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A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

Bone Research 2020年第2期8卷 157-168页

作者： Tobias Schwerd Freia Krause Stephen R.F.Twigg Dominik Aschenbrenner Yin-Huai Chen Uwe Borgmeyer Miryam Müller Santiago Manrique Neele Schumacher Steven A.Wall Jonathan Jung Timo Damm Claus-Christian Glüer Jürgen Scheller Stefan Rose-John e.yvonne jones Arian Laurence Andrew O.M.Wilkie Dirk Schmidt-Arras Holm H.Uhlig Translational Gastroenterology Unit John Radcliffe HospitalUniversity of OxfordOxfordUK Department of Pediatrics Dr von Hauner Children’s HospitalLMU MunichMunichGermany Christian-Albrechts-University Kiel Institute of BiochemistryKielGermany Clinical Genetics Group MRC Weatherall Institute of Molecular MedicineUniversity of OxfordJohn Radcliffe HospitalOxfordUK Center for Molecular Neurobiology Hamburg(ZMNH) University Medical Center Hamburg-EppendorfHamburgGermany Division of Structural Biology Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK Craniofacial Unit Department of Plastic and Reconstructive SurgeryOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxfordUK Section Biomedical Imaging Department of Radiology and NeuroradiologyUniversity Medical Center Schleswig-HolsteinKielGermany Institute of Biochemistry and Molecular Biology Ⅱ Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany Department of Paediatrics University of OxfordOxfordUK NIHR Oxford Biomedical Research Centre OxfordUK The Beatson Institute for Cancer Research GlasgowUK School of Medicine University of GlasgowGlasgowUK

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

关键词： IL11 cytokine facial

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Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna e.Davies Mark G.jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(eCM)***-ing of disease pathogenesis remains limited and has prevented the development of effective *** an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully *** human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(eMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory *** review will focus on the role of eMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis epithelial-mesenchymal transition(eMT) Crosstalk

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.ewing Donna e.Davies Mark G.jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(eMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces eMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce eMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk eMT LKB1 Pulmonary fibrosis

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An alfalfa MYB-like transcriptional factor MsMYBH positively regulates alfalfa seedling drought resistance and undergoes MsWAV3-mediated degradation

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Journal of Integrative Plant Biology 2024年第4期66卷 683-699页

作者： Kun Shi Jia Liu Huan Liang Hongbin Dong Jinli Zhang Yuanhong Wei Le Zhou Shaopeng Wang Jiahao Zhu Mingshu Cao Chris S.jones Dongmei Ma Zan Wang College of Grassland Science and Technology China Agricultural UniversityBeijing 100193China Institute of Animal Sciences Chinese Academy of Agricultural SciencesBeijing 100193China AgResearch Grasslands Research Centre Palmerston North 4442New Zealand International Livestock Research Institute Nairobi 00100Kenya School of ecology and environment Ningxia UniversityYinchuan 750021China

Drought is a major threat to alfalfa(Medicago sativa L.)*** discovery of important alfalfa genes regulating drought response will facilitate breeding for drought-resistant alfalfa ***,we report a genome-wide association study of drought resistance in *** identified and functionally characterized an MYB-like transcription factor gene(MsMYBH),which increases the drought resistance in *** with the wild-types,the biomass and forage quality were enhanced in MsMYBH overexpressed *** RNA-seq,proteomics and chromatin immunoprecipitation analysis showed that MsMYBH can directly bind to the promoters of MsMCP1,MsMCP2,MsPRX1A and MsCARCAB to improve their *** outcomes of such interactions include better water balance,high photosynthetic efficiency and scavenge excess H_(2)O_(2)in response to ***,an e3 ubiquitin ligase(MsWAV3)was found to induce MsMYBH degradation under long-term drought,via the 26S proteasome ***,variable-number tandem repeats in MsMYBH promoter were characterized among a collection of germplasms,and the variation is associated with promoter ***,our findings shed light on the functions of MsMYBH and provide a pivotal gene that could be leveraged for breeding drought-resistant *** discovery also offers new insights into the mechanisms of drought resistance in alfalfa.

