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特应性皮炎生物标志物鉴定及其免疫浸润研究

浙江科技学院学报 2023年第6期35卷 475-483页

作者：朱玉珍吴紫薇高贻宙 Ulf Meyer-hoffert 吴志宏浙江科技学院生物与化学工程学院杭州310023 德国基尔大学医学院皮肤学研究所德国基尔24105

【目的】探索与特应性皮炎(atopic dermatitis,AD)相关的生物标志物,并分析免疫细胞浸润在该疾病中的病理作用。【方法】首先从基因表达综合数据库(Gene Expression Omnibus,GEO)下载与AD相关的转录组测序数据,并利用RStudio软件对数据... 详细信息

【目的】探索与特应性皮炎(atopic dermatitis,AD)相关的生物标志物,并分析免疫细胞浸润在该疾病中的病理作用。【方法】首先从基因表达综合数据库(Gene Expression Omnibus,GEO)下载与AD相关的转录组测序数据,并利用RStudio软件对数据集进行差异表达分析;其次通过最小绝对收缩和选择算子回归分析(least absolute shrinkage and selection operator,LASSO)、支持向量机递归特征消除特征选择(support vector machine-recursive feature elimination,SVM-RFE)和随机森林(random forest,RF)3种机器学习算法,综合筛查与AD相关的生物标志物;再次构建受试者工作特征(receiver operating characteristic,ROC)曲线,评估潜在生物标志物的预测价值;最后通过估计RNA转录本的相对亚群(cell-type identification by estimating relative subsets of RNA transcripts,CIbERSORT)进行细胞类型识别,评估特应性皮炎的免疫细胞浸润情况,并分析潜在生物标志物与免疫浸润细胞之间的相关性。【结果】确定了2个与AD相关的生物标志物,即基质金属肽酶12(matrix metalloproteinase 12,MMP12)和WNT抑制因子1(WNT inhibitory factor 1,WIF1),并且通过ROC曲线说明了这两个基因的诊断价值较高;AD的发病机制与静息肥大细胞、滤泡辅助性T细胞、记忆CD4+T细胞、初始CD4+T细胞、树突状细胞、活化自然杀伤细胞、记忆b细胞及巨噬细胞相关。【结论】本研究结果为特应性皮炎的靶向治疗提供了新思路。

关键词：特应性皮炎生物信息学机器学习免疫浸润生物标志物

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效率金字塔

QTL analysis of soft scald in two apple populations

作者： (巴西)塔玛拉·迈尔斯(Tamara myles)

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Horticulture Research 2016年第1期3卷 117-123页

作者： Kendra A McClure Kyle M Gardner Peter MA Toivonen Cheryl R Hampson Jun Song Charles F Forney John DeLong Istvan Rajcan Sean myles Department of Plant and Animal Sciences Faculty of AgricultureDalhousie UniversityTruroB2N 5E3Nova ScotiaCanada Department of Plant Agriculture Crop Science BuildingUniversity of GuelphGuelphN1G 2W1OntarioCanada Agriculture and Agri-Food Canada Fredericton Research and Development CentreFrederictonE3B 4Z7New BrunswickCanada Agriculture and Agri-Food Canada Summerland Research and Development CentreSummerlandV0H 1Z0British ColumbiaCanada Agriculture and Agri-Food Canada Kentville Research and Development CentreKentvilleB4N 1J5Nova ScotiaCanada

The apple(Malus×domestica borkh.)is one of the world’s most widely grown and valuable fruit *** demand for apples year round,storability has emerged as an important consideration for apple breeding *** scald is a cold storage-related disorder that results in sunken,darkened tissue on the fruit *** breeders are keen to generate new cultivars that do not suffer from soft scald and can thus be marketed year *** breeding approaches are protracted and labor intensive,and therefore marker-assisted selection(MAS)is a valuable tool for *** advance MAS for storage disorders in apple,we used genotyping-by-sequencing(GbS)to generate high-density genetic maps in two F1 apple populations,which were then used for quantitative trait locus(QTL)mapping of soft *** total,900 million DNA sequence reads were generated,but after several data filtering steps,only 2%of reads were ultimately used to create two genetic maps that included 1918 and 2818 single-nucleotide *** QTL associated with soft scald were identified in one of the bi-parental populations originating from parent 11W-12-11,an advanced breeding *** study demonstrates the utility of next-generation DNA sequencing technologies for QTL mapping in F1 populations,and provides a basis for the advancement of MAS to improve storability of apples.

