Background and aimsOverweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model. Materials and methodsBeagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays. ResultsTwenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways. ConclusionThe prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.

近年来,我国老年人口的养老问题面临着日益严峻的挑战,家庭养老不再足以支撑全社会的养老需求.商业养老保险在解决养老问题上的重要性日益凸显,但在经营过程中可能面临逆向选择问题.文章选取2018年中国综合社会调查数据使用Probit模型实证检验发现我国商业养老保险市场存在逆向选择问题.异质性分析结果显示,仅青年群体中不存在逆向选择问题,中年群体中的逆向选择问题比老年群体严重,城镇人口比农村人口严重,收入较高者比收入较低者严重.使用2015年数据和2018年剔除老年人群的数据进行稳健性检验、采用工具变量法进行内生性检验后的结果依然稳健.进一步利用双变量Probit模型研究风险感知、心理状况和风险态度对逆向选择行为内在影响的结果显示,感知到自身健康的个人更可能有逆向选择行为,良好的心理状况也促进了逆向选择行为的发生,对风险的偏好态度则抑制了逆向选择行为的发生.

HepatologyVolume 74, Issue 5 p. 2831-2838 Concise Review Therapeutic Potential of G Protein-Coupled Receptors Against Nonalcoholic Steatohepatitis Dating Sun, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorXia Yang, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorBin Wu, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorXiao-Jing Zhang, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China Basic Medical School, Wuhan University, Wuhan, ChinaSearch for more papers by this authorHongliang Li, Corresponding Author lihl@whu.edu.cn Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China Basic Medical School, Wuhan University, Wuhan, China Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Zhi-Gang She, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: zgshe@whu.edu.cn Tel.: +1-86-27-68750276 or Hongliang Li, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: lihl@whu.edu.cn Tel.: +1-86-27-68759302Search for more papers by this authorZhi-Gang She, Corresponding Author zgshe@whu.edu.cn Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Zhi-Gang She, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: zgshe@whu.edu.cn Tel.: +1-86-27-68750276 or Hongliang Li, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: lihl@whu.edu.cn Tel.: +1-86-27-68759302Search for more papers by this author Dating Sun, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorXia Yang, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorBin Wu, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, ChinaThese authors contributed equally to this work.Search for more papers by this authorXiao-Jing Zhang, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China Basic Medical School, Wuhan University, Wuhan, ChinaSearch for more papers by this authorHongliang Li, Corresponding Author lihl@whu.edu.cn Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China Basic Medical School, Wuhan University, Wuhan, China Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Zhi-Gang She, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: zgshe@whu.edu.cn Tel.: +1-86-27-68750276 or Hongliang Li, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: lihl@whu.edu.cn Tel.: +1-86-27-68759302Search for more papers by this authorZhi-Gang She, Corresponding Author zgshe@whu.edu.cn Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Institute of Model Animal, Wuhan University, Wuhan, China ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Zhi-Gang She, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: zgshe@whu.edu.cn Tel.: +1-86-27-68750276 or Hongliang Li, M.D., Ph.D. Department of Cardiology, Renmin Hospital of Wuhan University #238 Jiefang Road 430060 Wuhan, China E-mail: lihl@whu.edu.cn Tel.: +1-86-27-68759302Search for more papers by this author First published: 07 April 2021 https://doi.org/10.1002/hep.31852Citations: 1 Supported by grants from National Key R&D Program of China (2016YFF0101504 to Z.G.S.), the National Science Foundation of China (81630011 to H.L., 81970364 to Z.G.S., and 81970070 to X.J.Z.), the Major Research Plan of the National Natural Science Foundation of China (91639304 to H.L.), the Creative Groups Project of Hubei Province (2016CFA010 to H.L.), the Hubei Science and Technology Support Project (2018BEC473 to H.L.), and the Hubei Construction Project of Science and Technology Condition Platform in Province (2017BEC001 to H.L.). Potential conflict of interest: Nothing to report. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Citing Literature Volume74, Issue5November 2021Pages 2831-2838 RelatedInformation

BACKGROUND AND AIMS:NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms.METHODS AND RESULTS:In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition.CONCLUSION:SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