关键词： alfalfa drought resistance e3 ubiquitin ligase MsMYBH MsWAV3 MYB-like transcriptional factor

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There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

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Journal of Sport and Health Science 2024年第4期13卷 521-536页

作者： Helder S.Lopes Marina C.Waiteman Liliam B.Priore Neal R.Glaviano David M.Bazett-jones Ronaldo V.Briani Fabio M.Azevedo School of Science and Technology Physical Therapy DepartmentSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Department of Kinesiology College of AgricultureHealth and Natural ResourcesUniversity of ConnecticutStorrsCT 06269USA School of exercise and Rehabilitation Sciences College of Health and Human ServicesUniversity of ToledoToledoOH 43606USA

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and *** the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and *** systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee ***:Five databases(MeDLINe,embase,CINAHL,SPORTDiscus,and Web of Science)were searched from inception to September *** studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were ***-analyses for each knee disorder were ***-level certainty was assessed using the Grading of Recommendations Assessment,Development,and evaluation,and evidence gap maps were ***:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were *** with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SMD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SMD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SMD=-0.48,95%CI:-0.82 to-0.14),concentric(SMD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SMD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar *** with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SMD=-0.76,95%CI:-1.15 to-0.36).evidence gap maps identified insufficient evidence for chondromalacia patel

关键词： Chondromalacia patellae Knee flexors Knee osteoarthritis Patellar tendinopathy Patellofemoral pain

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Urban heat mitigation by green and blue infrastructure:Drivers,effectiveness,and future needs

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The Innovation 2024年第2期5卷 145-166页

作者： Prashant Kumar Sisay e.Debele Soheila Khalili Christos H.Halios Jeetendra Sahani Nasrin Aghamohammadi Maria de Fatima Andrade Maria Athanassiadou Kamaldeep Bhui Nerea Calvillo Shi-Jie Cao Frederic Coulon Jill L.edmondson David Fletcher edmilson Dias de Freitas Hai Guo Matthew C.Hort Madhusudan Katti Thomas Rodding Kjeldsen Steffen Lehmann Giuliano Maselli Locosselli Shelagh K.Malham Lidia Morawska Rajan Parajuli Christopher D.F.Rogers Runming Yao Fang Wang Jannis Wenk Laurence jones Global Centre for Clean Air Research(GCARe) School of SustainabilityCivil and Environmental EngineeringFaculty of Engineering and Physical SciencesUniversity of SurreyGuildford GU27XHUK Institute for Sustainability University of SurreyGuildford GU27XHSurreyUK School of Built environment University of ReadingWhiteknightsReading RG66BUUK School Design and the Built environment Curtin University Sustainability Policy InstituteKent StBentley 6102Western Australia Harry Butler Institute Murdoch UniversityMurdoch 6150Western Australia Atmospheric Sciences Department Institute of AstronomyGeophysics and Atmospheric SciencesUniversity of Sao PauloSao Paulo 05508-090Brazil Met Office FitzRoy RoadExeter EX13PBUK Department of Psychiatry and Nuffield Department of Primary Care Health Sciences Wadham CollegeUniversity of OxfordOxfordUK Centre for Interdisciplinary Methodologies University of WarwickWarwickUK School of Architecture Southeast University2 SipailouNanjing 210096China Cranfield University School of WaterEnvironment and EnergyCranfield MK430ALUK Plants PhotosynthesisSoil ClusterSchool of BiosciencesUniversity of SheffieldSheffield S102TNUK UK Centre for ecology&Hydrology Environment Centre WalesDeiniol RoadBangor LL572UWUK Air Quality Studies Department of Civil and Environmental EngineeringThe Hong Kong Polytechnic UniversityHong KongChina Department of Forestry and environmental Resources Faculty Excellence Program for Leadership in Public ScienceNorth Carolina State UniversityChancellorRaleighNC 27695USA Departments of Architecture&Civil engineering and Chemical EngineeringUniversity of BathBath BA27AYUK School of Architecture University of NevadaLas VegasNV 89154USA Department of Tropical ecosystems Functioning Center of Nuclear Energy in AgricultureUniversity of São PauloPiracicaba 13416-000Sao PauloBrazil School of Ocean Sciences Bangor UniversityMenai BridgeAnglesey LL595 ABUK International Laboratory for Air Quality and Health Science and Engine

