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Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection

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Signal Transduction and Targeted Therapy 2021年第7期6卷 2154-2163页

作者： Qinqin Pu Kai Guo Ping Lin Zhihan Wang Shugang Qin Pan Gao Colin Combs Nadeem Khan Zhenwei Xia Min Wu department of Biomedical Sciences School of Medicine and Health SciencesUniversity of North DakotaGrand ForksNDUSA department of Neurology University of MichiganAnn ArborMlUSA Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqingChina Biological Science Research Center Southwest UniversityChongqing 400716China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengduSichuanChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuanChina department of pediatrics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China

Bitter receptors function primarily in sensing taste,but may also have other functions,such as detecting pathogenic organisms due to their agile response to foreign *** mouse taste receptor type-2 member 138(TAS2R138)is a member of the G-protein-coupled bitter receptor family,which is not only found in the tongue and nasal cavity,but also widely distributed in other organs,such as the respiratory tract,gut,and *** its diverse functions,the role of TAS2R138 in host defense against bacterial infection is largely ***,we show that TAS2R138 facilitates the degradation of lipid droplets(LDs)in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG(peroxisome proliferator-activated receptor gamma)antagonist:A/-(3-oxododecanoyl)-L-homoserine lactone(AHL-12),which coincidently is a virulence-bound signal produced by this bacterium(***).The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2(perilipin-2).Subsequently,the TAS2R138-AHL-12 complex targets LDs to augment their degradation,and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local *** findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against *** infection.

关键词： thereby maintain migrate

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Region-specific microRNA signatures in the human epididymis

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Asian Journal of Andrology 2018年第6期20卷 539-544页

作者： James A Browne Shih-Hsing Leir Scott E Eggener ann Harris department of Genetics and Genome Sciences Case Western Reserve UniversityClevelandOH 44106USA Human Molecular Genetics Program Lurie Children＇s Research CenterChicagoIL 60614USA department of pediatrics Northwestern University Feinberg School of MedicineChicagoIL 60611USA Section of Urology University of Chicago Medical CenterChicagoIL 60611USA.

The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.

关键词： caput cauda corpus human epididymis microRNA

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Targeting multiple signaling pathways:the new approach to acute myeloid leukemia therapy

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Signal Transduction and Targeted Therapy 2021年第1期6卷 41-69页

作者： Jenna LCarter Katie Hege Jay Yang Hasini AKalpage Yongwei Su Holly Edwards Maik Hüttemann Jeffrey WTaub Yubin Ge Cancer Biology Graduate Program Wayne State University School of MedicineDetroitMIUSA MD/PhD Program Wayne State University School of MedicineDetroitMIUSA department of Oncology Wayne State University School of MedicineDetroitMIUSA Molecular Therapeutics Program Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitMIUSA Center for Molecular Medicine and Genetics Wayne State University School of MedicineDetroitMIUSA National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and EngineeringThe Ministry of EducationSchool of Life SciencesJilin UniversityChangchunChina Division of Pediatric Hematology/Oncology Children’s Hospital of MichiganDetroitMIUSA department of pediatrics Wayne State University School of MedicineDetroitMIUSA

Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in *** this,very little improvement in survival rates has been achieved over the past few *** is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 *** the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and *** we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc *** has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML *** addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival *** also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC *** comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.

关键词： myeloid approach approval

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Osteoblasts dictate B lymphocyte commitment and differentiation

Osteoblasts dictate B lymphocyte commitment and differentiat...

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中国遗传学会“发育、遗传和疾病”研讨会

作者： Younghun Jung Nacksung Kim Gerard J.Joe Russell Taichman Stephen G.Emerson department of Periodontics Prevention & Geriatrics University of Michigan School of Dentistry ann Arbor MI 48109-1078. Abramson Cancer Center University of Pennsylvania School of Medicine Philadelphia PA 19104 departments of Medicine and pediatrics University of Pennsylvania School of Medicine Philadelphia PA 19104 department of Periodontics Prevention & Geriatrics University of Michigan School of Dentistry ann Arbor MI 48109-1078. departments of Medicine and pediatrics and Abramson Cancer Center University of Pennsylvania School of Medicine Philadelphia PA 19104.

