Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid β-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis.
Mitochondria are important organelles of eukaryotic cells and involved in a variety of cellular processes including oxidative phosphorylation for generating ATP, apoptosis, steroid synthesis, and signal transduction. Mitochondrion contains double membranes, which are mainly composed of phospholipids. Although mitochondria can synthesize some of phospholipids, most of phospholipids are biosynthesized in the endoplasmic reticulum (ER). ER-mitochondria contacts are required for the transfer of some phospholipids, which are critical for mitochondrial phospholipids metabolism, membrane organization and functions. In this review, we will focus on the synthesis, metabolism and function of mitochondrial phospholipids and the role of mitochondria in lipid metabolism. Additionally, we will discuss the connection between mitochondrial phospholipids disorder and human diseases.
保罗·克利在探寻摆脱物象模仿的纯粹化视觉体验的变革路径上,从中国绘画艺术中汲取养分,以反常规的图画比例、书写性、平面性、诗歌意象反叛熟练的绘画技法,以纯然的、未被教化的纯真稚拙对抗传统艺术规范,实现了西方绘画创作观念与实践的革新,获得了与中国绘画"写意性"共同追求的超越维度.本文从"对西方绘画写实传统的颠覆"、"对诗与画的一体融贯"、"对'心物一体'的精神追求"三个方面探寻保罗·克利绘画与中国绘画的内在契合之处,力图在平等对话的进程中对保罗·克利的绘画思想与创作路径有更为深刻、系统的把握.
保罗·克利被誉为西方现代最具创造性与思想性的艺术家之一,他既反对艺术的模仿论,也不同意将艺术归结为脱离自然的抽象形式,主张艺术并不呈现可见东西,而是把不可见的东西创造出来.本文立足于他的作品,从变形、符号、透明三个部分分析作品的图像特征,揭示保罗·克利的艺术及其美学思想的基本特征.
道在中西方哲学思想的发展历程中具有重要意义,本文从道的语义、中西方哲学思想对道的不同阐释、中国传统思想中道的伦理特征、西方哲学中道的逻辑和宗教特征等四个方面进行分析和比较,揭示道在中西方哲学思想中的主题、内涵、思想形态及各自特征.
Many cancer cells maintain enhanced aerobic glycolysis due to irreversible defective mitochondrial oxidative phosphorylation (OXPHOS). This phenomenon, known as the Warburg effect, is recently challenged because most cancer cells maintain OXPHOS. However, how cancer cells coordinate glycolysis and OXPHOS remains largely unknown. Here, we demonstrate that OMA1, a stress-activated mitochondrial protease, promotes colorectal cancer development by driving metabolic reprogramming. OMA1 knockout suppresses colorectal cancer development in AOM/DSS and xenograft mice models of colorectal cancer. OMA1-OPA1 axis is activated by hypoxia, increasing mitochondrial ROS to stabilize HIF-1 alpha, thereby promoting glycolysis in colorectal cancer cells. On the other hand, under hypoxia, OMA1 depletion promotes accumulation of NDUFB5, NDUFB6, NDUFA4, and COX4L1, supporting that OMA1 suppresses OXPHOS in colorectal cancer. Therefore, our findings support a role for OMA1 in coordination of glycolysis and OXPHOS to promote colorectal cancer development and highlight OMA1 as a potential target for colorectal cancer therapy.
通过研究姑苏、绍兴两地古城发展现状,将两地古城保护基金的筹集、管理、运作模式进行了研究并作比较分析,探讨了姑苏古城保护基金及古城保护发展中存在的主要问题,根据绍兴古城保护基金的成功经验提出了符合姑苏区实际情况的对策和建议.
《庄子内篇—秋水》的最后一段是庄惠的濠梁之辩,这一段对话讲述了庄子和惠子在濠水的一座桥上看到鲦鱼在水中游动,围绕着"人能否知道鱼在水里游的快乐"为主题所展开的辩论.立足于他们各自不同的思维方式与感知事物的态度,分析他们思想的同异.从情感、移情、忘情三个层面,由外及内的阐明快乐及快乐的本性,揭示出庄子思想意义上的"快乐"就是去掉情感束缚、超越移情、忘情意义上的自由.
Mitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains largely unknown. Here, we discovered that Mic19, a core component of MICOS (mitochondrial contact site and cristae organizing system) complex, can be cleaved at N-terminal by mitochondrial protease OMA1 under certain physiological stresses. Mic19 directly interacts with mitochondrial outer-membrane protein Sam50 (the key subunit of SAM complex) and inner-membrane protein Mic60 (the key component of MICOS complex) to form Sam50–Mic19–Mic60 axis, which dominantly connects SAM and MICOS complexes to assemble MIB (mitochondrial intermembrane space bridging) supercomplex for mediating mitochondrial outer- and inner-membrane contact. OMA1-mediated Mic19 cleavage causes Sam50–Mic19–Mic60 axis disruption, which separates SAM and MICOS and leads to MIB disassembly. Disrupted Sam50–Mic19–Mic60 axis, even in the presence of SAM and MICOS complexes, causes the abnormal mitochondrial morphology, loss of mitochondrial cristae junctions, abnormal cristae distribution and reduced ATP production. Importantly, Sam50 displays punctate distribution at mitochondrial outer membrane, and acts as an anchoring point to guide the formation of mitochondrial cristae junctions. Therefore, we propose that Sam50–Mic19–Mic60 axis-mediated SAM–MICOS complexes integration determines mitochondrial cristae architecture.
