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

Strategic Thinking of Top-level Design for Public Service Standardization

国外经验显示,建立整体性管理框架是政府管理创新进入顶层设计的一种重要模式,顶层设计指导未来发展、把握整体方向,公共服务标准化进入顶层设计阶段,一定要在把握服务业标准化无形性、生产和消费的同时性、不可储存性以及不确定性等一般特征的基础上,明确自身的个性特征。为了解决目前公共服务标准化界点勘探的困惑,必须在理念上解决导向上与过程中的公共性问题,解决政府主导性问题,并在规范上考虑因此而引发的经济影响因素、内在动力、协调成本等诸多操作性问题。Foreign experience shows that the integrity management framework is an important mode of government management innovation in top-level design.The top-level design guides the future development and grasps the overall direction.The public service standardization should basically grasp the general characteristics of service standardization,such as intangibility,simultaneity of production and consumption,not be stored and uncertainty,to clear its own personality.In order to solve the confusion of public service standardization boundary point,on the one hand,we must solve the theoretical problems like the publicity in orientation and process as well as the government domination.On the other hand,we should consider many operational problems of economic factors,internal motivation and coordination cost in the process of the top-level design.教育部哲学社会科学研究重大课题攻关项目“事业单位分类改革实施战略研究”(编号:12JZD024); “厦门大学‘985工程’及‘211工程’公共管理重点学科建设项目成果”; 国家社会科学基金重点项目“十二五时期公共服务标准化创新机制研究”(编号:10AZD005

Research of CNC Grinding Forming Technology for Extrusion Tap

研究了挤压丝锥的成形方法,根据机床的结构运动关系建立了五轴数控工具磨床的虚拟样机,对磨削工艺技术进行了虚拟仿真,确保实际加工形状的准确性和可靠性。针对小型挤压丝锥加工磨削过程存在刚性差、让刀严重、砂轮钝化等问题,设计了顶尖和砂轮修整器的相应工装。通过磨削试验,证明所用成形技术可以满足5μM以内的挤压丝锥制造精度。This paper studies the method of forming extrusion tap.A virtual prototype of the five-axis CNC tool grinder is established according to the structure movement relationship of the machine for the virtual simulation of grinding technology to ensure the Accuracy and reliability of the actual machining shape.The Top and Dresser corresponding tooling are also designed to solve the problems of poor rigidity,tool recession and wheel dull of small extrusion tap.The result of processing test has proved the presented forming technology can achieve the machining accuracy of 5μm.国家“高档数控机床与基础制造装备”科技重大专项资助(2010ZX04001-162

The Development of a Deep-sea Oil Bladder Type Buoyancy Adjustment System

浮力调节系统是深海潜水器的重要组成部分,可用来补偿潜水器浮力变化和调整潜水器姿态,基于6000 m无人遥控潜水器浮力调节需求,研制了一套深海油囊式浮力调节系统。详细介绍了系统组成、工作原理及关键部件的设计,对关键承压部件耐压油舱进行了强度分析、稳定性校核和深海模拟压力环境测试。试验表明该系统能够向油囊排出60 MPa高压油,深海模拟压力试验结果显示油舱能够承受66 MPa压力,两项试验说明该系统可在6000 m深海进行浮力调节;此外还对系统进行了水池姿态调节模拟实验,进一步验证了该系统进行浮力和姿态调节的有效性和可行性

A Real-time Reasoning Engine for Injection-production Optimization of Water and Oil Wells on Account of Bitmap

针对油田油水井采注优化业务中,油水井数据量大、地层结构复杂以及人类经验多的特点,分析了传统推理方法在油田采注实时优化处理过程中的不足,采用事件处理思想,提出了一种基于Bitmap事件编码与匹配机制的推理引擎,有效地实现了对无效事件的过滤并提升了事件与规则的匹配效率.在油田实际数据试验平台上对该方法进行了验证并与RETE算法、LFA(Linear forward-chaining)算法的性能对比,结果验证了本文方法在实时推理能力上的有效性

唐家山滑坡成因机制与堰塞坝整体稳定性研究

根据唐家山滑坡的地质背景,研究滑坡及堰塞体工程地质特征,分析唐家山滑坡类型及发生的地质成因机制;基于唐家山堰塞体的岩体结构稳定性分析、宏观现象监控与地表位移监测,研究堰塞体的整体稳定性。研究得出如下结论与启示:(1)唐家山滑坡属于基岩顺层滑坡,是典型的地震诱发高速滑坡,滑坡滑动带可能发育在层间剪切带,滑坡区发育的构造背景为复式倒转背斜的一翼。(2)唐家山堰塞体整体结构以块状岩体为主,上覆风化松散堆积物,整体地质稳定性较好;堰塞体地表位移监测显示,泄洪对地表位移有影响,最大位移约140 mm,随后位移增量较小,目前处于稳定状态。(3)应注重地震诱发滑坡→堰塞湖→溃决→洪水的"多米诺"链式灾变研究;应注重含层间剪切带斜坡的工程地质调查分析和地震滑坡危险性研究

STUDY OF GEOLOGICAL ORIGIN MECHANISM OF TANGJIASHAN LANDSLIDE AND ENTIRE STABILITY OF LANDSLIDE DAM

根据唐家山滑坡的地质背景,研究滑坡及堰塞体工程地质特征,分析唐家山滑坡类型及发生的地质成因机制;基于唐家山堰塞体的岩体结构稳定性分析、宏观现象监控与地表位移监测,研究堰塞体的整体稳定性。研究得出如下结论与启示:(1)唐家山滑坡属于基岩顺层滑坡,是典型的地震诱发高速滑坡,滑坡滑动带可能发育在层间剪切带,滑坡区发育的构造背景为复式倒转背斜的一翼。(2)唐家山堰塞体整体结构以块状岩体为主,上覆风化松散堆积物,整体地质稳定性较好;堰塞体地表位移监测显示,泄洪对地表位移有影响,最大位移约140mm,随后位移增量较小,目前处于稳定状态。(3)应注重地震诱发滑坡→堰塞湖→溃决→洪水的"多米诺"链式灾变研究;应注重含层间剪切带斜坡的工程地质调查分析和地震滑坡危险性研究