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

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 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 Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA Department of Biology New York University New York NY USA Program for Computational and Systems Biology Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY 10065 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 New York NY USA Clara D. Bloomfield Center for Leukemia Outcomes Research The Ohio State University Comprehensive Cancer Center Columbus OH USA Division of Hematology Department of Internal Medicine The Ohio State University Comprehensive Cancer Cen

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

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Piezoelectric and triboelectric nanogenerators: Promising technologies for self-powered implantable biomedical devices

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Nano Energy 2024年 119卷

作者： Khan, Arshad Joshi, Ravindra Sharma, Manish Kumar Ganguly, Anindita Parashar, Parag Wang, Ting-Wei Lee, Sangmin Kao, Fu-Cheng Lin, Zong-Hong Department of Biomedical Engineering National Taiwan University Taipei10167 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Materials Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Internet of Senses Research Center National Tsing Hua University Hsinchu30013 Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu30013 Taiwan School of Mechanical Engineering Chung-Ang University Seoul06974 Korea Republic of Department of Orthopaedic Surgery Chang Gung Memorial Hospital Taoyuan33305 Taiwan College of Medicine Chang Gung University Taoyuan33302 Taiwan Department of Chemical Engineering National Taiwan University Taipei10167 Taiwan

Implantable biomedical devices (IBDs) have garnered wide-scale attention in recent years due to their enormous contribution to the biomedical sector. However, an uninterrupted and reliable power source has consistently been the primary barrier for IBDs, which is greatly alleviated by batteries. The widespread application of battery-powered IBDs is hindered by several limitations, including bulkiness, limited capacity and shelf-life, and expenditure associated with surgery-based battery recharge/replacement. To address these challenges, state-of-the-art self-powering technologies have emerged, including implantable piezoelectric nanogenerators (iPENGs) and implantable triboelectric nanogenerators (iTENGs). These technologies enable IBDs to operate autonomously by harnessing the minute mechanical movements of internal organs, such as heartbeat, respiration, blood circulation, muscle contraction/relaxation, and lung vibration. This review focuses on the recent advancements in iTENGs and iPENGs for the development of self-powered IBDs with a wide range of applications, including energy harvesting from biomechanical and ultrasound sources and energy storage using batteries and capacitors. This study also explores the extensive sensing applications of IBDs in various areas including cardiac, gastrointestinal, bladder, and ligament-strain monitoring. Finally, therapeutic applications of IBDs, such as nerve stimulation, bone stimulation, cartilage therapy, tissue regeneration, muscle stimulation, drug delivery, and diabetes management are discussed. © 2023 Elsevier Ltd

关键词： Nanogenerators

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A triboelectric nanogenerator-based tactile sensor array system for monitoring pressure distribution inside prosthetic limb

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Nano Energy 2023年 111卷

作者： Chang, Kuie-Bin Parashar, Parag Shen, Li-Chien Chen, An-Rong Huang, Yan-Tsz Pal, Arnab Lim, Kee-Chin Wei, Po-Han Kao, Fu-Cheng Hu, Jin-Jia Lin, Zong-Hong Department of Mechanical Engineering National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biomedical Engineering National Taiwan University Taipei Taiwan Department of Material Science and Engineering National Tsing Hua University Hsinchu Taiwan Institute of Biomedical Engineering National Tsing Hua University Hsinchu Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu Taiwan Department of Orthopaedic Surgery Chang Gung Memorial Hospital Taoyuan Taiwan College of Medicine Chang Gung University Taoyuan Taiwan Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu30013 Taiwan

