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38th International Cosmic Ray Conference, ICRC 2023

作者： Di Pierro, F. Berti, A. de Menezes, R. Jobst, E. Ohtani, Y. Sitarek, J. Suda, Y. Visentin, E. Abe, H. Abe, K. Abe, S. Abhir, J. Acciari, V.A. Aguasca-Cabot, A. Agudo, I. Alvarez Crespo, N. Aniello, T. Ansoldi, S. Antonelli, L.A. Aramo, C. Arbet-Engels, A. Cornelia, A. Artero, M. Asano, K. Aubert, P. Baack, D. Babić, A. Baktash, A. Bamba, A. Baquero Larriva, A. Baroncelli, L. Barres de Almeida, U. Barrio, J.A. Batkovic, I. Baxter, J. Becerra González, J. Bednarek, W. Bernardini, E. Bernardos, M.I. Bernete Medrano, J. Besenrieder, J. Bhattacharjee, P. Biederbeck, N. Bigongiari, C. Biland, A. Bissaldi, E. Blanch, O. Bonnoli, G. Bordas, P. Bošnjak, Ž. Bulgarelli, A. Burelli, I. Burmistrov, L. Buscemi, M. Busetto, G. Campoy-Ordaz, A. Cardillo, M. Caroff, S. Carosi, A. Carosi, R. Carrasco, M.S. Carretero-Castrillo, M. Cassol, F. Castro-Tirado, A.J. Cauz, D. Cerasole, D. Ceribella, G. Chai, Y. Cheng, K. Chiavassa, A. Chikawa, M. Chilingarian, A. Chytka, L. Cifuentes, A. Cikota, S. Colombo, E. Contreras, J.L. Cortina, J. Costantini, H. Covino, S. D’Amico, G. Dalchenko, M. D’Elia, V. Da Vela, P. Dazzi, F. De Angelis, A. de Bony de Lavergne, M. De Lotto, B. De Lucia, M. de Menezes, R. Del Peral, L. Deleglise, G. Delfino, M. Delgado, C. Delgado Mengual, J. della Volpe, D. Dellaiera, M. Del Popolo, A. Depaoli, D. Di Piano, A. Di Pierro, F. Di Pilato, A. Di Tria, R. Di Venere, L. Díaz, C. Dominik, R.M. Dominis Prester, D. Donini, A. Dorner, D. Doro, M. Eisenberger, L. Elsässer, D. Emery, G. Escudero, J. Fallah Ramazani, V. Fariña, L. Fattorini, A. Ferrara, G. Ferrarotto, F. Fiasson, A. Foffano, L. Font, L. Freixas Coromina, L. Fröse, S. Fukami, S. Fukazawa, Y. Garcia, E. Garcia López, R. Garczarczyk, M. Gasbarra, C. Gasparrini, D. Gasparyan, S. Gaug, M. Geyer, D. Giesbrecht Paiva, J. Giglietto, N. Giordano, F. Gliwny, P. Godinovic, N. Grau, R. Green, J. Green, D. Gunji, S. Günther, P. Hackfeld, J. Hadasch, D. Hahn, A. Hashiyama, K. Hassan, T. Hayashi, K. INFN Torino Via P. Giuria 1 Torino Italy Max-Planck-Institut für Physik Föhringer Ring 6 München Germany Università degli Studi di Torino Dipartimento di Fisica Via P. Giuria 1 Torino Italy University of Tokyo Institute for Cosmic Ray Research 5-1-5 Kashiwa-no-ha Chiba Kashiwa277-8582 Japan University of Lodz Faculty of Physics and Applied Informatics ul. Pomorska 149-153 Lodz Poland Hiroshima University Physics Program Graduate School of Advanced Science and Engineering Hiroshima739-8526 Japan Department of Physics Tokai University Japan ETH Zürich Switzerland Instituto de Astrofísica de Canarias Departamento de Astrofísica Universidad de La Laguna Spain Departament de Física Quàntica i Astrofísica Institut de Ciències del Cosmos Universitat de Barcelona IEEC-UB Spain Instituto de Astrofísica de Andalucía-CSIC Spain EMFTEL department IPARCOS Universidad Complutense de Madrid Spain Italy INFN Sezione di Trieste Università degli Studi di Udine Italy Italy INAF - Osservatorio Astronomico di Roma Italy INFN Sezione di Napoli Italy INFN Sezione di Padova Università degli Studi di Padova Italy The Barcelona Institute of Science and Technology Spain LAPP Univ. Grenoble Alpes Univ. Savoie Mont Blanc CNRS-IN2P3 Annecy France Department of Physics TU Dortmund University Germany Croatia Universität Hamburg Institut für Experimentalphysik Germany Graduate School of Science University of Tokyo Japan Universidad del Azuay Ecuador INAF - Osservatorio di Astrofisica e Scienza dello spazio di Bologna Italy Centro Brasileiro de Pesquisas Físicas Brazil CIEMAT Spain INFN Sezione di Bari Politecnico di Bari Italy INAF - Osservatorio Astronomico di Brera Italy University of Geneva Département de physique nucléaire et corpusculaire Switzerland INFN Sezione di Catania Italy Departament de Física CERES-IEEC Universitat Autónoma de Barcelona Spain Italy Università di Pisa INFN Pisa Italy Aix Marseille Univ CNRS IN2P3 CPPM France INFN Sezione di Bari

