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Optimizing near-carbon-free nuclear energy systems:advances in reactor operation digital twin through hybrid machine learning algorithms for parameter identification and state estimation

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nuclear Science and Techniques 2024年第8期35卷 177-203页

作者： Li‑Zhan Hong He‑Lin Gong Hong‑Jun Ji Jia‑Liang Lu Han Li Qing Li Paris Elite Institute of technology Shanghai Jiao Tong UniversityShanghai 200240China Science and technology on Reactor System Design technology Laboratory Nuclear Power Institute of ChinaChengdu 610041China

Accurate and efficient online parameter identification and state estimation are crucial for leveraging digital twin simulations to optimize the operation of near-carbon-free nuclear energy *** previous studies,we developed a reactor operation digital twin(RODT).However,non-differentiabilities and discontinuities arise when employing machine learning-based surrogate forward models,challenging traditional gradient-based inverse methods and their *** study investigated deterministic and metaheuristic algorithms and developed hybrid algorithms to address these *** efficient modular RODT software framework that incorporates these methods into its post-evaluation module is presented for comprehensive *** methods were rigorously assessed based on convergence profiles,stability with respect to noise,and computational *** numerical results show that the hybrid KNNLHS algorithm excels in real-time online applications,balancing accuracy and efficiency with a prediction error rate of only 1%and processing times of less than 0.1 ***,algorithms such as FSA,DE,and ADE,although slightly slower(approximately 1 s),demonstrated higher accuracy with a 0.3%relative L_2 error,which advances RODT methodologies to harness machine learning and system modeling for improved reactor monitoring,systematic diagnosis of off-normal events,and lifetime management *** developed modular software and novel optimization methods presented offer pathways to realize the full potential of RODT for transforming energy engineering practices.

关键词： Parameter identification State estimation Reactor operation digital twin Reduced order model Inverse problem

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A green route to synthesize low-cost and high-performance hard carbon as promising sodium-ion battery anodes from sorghum stalk waste

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Green Energy & Environment 2017年第3期2卷 310-315页

作者： Xiaoming Zhu Xiaoyu Jiang Xiaoling Liu Lifen Xiao Yuliang Cao hubei collaboration innovation center of non-power nuclear technology School of nuclear technology & Chemistry and Biology Hubei University of Science and Technology hubei Key Lab.of Electrochemical power Sources College of Chemistry and Molecular Sciences Wuhan University College of Chemistry Central China Normal University

Sodium-ion batteries(SIBs) have been considered to be potential candidates for next-generation low-cost energy storage systems due to the low-cost and abundance of Na resources. However, it is a big challenge to find suitable anode materials with low-cost and good performance for the application of SIBs. Hard carbon could be a promising anode material due to high capacity and expectable low-cost if originating from biomass. Herein, we report a hard carbon material derived from abundant and abandoned biomass of sorghum stalk through a simple carbonization method. The effects of carbonization temperature on microstructure and electrochemical performance are investigated. The hard carbon carbonized at 1300 ℃ delivers the best rate capability(172 mAh g^(-1) at 200 mA g^(-1)) and good cycling performance(245 mAh g^(-1) after 50 cycles at 20 mA g^(-1),96% capacity retention). This contribution provides a green route for transforming sorghum stalk waste into "treasure"of promising low-cost anode material for SIBs.

关键词： Sorghum stalk Hard carbon Anode Sodium-ion battery Carbonization

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Solution extraction of several lanthanides from nitric acid with isohexyl-BTP in [C_nmim][NTf_2] ionic liquid

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Journal of Rare Earths 2015年第11期33卷 1182-1188页

作者：赵龙董珍马国龙袁威津 non-power nuclear technology Collaborative innovation center School of Nuclear Technology and Chemistry & Life Science Hubei University of Science and Technology nuclear Chemical Engineering Laboratory School of Nuclear Science and Engineering Shanghai Jiao Tong University

The extraction behavior of several lanthanides（La^3＋, Eu^3＋, Lu^3＋） from nitric acid（HNO3） solution was studied using a novel extraction system based on 2,6-bis（5,6-dihexyl-1,2,4-triazin-3-yl） pyridine（isohexyl-BTP） as extractant in 1-alkyl-3-methylimidazolium bis（trifluoromethylsufonyl）imide（[Cnmim][NTf2]） ionic liquid. Isohexyl-BTP in ionic liquids exhibited remarkably better extraction performance for lanthanides than that in octanol-dodecane（3：7 v/v） system. Lower HNO3 concentration and short alkyl chain length of [Cnmim]^＋ were more favourable for removal of lanthanides. Besides, it was confirmed that isohexyl-BTP in ILs formed a 1：3 complex [Ln（BTP）3（NO3）n]^（3–n）＋（n=0, 1） by slope analysis. In addition, [C2mim][NTf2] preferred to extract lanthanides via a cation exchange mechanism at lower acidity, which was proved via UV-Vis measurement. It was speculated that extraction mechanism shifted from cation exchange to neutral species extraction with increase in HNO3 concentration and alkyl chain length of [Cnmim]^＋ due to the H^＋ completion, NO3^- inhibition and hydrophobicity of IL.

