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1Future Physics Programme of BESⅢ显示文摘There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESⅢ and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESⅢ, as well as the threshold measurements of charm mesons and charm baryons. We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESⅢ during the remaining operation period of BEPCⅡ. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCⅡ to higher luminosity.M.Ablikim M.N.Achasov P.Adlarson S.Ahmed M.Albrecht M.Alekseev A.Amoroso F.F.An Q.An Y.Bai O.Bakina R.Baldini Ferroli Y.Ban K.Begzsuren J.V.Bennett N.Berger M.Bertani D.Bettoni F.Bianchi J Biernat J.Bloms I.Boyko R.A.Briere L.Calibbi H.Cai X.Cai A.Calcaterra G.F.Cao N.Cao S.A.Cetin J.Chai J.F.Chang W.L.Chang J.Charles G.Chelkov Chen G.Chen H.S.Chen J.C.Chen M.L.Chen S.J.Chen Y.B.Chen H.Y.Cheng W.Cheng G.Cibinetto F.Cossio X.F.Cui H.L.Dai J.P.Dai X.C.Dai A.Dbeyssi D.Dedovich Z.Y.Deng A.Denig Denysenko M.Destefanis S.Descotes-Genon F.De Mori Y.Ding C.Dong J.Dong L.Y.Dong M.Y.Dong Z.L.Dou S.X.Du S.I.Eidelman J.Z.Fan J.Fang S.S.Fang Y.Fang R.Farinelli L.Fava F.Feldbauer G.Felici C.Q.Feng M.Fritsch C.D.Fu Y.Fu Q.Gao X.L.Gao Y.Gao Y.Gao Y.G.Gao Z.Gao B.Garillon I.Garzia E.M.Gersabeck A.Gilman K.Goetzen L.Gong W.X.Gong W.Gradl M.Greco L.M.Gu M.H.Gu Y.T.Gu A.Q.Guo F.K.Guo L.B.Guo R.P.Guo Y.P.Guo A.Guskov S.Han X.Q.Hao F.A.Harris K.L.He F.H.Heinsius T.Held Y.K.Heng Y.R.Hou Z.L.Hou H.M.Hu J.F.Hu T.Hu Y.Hu G.S.Huang J.S.Huang X.T.Huang X.Z.Huang Z.L.Huang N.Huesken T.Hussain W.Ikegami Andersson W.Imoehl M.Irshad Q.Ji Q.P.Ji X.B.Ji X.L.Ji H.L.Jiang X.S.Jiang X.Y.Jiang J.B.Jiao Z.Jiao D.P.Jin S.Jin Y.Jin T.Johansson N.Kalantar-Nayestanaki X.S.Kang R.Kappert M.Kavatsyuk B.C.Ke I.K.Keshk T.Khan A.Khoukaz P.Kiese R.Kiuchi R.Kliemt L.Koch O.B.Kolcu B.Kopf M.Kuemmel M.Kuessner A.Kupsc M.Kurth M.G.Kurth W.Kuhn J.S.Lange P.Larin L.Lavezzi H.Leithoff T.Lenz C.Li Cheng Li D.M.Li F.Li F.Y.Li G.Li H.B.Li H.J.Li J.C.Li J.W.Li Ke Li L.K.Li Lei Li P.L.Li P.R.Li Q.Y.Li W.D.Li W.G.Li X.H.Li X.L.Li X.N.Li X.Q.Li Z.B.Li H.Liang H.Liang Y.F.Liang Y.T.Liang G.R.Liao L.Z.Liao J.Libby C.X.Lin D.X.Lin Y.J.Lin B.Liu B.J.Liu C.X.Liu D.Liu D.Y.Liu F.H.Liu Fang Liu Feng Liu H.B.Liu H.M.Liu Huanhuan Liu Huihui Liu J.B.Liu J.Y.Liu K.Y.Liu Ke Liu Q.Liu S.B.Liu T.Liu X.Liu X.Y.Liu Y.B.Liu Z.A.Liu Zhiqing Liu Y.F.Long