检索结果-内蒙古大学图书馆

arXiv 2023年

作者： Eastman, Peter Galvelis, Raimondas Peláez, Raúl P. Abreu, Charlles R.A. Farr, Stephen E. Gallicchio, Emilio Gorenko, Anton Henry, Michael M. Hu, Frank Huang, Jing Krämer, Andreas Michel, Julien Mitchell, Joshua A. Pande, Vijay S. Rodrigues, João P.G.L.M. Rodriguez-Guerra, Jaime Simmonett, Andrew C. Singh, Sukrit Swails, Jason Turner, Philip Wang, Yuanqing Zhang, Ivy Chodera, John D. De Fabritiis, Gianni Markland, Thomas E. Department of Chemistry Stanford University StanfordCA94305 United States Acellera Labs C Dr Trueta 183 Barcelona08005 Spain C Dr. Aiguader 88 Barcelona08003 Spain Chemical Engineering Department School of Chemistry Federal University of Rio de Janeiro Rio de Janeiro68542 Brazil Redesign Science Inc. 180 Varick St. New YorkNY10014 United States EaStCHEM School of Chemistry University of Edinburgh EH9 3FJ United Kingdom Department of Chemistry and Biochemistry Brooklyn College The City University of New York NY United States Ph.D. Program in Chemistry Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States Stream HPC Koningin Wilhelminaplein 1 - 40601 Amsterdam1062 HG Netherlands Computational and Systems Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Key Laboratory of Structural Biology of Zhejiang Province School of Life Sciences Westlake University 18 Shilongshan Road Zhejiang Hangzhou310024 China Department of Mathematics and Computer Science Freie Universität Berlin Arnimallee 12 Berlin14195 Germany The Open Force Field Initiative Open Molecular Software Foundation DavisCA95616 United States Andreessen Horowitz 2865 Sand Hill Rd Menlo ParkCA94025 United States Department of Structural Biology Stanford University StanfordCA94305 United States Charité Universitätsmedizin Berlin In silico Toxicology and Structural Bioinformatics Virchowweg 6 Berlin10117 Germany Laboratory of Computational Biology National Heart Lung and Blood Institute National Institutes of Health BethesdaMD20892 United States Entos Inc. 9310 Athena Circle La Jolla CA92037 United States College of Engineering Virginia Polytechnic Institute State University BlacksburgVA24061 United States Simons Center for Computational Physical Chemistry Center for Data Science New York University 24 Waverly Place New YorkNY10004 United States T

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUDA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features on simulations of cyclin-dependent kinase 8 (CDK8) and the green fluorescent protein (GFP) chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations at only a modest increase in cost. Copyright © 2023, The Authors. All rights reserved.

关键词： Machine learning

来源：评论

学校读者我要写书评

暂无评论

Tribological properties of hydroxyapatite-coated nanorods on Ti-6Al-4V surfaces

引用

Scientific reports 2025年第1期15卷 19113页

作者： Sarah Akua Osafo Tabiri Asumadu Desmond Klenam Precious Etinosa John David Obayemi Benjamin Agyei-Tuffour Abu Yaya David Dodoo-Arhin Stanley Chijioke Eluu Wole Soboyejo Department of Materials Science and Engineering School of Engineering Sciences College of Basic and Applied Sciences University of Ghana Legon Accra Ghana. Department of Biomaterial Sciences Dental School University of Ghana Korle Bu Campus Accra Ghana. Department of Mechanical Engineering Program in Materials Science and Engineering Worcester Polytechnic Institute 100 Institute Road Worcester MA 01609 USA. Department of Materials Engineering Sunyani Technical University Sunyani Ghana. Global Center of Advanced Materials and Manufacturing Department of Mechanical Engineering College of Engineering State University of New York (SUNY) Polytechnic Institute 100 Seymour Street Utica NY 13502 USA. Next Frontiers in Advanced Material Laboratory School of Chemical and Metallurgical Engineering University of the Witwatersrand 1 Jan Smuts Avenue Johannesburg 2050 South Africa. Department of Biomedical Engineering Worcester Polytechnic Institute Gateway Park Life Sciences and Bioengineering Centre 60 Prescott Street Worcester MA 01609 USA. Department of Biotechnology Ebonyi State University Abakaliki Nigeria. Department of Pharmaceutical Microbiology and Biotechnology Faculty of Pharmaceutical Sciences Nnamdi Azikiwe University Awka Anambra State Nigeria. Department of Mechanical Engineering Program in Materials Science and Engineering Worcester Polytechnic Institute 100 Institute Road Worcester MA 01609 USA. soboyew@sunypoly.edu. Global Center of Advanced Materials and Manufacturing Department of Mechanical Engineering College of Engineering State University of New York (SUNY) Polytechnic Institute 100 Seymour Street Utica NY 13502 USA. soboyew@sunypoly.edu. Department of Biomedical Engineering Worcester Polytechnic Institute Gateway Park Life Sciences and Bioengineering Centre 60 Prescott Street Worcester MA 01609 USA. soboyew@sunypoly.edu.