The prototype Large-Sized Telescope (LST-1) of the Cherenkov Telescope Array Observatory (CTAO) is in commissioning phase at the Observatorio del Roque de Los Muchachos at 2200 m a.s.l. in La Palma (Canary Islands, Spain). LST-1 is a 23-m diameter telescope and is the first of four that will compose the LST part of the CTAO Northern array. The LST subarray is optimized to provide the best sensitivity for gamma rays in the 20 GeV - 200 GeV energy range. The MAGIC telescopes, which are located approximately 100 m from the LST-1, is operating as a two 17-m telescope stereoscopic system for more than 14 years. LST-1 and MAGIC routinely perform joint observations of gamma-ray sources to exploit the potential of the three-telescope system. This contribution describes the analysis pipeline and evaluates the performance of the system using Monte Carlo simulations and data on the Crab Nebula. The sensitivity achieved during joint observations with MAGIC and LST-1 is about 30% higher than that of MAGIC alone. © Copyright owned by the author(s) under the terms of the Creative Commons.

关键词： Stereo image processing

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Assessing The Monetary Value Of Ecosystem Services Provided By Gaung – Batang Tuaka Peat Hydrological Unit (Khg), Riau Province

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Heliyon 2021年第10期7卷 e08208页

作者： Rossita, Annuri Nurrochmat, Dodik Ridho Boer, Rizaldi Hein, Lars Riqqi, Akhmad Applied Climatology Study Program The Graduate School Of Ipb University Bogor Indonesia Center For Climate Risk And Opportunity Management In South East Asia And Pacific (Ccrom-Seap) Ipb University Bogor Indonesia Department Of Forest Management Faculty Of Forestry And Environment Ipb University Bogor 16680 Indonesia Environmental Science Analysis Group Wageningen University and Research Wageningen Netherlands Faculty of Earth Science and Technology Bandung Institute of Technology (ITB) Indonesia

