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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura j.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David j.Beech Frank timo Beil Michael Amling johannes Keller Anita Ignatius timur A.Yorgan tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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湿型砂铸铝:打开新的视角

铸造 2024年第1期73卷 135-138页

作者： Per Larsen tim j.Baron 陈之伟(译) 刘溢(译) DISA Industries A/S 迪砂中国

许多汽车零部件已经用铸铝件替代以前的铸铁件。铸铝件在电动汽车的过渡中至关重要。随着汽车行业的成功转型,大批量的新型电动汽车传动系统铝部件应运而生,如电机壳和机盖。众所周知,湿型砂工艺能高效,可低成本生产出高质量的铸铁件。... 详细信息

许多汽车零部件已经用铸铝件替代以前的铸铁件。铸铝件在电动汽车的过渡中至关重要。随着汽车行业的成功转型,大批量的新型电动汽车传动系统铝部件应运而生,如电机壳和机盖。众所周知,湿型砂工艺能高效,可低成本生产出高质量的铸铁件。随着全球对铸铝件的需求不断上升,降低成本的压力不断加大,越来越多的铸造厂和制造商开始探索湿型砂生产铸铝件的运用。铸铁厂用湿型砂生产的优势成功转移到铸铝件,带来低成本、快速成形和灵活性等优点。

关键词：铸铝件湿型砂铸铁件低成本生产快速成形汽车零部件汽车传动系统电机壳

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Prioritizing Strategies for Building the Resilience of Public Health Systems to Disasters Across Multiple Communities and Countries

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International journal of Disaster Risk Science 2024年第1期15卷 1-17页

作者： Benjamin j.Ryan Mayumi Kako Shelby Garner Rok Fink Ismail Tayfur jonathan Abrahams Sanjaya Bhatia Adriana Campelo Matthew Fendt Alicia Fontenot Nahuel Arenas Garcia tim Hatch Ryoma Kayano LaShonda Malrey‑Horne Makiko MacDermot Md Moshiur Rahman Chaverle Noel Shuhei Nomura jeremy P.Novak Maria Opazo Kendell Oliver Luciana Peters Sohel Rahman PerihanŞimşek Andrew Stricklin Raymond Swienton Bryan W.Brooks Frist College of Medicine Belmont UniversityNashvilleTN 37212USA Department of Environmental Science Environmental Health Science ProgramCollege of Arts and SciencesBaylor UniversityWacoTX 76798USA Division of Nursing Science School of Biomedical and Health SciencesHiroshima UniversityHiroshima 734-8553Japan Gordon E.Inman College of Health Sciences and Nursing Belmont UniversityNashvilleTN 37212USA Faculty of Health Sciences University of Ljubljana1000 LjubljanaSlovenia Department of Emergency Medicine University of Health Sciences34668 IstanbulTurkey Monash University Accident Research Center MelbourneVIC 3800Australia Global Education and Training Institute United Nations Ofce for Disaster Risk ReductionIncheon 22004Republic of Korea Regional Ofce for the Americas and Caribbean United Nations Ofce for Disaster Risk ReductionPanama City 0843-03441Panama Engineering and Computer Science Baylor UniversityWacoTX 76798USA Department of Public Health Robbins College of Health and Human SciencesBaylor UniversityWacoTX 76798USA Alabama Department of Public Health MontgomeryAL 36092USA World Health Organization Centre for Health Development(WHO Kobe Centre) Kobe 651-0073Japan Waco-McLennan County Public Health District WacoTX 76707USA Department of Health Policy and Management School of MedicineKeio UniversityTokyo 160-8582Japan Department of Global Health Policy Graduate School of MedicineThe University of TokyoTokyo 113-0033Japan Tokyo Foundation for Policy Research Tokyo 106-6234Japan Global Development College BrisbaneQLD 4000Australia Municipality of Pudahuel 13124 PudahuelChile City Hall of Porto Alegre Porto Alegre 90010-170Brazil Ministry of Health and Family Welfare Government of the People’s Republic of BangladeshDhaka 1000Bangladesh Department of Emergency Aid and Disaster Management Trabzon University61335 TrabzonTurkey Department of Emergency Medicine UT SouthwesternDallasTX 75390USA