This paper presents the tribological properties and bioactivity of nanostructured hydroxyapatite (HA) from biowaste sources and coated onto Ti-6Al-4V substrates using a novel pack cementation method. The process introduced HA pillars/nanorods on the surfaces of Ti-6Al-4V to enhance their osseointegration for dental implants. The mechanical and tribological properties were studied with nanoindentation, and pin-on-disk techniques, following the microstructural characterization of the coatings with atomic force microscopy, X-ray diffraction, Raman spectroscopy, scanning electron microscopy, and energy dispersive x-ray spectroscopy. The study also examines the surface bioactivity and elucidates the underlying friction and wear mechanisms of the HA-coated and annealed Ti-6Al-4V surface. The study results show a bone bonding capacity of the biowaste-derived HA-coated substrate with improved hardness and tribological properties. The implications of the study are discussed for the development of nano-structured HA-coated Ti-6Al-4V for dental implants with improved osseointegration for dental and biomedical applications.

关键词： Bioactivity Dental implants Osseointegration Surface modification Titanium alloys Wear resistance

来源：评论

学校读者我要写书评

暂无评论

MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming

Research Square

引用

Research Square 2021年

作者： Ismail, Wazim Mohammed Mazzone, Amelia Kaur, Jagneet Safgren, Stephanie Moore-Weiss, John Buciuc, Marina Shimp, Lynzie Duarte, Luis F. Nagi, Chandandeep S. Carcamo, Saul Chung, Chi-Yeh Hasson, Dan Dadgar, Neda Revzin, Alexander Zhong, Jian Lee, Jeong-Heon Ordog, Tamas Bernstein, Emily Gaspar-Maia, Alexandre Division of Experimental Pathology Department of Lab Medicine and Pathology Mayo Clinic RochesterMN United States Center for Individualized Medicine Epigenomics program Mayo Clinic RochesterMN United States Department of Oncological Sciences Icahn School of Medicine Mount Sinai New YorkNY United States Graduate School of Biomedical Sciences Icahn School of Medicine Mount Sinai New YorkNY United States Department of Pathology and Immunology Baylor College of Medicine HoustonTX United States Department of Physiology and Biomedical Engineering Mayo Clinic RochesterMN United States

Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined ‘macroH2A-Bound Enhancers’, that negatively modulate enhancer activity. We find macroH2A variants enriched at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and its repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling, we show that the loss of macroH2A2 leads to increased cellular heterogeneity that may help to explain the role of macroH2A variants in defining oncogenic transcriptional dependencies. © 2021, CC BY.

