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| 1 | Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine显示文摘Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases. | Xizhan Xu Zezheng Gao Fuquan Yang Yingying Yang Liang Chen Lin Han Na Zhao Jiayue Xu Xinmiao Wang Yue Ma Lian Shu Xiaoxi Hu Na Lyu Yuanlong Pan Baoli Zhu Linhua Zhao Xiaolin Tong Jun Wang | 2020 | Genomics, Proteomics & Bioinformatics2020，18，6： | 29 |
| 2 | Numerical modeling of tidal currents,sediment transport and morphological evolution in Hangzhou Bay,China显示文摘A 2D depth-averaged numerical model is set up to simulate the macro-scale hydrodynamic characteristics,sediment transport patterns and morphological evolution in Hangzhou Bay,a large macro-tidal estuary on the eastern coast of China.By incorporating the shallow water equations,the suspended sediment transport equation and the mass-balance equation for sediment;short-term hydrodynamics,sediment transport and long-term morphological evolution for Hangzhou Bay are simulated and the underlying physical mechanisms are analyzed.The model reproduces the spatial distribution patterns of suspended sediment concentration(SSC) in Hangzhou Bay,characterized by three high SSC zones and two low SSC zones.It also correctly simulates the residual flow,the residual sediment transport and the sediment accumulation patterns in Hangzhou Bay.The model results are in agreement with previous studies based on field measurements.The residual flow and the residual sediment transport are landwards directed in the northern part of the bay and seawards directed in the southern part.Sediment accumulation takes place in most areas of the bay.Harmonic analysis revealed that the tide is flood-dominant in the northern part of the bay and ebb-dominant in the southern part of the bay.The strength of the flood-dominance increases landwards along the northern Hangzhoii Bay.In turn sediment transport in Hangzhou Bay is controlled by this tidal asymmetry pattern.In addition,the direction of tidal propagation in the East China Sea,the presence of the archipelago in the southeast and the funnel-shaped geometry of the bay,play important roles for the patterns of sediment transport and sediment accumulation respectively. | Dong-feng XIE Shu GAO Zheng-bing WANG Cun-hong PAN | 2013 | International Journal of Sediment Research2013，28，3： | 23 |
| 3 | Assessment of left ventricular systolic synchronicity by real-time three-dimensional echocardiography in patients with dilated cardiomyopathy显示文摘Background Recent advances in real-time three-dimensional echocardiography (RT3DE) offer the potential to assess the left ventricular (LV) dyssynchrony simultaneously by analyzing the 17 segments time-volume curves. The purpose of this study was to test the feasibility and accuracy of RT3DE for quantitative evaluation of left ventricular systolic synchronicity. Methods Twenty-four patients with dilated cardiomyopathy (DCM) and twenty-five healthy volunteers were enrolled in this study. Full volume RT3DE was performed by using Philips IE33 with X3-1 probe. The global and 17-segmental