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Subchronic effects of arsenic,arsenate,MMA and DMA in drinking water in *** mice

Subchronic effects of arsenic,arsenate,MMA and DMA in drinki...

中国环境诱变剂学会抗诱变剂和抗癌剂专业委员会第三次全国学术会议、中国毒理学会生化与分子毒理专业委员会第五届学术交流会、贵州省环境诱变剂学会成立大会暨首届学术交流会

作者： Kevin Trouba Michael P.Waalkes Dori R.Germolec Environmental Immunology National Institute of Environmental Health SciencesP.O.Box 12233Mail Drop C1-03111 Alexander DriveResearch Triangle ParkNC 27709USA Inorganic Carcinogenesis Section Laboratory of Comparative CarcinogenesisNCI at NIEHSResearch Triangle ParkNCUSA

Previous research indicates that 12-tetradecanoylphorbol—13-acetate（TPA） increased the number of skin papillomas in *** transgenic mice that received sodium arsenite in drinking water, indicating that this model is useful for studying the toxic effects of arsenic in *** the present study,we examined the pathophysiological and molecular effects of inorganic and organic arsenical exposure on *** mouse *** mice were exposed to sodium arsenite（As）,sodium arsenate（As）,monomethylarsonic acid（MMA） and dimethylarsinic acid（DMA）,at the dosages of 150,200,1500 and 1000 ppm arsenic, respectively,in the drinking water for *** mice received unaltered *** exposure reduced body weight gain by 8—15%at the end of the exposure as compared to ***（including moribundity） incidence in mice treated with As,MMA,and DMAwas 20%,40%,and 15%respectively. Arsenic exposure resulted in a dose-dependent,but chemical species-independent accumulation of arsenic in the liver,and produced hepatic global DNA hypomethylation as assessed by the methyl-acceptance assay. CDNA micro array analysis revealed that all arsenicals induced similar yet distinct alterations in the expression of genes related to glutathione metabolism,stress,apoptosis and cell proliferation,and those associated with preneoplastic *** arsenicals（MMAand DMA） induced a dissimilar pattern of gene expression than in organic ***-time RT-PCR was used to corroborate the findings of our micro array analyses for numerous genes proposed to be involved in toxicity and *** summary,subchronic exposure to inorganic or organic arsenicals resulted in to toxic manifestations,hepatic arsenic accumulation,global DNA hypomethylation,and numerous gene expression *** effects in combination or alone may well play a role in arsenic toxicity and arsenic carcinogenesis.

关键词： MMA DMA Subchronic effects of arsenic,arsenate,MMA and DMA in drinking water in Tg.AC mice

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Heteromeric Coassembly of TRPV4,TRPC1 and TRPP2 to Form a Flow-sensitive Channel

Heteromeric Coassembly of TRPV4,TRPC1 and TRPP2 to Form a Fl...

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第八届海峡两岸心血管科学研讨会

作者： Lutz Birnbaumer National Institute of Environmenta Health Sciences National Institutes of HealthDepartment of Health and Human ServicesResearch Triangle ParkNorth CarolinaUSA

Background Transient receptor potential(TRP) channels function as cellular sensors to perceive and respond to a variety of environmental stimuli including temperature,pain,pressure and fluid *** channels can be divided into seven subfamilies,including TRPV,TRPC,TRPP,and four *** TRP channels are tetrameric complexes consisting of four pore - forming subunits,which could be identical (homotetrameric channels) or different(heterotetrameric channels).Tetrameric assembly usually occurs between members from the same *** and Finding In the present study,with the use of two -step co - immunoprecipitation,chemical cross - linking and fluorescence resonance energy transfer(FRET), we found that TRPV4,- C1,and - P2 associate together to form a physical *** function study,this TRPV4 - C1 - P2 complex mediates flow - induced Ca influx in HEK293 cells over - expressing TRPV4,- C1,and - P2 and in rat mesenteric artery endothelial cells(MAECs).Pore - dead mutant of each of these three TRP isoforms abolished or markedly reduced the flow - induced cation currents and Ca rises,suggesting all three TRPs contribute to the ion permeation pore of the *** Taken together,we identified the first heteromeric TRP channels composed of subunits from three different TRP subfamilies, namely heteromeric TRPV4 - C1- P2 *** type of heteromerization greatly increases the numeric numbers of different TRP channels that could be assembled,making the structure and function of TRP channels strikingly ***,heteromeric TRPV4 - C1- P2 are the main channels that mediate flow - induced Ca rises in native vascular endothelial cells,thus plays a key role in the control of vascular tone and blood pressure.