关键词： Acetylation

来源：评论

学校读者我要写书评

暂无评论

Genetics Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy

引用

Science Advances 2022年第16期8卷

作者： Zou, Yan Sun, Xinhong Yang, Qingshan Zheng, Meng Shimoni, Olga Ruan, Weimin Wang, Yibin Zhang, Dongya Yin, Jinlong Huang, Xiangang Tao, Wei Park, Jong Bae Liang, Xing-Jie Leong, Kam W. Shi, Bingyang Henan-Macquarie Uni Joint Centre for Biomedical Innovation Academy for Advanced Interdisciplinary Studies Henan Key Laboratory of Brain Targeted Bio-nanomedicine School of Life Sciences Henan University Henan Kaifeng475004 China Macquarie Medical School Faculty of Medicine Health and Human Sciences Macquarie University SydneyNSW2109 Australia Faculty of Science University of Technology Sydney 15 Broadway Ultimo SydneyNSW2007 Australia Center for Nanomedicine Department of Anesthesiology Harvard Medical School 25 Shattuck St. BostonMA02115 United States Department of Cancer Biomedical Science Graduate School of Cancer Science and Policy National Cancer Center Goyang10408 Korea Republic of Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nano-materials and Nanosafety National Center for Nanoscience and Technology Chinese Academy of Sciences Beijing100190 China Department of Biomedical Engineering Columbia University New YorkNY10032 United States

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases. Copyright © 2022 The Authors, some rights reserved.

关键词： Nanocapsules

来源：评论

学校读者我要写书评

暂无评论

A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes

Cell Reports Medicine

引用

Cell Reports Medicine 2025年第5期6卷 102084-102084页

作者： Han, Xudong Zhang, Yichi Petrosky, Jillian N. Bald, Sarah Sherva, Richard M. Labadorf, Adam Cherry, Jonathan D. Chung, Jaeyoon Farrell, Kurt Abdolmohammadi, Bobak Durape, Shruti Martin, Brett M. Palmisano, Joseph N. Farrell, John J. Alvarez, Victor E. Huber, Bertrand R. Dwyer, Brigid Daneshvar, Daniel H. Jun, Gyungah R. Lunetta, Kathryn L. Goldstein, Lee E. Katz, Douglas I. Cantu, Robert C. Shenton, Martha E. Cummings, Jeffrey L. Reiman, Eric M. Stern, Robert A. Alosco, Michael L. Tripodis, Yorghos Farrer, Lindsay A. Stein, Thor D. Crary, John F. McKee, Ann C. Mez, Jesse Bioinformatics Graduate Program Boston University Boston MA United States Section of Biomedical Genetics Department of Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Department of Neurology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston University Alzheimer's Disease Research Center Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston VA Healthcare System Boston MA United States Boston University Chronic Traumatic Encephalopathy Center Boston University Boston MA United States Department of Pathology and Laboratory Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Pathology Neuroscience and Artificial Intelligence & Human Health Neuropathology Brain Bank & Research CoRE Friedman Brain Institute Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai New York NY United States Biostatistics and Epidemiology Data Analytics Center Boston University School of Public Health Boston MA United States Bedford VA Healthcare System Bedford MA United States Braintree Rehabilitation Hospital Braintree MA United States Department of Physical Medicine and Rehabilitation Harvard Medical School Boston MA United States Department of Rehabilitation and Human Performance Brain Injury Research Center Icahn School of Medicine at Mount Sinai New York NY United States Department of Neurology Icahn School of Medicine at Mount Sinai New York NY United States Department of Biostatistics Boston University School of Public Health Boston MA United States Department of Ophthalmology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Biomedical Electrical & Computer Engineering Boston University College of Engineering Boston MA United States Departments of Radiology and Psychiatry Boston University Chobanian & Avedisia

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. Genetic variation in the 17q21.31 region, containing microtubule-associated protein tau (MAPT), has been implicated in tauopathies but has not been investigated in CTE. The region includes a megabase-long inversion (H1/H2) and copy-number variations, including α, β, and γ segments, which can be characterized as nine segregating structural haplotypes. We leveraged array SNP data and a reference panel across the 17q21.31 region to impute structural haplotypes and test their association with CTE endophenotypes in 447 European ancestry brain donors with RHI exposure. The H1β1γ1 haplotype was significantly associated with dementia and semi-quantitative tau burden in multiple cortical and medial temporal regions commonly affected in CTE. H1β1γ1 differential expression analyses in dorsolateral frontal cortex implicated cis-acting genes and inflammatory pathways. Taken together, the H1β1γ1 haplotype may help explain CTE heterogeneity among those with similar RHI exposure. © 2025 The Authors

