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Topological and evolutional relationships between HCV core protein and hepatic lipid vesicles: Studies in vitro and in conditionally transgenic mice

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World Journal of Gastroenterology 2007年第25期13卷 3472-3477页

作者： Ming-Ling Chang Jeng-Chang Chen Chau-Ting Yeh I-Shyan sheen Dar-In Tai Ming-Yu Chang Cheng-Tang Chiu Deng-Yn Lin D Montgomery Bissell Liver Research Center and Department of Hepatogastroenterology Chang Gung MemorialHospital Chang Gung University College of Medicine TaoyuanTaiwan China Department of Surgery Chang Gung Children's Hospital Taoyuan Taiwan China Liver Center and Department of Medicine University of California San FranciscoUnited States

AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core. METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline (dox) by immunohistochemistry (IHC) and Western blotting and by sequential liver biopsy. Hepatic steatosis was evaluated using oil red stain. 8-hydroxydeoxyguanosine (8-OHdG) stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked. RESULTS: The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associatedwith microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression. CONCLUSION: The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo, oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the f irst animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.

关键词： Hepatic steatosis Conditional transgenicmice HCV core Oxidative stress

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Is the expression of γ-glutamyl transpeptidase messenger RNA an indicator of biological behavior in recurrent hepatocellular carcinoma?

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World Journal of Gastroenterology 2003年第3期9卷 468-473页

作者： I-Shyan sheen Kuo-Shyang Jeng Yi-Chun Tsai Liver Research Unit Chang Gung Memorial Hospital Taipei Taiwan China Departments of Surgery Mackay Memorial Hospital Taipei Taiwan and Mackay Junior School of Nursing Taipei Taiwan China Medical Research Mackay Memorial Hospital Taipei Taiwan China

AIM: To investigate the correlation between gammaglutamyl transpeptidase (γ-GTP) expression in the primary HCC and post-resection recurrence and its biological ***: Forty consecutive patients having curative resection for HCC were included in this study. The primers for reverse-transcription polymerase chain reaction (RTPCR) were corresponding to the 5'-noncoding human γ-GTP mRNA of fetal liver (type A), HepG2 cells (type B),and placenta (type C). Both the cancer and non-cancerous tissues of the resected liver were analyzed. The correlations between the expression of γ-GTP and the clinicopathological variables and outcomes (recurrence and survival) were ***: Those with type B γ-GTP mRNA in cancer had significant higher recurrence rate than those without it (63.6 % vs 14.3 %). Both those with type B in cancer and in non-cancer died significantly more than those without it (45.5 % vs 0 % and 53.6 % vs 0 %, respectively). By multivariate analysis, the significant predictors of recurrence included high serum AFP (P=0.0108), vascular permeation (P=0.0084), and type B γ-GTP mRNA in non-cancerous liver (P=0.0107). The significant predictors of postrecurrence death included high serum AFP (P=0.0141),vascular permeation (P=0.0130), and daughter nodules (P=0.0053). As to the manifestations (recurrent number ≥2, recurrent extent≥2 segments, extra-hepatic metastasis, and death) in recurrent patients, there were no statistical significant differences between those with type B in the primary tumor and those without it. The difference between those with type B in non-cancerous liver and those without it also was not ***: Patients of HCC with type B γ-GTP mRNA both in cancer and in non-cancerous tissue had a worse outcome, earlier recurrence, and more post-recurrence death.

关键词：肝细胞癌 γ-谷氨酰转换酶肿瘤生物学信号因子聚合酶链反应

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Is p53 gene mutation an indicatior of the biological behaviors of recurrence of hepatocellular carcinoma?

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World Journal of Gastroenterology 2003年第6期9卷 1202-1207页

作者： I-Shyan sheen Kuo-Shyang Jeng Ju-Yann Wu Liver Research Unit Chang Gung Memorial HospitalTaipeiTaiwan Department of Surgery Mackay Memorial HospitalMackay Junior School of NursingTaipeiTaiwan Medical Research Mackay Memorial HospitalTaipeiTaiwan