关键词： breeding cultivar apple

Genome-wide association studies in apple reveal loci of large effect controlling apple polyphenols

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Horticulture Research 2019年第1期6卷 444-455页

作者： Kendra AMcClure YuiHui Gong Jun Song Melinda Vinqvist-Tymchuk Leslie Campbell Palmer Lihua Fan Karen burgher-MacLellan ZhaoQi Zhang Jean-Marc Celton Charles FForney ZoëMigicovsky Sean myles Department of Plant and Animal Sciences Faculty of AgricultureDalhousie UniversityTruroNS B2N 5E3Canada Agriculture and Agri-Food Canada Kentville Research and Development CentreKentvilleNS B4N 1J5Canada College of Horticulture South China Agriculture UniversityGuangzhou 510642China IRHS Agrocampus-OuestINRAUniversitéd’AngersSFR 4207 QuaSaVBeaucouzéFrance

Apples are a nutritious food source with significant amounts of polyphenols that contribute to human health and wellbeing,primarily as dietary *** numerous pre-and post-harvest factors can affect the composition of polyphenols in apples,genetics is presumed to play a major role because polyphenol concentration varies dramatically among apple *** we investigated the genetic architecture of apple polyphenols by combining high performance liquid chromatography(HPLC)data with~100,000 single nucleotide polymorphisms(SNPs)from two diverse apple *** found that polyphenols can vary in concentration by up to two orders of magnitude across cultivars,and that this dramatic variation was often predictable using genetic markers and frequently controlled by a small number of large effect genetic *** GWAS,we identified candidate genes for the production of quercitrin,epicatechin,catechin,chlorogenic acid,4-O-caffeoylquinic acid and procyanidins b1,b2,and *** observation that a relatively simple genetic architecture underlies the dramatic variation of key polyphenols in apples suggests that breeders may be able to improve the nutritional value of apples through markerassisted breeding or gene editing.

关键词： effect apple cultivar

Patterns of genomic and phenomic diversity in wine and table grapes

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Horticulture Research 2017年第1期4卷 181-191页

作者： ZoëMigicovsky Jason Sawler Kyle M Gardner Mallikarjuna K Aradhya bernard H Prins Heidi R Schwaninger Carlos D bustamante Edward S buckler Gan-Yuan Zhong Patrick J brown Sean myles Department of Plant Food and Environmental SciencesFaculty of AgricultureDalhousie UniversityTruroB2N 5E3NSCanada Anandia Labs VancouverV6T 1Z4BCCanada Agriculture and Agri-Food Canada Fredericton Research and Development CentreFrederictonE3B 4Z7NBCanada United States Department of Agriculture-Agricultural Research Service National Clonal Germplasm RepositoryUniversity of CaliforniaDavis95616CAUSA United States Department of Agriculture Agricultural Research ServiceGrape Genetics Research UnitNew York State Agricultural Experiment StationCornell UniversityGeneva14456NYUSA Department of Genetics Stanford UniversityStanfordCA 94305USA Department of Plant breeding and Genetics Cornell UniversityIthaca14853NYUSA United States Department of Agriculture Agricultural Research ServicePlant Genetic Resources UnitNew York State Agricultural Experiment StationCornell UniversityGeneva14456NYUSA Department of Crop Science University of IllinoisUrbana61801ILUSA

Grapes are one of the most economically and culturally important crops worldwide,and they have been bred for both winemaking and fresh *** we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one of the world’s largest grape gene banks,the grape germplasm collection of the United States Department of *** find that phenological events throughout the growing season are correlated,and quantify the marked difference in size between table and wine *** pairing publicly available historical phenotype data with genome-wide polymorphism data,we identify large effect loci controlling traits that have been targeted during domestication and breeding,including hermaphroditism,lighter skin pigmentation and muscat *** for larger berries in table grapes was traditionally concentrated in geographic regions where Islam predominates and alcohol was prohibited,whereas wine grapes retained the ancestral smaller size that is more desirable for winemaking in predominantly Christian *** uncover a novel locus with a suggestive association with berry size that harbors a signature of positive selection for larger *** results suggest that religious rules concerning alcohol consumption have had a marked impact on patterns of phenomic and genomic diversity in grapes.

关键词： harbor religious crops

b-Aware试验中bIS监测对远期生存率的影响

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麻醉与镇痛 2012年第2期8卷 88-96页

作者： Kate Leslie, MbbS Paul S. myles Andrew Forbes Matthew T. V. Chan 何欣（译）翁莹琪（校）郭曲练（校） Department of Anaesthesia and Pain Management Royal Melbourne Hospital Department ofPharmacology University of Melbourne Department of Anaesthesia and Perioperative Medi- cine Alfred Hospital Academic board of Anaesthesia and Perioperative Medicine Monash U-niversity Melbourne National Health and Medical Research CouncilCanberra Department ofEpidemiology and Preventive Medicine Monash University Melbourne Australia Departmentof Anaesthesia and Intensive Care The Chinese University of Hong I（ong Hong I（ong People＇sRepublic of China