In the prosthetic field, quantifying interfacial pressure distribution between the amputee's residual limb and the socket's internal environment is imperative for developing new technologies. However, the commercially available pressure sensors have several disadvantages, namely external power supply requirements, low stability, high cost, and complexities related to integrating the sensor system into prosthetic devices. Herein, we propose a self-powered triboelectric nanogenerator (TENG) based flexible tactile sensor array system to monitor prosthetic socket internal pressure distribution in real-time. The proposed sensor consists of biocompatible polydimethylsiloxane (PDMS) polymer and polycaprolactone (PCL) nanofiber membranes as triboelectric materials. The biodegradable PCL nanofiber membrane, fabricated via a scalable and cost-effective electrospinning process, possesses a high surface area-to-volume ratio, facilitating enhanced charge generation during triboelectrification. The as-fabricated TENG-based tactile sensor is highly stable up to 10,000 cycles. Furthermore, the voltage of the tactile sensor is independent of different temperature and humidity values, demonstrating the stability of the sensor under various environmental conditions. Finally, we successfully integrated the tactile sensor array within a prosthetic device to monitor real-time pressure distribution inside the prosthetic socket during gait simulation. We believe that the proposed novel design provides a new dimension for the rapid development of self-powered, low-cost, and highly stable pressure monitoring systems with considerable potential for commercialization. © 2023 Elsevier Ltd

关键词： Electrospinning

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Emergence of Non-photoresponsive Catalytic Techniques for Environmental Remediation and Energy Generation

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Chemistry - An Asian Journal 2023年第9期18卷 e202300090页

作者： Kumar Sharma, Manish Khan, Imran Kaswan, Kuldeep Roy Barman, Snigdha Saha, Subhajit Hsieh, Wu-Chiao Chueh, Yu-Lun Wang, Yu-Lin Lee, Sangmin Choi, Dukhyun Lin, Zong-Hong Department of Materials Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Institute of NanoEngineering and Microsystems National Tsing Hua University Hsinchu30013 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Renewable Energy Maulana Abul Kalam Azad University of Technology West Bengal741249 India Department of Obstetrics and Gynecology Chang Gung Memorial Hospital and College of Medicine Chang Gung University Taoyuan333 Taiwan Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu30013 Taiwan School of Mechanical Engineering Chung-Ang University Seoul06974 Korea Republic of Department of Mechanical Engineering Sungkyunkwan University Suwon16419 Korea Republic of Department of Biomedical Engineering National Taiwan University Taipei10617 Taiwan

Catalysis plays a crucial role in all the major applications and challenges in the environment, including energy generation and environmental remediation. Although photocatalysts and electrocatalysts are useful in addressing energy and environmental issues, they have some major drawbacks, such as low efficiency and easy charge recombination which limits their applications. Hence, it is imperative to design and explore new catalytic techniques that include non-photoresponsive catalysts. In this review, the detailed possibilities, characteristics and prospects of non-photoresponsive catalysts, such as piezocatalysts, thermocatalysts, pyrocatalysts, and tribocatalysts along with hybrid catalysts are described. The overall mechanism of each catalytic technique and its applications in different fields such as energy generation, environmental remediation, and carbon dioxide reduction are discussed. © 2023 Wiley-VCH GmbH.

关键词： Electrocatalysts

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CuO NWs boosted triboelectric microfluidic nanosensor functionalized by collagen-protein interactions for real-time platelet count monitoring

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Chemical engineering Journal 2024年 490卷

作者： Lin, Jia-Cheng Kaswan, Kuldeep Chatterjee, Subhodeep Wu, Yu-Wen Kumar Sharma, Manish Ranjan, Ashok Roy Barman, Snigdha Lin, Yu-Zih Burnouf, Thierry Boireau, Wilfrid Lu, Ming-Yen Tu, Yong-Kwang Su, I-Chang Wu, Ping-Hsiu Lin, Zong-Hong Fan, Yu-Jui School of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Taipei Neuroscience Institute Taipei Medical University Taipei11031 Taiwan Department of Biomedical Engineering National Taiwan University Taipei11031 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei11031 Taiwan Department of Material Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan International PhD Program in Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Université de Franche-Comté CNRS Institut FEMTO-ST BesançonF-25030 France Department of Neurosurgery Shuang Ho Hospital Taipei Medical University New Taipei City23561 Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Radiology School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Radiation Oncology Taipei Medical University Hospital Taipei11031 Taiwan Center for Precision Health and Quantitative Sciences Taipei Medical University Hospital Taipei 11031 Taiwan