It has long been hypothesized that early B lymphopoiesis in mammals is induced within the bone marrow(BM)microenvironment,but which cells specifically constitute this B cell niche is not known. Previous studies identified the osteoblast as an essential component of the BM niche for hematopoietic stem cells(HSCs)1,*** we show that selective depletion of endosteal osteoblasts in Col2.3Δ-TK transgenic mice leads to the acute loss of pre-pro-B and pro-B cells from BM,preceding a decline in HSCs. Conversely,purified osteoblasts support the differentiation of early B cell precursors from Lin-Sca-1+ primitive BM cells in vitro,inducing their development into IgM+ immature B ***-induced B lymphopoiesis is mediated via VCAM-1,SDF-1 and IL-7 signaling,which is stimulated by administration of parathyroid hormone(PTH).Thus,osteoblasts are necessary and sufficient for murine B cell commitment and maturation,and thereby constitute the cellular homologue of the avian Bursa of Fabricious.

关键词： Osteoblasts dictate B lymphocyte commitment and differentiation

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Azithromycin Exerts Bactericidal Activity and Enhances Innate Immune Mediated Killing of MDR Achromobacter xylosoxidans

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Infectious Microbes & Diseases 2020年第1期2卷 10-17页

作者： Erlinda R.Ulloa Armin Kousha Hannah Tsunemoto Joe Pogliano Carmelo Licitra John J.LiPuma George Sakoulas Victor Nizet Monika Kumaraswamy Collaborative to Halt Antibiotic-Resistant Microbes(CHARM) University of California San DiegoLa JollaCA 92093USA department of pediatrics University of California San DiegoLa JollaCA 92093USA Division of Infectious Disease Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA department of Basic Sciences and Aquatic Medicine Norwegian University of Life SciencesOsloNorway Division of Biological Sciences University of California San DiegoLa JollaCA 92093USA Infectious Diseases Orlando Health Medical GroupOrlandoFL 32806USA department of pediatrics University of MichiganAnn ArborMI 48109USA Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCA 92093USA Infectious Diseas Section VA San Diego Healthcare SystemSan DiegoCA 92161USA department of Medicine University of California San DiegoLa JollaCA 92093USA.

Azithromycin(AZM),the most commonly prescribed antibiotic in the United States,is thought to have no activity against multidrugresistant Gram-negative pathogens such as Achromobacter xylosoxidans(AX)per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton *** we provide the first report of AZM bactericidal activity against carbapenemresistant isolates of AX,with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human *** pharmaceutical activity,evident in eukaryotic tissue culture media,is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood,serum,and ***,AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable *** an illustrative case,AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis,sternal osteomyelitis,and aortic graft *** study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents,adversely affecting patient *** conclude that AZM merits further exploration in the treatment of drug-resistant AX *** approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered,especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality.

关键词： Achromobacter xylosoxidans antimicrobial susceptibility testing azithromycin treatment host defense multidrug resistance

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Bietti’s crystalline dystrophy in an African American patient: an unusual racial demographic for a condition more common in individuals of East Asian descent

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International Journal of Ophthalmology(English edition) 2021年第8期14卷 1291-1292页

作者： Virang Kumar Vikram Brar Jordyn Prell ann Jewell Natario Couser Virginia Commonwealth University School of Medicine RichmondVA 23298USA department of Ophthalmology Virginia Commonwealth University School of MedicineRichmondVA 23298USA department of Human and Molecular Genetics Virginia Commonwealth University School of MedicineRichmondVA 23298USA department of pediatrics Virginia Commonwealth University School of MedicineRichmondVA 23298USA

Dear Editor,The study outlining the manifestations of Bietti’s crystalline dystrophy(BCD)in five Chinese patients offered insights into common disease-causing variants associated with Chinese patients as well as a novel mutation[1].This genetic condition is commonly reported among East Asian populations and to some extent Mediterranean populations[2].