Peatland Plays A Pivotal Role In Providing Natural Resource Production And environmental Services For Human Welfare. However, Many Studies Have Mentioned The Impact Of Dryland Cultivation In Peatland On The Shifting Carbon Balance In The Ecosystem That Clearly Will Alter The Interaction Of These Two Ecosystem Services. The Goal Of This Study, Conducted Under The Framework Of The System Of environmental-Economic Accounting (Seea) Was To Monetary Value The Ecosystem Services (Es) Of Provisioning And Carbon Regulating Services Of The Gaung-Batang Tuaka Peat Hydrological Unit (Khg). We Focused On Khg In Response To Regulation No.57/2016, Which Highlights Ecosystem Boundary As A New Basis For Peatland Management. Under The Seea Framework, Ecosystem Services Become A Benefit When Utilized By Ecosystem Beneficiaries. In This Case, Provisioning Services Will Be Valued Only For Cultivated Land, While Carbon Services Calculated For The Entire Study Area (Global Beneficiaries). Our Study Showed That The Provisioning Services And Carbon Services Are Under The Trade-Off Condition, Where The Monetary Value Of Provisioning Services Increased At A Slower Rate (0.50 Million Usd Annually) Than The Monetary Loss Of The Benefit Of Carbon Services (5.28 Million Usd Annually), Greatly Exceeded The Monetary Value Of Provisioning Services. We Highlight Two Main Strategies To Increase The Monetary Value Of The Khg Towards A Synergy Condition, Namely Increased Value-Added By Reducing The Productivity Gap Among Es Beneficiaries And Large-Scale Adoption Of A Profitable Cultivation System With Minimum Peat Disturbance. The Main Enablers Required Include Financing Access And Incentives (E.G., Reduce Tax) And Disincentives To Allow For Peat-Adaptive Commodities To Compete With Dryland Commodities In The Future Market © 2021 The Authors. Published by Elsevier Ltd

关键词： Ecosystem Services Monetary Value Peat Hydrological Unit Peatland Management Riau

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Retraction notice to "Toxicity assessment of SARS-CoV-2-derived peptides in combination with a mix of pollutants on zebrafish adults: A perspective study of behavioral, biometric, mutagenic, and biochemical toxicity" [Sci. Total Environ. 858 Part 2 (2023) 159838]

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The science of the total environment 2024年 957卷 177710页

作者： Ítalo Nascimento Freitas Amanda Vieira Dourado Amanda Pereira da Costa Araújo Sindoval Silva de Souza Thiarlen Marinho da Luz Abraão Tiago Batista Guimarães Alex Rodrigues Gomes Abu Reza Md Towfiqul Islam Md Mostafizur Rahman Andrés Hugo Arias Davoodbasha Mubarak Ali Chinnasamy Ragavendran Chinnaperumal Kamaraj Guilherme Malafaia Laboratory of Toxicology Applied to the Environment Goiano Federal Institute Urutaí GO Brazil Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil. Laboratory of Toxicology Applied to the Environment Goiano Federal Institute Urutaí GO Brazil. Post-Graduation Program in Environmental Sciences Federal University of Goiás Goiânia GO Brazil. Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil. Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute Urutaí GO Brazil. Begum Rokeya University Department of Disaster Management Rangpur 5404 Bangladesh. Laboratory of Environmental Health and Ecotoxicology Department of Environmental Sciences Jahangirnagar University Dhaka 1342 Bangladesh. Instituto Argentino de Oceanografía (IADO) Universidad Nacional del Sur (UNS)-CONICET Florida 8000 Complejo CCT CONICET Bahía Blanca Edificio E1 B8000BFW Bahía Blanca Argentina. Petroleum and Chemical Engineering Faculty of Engineering Universiti Teknologi Brunei Bandar Seri Begawan BE1410 Brunei Darussalam. Department of Conservative Dentistry and Endodontics Saveetha Dental College and Hospitals Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai India. Interdisciplinary Institute of Indian System of Medicine (IIISM) Directorate of Research and Virtual Education SRM Institute of Science and Technology (SRMIST) Kattankulathur 603203 Tamil Nadu India. Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil

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Retraction notice to "Personal protective equipment-derived pollution during Covid-19 era: A critical review of ecotoxicology impacts, intervention strategies, and future challenges" [Sci. Total Environ. 887(2023) 164164]

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The science of the total environment 2025年 967卷 178758页