关键词： 17q21.31 chronic traumatic encephalopathy dementia differential gene expression immune system MAPT repetitive head impacts structural haplotypes tauopathy traumatic brain injury

来源：评论

学校读者我要写书评

暂无评论

Author Correction: Hybrid PET/MRI enables high-spatial resolution, quantitative imaging of amyloid plaques in an Alzheimer's disease mouse model

引用

Scientific reports 2020年第1期10卷 13826页

作者： Georgia R Frost Valerie Longo Thomas Li Lauren A Jonas Martin Judenhofer Simon Cherry Jason Koutcher Carl Lekaye Pat Zanzonico Yue-Ming Li Chemical Biology Program Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Program of Neuroscience Weill Graduate School of Medical Sciences of Cornell University New York NY 10021 USA. Small Animal Imaging Core Facility Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Program of Pharmacology Weill Graduate School of Medical Sciences of Cornell University New York NY 10021 USA. Department of Biomedical Engineering University of California Davis CA 95616 USA. Departments of Medical Physics Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Departments of Radiology Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Departments of Medical Physics Memorial Sloan Kettering Cancer Center New York NY 10065 USA. zanzonip@***. Chemical Biology Program Memorial Sloan Kettering Cancer Center New York NY 10065 USA. liy2@***. Program of Neuroscience Weill Graduate School of Medical Sciences of Cornell University New York NY 10021 USA. liy2@***. Program of Pharmacology Weill Graduate School of Medical Sciences of Cornell University New York NY 10021 USA. liy2@***.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

关键词：

来源：评论

学校读者我要写书评

暂无评论

HMGA1 Chromatin Regulators Disrupt 3D Genome Architecture and Chromatin Looping to Repress MHC II Genes and Drive Immune Evasion during MPN Progression

引用

Blood 2024年 144卷 756-756页

作者： Linda Resar Joseph Kim Audrey-Ann Supreme Hyunsung Woo Bailey West Mariah C. Antopia Zanshe Thompson Karen Reddy Jung-Hyun Kim Leslie Cope Raajit Rampal Richard Koche Alison R. Moliterno Jerry L. Spivak Division of Hematology Departments of Medicine Oncology & Pathology The Johns Hopkins University School of Medicine Baltimore MD Johns Hopkins University School of Medicine Baltimore MD Cellular and Molecular Medicine Graduate Program Johns Hopkins University School of Medicine Baltimore MD Doctoral Diversity Program Johns Hopkins University School of Medicine Baltimore MD Department of Medicine Division of Hematology Johns Hopkins University School of Medicine Baltimore MD Whiting School of Engineering The Johns Hopkins University Baltimore MD Pathobiology Graduate Program Johns Hopkins University School of Medicine Baltimore MD The Institute for Basic Biomedical Sciences Johns Hopkins University School of Medicine Baltimore MD Division of Hematology The Johns Hopkins University School of Medicine Owings Mills MD The Johns Hopkins University School of Medicine Baltimore MD Memorial Sloan Kettering Cancer Center New York NY Center for Epigenetics Research Memorial Sloan Kettering Cancer Center New York NY Human Oncology and Pathogenesis Program Leukemia Service Department of Medicine Center for Epigenetics Memorial Sloan Kettering Cancer Center New York NY Division of Hematology Department of Medicine Johns Hopkins University/Fda Silver Spring MD Department of Oncology Johns Hopkins University School of Medicine Baltimore MD

