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Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit

Cellular & Molecular Immunology 2023年第2期20卷 119-130页

作者： Peng Xiao Ziwei Hu Jiaheng Lang Tianyuan Pan randall tyler mertens Huilun Zhang Ke Guo Manlu Shen Hongqiang Cheng Xue Zhang Qian Cao Yuehai Ke Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Department of Pathology and Pathophysiology and Department of Gastroenterology at Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Immunological Disease Research Center Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Key Laboratory for Immunity and Inflammatory Diseases of Zhejiang Province HangzhouChina Department of Pathology and Pathophysiology Zhejiang University School of MedicineHangzhouChina Department of General Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Immunology Harvard Medical SchoolBostonMAUSA Zhejiang Laboratory for Systems and Precision Medicine Zhejiang University Medical CenterHangzhouChina

Mannose is a naturally occurring sugar widely consumed in the daily diet;however,mechanistic insights into how mannose metabolism affects intestinal inflammation remain ***,we reported that mannose supplementation ameliorated colitis development and promoted colitis ***-secreted inflammatory cytokines,particularly TNF-α,induced pathological endoplasmic reticulum stress(ERS)in intestinal epithelial cells(IECs),which was prevented by mannose via normalization of protein *** preserving epithelial integrity,mannose reduced the inflammatory activation of colonic *** the other hand,mannose directly suppressed macrophage TNF-αproduction translationally by reducing the glyceraldehyde 3-phosphate level,thus promoting GAPDH binding to TNF-α***,we found dysregulated mannose metabolism in the colonic mucosa of patients with inflammatory bowel ***,we revealed that activating PMM2 activity with epalrestat,a clinically approved drug for the treatment of diabetic neuropathy,elicited further sensitization to the therapeutic effect of ***,mannose metabolism prevents TNF-α-mediated pathogenic crosstalk between IECs and intestinal macrophages,thereby normalizing aberrant immunometabolism in the gut.

关键词： Colitis Mannose Macrophages Intestinal epithelial cells TNF-alpha Endoplasmic reticulum stress

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High rate of clinically relevant improvement following anatomical total shoulder arthroplasty for glenohumeral osteoarthritis

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World Journal of Orthopedics 2024年第2期15卷 156-162页

作者： Marc randall Kristensen Nyring Bo Sanderhoff Olsen Alexander Amundsen Jeppe Vejlgaard Rasmussen Section for Shoulder and Elbow Surgery Department of Orthopaedic SurgeryHerlev and Gentofte University HospitalHellerup 2900Denmark

BACKGROUND The minimal clinically important difference(MCID)is defined as the smallest meaningful change in a health domain that a patient would identify as ***,an improvement that exceeds the MCID can be used to define a successful treatment for the individual *** To quantify the rate of clinical improvement following anatomical total shoulder arthroplasty for glenohumeral *** Patients were treated with the Global Unite total shoulder platform arthroplasty between March 2017 and February 2019 at Herlev and Gentofte Hospital,*** patients were evaluated preoperatively and 3 months,6 months,12 months,and 24 months postoperatively using the Western Ontario Osteoarthritis of the Shoulder index(WOOS),Oxford Shoulder Score(OSS)and Constant-Murley Score(CMS).The rate of clinically relevant improvement was defined as the proportion of patients who had an improvement 24 months postoperatively that exceeded the *** on previous literature,MCID for WOOS,OSS,and CMS were defined as 12.3,4.3,and 12.8 *** Forty-nine patients with a Global Unite total shoulder platform arthroplasty were included for the final *** age at the time of surgery was 66 years(range 49.0-79.0,SD:8.3)and 65%were *** patient was revised within the two years *** mean improvement from the preoperative assessment to the two-year follow-up was 46.1 points[95%confidence interval(95%CI):39.7-53.3,P<0.005]for WOOS,18.2 points(95%CI:15.5-21.0,P<0.005)for OSS and 37.8 points(95%CI:31.5-44.0,P<0.005)for *** years postoperatively,41 patients(87%)had an improvement in WOOS that exceeded the MCID,45 patients(94%)had an improvement in OSS that exceeded the MCID,and 42 patients(88%)had an improvement in CMS that exceeded the *** Based on three shoulder-specific outcome measures we find that approximately 90%of patients has a clinically relevant *** is a clear message when informing patients about the