关键词： dystrophy crystalline condition

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Detailed description of Division I ice hockey concussions:Findings from the NCAA and department of Defense CARE Consortium

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Journal of Sport and Health Science 2021年第2期10卷 162-171页

作者： Kathryn L.Van Pelt Jaclyn B.Caccese James T.Eckner Margot Putukian MAlison Brooks Kenneth L.Cameron Megan N.Houston Matthew A.Posner Jonathan C.Jackson Gerald T.McGinty Cameron J.Hillis Thomas W.McAllister Michael A.McCrea Steven P.Broglio Thomas A.Buckley Sanders-Brown Center on Aging University of KentuckyLexingtonKY 40536-0230USA College of Medicine School of Health and Rehabilitation Sciences The Ohio State UniversityColumbusOH 43210USA department of Physical Medicine and Rehabilitation Michigan MedicineUniversity of MichiganAnn ArborMI 48108USA University Health Services Princeton UniversityMcCosh Health CenterPrincetonNJ 08544USA department of Orthopedics and Rehabilitation Department of PediatricsUniversity of Wisconsin School of Medicine and Public HealthMadisonWI 53705-2281USA Keller Army Hospital United States Military AcademyWest PointNY 10996USA th Medical Group United States Air Force AcademyColorado SpringsCO 80840-4000USA Sports Medicine Athletic DepartmentUnited States Air Force AcademyU.S.Air Force AcademyCO 80840-9500USA Novant Health Charlotte Independence Soccer ClubCorneliusNC 28031USA department of Psychiatry Indiana UniversityIndianapolisIN 46202USA Neurosurgery Medical College of WisconsinMilwaukeeWI 53226USA Michigan Concussion Center University of MichiganAnn ArborMI 48109USA Kinesiology and Applied Physiology University of DelawareNewarkDE 19713USA

Objective:Since concussion is the most common injury in ice hockey,the objective of the current study was to elucidate risk factors,specific mechanisms,and clinical presentations of concussion in men’s and women’s ice ***:Ice hockey players from 5 institutions participating in the Concussion Assessment,Research,and Education Consortium were eligible for the current *** who sustained a concussion outside of this sport were *** were 332(250 males,82 females)athletes who participated in ice hockey,and 47(36 males,11 females)who sustained a ***:Previous concussion(odds ratio(OR)=2.00;95%confidence interval(95%CI):1.02‒3.91)was associated with increased incident concussion odds,while wearing a mouthguard was protective against incident concussion(OR=0.43;95%CI:0.22‒0.85).Overall,concussion mechanisms did not significantly differ between *** were specific differences in how concussions presented clinically across male and female ice hockey players,***(9.09%)were less likely than males(41.67%)to have a delayed symptom onset(p=0.045).Additionally,females took significantly longer to reach asymptomatic(p=0.015)and return-to-play clearance(p=0.005).Within the first 2 weeks post-concussion,86.11%of males reached asymptomatic,while only 45.50%of females reached the same phase of *** males(91.67%)were cleared for return to play within 3 weeks of their concussion,compared to less than half(45.50%)of ***:The current study proposes possible risk factors,mechanisms,and clinical profiles to be validated in future concussions studies with larger female sample *** specific risk factors,concussion mechanisms,and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies.

关键词： Concussion risk Injury mechanism Recovery

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Semistructured interviewing in primary care research:a balance of relationship and rigour

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Family Medicine and Community Health 2019年第2期7卷 30-37页

作者： Melissa DeJonckheere Lisa M Vaughn department of Family Medicine University of MichiganAnn ArborMichiganUSA department of pediatrics University of Cincinnati College of MedicineCincinnatiOhioUSA Division of Emergency Medicine Cincinnati Children's Hospital Medical CenterCincinnatiOhioUSA

Semistructured in-depth interviews are commonly used in qualitative research and are the most frequent qualitative data source in health services *** method typically consists of a dialogue between researcher and participant,guided by a flexible interview protocol and supplemented by follow-up questions,probes and *** method allows the researcher to collect open-ended data,to explore participant thoughts,feelings and beliefs about a particular topic and to delve deeply into personal and sometimes sensitive *** purpose of this article was to identify and describe the essential skills to designing and conducting semistructured interviews in family medicine and primary care research *** reviewed the literature on semistructured interviewing to identify key skills and components for using this method in family medicine and primary care research ***,semistructured interviewing requires both a relational focus and practice in the skills of *** include:(1)determining the purpose and scope of the study;(2)identifying participants;(3)considering ethical issues;(4)planning logistical aspects;(5)developing the interview guide;(6)establishing trust and rapport;(7)conducting the interview;(8)memoing and reflection;(9)analysing the data;(10)demonstrating the trustworthiness of the research;and(11)presenting findings in a paper or *** interviews provide an effective and feasible research method for family physicians to conduct in primary care research *** using semistructured interviews for data collection should take on a relational focus and consider the skills of interviewing to ensure *** interviewing can be a powerful tool for family physicians,primary care providers and other health services researchers to use to understand the thoughts,beliefs and experiences of *** the utility,semistructured interviews can be intimidating and challenging for