关键词： lanthanides extraction ionic liquids isohexyl-BTP rare earths

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Polymerization of Butyl Methacrylate Catalyzed by Salicylaldehyde-Imine Zirconium/Al(i-Bu)_3 System

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Journal of Wuhan University of technology(Materials Science) 2018年第2期33卷 492-499页

作者：程正载 TANG Ran 谢聪 WANG Yun DING Ling WANG Handing YAN Xiaochao ZHU Sanyong Gauthier Mario School of Chemisty and Chemical Engineering Wuhan University of Science and Technology hubei Province Key Laboratory of Coal Conversion And Novel Carbon Materials Chemistry Department University of Florida hubei collaboration Innovative center for non-power nuclear technology Hubei University of Science and Technology

A new kind of zirconium（Zr） complex containing ligand of salicylaldehyde-imine was successfully synthesized with ZrCl_4·2 THF and salicylaldehyde-imine as raw materials. The ligand was characterized by means of ~1HNMR, IR, and GC-MS, and Zr complex was characterized by means of ~1HNMR and IR, respectively. The Zr complex, combined with co-catalyst of Al（i-Bu）_3, was explored to be effective catalytic system for the polymerization of butyl methacrylate（BMA）, to prepare poly-n-butyl methacrylate（PBMA）, which was characterized by IR, ~13C-NMR and GPC. Compared with other double-component（MAO/Cat, AlEt_3/Cat） catalytic systems, catalytic system of Al（i-Bu）_3 and the Zr complex provided the best catalytic activity under the same conditions. The influence of polymerization parameters, such as molar ratio of Al（i-Bu）_3/Cat and BMA/Cat, polymerization temperature and polymerization time, was studied with Zr complex/Al（i-Bu）_3 system. With increasing polymerization time from 4 to 24 hour, the monomer conversion increased from 40.14% to 96.56%. Viscosity-average molecular weight（M_v） of PBMA, detected by the viscosity methodology, increased from 12.67×10~4Da to 44.97×10~4Da and lower molecular weight distribution was obtained. According to these results, the Zr complex contained ligand of salicylaldehyde-imine was a kind of readily, long lifetime and high activity catalyst for BMA polymerization.

关键词： salicylaldehyde-imine zirconium catalyzed polymerization butyl methacrylate

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Differentiation of Chemisorption and Physisorption of Carbon Dioxide on Imidazolium-type Poly(ionic liquid)Brushes

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Journal of Wuhan University of technology(Materials Science) 2020年第4期35卷 750-757页

作者： ZHANG Dongyu QU Rong ZHANG Haining ZHANG Fangfang technology center China Tobacco Henan Industrial Co.Ltd.Zhengzhou 450000China non-power nuclear technology Collaborative innovation center Hubei University of Science and TechnologyXianning 437100China State Key Laboratory of Advanced technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China

Amine-functionalized imidazolium-based poly(ionic liquid)brushes on mesoporous silica were synthesized via"grafting through"technique and were applied as model sorbents to understand physisorption and chemisorption of carbon dioxide *** experimental results reveal that the total adsorption capacity of model sorbents derived from temperature programmed desorption(TPD)approach reaches 1.72 mmol·g^-1 that is much higher than the sum of adsorption capacity of bare mesoporous silica and free polymers at 25℃under carbon dioxide partial pressure of 0.2 *** proposed physical adsorption and chemical adsorption of carbon dioxide molecules in TPD response curves were validated by volumetric desorption *** is also observed that physical adsorption is completely reversible and chemical adsorption is *** results demonstrate that the temperature programmed desorption technique is an effective approach to differentiate chemisorption and physisorption of gaseous species on solid sorbents,which is beneficial for understanding of adsorption mechanism and materials design.

关键词： adsorption surface-attachment poly(ionic liquid) grafting through carbon dioxide

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological Research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou Key Laboratory of Genetic Evolution and Animal Models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health center and Psychiatric Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical Medical Research center for Mental Disorders ChengduSichuan 610044China German Primate center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary Animal Diseases center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering Research center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew Animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

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Th(Ⅳ) and U(Ⅵ) removal by TODGA in ionic liquids:extraction behavior and mechanism,and radiation effect

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nuclear Science and Techniques 2017年第5期28卷 28-34页

作者： Zhen Dong Wei-Jin Yuan Chao Liu Long Zhao Chao Zhao Fang-Dong Tang Lin-Feng He non-power nuclear technology Collaborative innovation center School of Nuclear Technology and Chemistry & Biology Hubei University of Science and TechnologyXianning 437100 China School of nuclear Science and Engineering Shanghai Jiao Tong University Shanghai 200240 China Division of Chemistry and Ionizing Radiation Measurement technology Shanghai Institute of Measurement and Testing Technology Shanghai 201203 China