Introduction: Myeloproliferative neoplasms (MPN) are clonal blood disorders with hyperactive JAK/STAT signaling and an increased risk of transformation to acute myeloid leukemia (AML). Importantly, AML in MPN is almost universally fatal and targetable mechanisms remain elusive. We discovered that High Mobility Group A1 (HMGA1) chromatin regulators are required for MPN progression and leukemic transformation in JAK2 V617F mouse models (Li et al, Blood 2022). Immune escape is a fundamental mechanism of tumor progression in solid tumors, although its role in MPN is unknown. We therefore sought to test the hypotheses that: 1) HMGA1 drives MPN progression by activating gene networks involved in immune evasion, 2) Targeting HMGA1 networks with therapy in advanced MPN will trigger an anti-tumor immune attack. Methods: To dissect mechanisms underlying HMGA1, we performed multiomic sequencing (seq) approaches, including RNAseq, chromatin immunoprecipitation (ChIPseq), and assays of chromatin accessibility (ATACseq) in JAK2 V617F mutant AML cell lines (DAMI, SET-2, UKE-1). HMGA1 was inactivated via CRISPR or short hairpin RNA (shRNA). To examine three dimensional (3D) genome architecture, we employed chromatin conformation capture (3C). ChIP was used to detect chromatin binding of repressive histones and CCCTC-binding factor (CTCF) complexes. To define pathways relevant to MPN patients, we assessed bulk and single cell (sc) RNAseq of peripheral blood mononuclear cells (PBMCs) and CD34 + cells. Artificial intelligence (AI) was used to identify drugs targeting HMGA1. Results: To elucidate transcriptional networks governed by HMGA1 in MPN, we integrated multiomic approaches (RNA/ChIP/ATACseq) in JAK2 V617F mutant AML cells, which revealed that HMGA1 represses gene networks involved in interferon γ signaling and antigen presentation (AP), including genes encoding major histocompatibility complex (MHC) class I and II proteins. HMGA1 also represses the CD74 gene, which encodes the

关键词：

来源：评论

学校读者我要写书评

暂无评论

Author Correction: Senolytic CAR T cells reverse senescence-associated pathologies

引用

Nature 2024年第8004期627卷 E9页

作者： Corina Amor Judith Feucht Josef Leibold Yu-Jui Ho Changyu Zhu Direna Alonso-Curbelo Jorge Mansilla-Soto Jacob A Boyer Xiang Li Theodoros Giavridis Amanda Kulick Shauna Houlihan Ellinor Peerschke Scott L Friedman Vladimir Ponomarev Alessandra Piersigilli Michel Sadelain Scott W Lowe Louis V. Gerstner Jr Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer Center New York NY USA. Department of Cancer Biology and Genetics Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. Center for Cell Engineering Memorial Sloan Kettering Cancer Center New York NY USA. Immunology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. Molecular Pharmacology and Chemistry Program Memorial Sloan Kettering Cancer Center New York NY USA. Weill Cornell Graduate School of Medical Sciences New York NY USA. Department of Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA. Division of Liver Diseases Icahn School of Medicine at Mount Sinai New York NY USA. Department of Radiology Memorial Sloan Kettering Cancer Center New York NY USA. Laboratory of Comparative Pathology Rockefeller University Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center New York NY USA. Center for Cell Engineering Memorial Sloan Kettering Cancer Center New York NY USA. m-sadelain@***. Immunology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. m-sadelain@***. Department of Cancer Biology and Genetics Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. lowes@***. Howard Hughes Medical Institute Chevy Chase MD USA. lowes@***.

来源：评论

学校读者我要写书评

暂无评论

P-selectin Targeting Stimulates Caveolin-1-Mediated Endothelial Transcytosis in Medulloblastoma

