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Tau in Alzheimer’s Disease:Pathological Alterations and an Attractive Therapeutic Target

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Current Medical Science 2020年第6期40卷 1009-1021页

作者： Jian-lan GU fei LIU Department of Biochemistry and Molecular Biology School of MedicineNantong UniversityNantong 226001China Key Laboratory of Neuroregeneration and Ministry of Education of Jiangsu Co-innovation Center of NeuroregenerationNantong 226001China Department of Neurochemistry Inge Grundke-Iqbal Research FloorNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandNY 10314USA

Alzheimer’s disease(AD)is an age-related neurodegenerative disease with two major hallmarks:extracellular amyloid plaques made of amyloid-β(Aβ)and intracellular neurofibrillary tangles(NFTs)of abnormally hyperphosphorylated *** number of NFTs correlates positively with the severity of dementia in AD ***,there is still no efficient therapy available for AD treatment and prevention so far.A deeper understanding of AD pathogenesis has identified novel strategies for the generation of specific therapies over the past few *** studies have suggested that the prion-like seeding and spreading of tau pathology in the brain may be a key driver of *** protein is considered as a promising candidate target for the development of therapeutic interventions due to its considerable pathological role in a variety of neurodegenerative *** tau hyperphosphorylation plays a detrimental pathological role,eventually leading to *** the present review,we describe the recent research progresses in the pathological mechanisms of tau protein in AD and briefly discuss tau-based therapeutic strategies.

关键词： Alzheimer’s disease tau protein hyperphosphorylation propagation of tau pathology

Forecast for weighing neutrinos in cosmology with SKA

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Science China(Physics,Mechanics & Astronomy) 2020年第8期63卷 53-60页

作者： Jing-fei Zhang bo Wang Xin Zhang Department of Physics College of SciencesNortheastern UniversityShenyang 110819China Ministry of Education’s Key Laboratory of Data Analytics and Optimization for Smart Industry Northeastern UniversityShenyang 110819China Center for High Energy Physics Peking UniversityBeijing 100080China

We investigate what role the SKA neutral hydrogen(HI)intensity mapping(IM)and galaxy sky surveys will play in weighing neutrinos in *** use the simulated data of the baryon acoustic oscillation(BAO)measurements from the HI surveys based on SKA1(IM)and SKA2(galaxy)to do the *** the current observations,we use the Planck 2015 cosmic microwave background(CMB)anisotropies observation,the optical BAO measurements,the type Ia supernovae(SN)observation(Pantheon compilation),and the latest H0 *** consider three mass ordering cases for massive neutrinos,i.e.,the normal hierarchy(NH),inverted hierarchy(IH),and degenerate hierarchy(DH)*** is found that the SKA observation can significantly improve the constraints on?m and *** to the current observation,the SKA1 data can improve the constraints on?m by about 33%,and on H0 by about 36%;the SKA2 data can improve the constraints on?m by about 58%,and on H0 by about 66%.It is also found that the SKA observation can only slightly improve the constraints on∑mν.Compared to the current observation,the SKA1 data can improve the constraints on∑mνby about 4%,3%,and 10%,for the NH,IH,and DH cases,respectively;the SKA2 data can improve the constraints on∑mνby about 7%,7%,and 16%,for the NH,IH,and DH cases,respectively.

关键词： 21 cm observation intensity mapping survey Square Kilometre Array baryon acoustic oscillations neutrino mass

Investigation into Improvement for Anti-Rollover Propensity of SUV

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Chinese Journal of Mechanical Engineering 2017年第3期30卷 698-710页

作者： fei Xiong Fengchong lan Jiqing Chen Yuedong Yang School of Mechanical and Automotive Engineering South China University of TechnologyGuangzhou 510640China Guangzhou Automobile Group Co.Ltd Automotive Engineer Institute Guangzhou 511434China

