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Science Bulletin 2024年第12期69卷 1964-1979页

作者：黄梅周静璇李潇骁刘冉姜洋子陈开璇焦玉睿尹欣刘玲孙宇晨王维山肖业苏甜郭奇黄燕杨觅魏婕 l.darryl quarles 肖洲生曾超罗湘杭雷光华李长俊 Department of Endocrinology Endocrinology Research CenterXiangya HospitalCentral South UniversityChangsha 410008China Hunan Key laboratory of Joint Degeneration and Injury Changsha 410008China Key laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment Ministry of EducationXiangya HospitalCentral South UniversityChangsha 410008China School of Biomedical Sciences Institute for Tissue Engineering and Regenerative MedicineFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Key laboratory for Regenerative Medicine Ministry of EducationSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Center for Neuromusculoskeletal Restorative Medicine(CNRM) The Chinese University of Hong KongHong Kong 999077China Department of Orthopaedics The First Affiliated Hospital of Shihezi UniversityShihezi 832061China Department of Orthopaedics Xiangya HospitalCentral South UniversityChangsha 410008China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangsha 410008China Department of Medicine University of Tennessee Health Science CenterMemphis 38163USA National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China laboratory Animal Center Xiangya HospitalCentral South UniversityChangsha 410008China

Mechanical loading is required for bone homeostasis,but the underlying mechanism is still *** previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone ***,the role of PC1 in bone resorption is ***,we found that PC1directly regulates osteoclastogenesis and bone *** conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts,decreased bone resorption,and increased bone mass.A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease,which is mainly caused by loss-of-function mutation of the PKD1 gene,is associated with a lower risk of hip fracture than those with other chronic kidney ***,mice with osteoclastspecific knockout of Pkd1 showed complete resistance to unloading-induced bone loss.A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone *** regulation of the PC1-TAZ axis alleviated unloading-and estrogen deficiency-induced bone ***,the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

关键词： Polycystin1 Osteoclastogenesis Bone resorption Mechanical stress

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The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

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Bone Research 2016年第2期4卷 85-90页

作者： Qian Zhang Michele Doucet Ryan E Tomlinson Xiaobin Han l.darryl quarles Michael T Collins Thomas l Clemens Department of Orthopaedic Surgery Johns Hopkins University Baltimore MD USA Department of Medicine University of Tennessee Health Science Center Memphis TN USA Skeletal Clinical Studies Unit craniofacial and Skeletal Diseases Branch National Institutes of HealthBethesda MD USA Baltimore Veterans Administration Medical Center Baltimore MD USA

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-la inhibitors decreased HIF-la and FGF23 protein accumulation and inhibited HIF-la-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-la consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-la inhibitor. These results show for the first time that HIF-la is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-la activity in TIO contributes to the aberrant FGF23 production in these patients.

关键词： The hypoxia-inducible factor-1 activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia HIF

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Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

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Bone Research 2023年第4期11卷 772-783页

作者： Zhousheng Xiao li Cao Micholas Dean Smith Hanxuan li Wei li Jeremy C.Smith leigh darryl quarles Department of Medicine University of Tennessee Health Science CenterMemphisTN 38163USA UT/ORNl Center for Molecular Biophysics Oak Ridge National LaboratoryOak RidgeTN 37830USA Department of Biochemistry and Cellular and Molecular Biology The University of Tennessee-KnoxvilleKnoxvilleTN 37996-1939USA Department of Pharmaceutical Sciences University of Tennessee Health Science CenterMemphisTN 38163USA

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly ***,we used mouse genetics,mechanical loading,and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in *** created and compared the skeletal phenotypes of control Pkd1^(flox/)+;Wwtr1^(flox/)+,Pkd1^(Oc-cKO),Wwtr1^(Oc-cKO),and Pkd1/Wwtr1^(Oc-cKO)mice to investigate genetic *** with an interaction between polycystins and Wwtr1 in bone in vivo,Pkd1/Wwtr1^(Oc-cKO)mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1Oc-cKOor Pkd1^(Oc-cKO)***-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***1/Wwtr1^(Oc-cKO)mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***,we found that Pkd1/Wwtr1^(Oc-cKO)mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of loadinduced mechanosensing gene expression compared to control ***,control mice treated with a small molecule mechanomimetic,MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle *** contrast,Pkd1/Wwtr1^(Oc-cKO)mice were resistant to the anabolic effects of *** findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

关键词： mec impaired additive

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An improved protocol for the treatment of fulminant myocarditis

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Science China(life Sciences) 2019年第3期62卷 433-434页

作者： Matthew l.Edin darryl C.Zeldin Division of Intramural Research National Institute of Environmental Health Sciences National Institutes of HealthResearch Triangle Park

Fulminant myocarditis is a rare form of severe myocarditis that is most commonly caused by viral *** myocarditis is often pathophysiologically indistinguishable from milder forms of acute myocarditis but is categorically defined based on clinical disease *** may initially present with mild symptoms,such as fever,shortness of breath or heart palpitations,but rapidly progress to severe respiratory distress,arrhythmias,and cardiogenic shock.