The purpose of social basic medical insurance is to solve the problem that “medical treatment is difficult and expensive.” With the implementation of new technologies and new diagnosis and treatment methods, the price of medicine has risen sharply. Under this background, can basic medical insurance still relieve the economic pressure of patients? Based on the tracking data of China Health and Nutrition Survey (CHNS) from 2006 to 2015, by constructing Heckman sample selection model, the paper finds that the basic medical insurance for urban employees (UEBMI) leads to an increase in medical expenses, among which only 0.61% can be attributed to the release of normal medical demand and 114.47% can be attributed to moral hazard; for flexible employees, 249.52% increase can be attributed to adverse selection. Based on this, the paper puts forward two suggestions: first, promoting Hierarchical Treatment Model to control the growth of medical expenses and second, guiding flexible employees to participate in the UEBMI.

Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation of the arachidonic acid pathway, in particular the arachidonate 12-lipoxygenase (ALOX12) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.

新冠肺炎等重大公共卫生事件对保险业的影响包括需求与供给两方面.在需求端,存在影响保险需求的多个直接和间接机制,机制间效应此消彼长;采用2002～2003年277个城市554组样本,以DID和PSM-DID方法实证检验了SARS为代表的重大公共卫生事件对保险需求的影响.实证结果表明,SARS疫情对于当年人身保险需求和财产保险需求均无显著影响.在供给端,采用识别—评估—应对的风险管理流程分析法,研究了新冠肺炎疫情对保险供给带来的挑战,包括:生物安全灾难成为保险业面对的第四类灾难;生物病毒风险引发系统性风险向非系统性风险的转化;保险业可以通过设计弹性保险产品和提供综合风险管理服务来应对有关风险.

施蛰存致《辛报》编者、致熊庆来以及致朱雯、罗洪伉俪的3封信,《施蛰存全集》及其他有关施蛰存的著作均未见收录.这3通佚简对于考察和研究20世纪三四十年代施蛰存的人生轨迹、交游情况及文学活动,具有一定的史料价值.

我国现行党政机关公文文种设置科学合理,但在实际运行中也出现了一些需要改进和完善的方面.现行公文文种数量较多、外延交叉、功能重叠、方向失衡,本文建议文种稳中求降、明晰适用范围、厘清文体功用、平衡行文方向,通过提出文种设置及使用建议,继续强化文种功能和发挥公文效用,为现在和将来的公文建设提供必备的专业支撑和具体的借鉴参考.

近年来,古代公文文种流变受到了众多学者的关注,但围绕近代以来的公文文种流变展开的研究则相对较少.从晚清时期、太平天国时期、北洋军阀时期、中华民国时期到新中国成立以来,公文文种既有直接或间接继承前代者,又有为适应社会需要而新增者.全面、系统地考察近代以来公文文种的流变过程及其规律,可以维护公文文种的合法性和权威性,促进公文学科的发展,从而提升党政机关公文处理工作水平和行政效能.

墨家以"贵义"为宗旨,力求所有人以纯粹无私的动机("一爱")、全面关怀的方式("周爱")、与人为义的本质("利爱")以及兼以易别("兼爱")的指向达到"交相利"."兼爱"倡导给予所有人以"佩得"的福利,寻求获取机会与分配资源的平等,这有助于从根源上消除"看病难"和"看病贵";"利爱"断言"爱"的本质是利益的流动与转存,只有将"爱"的奉献与"利"的让渡统一起来,才能增进医患信任,营造互利共赢的和谐医疗情境;"周爱"强调"爱"之手段、方法的周全与科学性,可以熄灭医患冲突的导火索(沟通不畅);"一爱"即动机纯洁的爱,弘扬"一爱"理念,纯洁执医动机,调适医者行医心态,有利于重塑医患互信,重建医患和谐.和谐医患关系的构建是一项复杂的综合性工程,不仅需要"四爱"思想给以精神层面的情感培育,同时也离不开物质层面的财政支持、制度结构的深化改革与外显行为的规范约束,还有政府、大众媒体等多种不同主体的共同参与,只有充分投入并联结各项有益的社会资源,才能够早日落实"健康中国"的战略规划.