AIM: To evaluate mutant p53 gene in primary hepatocellular carcinoma and to investigate the correlation between it and the recurrence of hepatocellular ***: Mutations of p53 gene were examined using antihuman p53 monoclonal antibody and immunohistochemical staining in 79 resected hepatocellular carcinomas. The correlations among variables of p53 positivity and invasiveness, disease free interval and survival were *** addition, in those who developed recurrence, the correlation among p53 positivity, clinical features and postrecurrence survival were also ***: Of these 79 cases, 64 (81%) had p53 *** patients with mutant p53 positivityhad significantly more tumor recurrence (76.6 % vs 40.0 %, P=0.0107).However, the COX proportional hazards model showed that p53 overexpression had only weak correlations with recurrence free interval and survival time (P=0.088 and 0.081), which was probably related to the short duration of follow-up. The invasiveness variables may be predictors of HCC recurrence. On univariate analysis, more patients with mutant p53 positivity had vascular permeation [78.1vs 40.0 %, P=0.0088, O.R. (odds ratio) =5.3], grade Ⅱ-ⅣV differentiation (98.4 vs 80.0 %, P=0.0203, O.R. =15.7), no complete capsule (82.8 vs 53.3 %, P=0.0346, O.R. =4.2)and daughter nodules (60.9 vs. 33.3 %, P=0.0527, O.R.=3.1) than patients with negative p53 staining. Onmultivariate analysis, only vascular permeation and grade of differentiation remained significant (P=0.042 and 0.012).There was no statistically significant correlation betweenthe status of p53 in the primary lesion and the clinical features of recurrent hepatocellular carcinomas examined,including extrahepatic metastasis (P=0.1103) and the number of recurrent tumors (P= 1.000) except for diseaseover more than one segment in the extent of recurrent tumors (P=0.0043). The post-recurrence median survival was lower in patients in whom p53 mutation had been detected in the primar

关键词：肝细胞癌复发 p53基因基因表达生物学行为

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Impact of Chlorine, Temperature and Freezing Shock on the Survival Behavior of <i>Escherichia coli</i>O157:H7 on Ready-to-Eat Meats

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Food and Nutrition Sciences 2012年第4期3卷 530-538页

作者： Shiowshuh sheen Cheng-An Hwang Vijay K. Juneja Food Safety and Intervention Technologies Research Unit USDA Agricultural Research Service Research Facility Eastern Regional Research Center Wyndmoor USA Residue Chemistry and Predictive Microbiology Research Unit USDA Agricultural Research Service Research Facility Eastern Regional Research Center Wyndmoor USA.

Foodborne pathogens continue to pose a potential food safety hazard in ready-to-eat (RTE) meat. Chlorine is commonly used to sanitize processing equipment where Escherichia coli O157:H7 (Ec) may survive and contaminate food products. The objective of this study was to characterize the survival behavior of Ec with different stresses on RTE meats. A multi-strain cocktail of Ec was pre-treated with freezing shock for 15 - 20 h and/or chlorine (0, 25, and 50 ppm) for one hour, and then inoculated onto RTE meat surfaces to obtain about 3.0 log CFU/g. Samples were stored at three abuse temperatures (12℃, 18℃, and 24℃) and Ec was enumerated during the storage. The freezing shock impact was studied using the Ec cocktail stored in a freezer overnight followed by chlorine exposure for one hour. The lag phase and growth rate of Ec were estimated using DMFit (Combase, Baranyi’s model). Results indicated that Ec growth was suppressed by chlorine treatment. Freezing shock was found to have little impact in terms of lag time and growth rate. The lag phase of Ec after exposure to 0 ppm of chlorine (50.3 h) was shorter than that of Ec treated with 25 ppm (54.6 h) and 50 ppm (164.1 h) at 12℃. However, the lag phase decreased with an increase in temperature, e.g. at 25 ppm, lag times were 54.6, 51.1 and 48.9 h for 12℃, 18℃ and 24℃, respectively. Lag times increased with an increase in chlorine concentration. At 24℃, lag times were 15.8, 48.9, and 52.4 h for 0, 25, and 50 ppm, respectively. The growth rate increased with an increase in temperature for 0 and 25 ppm chlorine levels, but decreased at 50 ppm level. Growth rate and lag phase as a function of temperature and chlorine concentration can be described by polynomial models and modified Ratkowsky-type and Zwietering-type models. Results of this study will contribute to risk assessment of RTE meats.

关键词： Chlorine Lag Time Growth Rate E. coli O157:H7 Modeling

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Glucose-TOR signalling orchestrates metabolic transcriptome and meristem establishment

Glucose-TOR signalling orchestrates metabolic transcriptome ...

