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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： helen m.Knight merve DemirbugenÖz Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular GeneticsSchool of Life SciencesUniversity of NottinghamNottinghamUK Department of Pharmaceutical Toxicology Faculty of PharmacyAnkara UniversityAnkaraTurkey

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying *** of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding *** emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these *** processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of *** this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive *** studies first identified mutations within FmR1 to cause intellectual disability Fragile X syndromes several years before FmR1 was identified as an m^(6)A RNA reader ***,familial mutations within the m^(6)A writer gene mETTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development ***,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain ***,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are *** parahippocampal brain tissue,m^(6)A modification is enri

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Adiponectin signalling in bone homeostasis,with age and in disease

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Bone Research 2021年第1期9卷 15-25页

作者： jonathan W.Lewis james R.Edwards amy j.naylor.helen m.mcgettr.ck Rheumatology Research Group Institute of Inflammation and AgeingUniversity of BirminghamBirmingham B152TTUK Ageing&Regeneration Research Group Botnar Research CentreUniversity of OxfordOxford OX37LDUK

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin *** the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and *** studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of ***,human studies often demonstrate an inverse relationship between adiponectin concentration and bone ***,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional *** such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in *** this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in ***,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.

关键词： homeostasis metabolism consequences

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Storylines of family medicine Ⅳ:perspectives on practice—lenses of appreciation

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Family medicine and Community Health 2024年第S3期12卷 33-42页

作者： William B Ventres Leslie A Stone Radeeb Akhtar jeffrey m Ring Lucy m Candib Erick messias Ronald m Epstein marc Tunzi amy L Lee Christopher P morley Carina m Brown David Slawson jill Konkin David G Campbell Ian Couper Susan Williams Robert Brooks Lucie Walters Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family medicine and Community Health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Independent Health Psychologist Los AngelesCaliforniaUSA Family medicine and Community Health UMass Chan Medical SchoolWorcesterMassachusettsUSA Psychiatry and Behavioral Neurosciences Saint Louis University School of MedicineSaint LouisMissouriUSA Family medicine University of Rochester Medical CenterRochesterNew YorkUSA Family medicine Residency Program Natividad Medical CenterSalinasCaliforniaUSA Family medicine Tufts University School of MedicineBostonMassachusettsUSA Public Health and Preventive medicine SUNY Upstate Medical UniversitySyracuseNew YorkUSA Cone Health Family medicine Residency The University of North Carolina School of MedicineGreensboroNorth CarolinaUSA Family medicine Atrium HealthCharlotteNorth CarolinaUSA Family medicine University of Alberta Faculty of Medicine&DentistryEdmontonAlbertaCanada Cunninghame Arm medical Centre Australian College of Rural and Remote MedicineLakes EntranceQueenslandAustralia Ukwanda Centre for Rural Health Stellenbosch University Faculty of Medicine and Health SciencesCape TownWestern CapeSouth Africa Adelaide Rural Clinical School The University of AdelaideAdelaideSouth AustraliaAustralia Department of Rural Health Broken Hill UniversityBroken HillNew South WalesAustralia Adelaide Rural Clinical School The University of Adelaide Faculty of Health and Medical SciencesMount GambierSouth AustraliaAustralia

Storylines of Family medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’may readers nurture their curiosity through these essays.

关键词： thematic illustration doctor

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中草药 2024年第1期55卷 181-189页

作者：崔高畅 amy Yi Hsan Saik 张新慧马玉玮杨早东姑阿都拉曼大学m.Kandiah医学与健康科学学院雪兰莪加影43000 宁夏医科大学药学院宁夏银川750004

目的利用生物信息学方法筛选湿性年龄相关性黄斑变性(wet age-related macular degeneration,w AmD)的氧化应激相关差异表达基因及靶向中药,以期为wAmD的预防和治疗提供新思路。方法从GEO数据库中筛选数据集,利用R软件limma包筛选差异基... 详细信息

目的利用生物信息学方法筛选湿性年龄相关性黄斑变性(wet age-related macular degeneration,w AmD)的氧化应激相关差异表达基因及靶向中药,以期为wAmD的预防和治疗提供新思路。方法从GEO数据库中筛选数据集,利用R软件limma包筛选差异基因,从Genecard数据库筛选氧化应激差异基因,并利用韦恩图得到共有基因。应用metascape对氧化应激差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析,并通过String数据库构建蛋白质相互作用(protein-protein interaction,PPI)网络,再通过Cytoscape软件筛选出wAmD中氧化应激的关键(Hub)基因。采用GSE103060数据集验证Hub基因的差异表达。利用Coremine medical预测靶向中药。结果经筛选共得到差异表达基因1874个,其中上调基因747个,下调基因1127个。KEGG富集分析表明,差异表达基因主要富集于细胞外基质受体相互作用、黏附斑激酶通路、河马(Hippo)信号通路、晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路、钙信号通路和磷脂酰肌醇-3-羟激酶(phosphatidylinositol-3-hydroxykinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路。通过PPI网络筛选得到与w AmD氧化应激密切相关的8个Hub基因,分别为IL6、EGFR、HIF1A、APOE、FN1、PPARG、EDN1和NGF。最后在GSE103060数据集中验证了以上Hub基因的显著差异表达。利用Coremine medical预测人参、黄芪、枸杞子、丹参、银杏叶等可作为预防或治疗wAmD的靶向中药。结论通过对w AmD芯片的挖掘和生物信息分析,差异基因主要富集于氧化应激的相关通路与wAmD的氧化应激相关基因引起的。防治wAmD的首选中药为人参、黄芪、枸杞子、丹参和银杏叶等26种。这将对理解和探索wAmD的中医药防治策略有重要意义。

关键词：生物信息学湿性年龄相关性黄斑变性氧化应激中药筛选人参黄芪枸杞子丹参银杏叶

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Impower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen jianxing He jifeng Feng Yiping Zhang Liyan jiang Hongming Pan jianhua Chang jian Fang amy Cai Lilian Bu jane Shi jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: Impower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab *** as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian ***: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT ***: median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel ***: Impower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

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Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

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World journal of Gastroenterology 2009年第38期15卷 4741-4744页

作者： Hugh j Freeman helen R Gillett Peter m Gillett joel Oger Department of medicine (Gastroenterology and Neurology) University of British Columbia

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.

