Kinases Mst1 and Mst2 positively regulate phagocytic bactericidal activity

致病菌引发的恶性化脓和不可控感染一直是临床治疗的一项棘手难题。当细菌侵入后，天然防御细胞如巨噬细胞、嗜中性粒细胞等立即响应，识别并吞噬致病菌的同时调动胞内线粒体和NADPH氧化酶向吞噬泡内释放大量的活性氧（ROS），进而实现杀伤和清除细菌的功能。当这类细胞不能充分发挥杀伤和清除病原体的功能时，即使入侵的细菌数量较少或是致病力不强，也可能诱发机体破损部位或组织器官产生脓肿溃烂、炎症因子风暴和组织坏死，最终导致败血症或致死性脓毒性休克。 而在这一过程中吞噬细胞如何驱动线粒体向吞噬泡募集并将产生的ROS释放到吞噬泡内就显得尤为关键，然而其中的调控机制并不为人所知。本文研究发现，Mst1和Mst2蛋...Phagocytes are specialized immune cells that engulf harmful microorganisms and destroy them in phagosomes. The destruction process mainly depends on the production of large amounts of reactive oxygen species (ROS). Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit si...学位：理学博士院系专业：生命科学学院_微生物学学号：2162012015378

The functions of the Hippo signaling pathway in immune cells

Hippo信号通路最初是在果蝇(Drosophila)中被发现的,是在进化上高度保守并能调控器官大小的信号转导通路。在哺乳动物多种组织器官中,H; ippo信号通路的关键激酶MST1和MST2(果蝇Hippo激酶的同源分子)通过抑制下游的转录共激活分子YAP(果蝇中为Yorki)的活性来实现; 对细胞增殖和凋亡的调控。在这些组织器官中条件性敲除Mst1和Mst2或过表达Yap大都会造成细胞过度增殖或肿瘤的发生。近年来,随着研究的不断深入; ,Hippo信号通路不依赖于YAP的非经典功能也逐渐被发现。其中,Hippo信号通路多个成员在免疫系统中的调控功能逐渐成为该领域的研究热点,特别; 是在免疫细胞发育分化、机体自身免疫性疾病及应对病毒和细菌入侵等过程中所发挥的调控作用。本文重点阐述了Hippo信号通路在T淋巴细胞中发育、分化、; 活化和迁移等方面及在部分天然免疫细胞抗感染过程中的功能和调控。The Hippo signaling pathway, first identified in Drosophila, has emerged; as a critical regulator for controlling the size of organs. Activation; of the Hippo signaling pathway negatively regulates the Yorkie ortholog; YAP in multiple organs, important in the regulation of cell; proliferation, differentiation, and apoptosis during development. The; Serine/Threonine protein kinases MST1 and MST2, mammalian homologs of; the Drosophila Hippo kinase, play central roles in the Hippo signaling; pathway in mammals. Recent studies reveal that non-canonical Hippo; signaling pathways are also involved in the regulation of various other; biological processes, particularly the important roles of MST1 and MST2; kinases in immune cell activation, adhesion, migration, growth, and; apoptosis. In this review, we summarize the recent advances in; understanding the roles of MST1 and MST2 kinases in the regulation of; the functions of T lymphocytes and innate immune cells.国家重点基础研究发展规划(973计划)项目; 国家自然科学基金项目; 厦门市重大疾病科研攻关项

Research advances in functions of Hippo signaling in the immune system

Hippo信号通路是最早在果蝇(Drosophila)中发现的,在进化上高度保守,具有调控细胞增殖与凋亡作用的一条关键信号转导通路。在哺乳动物中; ,Hippo信号通路在调控细胞增殖、细胞死亡、细胞分化和肿瘤生成等生物学过程中有着十分重要的作用。近年来,Hippo信号通路在免疫系统以及多种功; 能性免疫细胞中发挥的重要作用逐渐成为该领域的研究热点,特别是Hippo信号通路各成员在免疫细胞应对病毒、细菌入侵或肿瘤发生以及维持自身稳态过程中; 发挥着重要的作用。因此,深入了解Hippo信号通路各成员对多种功能性免疫细胞的调控机制,有助于绘制新的免疫系统调控网络,阐明各类免疫系统相关疾病; 的发病机制,期望为诊断、治疗和预防相关疾病提供新的治疗策略或靶点。The Hippo signaling pathway was first discovered as a result of genetic; studies of tissue growth in Drosophila to mediate organ size control.; This pathway is evolutionally conserved and the orthologs to its main; components have been identified in mammals respectively. The Hippo; signaling pathway consists of a core kinase cascade which plays central; roles in the Hippo pathway controlling the cell proliferation,; apoptosis, and differentiation during development and tumorigenesis. In; recent years, numerous studies reported that Hippo signaling also plays; diverse and important roles in the immune system. In this review, we; summarize recent findings related to the new function of core components; of the Hippo signaling pathway in immune regulation. A better; understanding of how Hippo signaling regulated the immune function will; help us to draw a novel immune regulatory network and provide a new; treatment strategies or targets for immune-related diseases.国家重点基础研究发展规划("973"项目); 国家自然科学基金项