time-volume curves were obtained by the on-line Qlab software (version 4.2). The time to minimal systolic volume in each segment (Tmsv) was taken to derive the following indexes of systolic asynchrony: Tmsv 16-SD, Tmsv 16-Dif, Tmsv 12-SD, Tmsv 12-Dif, Tmsv 6-SD and Tmsv 6-Dif, which meant the standard deviation or the maximal difference of Tmsv among the 16, 12 and 6 segments of the left ventricle respectively. The software also provided with each of the above parameters as a percentage of the cardiac cycle. Results Tmsv 16-SD, Tmsv 12-SD and Tmsv 6-SD were all significantly larger in the DCM group than those of the control group [Tmsv 16-SD: (52.9±40.6) ms vs (8.8±6.2) ms; Tmsv 12-SD: (29.5±30.8) ms vs (6.9±4.0) ms; Tmsv 6-SD: (28.9±34.6) ms vs (7.0±4.7) ms, all P≤0.001]. Tmsv 16-Dif, Tmsv 12-Dif and Tmsv 6-Dif were also significantly larger in the DCM group. There were close negative relations between the LVEF determined by RT3DE and each of the indexes of systolic asynchrony, among which the indexes of Tmsv-16-SD% and Tmsv-16-Dif% correlated most closely (r=-0.703 and r =-0.701, respectively). The DCM patients had significantly larger EDV and ESV, with significantly reduced LVEF compared with the healthy subjects. Conclusion RT3DE provides a simple, useful and unique approach to assess the systolic synchronicity of all the left ventricular segments simultaneously. | ZENG Xin SHU Xian-hong PAN Cui-zhen CHEN Rui-zhen CHENG Kuan LIU Shi-zhen CHEN Hao-zhu | 2006 | Chinese Medical Journal2006，，11： | 16 |
| 4 | "Fast-track" and "Minimally Invasive" Surgery for Gastric Cancer显示文摘 | Xin-Xin Liu Hua-Feng Pan Zhi-Wei Jiang Shu Zhang Zhi-Ming Wang Ping Chen Yan Zhao Gang Wang Kun Zhao Jie-Shou Li | 2016 | Chinese Medical Journal2016，，19： | 15 |
| 5 | A new triterpene glycoside from sea cucumber Holothuria leucospilota显示文摘A new triterpene glycoside, leucospilotaside A, along with a known saponin, isolated from sea cucumber Holothuria leucospilota, and its structure was elucidated as 3β-O-[4-O-sodiumsulfate-β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyl]-holosta-22-ketone-9-en-17α,25α-diol (1) by extensive spectroscopic analysis and chemical methods. Leucospilotaside A (1) has a ketone carbonyl group (22) in the aglycon side chain. | Hua Han Yang Hua Yi Ling Li Xiao Hua Wang Bao Shu Liu Peng Sun Min Xiang Pan | 2007 | Chinese Chemical Letters2007，18，2： | 13 |
| 6 | Antioxidant and cardioprotective effects of Ilex cornuta on myocardial ischemia injury显示文摘Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and antiinflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root(ICR) were measured by 2, 2-diphenyl-1- picrylhydrazyl(DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by H_2O_2 or Na_2S_2O_4 in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease. | YUAN Yan PAN Shu YANG Shi-Lin LIU Yan-Li XU Qiong-Ming | 2017 | Chinese Journal of Natural Medicines2017，15，2： | 13 |
| 7 | The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment. | ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 11 |