The COVID-19 pandemic highlighted the urgent need to strengthen public health *** response,the United Nations Disaster Risk Reduction(UNDRR) Public Health System Resilience Scorecard(Scorecard) was applied in workshops across multiple *** aim of our research was to explore the workshop findings to develop priority strategies for strengthening public health system *** conducted a workshop from 14 to 16 March 2023,at the UNDRR Global Education and Training Institute in Incheon,Republic of Korea.A sequential modified Delphi method was utilized to develop a set of prioritized resilience *** were drawn from 70 strategies identified from 13 distinct workshops in eight *** two surveys,23 strategies were *** received ratings of "High" or Very High" from89% of *** related to the inclusion of public health risks in emergency plans,integrating multidisciplinary teams into public health,enabling local transport mechanisms,and improving the ability to manage an influx of *** Scorecard provides an adaptable framework to identify and prioritize strategies for strengthening public health system *** leveraging this methodology,our study demonstrated how resilience strategies could inform disaster risk reduction funding,policies,and actions.

关键词： Health system resilience Public policy Resilience scorecard Workshops

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High-resolution peat records for Holocene monsoon history in the eastern Tibetan Plateau

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Science China Earth Sciences 2006年第6期49卷 615-621页

作者： Lars G. Franzen A.j.tim jull Department of Earth Sciences Goteborg University P.O. Box 460 SE-405 30 Goteborg Sweden NSF-AMS Facility University of Arizona Arizona AZ85721 USA

The variations of summer and winter monsoons during the Holocene in theeastern Tibetan Plateau are shown to follow two basic models based on the reliable dating andhigh-resolution monsoon proxies determinations, one being a synchronous model in that both summerand winter monsoons are strengthening or decreasing, and the other to form a complementary *** two different patterns evenly interact with each other on different time scales and togethercompose a complicated monsoon climatic model in this region. The climatic condition integrated bywinter and summer monsoons is synchronous to the global pattern, which also shows the instability ofthe Holocene climate on centennial-millennial timescale. The abrupt monsoon event in about 6.2 kacat. BP is much more severe than that in ca. 8.0 ka cal. BP, which indicates the regional characterof the Asian monsoon and that the Asian monsoon climate is indeed a window on the global climatesystem.

关键词： eastern Tibetan Plateau, Holocene, winter and summer monsoons, asynchronous, peat, climate instability.

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A discussion of‘optimal reinsurance designs based on risk measures:a review’

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Statistical Theory and Related Fields 2020年第1期4卷 14-15页

作者： tim j.Boonen Amsterdam School of Economics University of AmsterdamAmsterdamThe Netherlands

I congratulate the authors on their review article(Cai and Chi,2020).Their paper reviews the academic literature on optimal reinsurance problems with risk *** optimal reinsurance,an insurer seeks to share the exogenou... 详细信息

关键词： academic insurance optimal

Impact of smoking cannabidiol (CBD)-rich marijuana on driving ability

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Forensic Sciences Research 2021年第4期6卷 195-207页

作者： tim j.Gelmi Wolfgang Weinmann Matthias Pfäffli Department of Forensic Toxicology and chemistry institute of Forensic MedicineUniversity of BernBernswitzerland Graduate school for cellular and Biomedical sciences(GcB) University of BernBernswitzerland Department of Traffic sciences institute of Forensic MedicineUniversity of BernBernswitzerland

To investigate effects of smoking cannabidiol(CBD)-rich marijuana on driving ability and determine free CBD andΔ9-tetrahydrocannabinol(THC)concentrations in capillary blood samples,a randomised,double-blind,placebo-controlled,two-way crossover pilot study was conducted with 33 *** smoked a joint containing 500 mg of tobacco and either 500 mg of CBD-rich marijuana(16.6%total CBD;0.9%total THC)or 500 mg of a placebo substance,then performed three different dimensions of the Vienna Test System TRAFFIC examining reaction time,behaviour under stress,and concentration *** further assessment of participants’fitness to drive,three tests of balance and coordination were evaluated and vital signs(blood pressure and pulse)were *** blood spot samples of capillary blood were taken after smoking and after completion of the tests to determine the cannabinoid concentrations(CBD,THC and THC-metabolites).The results revealed no significant differences between the effects of smoking CBD-rich marijuana and placebo on reaction time,motor time,behaviour under stress,or concentration *** free CBD and THC concentrations in capillary blood were detected shortly after smoking,ranging between 2.6-440.0 ng/mL and 6.7-102.0 ng/mL,*** 45 min,capillary blood concentrations had already declined and were in the range of 1.9-135.0 ng/mL(free CBD)and 0.9-38.0 ng/mL(free THC).Although the observed levels of free THC concentrations have been reported to cause symptoms of impairment in previous studies in which THC-rich marijuana was smoked,no signs of impairment were found in the current *** finding suggests that higher CBD concentrations cause a negative allosteric effect in the endocannabinoid system,preventing the formation of such ***,it is recommended that consumers refrain from driving for several hours after smoking CBD-rich marijuana,as legal THC concentration limits may be exceeded.