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从植物科学到农业发展——2012全国植物生物学大会

作者： Matthew McMcormark Qi Hall Jen sheen Department of Molecular Biology Massachusetts General Hospitaland Department of GeneticsHarvard Medical School School of Life Science University of Science and Technology of China

Meristems encompass stem/progenitor cells that sustain postembryonic growth of all plant *** meristems are established and stimulated by nutrient signaling remains enigmatic in photosynthetic *** chemical manipulations and chemical genetics at the photoautotrophic transition checkpoint,we reveal that shoot photosynthesis drives long-distance glucose-target-of-rapamycin(TOR) signaling relays through glycolysis and mitochondrial bioenergetics to control root meristem establishment and accelerate growth, which is decoupled from direct glucose sensing,growth-hormone signaling,and stem-cell ***,glucose-TOR signaling dictates transcriptional reprogramming of remarkable gene sets involved in cell cycle,transcription,signaling,metabolism, transport and ***,cellular and genetic analyses uncover TOR phosphorylation of E2Fa transcription factor for an unconventional activation of S-phase genes,and glucose-insensitive e2fa root-meristem *** findings establish pivotal roles of glucose-TOR signaling in unprecedented transcriptional networks wiring central metabolism/biosynthesis for energy/biomass production,and integrating localized stem/progenitor-cell proliferation through inter-organ nutrient signaling to control developmental transition and growth.

关键词： Target of rapamycin glucose mitochondrial bioenergetics meristem photoautotrophic transition inter-organ signaling E2Fa transcription factor.

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Garlic Essential Oil Attenuates Hepatic Oxidative Stress,Inflammatory Response,and Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease

Garlic Essential Oil Attenuates Hepatic Oxidative Stress,Inf...

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第十四届全国中药和天然药物学术研讨会

作者： Yi-Syuan Lai Lee-Yan sheen National Taiwan University

Garlic（Allium sativum L.） is an important agricultural product,and has variety of dietary and medicinal *** study investigated the protective properties of garlic essential oil（GEO） and its major organosulfur component（diallyl disulfide,DADS） against the development of nonalcoholic fatty liver disease（NAFLD）.C57BL/6J mice were fed a normal diet or high-fat diet（HFD） with/without GEO（25,50,and 100 mg/kg） or DADS（10 and 20mg/kg） for 12 *** significantly increased glucose,insulin,FFA,triglycerides,total cholesterol,AST and ALT serum levels,hepatic triglycerides and total cholesterol levels,and liver steatosis compared to the control *** addition,moderate levels of oxidative stress and inflammation were *** the statistical analysis of metabolomics data,several key metabolites were found to be influenced by HFD *** and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain,adipose tissue weight and serum biochemical *** of 50,100 mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro-inflammatory cytokines in liver,accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression during NAFLD *** anti-NAFLD effects of GEO and DADS were mediated through down-regulation of sterol regulatory element binding protein-1c,acetyl-CoA carboxylase,fatty acid synthase,and3-hydroxy-3-methylglutaryl-coenzyme A reductase,as well as stimulation of peroxisome proliferator-activated receptor alpha and carnitine *** results demonstrate that GEO and DADS dose-dependently protected obese mice with long-term HFD-induced NAFLD from lipid accumulation,inflammation,and oxidative damage by ameliorating lipid metabolic disorders and oxidative *** dose of 20 mg/kg DADS was equally effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS,which demonstrates that DADS

关键词： garlic essential oil diallyl disulfide nonalcoholic fatty liver disease metabolites lipid metabolism

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“给自己多一份关心”——谈谈电脑桌椅的选购

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计算机应用文摘 2000年第11期16卷 35-36页

作者： sheen

时下的电脑爱好者们在配置电脑方面可谓毫不吝啬，动辄上万元的配置已是屡见不鲜了，而且总是千挑万选，货比三家。可是对于一些配套的设施，比如电脑的桌椅，却是很少有人会注意的。据我所知很多的朋友并没有专门的电脑桌椅，只是普通... 详细信息