| 8 | Nature:研究鉴定出蛋白Nlrp9b抵抗轮状病毒感染机制显示文摘轮状病毒(rotavirus)是婴儿和儿童罹患肠胃炎和腹泻的一种最为常见的原因,每年导致全世界大约21.5万人死亡。它是高度传染性的和潜在致命性的。这种病毒特异性地感染宿主小肠中的肠上皮细胞,并且已进化出抵抗干扰素和NF-KB信号的策略来躲避免疫系统,这就提出一个问题:其他的宿主因子是否参与肠道粘膜中的抗病毒反应。不过,针对体内(特别是通过NLR炎性体)检测和限制肠道病毒的机制,人们知之甚少。 | Shu Zhu, Zheng Wei, Noah W. Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R. de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Liang Shan, Richard A. Flavell Siyuan Ding, Ningguo Feng, Harry B. Greenberg Siyuan Ding, Harry B. Greenberg Penghua Wang, Yujiao Zhao Wen Pan, Jun Lu Jun Zhao, Yuval Kluger Kellie A. Jurado, Clara Abraham, Erol Fikrig Erol Fikrig, Richard A. Flavell | 2017 | 现代生物医学进展2017，17，27： | 10 |
| 9 | Modification on the tribological properties of ceramics lubricated by water using fullerenol as a lubricating additive显示文摘It is necessary to modify the running-in process for the application of ceramics using water as a lubricant in real conditions because ceramics sliding in water are characterized by a running-in period with severe friction and wear.Fullerenol,a kind of highly water-soluble nanoparticle,was synthesized and then used to ameliorate the tribological properties of Si 3 N 4 sliding against Al 2 O 3 in pure water.With the addition of fullerenol,the running-in period was shortened from 30 min to 100 s at a speed of 250 mm/s.The speed threshold above which ultralow friction can be obtained in a short time was expanded from 450 mm/s to 80 mm/s.Meanwhile,the load-carrying ability of water film was increased.The role of fullerenol was discussed based on observation of the wear scar by an optical interferometer and XPS characterization of the tribo-film on the wear track. | LIU YuHong WANG XiaoKang LIU PengXiao ZHENG JunPeng SHU ChunYing PAN GuoShun LUO JianBin | 2012 | Science China(Technological Sciences)2012，55，9： | 9 |
| 10 | 浆液 M2-pyruvate kinase : 为屏蔽的 colorectal 癌症质量的有希望的非侵略的 biomarker显示文摘 AIM: To explore the value of serum M2-pyruvate kinase (M2-PK) in colorectal cancer (CRC) mass screening. METHODS: We conducted a molecular epidemiology study in Hangzhou, China, from year 2006 to year 2008. Serum samples were collected from 93 CRC, 41 advanced adenomas, 137 adenomas, 47 non-adenomatous polyps, and 158 normal participants in a community setting. Serum M2-PK and carcinoembryonic antigen (CEA) were measured using Enzyme-linked immuno-sorbent assay. SPSS 16.0 software was used to perform data analysis. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificities were estimated for serum M2-PK in diagnosis of colorectal lesions and compared with CEA. RESULTS: Average serum M2-PK value among 158 normal people was 2.96 U/mL and not affected by gender (P = 0.47) or age (P = 0.59). Average serum M2-PK (U/mL) was 14.75 among stage Ⅲ and 13.10 among stage Ⅰ and Ⅱ CRC patients, about 4 times higher than that among normal people. Average serum M2-PK was 8.58, 6.70, 5.13 and 2.51 U/mL among advanced adenoma, adenomas, non-adenomatous polyps, and inflammatory bowel disease patients, respectively. AUC for serum M2-PK was greater than that for CEA among all colorectal lesions. AUC for serum M2-PK was 0.89 (0.84, 0.94) (95% confidence interval), higher than