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HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

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Science China(Life Sciences) 2021年第9期64卷 1449-1462页

作者： Jian-Ping Zhang Zhi-Xue Yang Feng Zhang Ya-Wen Fu Xin-Yue Dai Wei Wen Beldon Zhang hannah Choi Wanqiu Chen meredith Brown David Baylink Lei Zhang Hongyu Qiu Charles Wang Tao Cheng Xiao-Bing Zhang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China School of medicine Loma Linda UniversityLoma LindaCA 92354USA Center for Genomics School of MedicineLoma Linda UniversityLoma LindaCA 92350USA CAmS Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center for Stem Cell medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem Cell&Regenerative medicine Peking Union Medical CollegeTianjin 300020China Tianjin Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center of molecular and Translational medicine Institution of Biomedical ScienceGeorgia State UniversityAtlantaGA 30303USA

Genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic ***,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent *** is partially due to chromatin compaction,inevitably limiting Cas9 access to the target *** the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable *** inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA ***,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

关键词： HDAC inhibitors CRISPR-Cas9 genome editing iPSC

Ultrasmall,elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1660-1670页

作者： Lu Su Kellie S.Dalby hannah Luehmann Sussana A.Elkassih Sangho Cho Xun He Lisa Detering Yen-Nan Lin Nari Kang Dennis A.moore Richard Laforest Guorong Sun Yongjian Liu Karen L.Wooley Department of Chemistry Department of Materials Science and Engineeringand Department of Chemical EngineeringTexas A&M UniversityCollege StationTX 77842USA Laboratory of macromolecular and Organic Chemistry and Institute for Complex molecular Systems Eindhoven University of TechnologyEindhovenMB 5600The Netherlands mallinckrodt Institute of Radiology Washington University School of MedicineSaint LouisMO 63110USA Bayer AG Creve CoeurMO 63167USA

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity,and well-defined spatial and temporal resolutions,a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media(nano-XRCm)as dual-modality imaging agents for positron emission tomography(PET)and computed tomography(CT)has been *** from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide)acrylate monomers,the amphiphilic statistical iodocopolymers(ICPs)could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations(>140 mg iodine/mL water)and comparable viscosities to conventional small molecule *** formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca.10 nm in water was confirmed by dynamic and static light scattering *** a breast cancer mouse model,in vivo biodistribution studies revealed that the64Cu-chelator-functionalized iodinated nano-XRCm exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging ***/CT imaging of tumor over 3 days showed good correlation between PET and CT signals,while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection,enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCm.

关键词： Amphiphilic statistical iodocopolymer CT X-ray contrast media Ultrasmall nanoassembly PET/CT Longitudinal tumor monitoring

Science to support conservation action in a large river system:The Willamette River,Oregon,USA

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Water Biology and Security 2023年第4期2卷 20-35页

作者： Rebecca Flitcroft Luke Whitman James White Rose Wallick Laurel Stratton Garvin Cassandra Smith Robert Plotnikoff michael mulvey Tobias Kock Krista Jones Peter Gruendike Carolyn Gombert Guillermo Giannico Andrew Dutterer Daniel Brown hannah Barrett Brian Bangs Robert m.Hughes U.S.D.A.Forest Service Pacific Northwest Research Station3200 SW Jefferson WayCorvallisOR97331USA Oregon Department of Fish and Wildlife 28655 OR-34CorvallisOR9733USA U.S.Geological Survey Oregon Water Science Center601 SW 2nd AveSuite 1950PortlandOR97204USA Snohomish County Department of Conservation and Natural Resources 3000 Rockefeller AvenueEverettWA98201USA Oregon Department of Environmental Quality Laboratory and Environmental Assessment Division 7202 NE Evergreen ParkwaySuite 150HillsboroOR97124USA U.S.Geological Survey Western Fisheries Research Center5501A Cook-Underwood RoadCookWashington WA 98605USA River Design Group 311 SW Jefferson AvenueCorvallisOR97333USA Bureau of Reclamation Sedimentation and River Hydraulics GroupDenver Federal CenterDenverCO80225USA Oregon State University Department of FisheriesWildlifeand Conservation SciencesNash 104CorvallisOR97331USA Oregon Watershed Enhancement Board 775 Summer Street NESalemOR97301USA U.S.Fish and Wildlife Service 911 NE 11th AvenuePortlandOR97204USA Amnisopes Institute 2895 SE GlennCorvallisOR97333USA