Extraction behavior of thorium(Ⅳ) and uranium(Ⅵ) from nitric acid(HNO_3) was studied using N,N,N',N'-tetraoctyldiglycolamide(TODGA) as extractant in different ionic liquids, and isooctane as *** analyses with varying HNO_3 concentrations and diluents revealed the extraction mechanism. With increasing length of alkyl chain and HNO_3 concentration, the extraction mechanism of TODGA/IL system changed from cation exchange to neutral complex and/or anion exchange,and the molar ratio between TODGA and metal ions varied gradually from 2:1 to 1:1 for Th(Ⅳ) and 3:1 to 1:1 for U(Ⅵ). The kinetics and thermodynamic studies of Th(Ⅳ)and U(Ⅵ) by the best TODGA/[C_2mim][NTf_2] system showed that the extraction equilibrium was reached within 2 h and extraction reactions were endothermic. Compared to TODGA/isooctane system, TODGA/[C_2mim][NTf_2]system presented higher radiation stability under c-irradiation. Therefore, it would have a promising application in spent fuel reprocessing.

关键词： Extraction TODGA Ionic liquids Thorium(IV) and uranium(VI) Radiation effect

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Systematic study of two-proton radioactivity within a Gamow-like model

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Chinese Physics C 2021年第4期45卷 359-365页

作者： Hong-Ming Liu Xiao Pan You-Tian Zou Jiu-Long Chen Jun-Hao Cheng Biao He Xiao-Hua Li School of nuclear Science and technology University of South ChinaHengyang 421001China Xiang Yang NO.1 People's Hospital Xiangyang 441000China nuclear power Institute of China Chengdu 610041China College of Physics and Electronics Central South UniversityChangsha 410083China National Exemplary Base for International Sci&Tech.collaboration of nuclear Energy and nuclear Safety University of South ChinaHengyang 421001China Cooperative innovation center for nuclear Fuel Cycle technology&Equipment University of South ChinaHengyang 421001China

In this study,based on the Gamow-like model,we systematically analyze two-proton(2p) radioactivity half-lives of nuclei near or beyond the proton drip *** is found that the calculated results can reproduce experimental data ***,using this model,we predict the half-lives of possible 2p radioactivity candidates whose 2p radioactivity is energetically allowed or observed but not yet quantified in the latest table of evaluated nuclear properties,i.e.,*** predicted results are in good agreement with those from other theoretical models and empirical formulas,namely the effective liquid drop model(ELDM),generalized liquid drop model(GLDM),Sreej a formula,and Liu formula.

关键词： two-proton radioactivity Gamow-like model half-life

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CEPC Technical Design Report

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Radiation Detection technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai Yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen Huirun Chen Jinhui Chen Ji-Yuan Chen Kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH University of Science and technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu KaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China center of Advanced Science and technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of nuclear Problems of Joint Institute for nuclear Research(DLNP JINR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

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Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

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Acta Pharmaceutica Sinica B 2023年第1期13卷 213-226页

作者： Ahmed Haider Xiaoyun Deng Olivia Mastromihalis Stefanie K.Pfister Troels E.Jeppesen Zhiwei Xiao Vi Pham Shaofa Sun Jian Rong Chunyu Zhao Jiahui Chen Yinlong Li Theresa R.Connors April T.Davenport James B.Daunais Vahid Hosseini Wenqing Ran Arthur Christopoulos Lu Wang Celine Valant Steven H.Liang Department of Radiology Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical SchoolBostonMA 02114USA Department of nuclear Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Drug Discovery Biology Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia Neuromedicines Discovery Centre Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia hubei Collaborative innovation Centre for non-power nuclear technology College of Nuclear Technology&Chemistry and BiologyHubei University of Science and TechnologyXianning 437100China Department of Neurology Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Physiology and Pharmacology Wake Forest School of MedicineWinston SalemNC 27157USA Terasaki Institute for Biomedical innovation(TIBI) Los AngelesCA 90024USA center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI Centerthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor4(M4)in schizophrenia and dementia with Lewy bodies,however,a clinically validated M4positron emission tomography(PET)radioligand is currently *** such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the ***-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12—a subtype-selective positive allosteric modulator(PAM).The radiofluorinated analogue,[18F]12,was synthesized in 28±10%radiochemical yield,>37 GBq/μmol and an excellent radiochemical purity>99%.Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of[18F]12 for the M4-rich ***,in the presence of carbachol,a significant increase in tracer binding was observed in the rat striatum,which was reduced by>60%under blocking conditions,thus indicating that orthosteric ligand interaction is required for efficient binding o f[18F]12 to the allosteric ***,however,the presence of carbachol was not required for high specific binding in the non-human primate(NHP)and human striatum,and did not further improve the specificity and selectivity of[18F]12 in higher *** results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP,where peak brain uptake of[18F]12 was found in the putamen and temporal *** conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising *** availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

关键词： Muscarinicacetylcholine receptor Positronemission tomography Neuroimaging Neuropharmacology Neurological disorders

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