作者： Mehedi Hasan Abu Reza Md Towfiqul Islam Most Mastura Munia Farjana Jion Md Naimur Rahman Susmita Datta Peu Arnob Das A B M Mainul Bari Md Saiful Islam Subodh Chandra Pal Aznarul Islam Tasrina Rabia Choudhury Md Refat Jahan Rakib Abubakr M Idris Guilherme Malafaia Department of Disaster Management Begum Rokeya University Rangpur 5400 Bangladesh. Department of Disaster Management Begum Rokeya University Rangpur 5400 Bangladesh Department of Development Studies Daffodil International University Dhaka 1216 Bangladesh. Department of Geography and Environmental Science Begum Rokeya University Rangpur 5400 Bangladesh. Department of Agriculture Hajee Mohammad Danesh Science and Technology University Dinajpur 5200 Bangladesh. Department of Mechanical Engineering Rajshahi University of Engineering & Technology 6 Rajshahi 6204 Bangladesh. Department of Industrial and Production Engineering Bangladesh University of Engineering and Technology Dhaka 1000 Bangladesh. Department of Soil Science Patuakhali Science and Technology University Dumki Patuakhali 8602 Bangladesh. Department of Geography The University of Burdwan Bardhaman 713104 West Bengal India. Department of Geography Aliah University 17 Gorachand Road Kolkata 700 014 West Bengal India. Analytical Chemistry Laboratory Chemistry Division Atomic Energy Centre Dhaka (AECD) Bangladesh Atomic Energy Commission Dhaka 1000 Bangladesh. Department of Fisheries and Marine Science Faculty of Science Noakhali Science and Technology University Noakhali Bangladesh. Department of Chemistry College of Science King Khalid University Abha 62529 Saudi Arabia Research Center for Advanced Materials Science (RCAMS) King Khalid University Abha Saudi Arabia. Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute Urutaí GO Brazil Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil.

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Retraction notice to "Traditionally used medicinal plants mediate the biosynthesis of silver nanoparticles: Methodological, larvicidal, and ecotoxicological approach" [Sci. Total Environ. 873 (2023) 162402]

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The science of the total environment 2024年 957卷 177709页

作者： Chinnaperumal Kamaraj Sugumar Vimal Chinnasamy Ragavendran Arumugam Priyadharsan K Marimuthu Guilherme Malafaia Interdisciplinary Institute of Indian System of Medicine (IIISM) Directorate of Research SRM Institute of Science and Technology (SRMIST) Kattankulathur 603203 Tamil Nadu India. Department of Biochemistry Saveetha Medical College & Hospital Saveetha Institute of Medical and Technical Sciences (SIMATS) Thandalam Chennai 602105 Tamil Nadu India. Department of Conservative Dentistry and Endodontics Saveetha Dental College and Hospitals Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai 600 077 India. Department of Environmental Science Tezpur University Napaam Tezpur Assam 784028 India. Laboratory of Toxicology Applied to the Environment Goiano Federal Institute Urutaí GO Brazil Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute Urutaí GO Brazil Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil.

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Influence of Dentin Priming with Tannin-Rich Plant Extracts on the Longevity of Bonded Composite Restorations

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Scientific World Journal 2021年第1期2021卷 1614643页

作者： Polassi, Mackeler Ramos Oliveira, Thales De Sá Carvalho, Ana Calheiros De Medeiros, Lívia Soman De Medeiros Veiga, Thiago André Moura Graeff, Carlos Frederico De Oliveira González, Alejandra Hortencia Miranda Marcucci, Maria Cristina Grecco, Simone Dos Santos Dalpino, Paulo Henrique Perlatti Universidade Anhanguera de São Paulo São Paulo Brazil Department of Chemistry Universidade Federal de São Paulo SP Diadema Brazil São Paulo State University (UNESP) School of Sciences POSMAT - Post-Graduate Program in Materials Science and Technology SP Bauru Brazil Triplet Biotechnology Solutions São Paulo Brazil Science and Technology Institute Universidade Estadual Paulista - UNESP SP São José dos Campos Brazil