that for CEA [0.70 (0.62-0.79)] in CRC stageⅠ and Ⅱ, 0.89 (0.84-0.94) vs 0.73 (0.63-0.83) in CRC stage Ⅲ, 0.81 (0.74-0.86) vs 0.63 (0.53 -0.73) in advanced adeno- mas, 0.69 (0.64-0.76) vs 0.54 (0.47-0.60) in adenomas, and 0.69 (0.62-0.78) vs 0.58 (0.48-0.68) in nonadenomatous polyps. The diagnostic sensitivity for all colorectal lesions increased with decrease in the cut-off value of serum M2-PK. The diagnostic sensitivity (%) of serum M2-PK was 100.00 for CRC, 95.12 advanced ad- enoma, 82.48 adenoma, and 82.98 non-adenomatous polyp. There were no CRC cases missed and 40.51% of unnecessary colonoscopies were avoided when the cut-off value was 2.00 U/mL. CONCLUSION: Serum M2-PK can be used as a primary screening test in CRC mass screening. It may be a promising non-invasive biomarker for CRC early detection. | Wen Meng Hong-Hong Zhu Ze-Feng Xu Shan-Rong Cai Qi Dong Qiang-Rong Pan Shu Zheng Su-Zhan Zhang | 2012 | World Journal of Gastrointestinal Oncology2012，4，6： | 9 |
| 11 | Fourth C hinese National Consensus Report on the management of H elicobacter pylori infection显示文摘 | Wen Zhong Liu Yong Xie Hong Cheng Nong Hua Lu Fu Lian Hu Wan Dai Zhang Li Ya Zhou Ye Chen Zhi Rong Zeng Chong Wen Wang Shu Dong Xiao Guo Zong Pan Pin Jin Hu | 2013 | Journal of Digestive Diseases2013，，5： | 9 |
| 12 | Genome analysis and signature discovery for diving and sensory properties of the endangered Chinese alligator显示文摘Crocodilians 正在潜水能为时间的长时期在水下面屏息并且是有优秀感觉能力的黄昏的动物的爬行动物。他们包括鸟的一个姐妹系并且没有性染色体。这里,我们报导危及的中国短吻鳄(短吻鳄 sinensis ) 的染色体顺序并且描述它的唯一的特征。下一代的定序产生了未加工的顺序的 314 Gb,产出 2.3 Gb 的一种染色体尺寸。22 200 基因的一个总数用 de novo 在短吻鳄 sinensis 被预言,基于相同、基于 RNA 的联合模型。长潜水的行为的基因基础包括酸式碳酸盐绑定血红素基因,磷酸盐绑定和特殊酸式碳酸盐绑定氧搬运的常规的 co-functioning,和断然选择的精力的复制新陈代谢,铵酸式碳酸盐排泄和心肌收缩。进一步,我们阐明了柔韧的短吻鳄 sinensis 感觉系统包括一个显著地扩展的嗅觉的受体全部剧目,很快演变神经相关的细胞的部件和视觉感觉,和夜里的积极选择视觉相关的视蛋白和健全联系察觉的 otopetrin。我们也为抗菌剂肽的天生的免疫和表示为分成三部分的包含主题的 C 类型 lectin 和 butyrophilin 基因的适应免疫以及扩大与系特定的抗原演讲基因的一个可观的数字发现了一个开发得好的免疫系统。在 situ 杂交的 Multifluorescence 显示出那个短吻鳄染色体 3,它编码 DMRT1,与鸡染色体 Z 一起展出重要 synteny。最后,人口历史分析百万年以前显示了人口混合 0.60-1.05,当 Qinghai 西藏的高原被高举时。 | Qiu-Hong Wan Sheng-Kai Pan Li Hu Ying Zhu Peng-Wei Xu Jin-Quan Xia Hui Chen Gen-Yun He Jing He Xiao-Wei Ni Hao-Long Hou Sheng-Guang Liao Hai-Qiong Yang Ying Chen Shu-Kun Gao Yun-Fa Ge Chang-Chang Cao Peng-Fei Li Li-Ming Fang Li Liao Shu Zhang Meng-Zhen Wang Wei Dong Sheng-Guo Fang | 2013 | Cell Research2013，23，9： | 8 |
| 13 | Genetic Polymorphisms in the Precursor MicroRNA Flanking Region and Non-Small Cell Lung Cancer Survival显示文摘 | Hu, Zhibin Shu, Yongqian Chen, Yijiang Chen, Jiaping Dong, Jing Liu, Yao Pan, Shiyang Xu, Lin Xu, Jing Wang, Yi Dai , Juncheng Ma, Hongxia Jin, Guangfu Shen,Hongbing | 2011 | 南京医科大学学报(自然科学版)2011，31，6： | 8 |
| 14 | Influence of chronic HBV infection on superimposed acute hepatitis E显示文摘AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection. | Si-Hong Cheng Li Mai Feng-Qin Zhu Xing-Fei Pan Hai-Xia Sun Hong Cao Xin Shu Wei-Min Ke Gang Li Qi-Huan Xu | 2013 | World Journal of Gastroenterology2013，19，35： | 8 |