时下的电脑爱好者们在配置电脑方面可谓毫不吝啬，动辄上万元的配置已是屡见不鲜了，而且总是千挑万选，货比三家。可是对于一些配套的设施，比如电脑的桌椅，却是很少有人会注意的。据我所知很多的朋友并没有专门的电脑桌椅，只是普通的书桌和坐椅代替，即使有专业桌椅的人，也不会花太多金钱和精力在上面，往往是一些百元左右的低廉货色。

关键词：电脑桌电脑椅选购注意事项

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人工智能与公共管理研究:技术可能性、议题重构和治理创新

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中国行政管理 2020年第3期 6-11页

作者：禹信崔之元清华大学公共管理学院北京100081

人工智能对于人类社会的变革影响引起了公共管理领域的普遍重视,但在强人工智能以及人工智能必然导致自动化、智能化社会形态的前提假设下,相关研究可能继承了技术决定论的局限思维,从而低估了人工智能对于人类社会的潜在贡献。自然科... 详细信息

人工智能对于人类社会的变革影响引起了公共管理领域的普遍重视,但在强人工智能以及人工智能必然导致自动化、智能化社会形态的前提假设下,相关研究可能继承了技术决定论的局限思维,从而低估了人工智能对于人类社会的潜在贡献。自然科学视角对于强人工智能的否定揭示了人工智能所具有的多种技术可能性,在此基础上从个体、组织、全球三个层面的议题重构更多强调人类自身以及人类社会活动的产物对于人工智能发展及其社会变革过程的影响,而由此启发学科、制度、政策三方面治理创新进而推动相关理论和实践以更为开放的态度面对新技术带来的变革与影响。

关键词：人工智能公共管理技术可能性治理创新

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能够满足30mW待机功耗要求的实用手机充电器解决方案

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今日电子 2011年第8期 38-39页

作者： James sheen 飞兆半导体公司

做一个简单的数学计算，就很容易理解为什么政府机构和手机制造商突然积极致力降低手机充电器的待机功耗了：全球手机用户超过40亿，而其中大多数用户都习惯于即使在电池完全充满并拔掉手机之后，仍然让自己的充电器保持连接状态，因而... 详细信息

做一个简单的数学计算，就很容易理解为什么政府机构和手机制造商突然积极致力降低手机充电器的待机功耗了：全球手机用户超过40亿，而其中大多数用户都习惯于即使在电池完全充满并拔掉手机之后，仍然让自己的充电器保持连接状态，因而会继续耗电。根据诺基亚的统计，移动设备使用期间用电量的三分之二是在空载模式下消耗的。

关键词：手机充电器待机功耗手机用户手机制造商数学计算政府机构连接状态移动设备

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外语教学中使用对比分析的优势

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外语教学理论与实践 1998年第1期 24-30页

作者： Ronald sheen 黄子东加拿大魁北克大学现代语言系广东外语外贸大学

在70年代的北美,语言教学材料中的对比分析输入语言(CA input)遭到了否定,这种否定不是由实验数据表明了它的不适当而引起的,而是由它跟受攻击的结构法(structural method)有密切联系而引起的。80年代由于Dulay、Butr和Krashen(1982)的... 详细信息

在70年代的北美,语言教学材料中的对比分析输入语言(CA input)遭到了否定,这种否定不是由实验数据表明了它的不适当而引起的,而是由它跟受攻击的结构法(structural method)有密切联系而引起的。80年代由于Dulay、Butr和Krashen(1982)的误差分析(Error Analysis)研究结果得到了选择性的引用,它在该领域中的“不受欢迎”地位得到了进一步“加强”。但是,尤其在欧洲,有关归纳法和演绎法的比较研究并没有证实这些研究结果,这些比较研究表明,以对比分析和解释为基础的演绎法最有效。与此同时,第二语言习得(SLA)领域的研究人员重新对负向转移,即现在所称的跨语言影响(Crosslinguistic InfIuence(CUI))产生了兴趣,但他们的发现尚未对教材编写产生影响。因此,我们有必要对外语教学中对比分析输入语言的有效性重新进行评估。这里所报告的实验研究就是为了满足这种需要而做的。本研究假设,使用对比分析输入语言的演绎法在减少误差率(error rates)方面比不使用对比分析输入语言的归纳法更有效。研究结果不仅证实了假设,也给外语教学提供了启发。

关键词：非对比分析输入语言演绎法外语教学归纳法第二语言习得比较研究跨语言影响误差率控制组

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