Research Square

引用

Research Square 2021年

作者： Tylawsky, Daniel E. Kiguchi, Hiro Vaynshteyn, Jake Gerwin, Jeffrey Shah, Janki Islam, Taseen Snuderl, Matija Greenblatt, Matthew B. Boué, Daniel R. Shamay, Yosi Raju, G. Praveen Heller, Daniel A. Molecular Pharmacology Program Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Department of Pharmacology Weill Cornell Graduate School of Medical Sciences New YorkNY10065 United States Department of Pediatrics Weill Cornell Medicine New YorkNY10065 United States Department of Pediatrics Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Departments of Pathology & Laboratory Medicine Nationwide Children’s Hospital The Ohio State University ColumbusOH43205 United States Division of Neuropathology Department of Pathology NYU Langone Medical Center New YorkNY10016 United States Department of Pathology and Laboratory Medicine Weill Cornell Medicine & Research Division Hospital for Special Surgery New YorkNY10065 United States Faculty of Biomedical Engineering The Technion Israel Institute of Technology Haifa Israel Departments of Neurology and Pediatrics Icahn School of Medicine at Mount Sinai New YorkNY10029 United States

Medulloblastoma (MB) is the most common malignant pediatric brain tumor with ~30% mediated by Sonic hedgehog (SHH) signaling. While SHH effector Smoothened inhibition is promising, therapeutic index is reduced by high systemic doses required for sufficient intracranial drug concentrations. Treatment-related toxicities associated with radiation therapy result in lifelong morbidity, and SHH pathway inhibition in children notably results in permanent bone defects. Here, we found that nanoparticle-mediated P-selectin targeting on tumor vasculature induces caveolin-1-dependent transcellular passage across the blood-brain barrier. A vismodegib nanocarrier that targets P-selectin exhibited striking efficacy and markedly reduced both bone-related toxicities and drug exposure to healthy brain. These findings demonstrate a potent strategy and novel mechanism for targeted intracranial pharmacodelivery that overcomes the restrictive endothelial barrier to achieve enhanced tumor-selective penetration and has therapeutic implications for other diseases within the central nervous system. © 2021, CC BY.

关键词： Toxicity

来源：评论

学校读者我要写书评

暂无评论

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia

引用

Cell stem cell 2025年

作者： Maria Sirenko Soobeom Lee Zhengxi Sun Ronan Chaligne Sanam Loghavi Georgios Asimomitis Charlotte K Brierley Elsa Bernard Sheng F Cai Robert M Myers Bettina Nadorp Junya Sango Morgan Lallo Max F Levine Dylan Domenico Juan E Arango Ossa Juan S Medina-Martinez Kamal Menghrajani Audrey Lasry Alice S Mims Helee Desai Andrea Laganson Chris Famulare Minal Patel Gerard Lozanski Kelly L Bolton Aaron D Viny Mikhail Roshal Ross L Levine Eirini P Papapetrou Eytan M Stein Dan A Landau Ann-Kathrin Eisfeld Iannis Aifantis Elli Papaemmanuil Department of Pathology New York University Grossman School of Medicine New York NY USA Laura and Isaac Perlmutter Cancer Center New York University Grossman School of Medicine New York NY USA Louis V. Gerstner Jr. Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer Center New York NY USA Computational Oncology Service Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA. Department of Biology New York University New York NY USA. Laura and Isaac Perlmutter Cancer Center New York University Grossman School of Medicine New York NY USA. Program for Computational and Systems Biology Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY 10065 USA. Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA. Computational Oncology Service Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Biomedical Systems Laboratory Department of Mechanical Engineering National Technical University of Athens Athens Greece. Medical Research Council Weatherall Institute of Molecular Medicine University of Oxford Oxford UK NIHR Biomedical Research Centre University of Oxford Oxford UK. Leukemia Service Department of Medicine Center for Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York NY USA. Tri-Institutional MD-PhD Program Weill Cornell Medicine Rockefeller University Memorial Sloan Kettering Cancer Center New York NY USA. Division of Precision Medicine Department of Medicine New York University School of Medicine New York NY USA. Department of Oncological Sciences Tisch Cancer Institute Center for Advancement of Blood Cancer Therapies Icahn School of Medicine at Mount Sinai New York NY USA. Vilcek Institute of Graduate Biomedical Sciences NYU Grossman School of Medicine N

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.

关键词： IDH inhibitors IDH1/2 mutations acute myeloid leukemia cellular hierarchy clonal architecture clonal evolution relapse single-cell transcriptomics targeted therapy treatment resistance

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：