关键词： protocol the treatment myocarditis

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Synthesis and Characterization of a Novel Perfluorinated Ionomer Polymer Containing Sulfonimide Functionality

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Chinese Journal of Chemistry 2003年第7期21卷 921-925页

作者：朱士正章云祥金桂芳 DesMarteau darryl D Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China Department of Chemistry H. L. Hunter Chemistry Laboratory Clemson University Clemson SC 29634-1905

The novel perfluorinated vinyl ether containing sulfonimide functionality CF2 = CFORfSO2NHSO2CF3 was synthesized by multiple reaction steps. It could be copolymerized with tetraflu-oroethylene by radox initiator to gi... 详细信息

关键词： perfluorinated vinyl ether sulfonimide copolymer-ization ionomer resin

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The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension:Findings from the Prospective Urban Rural Epidemiology China Study

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Journal of Sport and Health Science 2021年第6期10卷 629-636,F0003页

作者： Weida liu darryl P leong Bo Hu lap AhTse Sumathy Rangarajan Yang Wang Chuangshi Wang Fanghong lu Yindong li Salim Yusuf lisheng liu Wei li Medical Research&Biometrics Center Fuwai HospitalNational Center for Cardiovascular DiseasesPeking Union Medical College&Chinese Academy of Medical SciencesBeijing 102300China The Population Health Research Institute McMaster University and Hamilton Health SciencesHamiltonONL8S4L8Canada Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Cardio-Cerebrovascular Control and Research Center Institute of Basic MedicineShandong Academy of Medical SciencesJinan 250002China Shunyi Center for Disease Control and Prevention Beijing 101300China

Background:Both hypertension and grip strength(GS)are predictors of mortality and cardiovascular disease(CVD),but whether these risk factors interact to affect CVD and all-cause mortality is *** study sought to investigate the associations of GS with the risk of major CVD incidence,CVD mortality,and all-cause mortality in patients with ***:GS was measured using a Jamar dynamometer(Sammons Preston,Bolingbrook,Il,USA)in participants aged 3570 years from 12 provinces included in the Prospective Urban Rural Epidemiology China *** frailty proportional hazards models were used to examine the associations of GS and hypertension and the outcomes of all-cause mortality and CVD incidence/***:Among 39,862 participants included in this study,15,964 reported having hypertension,and 9095 had high GS at *** a median follow-up of 8.9 years(interquartile range,6.79.9 years),1822 participants developed major CVD,and 1250 deaths occurred(388 as a result of CVD).Compared with normotensive participants with high GS,hypertensive patients with high GS had a higher risk of major CVD incidence(hazard ratio(HR)=2.39;95%confidence interval(95%CI):1.863.06;plity(HR=3.11;95%CI:1.596.06;ply increased risk of all-cause mortality(HR=1.24;95%CI:0.921.68;p=0.159).These risks were further increased if hypertensive participants whose GS level was low(major CVD incidence,HR=3.31,95%CI:2.604.22,plity,HR=4.99,95%CI:2.649.43,pll-cause mortality,HR=1.93,95%CI:1.472.53,plusion:The present study demonstrates that low GS is associated with the highest risk of major CVD incidence,CVD mortality,and all-cause mortality among hypertensive *** levels of GS appear to mitigate long-term mortality risk among hypertensive patients.

关键词： Cardiovascular disease Cohort study Grip strength Hypertension Mortality

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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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Gynecologic oncologists involvement on ovarian cancer standard of care receipt and survival

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World Journal of Obstetrics and Gynecology 2016年第2期5卷 187-196页

作者： Sun Hee Rim Shawn Hirsch Cheryll C Thomas Wendy R Brewster darryl Cooney Trevor D Thompson Sherri l Stewart Division of Cancer Prevention and Control National Center for Chronic Disease Prevention and Health PromotionCenters for Disease Control and Prevention Sci Metrika llC University of North Carolina at Chapel Hill