X.C.Lou H.J.Lu J.D.Lu J.G.Lu Y.Lu Y.P.Lu C.L.Luo M.X.Luo P.W.Luo T.Luo X.L.Luo S.Lusso X.R.Lyu F.C.Ma H.L.Ma L.L.Ma M.M.Ma Q.M.Ma X.N.Ma X.X.Ma X.Y.Ma Y.M.Ma F.E.Maas M.Maggiora S.Maldaner S.Malde Q.A.Malik A.Mangoni Y.J.Mao Z.P.Mao S.Marcello Z.X.Meng J.G.Messchendorp G.Mezzadri J.Min T.J.Min R.E.Mitchell X.H.Mo Y.J.Mo C.Morales Morales N.Yu.Muchnoi H.Muramatsu A.Mustafa S.Nakhoul Y.Nefedov F.Nerling I.B.Nikolaev Z.Ning S.Nisar S.L.Niu S.L.Olsen Q.Ouyang S.Pacetti Y.Pan M.Papenbrock P.Patteri M.Pelizaeus H.P.Peng K.Peters A.A.Petrov J.Pettersson J.L.Ping R.G.Ping A.Pitka R.Poling V.Prasad M.Qi T.Y.Qi S.Qian C.F.Qiao N.Qin X.P.Qin X.S.Qin Z.H.Qin J.F.Qiu S.Q.Qu K.H.Rashid C.F.Redmer M.Richter M.Ripka A.Rivetti V.Rodin M.Rolo G.Rong J.L.Rosner Ch.Rosner M.Rump A.Sarantsev M.Savrie K.Schoenning W.Shan X.Y.Shan M.Shao C.P.Shen P.X.Shen X.Y.Shen H.Y.Sheng X.Shi X.D Shi J.J.Song Q.Q.Song X.Y.Song S.Sosio C.Sowa S.Spataro F.F.Sui G.X.Sun J.F.Sun L.Sun S.S.Sun X.H.Sun Y.J.Sun Y.K Sun Y.Z.Sun Z.J.Sun Z.T.Sun Y.T Tan C.J.Tang G.Y.Tang X.Tang V.Thoren B.Tsednee I.Uman B.Wang B.L.Wang C.W.Wang D.Y.Wang H.H.Wang K.Wang L.L.Wang L.S.Wang M.Wang M.Z.Wang Wang Meng P.L.Wang R.M.Wang W.P.Wang X.Wang X.F.Wang X.L.Wang Y.Wang Y.F.Wang Z.Wang Z.G.Wang Z.Y.Wang Zongyuan Wang T.Weber D.H.Wei P.Weidenkaff H.W.Wen S.P.Wen U.Wiedner G.Wilkinson M.Wolke L.H.Wu L.J.Wu Z.Wu L.Xia Y.Xia S.Y.Xiao Y.J.Xiao Z.J.Xiao Y.G.Xie Y.H.Xie T.Y.Xing X.A.Xiong Q.L.Xiu G.F.Xu L.Xu Q.J.Xu W.Xu X.P.Xu F.Yan L.Yan W.B.Yan W.C.Yan Y.H.Yan H.J.Yang H.X.Yang L.Yang R.X.Yang S.L.Yang Y.H.Yang Y.X.Yang Yifan Yang Z.Q.Yang M.Ye M.H.Ye J.H.Yin Z.Y.You B.X.Yu C.X.Yu J.S.Yu C.Z.Yuan X.Q.Yuan Y.Yuan A.Yuncu A.A.Zafar Y.Zeng B.X.Zhang B.Y.Zhang C.C.Zhang D.H.Zhang H.H.Zhang H.Y.Zhang J.Zhang J.L.Zhang J.Q.Zhang J.W.Zhang J.Y.Zhang J.Z.Zhang K.Zhang L.Zhang S.F.Zhang T.J.Zhang X.Y.Zhang Y.Zhang Y.H.Zhang Y.T.Zhang Yang Zhang Yao Zhang Yi Zhang Yu Zhang Z.H.Zhang Z.P.Zhang Z.Q.Zhang Z.Y.Zhang G.Zhao J.W.Zhao J.Y.Zhao J.Z.Zhao Lei Zhao Ling Zhao M.G.Zhao Q.Zhao S.J.Zhao T.C.Zhao Y.B.Zhao Z.G.Zhao A.Zhemchugov B.Zheng J.P.Zheng Y.Zheng Y.H.Zheng B.Zhong L.Zhou L.P.Zhou Q.Zhou X.Zhou X.K.Zhou Xingyu Zhou Xiaoyu Zhou Xu Zhou A.N.Zhu J.Zhu J.Zhu K.Zhu K.J.Zhu S.H.Zhu W.J.Zhu X.L.Zhu Y.C.Zhu Y.S.Zhu Z.A.Zhu J.Zhuang B.S.Zou J.H.Zou 2020Chinese Physics C2020,44,4:517
