protein thioester for EPL have predominantly relied on the recombinant intein fusion expressed in Escherichia coli(***).Despite its powerful applications,the expression of thioester derived from eukaryotic protein in *** inherently suffers from its limited solubility,the inactivity of intein,premature hydrolysis and low *** overcome these obstacles,we present herein the facile one-flask synthesis of inaccessible proteinα-thioester via a SUMO-protein-intein(SPI)sandwich *** utility of SUMO enhances the protein fusion yield and solubility,prevents premature hydrolysis and simplifies the purification *** inaccessible protein thioester with internal Cys residues can be readily produced and is compatible with the EPL-desulfurization protocol used to prepare complex proteins,which is otherwise difficult to obtain using traditional *** utility has been highlighted through the synthesis of human granulocyte colony-stimulating factor(G-CSF).

关键词： Desulfurization Glycoproteins Glycopeptides Protein expression Peptide thioester

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