关键词： Minimal clinically important difference Patient reported outcome measures Glenohumeral osteoarthritis Anatomical total shoulder arthroplasty Clinically relevant improvement

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Surgical management of the diabetic foot:The current evidence

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World Journal of Orthopedics 2024年第5期15卷 404-417页

作者： Richard Henry randall Roberts Gareth Rhys Davies-Jones James Brock Vaishnav Satheesh Greg AJ Robertson Department of Trauma and Orthopaedics Wrexham Maelor HospitalWrexham LL137TDUnited Kingdom Department of Trauma and Orthopaedics The Robert Jones and Agnes Hunt Orthopaedic HospitalOswestry SY107AGUnited Kingdom

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens *** review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,*** escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality *** review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse *** addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot *** integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

关键词： Diabetes Diabetic foot Charcot Osteomyelitis Amputation Diabetic foot attack Conservative surgery

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Network analyses:Inhibition of androgen receptor signaling reduces inflammation in the lung through AR-MAF-IL6 signaling axes

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Genes & Diseases 2024年第3期11卷 140-143页

作者： Albert R.Wang Andrew M.Baschnagel Zijian Ni Sean R.Brennan Hypatia K.Newton Darya Buehler Christina Kendziorski randall J.Kimple Gopal lyer Department of Human Oncology University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA Department of Biomedical Engineering University of Wisconsin-MadisonMadisonWI 53705USA University of Wisconsin Carbone Cancer Center MadisonWI 53705USA Department of Biostatistics and Medical Informatics University of Wisconsin-MadisonMadisonWI 53706USA Department of Biology Tufts UniversityMedfordMA 02155USA Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA

Androgen receptor(AR)is a major transcription factor that plays a role in inflammatory response including interleukin-6(IL6)signaling.1 While AR regulation through paracrine loop signaling in prostate tissue is well-studied,its impact through an IL6 autocrine loop in the lung has not been wellstudied despite the organ's response to respiratory viral *** inhibition and RNA knockdown of AR identified a bZIP transcription factor MAF to be a common target of inflammation using these perturbations in lung cells.

关键词： inflammation lung respiratory

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Combined Effect of Outdoor Time and Other Modifiable Factors on Myopia Incidence Among Children and Adolescents—9 PLADs,China,2020

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China CDC weekly 2024年第9期6卷 151-156,I0001,I0002页

作者： Panliang Zhong Yunfei Liu Ning Ma Jiajia Dang Di Shi Shan Cai Ziyue Chen Yanhui Dong Peijin Hu Jun Ma Patrick W.C Lau randall S.Stafford Yi Song Institute of Child and Adolescent Health School of Public HealthPeking UniversityNational Health Commission Key Laboratory of Reproductive HealthBeijingChina Department of Sport Physical Education&HealthHong Kong Baptist UniversityKowloon TongHong Kong Special Administrative RegionChina Department of Medicine Stanford Prevention Research CenterStanford University School of MedicineStanfordCAUnited States

Summary What is already known about this topic?Myopia has been identified as a significant emerging challenge and policy priority among children and adolescents in China by the Ministry of Education and seven other *** research has been conducted to investigate the collective impact of outdoor time and other modifiable factors on the incidence of myopia.

关键词： Incidence collective policy

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Visual rating and the use of image analysis for assessing canopy density in a pecan provenance collection during leaf fall

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林业研究:英文版 2023年第6期34卷 1843-1854页

作者： Cristina Pisani Clive H.Bock Jennifer randall United States Department of Agriculture−Agricultural Research Service (USDA-ARS)Southeastern Fruit and Tree Nut Research Station(SEFTNRS)ByronGA 31008USA Department of Entomology Plant Pathology and Weed ScienceNew Mexico State UniversityLas CrucesNM 88003USA

A collection representing the native range of pecan was planted at the US DA-ARS Southeastern Fruit and Tree Nut Research Station,Byron,*** collection(867 trees)is a valuable genetic resource for characterizing important horticultural *** density during leaf fall is important as the seasonal canopy dynamics provides insights to environmental cues and breeding potential of *** ability of visual raters to estimate canopy density on a subset of the provenance collection(76 trees)as an indicator of leaf shed during autumn along with image analysis values was *** canopy density using the image analysis software was less compared to visual estimates(11.9%vs 18.4%,respectively).At higher canopy densities,the raters overestimated foliage density,but overall agreement between raters and measured values was good(ρc=0.849 to 0.915),and inter-rater reliability was high(R^(2)=0.910 to 0.953).The provenance from Missouri(MOL),the northernmost provenance,had the lowest canopy density in November,and results show that the higher the latitude of the provenance,the lower the canopy *** on regression,the source provenance latitude explained 0.609 of the variation using image analysis,and0.551 to 0.640 when based on the rater estimates of canopy *** assessment of pecan canopy density due to late season leaf fall for comparing pecan genotypes provides accurate and reliable estimates and could be used in future studies of the whole provenance collection.