The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate ***,the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure(GBGI),such as parks,wetlands,and engineered greening,which have the potential to effectively reduce summer air *** many reviews,the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are *** systematic literature review synthesizes the evidence base for heat mitigation and related co-benefits,identifies knowledge gaps,and proposes recommendations for their implementation to maximize their *** screening 27,486 papers,202 were reviewed,based on 51 GBGI types categorized under 10 main *** GBGI(green walls,parks,street trees)have been well researched for their urban cooling ***,several other GBGI have received negligible(zoological garden,golf course,estuary)or minimal(private garden,allotment)*** most efficient air cooling was observed in botanical gardens(5.0±3.5℃),wetlands(4.9±3.2℃),green walls(4.1±4.2℃),street trees(3.8±3.1℃),and vegetated balconies(3.8±2.7℃).Under changing climate conditions(2070–2100)with consideration of RCP8.5,there is a shift in climate subtypes,either within the same climate zone(e.g.,Dfa to Dfb and Cfb to Cfa)or across other climate zones(e.g.,Dfb[continental warm-summer humid]to BSk[dry,cold semi-arid]and Cwa[temperate]to Am[tropical]).These shifts may result in lower efficiency for the current GBGI in the *** the importance of multiple services,it is crucial to balance their functionality,cooling performance,and other related co-benefits when planning for the future *** global GBGI heat mitigation inventory can assist policymakers and urban planners in prioritizing effective interventions to reduce the risk of urban overheating,fi

关键词： estuary walls extreme

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Influence of biological sex and exercise on murine cardiac metabolism

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Journal of Sport and Health Science 2022年第4期11卷 479-494页

作者： Kyle Fulghum Helen e.Collins Steven P.jones Bradford G.Hill Diabetes and Obesity Center Department of MedicineDivision of Environmental MedicineChristina Lee Brown Envirome InstituteUniversity of LouisvilleLouisvilleKY 40202USA Department of Physiology University of LouisvilleLouisvilleKY 40202USA

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain *** this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill *** the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial *** both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate *** both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise *** metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male *** after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body *** from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosi

关键词： Ketone bodies Metabolomics Mitochondria Physical activity Sex difference

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Spectrum of anemia associated with chronic liver disease

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World Journal of Gastroenterology 2009年第37期15卷 4653-4658页

作者： Rosario Gonzalez-Casas e Anthony jones Ricardo Moreno-Otero Digestive Disease Service and Center for Investigation of Hepatic and Digestive Diseases University Hospital La Princesa Autonomous University of Madrid Madrid 28006 Spain

Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically signif icant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirininduced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by defi ciency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.

关键词：再生障碍性贫血慢性肝病消化道出血病毒性肝炎频谱维生素B12 凝血因子

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Impacts of timing,length,and intensity of behavioral interventions to COVID-19 dynamics:North Carolina countylevel examples

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Infectious Disease Modelling 2022年第3期7卷 535-544页

作者： Claire Quiner Kasey jones Georgiy Bobashev RTI International 3040 E.Cornwallis RoadPO Box 12194Research Triangle ParkNC27709USA

We sought to examine how the impact of revocable behavioral interventions,e.g.,shelterin-place,varies throughout an epidemic,as well as the role that the proportion of susceptible individuals had on an intervention's *** estimated the theoretical impacts of start day,length,and intensity of interventions on disease transmission and illustrated them on COVID-19 dynamics inWake County,North Carolina,to inform how interventions can be most *** used a Susceptible,exposed,Infectious,and Recovered(SeIR)model to estimate epidemic curves with modifications to the disease transmission parameter(β).We designed modifications to simulate events likely to increase transmission(e.g.,long weekends,holiday seasons)or behavioral interventions likely to decrease it(e.g.,shelter-in-place,masking).We compared the resultant curves'shape,timing,and cumulative case count to baseline and across other modified *** led to changes in COVID-19 dynamics,including moving the peak's location,height,and *** proportion susceptible,at the start day,strongly influenced their *** interventions shifted the curve,while interventions near the peak modified shape and case *** some scenarios,in which the transmission parameter was decreased,the final cumulative count increased over *** showed that the timing of revocable interventions has a strong impact on their *** same intervention applied at different time points,corresponding to different proportions of susceptibility,resulted in qualitatively differential *** estimation of the proportion susceptible is critical for understanding an intervention's *** findings presented here provide evidence of the importance of estimating the proportion of the population that is susceptible when predicting the impact of behavioral infection control *** emphasis should be placed on the estimation of this epidemic component in intervention design and decision-makin

