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Chlorpromazine protects against acetaminophen-induced liver injury in mice by modulating autophagy and c-Jun N-terminal kinase activation

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Liver Research 2019年第1期3卷 65-74页

作者： Yuan Li Hong-Min Ni hartmut Jaeschke Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsThe University of Kansas Medical CenterKansas CityKSUSA

Background and aim:Overdose of acetaminophen(APAP)leads to liver injury,which is one of the most common causes of liver failure in the United *** previously demonstrated that pharmacological activation of autophagy protects against APAP-induced liver injury in mice via removal of damaged mitochondria and APAP-adducts(APAP-ADs).Using an image-based high-throughput screening for autophagy modulators,we recently identified that chlorpromazine(CPZ),a dopamine inhibitor used for anti-schizophrenia,is a potent autophagy inducer in ***,the aim of the present study is to determine whether CPZ may protect against APAP-induced liver injury via inducing ***:Wild type C57BL/6J mice were injected with APAP to induce liver *** was administrated either at the same time with APAP(co-treatment)or 2 h later after APAP administration(post-treat-ment).Hemotoxyline and eosin(H&E)staining of liver histology,terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining of necrotic cell death as well as serum levels of alanine aminotransferase(ALT)were used to monitor liver ***:We found that CPZ markedly protected against APAP-induced liver injury as demonstrated by decreased serum levels of ALT,liver necrotic areas as well as TUNEL-positive cells in mice that were either co-treated or post-treated with ***,we observed that CPZ increased the number of autolysosomes and decreased APAP-induced c-Jun N-terminal kinase activation without affecting the metabolic activation of *** inhibition of autophagy by chloroquine partially weak-ened the protective effects of CPZ against APAP-induced liver ***:Our results indicate that CPZ ameliorates APAP-induced liver injury partially via activating hepatic autophagy and inhibiting JNK activation.

关键词： Chlorpromazine(CPZ) Acetaminophen(APAP) Drug-induced liver injury Necrosis Autolysosome Hepatotoxicity Glutathione(GSH) Oxidant stress

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Priority areas for watershed service conservation in the Guapi-Macacu region of Rio de Janeiro,Atlantic Forest,Brazil

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Ecological Processes 2014年第1期3卷 95-115页

作者： Vanesa Rodriguez Osuna Jan Borner Udo Nehren Rachel Bardy Prado hartmut Gaese Jurgen Heinrich Center for Development Research(ZEF) Department of Economic and Technological ChangeUniversity of BonnWalter-Flex-Str.353117 BonnGermany Institute for Technology and Resources Management in the Tropics and Subtropics(ITT) Cologne University of Applied SciencesBetzdorfer Str.250679 CologneGermany Empresa Brasileira de Pesquisa Agropecuária(EMBRAPA Soils) Brazilian Enterprise for Agricultural ResearchGeotechnologies and Environmental MonitoringRua Jardim BotanicoCEP 22460-000 Rio de JaneiroBrazil Institute for Geography Department of Physical GeographyUniversity of LeipzigJohannisallee 19a04103 LeipzigGermany

Introduction:Land use intensification and urbanisation processes are degrading hydrological ecosystem services in the Guapi-Macacu watershed of Rio de Janeiro.A proposal to pay farmers to restore natural watershed services might be an alternative to securing the water supply in the long-term for the around 2.5 million urban water users in the study *** study quantifies the costs of changing current land use patterns to enhance watershed services and compares these costs to the avoided costs associated with water treatment for public ***:We use farm-household data to estimate the opportunity costs of abandoning current land uses for the recovery of natural vegetation;a process that is very likely to improve water quality in terms of turbidity due to reduced inputs from *** cost estimates are extrapolated to the watershed scale based on remote sensing land use classifications and vulnerability analysis to identify priority zones for watershed management *** assess the potential demand for watershed services,we analyse water quality and treatment cost data from the main local water treatment ***:Changing agricultural land uses for watershed services provision generally comes at high opportunity costs in our study area near to the metropolis of Rio de *** low cost watershed conservation options do exist in the livestock production *** options have the potential to directly reduce the amount of sediments and nutrients reaching the water bodies,and in turn decrease the costs of treatment needed for drinking *** cover changes at the scale needed to improve water quality will,nonetheless,likely exceed the cost of additional investments in water ***:The state water utility company’s willingness to pay for watershed services alone will not be enough to induce provision of additional watershed *** conclude that monetary incentives conditioned on specific adjustme

关键词： Water services Drinking water treatment Water quality Incentive-based watershed management

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A statistic comparison of multi-element analysis of low atmospheric fine particles(PM_(2.5)) using different spectroscopy techniques

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Journal of Environmental Sciences 2022年第4期34卷 194-203页

