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Structural characterization of SARS-CoV-2 dimeric ORF9b reveals potential fold-switching trigger mechanism

Science China(Life Sciences) 2023年第1期66卷 152-164页

作者： Xiyue Jin Xue Sun Yan Chai Yu Bai Ying Li Tianjiao Hao Jianxun Qi Hao Song catherine CL Wong George F.Gao School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Peking University First Hospital Peking UniversityBeijing 100034China Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking UniversityBeijing 100191China University of Chinese Academy of Sciences Beijing 100049China Research Network of Immunity and Health(RNIH) Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China School of Basic Medical Sciences Peking University Health Science CenterPeking UniversityBeijing 100191China

The constant emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants indicates the evolution and adaptation of the *** innate immune evasion through increased expression of viral antagonist proteins,including ORF9b,contributes to the improved transmission of the Alpha variant;hence,more attention should be paid to these viral ***9b is an accessory protein that suppresses innate immunity via a monomer conformation by binding to ***,we solved the dimeric structure of SARS-CoV-2 ORF9b with a long hydrophobic tunnel containing a lipid molecule that is crucial for the dimeric conformation and determined the specific lipid ligands as monoglycerides by conducting a liquid chromatography with tandem mass spectrometry analysis,suggesting an important role in the viral life ***,a long intertwined loop accessible for host factor binding was observed in the *** phosphorylated residues in ORF9b were identified,and residues S50 and S53 were found to contribute to the stabilization of dimeric ***,we proposed a model of multifunctional ORF9b with a distinct conformation,suggesting that ORF9b is a fold-switching protein,while both lipids and phosphorylation contribute to the ***,the ORF9b monomer interacts with Tom70 to suppress the innate immune response,whereas the ORF9b dimer binds to the membrane involving mature virion *** results provide a better understanding of the multiple functions of ORF9b.

关键词： SARS-CoV-2 ORF9b immune escape viral antagonist membrane association fold switch lipid binding

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活动期糖尿病夏科神经性骨关节病诊疗指南——《国际糖尿病足工作组:糖尿病相关的足病预防与管理指南(2023)》的一部分

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感染、炎症、修复 2024年第1期25卷 52-71页

作者： Dane K.Wukich Nicolaas C.Schaper catherine Gooday Arun Bal Robert Bem Avneesh Chhabra Mary Hastings Crystal Holmes Nina L.Petrova Maria Gala Santini Araujo Eric Senneville Katherine M.Raspovic on behalf of the International Working Group on the Diabetic Foot 赵宏谋徐俊(译) 张明珠(审校) Department of Orthopaedic Surgery University of Texas Southwestern Medical CenterDallasTexasUSA Division of Endocrinology MUMC+CARIM and CAPHRI InstituteMaastrichtthe Netherlands Elsie Bertram Diabetes Centre Norfolk&Norwich University Hospitals NHS Foundation TrustNorfolkUK Secretary International Association of Diabetic Foot SurgeonsMumbaiIndia Diabetes Centre Institute for Clinical and Experimental MedicinePrague Department of Radiology UT Southwestern Medical CenterDallasTexasUSA Program in Physical Therapy Washington University School of MedicineSt.LouisMissouriUSA The Division of Metabolism Endocrinology and DiabetesThe University of Michigan Medical SchoolAnn ArborMichiganUSA Department of Diabetes Diabetic Foot ClinicKing’s College Hospital NHS Foundation TrustLondonUK Italian Hospital of Buenos Aires Buenos AiresArgentina Department of Infectious Diseases Gustave Dron HospitalTourcoingFrance 不详西安交通大学医学院附属红会医院陕西西安710054 天津医科大学朱宪彝纪念医院天津300314 首都医科大学附属同仁医院北京100730

国际糖尿病足工作组(IWGDF)自1999年以来发布了糖尿病足病预防和治疗的循证指南。这是IWGDF发布的第一部关于糖尿病患者活动期夏科神经性骨关节病诊断和治疗的指南。我们遵循GRADE方法,以人群-评估-比较-结局(PACO)和人群-干预-比较-结... 详细信息

国际糖尿病足工作组(IWGDF)自1999年以来发布了糖尿病足病预防和治疗的循证指南。这是IWGDF发布的第一部关于糖尿病患者活动期夏科神经性骨关节病诊断和治疗的指南。我们遵循GRADE方法,以人群-评估-比较-结局(PACO)和人群-干预-比较-结局(PICO)的格式设计临床问题,系统检索医学文献,并提出有依据的推荐。这些推荐是基于我们系统综述的证据,如无证据则参考专家意见,并考虑到与干预相关的受益和危害、患者偏好、可行性和适用性以及成本的权衡。我们在本章节介绍了2023年糖尿病患者活动期夏科神经性骨关节病的诊断和治疗指南,并提出了未来的关键研究方向。

关键词：糖尿病夏科神经性骨关节病,活动期诊断治疗国际糖尿病足工作组指南

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Plasma phospholipid transfer protein (PLTP) as an emerging determinant of the adaptive immune response

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Cellular & Molecular Immunology 2018年第12期15卷 1077-1079页

作者： catherine Desrumaux Laurent Lagrost UniversitéMontpellier Montpellier F-34095France Team‘Environmental Impacts in Alzheimer’s Disease and Related Disorders’(EiAlz) InsermU1198Montpellier F-34095France EPHE Paris F-75007France LipSTIC LabEx Fondation de Coopération Scientifique Bourgogne-Franche ComtéDijon F-21000France INSERM LNC UMR1231Dijon F-21000France University Bourgogne Franche-Comté LNC UMR1231Dijon F-21000France

Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid *** addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and *** addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune *** modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic *** addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune *** modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 *** novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).