2Study of BESIII trigger efficiencies with the 2018 J/ψ data显示文摘Using a dedicated data sample taken in 2018 on the J/ψpeak,we perform a detailed study of the trigger efficiencies of the BESIII detector.The efficiencies are determined from three representative physics processes,namely Bhabha scattering,dimuon production and generic hadronic events with charged particles.The combined efficiency of all active triggers approaches 100%in most cases,with uncertainties small enough not to affect most physics analyses.M.Ablikim M.N.Achasov P.Adlarson S.Ahmed M.Albrecht R.Aliberti A.Amoroso M.R.An Q.An X.H.Bai Y.Bai O.Bakina R.Baldini Ferroli I.Balossino Y.Ban K.Begzsuren N.Berger M.Bertani D.Bettoni F.Bianchi J.Bloms A.Bortone I.Boyko R.A.Briere H.Cai X.Cai A.Calcaterra G.F.Cao N.Cao S.A.Cetin J.F.Chang W.L.Chang G.Chelkov D.Y.Chen G.Chen H.S.Chen M.L.Chen S.J.Chen X.R.Chen Y.B.Chen Z.J Chen W.S.Cheng G.Cibinetto F.Cossio X.F.Cui H.L.Dai X.C.Dai A.Dbeyssi R.E.de Boer D.Dedovich Z.Y.Deng A.Denig I.Denysenko M.Destefanis F.De Mori Y.Ding C.Dong J.Dong L.Y.Dong M.Y.Dong X.Dong S.X.Du Y.L.Fan J.Fang S.S.Fang Y.Fang R.Farinelli L.Fava F.Feldbauer G.Felici C.Q.Feng J.H.Feng M.Fritsch C.D.Fu Y.Gao Y.Gao Y.Gao Y.G.Gao I.Garzia P.T.Ge C.Geng E.M.Gersabeck A Gilman K.Goetzen L.Gong W.X.Gong W.Gradl M.Greco L.M.Gu M.H.Gu S.Gu Y.T.Gu C.Y Guan A.Q.Guo L.B.Guo R.P.Guo Y.P.Guo A.Guskov T.T.Han W.Y.Han X.Q.Hao F.A.Harris H Hüsken K.L.He F.H.Heinsius C.H.Heinz T.Held Y.K.Heng C.Herold M.Himmelreich T.Holtmann Y.R.Hou Z.L.Hou H.M.Hu J.F.Hu T.Hu Y.Hu G.S.Huang L.Q.Huang X.T.Huang Y.P.Huang Z.Huang T.Hussain W.Ikegami Andersson W.Imoehl M.Irshad S.Jaeger S.Janchiv Q.Ji Q.P.Ji X.B.Ji X.L.Ji H.B.Jiang X.S.Jiang J.B.Jiao Z.Jiao S.Jin Y.Jin T.Johansson N.Kalantar-Nayestanaki X.S.Kang R.Kappert M.Kavatsyuk B.C.Ke I.K.Keshk A.Khoukaz P.Kiese R.Kiuchi R.Kliemt L.Koch O.B.Kolcu B.Kopf M.Kuemmel M.Kuessner A.Kupsc M.G.Kurth W.Kühn J.J.Lane J.S.Lange P.Larin A.Lavania L.Lavezzi Z.H.Lei H.Leithoff M.Lellmann T.Lenz C.Li C.H.Li Cheng Li D.M.Li F.Li G.Li H.Li H.Li H.B.Li H.J.Li J.L.Li J.Q.Li J.S.Li Ke Li L.K.Li Lei Li P.R.Li S.Y.Li W.D.Li W.G.Li X.H.Li X.L.Li Z.Y.Li H.Liang H.Liang H.Liang Y.F.Liang Y.T.Liang L.Z.Liao J.Libby C.X.Lin B.J.Liu C.X.Liu D.Liu F.H.Liu Fang Liu Feng Liu H.B.Liu H.M.Liu Huanhuan Liu Huihui Liu J.B.Liu J.L.Liu J.Y.Liu K.Liu K.Y.Liu Ke Liu L.Liu M.H.Liu P.L.Liu Q.Liu Q.Liu