作者： Minkang Zhi Kai Zhang Xi Zhang hartmut Herrmann Jian Gao Khanneh Wadinga Fomba Wei Tang Yuqian Luo Huanhuan Li Fan Meng State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Faculty of Environmental Engineering The University of Kitakyushu1-1 HibikinoWakamatsuKitakyushuFukuoka 808-0135Japan Atmospheric Chemistry Department(ACD) Leibniz-Institute for Tropospheric Research(TROPOS)Leipzig 04318Germany

Over the past few decades,the metal elements(MEs)in atmospheric particles have aroused great *** well-established techniques have been used to measure particlebound ***,each method has its own advantages and disadvantages in terms of complexity,accuracy,and specific elements of *** this study,the performances of inductively coupled plasma-optical emission spectrometry(ICP-OES)and total reflection X-ray fluorescence spectroscopy(TXRF)were evaluated for quality control to analyze data accuracy and *** statistic methods(Deming regression and significance testing)were applied for intercomparison between ICP-OES and TXRF measurements for same lowloading PM_(2.5)samples in Weizhou *** results from the replicate analysis of standard filters(SRM 2783)and field filters samples indicated that 10 MEs(K,Ca,V,Cr,Mn,Fe,Ni,Cu,Zn,and Pb)showed good accuracies and precision for both *** higher accuracy tended to the higher precision in the MEs analysis *** addition,the interlab comparisons illustrated that V and Mn all had good agreements between ICP-OES and *** measurements of K,Cu and Zn were more reliable by TXRF analysis for low-loading PM_(2.5).ICP-OES was more accurate for the determinations for Ca,Cr,Ni and Pb,owing to the overlapping spectral lines and low sensitivity during TXRF *** measurements of Fe,influenced by low-loading PM_(2.5),were not able to determine which instrument could obtain more reliable *** conclusions could provide reference information to choose suitable instrument for the determination of MEs in low-loading PM_(2.5)samples.

关键词： Multielement analysis Low-loading fine particles Inductively coupled plasma-optical emission spectrometry Total reflection X-ray fluorescence spectroscopy Inter-laboratory comparison

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Self-repairing material systems―a dream or a reality?

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Natural Science 2010年第8期2卷 873-901页

作者： hartmut Fischer 不详

Currently, most industrial materials rely entirely on passive protection mechanisms;such me chanisms are readily applicable and universal for many different materials systems. However, they will always stay passive, and therefore their lifetime and functionality is limited and related to the amount of protective additives and the intensity of their consumption. Therefore, better, and preferentially active process for the protection/repair of damaged materials―selfrepairing processes―were developed and need to be developed further. Although it sounds futuristic or like a fiction in the modern, trendy times, which in many ways affects also directions of research;self healing of material systems exists already for a long time in all sorts of systems of materials or functionalities. The aim of this work is to go beyond the scope of a classical review the ones published recently in this field which almost entirely focused only onto polymeric systems. In this work, an analysis of the underlying functional and constructional principles of existing natural and synthetically selfhealing systems spanning over a range of classes of materials is given leading to general rules and principles for the design of new and application tailored selfhealing material systems.

关键词： Self Healing Systems Sensors

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ANATOMICAL STRUCTURE OF ACUPOINTS

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Journal of Traditional Chinese Medicine 1988年第3期8卷 207-212页

作者： hartmut Heine Institute of Anatomy University of Witten/Herdecke West Germany Federal Republic of Germany

The anatomical,histological and electrophysiolo-gical findings presented strengthen the theory thatacupuncture points have a well defined *** of the acupoints are sharp delineatedperforations of the superficial fascia of the body(fascia corporis superficialis).A cutaneous nerve-vessel bundle wrapped in a sheath of loose connec-tive tissue passes through each *** regionswhere no superficial fascia exists as in the face,fingers and toes,corresponding nerve-vessel bundlespass from the dermis to the *** loose con-nective tissue lining the perforation area is of *** tissue is able to bind water and actsas an *** it could become in-flamed,and there has been discussion whether acu-points themselves could develop special clinical ***,the congruency of traditionally locat-ed acupoints with those demonstrated by anatomicalpreparation leads us to discuss a genetical influencewith the distribution of acupoints.

关键词： ANATOMICAL STRUCTURE OF ACUPOINTS

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Catholicism and Machismo： The Impact of Religion on Hispanic Gender Identity

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Cultural and Religious Studies 2014年第2期2卷 100-108页

作者： hartmut Heep Pennsylvania State University Washington USA

Masculinity is strictly a cultural concept. Each society interprets and applies arbitrary gender definitions differently. This study will make a distinction between cultural masculinity and biological maleness. Gender disparity, he will argue, is deeply rooted in the Judeo-Christian tradition and remains the basis for feminine and masculine gender stereotypes in Spanish speaking Latin America. Mary, as virgin and mother, represents the sole role model for Hispanic women, while the male identity will be traced to Adam, Joseph and Catholic priesthood with the church as ultimate wedded partner. In addition, the Spanish conquest influenced male gender identity in Latin America. The small physique of the indigenous peoples of Latin America, combined with the loss of land to the Spaniards questioned the social identity of the male. In order to compensate for their military inferiority and physical weakness, indigenous males developed an elaborate system of masculine behaviors, in short machismo. Simultaneously, the acceptance of Catholic doctrines replaced the natural biology of men and women. This study will analyze the social impact of Hispanic gender identity as interaction between Spanish conquest and Catholic doctrine.