AIM： To examine the infuence of gynecologic oncolo-gists （GO） in the United States on surgical/chemothe-rapeutic standard of care （SOC）, and how this translates into improved survival among women with ovarian cancer （OC）.METHODS： Surveillance, Epidemiology, and End Result （SEER）-Medicare data were used to identify 11688 OC patients （1992-2006）. Only Medicare recipients with an initial surgical procedure code （n = 6714） were included. Physician specialty was identified by linking SEER-Medicare to the American Medical Association Masterfile. SOC was defined by a panel of GOs. Mul-tivariate logistic regression was used to determine predictors of receiving surgical/chemotherapeutic SOC and proportional hazards modeling to estimate the effect of SOC treatment and physician specialty on survival. RESUlTS： About 34% received surgery from a GO and 25% received the overall SOC. One-third of women had a GO involved sometime during their care. Women receiving surgery from a GO vs non-GO had 2.35 times the odds of receiving the surgical SOC and 1.25 times the odds of receiving chemotherapeutic SOC （P 〈 0.01）. Risk of mortality was greater among women not receiving surgical SOC compared to those who did [hazard ratio = 1.22 （95%CI： 1.12-1.33）, P 〈 0.01], and also was higher among women seen by non-GOs vs GOs （for surgical treatment） after adjusting for covariates. Median survival time was 14 mo longer for women receiving combined SOC. CONClUSION： A survival advantage associated with receiving surgical SOC and overall treatment by a GO is supported. Persistent survival differences, particularly among those not receiving the SOC, require further investigation.

关键词： Ovarian neoplasms Gynecologic oncologist Guidelines-based care Surveillance Epidemiology and End Result Medicare

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气相色谱三重四极杆气质联用系统分析水样中的N-亚硝基二甲胺

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环境化学 2016年第11期35卷 2442-2444页

作者： Alandra Kahl.darryl Jones lisa lowe Shane Snyder Anthony Macherone 亚利桑那州图森市亚利桑那大学美国85721 特拉华州威尔明顿安捷伦科技有限公司美国19808

本文使用Agilent 7890A系列气相色谱仪与Agilent 7000B三重四极杆气质联用系统以正化学电离(PCI)模式开发了灵敏度可达ng·l^(-1)或更低的N-亚硝基二甲胺(NDMA)的分析方法.该方法还为需要采用常规离子阱质谱法分析但又没有离子阱仪器的... 详细信息

本文使用Agilent 7890A系列气相色谱仪与Agilent 7000B三重四极杆气质联用系统以正化学电离(PCI)模式开发了灵敏度可达ng·l^(-1)或更低的N-亚硝基二甲胺(NDMA)的分析方法.该方法还为需要采用常规离子阱质谱法分析但又没有离子阱仪器的实验室提供了一种可行的替代方案,方法的检测限(lOD)达0.20 ng·l^(-1),定量限(lOQ)达0.56 ng·l^(-1).

关键词：气相色谱三重四极杆气质联用 N-亚硝基二甲胺分析方法

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Components Qualification for the Safe Operation of Nuclear Power Plants

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Journal of Energy and Power Engineering 2016年第10期10卷 581-590页

作者： Holger Schmidt Martin Beetz Ingo Ganzmann Achim Beisiegel Thomas Wagner Christian Bonneau darryl Gordon Sun Jing AREVA GmbH-Thermal Hydraulics and Components Testing Paul-Gossenstr 100 Erlangen 91052 Germany ARE VA GmbH-Thermal Hydraulics and Components Testing Seligenstadter Strasse 100 Karlstein 63791 Germany AREVA SAS-Thermal Hydraulics and Components Testing 30 boulevard de l'Industrie Le Creusot 71205 France ARE VA Inc.-Thermal Hydraulics and Components Testing 3315 Old Forest Road Lynchburg VA 24501 USA Keysur International F11 Tower A Millennium Plaza No. 72 Beijing 100037 China

AREVA operates a world-wide unique thermal hydraulic platform to ensure high safety standards in the nuclear industries. This platform is operated as an accredited test and inspection body according to ISO 17025 and 17020 to grant a high and independently confmned quality standard. The accreditation also ensures the independency of the organization and confidentiality to the individual stakeholders, for example research centers, utilities, components suppliers, engineering companies and vendors. Especially for nuclear power plants, it is very relevant to consider that reliability depends on the integrity of its components during its life time-from design through construction, operation and maintenance. For example, a typical NPP （nuclear power plant） has 1,000 to 2,000 large valves and 7,500 to 12,500 small valves, of which about 200 to 400 are designated Safety Class 1. The qualification of these Safety Class 1 components is relevant for reactor new builds but also for installed plants. This paper explains newly established qualification tasks, the corresponding testing infrastructure, and the state of the art of testing technology. By way of example, the paper describes the program and possible sequence of qualifying NPP safety-related components.

关键词： Components testing nuclear qualification thermal hydraulics testing nuclear safety

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