背景当使用脑电双频指数（bispectral index，bis）监测指导麻醉药用量时，通常仅需要较低剂量的镇静药，如果用较低剂量的麻醉药，术中低血压和器官毒性作用也许能避免。然而，这是否能减少严重并发症和术后死亡率还存争议。***试验将2... 详细信息

背景当使用脑电双频指数（bispectral index，bis）监测指导麻醉药用量时，通常仅需要较低剂量的镇静药，如果用较低剂量的麻醉药，术中低血压和器官毒性作用也许能避免。然而，这是否能减少严重并发症和术后死亡率还存争议。***试验将2463例术中知晓高危的患者随机分为bIS指导麻醉组和常规麻醉组。我们假设使用bIS指导麻醉组患者死亡、心肌梗死（myocardial infarction，MI）和卒中的风险都低于常规麻醉组患者。方法对术后30天尚存活的所有患者的医疗记录进行回顾，记录他们的死亡日期、死亡原因以及心肌梗死或卒中的发生情况．然后对所有存活的点者主牛行由话随访．本研究的主要终点是存活。结果随访时间中位值4．1年（全距：0－6．5年），参加试验的患者中有548例（22．2％）术后死亡，220例（8．9％）发生了心肌梗死，115例（4．7％）发生卒中。bIS监测组与常规麻醉组的死亡风险没有显著差异{危害比=0．86[95％可信区间（CI）：0．72-1．01]；P=0．07]。但是，倾向性评分分析显示，bIS值〈40、持续时间〉5分钟的患者与其他bIS监测组的患者相比，死亡的危害比为1．41（95％CI：1．02-1．95；P=0．039），并且心肌梗死的优势比（OR）为1．94（95％CI：1．12-3．35；P=0．01），卒中的优势比为3．24（95％CI：1.29-8．07；P=0．01）。结论在b-Aware试验患者中，采用了bIS指导麻醉且从未出现bIS值低于40并持续超过5分钟，与存活率的增加及并发症的减少相关。

关键词： bIS监测 e试验远期生存率麻醉药用量术后死亡率严重并发症心肌梗死脑电双频指数

Apple whole genome sequences:recent advances and new prospects

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Horticulture Research 2019年第1期6卷 1247-1270页

作者： Cameron P.Peace Luca bianco Michela Troggio Eric van de Weg Nicholas P.Howard Amandine Cornille Charles-Eric Durel Sean myles ZoëMigicovsky Robert J.Schaffer Evelyne Costes Gennaro Fazio Hisayo Yamane Steve van Nocker Chris Gottschalk Fabrizio Costa David Chagné Xinzhong Zhang Andrea Patocchi Susan E.Gardiner Craig Hardner Satish Kumar Francois Laurens Etienne bucher Dorrie Main Sook Jung Stijn Vanderzande Department of Horticulture Washington State UniversityPullmanWA 99164USA Computational biology Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Department of Genomics and biology of Fruit Crops Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Plant breeding Wageningen University and ResearchWageningen 6708PBThe Netherlands Department of Horticultural Science University of MinnesotaSt.PaulMN 55108USA Institut für biologie und Umweltwissenschaften Carl von Ossietzky Universität26129 OldenburgGermany GQE-Le Moulon Institut National de la Recherche AgronomiqueUniversity of Paris-SudCNRSAgroParisTechUniversitéParis-Saclay91190 Gif-sur-YvetteFrance Institut National de la Recherche Agronomique Institut de Recherche en Horticulture et SemencesUMR 134549071 BeaucouzéFrance Department of Plant Food and Environmental SciencesFaculty of AgricultureDalhousie UniversityTruroNS B2N 5E3Canada The New Zealand Institute for Plant and Food Research Ltd Motueka 7198New Zealand School of biological Sciences University of AucklandAuckland 1142New Zealand AGAP INRACIRADMontpellier SupAgroUniversity of MontpellierMontpellierFrance Plant Genetic Resources Unit USDA ARSGenevaNY 14456USA Laboratory of Pomology Graduate School of AgricultureKyoto UniversityKyoto 606-8502Japan Department of Horticulture Michigan State UniversityEast LansingMI 48824USA The New Zealand Institute for Plant and Food Research Ltd(Plant&Food Research) Palmerston North Research CentrePalmerston North 4474New Zealand College of Horticulture China Agricultural University100193 BeijingChina Agroscope 8820 WädenswilSwitzerland Queensland Alliance of Agriculture and Food Innovation University of QueenslandSt Lucia 4072Australia New Cultivar Innovation Plant and Food ResearchHavelock North 4130New Zealand Agroscope 1260 ChanginsSwitzerland