中国艺术中的意象构成了中国艺术的本质性特征.其中"意"就包含情感因素,而中国艺术的情感表现又是一个客观存在的本质性现象,因此探究"意象"这一中国核心审美问题必然离不开"情感"这一范畴.正是情感表现的需要才形成了中国艺术的意象性特征.文章分析情感及阐明情感与意象的内在关联,揭示情感在中国意象艺术形成过程中的独特作用与审美价值.
在分析城乡卫生一体化概念和政策目标的基础上,通过剖析我国典型地区城乡卫生一体化改革实践发现,我国当前的城乡卫生一体化改革主要以市或区为单位,形成市、乡、镇纵向一体化管理体系,借助政府的财政投入加强乡镇卫生院建设,在不同层级医疗卫生机构间建立协作关系,通过双向转诊机制形成城乡一体化的卫生服务提供体系,然后就我国目前城乡卫生一体化改革中存在的问题进行了分析.
公共机构的僵化往往无法较好适应外部环境的变化和刺激,且无法满足患者的期望和需求,在这种情况下,一些欧美国家开始在卫生领域引入私人资本,改革公立医院所有制。笔者通过分析欧美的私有化经验,认为公立医院私有化可以作为改善公立医院的一种重要方式,但是同时公立医院私有化也面临公平性、透明性、公益性等各种风险,政策制定者在发挥私有化优势的同时,要清晰地界定政策目标及卫生服务的特殊性,对公立医院私有化建立相应的监督、调控和评估机制。
By analyzing the first hand data on MPA students, the effects of public service motivation (PSM) on performance have been explored. The results suggest the positive relationship between public service motivation and performance. Those government employees with higher PSM also have higher performance. PSM can explain the most variance of two kinds of contextual performance as well as task performance.
卫生一体化是个全方位、多层次的概念,理想的卫生一体化状态是卫生体系的功能、组织机构、服务全面一体化状态.卫生一体化以提供理想的卫生服务为最终目标,依赖于资源的整合与共享,合作、协调与协作机制实现,对不同的利益相关者含义不同.卫生一体化能提高卫生资源利用效率;有助于改进医疗服务质量,提高健康产出;能促使医疗卫生费用降低,最大限度地方便患者;有利于实现医疗卫生服务均等化,实现社会公平.
Based on the analysis of health trust, this article describes the actualities of health trust loss in China from the interpersonal, institutional as well as health system levels, and suggests that China's health care system has important effects on the health trust loss, health corruption is the main social cause, the weakening moral constraints as well as the psychological effect about law is not responsible for the public are the main individual causes.
By analyzing China's health policy transition, its characteristics in five aspects were summarized: from isolated measures to systemic measures, from instrumental value to ultimate value, from efficiency orientation to fairness orientation, from unitary means to diversified means, from elite model to public participation model.
Trust deficiency in health field is an issue worth concerning in China.Based on the analysis of health trust loss in the area of doctor-patient interpersonal relationship,health organizations and institutions as well as health system,the deficiency causes were explored from the institutional,social and individual levels.The possible solutions were offered as follows: consummating health system,improving the health policy implement,governing health corruption and enhancing the moral of health from system,social environment and individual moral quality.
The purpose of this study is to examine several key elements of organizational performance in the public sector empirically. By exploring the effects of socioeconomic, organizational as well as individual factors based on responses from a primary survey, the authors find that those governmental organizations with more public orientation, more employee orientation, clearer goals, less procedure constraints are more effective than their counterparts. Governmental organizations located in the area of higher new economic index usually have higher levels of performance than those lower. Those employees with higher levels of public service motivation tend to report higher organizational performance perception than those less. The study suggests that strengthening the culture of public interest, improving organizational management, and enhancing employees' public service motivation may be the efficient ways to improve the performance.
<正>追求顾客完全满意是20世纪90年代国际流行的营销观念,这一观念也已被广大医院管理者所接受,在医院经营管理中制定了以病人满意为目标的医院发展战略。以病人满意为目标制定医院发展战略就必须对病人满意进行评价;然而,在当今我国医院病人满意度评价中还存在着许多错误,
How to deploy talents is an art.Facing today's fierce competition,it is essential how to take good advantages of great talents.Ancient China and some western countries have accumulated a lot of experience of talent deployment that we can learn from.Based on an analysis of ancient Chinese ideas and American concepts of talent deployment,this paper compares the differences between ancient China and the United States in the concept of talents,the value of talents,the basis of talent deployment,and so on.It also raises some suggestions in the light of some Chinese mistakes of talent deployment.These suggestions include improving the criterion of talents and adopting the scientific concept of talents;establishing the mechanism for the flow of talents and promoting talent's socialization;changing the thinking angle and strengthening group interests of talent deployment;recognizing talent's value and widening income gap reasonably;and caring for talents and ensuring the sustainable development of talents.