Currently, many research from domestic and foreign on improving anti-rollover performance of vehicle mainly focus on the electronic control of auxiliary equip- ment, do not make full use of suspension layout to optimize anti-rollover performance of vehicle. This investigation into anti-rollover propensity improvement concentrates on the vehicle parameters greatly influencing on anti-rollover propensity of vehicle. A simulation based on fishhook procedure is used to perform design trials and evaluations aimed at ensuring an optimal balance between vehicle＇s design parameters and various engineering capacities, the anti-rollover propensity is optimized at the detailed design stage of a new SUV model. Firstly a four-DOF theoretical kinematic model is established, then a complete multi-body dynamics model built in ADAMS/car based on the whole vehicle parameters is correlated to the objective handing and stability test results of a mule car. Secondly, in fish- hook test simulations, the Design of Experiments method is used to quantify the effect of the vehicle parameters on the anti-rollover performance. By means of the simulation, the roll center height of front suspension should be more than 30 mm, that of rear suspension less than 150 mm, and the HCG less than 620 mm for the SUV. The ratio of front to rear suspension roll stiffness should be ranged from 1.4 to1.6 for the SUV. As a result, at the detailed design stage of product, the anti-rollover performance of vehicle can be improved by optimizing chassis and integrated vehicle parameters.

关键词： Fishhook test Tire normal force Roll center Roll stiffness

Experimental Investigation on Cooling/Heating Characteristics of Ultra-Thin Micro Heat Pipe for Electric Vehicle Battery Thermal Management

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Chinese Journal of Mechanical Engineering 2018年第3期31卷 179-188页

作者： fei-fei Liu Feng-Chong lan Ji-Qing Chen Yi-Gang Li School of Mechanical&Automotive Engineering Guangdong Key Laboratory of Automotive EngineeringSouth China University of Technology School of Mechatronics&Vehicle Engineering East China Jiaotong UniversityNanchang 330013China

Due to the heat pipes’ transient conduction,phase change and fluid dynamics during cooling/heating with high frequency charging/discharging of batteries,it is crucial to investigate in depth the experimental dynamic thermal characteristics in such complex heat transfer processes for more accurate thermal analysis and design of a BTMS. In this paper,the use of ultra?thin micro heat pipe(UMHP) for thermal management of a lithium?ion battery pack in EVs is explored by experiments to reveal the cooling/heating characteristics of the UMHP pack. The cooling performance is evaluated under di erent constant discharging and transient heat inputs conditions. And the heating e ciency is assessed under several sub?zero temperatures through heating films with/without UMHPs. Results show that the pro?posed UMHP BTMS with forced convection can keep the maximum temperature of the pack below 40 °C under 1 ~ 3 C discharging,and e ectively reduced the instant temperature increases and minimize the temperature fluctuation of the pack during transient federal urban driving schedule(FUDS) road conditions. Experimental data also indicate that heating films stuck on the fins of UMHPs brought about adequate high heating e ciency comparing with that stuck on the surface of cells under the same heating power,but has more convenient maintenance and less cost for the BTMS. The experimental dynamic temperature characteristics of UMHP which is found to be a high?e cient and low?energy consumption cooling/heating method for BTMSs,can be performed to guide thermal analysis and optimiza?tion of heat pipe BTMSs.

关键词： Electric vehicle Lithium?ion battery Thermal management Ultra?thin micro heat pipe

Two folate-derived analogues from an aqueous decoction of Uncaria rhynchophylla

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Chinese Journal of Natural Medicines 2019年第12期17卷 928-934页

作者： WANG Yue GUO Qing-lan LI Ruo-fei XU Cheng-bo ZHU Cheng-Gen SHI Jian-Gong State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey’s derivatization,along with comparison of their specific rotation and Cotton effect(CE)data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism(ECD)spectra.A plausible biosynthetic pathway of 1 and 2,associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus,is discussed.

关键词： Rubiaceae Uncaria rhynchophylla Folate derivative Uncarophyllofolic acid Folate metabolism

Effect of WFDC 2 silencing on the proliferation,motility and invasion of human serous ovarian cancer cells in vitro

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Asian Pacific Journal of Tropical Medicine 2013年第4期6卷 265-272页

作者： Ya-fei Zhu Guo-lan Gao Sheng-bo Tang Zhen-Dong Zhang Qing-Shui Huang Department of Gynaecology and Obstetrics First Affiliated Hospital of Nanchang University Department of Clinical Laboratory First Affiliated Hospital of Nanchang University Department of Oncology First Affiliated Hospital of Nanchang University Department of Pathology First Affiliated Hospital of Nanchang University Department of Obstetrics and Gynecology Aviation General Hospital

