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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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Sweet regulation——The emerging immunoregulatory roles of hexoses

Sweet regulation——The emerging immunoregulatory roles of h...

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浙江省免疫学会第十三次学术大会

作者： Yuening Zhao Junjie Xu randall tyler mertens Yimin Ding Peng Xiao Sir Run Run Shaw Hospital Zhejiang University School of Medicine Department of Immunology Harvard Medical School Institute of Immunology Zhejiang University School of Medicine

It is well-accepted that dietary habits have profound impacts on human health and *** the most important sweeteners and energy sources in human diets,hexoses take part in a broad range of physiopathological *** are a class of simple sugars containing six carbon atoms with the chemical formula C6 H1206,which exist in high abundance in human *** common hexoses include glucose,fructose,mannose and *** and their metabolic intermediates are pivotal for maintaining the fundamental functions of cells,such as serving as energy sources,taking part in protein glycosylation and modification,or regulating intracellular signaling *** recent years,emerging evidence has uncovered the crucial roles of hexoses on controlling the differentiation or function of immune *** exerting diverse immunoregulatory effects,hexoses affect the initiation and progression of various types of immune disorders,including inflammatory disease,autoimmune diseases,or tumor immune *** to their high abundances in our daily diet,it is of great significance to understand how hexoses impacts human immune system and the underlying mechanisms,in order to provide instructions to the dietary habits of *** addition,compared to other drugs,hexoses with immunotherapy functions have advantages in their relatively low price,high safety,and ideal bioavailablity,and thus have the potential to become the therapeutic strategies in immune *** this review,we summarized the recent research progresses in the hexose-mediated modulation of immune responses,and discussed the unresolved questions in this field.

关键词： hexose immune response metabolism cancer inflammation

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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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Robotic management of urinary fistula

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Asian Journal of Urology 2024年第3期11卷 357-365页

作者： Luis G.Medina randall A.Lee Valeria Celis Veronica Rodriguez Jaime Poncel Aref S.Sayegh Rene Sotelo The Catherine and Joseph Aresty Department of Urology USC Institute of UrologyKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Division of Urology Department of SurgeryFox Chase Cancer CenterTemple University Health SystemPhiladelphiaPAUSA

Objectives:To highlight critical preoperative and intraoperative considerations in approaching fistula repair ***:A search of the literature was conducted to identify relevant articles pertaining to robotic management of urinary ***:Fistulae of the genitourinary tract can be a challenging dilemma for urologists,as definitive management may require surgical *** of both enteric and non-enteric fistulae are multifactorial,and successful repair hinges on the meticulous perioperative evaluation,planning,and *** open techniques can subject patients to increased morbidity and prolonged *** its introduction,the robotic surgical platform has continued to expand its *** three-dimensional visualization and tremor free wristed instrument movements have made the robotic platform an attractive option for genitourinary fistula ***:Robotic management of complex urinary fistulae is feasible in expert hands;more studies are needed to define its role in the treatment algorithm of this devastating conditions.

关键词： Fistula Robotic surgery Rectourethral Rectovesical Vesicovaginal

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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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力-化学偶联信号促进皮肤类器官自组装的机制研究

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医用生物力学 2024年第S1期 281-282页

作者：雷明星蒋璟玮王梦月 Hans I Harn Ting-Xin Jiang randall Widelitz 杨力 Cheng-Ming Chuong 重庆大学生物工程学院美国南加州大学凯克医学院

目的基于皮肤类器官模型探索生物力学-化学信号促进皮肤及毛囊再生的机制,为解决皮肤创伤和脱发问题提供新的思路。方法本研究通过微流控类器官培养模型、细胞延时摄影、单细胞多组学技术、力学环境重编程、分子功能干扰等技术探究了...

目的基于皮肤类器官模型探索生物力学-化学信号促进皮肤及毛囊再生的机制,为解决皮肤创伤和脱发问题提供新的思路。方法本研究通过微流控类器官培养模型、细胞延时摄影、单细胞多组学技术、力学环境重编程、分子功能干扰等技术探究了生物力学-化学信号如何参与皮肤类器官的自组装过程,通过裸鼠移植实验评价了类器官诱导毛发再生的效果。结果通过延时摄影对类器官自组装过程中的细胞行为进行追踪,发现真皮细胞和表皮细胞经历了“聚集-极化-联合-平面化”4个阶段,形成功能性皮肤结构。真皮细胞的收缩力激活了表皮聚集体的Piezo1信号,进而形成极化的细胞形态发生单位,此结构通过局部微环境力学硬度增加激活了Yap1及下游的Wnt/Mmp信号,诱导相邻的CMU结构联合。在缺氧诱导因子Hif1a的驱动下真皮细胞和表皮细胞通过代谢适应完成相位分离,形成功能性平面化皮肤。将完成自组装的类器官移植裸鼠背部后,成功诱导移植部位的毛发再生。结论本研究深入分析了皮肤类器官的自组装过程,揭示了力学-化学信号引起的组织形态相变影响毛囊再生的机制。这一自组装途径为利用解离的皮肤前体细胞提供了一种重塑形态的有效途径,也为未来修复或改造器官提供了可能性。

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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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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

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Nano Research 2024年第10期17卷 9052-9064页

作者： Savannah E.Est-Witte Sydney R.Shannon Dennis H.Gong Kaitlyn G.Calabresi Jawaun J.Harris Kaitlyn Storm Edwin J.Yoo Ariel Isser Vivek P.Jani Natalie K.Livingston Mary O.Omotoso Kelly Rhodes Elana Ben-Akiva randall A.Meyer Zoe T.Hsieh Simone Sidoli Stephany Y.Tzeng Jonathan P.Schneck Jordan J.Green Translational Tissue Engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell Engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

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