关键词： TRPV4 TRPC1 TRPP2 heteromeric coassembly flow-induced Ca2+ influx flow-induced cation current

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Changes in Bone Mineral Density through 96 Weeks in Antiretroviral-Naïve HIV-1 Infected Patients Receiving Abacavir/Lamivudine and Raltegravir in the SHIELD Trial

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World Journal of AIDS 2014年第1期4卷 38-44页

作者： Linda Battalora Amy Thomas Brian Wine Belinda Ha Benjamin Young APEX research/Family Medicine Denver USA APEX research/Family Medicine Denver USA International Association of Providers of AIDS Care Washington USA Colorado School of Mines Golden USA APEX research/Family Medicine Denver USA GlaxoSmithKline Research Triangle Park USA

Decreased bone mineral density (BMD) and osteoporotic fractures are areas of increasing concern among HIV-infected persons. Particular concern is the rapid decline in BMD after initiation of antiretroviral treatment (ART). This report describes DEXA-assessed changes in BMD and body fat in a study of fifteen antiretroviral-na?ve adults initiating abacavir/lamivudine and raltegravir for 96 weeks. Median percent changes from baseline at weeks 48 and 96 in BMD were 0.29% and -0.11% (spine);-1.25% and -1.75% (left hip). Median percent changes from baseline in fat from baseline were -0.82% and -3.04% (trunk);2.12% and 2.01% (limb). In this pilot study, ABC/3TC + RAL treatment had limited impact on BMD and body fat.

关键词： Bonedensity Abacavir HIV Integrase Lamivudine Raltegravir

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SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1265-1279页

作者： Yuesheng Lv Wenjing Zhang Jinyao Zhao Bing Sun Yangfan Qi Haoyu Ji Chaoqun Chen Jinrui Zhang Junxiu Sheng Taishu Wang Daniel Dominguez Han Liu Quentin Liu Songshu Meng Xiaoling Li Yang Wang Second Affiliated Hospital Institute of Cancer Stem CellDalian Medical UniversityDalianChina Department of Thoracic Surgery First Affiliated HospitalDalian Medical UniversityDalianChina Department of Radiation Oncology First Affiliated HospitalDalian Medical UniversityDalianChina Department of Pharmacology University of North Carolina at Chapel HillChapel HillNCUSA Signal Transduction Laboratory National Institute of Environmental Health SciencesResearch Triangle ParkNCUSA

Alternative splicing is a critical process to generate protein ***,whether and how alternative splicing regulates autophagy remains largely *** we systematically identify the splicing factor SRSF1 as an autophagy ***,SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-ⅡI and numbers of autophagosomes in different cell ***,SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclinl,thereby dissociating the Beclin1-PIK3C3 *** addition,SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclinl and ***,the decrease of SRSF1 stabilizes the Beclinl and PIK3C3 complex and activates ***,SRSF1 can be degraded by starvation-and oxidative stresses-induced autophagy through interacting with LC3-Ⅱ,whereas reduced SRSF1 further promotes *** positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in ***,the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer *** study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis,thereby offering a novel avenue for potential cancer therapeutics.

关键词： Beclin1 Beclin thereby

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秦淮河流域土地利用/覆被变化对蒸散量变化的贡献

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中国农业气象 2019年第5期40卷 269-283页

作者：秦孟晟郝璐郑箐舟金楷仑孙阁南京信息工程大学江苏省农业气象重点实验室南京210044 Eastern Forest Environmental Threat Assessment Center Southern Research StationUSDA Forest ServiceResearch Triangle Park

为评估城市化造成的土地利用/覆被类型变化(Land use/cover change,LUCC)对流域尺度蒸散量变化的影响,选取长三角地区秦淮河流域为研究区,基于Landsat系列卫星数据和站点气象数据,构建决策树模型,提取2000年和2013年土地利用/覆被类型数... 详细信息