关键词： interview qualitative thoughts

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男性健康离不开为人父

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美国医学会杂志（中文版） 2007年第2期26卷 109-112页

作者： Craig F. Garfield Elizabeth Clark-Kauffman Matthew M. Davis 张鹏（译） department of pediatrics Evanston Northwestern Healthcare Research Institute and Feinberg School of MedidneDepartment of Pediatrics Northwestern University Evanston Ill and Child Health Evaluation and Research Unit department of pediatrics Northwestern University Evanston Ill and Child Health Evaluation and Research Unit departments of pediatrics and Internal Medicine and Gerald R. Ford School of Public Policy University of Michigan Ann Arbor 不详

现代医学已开始逐步了解男性健康现象。“男性健康”这一理念有别于“女性健康”，它往往立足于以下方面存在的性别差异：生殖系统疾病、心血管病等部分受到性激素影响的疾病以及预期寿命（男性〈女性）。本文抓住男性健康的概念，对为... 详细信息

现代医学已开始逐步了解男性健康现象。“男性健康”这一理念有别于“女性健康”，它往往立足于以下方面存在的性别差异：生殖系统疾病、心血管病等部分受到性激素影响的疾病以及预期寿命（男性〈女性）。本文抓住男性健康的概念，对为人父这一许多男性生活中的重要环节进行了概述。

关键词：男性健康生殖系统疾病女性健康现代医学性别差异预期寿命心血管病性激素

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Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents

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四川生理科学杂志 2021年第11期43卷 1723-1723页

作者： Samantha M Olson From the Covid-19 Response Team Centers for Disease Control and Prevention (S.M.O. A.M.P. L.D.Z. A.P.C. M.M.P.) and the Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta and the Department of Pediatrics Emory University School of Medicine (S.K.) - both in Atlanta the department of Anesthesiology Critical Care and Pain Medicine Boston Children's Hospital (M.M.N. A.G.R.) and the Departments of Anaesthesia and Pediatrics Harvard Medical School (A.G.R.) - both in Boston the Division of Pediatric Infectious Diseases Department of Pediatrics Vanderbilt University Medical Center Nashville (N.B.H.) the department of pediatrics Baylor College of Medicine Immunization Project Texas Children's Hospital Houston (J.A.B. L.C.S.) and the Department of Pediatrics Division of Critical Care Medicine University of Texas Southwestern Children's Medical Center Dallas Dallas (M.M.) the Division of Infectious Diseases Children's Hospital Los Angeles and Departments of Pediatrics and Molecular Microbiology and Immunology University of Southern California Los Angeles (P.S.P.) the Division of Pediatric Hospital Medicine UC San Diego-Rady Children's Hospital San Diego (M.A.C.) the Division of Critical Care Medicine UCSF Benioff Children's Hospital Oakland (N.Z.C.) and the Department of Pediatrics Divisions of Critical Care Medicine and Allergy Immunology and Bone Marrow Transplant University of California San Francisco San Francisco (M.S.Z.) - all in California Section of Pediatric Critical Care Department of Pediatrics Arkansas Children's Hospital Little Rock (K.I.) the department of pediatrics University of North Carolina at Chapel Hill Children's Hospital Chapel Hill (T.C.W. S.P.S.) the department of pediatrics Section of Critical Care Medicine University of Colorado School of Medicine and Children's Hospital Colorado Aurora (A.B.M.) the Division of Pediatric Critical Care Medicine Medical University of South Carolina Charleston (E.H.M.) the department of

Background:The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019(Covid-19)caused by the B.1.617.2(delta)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of ***:We used a case-control,test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization,admission to an intensive care unit(ICU),the use of life-supporting interventions(mechanical ventilation,vasopressors,and extracorporeal membrane oxygenation),or *** July 1 and October 25,2021,we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 *** estimated vaccine effectiveness by comparing the odds of antecedent full vaccination(two doses of BNT162b2)in case patients as compared with two hospitalbased control groups:patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2(test-negative)and patients who did not have Covid-19-like symptoms(syndrome-negative).

关键词： vaccine doses acute

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