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TREM in Alzheimer's Disease: Genetics, Mechanisms and Therapy

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TREM in Alzheimer's Disease: Genetics, Mechanisms and Therap...

Ancient Y-DNA with reconstructed phylogeny provides insights into the demographic history of paternal haplogroup N1a2-F1360

中国神经科学学会第十二届全国学术会议

作者： lan Tan Jin-Tai Yu Department of Neurology Qingdao Municipal Hospital Qingdao University

Triggering receptor expressed on myeloid cells(TREMs) receptors constitute a family modulator in human innate immunity system that encode by a gene cluster, including TREM1、TREM2、TLT-1 and TLT-2. Two recent studies have identified that a rare coding variant(p. R47 H) in exon 2 of TREM2 gene increases susceptibility to lateonset Alzheimer’s disease(LOAD) with an odds ratio similar to that of the apolipoprotein E ε4 allele in Caucasian population, suggesing TREM2 represents an important susceptibility gene for LOAD. We then resequenced all exons of TREM2 and provided the first evidence that a rare coding variant(p.H157 Y) in TREM2 exon 3 conferred a considerable risk of AD with an odds ratio of 11.01. Furthermore, we decipher the expression and biologic functions of TREM2 under AD context. We showed that TREM2 was upregulated in microglia during disease progression. By knockdown and overexpression of TREM2 in cultured primary microglia, we revealed that TREM2 modulated microglial functions under AD context, as it facilitated Aβ(1-42) phagocytosis and inhibited Aβ(1-42)-triggered proinflammatory responses. Besides, TREM2 overexpression rescued spatial cognitive impairments and ameliorated neuropathologies by suppressing neuroinflammation and subsequently attenuating tau kinase activity. For the first time, we declare the crucial role of TREM2 in AD pathogenesis. More importantly, overexpression of TREM2 in the brain of APPswe/PS1 d E9 mice/P301 S mice markedly ameliorated AD-related neuropathology including Aβ deposition, tau hyperphosphorylation, neuroinflammation, neuronal and synaptic losses. These findings provide insights into the role of TREM2 in AD pathogenesis, and highlight TREM2 as a novel potential therapeutic target for this disease. At the same time, rs6910730, an intronic variant of TREM1, is associated with an increased Aβ neuropathology in the brains of elderly subjects. We further provided evidence that rs6910730 reduced the ability of human monocytes

关键词： Alzheimer’s disease TREM1 TREM2 Rare variant Aβ Tau phosphorylation Therapeutic target

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Journal of Genetics and Genomics 2021年第12期48卷 1130-1133页

作者： Pengcheng Ma Xuan Yang Shi Yan Chunxiang Li Shizhu Gao Binghua Han Kan Hou Martine Robbeets lan-Hai Wei Yinqiu Cui School of Life Sciences Jilin UniversityChangchun 130012China School of Ethnology and Sociology Minzu University of ChinaBeijing 100081China College of Pharmacia Sciences Jilin UniversityChangchun 130021China Shanxi Provincial Institute of Archaeology Taiyuan 030001China School of History and Culture Shanxi UniversityTaiyuan 030006China Max Planck Institute for the Science of Human History Jena 07745Germany Department of Anthropology and Ethnology Institute of AnthropologyXiamen UniversityXiamen 361005China B&R International Joint Laboratory for Eurasian Anthropology Fudan UniversityShanghai 200438China Research Center for Chinese Frontier Archaeology of Jilin University Jilin UniversityChangchun 130012China

Northern Eurasia (nEA) has been considered crucial for the dispersal of the anatomically modern human (AMH) in recent *** the Last Glacial Maximum (LGM),ancient populations from different locations were redistributed throughout the region (Sikora et al.,2019;Yu et al.,2020;Kílínc et al.,2021;Mao et al.,2021).It is suggested that the emergence of many diverse ethnolinguistic groups.

关键词： insight phylogeny

Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents

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Chinese Chemical Letters 2019年第12期30卷 2157-2159页

作者： Erfang Huang lan Zhang Chuying Xiao Guangpeng Meng Bingqi Zhang Jianshu Hu David Chi-Cheong Wan Qingguo Meng Zhe Jin Chun Hu Key Laboratory of Structure-based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Pharmacy Yantai UniveristyYantai 264005China

Oxidative stress results in various pathologies and as consequence antioxidant agents have attracted uninterrupted *** this paper,a novel series of indole-3-carboxamide derivatives(6 a-61) were designed and synthesized based on the melatonin structure as novel *** of them were evaluated for the antioxidant activities in vitro against human neuroblastoma SH-SY5 Y cell line using H2 O2 radical scavenging *** target compounds 6 a,6 f and 6 i indicated better activities than the positive control,ascorbic acid,and 6 a exhibited the best antioxidant *** addition,the structureactivity relationships of the target compounds were also preliminarily summarized based on the obtained experimental data.