为评估城市化造成的土地利用/覆被类型变化(Land use/cover change,LUCC)对流域尺度蒸散量变化的影响,选取长三角地区秦淮河流域为研究区,基于Landsat系列卫星数据和站点气象数据,构建决策树模型,提取2000年和2013年土地利用/覆被类型数据,同时借助SEBAL模型估算研究区四季典型日(春季:2014-05-26、夏季:2013-08-11、秋季:2013-10-14、冬季:2014-01-02)栅格尺度蒸散,探讨2000-2013年秦淮河流域主要土地利用/覆被类型间转化过程对流域尺度日蒸散量变化的贡献。结果表明:(1)相较于2000年,2013年秦淮河流域不透水面增加183.8%,而水稻田、旱地、林地和水域分别减少19.1%、10.7%、12.8%和9.5%。2000-2013年主要土地利用/覆被类型转化方向包括水稻田→不透水面、旱地→不透水面、水稻田→旱地和旱地→水稻田,转化面积分别为208、168、282和232km^2;(2)仅考虑LUCC的影响,对比2000年,2013年研究区流域尺度日蒸散总量在四季典型日分别减少134万、109万、60万和5万m^3。在春、夏、秋三季典型日,水稻田和旱地向不透水面转化过程造成的贡献率分别为-58.5%、-59.5%、-54.4%和-35.1%、-36.3%、-39.8%,负贡献会抵消旱地向水稻田转化过程造成的正贡献(分别为16.8%、16.3%、5.7%),导致春、夏、秋三季典型日流域尺度日蒸散量下降;而在冬季典型日,水稻田向不透水面、旱地向不透水面和水稻田向旱地转化过程造成的负贡献(分别为-48.8%、-20.5%和-31.8%)会抵消旱地向水稻田转化过程造成的正贡献(26.1%),导致冬季典型日流域尺度日蒸散量下降。总体而言,2000-2013年秦淮河流域城市化带来土地利用/覆被的显著变化,使蒸散较高的水稻田和旱地向蒸散较低的不透水面大面积转化,导致流域尺度日蒸散量在四季均呈下降趋势。

关键词：蒸散 SEBAL模型土地利用/覆被变化秦淮河流域 Landsat卫星影像

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Burden and outcomes for complex perianal fistulas in Crohn's disease:Systematic review

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World Journal of Gastroenterology 2018年第42期24卷 4821-4834页

作者： Julian Panes Walter Reinisch Ewa Rupniewska Shahnaz Khan Joan Forns Javaria Mona Khalid Daniela Bojic Haridarshan Patel Department of Gastroenterology Hospital Clínic de BarcelonaIDIBAPSCIBERehdBarcelona 08036Spain Medical University of Vienna Vienna 1090Austria RTI Health Solutions Manchester M20 2LSUnited Kingdom RTI Health Solutions Research Triangle ParkNC 27709United States RTI Health Solutions Barcelona 08028Spain Takeda DeerfieldIL 60015United States

AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal *** PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in *** Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

关键词： Burden Complex perianal fistulas Crohn’s disease Epidemiology Outcomes Systematic literature review Treatment

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Dimethyltyrosine, the Viagra of Opioids

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Chemical research in Chinese Universities 2006年第2期22卷 258-262页

作者： Lawrence H. Lazarus Sharon D. Bryant Severo Salvadori Remo Geurrini Gianfranco Balboni Yuko Tsuda Yoshio Okada Peptide Neurochemistry LCBRA National Institute of Environmental Health Sciences Research Triangle Park NC 27709 USA Department of Pharmaceutical Science University of Ferrara I-44100 Ferrara Italy Department of Pharmaceutical Science University of Ferrara I-44100 Ferrara Italy Department of Toxicology University of Cagliary Cagliary 109126 Italy Faculty of Pharmaceutical Science Kobe Gakuin University Nishi-ku Kobe 651-2180 Japan

Introduction The introduction of 2＇ ,6＇-dimethyl-L＇tyrosine （Dmt） at the N-terminus of Tyr-Tic （1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid ）-containing δ-opioid antagonists enhances receptor affinity and in vitro bioactivity to several orders of magnitude and its application in the formation of ligands with new properties, such as potent inverse agonism. For example, the δ2 agonist,

关键词： Dimethyltryrosine Opioid Agonist

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Elemental Compositions and Chemical Mass Closure of Fine Particulate in an Animal Feeding Operation Facility and Its Vicinity

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Journal of Environmental Protection 2015年第5期6卷 409-425页

作者： Qian-Feng Li Lingjuan Wang-Li R. K. M. Jayanty Sanjay Shah Department of Animal Science Michigan State University East Lansing USA Department of Biological and Agricultural Engineering North Carolina State University Raleigh USA RTI International Research Triangle Park USA