management and conservation efforts that support the recovery and protection of large rivers are daunting,reflecting the complexity of the challenge and extent of effort(in terms of policy,economic investment,and spatial extent)needed to afford measurable *** large systems have generally experienced intensive development and regulation,compromising their capacity to respond to disturbances such as climate change ***,large river and basin management require insights gained from social,ecological,geophysical,and hydrological *** multidisciplinary perspective can unveil the integrated relationship between a river network's biotic community and seasonally variableenvironmental conditions that are *** rivers andtheir basins are constantly changing due to anthropogenic influences and as climate modifies patterns of temperature and *** of these factors,the state of knowledge must advance to address changing *** Willamette River,in western Oregon,USA,is a prime example of a basin that has experienced significant degradation and investment in rehabilitation in recent *** science has facilitated development of fine-scale,spatially extensive datasets and models that can generate targeted conservation and rehabilitation actions that are prioritized across the entire river *** prioritization allows investment decisions to be driven by site-specific conditions while simultaneously considering potentials for ecological ***,we review hydrologic,geomorphic,ecologic,and social conditions in the Willamette River basin through time—including pre-settlement,river development,andcontemporary periods—andoffer a futurevisionfor ***,detailed informationaboutfish populations and habitat,hydrologic conditions,geomorphology,water quality,and land use can be leveraged to make informed decisions about protection,rehabilitation,and develop

关键词： Rehabilitation Flood mitigation Hydropower Fish multidisciplinary

Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications

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Bioactive materials 2021年第11期6卷 3947-3961页

作者： Sina Sharifi mohammad mirazul Islam hannah Sharifi Rakibul Islam Darrell Koza Felisa Reyes-Ortega David Alba-molina Per H.Nilsson Claes H.Dohlman Tom Eirik mollnes James Chodosh miguel Gonzalez-Andrades massachusetts Eye and Ear and Schepens Eye Research Institute Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Department of Immunology Oslo University HospitalRikshospitaletUniversity of OsloOsloNorway Department of Physical Sciences Eastern Connecticut State UniversityWillimanticCTUSA Linnaeus Center for Biomaterials Chemistry Linnaeus UniversityKalmarSweden Research Laboratory Nordland HospitalBodøNorway Centre of molecular Inflammation Research Norwegian University of Science and TechnologyTrondheimNorway maimonides Biomedical Research Institute of Cordoba(ImIBIC) Department of OphthalmologyReina Sofia University Hospital and University of CordobaCordobaSpain Faculty of Health Sciences K.G.Jebsen TRECUniversity of TromsøNorway

Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility,easy processability,transparency,non-toxicity,and reasonable mechanical properties to mimic the extracellular matrix(ECm).Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular *** herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor,utilizing epoxide ring-opening reactions and visible *** chemical modification allows the obtaining of an elastic protein-based hydrogel(GELGYm)with excellent biomimetic properties,approaching those of the native *** can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 mPa with compressive strains as high as 80%compared to Gelatin-methacryloyl(GeImA),the most studied derivative of gelatin used as a *** is also highly biocompatible and supports cellular adhesion,proliferation,and migration in both 2 and 3-dimensional *** characteristics along with its super adhesion to biological tissues such as cornea,aorta,heart,muscle,kidney,liver,and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation,tissue adhesive,wound dressing,bioprinting,and drug and cell delivery.

关键词： Natural-based hydrogel Gelatin Biocompatible Biomimetic Bioadhesive Cornea

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美国临床药学的发展与实践

中国药房 2015年第26期26卷 3601-3611页

作者： Kimberly K.Scarsi Emily A.Prinz hannah K.Snyder Keith m.Olsen 张伶俐曾力楠归舸内布拉斯加大学医学中心药学院临床药学系四川大学华西第二医院药学部成都610041 四川大学华西第二医院循证药学中心成都610041 出生缺陷与相关妇儿疾病教育部重点实验室成都610041 四川大学华西药学院成都610041

目的:介绍美国临床药学的发展史及其实践领域的拓展。方法:简要总结20世纪美国临床药学发展史及其临床实践领域从住院部拓展到门诊,并描述临床药师的主要职责。结果与结论:美国临床药学的重心已从用药和药物调剂向"以患者为中心"、以提... 详细信息

目的:介绍美国临床药学的发展史及其实践领域的拓展。方法:简要总结20世纪美国临床药学发展史及其临床实践领域从住院部拓展到门诊,并描述临床药师的主要职责。结果与结论:美国临床药学的重心已从用药和药物调剂向"以患者为中心"、以提高用药安全和有效为目标的临床实践上倾斜。20世纪初,在大多数医院尚无雇佣药师时,一些药师中的有识之士就已开始参加患者监护查房。此后,出现了更多开创性临床实践模式,昭示着药学职业的巨大潜力。这一系列改变也催生了药学博士项目发展,将药师更好地培养为临床人员,运用其药学专长优化患者监护。虽然临床药学的进步并非一蹴而就和一帆风顺,但经过药师和专业组织的努力,临床药学发展方向发生转变,药师已成为多学科团队中不可或缺的一员。