关键词： Heterocycle Melatonin Indole-3-carboxamide derivatives Synthesis Antioxidant activity Structure-activity relationship

Whole lifecycle observation of single‐spore germinated Streptomyces using a nanogap‐stabilized microfluidic chip

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mLife 2022年第3期1卷 341-349页

作者： Dongwei Chen Mengyue Nie Wei Tang Yuwei Zhang Jian Wang Ying lan Yihua Chen Wenbin Du State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijingChina College of Life Sciences University of the Chinese Academy of SciencesBeijingChina Savaid Medical School University of the Chinese Academy of SciencesBeijingChina

Streptomyces is a model bacterium to study multicellular differentiation and the major reservoir for antibiotics ***,the cellular‐level lifecycle of Streptomyces has not been well studied due to its complexity and lack of research tools that can mimic their natural *** this study,we developed a simple microfluidic chip for the cultivation and observation of the entire lifecycle of Streptomyces development from the single‐cell *** chip consists of channels for loading samples and supplying nutrients,microwell arrays for the seeding and growth of single spores,and air chambers beside the microwells that facilitate the development of aerial hyphae and spores.A unique feature of this chip is that each microwell is surrounded by a 1.5µm nanogap connected to an air chamber,which provides a stabilized water–air *** used this chip to observe the lifecycle development of Streptomyces coelicolor and Streptomyces griseus germinated from single spores,which revealed differentiation of aerial hyphae with progeny spores at micron‐scale water–air interfaces and air ***,we demonstrated the applicability of this chip in phenotypic assays by showing that the microbial hormone A‐Factor is involved in the regulatory pathways of aerial hyphae and spore *** microfluidic chip could become a robust tool for studying multicellular differentiation,single‐spore heterogeneity,and secondary metabolism of single‐spore germinated Streptomyces.

关键词： microfluidics multicellular differentiation single cell analysis single‐spore germination Streptomyces

Inhibiting water evaporation of sandy soil by the soil particles modified with Japanese wax

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Journal of Forestry Research 2009年第1期20卷 59-62页

作者： ZHANG Zeng-Zhi WANG Hong-Juan Li Cui-lan Research institute of Ecological and Functional Material China University of Mining and Technology Beijing 100083

This study was conducted to resolve the problems of water conservation of sandy soil in desertification areas. The surface of soil particles was modified by molecules of natural Japanese wax through some specially screened surfactant. The modified particles were then well sprayed onto the sand, which was placed in an artificial climate box with simulating desert environment, to form a soil film with effect of suppressing water and gas-permeability. Structure of soil film was analyzed by means of X-ray diftYaction （XRD） and infrared spectrometry （IR）. And its mechanism of water inhibition was illustrated with DSC and TG curves. Its influence on grass-planting was tested through the instruments of water detector. The results show that sorbitol anhydride stearate （ Span 80） could well disperse the Japanese wax and make it combine with the clay which is also dispersed. The pores among soil particles grew smaller and turned from hydrophilic into hydrophobic, in which way resistance to water penetrating through the film was increased. Experimental grass grows normally on sandy soil with the soil film in the artificial desert climate box, indicating that the soil particles modified with Japanese wax is an effective method to inhibit water evaporation.

关键词： Japanese wax surfactant desert soil hydrophobic soil film

Comparison of the Safety and Effectiveness of Lower Extremity Artery Bypass Grafting and Endovascular Angioplasty in the Treatment of Lower Extremity Arteriosclerosis Obliterans in the Elderly

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Chinese Journal of Biomedical Engineering(English Edition) 2019年第1期28卷 13-21页

作者： LI Gang-zhi ZHAO Jin-jie MA Ronga LI lan-lan ZHAO Jing-hao Department of Vascular Surgery Suining Central HospitalSichuang Province Suining 629000China

Objective:To compare the safety and effectiveness of lower extremity artery bypass grafting and endovascular angioplasty in the treatment of lower extremity arteriosclerosis obliterans in the ***:The data of 87 elderly patients with lower extremity arteriosclerosis obliterans treated in our hospital from August 2015 to August 2017 were analyzed *** to the different treatment methods,they were divided into angioplasty group(n=45,intravascular angioplasty)and bypass grafting group(n=42,lower extremity artery bypass grafting).The success rate,hemodynamics of dorsalis pedis artery and nerve conduction of lower extremity were compared between the two groups Velocity,VAS score,late target vessel lumen loss(LLL),patency rate,restenosis rate,ankle brachial index(ABI)and clinical adverse ***:There was no significant difference between angioplasty group and bypass group(P>0.05).One month after operation,the hemodynamics of dorsalis pedis artery and nerve conduction velocity of lower limbs in the two groups were better than those before operation,the difference was statistically significant(P0.05).The VAS score of the two groups was significantly lower than that of the preoperative group(P0.05).The ABI of the two groups was significantly improved after operation,the difference was statistically significant(P0.05).There was no significant difference in LLL,patency rate and restenosis rate between the two groups(P>0.05).There was statistical difference in the incidence of complications between the two groups(P<0.05).During the follow-up period,no serious adverse events such as death or amputation occurred in both ***:Endovascular angioplasty and lower extremity artery bypass grafting have the s

