Trisomy 21-induced Dysregulation of Microglial Homeostasis in Alzheimer’s Brains is Mediated by USP25

阿尔茨海默病（Alzheimer’s disease, AD）是一种最为常见的与记忆、认知能力退化相关的渐进性神经退行性疾病。唐氏综合征（Down’s syndrome, DS）是早发型阿尔茨海默病的一个重要风险因素，作为最常见的智力障碍遗传疾病，厦门大学医学院神经科学研究所王鑫教授团队揭示了治疗阿尔茨海默病和唐氏综合征新的治疗靶点，并且在小鼠模型上利用USP25小分子抑制剂成功地改善了阿尔茨海默病小鼠的认知功能，缓解了神经退行性病变的病理进程。该研究工作由王鑫教授指导完成，厦门大学医学院助理教授郑秋阳和博士生李桂林完成主要实验工作，王世华、朱琳、高月、邓青芳、张洪峰、张丽珊、吴美玲、狄安洁参与了部分研究工作。厦门大学医学院许华曦、赵颖俊和孙灏教授在研究过程中给予大力帮助和支持，清华大学董晨教授提供了Usp25基因敲除小鼠，厦门大学附属妇女儿童医院周裕林教授和郑良楷博士帮助收集了脑组织样品。Down syndrome (DS), caused by trisomy of chromosome 21, is the most significant risk factor for early-onset Alzheimer’s disease (AD); however, underlying mechanisms linking DS and AD remain unclear. Here, we show that triplication of homologous chromosome 21 genes aggravates neuroinflammation in combined murine DS-AD models. Overexpression of USP25, a deubiquitinating enzyme encoded by chromosome 21, results in microglial activation and induces synaptic and cognitive deficits, whereas genetic ablation of Usp25 reduces neuroinflammation and rescues synaptic and cognitive function in 5×FAD mice. Mechanistically, USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination. Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5×FAD mice. In summary, we demonstrate an unprecedented role for trisomy 21 and pathogenic effects associated with microgliosis as a result of the increased USP25 dosage, implicating USP25 as a therapeutic target for neuroinflammation in DS and AD.This work was supported by the National Natural Science Foundation of China (31871077, 81822014, and 81571176 to X.W.; 81701130 to Q.Z.), the National Key R&D Program of China (2016YFC1305900 to X.W.), the Natural Science Foundation of Fujian Province of China (2017J06021 to X.W.), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to X.W.), and the BrightFocus Foundation (A2018214F to Yingjun Zhao). 该研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

2013 Annual Review on Distance Education Research of China

采用内容分析、元分析和社会网络分析等非反应测量法,从研究主题、研究方法、研究主体、主要共现等多重角度,对2013年度我国远程教育研究进行计量分析和客观述评。远程教与学、管理、资源、学习者、技术与媒体等是年度热点主题,开放大学、交互、MOOCS、移动学习、开放课程、学习资源、网络课程、影响因素、网络学习、精品课程、学习支持服务、调查研究、学习平台、终身学习等是年度热词;观照实践的应用研究是绝对主流,基础理论研究明显薄弱;研究方法的规范应用意识仍需进一步提升,定量研究渐成主流;研究力量分布不均衡,主要集中在经济发达地区和非远程教育机构。The status of distance education research of China in 2013 is objectively reviewed and analyzed quantitatively from the aspects of research topic,research method,principal researcher and co-occurrence analysis by means of content analysis,metaanalysis and social network analysis.The findings are the following:(1) Distance teaching and learning,management,resource,learner,technology and media are the Annual Hot Topics;(2) Open University,interaction,MOOCs,mobile learning,open course,learning resource,network course,influencing factor,e-learning,fine quality course,learning support service,investigation,learning platform and lifelong learning are the Annual Hot Words;(3) The practice research is on the absolute mainstream,while the basic theory research is very weak.The awareness should be raised to develop standard application of research methods,and quantitative research has gradually become the mainstream.Research power distribution is not balanced,which is mainly concentrated in the economically developed areas and non-distance education institutions.全国教育科学规划教育部重点课题“成人在线学习心理与行为的监控与评价研究”(课题批准号:GKA103007); 国家开放大学重点课题“近三十年来我国远程教育研究方法的演变及其方法论反思”(课题批准号:GAQ1805)研究成

石墨表面化学镀Cu对天然鳞片石墨/Al复合材料热物理性能的影响

对天然鳞片石墨(GF)进行化学镀Cu的表面处理,对化学镀Cu石墨(Cu-GF)和Al粉采用真空热压的工艺制备出镀Cu石墨/Al(Cu-GF/Al)复合材料。研究了Cu-GF/Al复合材料的微观结构和微观界面,同时也研究了Cu-GF对Cu-GF/Al复合材料热导率和抗弯性能的影响。结果表明,GF上的Cu层能抑制界面脆弱相Al_4C_3的产生,使Cu-GF/Al复合材料的抗弯性能有了显著提升。当Cu-GF体积分数从50%增加到70%时,Cu-GF/Al复合材料的抗弯强度也从104 MPa降低到74 MPa。当GF体积分数为70%时,Cu-GF/Al复合材料的热导率达到最高值为522 W/(m·K)