| 15 | Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study)显示文摘 | Lin Shen Jin Li Jianming Xu Hongming Pan Guanghai Dai Shukui Qin Liwei Wang Jinwan Wang Zhenzhou Yang Yongqian Shu Ruihua Xu Lei Chen Yunpeng Liu Shiying Yu Lilian Bu Yongzhe Piao | 2015 | Gastric Cancer2015，，1： | 7 |
| 16 | Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection显示文摘Missense mutations in Leucine-Rich Repeat Kinase 2(LRRK2)cause the majority of familial and some sporadic forms of Parkinson’s disease(PD).The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity,promoting the development of LRRK2 kinase inhibitors as therapeutics.Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise.However,nearly all inhibitors are ATP competitive—some with unwanted side effects and unclear clinical outcome—alternative types of LRRK2 inhibitors are lacking.Herein we identify 5′-deoxyadenosylcobalamin(AdoCbl),a physiological form of the essential micronutrient vitamin B12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity.Multiple assays show that AdoCbl directly binds LRRK2,leading to the alterations of protein conformation and ATP binding in LRRK2.STD-NMR analysis of a LRRK2 homologous kinase reveals the contact sites in AdoCbl that interface with the kinase domain.Furthermore,we provide evidence that AdoCbl modulates LRRK2 activity through disrupting LRRK2 dimerization.Treatment with AdoCbl inhibits LRRK2 kinase activity in cultured cells and brain tissue,and prevents neurotoxicity in cultured primary rodent neurons as well as in transgenic C.elegans and D.melanogaster expressing LRRK2 disease variants.Finally,AdoCbl alleviates deficits in dopamine release sustainability caused by LRRK2 disease variants in mouse models.Our study uncovers vitamin B12 as a novel class of LRRK2 kinase modulator with a distinct mechanism,which can be harnessed to develop new LRRK2-based PD therapeutics in the future. | Adam Schaffner Xianting Li Yacob Gomez-Llorente Emmanouela Leandrou Anna Memou Nicolina Clemente Chen Yao Farinaz Afsari Lianteng Zhi Nina Pan Keita Morohashi Xiaoluan Hua Ming-Ming Zhou Chunyu Wang Hui Zhang Shu G.Chen Christopher J.Elliott Hardy Rideout Iban Ubarretxena-Belandia Zhenyu Yue | 2019 | Cell Research2019，29，4： | 7 |
| 17 | Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C →T mutation of low-density lipoprotein receptor gene显示文摘背景家庭血胆脂醇过多(FH ) ,由低密度引起了脂蛋白(LDL ) 受体(LDL-R ) 基因变化,与早熟的冠的心疾病的增加的风险被联系。直到现在,有关 FH 的有限分子的数据在中国是可得到的。现在的学习描述了临床的侧面和房间有新奇 LDL-R 基因 mutation.Methods 的一个中国 FH 家族的生物缺点病人编码区域的 LDL-R 基因被定序。病人的淋巴细胞被孤立, LDL-R 表达式,绑定和举起函数被 immunohistochemistry 染色和流动 cytometry 察觉观察。病人的心和主要大容器被容器超声检查和病人的 LDL-R 表示, LDL 绑定和举起功能是的心肌的灌注成像(MPI ).Results 检测比正常控制显著地低(39% , 63% 和 76% 分别地) 。一篇小说同型结合 LDL-R 基因的 1439 CT 变化在病人和他的家庭被检测。ECG 显示出不正常的心绞痛。Echocardiogram 显示出冠的动脉的狭窄和大动脉的阀门和它的根的石灰化。血容器超声检查显示出大容器 intima 的厚度,并且容器腔被 71% 缩小。MPI 显示出的 ischemic changes.Conclusions FH 病人的 LDL-R 合成机能障碍导致动脉的狭窄和石灰化,它是临床的混乱的主要显型。LDL-R 基因的变化是坚定的。这些数据增加在中国的 FH 的 mutational 光谱。 | LIN Jie WANG Lu-ya LIU Shu XIA Jun-hui YONG Qiang DU Lan-ping PAN Xiao-dong XUE Hong CHEN Bao-sheng JIANG Zhi-sheng | 2008 | Chinese Medical Journal2008，，9： | 7 |