Blood platelet count significantly affects the development of severe conditions like myocardial infarction, peripheral arterial ischemia, respiratory compromise, stroke, diabetes, coronavirus disease 2019 (COVID-19), along with chemotherapy patients and those suffering cardiovascular diseases (CVDs). These conditions necessitate frequent monitoring of platelet counts to guide diagnostic and therapeutic decisions. However, existing techniques are relatively time-consuming, lack of accuracy and require precise operation. The emergence of these severe diseases underscored the need to develop advanced platelet count-monitoring techniques which are rapid, highly precise, and conveniently portable for point-of-care applications. In this study, we emphasized the development of a triboelectric microfluidic nanosensor (TMNS) for platelet quantification through the assessment of flow resistance. The functionality of TMNS device is based on immobilization of platelets on a collagen layer coated inside a microfluidic channel. The triboelectric voltage output is measured as a detection signal of the flow resistance and is enhanced by incorporating high surface area copper oxide nanowires (CuO NWs) on the interior of copper tubes. These copper tubes serve as terminal electrodes and for flow guiding. The flow resistance of plasma solutions is elevated when the platelet concentration increases due to heightened adherence of platelets onto the collagen layer. Variations in flow resistance induce alterations in contact electrification, causing changes in output voltage at load terminals. Fine-tuning of the TMNS device was achieved by optimizing the channel width and length, flowing liquid viscosity, and voltage measurement technique. Platelet quantification sensing data were acquired through the combination of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) solutions. The described device exhibits promising capabilities for platelet-count monitoring in whole-blood samples c

关键词： Copper oxides

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Microfluidic nanodevices for drug sensing and screening applications

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Biosensors and Bioelectronics 2023年 219卷 114783页

作者： Pal, Arnab Kaswan, Kuldeep Barman, Snigdha Roy Lin, Yu-Zih Chung, Jun-Hsuan Sharma, Manish Kumar Liu, Kuei-Lin Chen, Bo-Huan Wu, Chih-Cheng Lee, Sangmin Choi, Dongwhi Lin, Zong-Hong Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Materials Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Chemistry National Tsing Hua University Hsinchu30013 Taiwan Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu30013 Taiwan Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital Linkou Medical Center Taoyuan333 Taiwan Center of Quality Management National Taiwan University Hospital Hsinchu Branch Hsinchu30059 Taiwan College of Medicine National Taiwan University Taipei10051 Taiwan Institute of Cellular and System Medicine National Health Research Institute Zhunan 35053 Taiwan School of Mechanical Engineering Chung-Ang University Seoul06974 Korea Republic of Kyung Hee University Gyeonggi 17104 Korea Republic of

The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development. © 2022 Elsevier B.V.

关键词： Microfluidics

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Front Cover: Emergence of Non-photoresponsive Catalytic Techniques for Environmental Remediation and Energy Generation (Chem. Asian J. 9/2023)

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Chemistry – An Asian Journal 2023年第9期18卷

作者： Manish Kumar Sharma Dr. Imran Khan Kuldeep Kaswan Dr. Snigdha Roy Barman Prof. Dr. Subhajit Saha Wu-Chiao Hsieh Prof. Dr. Yu-Lun Chueh Prof. Dr. Yu-Lin Wang Prof. Dr. Sangmin Lee Prof. Dr. Dukhyun Choi Prof. Dr. Zong-Hong Lin Department of Materials Science and Engineering National Tsing Hua University Hsinchu 30013 Taiwan Institute of NanoEngineering and Microsystems National Tsing Hua University Hsinchu 30013 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu 30013 Taiwan Department of Renewable Energy Maulana Abul Kalam Azad University of Technology West Bengal 741249 India Department of Obstetrics and Gynecology Chang Gung Memorial Hospital and College of Medicine Chang Gung University Taoyuan 333 Taiwan Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu 30013 Taiwan School of Mechanical Engineering Chung-Ang University Seoul 06974 South Korea Department of Mechanical Engineering Sungkyunkwan University Suwon 16419 South Korea Department of Biomedical Engineering National Taiwan University Taipei 10617 Taiwan