S.B.Liu Shuai Liu T.Liu W.M.Liu X.Liu Y.Liu Y.B.Liu Z.A.Liu Z.Q.Liu X.C.Lou F.X.Lu H.J.Lu J.D.Lu J.G.Lu X.L.Lu Y.Lu Y.P.Lu C.L.Luo M.X.Luo b P.W.Luo T.Luo X.L.Luo S.Lusso X.R.Lyu F.C.Ma H.L.Ma L.L.Ma M.M.Ma Q.M.Ma R.Q.Ma R.T.Ma X.X.Ma X.Y.Ma F.E.Maas M.Maggiora S.Maldaner S.Malde Q.A.Malik A.Mangoni Y.J.Mao Z.P.Mao S.Marcello Z.X.Meng J.G.Messchendorp G.Mezzadri T.J.Min R.E.Mitchell X.H.Mo Y.J.Mo N.Yu.Muchnoi H.Muramatsu S.Nakhoul Y.Nefedov F.Nerling I.B.Nikolaev Z.Ning S.Nisar S.L.Olsen Q.Ouyang S.Pacetti X.Pan Y.Pan A.Pathak P.Patteri M.Pelizaeus H.P.Peng K.Peters J.Pettersson J.L.Ping R.G.Ping R.Poling V.Prasad H.Qi H.R.Qi K.H.Qi M.Qi T.Y.Qi T.Y.Qi S.Qian W.-B.Qian Z.Qian C.F.Qiao L.Q.Qin X.S.Qin Z.H.Qin J.F.Qiu S.Q.Qu K.H.Rashid K.Ravindran C.F.Redmer A.Rivetti V.Rodin M.Rolo G.Rong Ch.Rosner M.Rump H.S.Sang A.Sarantsev Y.Schelhaas C.Schnier K.Schoenning M.Scodeggio D.C.Shan W.Shan X.Y.Shan J.F.Shangguan M.Shao C.P.Shen P.X.Shen X.Y.Shen H.C.Shi R.S.Shi X.Shi X.D Shi W.M.Song Y.X.Song S.Sosio S.Spataro K.X.Su P.P.Su F.F.Sui G.X.Sun H.K.Sun J.F.Sun L.Sun S.S.Sun T.Sun W.Y.Sun X Sun Y.J.Sun Y.K.Sun Y.Z.Sun Z.T.Sun Y.H.Tan Y.X.Tan C.J.Tang G.Y.Tang J.Tang J.X.Teng V.Thoren I.Uman B.Wang C.W.Wang D.Y.Wang H.J.Wang H.P.Wang K.Wang L.L.Wang M.Wang M.Z.Wang Meng Wang W.Wang W.H.Wang W.P.Wang X.Wang X.F.Wang X.L.Wang Y.Wang Y.D.Wang Y.F.Wang Y.Q.Wang Y.Y.Wang Z.Wang Z.Y.Wang Ziyi Wang Zongyuan Wang D.H.Wei P.Weidenkaff F.Weidner S.P.Wen D.J.White U.Wiedner G.Wilkinson M.Wolke L.Wollenberg J.F.Wu L.H.Wu L.J.Wu X.Wu Z.Wu L.Xia H.Xiao S.Y.Xiao Z.J.Xiao X.H.Xie Y.G.Xie Y.H.Xie T.Y.Xing G.F.Xu Q.J.Xu W.Xu X.P.Xu F.Yan L.Yan W.B.Yan W.C.Yan Xu Yan H.J.Yang H.X.Yang L.Yang S.L.Yang Y.X.Yang Yifan Yang Zhi Yang M.Ye M.H.Ye J.H.Yin Z.Y.You B.X.Yu C.X.Yu G.Yu J.S.Yu T.Yu C.Z.Yuan L.Yuan X.Q.Yuan Y.Yuan Z.Y.Yuan C.X.Yue A.Yuncu A.A.Zafar Y.Zeng B.X.Zhang Guangyi Zhang H.Zhang H.H.Zhang H.Y.Zhang J.J.Zhang J.L.Zhang J.Q.Zhang J.W.Zhang J.Y.Zhang J.Z.Zhang Jianyu Zhang Jiawei Zhang L.Q.Zhang Lei Zhang S.Zhang S.F.Zhang Shulei Zhang X.D.Zhang X.Y.Zhang Y.Zhang Y.H.Zhang Y.T.Zhang Yan Zhang Yao Zhang Yi Zhang Z.H.Zhang Z.Y.Zhang G.Zhao J.Zhao J.Y.Zhao J.Z.Zhao Lei Zhao Ling Zhao M.G.Zhao Q.Zhao S.J.Zhao Y.B.Zhao Y.X.Zhao Z.G.Zhao A.Zhemchugov B.Zheng J.P.Zheng Y.Zheng Y.H.Zheng B.Zhong C.Zhong L.P.Zhou Q.Zhou X.Zhou X.K.Zhou X.R.Zhou A.N.Zhu J.Zhu K.Zhu K.J.Zhu S.H.Zhu T.J.Zhu W.J.Zhu W.J.Zhu Y.C.Zhu Z.A.Zhu B.S.Zou J.H.Zou 2021Chinese Physics C2021,45,2:33