关键词： PLTP immunity metabolism

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Role of retinoids in the prevention and treatment of colorectal cancer

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World Journal of Gastrointestinal Oncology 2015年第10期7卷 184-203页

作者： catherine C Applegate Michelle A Lane School of Family and Consumer Sciences Nutrition and Foods Program Texas State University

Vitamin A and its derivatives, retinoids, have been widely studied for their use as cancer chemotherapeutic agents. With respect to colorectal cancer(CRC), several critical mutations dysregulate pathways implicated in progression and metastasis, resulting in aberrant Wnt/β-catenin signaling, gain-of-function mutations in K-ras and phosphatidylinositol-3-kinase/Akt, cyclooxygenase-2 over-expression, reduction of peroxisome proliferatoractivated receptor γ activation, and loss of p53 function. Dysregulation leads to increased cellular proliferation and invasion and decreased cell-cell interaction and differentiation. Retinoids affect these pathways by various mechanisms, many involving retinoic acid receptors(RAR). RAR bind to all-trans-retinoic acid(ATRA) to induce the transcription of genes responsible for cellular differentiation. Although most research concerning the chemotherapeutic efficacy of retinoids focuses on the ability of ATRA to decrease cancer cell proliferation, increase differentiation, or promote apoptosis; as CRC progresses, RAR expression is often lost, rendering treatment of CRCs with ATRA ineffective. Our laboratory focuses on the ability of dietary vitamin A to decrease CRC cell proliferation and invasion via RAR-independent pathways. This review discusses our research and others concerning the ability of retinoids to ameliorate the defective signaling pathways listed above and decrease tumor cell proliferation and invasion through both RAR-dependent and RAR-independent mechanisms.

关键词： Colorectal cancer Retinoid Vitamin A β-catenin Pho

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Neuroendocrine control of natural killer cell function through the checkpoint molecule PD-1

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Cellular & Molecular Immunology 2019年第2期16卷 109-111页

作者： Justine Devulder Anne Tsicopoulos catherine Duez Pulmonary Immunity Institut National de la SantéEt de la Recherche MédicaleU1019F-59019 LilleFrance Institut Pasteur de Lille Center for Infection and Immunity of LilleF-59019 LilleFrance CNRS UMR 8204 F-59000 LilleFrance Univ Lille Nord de France F-59000 LilleFrance Clinique des Maladies Respiratoires et Centre Hospitalier Régional et Universitaire de Lille 59037 LilleFrance

Host defense strategies encompass resistance to reduce pathogen burden,and disease tolerance to preserve host fitness.1 Immunedriven resistance mechanisms have inevitably a negative impact on host fitness and can lead to *** tolerance limit immunopathology and therefore disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen *** pathways cooperate to protect the *** pathways include metabolic and oxidative stress responses,2 and the interaction between neuroendocrine system and the immune system3 to favor resolution of inflammation and to prevent tissue damage.

关键词： damage killer inflammation

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Do clinical factors help to predict disease course in inflammatory bowel disease?

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World Journal of Gastroenterology 2010年第21期16卷 2600-2603页

作者： Edouard Louis Jacques Belaiche catherine Reenaers Department of Gastroenterology CHU Liègeand GIGA ResearchLiège University4000 LiègeBelgium

While therapeutic strategies able to change the natural history of the disease are developing,it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic *** predictors have probably been the most broadly *** both Crohn's disease(CD) and ulcerative colitis(UC),age at diagnosis,disease location and smoking habit are currently the strongest predictors of disease course.A younger age at onset is associated with more aggressive disease both in CD and *** location in CD is associated with different types of complications:surgery and recurrence in upper gastrointestinal and proximal small bowel disease;and surgery in distal small bowel disease and peri-anal lesions in rectal *** UC,extensive colitis is clearly been associated with more severe ***,active smoking globally increases disease severity in CD but decreases it in *** these important factors,others may predispose to some specific disease evolution and complications,and are also reviewed in the present paper.