免疫细胞代谢及其功能调节研究进展

免疫系统是维持机体正常生长发育和生存的重要组分之一,而物质和能量代谢在种类多样的免疫细胞维持自身和机体稳态过程中是不可或缺的。不同代谢物对免疫细胞会产生不同的生物学效应,同时代谢组失衡也与免疫细胞功能紊乱互为因果,从代谢组学视角深入研究免疫细胞失调的内在机制已经成为近些年免疫学研究的新热点。该文将从不同代谢物对免疫细胞的增殖、分化或功能影响的角度进行阐述,希望能找到相关代谢通路或分子来调控免疫细胞增殖、分化或功能,这将有助于我们更加深刻理解免疫学现象和分子机制,并对免疫系统相关疾病的治疗或预防发挥潜在的指导作用

Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity

该研究成果揭示了吞噬性细胞内Hippo信号通路关键激酶Mst1和Mst2通过活化Rac家族蛋白来调节线粒体向吞噬小泡募集并释放ROS来清除病原体，这个生物学过程在天然免疫和宿主防御中发挥着重要作用。该成果解析了人的Mst1基因缺失或Rac2基因突变引发免疫缺陷综合症的致病机理，为研究人类感染性疾病提供了全新的视角。 该论文的主要工作由2012级博士生耿晶、2013级博士生孙秀峰以及王平、张世浩和王晓珍等学生共同承担，并与厦门市第一医院、台湾长庚大学、中国科学技术大学等单位合作完成，通讯作者为周大旺教授和陈兰芬教授。该研究工作获得了“青年千人计划”、国家自然科学基金委和科技部的资助。Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to X.L.), the Natural Science Foundation of Fujian (2013J06011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Occurrence and Control of Tomato Root Rot in Hetao Irrigation District

简述了番茄根腐病的发病症状、病原菌、传播途径和影响发病的因素;指出了河套灌区番茄根腐病发生较重的主要原因是重茬严重,大水漫灌,缺乏有机肥;提出了防治番茄根腐病应减少重茬,高垄栽培,合理调整土壤温湿度,增施有机肥和苗床消毒,培育壮苗、大苗等,并积极开展化学防治

戊糖乳杆菌发酵废甘油生产乳酸的条件优化在

对废甘油生产乳酸的发酵条件进行优化。得到乳酸发酵最佳条件:废甘油60 g/l,酵母粉2.8 g/l,蛋白胨4 g/l,硫酸铵5.82 g/l,乙酸钠6 g/l,磷酸氢二钾1.5 g/l,PH中和剂为氨水,控制PH值6.0,发酵温度34°C。在此条件下发酵70 H,乳酸产量达到51.43 g/l,不仅比优化前提高了约2%,而且减少了50%多的培养基费用,较大程度地减低培养基成本,为实现乳酸发酵产业化奠定基础。这是首次报道戊糖乳杆菌发酵废甘油生产乳酸。国家“863”计划项目(2006AA020102

Effect of renewal pruning on apple photosynthetic ability and fruit quality in final full productive stage

【目的】探讨更新修剪对盛果末期苹果树光合能力及枝条生长、果实品质的影响。【方法】在渭北旱原,对盛果末期苹果树进行更新修剪和长放修剪(对照),利用LI-6400光合仪测定2种修剪方式下不同枝条叶片的光合能力,并测定枝条生长状况和果实品质的相关指标。【结果】盛果末期苹果树果台副梢、叶丛枝、发育枝叶片的光合速率和气孔导度日变化曲线均呈双峰曲线,蒸腾速率则呈单峰曲线,胞间CO2浓度呈"反抛物线";更新修剪极显著提高了不同枝条叶片的光合速率、气孔导度和蒸腾速率,极显著降低了叶片胞间CO2浓度;更新修剪显著或极显著提高了中枝、长枝的数量,显著或极显著提高了果实单株产量、单果质量、果形指数及有机酸、可溶性固形物和可溶性糖含量,对果实硬度及维生素C含量无显著影响。【结论】更新修剪提高了盛果末期苹果树叶片的光合能力,促进了枝条生长,提高了果实产量和单果质量。【Objective】 The study was to investigate the effect of renewal pruning on photosynthetic ability and shoots growth,fruit quality of apple tree in final full productive stage.【Method】 In Weibei Plateau,renewal pruning and long branch pruning(control) on final full productive stage,photosynthetic ability of different shoots with two types of pruning were measured by LI-6400 photosynthetic,and shoot growth and related indicators of fruit quality were measure.【Result】 The diurnal variation of photosynthetic rat..