关键词：美国临床药学医院药学门诊监护

A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

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Translational Neurodegeneration 2023年第1期12卷 568-571页

作者： Kelsie m.LaBarbera Yvette I.Sheline Nicholas J.Izzo Carla m.Yuede Lora Waybright Raymond Yurko hannah m.Edwards Woodrow D.Gardiner Kaj Blennow Henrik Zetterberg Anne Börjesson-Hanson Roger morgan Charles S.Davis Robert J.Guttendorf Lon S.Schneider Steven DeKosky Harry LeVine III michael Grundman Anthony O.Caggiano John R.Cirrito Susan m.Catalano mary E.Hamby Cognition Therapeutics Inc. PittsburghPAUSA University of Pennsylvania PhiladelphiaUSA Washington University St.LouisUSA University of Gothenburg MölndalSweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden Clinical Neurochemistry Laboratory Sahlgrenska University HospitalMölndalSweden Department of Neurodegenerative Disease UCL Institute of NeurologyQueen SquareLondonUK UK Dementia Research Institute at UCL LondonUK Hong Kong Center for Neurodegenerative Diseases Clear Water BayHong KongChina Wisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWIUSA Karolinska University Hospital StockholmSweden medSurgPI LLCRaleighNCUSA CSD Biostatistics Inc.Oro ValleyAZUSA Aclairo Pharmaceutical Development Group IncViennaVAUSA Keck School of medicine of USC Los AngelesCAUSA mcKnight Brain Institute University of FloridaGainesvilleFLUSA Sanders-Brown Center on Aging University of KentuckyLexingtonKYUSA Global R&D Partners LLCSan DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoUSA

Trial Registration:may 11th,2018 *** Identifier:NCT03522129 https://clini caltr ***/ct2/show/*** therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet *** evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].

关键词： Alzheimer Aβ damage

Tumor heterogeneity and therapy resistance-implications for future treatments of prostate cancer

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Journal of Cancer metastasis and Treatment 2017年第1期3卷 302-314页

作者： Fiona m.Frame Amanda R.Noble Sandra Klein hannah F.Walker Rakesh Suman Richard Kasprowicz Vin m.mann matt S.Simms Norman J.maitland Cancer Research Unit Department of BiologyUniversity of YorkHeslingtonNorth Yorkshire YO105DDUK Black Family Stem Cell Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Phase Focus Limited Electric WorksSheffield Digital CampusSheffield S12BJUK Department of Urology Castle Hill Hospital(Hull and East Yorkshire Hospitals NHS Trust)Cottingham HU165JQUK Hull York medical School University of HullHull HU67RXUK.

Aim:To develop new therapies for prostate cancer,disease heterogeneity must be *** includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic *** requires more representative models to be used in more innovative ***:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient *** assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet *** quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population ***:A combination of radiation and Vorinostat may be more effective than radiation *** prostate cancer stem-like cells are more resistant to etoposide than more differentiated *** of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary ***:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular *** of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

关键词： Prostate ptychography live-cell imaging primary cells quantitative phase imaging

3m收购的脚环电子监视器公司给自己惹来了麻烦

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商业周刊（中文版） 2017年第11期 58-63页

作者： LAUREN ETTER hannah WHITAKER

在2012年，美国马萨诸塞州执法部门达成一项交易，与一家生产电子脚环的一流制造商签订了供货合同。这种脚环是一种小型全球定位系统（GPS）装置，

关键词：电子监视器公司收购全球定位系统马萨诸塞州执法部门供货合同

541m高处的安全——美国新世贸中心尖顶施工安装保护措施

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现代职业安全 2013年第11期 99-101页

作者： hannah Addison 王梦蓉

具有历史意义的541 m高度,使位于美国纽约市的新世贸中心不仅成为西半球最高的摩天大楼,也成为了美国人的骄傲和坚韧的象征。由斯基德摩尔家族的大卫·查尔兹、欧文斯和美林共同设计的这栋面积为24万1 548 m2的建筑物内既有办公区、观景... 详细信息

具有历史意义的541 m高度,使位于美国纽约市的新世贸中心不仅成为西半球最高的摩天大楼,也成为了美国人的骄傲和坚韧的象征。由斯基德摩尔家族的大卫·查尔兹、欧文斯和美林共同设计的这栋面积为24万1 548 m2的建筑物内既有办公区、观景台,也有世界级的餐厅及广播天线设施。新世贸中心投入运行后,将会有成千上万的人在其中工作。

关键词：世贸中心美国人保护措施施工安装安全历史意义摩天大楼技术人员