关键词： Sars-cov-2 Public health decision-making Infection control policies

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Profile of Bionectriaceae,Calcarisporiaceae,Hypocreaceae,Nectriaceae,Tilachlidiaceae,Ijuhyaceae ***.,Stromatonectriaceae *** Xanthonectriaceae ***

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Fungal Diversity 2023年第1期118卷 95-271页

作者： R.H.Perera K.D.Hyde e.B.G.jones S.S.N.Maharachchikumbura D.Bundhun e.Camporesi A.Akulov J.K.Liu Z.Y.Liu Guizhou Key Laboratory of Agricultural Biotechnology Guizhou Academy of Agricultural SciencesGuiyang 550006GuizhouPeople’s Republic of China Center of excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand School of Science Mae Fah Luang UniversityChiang Rai 57100Thailand Mushroom Research Foundation 128 M.3 Ban Pa Deng T.Pa PaeA.Mae TaengChiang Mai 50150Thailand Key Laboratory for Plant Diversity and Biogeography of east Asia Kunming Institute of BotanyChinese Academy of ScienceKunming 650201YunnanPeople’s Republic of China World Agroforestry Centre East and Central AsiaKunming 650201YunnanPeople’s Republic of China Innovative Institute of Plant Health Zhongkai University of Agriculture and EngineeringHaizhu DistrictGuangzhou 510225People’s Republic of China School of Life Science and Technology University of Electronic Science and Technology of ChinaChengdu 611731People’s Republic of China Department of entomology and Plant Pathology Faculty of AgricultureChiang Mai UniversityChiang Mai 50200Thailand Department of Botany and Microbiology College of ScienceKingdom of Saudi ArabiaKing Saud UniversityP.O Box 2455Riyadh 11451Saudi Arabia A.M.B Circolo Micologico“Giovanni Carini”C.P.314BresciaItaly A.M.B.Gruppo Micologico Forlivese“Antonio Cicognani”Via Roma 18ForliItaly Societaper Gli Studi Naturalistici Della Romagna C.P.143BagnacavalloRAItaly Department of Mycology and Plant Resistance V.N.Karazin Kharkiv National UniversityMaidan Svobody 4Kharkiv 61022Ukraine

This paper provides outlines for Bionectriaceae,Calcarisporiaceae,Hypocreaceae,Nectriaceae,Tilachlidiaceae,Ijuhy-aceae,Stromatonectriaceae and Xanthonectriaceae with taxonomic *** provide up-to-date DNA sequence-based phylogenies including combined gene analysis of ITS,LSU,rpb2,tef1 and tub2 for Hypocreales and accept 17 *** new families and 12 new species are introduced with descriptions and illustrations,while 13 new records and one new species combination are *** we mainly detail the taxonomy of Bionectriaceae,Hypocreaceae,Nectriaceae and Tilachlidiaceae,Ijuhyaceae ***.,Stromatonectriaceae *** Xanthonectriaceae *** introduced in this study based on phenotypic and molecular *** each family we provide a list of accepted genera,the taxo-nomic history,morphological descriptions,taxonomic placement based on DNA sequence data and illustrate the type *** of each family are illustrated based on the type herbarium material or fresh specimens where available,or provide relevant *** on ecological and economic importance of the families are also given.

关键词： 15 New taxa Genera incertae sedis Hypocreales New records Outline Phylogeny Sordariomycetes Taxonomy

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