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metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & molecular Immunology 2024年第1期21卷 33-46页

作者： Anja meyer Stephanie R.Zack wes nij.m Adel Burgos Vishwa Patel Brian Zanotti michael V.Volin m.Asif Amin myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA medical Center ChicagoILUSA Department of medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AmPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Risk factors for musculoskeletal injuries in the military: a qualitative systematic review of the literature from the past two decades and a new prioritizing injury model

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military medical Research 2022年第4期9卷 444-483页

作者： Stefan Sammito Vedran Hadzic Thomas Karakolis Karen R.Kelly Susan P.Proctor Ainars Stepens Graham White wes O.Zimmermann Section Experimental Aerospace medicine Research German Air Force Centre of Aerospace MedicineFlughafenstraBe 151147 CologneGermany Occupational medicine Faculty of MedicineOtto-Von-Guericke-University of Magdeburg39120 MagdeburgGermany Faculty of Sport University of Ljubljana1000 LjubljanaSlovenia Defence Research and Development Canada TorontoON M3K 2C9Canada Warfighter Performance Naval Health Research CenterSan DiegoCA 921063599USA military Performance Division US Army Research Institute of Environmental MedicineNatickMA 01760USA Research Service VA Boston Healthcare SystemBostonMA 02130USA Centre for military medicine Research Riga Stradins UniversityRiga 1007Latvia Human and Social Sciences Group Defense Science and Technology LaboratoryPortsdown Hill RoadFareham PO176ADUK Department of military Sports medicine Royal Netherlands Army3584 AB UtrechtThe Netherlands Department of military/Emergency medicine Uniformed Services University of the Health SciencesBethesdaMD 20814USA.

Background: musculoskeletal injuries(mSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. mSkIs affect members of the military during initial training,operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for mSkIs in the military is not ***: A systematic literature search was carried out using the Pubmed, Ovid/medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed(using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was ***: In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/nonmodifiable, as well as extrinsic/intrinsic risk ***: This is the qualitative systematic review of studies on risk factors for mSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.

关键词： military musculoskeletal injuries Risk factors Prevention Intervention Injury

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柏林朵尔蒂街区

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景观设计 2006年第1期 52-55页

作者： wes ＆ Partner

一个比较狭小的内院（25m高，28m宽），光透进来，光与云映在地面上，光又反射在墙壁上，那水因天然石而显得幽深；人们透过水面可以瞥见石砌的池底，发现水中游鱼，在低凹的方形池中央有纤细的，只在顶端长着叶子的勃兰登堡松和高高的... 详细信息

一个比较狭小的内院（25m高，28m宽），光透进来，光与云映在地面上，光又反射在墙壁上，那水因天然石而显得幽深；人们透过水面可以瞥见石砌的池底，发现水中游鱼，在低凹的方形池中央有纤细的，只在顶端长着叶子的勃兰登堡松和高高的摇曳的竹状细杆，此情此景会让人惊喜，惹人沉思，也许会让人沉浸在这自然之隅的奇境梦幻中，从高处俯瞰大地，岛屿和水面，熟悉的景色变成了和梦似幻的画面。

关键词：街区柏林水面天然石地面墙壁

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莱比锡博览会新馆

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景观设计 2005年第6期 66-69页

作者： wes ＆ Partner

设计此项目的目标是创作一个由风景，城市建筑，建筑艺术和技术构成的综合性艺术作品，桑肯公园不沉6m，宽100m，长2km，是莱比锡的壕沟风景，风光多变，一步一景，从野鹿火车站绵延越过展览馆，是此地的中心，是展览馆的绿色命脉，目... 详细信息

设计此项目的目标是创作一个由风景，城市建筑，建筑艺术和技术构成的综合性艺术作品，桑肯公园不沉6m，宽100m，长2km，是莱比锡的壕沟风景，风光多变，一步一景，从野鹿火车站绵延越过展览馆，是此地的中心，是展览馆的绿色命脉，目前这个尚无太多人居住的地方已成为颇受欢迎的休闲场所。有空莘和树木的大厅也可当作带顶棚的休闲区使用，这旨一个绿色的静地，与旁边黑色展厅的繁忙喧嚣，熙熙攘攘形成对照。