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Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

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Nature medicine 2024年第12期30卷 3779页

作者： Sebastian Moguilner Sandra Baez Hernan Hernandez Joaquín Migeot Agustina Legaz Raul Gonzalez-Gomez Francesca R Farina Pavel Prado Jhosmary Cuadros Enzo Tagliazucchi Florencia Altschuler Marcelo Adrián Maito María E Godoy Josephine Cruzat Pedro A Valdes-Sosa Francisco Lopera John Fredy Ochoa-Gómez Alfredis Gonzalez Hernandez Jasmin Bonilla-Santos Rodrigo A Gonzalez-Montealegre Renato Anghinah Luís E d'Almeida Manfrinati Sol Fittipaldi Vicente Medel Daniela Olivares Görsev G Yener Javier Escudero Claudio Babiloni Robert Whelan Bahar Güntekin Harun Yırıkoğulları Hernando Santamaria-Garcia Alberto Fernández Lucas David Huepe Gaetano Di Caterina Marcio Soto-Añari Agustina Birba Agustin Sainz-Ballesteros Carlos Coronel-Oliveros Amanuel Yigezu Eduar Herrera Daniel Abasolo Kerry Kilborn Nicolás Rubido Ruaridh A Clark Ruben Herzog Deniz Yerlikaya Kun Hu Mario A Parra Pablo Reyes Adolfo M García Diana L Matallana José Alberto Avila-Funes Andrea Slachevsky María I Behrens Nilton Custodio Juan F Cardona Pablo Barttfeld Ignacio L Brusco Martín A Bruno Ana L Sosa Ortiz Stefanie D Pina-Escudero Leonel T Takada Elisa Resende Katherine L Possin Maira Okada de Oliveira Alejandro Lopez-Valdes Brian Lawlor Ian H Robertson Kenneth S Kosik Claudia Duran-Aniotz Victor Valcour Jennifer S Yokoyama Bruce Miller Agustin Ibanez Latin American Brain Health Institute Universidad Adolfo Ibañez Santiago de Chile Chile. Cognitive Neuroscience Center Universidad de San Andrés Buenos Aires Argentina. Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston MA USA. Universidad de los Andes Bogota Colombia. Global Brain Health Institute (GBHI) University of California San Francisco CA USA. Global Brain Health Institute (GBHI) Trinity College Dublin Dublin Ireland. The University of California Santa Barbara (UCSB) Santa Barbara CA USA. Escuela de Fonoaudiología Universidad San Sebastián Santiago de Chile Chile. Grupo de Bioingeniería Decanato de Investigación Universidad Nacional Experimental del Táchira San Cristóbal Venezuela. Advanced Center for Electrical and Electronic Engineering Universidad Técnica Federico Santa María Valparaíso Chile. University of Buenos Aires Buenos Aires Argentina. The Clinical Hospital of Chengdu Brain Sciences Institute University of Electronic Sciences and Technology of China Chengdu China. Technology of China Chengdu China. Cuban Neuroscience Center La Habana Cuba. Grupo de Neurociencias de Antioquia (GNA) University of Antioquia Medellín Colombia. Department of Psychology Master Program of Clinical Neuropsychology Universidad Surcolombiana Neiva Neiva Colombia. Department of Psychology Universidad Cooperativa de Colombia Arauca Colombia. Neurocognition and Psychophysiology Laboratory Universidad Surcolombiana Neiva Colombia. Reference Center of Behavioural Disturbances and Dementia School of Medicine University of Sao Paulo Sao Paulo Brazil. Traumatic Brain Injury Cognitive Rehabilitation Out-Patient Center University of Sao Paulo Sao Paulo Brazil. Center for Social and Cognitive Neuroscience School of Psychology Universidad Adolfo Ibáñez Santiago Chile. Neuropsychology and Clinical Neuroscience Laboratory (LANNEC) Physiopathology Program-Institute of Biomedical Sciences (ICBM) Neuroscience and East Neuroscience Dep

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