关键词： Forensic sciences forensic toxicology cannabidiol driving while impaired road safety driving assessment

Hemolysis results in impaired intestinal microcirculation and intestinal epithelial cell injury

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World journal of Gastroenterology 2011年第2期17卷 213-218页

作者： Sebastiaan j Hanssen tim Lubbers Caroline M Hodin Frits W Prinzen Wim A Buurman Michael j jacobs Department of Surgery Maastricht University Medical Center Cardiovascular Research Institute Maastricht Maastricht University Medical Center European Vascular Center Aachen-Maastricht Department of Vascular SurgeryUniversity Hospital Aachen Nutrition and Toxicology Research Institute Maastricht Maastricht University Medical Center Department of Physiology Maastricht University Medical Center

AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Sprague-Dawley rats received water or FHb *** changes in jejunum,ileum and colon were evaluated using fluorescent *** injury was quantified as plasmatic release of ileal lipid binding protein(iLBP) and verified by histological analysis of the ileum. RESULTS:Water and FHb infusions resulted,when compared with saline infusion,in reduced intestinal microcirculation(after 30 min Pjejunum and colon) .Circulating FHb levels correlated significantly with release of iLBP(Spearman r=0.72,P=0.0011) .Epithelial cell injury of the villi was histologically observed after water and FHb infusions. CONCLUSION:This study shows that circulating FHb leads to a reduction in intestinal microcirculatory blood flow with marked injury to intestinal epithelial cells. These data support the hypothesis that circulating FHb contributes to the development of intestinal injury.

关键词： Hemoglobin Microcirculation Organ injury Vasoconstriction

Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment

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World journal of Gastroenterology 2008年第16期14卷 2474-2486页

作者： tim CMA Schreuder Bart j Verwer Carin Mj van Nieuwkerk Chris jj Mulder Department of Gastroenterology and Hepatology VU University Medical Center

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a signifi- cant correlation between hepatic steatosis, cardiovascu- lar disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to devel- op hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. There- fore, training programmes in internal medicine, gastroen- terology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and con- comittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging tech- niques and the readily available therapeutic options.

关键词： Non-alcoholic fatty liver disease Non-alcoholicsteatohepatitis Insulin resistance Liver Obesity Steatosis

Non-invasive Angiographic-based Fractional Flow Reserve:Technical Development,Clinical Implications,and Future Perspectives

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当代医学科学(英文) 2023年第3期43卷 423-433页

作者： joyce Peper Michiel L.Bots tim Leiner Martin j.Swaans Department of Cardiology St.Antonius HospitalNieuwegein 3435 CMThe Netherlands Department of Radiology University Medical Center UtrechtUtrecht 3508 GAThe Netherlands julius Center for Health Sciences and Primary Care University Medical Center UtrechtUtrecht 3584 CGThe Netherlands

New non-and less-invasive techniques have been developed to overcome the procedural and operator related burden of the fractional flow reserve(FFR)for the assessment of potentially significant stenosis in the coronary *** FFR-techniques can obviate the need for the additional flow or pressure wires as used for FFR *** review provides an overview of the developments and validation of the virtual FFR-algorithms,states the challenges,discusses the upcoming clinical trials,and postulates the future role of virtual FFR in the clinical practice.

关键词： coronary artery disease quantitative flow ratio fractional flow reserve diagnostic accuracy physiology guided percutaneous coronary intervention