关键词： Carya illinoinensis Accuracy Reliability Canopy Foliage density Leaf area density Leaf area index

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Security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

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中国神经再生研究：英文版 2023年第1期18卷 64-67页

作者： Igor Lupinski Allison SLiang randall D.McKinnon Department of Neurosurgery and Member The Cancer Institute of New JerseyRutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde *** further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond *** propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.

关键词： amyotrophic lateral sclerosis bioaccumulation neurodegeneration neuropathology neurotoxins peripheral nerves retrograde transport retrotoxicity suicide transport

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Rapid design of top-performing metal-organic frameworks with qualitative representations of building blocks

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npj Computational Materials 2023年第1期9卷 585-598页

作者： Yigitcan Comlek Thang Duc Pham randall Q.Snurr Wei Chen Department of Mechanical Engineering Northwestern UniversityEvanstonILUSA Department of Chemical and Biological Engineering Northwestern UniversityEvanstonILUSA

Data-driven materials design often encounters challenges where systems possess qualitative(categorical)***,representing Metal-organic frameworks(MOFs)through different building blocks poses a challenge for designers to incorporate qualitative information into design optimization,and leads to a combinatorial challenge,with large number of MOFs that could be *** this work,we integrated Latent Variable Gaussian Process(LVGP)and Multi-Objective Batch-Bayesian Optimization(MOBBO)to identify top-performing MOFs adaptively,autonomously,and *** showcased that our method(i)requires no specific physical descriptors and only uses building blocks that construct the MOFs for global optimization through qualitative representations,(ii)is application and property independent,and(iii)provides an interpretable model of building blocks with physical *** searching only~1%of the design space,LVGP-MOBBO identified all MOFs on the Pareto front and 97%of the 50 top-performing designs for the CO_(2) working capacity and CO_(2)/N2 selectivity properties.

关键词： properties qualitative autonomous

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Practical Application of Altitude/Hypoxic Training for Olympic Medal Performance:The Team USA Experience

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Journal of Science in Sport and Exercise 2022年第4期4卷 358-370页

作者： randall L.Wilber United States Olympic&Paralympic Committee 1 Olympic PlazaColorado SpringsCO 80909USA

Although scientific conclusions remain equivocal,there is evidence-based research,as well as anecdotal support,suggesting that altitude training can enhance performance among Olympic level athletes,particularly in endurance *** appears to be due primarily to hypoxia-induced increases in total hemoglobin mass and subsequent improvements in maximal oxygen uptake and other factors contributing to aerobic *** less clear,it is possible that non-hematological adaptations may contribute secondarily to improvements in post-altitude *** physiological effects are most likely realized when the altitude exposure is of sufficient“hypoxic dose”to provide the necessary stimuli for performance-affecting changes to occur via hypoxia-inducible factor 1α(HIF-1α)and hypoxia-inducible factor 2α(HIF-2α)pathways and their downstream molecular *** USA has made a strong commitment over the past 20 years to utilizing altitude training for the enhancement of performance in elite athletes in preparation for the Olympic Games and World *** USA’s strongest medal-producing Olympic sports-USA Swimming and USA Track and Field-embraced altitude training several years ago,and they continue to be leaders within Team USA in the practical and successful application of altitude *** USA Swimming utilizes traditional“live high and train high”(LH+TH)altitude training,USA Track and Field tends more toward the use of the altitude training strategy whereby athletes live high(and potentially sleep higher,either naturally or via simulated altitude),while training high during moderate-intensity(lactate threshold 2)training sessions(LH+TH_([LT])).Although USA Swim-ming and USA Track and Field have taken different approaches to altitude training,they have been equally successful at the Olympic Games and World Championships,both teams being ranked first

关键词： Hypoxia Live high-train high Live high-train low Intermittent hypoxic training Elite performance

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