关键词： Crohn’s disease Ulcerative colitis Clinical predictors

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Impact of medical therapies on inflammatory bowel disease complication rate

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World Journal of Gastroenterology 2012年第29期18卷 3823-3827页

作者： catherine Reenaers Jacques Belaiche Edouard Louis Department of Gastroenterology CHU Sart-TilmanUniversity of Liège4000 LiègeBelgium

Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures,fistulae,perianal complications,surgery,and colorectal *** the natural history and avoiding evolution to a disabling disease should be the main goal of *** recent studies,mucosal healing has been associated with longer-term remission and fewer *** therapies with immunosuppressive drugs are able to induce mucosal healing in a minority of cases but their impact on disease progression appears *** rates of mucosal healing can be achieved with anti-tumor necrosis factor therapies that reduce the risk of relapse,surgery and hospitalization,and are associated with perianal fistulae *** drugs might be able to change the natural history of the disease mainly when introduced early in the course of the *** strategy in inflammatory bowel diseases should thus be tailored according to the risk that each patient could develop disabling disease.

关键词：肠道疾病药物治疗并发症发生率溃疡性结肠炎肿瘤坏死因子愈合率免疫抑制

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An Investigation on the Utilization of Intra Uterine Contraceptive Device among Women in Kabwe, Central Province

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Open Journal of Obstetrics and Gynecology 2023年第12期13卷 1994-2020页

作者： Janet Mazuba Mweempwa catherine M. Ngoma Department of Public Health Nursing School of Nursing Sciences University of Zambia Lusaka Zambia Department of Midwifery Women and Child Heath School of Nursing Sciences University of Zambia Lusaka Zambia

Introduction: Intrauterine contraceptive device (IUCD) is an effective long acting reversible contraceptive but its use is low. This study examined factors contributing to the utilization of intrauterine contraceptive devices (IUCDs) among women in Kabwe Central Province. Methodology: This was an analytical cross sectional study. Primary data was collected from 150 respondents in using simple random sampling method. Data was analysed using the statistical package of social sciences (SPSS) version 22. Chi-square test was used to test associations among the dependent and independent variables. Logistic regression analysis was conducted. The confidence interval was set at 95% and significant level was at 0.05%. Findings: The study found that 44% of the respondents had high level of knowledge about IUCD. About 28% of the respondents, said that they used IUCD because it maintains menstrual bleeding, 26% said that they used because IUCD it does not cause infections, and 19% said that they used IUCD because it does not migrate to other body parts. Majority (81%) of the respondents agreed with a statement that age contributes to underutilization of IUCD. About 77% of the respondents agreed with a statement that marital status contributes to underutilization of IUCD and 75% agreed with a statement that, education level contributes to underutilization of IUCD and was significant. Furthermore, 91% of the respondents agreed with a statement that lack of knowledge about IUCD contributes to underutilization of IUCD and 74% agreed with a statement that religion contributes to underutilization of IUCD. Age (p = 0.003), marital status (p = 0.002), education level (p = 0.003), and employment status (p = 0.02), were found to have a significant relationship with the utilization of IUCD. About 36% of the respondents said that knowledge or education affects the utilization of IUCD at a large extent. The study showed a positive relationship between the utilization of IUCD and all explanat

关键词： Utilization Intra Uterine Contraceptive Device Women Contraceptives Long Acting Reversible Contraceptive

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Mycorrhizal Fungi Spore Abundance in Old-Growth Forest Soil

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Open Journal of Soil Science 2023年第12期13卷 534-546页

作者： catherine MacKenzie Holland Jessique L. Haeft Department of Natural Resources & Environmental Managment Ball State University Muncie Indiana USA

Soil samples were collected from the base of Aplectrum hymale individuals to assess mycorrhizal spores abundance. The hypothesis that mycorrhizal spore abundance would increase with proximity to the plant was not supp... 详细信息

关键词： Mycorrhizal Fungi Glomus Spore Abundance Aplectrum hymale Orchid

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Influence of heterogeneity on rock strength and stiffness using discrete element method and parallel bond model

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Journal of Rock Mechanics and Geotechnical Engineering 2017年第4期9卷 575-584页

作者： Spyridon Liakas catherine O’Sullivan Charalampos Saroglou Arup Geotechnics Solihull UK Department of Civil & Environmental Engineering Imperial College London London UK Department of Geotechnical Engineering School of Civil Engineering National Technical University Athens Athens Greece

The particulate discrete element method(DEM) can be employed to capture the response of rock,provided that appropriate bonding models are used to cement the particles to each *** of laboratory tests are important to establish the extent to which those models can capture realistic rock *** the focus in such comparison studies has either been on homogeneous specimens or use of two-dimensional(2D) *** situ rock formations are often heterogeneous,thus exploring the ability of this type of models to capture heterogeneous material behavior is important to facilitate their use in design *** situ stress states are basically three-dimensional(3D),and therefore it is important to develop 3D models for this *** paper revisits an earlier experimental study on heterogeneous specimens,of which the relative proportions of weaker material(siltstone) and stronger,harder material(sandstone) were varied in a controlled *** a 3D DEM model with the parallel bond model,virtual heterogeneous specimens were *** overall responses in terms of variations in strength and stiffness with different percentages of weaker material(siltstone) were shown to agree with the experimental *** was also a good qualitative agreement in the failure patterns observed in the experiments and the simulations,suggesting that the DEM data enabled analysis of the initiation of localizations and micro fractures in the specimens.

关键词： Discrete element method(DEM) Heterogeneous rocks Strength and stiffness Parallel bond model

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