In 2010,a major scientific milestone was achieved for tree fruit crops:publication of the first draft whole genome sequence(WGS)for apple(Malus domestica).This WGS,v1.0,was valuable as the initial reference for sequence information,fine mapping,gene discovery,variant discovery,and tool development.A new,high quality apple WGS,GDDH13 v1.1,was released in 2017 and now serves as the reference genome for *** the past decade,these apple WGSs have had an enormous impact on our understanding of apple biological functioning,trait physiology and inheritance,leading to practical applications for improving this highly valued *** gene identities for phenotypes of fundamental and practical interest can today be discovered much more ***-wide polymorphisms at high genetic resolution are screened efficiently over hundreds to thousands of individuals with new insights into genetic relationships and ***-density genetic maps are constructed efficiently and quantitative trait loci for valuable traits are readily associated with positional candidate genes and/or converted into diagnostic tests for *** understand the species,geographical,and genomic origins of domesticated apple more precisely,as well as its relationship to wild *** WGS has turbo-charged application of these classical research steps to crop improvement and drives innovative methods to achieve more durable,environmentally sound,productive,and consumer-desirable apple *** review includes examples of basic and practical breakthroughs and challenges in using the apple *** for“what’s next”focus on necessary upgrades to the genome sequence data pool,as well as for use of the data,to reach new frontiers in genomics-based scientific understanding of apple.

关键词： breakthrough hundreds frontier

b-Aware研究中术中知晓患者的创伤后应激障碍

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麻醉与镇痛 2011年第5期7卷 68-74页

作者： Kate Leslie, MbbS, MD, MEpi, FANZCA Matthew T. V. Chan, MbbS, FANZCA Paul S. myles, MbbS, MD, MPH, FANZCA, FCARSCI, FRCA Andrew Forbes, MSc, PhD Timothy J. McCulloch, MbbS, bSc （Med）, FANZCA 谢珺田（译） Department of Anaesthesia and Pain Management Royal Melbourne Hospital Department of Pharmacology University of Melbourne Melbourne Australia Department of Anaesthesia and Intensive Care The Chinese University of Hong Kong Hong Kong People＇s Republic of China Department of Anaesthesia and Perioperative Medicine Alfred Hospital Academic board of Anaesthesia and Perioperative Medicine Monash University Melbourne National Health and Medical Research Council Canberra Department of Epidemiology and Preventive Medicaine Monash University Melbourne Department of Anaesthetics University of Sydney Department of Anaesthetics Royal Prince Alfred Hopital Sydney Australia 不详

背景术中知晓的长期影响差异巨大，部分患者没有任何长期影响，而另一些患者则可导致严重和持久的心理障碍。本研究比较了随机化b—Aware研究中，发生明确术中知晓患者与未发生明确术中知晓患者创伤后应激障碍（postlraumaticstressdiso... 详细信息

背景术中知晓的长期影响差异巨大，部分患者没有任何长期影响，而另一些患者则可导致严重和持久的心理障碍。本研究比较了随机化b—Aware研究中，发生明确术中知晓患者与未发生明确术中知晓患者创伤后应激障碍（postlraumaticstressdisorder，PTSD）的发生率。方法我们采用配对群体设计，旨在随访发生明确术中知晓的13例患者。每1例发生术中知晓的患者均按年龄、性别、手术类型、手术日期及手术医院配比4例对照。以临床术后应激障碍评分对每1例术中知晓及对照患者进行面对面的访谈。结果本研究收集数据资料的时间从2006年6月到2007年3月，随访的中位数时间5．3年（范围4．3-5．7年）。其间发生明确术中知晓的13例患者中6例去世，7例患者中的5例（71％）与25例对照中的3例（12％）在随访时点表现符合PTSD的诊断标准（校正的比值比=13．3[95％的可信区间为1．4-650]，P=0．02）。症状出现时间中位数时间为术后14天（范围7-243天），症状持续时间的中位数为4．7年（范围4．4-5．6年）。结论PTSD在b-Aware研究中有明确术中知晓的患者中常见而且持久。全麻下应强化预防患者术中知晓的措施。

关键词：创伤后应激障碍术中知晓患者手术类型 PTSD 中位数心理障碍数据资料

估测肾小球滤过率分级在评估静脉注射低渗对比剂肾病危险度中的应用价值

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国际医学放射学杂志 2013年第6期 572-572页

作者： M.S.Davenport S.Khalatbari R.H.Cohan J.R.Dillman J.D.myles J.H.Ellis 李亮 Department of Radiology University of Michigan Health System 1500 E Medical Center Dr B2-A209P Ann ArborMI 48103 USA

摘要目的通过CT增强前对估测肾功能稳定病人肾小球滤过率(eGFR)分级,评估静脉注射(IV)低渗透压碘对比剂(LOCM)CT增强检查后急性肾损伤(AKI)的危险度。材料

关键词：肾小球 AKI 肾单位静脉注射滤过危险度危险系数对比剂肾病