3基于公共领域理论的传统医药知识及相关资源保护显示文摘以知识产权法的公共领域理论为视角,讨论公共领域知识的特征、权益主体、利益原则,结合国际知识产权制度框架下传统医药知识的公共领域属性和法律地位,对传统医药知识及相关资源保护的策略进行了分析。思考和梳理我国传统医学知识及相关资源保护的制度架构与缺陷。提出在经济和文化全球化的背景下,政府需要采取相关措施,努力争取我国传统医药和相关资源在国际知识产权体系中的法律地位和知识权益,实现中医传统知识与现代科学及国际医药知识体系的对接,促进传统医药知识的保护与发展。魏晋才 方志耕 Matthew H.Liang 2017科技管理研究2017,37,4:6
4Search for electron-antineutrinos associated with gravitational-wave events GW150914,GW151012,GW151226,GW170104,GW170608,GW170814,and GW170817 at Daya Bay显示文摘The establishment of a possible connection between neutrino emission and gravitational-wave(GW)bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge.In the Daya Bay experiment,using the data collected from December 2011 to August 2017,a search was per-formed for electron-antineutrino signals that coincided with detected GW events,including GW150914,GW151012,GW151226,GW170104,GW170608,GW 170814,and GW 170817.We used three time windows of±10,±500,and±1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates.The detected electron-antineutrino candidates were consistent with the expected background rates for all the three time windows.Assuming monochromatic spectra,we found upper limits(90%confidence level)of the electron-antineutrino fluence of(1.13-2.44)×10^(11)cm^(-2)at 5 MeV to 8.0×10^(7)cm^(-2)at 100 MeV for the three time w indows.Under the assumption of a Fermi-Dirac spectrum,the upper limits were found to be(5.4-7.0)×10^(9)cm^(2)for the three time windows.F.P.An A.B.Balantekin H.R.Band M.Bishai S.Blyth G.F.Cao J.Cao J.F.Chang Y.Chang H.S.Chen S.M.Chen Y.Chen Y.X.Chen J.Cheng Z.K.Cheng J.J.Cherwinka M.C.Chu J.P.Cummings O.Dalager F.S.Deng Y.Y.Ding M.V.Diwan T.Dohnal J.Dove M.Dvorak D.A.Dwyer J.P.Gallo M.Gonchar G.H.Gong H.Gong W.Q.Gu J.Y.Guo L.Guo X.H.Guo Y.H.Guo Z.Guo R.W.Hackenburg S.Hans M.He K.M.Heeger Y.K.Heng A.Higuera Y.K.Hor Y.B.Hsiung B.Z.Hu J.R.Hu T.Hu Z.J.Hu H.X.Huang X.T.Huang Y.B.Huang P.Huber D.E.Jaffe K.L.Jen X.L.Ji X.P.Ji R.A.Johnson D.Jones L.Kang S.H.Kettell S.Kohn M.Kramer T.J.Langford J.Lee J.H.C.Lee R.T.Lei R.Leitner J.K.C.Leung F.Li J.J.Li Q.J.Li S.Li S.C.Li W.D.Li X.N.Li X.Q.Li Y.F.Li Z.B.Li H.Liang C.J.Lin G.L.Lin S.Lin J.J.Ling J.M.Link L.Littenberg B.R.Littlejohn J.C.Liu J.L.Liu C.Lu H.Q.Lu J.S.Lu K.B.Luk X.B.Ma X.Y.Ma Y.Q.Ma C.Marshall D.A.Martinez Caicedo K.T.MeDonald R.D.McKeown Y.Meng J.Napolitano D.Naumov E.Naumova J.P.Ochoa-Ricoux A.OIshevskiy H.