Objective. This in vitro study evaluated the influence of bioactive plant extracts as dentin biomodifying agents to improve the longevity of bonded restorations. For that, plant extracts were applied to the dentin surface prior to the adhesive system. Materials and Methods. Bovine incisors were ground flat to obtain 2 mm thick slices in which conical preparations were made (N = 10). Tannin-containing plant extracts were applied to dentin before the application of the restorative system, as follows: control group (untreated, CTL), chlorhexidine 0.12% (CHX), mastruz (Dysphania ambrosioides, MTZ), cat's claw (Uncaria tomentosa, CTC), guarana (Paullinia cupana, GUA), galla chinensis (Rhus chinensis, GCH), and tannic acid (extracted from Acacia decurrens, TNA). The push-out bond strength test was conducted (0.5 mm/min). Dentin biomodification was assessed by the modulus of elasticity and mass change in bovine tooth sections (0.5 × 1.7 × 7.0 mm). The dentin staining after extract treatments of dentin slices was compared. The dentin surface wettability was also evaluated by means of the contact angles of the adhesive system with the dentin surface and compared with the untreated control group. Data were subjected to ANOVA/Tukey's test (α = 0.05). Results. The bond strength of the restoratives to dentin was not significantly improved by the plant extracts, irrespective of the evaluation time (p>0.05). Except for TNA, the elastic modulus of demineralized dentin significantly reduced after treatment with the plant extracts (p<0.05). The dentin staining correlated with the tannin content of the extracts. The contact angle was significantly reduced when treated with CTC, GCH, and TNA. Conclusions. The tannin-containing extracts had a questionable effect on the longevity of bonded restorations. The dentin modulus was negatively affected by the extract treatments. Although some of the extracts changed the contact angle, which seems to improve the adhesive monomer permeation, the

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Frailty in chronic myeloid leukemia: evidence from 2016–2018 Nationwide Inpatient Sample of the US

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BMC Geriatrics 2023年第1期23卷 334-334页

作者： Huan-Tze, Lin Yun-Ru, Liu Kuan-Der, Lee Huey-En, Tzeng Department of Internal Medicine Division of Hematology and Oncology Taipei Medical University Hospital Taipei Taiwan Joint Biobank Office of Human Research Taipei Medical University Taipei Taiwan Department of Medical Research Taichung Veterans General Hospital 1650 Boulevard Sect. 4 Taichung City 40705 Taiwan Department of Medicine Division of Hematology/Medical Oncology Taichung Veterans General Hospital Taichung City Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery and Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan

Background: Frailty is a marker of poor prognosis in older adults with hematologic malignancies and contributes to the severe vulnerability of the aging population to adverse health outcomes. This study aimed to determine the association between frailty and outcomes in hospitalized patients with chronic myeloid leukemia (CML). Methods: The International Classification of Diseases (ICD-10) identified data on hospitalized patients 20 years or older admitted with CML between 2016 and 2018 in the US National Inpatient Sample (NIS) database. The cohort was further divided into groups of patients with or without frailty. Logistic regression analysis was performed to determine associations between study variables and clinical outcomes. A stratified analysis of the association between frailty and in-hospital mortality by age group was also performed. Results: A total of 13,849 hospitalized patients with CML were included, 49.6% of whom had frailty. The mean age of the patients was 65.1 years, and 7,619 (56.2%) of them were male. Frailty was associated with nearly 4 times the risk of in-hospital mortality, 3 times the risk of unfavorable discharge, 3 times the risk of prolonged LOS, and significantly more in total hospital costs. In addition, frailty was associated with a significantly increased risk of in-hospital mortality in all age subgroups (< 40 years, 40–59 years, and > 60 years) compared with no frailty. Conclusions: Frailty strongly predicts poor clinical outcomes in US patients with CML. © 2023, The Author(s).