《穆时英全集》自出版以来,学者们先后发现了三十余篇穆时英佚文.但穆时英佚文尚有进一步发掘的空间,其致胡适一通信函,《社会日报·每周电影》上的《关于“尘无随笔”》,上海《晨报·晨曦》上的一篇《社中偶语》,以“龙七”笔名发表的《论战时颓废》,被暗杀前所拟一则启事稿,均未收入《穆时英全集》.《国民新闻》上的数十篇社论,大多出自穆时英之手笔.另外,《晨报》《时代日报》上署名“伐扬”的文章,《国民新闻》“每日座谭”栏内署名“真一”的文章,亦疑为穆时英所作.

近年来银行系寿险公司异军突起,扩容速度之快、规模增长之巨令行业侧目,俨然成为中国银行保险发展的“救赎者”.在此情形下,我们聚焦于银行系寿险公司经营效率及其影响因素的研究,探讨其快速发展的原因是否在于银行股东背景.采用2010--2015年间10家银行系与1 2家非银行系寿险公司样本的DEA效率实证结果显示:平均而言银行系寿险公司的经营效率仍低于非银行系寿险公司,但其间差距有所缩小;银行系寿险公司中,银行直接控股的寿险公司在经营效率上要高于银行主导的金融集团控股的寿险公司;银行系寿险公司整体呈现规模报酬递增的特点,而非银行系寿险公司则整体呈现规模报酬递减的特点.针对上述经营效率的差异,运用Tobit回归的实证进一步发现:银保专业化程度、公司性质、公司规模等指标与经营效率之间存在正向关系,而股东背景、成立年限等因素对经营效率的影响并未通过检验.

2017年国务院印发的《“十三五”国家老龄事业发展和养老体系建设规划》中,对于养老服务体系的表述,从“十二五”规划中的“居家为基础、社区为依托、机构为支撑”转变为“居家为基础、社区为依托、机构为补充、医养相结合”,不仅将机构养老的定位由“支撑”调整为“补充”,而且将“医养结合”纳入顶层设计,使得“医养结合”成为养老服务体系的突出特征.

Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. Lack of effective pharmacotherapies for NASH is largely attributable to an incomplete understanding of its pathogenesis. The deubiquitinase cylindromatosis (CYLD) plays key roles in inflammation and cancer. Here we identified CYLD as a suppressor of NASH in mice and in monkeys. CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity. We observed that overexpression of Cyld in hepatocytes concomitantly inhibits lipid accumulation, insulin resistance, inflammation and fibrosis in mice with NASH induced in an experimental setting. Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. Notably, reconstitution of hepatic CYLD expression effectively reverses disease progression in mice with dietary or genetically induced NASH and in high-fat diet-fed monkeys predisposed to metabolic syndrome. Collectively, our findings demonstrate that CYLD mitigates NASH severity and identify the CYLD-TAK1 axis as a promising therapeutic target for management of the disease.