Particulate matter (PM) emissions from animal feeding operations (AFOs) have been considered as an important contributor to ambient PM in rural areas. Investigation of the chemical compositions of PM2.5 inside and in the vicinity of AFOs can enhance our understanding of the AFO emissions impact on ambient PM characteristics. This year-long field study was conducted on a commercial egg production farm to investigate ambient PM chemical compositions as impacted by the air emissions from the production houses. The PM2.5 samples were collected from five sampling stations (one in-house station and four ambient locations in four wind directions). The trace elements, major ions, organic carbon (OC) and element carbon (EC) were analyzed by X-ray florescence (XRF), ion chromatography (IC), and thermo-optical analyzer, respectively. There were significant differences in elemental compositions between PM samples from in-house station (ST1) and ambient stations (ST2-ST5). The chemical mass balance analysis revealed that OC accounted for above 50% of PM2.5 mass at in-house and ambient stations;NH4+, SO42-, and NO3- accounted for about 40.0% of the total PM2.5 mass in ambient locations and for only 12% of the total PM2.5 mass in house. The measured PM2.5 masses agreed with the sums of the masses of chemical compositions at all stations except for the in-house station. Knowledge gained from this study, with additional consideration of NH3 concentrations and emissions, will lead to better understanding of PM2.5 source and formation, fate and transport, and their atmospheric dynamics.

关键词： Animal Feeding Operations PM2.5 Chemical Speciation Elemental Composition Mass Balance

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Effect of gynecologic oncologist availability on ovarian cancer mortality

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World Journal of Obstetrics and Gynecology 2014年第2期3卷 71-77页

作者： Sherri L Stewart Darryl Cooney Shawn Hirsch Lauren Westervelt Thomas B Richards Sun Hee Rim Cheryll C Thomas Division of Cancer Prevention and Control Centers for Disease Control and Prevention Atlanta GA 30341 United States Sci Metrika LLC Research Triangle Park North Carolina NC 27703 United States

AIM: To determine the association between the distribution of gynecologic oncologist(GO) and populationbased ovarian cancer death rates. METHODS: Data on ovarian cancer incidence and mortality in the United States was supplemented with United States census data, and analyzed in relation to practicing GOs. GO locations were geocoded to link association between county variables and GO availability. Logistic regression was used to measure areas of high and low ovarian cancer mortality, adjusting for contextual variables. RESULTS: Practicing GOs were unevenly distributed in the United States, with the greatest numbers in metropolitan areas. Ovarian cancer incidence and death rates increased as distance to a practicing GO increased. A relatively small number(153) of counties within 24 miles of a GO had high ovarian cancer death rates compared to 577 counties located 50 or more miles away with high ovarian cancer death rates. Counties located 50 or more miles away from a GO practice had an almost 60% greater odds of high ovarian cancer mortality compared to those with closer practicing GOs(OR = 1.59, 95%CI: 1.18-2.15). CONCLUSION: The distribution of GOs across the United States appears to be significantly associated with ovarian cancer mortality. Efforts that facilitate outreach of GOs to certain populations may increase geographic access.

关键词： Ovarian cancer Gynecologic oncologists Mortality Access to care

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Organic and Elemental Carbon in Atmospheric Fine Particulate Matter in an Animal Agriculture Intensive Area in North Carolina: Estimation of Secondary Organic Carbon Concentrations

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Open Journal of Air Pollution 2013年第1期2卷 7-18页

作者： Qian-Feng Li Lingjuan Wang-Li R. K. M. Jayanty Sanjay B. Shah Department of Animal Science Michigan State University East Lansing USA Department of Biological and Agricultural Engineering North Carolina State University Raleigh USA RTI International Research Triangle Park USA

Carbonaceous components contribute significant fraction of fine particulate matter (PM2.5). Study of organic carbon (OC) and elemental carbon (EC) in PM2.5 may lead to better understanding of secondary organic carbon (SOC) formation. This year-long (December 2008 to December 2009) field study was conducted in an animal agriculture intensive area in North Carolina of United States. Samples of PM2.5 were collected from five stations located in an egg production facility and its vicinities. Concentrations of OC/EC and thermograms were obtained using a thermal-optical carbon analyzer. Average levels of OC in the egg production house and at ambient stations were 42.7 μg/m3 and 3.26 - 3.47 μg/m3, respectively. Average levels of EC in the house and at ambient stations were 1.14 μg/m3 and 0.36 - 0.42 μg/m3, respectively. The OC to total carbon (TC) ratios at ambient stations exceeded 0.67, indicating a significant fraction of SOC presented in PM2.5. Principal factor analysis results suggested that possible major source of in-house PM2.5 was from poultry feed and possible major sources of ambient PM2.5 was from contributions of secondary inorganic and organic PM. Using the OC/EC primary ratio analysis method, ambient stations SOC fractions ranged from 68% to 87%. These findings suggested that SOC could appreciably contribute to total PM2.5 mass concentrations in this agriculture intensive area.

关键词： Secondary Organic Carbon (SOC) Organic Carbon (OC) Elemental Carbon (EC) PM2.5 Agriculture Area

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