关键词： lower extremity artery bypass grafting endovascular angioplasty arteriosclerosis obliterans of lower extremity

强酸性阳离子交换树脂负载金属离子改性催化合成乙酸丁酯

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离子交换与吸附 2008年第4期24卷 368-373页

作者：廖安平蓝丽红蓝平张雷童张法广西大学化学化工学院广西民族大学化学与生态工程学院

用两种强酸性阳离子交换树脂进行金属离子负载改性制备酯化催化剂,考察了金属盐种类,盐浓度,沉浸时间,沉浸温度等因素对催化剂性能的影响。用在优化条件下制备的催化剂催化乙酸和正丁醇酯化反应体系,反应1h乙酸的转化率达到69%。

关键词：强酸性阳离子交换树脂负载催化乙酸丁酯

Study of the Effect of Zhuang Medicine Aponeurotic System Triple Therapy on Lumbar Disc Herniation and Alpha-1 Acid Glycoprotein Level

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Journal of Clinical and Nursing Research 2023年第2期7卷 92-99页

作者： Yun Zhang Yuying lan Yingcai Wei Guangxi University of Chinese Medicine Nanning 530001Guangxi Zhuang Autonomous RegionChina

Objective:To analyze the application effect of Zhuang medicine aponeurotic system triple therapy in the treatment of lumbar disc herniation and its effect on the level of alpha-1 acid glycoprotein(alpha-1 AGP).Methods:200 patients with lumbar disc herniation were selected and randomly divided into a treatment group and a control group,100 cases in each *** control group was given conventional acupuncture,and the treatment group was treated with manipulation+fire needling+*** alpha-1-AGP levels before and after treatment,as well as the lumbar spine function and pain scores before and after treatment,and the adverse reactions occurred during treatment between the two groups were ***:Before treatment,there was no significant difference in alpha-1 AGP levels,lumbar function,and pain scores between the two groups(P>0.05).After treatment,the lumbar function scores of the two groups were significantly increased,with the treatment group having higher scores than the control group(P0.05).Conclusion:Appropriate application of Zhuang medicine aponeurotic system triple therapy in the clinical treatment of lumbar disc herniation can promote the improvement of alpha-1 AGP index level,reduce the pain degree of patients,and improve their lumbar spine *** the same time,Zhuang medicine also has significant advantages in terms of safety,while ensuring the efficacy and safety of the treatment.

关键词： Zhuang medicine aponeurotic system triple therapy Lumbar disc herniation Application effect Alpha-1 acid glycoprotein

Effects of propofol anesthesia and sevoflurane anesthesia on the differentiation of human T-helper cells during surgery

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Chinese Medical Journal 2011年第4期124卷 525-529页

作者： JI Fu-hai WANG Yu-lan YANG Jian-ping Department of Anesthesiology First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China

Background Surgical stress causes a helper T-cell type 2 （Th2）-dominant status and disturbs the Th1/Th2 cytokine balance. Anesthesia can suppress the stress response to surgery, therefore it may inhibit the imbalance in the Th1/Th2 ratio. In this study, we assessed if propofol anesthesia and sevoflurane anesthesia influence the Th1/Th2 cytokine balance, and which anesthesia method better attenuates this *** Twenty-eight patients with an American Society of Anesthesiologists （ASA） physical status of I undergoing laparoscopic cholecystectomy were selected. They were randomly allocated into two groups of 14. Group 1 received propofol anesthesia by a target-controlled-infusion （TCI） pump and group 2 received sevoflurane ***-invasive blood pressure, heart rate, and end-expiration CO2 partial pressure were monitored during anesthesia. The depth of anesthesia was measured using the bispectral index （BIS）, and maintained between 50 and 60. During surgery we adjusted the doses of propofol and sevoflurane according to the BIS. Samples of peripheral blood were taken before the induction of anesthesia （T1）, after the induction of anesthesia （T2）, at the beginning of surgery （T3）, at the end of surgery （T4） and on the first day after surgery （D1）. Blood samples were analyzed to give the Th1/Th2 ratio and plasma level of *** Non-invasive blood pressure, heart rate and end-expiration CO2 partial pressure were not notably different in the two groups. At T4, the percentage of T1 cells was higher in group 1 and had statistical significance （P 〈0.05）. The percentage of T2 cells was not significantly different in the two groups. At T4, the difference in the Th1/Th2 ratio was significantly different. At T3, T4, and D1, the plasma level of cortisol was lower in group 1（P 〈0.05）.Conclusion Compared with sevoflurane, propofol can preferably promote Th cells to differentiate into Th1 cells and inhibit surgical stress. Propofol may therefore be immunoprotect

关键词： anesthesia propofol human T helper cells laparoscopic cholecystectomy