受自然与人为因素综合影响,灌区水转化过程复杂多变.以湖北漳河水库灌区为例,分别从水平和垂直方向描述典型灌排系统的水转化过程,以水量平衡原理为基础,研发灌排系统边界处置、稻作区田间多层土壤、塘坝及排水沟道之间多个水转化模拟子模块,由此构建一种客观描述灌排系统边界半封闭结构及其水平输送、垂直运动与渠—田—沟—塘水转化过程的耦合模拟模型,解决了应用流域分布式水文模型求解灌区水转化过程中面临的灌区边界不确定、分层土壤简化处理等问题.利用漳河灌区谭店灌排系统2014-2015年水平衡测试观测数据对该模型进行检验,采用拉丁超立方抽样法对模型参数进行分层抽样,并利用偏相关法分析参数敏感性.通过模型计算可得,支沟率定期和验证期模拟结果的复相关系数分别为0.83、0.70,Ens系数分别为0.81、0.68,斗沟率定期和验证期模拟结果的复相关系数分别为0.79、0.68,Ens系数分别为0.73、0.62,结果表明该模型适用于灌排系统水转化过程模拟.与SWAT模型对比,对于同一研究区域,复相关系数由0.11提高到0.73,Ens系数由-0.71提高到0.70,进一步验证了该模型的先进性,为灌排系统尺度水转化模拟和机制研究提供了新方法.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Despite such public and clinical health importance, very few effective therapies are currently available for NAFLD. We report a protective function and the underlying mechanism of dual-specificity phosphatase 14 (DUSP14) in NAFLD and related metabolic disorders. Insulin resistance, hepatic lipid accumulation, and concomitant inflammatory responses, key pathological processes involved in NAFLD development, were significantly ameliorated by hepatocyte-specific DUSP14 overexpression (DUSP14-HTG) in high-fat diet (HFD)-induced or genetically obese mouse models. By contrast, specific DUSP14 deficiency in hepatocytes (DUSP14-HKO) aggravated these pathological alterations. We provided mechanistic evidence that DUSP14 directly binds to and dephosphorylates transforming growth factor -activated kinase 1 (TAK1), resulting in the reduced activation of TAK1 and its downstream signaling molecules c-Jun N-terminal kinase 1 (JNK), p38, and nuclear factor kappa B NF-B. This effect was further evidenced by the finding that inhibiting TAK1 activity effectively attenuated the deterioration of glucolipid metabolic phenotype in DUSP14-HKO mice challenged by HFD administration. Furthermore, we identified that both the binding domain and the phosphatase activity of DUSP14 are required for its protective role against hepatic steatosis, because interruption of the DUSP14-TAK1 interaction abolished the mitigative effects of DUSP14. Conclusion: Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. (Hepatology 2018;67:1320-1338).

为揭示东北寒区黑土稻田分层土壤水分二维运动规律,选择黑龙汀省庆安灌溉试验站稻田土壤开展控制灌溉水层及地下水位条件下分层土壤与均质土壤室内入渗试验.设计装置分层收集侧渗水量,定量识别分层土壤垂直渗漏与侧向渗漏,并基于HYDRUS-2D软件建立水分二维运动模型.结果表明土壤水力特性参数反演效果较好,模型模拟值与实测值吻合;土壤的分层结构抑制了水分入渗,降低了水平侧渗速率及垂直渗漏速率,分层土柱犁底层基本无侧渗输出,耕作层与底土层稳定后的侧渗速率分别为0.007和0.023cm/h.进行水量平衡分析,分层土柱入渗稳定后侧向渗漏占总渗漏的72.45％,主要通过底土层输出(63.42％);引入“单宽侧渗量”表示不同控制条件下土壤的侧渗输出,灌溉水层的增加显著增大了耕作层与底土层土壤的单宽侧渗量,控制灌溉水层有利于减少侧渗,提高用水效率;犁底层厚度增加主要贡献底土层的单宽侧渗量,反之,地下水位埋深增大则降低了底土层的单宽侧渗量,因此维持稻田适宜的犁底层厚度及地下水位埋深有利于减少深层渗漏损失.

With undulating conditions in hilly region of southern China,the mechanism of soil water transformation is complicated due to different soil textures between upstream and downstream fields as well as different layers within field.In order to reveal the influence of field different layers on soil water movement,field experiment was conducted in Tuanlin experimental irrigation station of Zhanghe irrigation district in Hubei province.Both water lateral infiltration through the cultivated horizon layer(CHL) and vertical infiltration through plow pan layer(PPL) under variable water table in field were monitored or estimated in the experiment.The processes were also simulated by a two-dimensional soil water movement model under variable water head using HYDRUS-2D,which show that the simulated results agree well with observed values.The results demonstrate that the PPL with compact structure in field,decreased deep percolation by retarding water vertical movement,but at the same time enhanced water lateral movement through the CHL.The average soil stable vertical infiltration rate through the PPL was 0.006cm/min,while the average soil stable lateral infiltration rate through the CHL was 0.05cm/min.Based on the analysis of soil water balance at the stage of steadily infiltration,the total percolation in experiment area accounted for 21.11％ of the cumulative infiltration,0.46％ and 20.65％ of which were attributed to the vertical percolation and lateral seepage,respectively,and the CHL contributed 81.06％ to the lateral seepage.The study illustrates that the lateral seepage plays an important role in water losses so that it is very essential to control percolation especially lateral seepage for water-saving and drainage reduction in southern China.