关键词： Chronic myeloid leukemia (CML) Frailty In-hospital outcome Nationwide Inpatient Sample (NIS)

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Retraction notice to "Gene expression profiling in liver of zebrafish exposed to ethylhexyl methoxycinnamate and its photoproducts" [Sci. Total Environ. 826 (2022) 154046]

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The science of the total environment 2024年 957卷 177655页

作者： Bojan Nataraj Kannan Maharajan Guilherme Malafaia Devan Hemalatha Mohamed Ahmed Ibrahim Ahmed Mathan Ramesh Unit of Toxicology Department of Zoology School of Life Sciences Bharathiar University Coimbatore 641046 India. Unit of Toxicology Department of Zoology School of Life Sciences Bharathiar University Coimbatore 641046 India Biology Institute Qilu University of Technology (Shandong Academy of Sciences) 28789 East Jingshi Road Jinan 250103 Shandong Province PR China. Post-Graduation Program in Environmental Sciences Federal University of Goiás Goiânia GO Brazil Post-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia Uberlândia MG Brazil Post-Graduation Program in Biotechnology and Biodiversity Federal University of Goiás Goiânia GO Brazil. Department of Zoology PSG College of Arts & Science Coimbatore Tamil Nadu 641014 India. Plant Protection Department Faculty of Agriculture Assiut University Assiut 71526 Egypt.

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Evaluation of Pollution Sources of Zinc in Tokyo Bay Based on Zinc Isotope Ratio in Sediment Core

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Journal of Geoscience and Environment Protection 2019年第8期7卷 141-154页

作者： Masahiro Sakata Shohei Okuizumi Asami Suzuki Mashio Takeshi Ohno Shuhei Sakata Graduate Program in Environmental Health Sciences University of Shizuoka Shizuoka Japan Graduate School of Natural Science and Technology Kanazawa University Kanazawa Japan Department of Chemistry Faculty of Science Gakushuin University Tokyo Japan

This study evaluated the sources of Zn pollution in Tokyo Bay, Japan, on the basis of δ66Zn in a sediment core. The Zn concentration in sediments in the 1980s-2000s was considerably higher than the background concentration, suggesting that there remain important sources of Zn in the bay. The δ66Zn (+0.51‰) of anthropogenic Zn estimated in the core was significantly higher than those (approximately –0.1‰ - +0.2‰) of treated water from sewage treatment plants and vehicle-related sources. A large number of electroplating plants are located in Tokyo areas. It is assumed that Zn in effluents from electroplating operations is isotopically heavier owing to a negative isotopic effect on Zn electroplating. This tends to support the hypothesis that river bottom sediments, which were contaminated with Zn in the untreated effluents from electroplating plants in the past, are the principal sources of anthropogenic Zn in Tokyo Bay in the 1980s-2000s.

关键词： Zinc Pollution Sources Sediment Core Zinc Isotope Ratio Tokyo Bay

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MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice

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Molecular therapy. Nucleic acids 2023年 32卷 144-160页

作者： Tai-Heng Chen Shih-Hsin Chang Yu-Fu Wu Ya-Ping Yen Fang-Yu Hsu Yen-Chung Chen Yang Ming Ho-Chiang Hsu Yi-Ching Su Sheng-Tang Wong Jui-Hung Hung Shih-Hwa Chiou Yuh-Jyh Jong Jun-An Chen PhD Program in Translational Medicine Kaohsiung Medical University Kaohsiung 80708 and Academia Sinica Taipei 11529 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan. Department of Pediatrics Kaohsiung Medical University Kaohsiung 80708 Taiwan. School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Neuroscience Program of Academia Sinica Academia Sinica Taipei 11529 Taiwan. Department of Computer Science National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan. Institute of Pharmacology School of Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan. Innovative Cellular Therapy Center Department of Medical Research Taipei Veterans General Hospital Taipei 11217 Taiwan. Department of Laboratory Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 80708 Taiwan. Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 80708 Taiwan. Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

关键词： ASO MT: Non-coding RNAs MiR34 SMA biomarker microRNA nusinersen spinal muscular atrophy

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