关键词：博览会锡城市建筑艺术作品技术构成建筑艺术休闲场所展览馆

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Ballistic impact properties of woven bamboo-woven E-glass-unsaturated polyester hybrid composites

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Defence Technology（防务技术） 2019年第3期15卷 282-294页

作者： Aidy Ali Rabiatun Adawiyah Kannan Rassiah Wei Kuan Ng Faiz Arifin Faiz Othman muhammad Shauqi Hazin m.K. Faidzi m.F. Abdullah m.m.H. megat Ahmad Department of mechanical Engineering Faculty of Engineering Universiti Pertahanan Nasional Malaysia (UPNM) National Defense University of Malaysia (NDUM) Kem Sg. Besi 57000 Kuala Lumpur Malaysia Department of mechanical Engineering Politeknik Port Dickson (PPD) KM 14 Jalan Pantai Si Rusa Negeri Sembilan Malaysia

In this study, a laminated woven bamboo/woven E glass/unsaturated polyester composite is developed to combat a ballistic impact from bullet under shooting test. The aim of this study is to understand the fundamental effects of the woven bamboo arrangement towards increasing ballistic resistance properties. The work focusses on the ballistic limit test known as nij V50, which qualifies materials to be registered for use in combat armor panels. The results show that the composites withstood 482.5 m/s ± 5 limit of bullet velocity, satisfying the nij test at level II. The findings give a strong sound basis decision to engineers whether or not green composites are qualified to replace synthetic composites in certain engineering applications.

关键词： Woven bamboo E glass Hybrid composites Ballistic limit velocity Energy absorption

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Comprehensive validation of a diagnostic strategy for sequencing genes with one or multiple pseudogenes using pseudoxanthoma elasticum as a model

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Journal of Genetics and Genomics 2021年第4期48卷 289-299页

作者： Wouter Steyaert Shana Verschuere Paul J.Coucke Olivier m.Vanakker Center for medical Genetics Ghent University HospitalGhentBelgium bDepartment of Biomolecular medicine Ghent UniversityGhentBelgium Department of Human Genetics Radboud Institute for Molecular Life SciencesRadboud University Medical CenterNijmegenthe Netherlands

Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding *** this reason,their presence is often considered troublesome in molecular *** pseudoxanthoma elasticum(PXE),a disease predominantly caused by mutations in ATPbinding cassette family C member 6(ABCC6),the presence of two pseudogenes complicates the analysis of sequence *** whole-exome sequencing(wes)becoming the standard of care in molecular diagnostics,we wanted to evaluate whether this technique is as reliable as gene-specific targeted enrichment analysis for the analysis of *** established a PCR-based targeted enrichment and next-generation sequencing testing approach and demonstrated that the ABCC6-specific enrichment combined with the applied mapping algorithm overcomes the complication of ABCC6 pseudogene aspecificities,contrary to *** propose a time-and cost-efficient diagnostic strategy for comprehensive and accurate molecular genetic testing of PXE,which is highly automatable.

关键词： Pseudoxanthoma elasticum ABCC6 Pseudogenes Next-generation sequencing Whole-exome sequencing Targeted enrichment

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Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

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World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi Katalin Bartyik Krisztina míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss miklós Garami István Peták Oncompass medicine Hungary Kft Retek Str.34Budapest 1024Hungary Division of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary Department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(m,and samples from 100 patients were eligible for further *** or blood samples were analyzed by whole-exome(wes)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision ***,a molecular tumor board(mTB)evaluated the results to provide therapy *** Of the 100 cases with comprehensive molecular diagnostic data,88 yielded wes and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the evidence *** approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of wes results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

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月球模拟任务中的乘组人际互动——基于午餐中互动行为与心理量表的相关分析（英文）

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航天医学与医学工程 2018年第3期31卷 301-310页