关键词： Catholicism Machismo Hispanic Gender Identity

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＂Blurred Lines＂： Robin Thicke and Madonna Ciccone between Madonna and Whore

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Cultural and Religious Studies 2014年第1期2卷 17-28页

作者： hartmut Heep The Pennsylvania State University U.S.A

Robin Thicke＇s song ＂Blurred Lines＂ rekindled the debate about women who must choose an existence as Madonna or as whore. Biblical archetypes, such as Eve and Mary, are normative role models for women, even within secular societies. This study follows a pre-Fall Eve, who experiences shameless sexual pleasures, to a post-Fall shamed Eve, to the Virgin Mary, who is mother but virgin. Robin Thicke＇s video ＂Blurred Lines,＂ and Madonna Ciccone＇s various videos reclaim sexual pleasures for womert outside of sin. Close readings of several visual texts will show that how meaning is redistributed among signifieds by deconstructing and redefining conventional signifiers, such as virgin and whore.

关键词： gender studies religious studies popular culture feminist theory social theory

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Digital single-operator video cholangioscopy improves endoscopic management in patients with primary sclerosing cholangitis-a retrospective observational study

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World Journal of Gastroenterology 2022年第20期28卷 2201-2213页

作者： Arne Bokemeyer Frank Lenze Viorelia Stoica Timur Selcuk Sensoy Iyad Kabar hartmut Schmidt Hansjoerg Ullerich Department of Medicine B(Gastroenterology HepatologyEndocrinologyClinical Infectiology)University Hospital MuensterMuenster 48149Germany Department of Gastroenterology Hepatology and Transplant MedicineUniversity Hospital EssenEssen 45147Germany

BACKGROUND Patients with primary sclerosing cholangitis(PSC)are at a high risk of developing cholestatic liver disease and biliary cancer,and endoscopy is crucial for the complex management of these *** To clarify the utility of recently introduced digital single-operator video cholangioscopy(SOVC)for the endoscopic management of PSC *** In this observational study,all patients with a history of PSC and in whom digital SOVC(using the SpyGlass DS System)was performed between 2015 and 2019 were included and retrospectively *** were performed at a tertiary referral centre in *** total,46 SOVCs performed in 38 patients with a history of PSC were *** primary endpoint was the evaluation of dominant biliary strictures using digital SOVC,and the secondary endpoints were the performance of selective guidewire passage across biliary strictures and the diagnosis and treatment of biliary stone disease in PSC *** The 22 of 38 patients had a dominant biliary stricture(57.9%).In 4 of these 22 patients,a cholangiocellular carcinoma was diagnosed within the stricture(18.2%).Diagnostic evaluation of dominant biliary strictures using optical signs showed a sensitivity of 75%and a specificity of 94.4%to detect malignant strictures,whereas SOVC-guided biopsies to gain tissue for histopathological analysis showed a sensitivity of 50%and a specificity of 100%.In 13%of examinations,SOVC was helpful for guidewire passage across biliary strictures that could not be passed by conventional methods(technical success rate 100%).Biliary stone disease was observed in 17.4%of examinations;of these,in 37.5%of examinations,biliary stones could only be visualized by SOVC and not by standard *** stone treatment was successful in all cases(100%);25%required SOVC-assisted electrohydraulic ***,such as postinterventional cholangitis and pancreatitis,occurred in 13%of examinations;however,no procedur

关键词： Cholangitis Sclerosing Biliary tract diseases Biliary strictures Endoscopy Gastrointestinal Cholangioscopy Digital single-operator video cholangioscopy

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The Directors’ Handbook Thomas J. Dougherty

The Directors’ Handbook Thomas J. Dougherty

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1000年

作者： Skadden arps Slate Meagher & Flom LLP

来源：畅想之星图书光盘版（南... 评论

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Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

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World Journal of Gastroenterology 2012年第39期18卷 5542-5550页

作者： Ramsi Siaj Vanessa Sauer Sandra Stppeler Hans-Ullrich Spiegel Gabriele Khler Andree Zibert hartmut HJ Schmidt Klinik und Poliklinik für Transplantationsmedizin Universittsklinikum MünsterD-48149 MünsterGermany Abteilung Chirurgische Forschung Klinik und Poliklinik für Allgemein-und ViszeralchirurgieUniversittsklinikum MünsterD-48149 MünsterGermany Gerhard-Domagk-Institut für Pathologie Universittsklinikum MünsterD-48149 MünsterGermany

AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. RESULTS： Regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. With regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is imp

关键词： Wilson's disease Fulminant hepatitis Acuteliver failure Dietary copper Long-Evans cinnamon rat A TP7B

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