石墨表面TiC涂层对高定向石墨/Cu复合材料热导率和抗弯强度的影响

以高温盐浴法对天然鳞片石墨粉体(GF)进行表面TiC镀层处理,然后采用真空热压烧结法制备TiCGF/Cu复合材料,研究了粉体表面涂层和GF体积分数对复合材料微观结构、热导率及抗弯强度的影响。系列测试结果表明:随着GF体积分数的降低以及粉体表面TiC镀层的形成,TiC-GF/Cu复合材料平行于GF片层方向的热导率有所降低,抗弯强度有所提升。其中在GF的体积分数占TiC-GF/Cu复合材料70%时,这种变化最为明显,平行于GF片层方向的TiC-GF/Cu复合材料热导率下降幅度最大,从676W/(m·K)下降到526 W/(m·K)。同时,TiC-GF/Cu复合材料的微观结构进一步说明,GF表面的TiC涂层对GF/Cu复合材料的断裂模型起着重要的作用

石墨表面镀Si对石墨/Al复合材料热物理性能的影响

研究了石墨粒径及表面镀Si处理对石墨/Al复合材料热物理性能的影响。结果表明:在盐浴过程中石墨表面形成了SiC层,这不仅增强了石墨-Si/Al复合材料的界面结合力,而且抑制了Al4C3相的产生。随着石墨鳞片体积分数从50%增加到70%,复合材料X-Y方向的热导率从492 W/(m·K)增加到654 W/(m·K),而且体积分数为50%的镀Si石墨/Al复合材料抗弯强度达到了81 MPa,相比未镀覆的提高了53%,是理想的定向导热电子封装材料。随着石墨粒径从500μm减小到150μm,石墨-Si/Al复合材料X-Y面方向的热导率由654 W/(m·K)降低到445 W/(m·K),但Z方向的热导率和复合材料抗弯强度变化不明显

Cr合金化对HRB400钢筋腐蚀行为的研究

应用动电位极化、电化学阻抗谱、周浸腐蚀实验的方法研究了HRB400普通碳钢钢筋和两种Cr合金化的低合金钢筋在2%Na Cl溶液中的腐蚀行为。结果表明:相比HRB400钢筋,Cr合金化的钢筋的开路电位明显正移,Cr加入提高了钢的热力学稳定性;随着Cr含量的增加,钢筋的自腐蚀电流密度减小,极化电阻增大,Cr合金化的钢筋具有相对较小的电化学腐蚀速率;周浸加速腐蚀72 h后,HRB400钢筋以均匀腐蚀为主,Cr合金化的钢筋以局部腐蚀为主,添加Cr可以显著降低HRB400钢筋的均匀腐蚀速率

Toxic effects of polystyrene microplastics and pyrene on Ruditapes philippinarum

The pollution of microplastics and polycyclic aromatic hydrocarbons (PAHs) in marine environment is increasingly serious. The toxic effects of polystyrene microplastics and pyrene on the clam Ruditapes philippinarum were investigated in this study. R. philippinarum was exposed to two polystyrene microplastics sizes (0.3 mum and 6 mum, 20 mug/L) and two pyrene concentrations (10 mug/L and 100 mug/L) for 21 days, respectively. For individuals in each treatment, physiological responses (condition index and clearance rate), immune defense and oxidative stress parameters were measured. It was found that except for the pyrene single exposure group, the clearance rate of R. philippinarum in the other exposure groups was significantly lower than that of the control group, but the two pollutants had no significant effect on the condition index of R. philippinarum. Exposure to microplastics and pyrene led to impaired immune function of R. philippinarum, manifested by increased hemocyte apoptosis and inhibited phagocytosis. The apoptosis rate of hemocytes in the exposure group with small size microplastics and high concentration pyrene was significantly higher than that in the control group,and the apoptosis rate of hemocytes in the combined exposure group was the highest. Except for the large size microplastic exposure group,the phagocytic activity of hemocytes in each exposure group was significantly lower than that of the control group. The antioxidant system of R. philippinarum could not remove the free radicals produced in the body in time,leading to oxidative damage in the body,which was manifested as the change of antioxidant enzyme activity and the increase of malonic dialdehyde (MDA) content. The combined exposure of microplastics and pyrene significantly increased the activities of glutathione S-transferase (GST) in gill tissues, and significantly decreased the activities of catalase (CAT) and superoxide dismutase (SOD) in digestive gland tissues. Integrated biomarker response (IBR) analysis showed that the stress caused by combined exposure on R. philippinarum was higher than that of the single exposure group