| 18 | Influence of Ce on Characteristics of Inclusions and Microstructure of Pure Iron显示文摘The experiments on adding Ce,Mn and S to molten iron have been carried out by means of the electric furnace,and the concentration of oxygen,the evolution of inclusions and microstructures of samples are analyzed,indicating that the concentration of dissolved oxygen decreases greatly after adding Ce. The calculated thermodynamics results at 1273 K performed on Factsage show that Ce2O2S and CeAlO3 are formed with the increase of Ce content for w(Ce)>0.0002 and w(S)<0.0001,while three cerium sulphides (CeS,Ce3S4 and Ce2S3,in sequence),MnS and Ce2O2S are formed with the increase of S content and the decrease of Ce content for w(Ce)>0.0002 and w(S)>0.0001. These results are consistent with the SEM observations. Finally,some possible reasons are given to explain the formation of intragranular ferrite in the pure iron. | WEN Bin SONG Bo PAN Ning SHU Qi-feng HU Xiao-jun MAO Jing-hong | 2011 | Journal of Iron and Steel Research(International)2011，18，2： | 7 |
| 19 | Morphological changes of blood spleen barrier in portal hypertensive spleen显示文摘背景:脾机能亢进和免疫者的致病与门静脉高血压(PH ) 在病人怒气工作仍然保持阴暗。这研究试图由于 PH 与脾机能亢进在怒气评估血怒气障碍的词法变化并且为怒气的有免疫力的功能的深入的调查向证据提供脾机能亢进和脾机能亢进的机制。方法:从有怒气的创伤的破裂的 12 个门 hypertensive 病人和 4 个病人的怒气样品被检验。怒气的样品被转变为病理学的节,与马森一起染色了三色的污点, Gomori 污点,和 CD68, CD34 免疫组织化学,并且是为在骨胶原纤维,网状纤维,巨噬细胞,和脉管的 endothelial 的分发的变化的检验用显微镜。在在缘带的巨噬细胞和 endothelial 的超微结构的变化被传播电子显微镜学也评估。结果:作为与正常怒气相比,在 PH 怒气的巨噬细胞的密度被减少,但是巨噬细胞主要位于缘带并且在脾小结附近散布了,与房间表面上的许多绒毛和像伪足的伸出。骨胶原纤维的增生在脾小结和中央动脉附近是明显的。增加的 reticulate 纤维环绕了有在纤维之间的更多的连接的脾小结。脉管的 endothelial 在传播分发,没有在 PH 怒气的任何 regionality,但是有扩大的腔的容器在红髓增加了。结论:血怒气障碍的词法变化能是为有免疫力的功能的反常和与 PH 位于病人的怒气的血细胞的增加的破坏的病理学的臀部之一。然而,这仍然必要澄清。 | LI Zong-fang ZHANG Shu HUANG Ying XIA Xian-ming LI Ai-min PAN Dun ZHANG Wei WANG Juan | 2008 | Chinese Medical Journal2008，，6： | 7 |
| 20 | Dexmedetomidine Attenuates High Glucose-induced HK-2 Epithelial-mesenchymal Transition by Inhibiting AKT and ERK显示文摘Objective To explore the protective effects of dexmedetomidine(Dex)against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms.Methods HK-2 cells were exposed to either glucose or glucose+Dex for 6 h.The production of ROS,morphology of HK-2 cells,and cell cycle were detected.Moreover,the expression of AKT,p-AKT,ERK,pERK,PI3 K,E-Cadherin,Claudin-1,andα-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3 K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126.Results Compared with HK-2 cells exposed to high level of glucose,the HK-2 cells exposed to both high level of glucose and Dex showed:(1)lower level of ROS production;(2)cell morphology was complete;(3)more cells in G1 phase;(4)lower expression of p-AKT,p-ERK andα-SMA,higher expression of ECadherin and Claudin-1.PI3 K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT,p-ERK andα-SMA,and increased the expression of E-Cadherin and Claudin-1.Conclusion Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK. | PAN Qi Zheng LI Kai YANG Zhuo Dong GAO Ming SHI Jia Hong REN Shu Ping ZHAO Guo Qing | 2020 | Biomedical and Environmental Sciences2020，33，5： | 7 |
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