Objective:To investigate effect and possible mechanisms of silencing human WFDC2（HE4） gene on biological behavior changes as cell proliferation,apoplosis,movement and invasion of human serous ovarian cancer cell line ***:Lentiviral WFDC2 gene sequence of small interfering siRNA was stablely transfected into SKOV3 identified by Q-PCR and western-blot. Obtained SKOV3 stable strains with silenced HE4 were measured by proliferation,apoplosis, migration,and ***:Gene sequencing showed that the oligonucleotides were successfully inserted into the expected *** silencing HE4 in the SKOV3,proliferation was significandy inhibited（P0/G1 phase was arrested by the cell cycle（P<0.01） and capacity of the migration and invasion decreased significandy（P<0.01）.Slight early apoptosis ratio and no change of late apoplosis were found without change of Caspase-3 or Bcl-2 *** involed in ERK pathway as phosphorylated protein as p-EGFR,p- ERK decreased and protease protein involved in tissue remoding as matrix metalloproteinases MMP-9,MMP-2 and cathepsin B decreased compared with control ***:HE4 gene plays an important role in regulating proliferation,apoptosis,migration,invasion of serous ovarian cancer cells by ERK pathway and protease *** role in apoptosis needs to be further explored,and it may be a potential target for serous ovarian cancer.

关键词： WFDC2 protein Human epididymal secretory protein 4 Ovarian neoplasms Cell proliferation Cell movement Invasion

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巴西龟代谢性骨病CT诊断病例报告

动物医学进展 2025年第1期46卷 141-144页

作者：孙嘉徐甘靖宇江蓝刘波俞峰中国农业大学北京100193

代谢性骨病(MBD)是一种因钙缺乏或维生素D 3摄入不足引起的骨骼代谢障碍疾病,其临床表现为骨折、脊椎异常、难产、脱垂等症状。计算机断层扫描(CT)在兽医临床中应用的逐渐增加为龟、鳖类MBD提供了新的诊断方式。该病例中红耳巴西龟血检... 详细信息

代谢性骨病(MBD)是一种因钙缺乏或维生素D 3摄入不足引起的骨骼代谢障碍疾病,其临床表现为骨折、脊椎异常、难产、脱垂等症状。计算机断层扫描(CT)在兽医临床中应用的逐渐增加为龟、鳖类MBD提供了新的诊断方式。该病例中红耳巴西龟血检结果提示其肾脏、肝脏功能损害,钙磷代谢异常。CT扫查提示患龟全身组织大面积矿化、背甲凹陷,定量测量患龟背椎骨、神经骨和胸膜骨3处的骨骼密度远低于正常龟,诊断患龟有严重的MBD。治疗方案为对症治疗、改善饲养管理条件,同时对该龟补充维生素D 3。该病例报告系统陈述了龟鳖MBD的诊疗流程,同时表明了CT扫查可为龟鳖MBD精确诊断、治疗和预后提供新的参考。

关键词：龟代谢性骨病计算机断层扫描骨密度

Humanity and Paternal Eros: The Father-Son Relationship in Comparative Perspective

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Frontiers of Philosophy in China 2015年第4期10卷 629-646页

作者： lan fei Department of Philosophy and Religion The University of Mississippi University MS 38677USA

This paper examines the human relational patterns presented in the philosophical writings of the Confucian thinker Dai Zhen (戴震1724-77) and the Jewish philosopher Emmanuel Levinas’s (1906-95) Totality and Infinity to uncover the ethical significance of the father-son relationship. I argue that for both thinkers the father-son relation is not just one type of human relationship among other social dyads, but rather, of greater significance, serves as the paradigmatic model of the ethical human relationship in bringing to light the idea of the ethical self as a responsible being in relation to others.

关键词： Confucianism Jewish thought Dai Zhen Emmanuel Levinas the father-son relationship responsibility

Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positive/HER-2-negative breast cancer

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Chinese Journal of Cancer Research 2022年第4期34卷 343-352页

作者： Dan Lyu Binliang Liu bo lan Xiaoying Sun Lixi Li Jingtong Zhai Haili Qian fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Breast Cancer Medical Oncology Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Medical Oncology Cancer Hospital of Huanxing Chaoyang DistrictBeijing 100122China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer ***: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 ***: The results suggest th

关键词： ctDNA next-generation sequencing breast cancer endocrine therapy