作者：吴瑞林马倩颖 Gro m.Sandal 王雅刘红北京航空航天大学心理学系北京100191 卑尔根大学心理学系挪威北京航空航天大学生物与医学工程学院北京100191

目的分析长期隔离和限制环境下乘组人际关系互动与心理状态变化,并探究乘组人员行为动作与心理状态之间的联系。方法三位乘组人员参与了月宫一号(空间基地生命保障人工闭合生态系统地基综合实验),完成80天的长期密闭隔离实验。乘员的行... 详细信息

目的分析长期隔离和限制环境下乘组人际关系互动与心理状态变化,并探究乘组人员行为动作与心理状态之间的联系。方法三位乘组人员参与了月宫一号(空间基地生命保障人工闭合生态系统地基综合实验),完成80天的长期密闭隔离实验。乘员的行为分析基于视频记录的午餐互动过程,并在后期通过Observer XT软件进行人工编码。同时,三位乘员还完成了每周1次的心理状态量表(profile of mood state,POmS)以及每2周1次的团队环境量表(group environment scale,GES)与工作环境量表(work environment scale,wes)。结果乘组午餐用时时长随实验开展而显著增长,并与乘组人员的精力显著相关。积极面部表情与3个心理量表的诸多维度存在显著相关。结论吃饭时长和积极面部情绪可以反映乘组人员的情绪状态,并可以帮助评估乘组人员对团队环境和工作环境的感知。

关键词：人际互动空间任务行为学分析极端、隔离与限制环境模拟任务

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军团菌外膜蛋白抗原基因的克隆并在原核系统中表达

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寄生虫病与感染性疾病 2004年第4期2卷 149-151页

作者：芦殿香陈建平张雷王涛刘明杰田玉陈宪四川大学华西基础医学与法医学院寄生虫学教研室形态学实验室四川成都610041

目的　克隆军团菌外膜蛋白抗原基因 omp m,构建重组质粒 p LPm,并在原核系统中表达。方法　采用聚合酶链反应 (PCR)从军团菌基因组 DNA中扩增得到 omp m基因 ,导入载体 p UC1 8,在 Jm1 0 9中表达 ,并用SDS-PAGE进行鉴定。结果　扩增出 7... 详细信息

目的　克隆军团菌外膜蛋白抗原基因 omp m,构建重组质粒 p LPm,并在原核系统中表达。方法　采用聚合酶链反应 (PCR)从军团菌基因组 DNA中扩增得到 omp m基因 ,导入载体 p UC1 8,在 Jm1 0 9中表达 ,并用SDS-PAGE进行鉴定。结果　扩增出 773 bp的 omp m基因 ;构建重组质粒 p LPm;表达出 2 5 k Da的蛋白质。结论　成功扩增军团菌 omp m基因 ,构建重组质粒 p LPm,并在原核系统中得到了表达。

关键词：军团菌 ompm PCR 基因表达

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聚-γ-苄基-L-谷氨酸酯的合成

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生物医学工程学杂志 1987年第1期 8-10页

作者：邓先模,J.m.Anderson 中国科学院成都有机化学所 Department of macromolecular Science Case wes tern Reserve University Cleveland Ohio 44106 U.S.A.

采用优于氢溴酸的硫酸法合成了γ-苄基-L-谷氨酸酯。溶剂经小心干燥和纯化,而在反应体系中将二氧六环改为四氢呋喃为溶剂以后,以直接光气化而制备了γ-苄基-L-谷氨酸酯的N-羧酸酐(NCA)。γ-苄基-L谷氨酸酯和NCA两者的产率均得到了高于... 详细信息

采用优于氢溴酸的硫酸法合成了γ-苄基-L-谷氨酸酯。溶剂经小心干燥和纯化,而在反应体系中将二氧六环改为四氢呋喃为溶剂以后,以直接光气化而制备了γ-苄基-L-谷氨酸酯的N-羧酸酐(NCA)。γ-苄基-L谷氨酸酯和NCA两者的产率均得到了高于文献报道的结果。

关键词：谷氨酸酯产率 NCA 苄基苯甲基芳基

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