关键词： Acetylcholine receptor antibodies Celiacdisease myasthenia gravis Transglutaminase antibodies

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SPECIAL ISSUE EDITORIAL ON mASS CUSTOmIZATION AND SUSTAINABLE VALUE SYSTEmS

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journal of Systems Science and Systems Engineering 2011年第3期20卷 257-259页

作者： amy j.C.TRAPPEY P.m.WOGNUm Charles V.TRAPPEY Department of Industrial Engineering and Engineering management National Tsing Hua University Department of Social Sciences Wageningen UniversityThe Netherlands Department of management Science National Chiao Tung University

Today, new products or services must be designed to satisfy ever changing consumer demand by companies to remain competitive. mass customization, personalized services, and integration of information and decision processes are needed to produce an increasingly diverse range of products and services. At the same time efficiency as well as flexibility of design and production processes need to be improved.

关键词： SPECIAL ISSUE EDITORIAL ON mASS CUSTOmIZATION AND SUSTAINABLE VALUE SYSTEmS

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Bridging the gap——Immune cells that can repair nerves

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Cellular & molecular Immunology 2021年第4期18卷 784-786页

作者： helen m.mcgettr.ck Institute of Inflammation and Aging University of BirminghamBirminghamUK

Immunity is critical for survival in a world plagued by *** that of most military operations,the strategy of the immune system is based on acceptable losses:determining the maximal amount of damage to uninfected tissues that is necessary to defeat or entrap any invading *** characteristic has devastating consequences for patients with immune-mediated diseases,including many neurological conditions.

关键词： Immune diseases damage

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Dietary supplementation of Bacillus subtilis influenced intestinal health of weaned pigs experimentally infected with a pathogenic E. coli

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journal of Animal Science and Biotechnology 2019年第4期10卷 969-980页

作者： Kwangwook Kim Yijie He Xia Xiong amy Ehrlich Xunde Li helen Raybould Edward R.Atwill Elizabeth A.maga jens jΦrgensen Yanhong Liu Department of Animal Science University of CaliforniaDavisCA 95616USA School of Veterinary medicine University of CaliforniaDavisCA 95616USA Chr.Hansen A/S HoersholmDenmark

Background: There is growing evidence to support the beneficial effects of supplementing direct-fed microbials(DFm) on performance, health status, and immune responses of weaned pigs. Therefore, the objective of this study was to investigate dietary supplementation of Bacillus subtilis(DSm 25841) on growth performance, diarrhea, gut permeability and immunity of weaned pigs experimentally infected with a pathogenic F-18 Escherichia coli(E. coli).Results: The F18 E. coli infection reduced(P mance and intestinal villi height, whereas increased(P meability in the jejunum compared with non-challenged control. Supplementation of Bacillus subtilis linearly enhanced average daily gain of E. coli infected pigs from d 0 to 5 post-inoculation(PI)(P mentation of high dose of Bacillus subtilis reduced(P meability on d 5 and d11 PI compared with the E. coli infected pigs fed with control diet. E. coli infection up-regulated(P m RNA expression of SLC5 A10(soluble carrier family 5 member 10) and mUC2(mucin 2) on d 5 PI, but down-regulated(P mUC2, and CLDN1 on d 11 PI in jejunal mucosa when pigs were fed with the control diet. Supplementation of Bacillus subtilis linearly up-regulated(P m RNA expression of CFTR and ZO1 on d 5 PI and SLC5 A10 and mUC2 on d 11 PI in jejunal mucosa of E. coli infected pigs. In addition, E. coli infection increased(P m RNA expression of several immune genes(IL1 A, IL1 B, and IL7 on d 5 PI, and IL1 B, IL6, IL7, and TNF on d 11 PI) in the ileal mucosa of weaned pigs. Inclusion of Bacillus subtilis to control diet linearly down-regulated gene expression of IL1 A on d 5 PI(P = 0.07) and IL6 on d 11 PI(P mucosa of E. coli infected ***: Supplementation of Bacillus subtilis(DSm 25841) enhanced growth r

关键词： Bacillus subtilis Growth rate Gut barrier function Intestinal inflammation Pathogenic Escherichia coli Weaned pigs

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Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2

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Cellular & molecular Immunology 2022年第9期19卷 1067-1069页

作者： Prerna Arora amy Kempf Inga Nehlmeier Luise Graichen Sebastian Schulz Anne Cossmann Alexandra Dopfer-jablonka martin S.Winkler Hans-martin jäck Georg m.N.Behrens Stefan Pöhlmann markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Division of molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany Centre for Individualised Infection medicine(Ciim) HannoverGermany Department of Anesthesiology University of Göttingen Medical CenterGöttingenGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany

The SARS-CoV-2 spike(S)protein engages ACE2 for cell entry,and the S protein/ACE2 interface is an important target for neutralizing *** the course of the COVID-19 pandemic,SARS-CoV-2 variants have emerged that harbor mutations in the S protein,which confer neutralization resistance and allow viral spread in immunologically nonnaive *** most prominent example is the highly mutated Omicron variant,which infects convalescent or vaccinated individuals with unprecedented efficiency[1,2].

关键词： ACE2 harbor neutral

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