-R.Pan J.Park S.Patton J.C.Peng C.S.J.Pun F.Z.Qi M.Qi X.Qian N.Raper J.Ren C.Morales Reveco R.Rosero B.Roskovec X.C.Ruan H.Steiner J.L.Sun T.Tmej K.Treskov W.-H.Tse C.E.Tull B.Viren V.Vorobel C.H.Wang J.Wang M.Wang N.Y.Wang R.G.Wang W.Wang W.Wang X.Wang Y.Wang Y.F.Wang Z.Wang Z.Wang Z.M.Wang H.Y.Wei L.H.Wei L.J.Wen K.Whisnant C.G.White H.L.H.Wong E.Worcester D.R.Wu F.L.Wu Q.Wu W.J.Wu D.M.Xia Z.Q.Xie Z.Z.Xing J.L.Xu T.Xu T.Xue C.G.Yang L.Yang Y.Z.Yang H.F.Yao M.Ye M.Yeh B.L.Young H.Z.Yu Z.Y.Yu B.B.Yue S.Zeng Y.Zeng L.Zhan C.Zhang F.Y.Zhang H.H.Zhang J.W.Zhang Q.M.Zhang X.T.Zhang Y.M.Zhang Y.X.Zhang Y.Y.Zhang Z.J.Zhang Z.P.Zhang Z.Y.Zhang J.Zhao L.Zhou H.L.Zhuang J.H.Zou 2021Chinese Physics C2021,45,5:1
5A novel monoacylglycerol lipase-targeted^(18)F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network显示文摘Monoacylglycerol lipase(MAGL)constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol(2-AG)to arachidonic acid(AA).As such,selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders,metabolic diseases and cancers.Based on a unique 4-piperidinyl azetidine diamide scaffold,we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand[^(18)F]FEPAD.Pharmacokinetics and binding studies on[^(18)F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue(BAT)–a tissue that is known to be metabolically active.We employed[^(18)F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT,which was confirmed by post-mortem tissue analysis.Given the negative regulation of endocannabinoids on the metabolic BAT activity,our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders.Further,we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits,thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system(ECS)-related pathologies.Ran Cheng Masayuki Fujinaga Jing Yang Jian Rong Ahmed Haider Daisuke Ogasawara Richard S.Van Tuo Shao Zhen Chen Xiaofei Zhang Erick R.Calderon Leon Yiding Zhang Wakana Mori Katsushi Kumata Tomoteru Yamasaki Lin Xie Shaofa Sun Lu Wang Chongzhao Ran Yihan Shao Benjamin Cravatt Lee Josephson Ming-Rong Zhang Steven H.Liang 2022Acta Pharmacologica Sinica2022,43,11:0
6Discovery of a highly specific ^(18)F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination显示文摘As a member of cyclic nucleotide phosphodiesterase(PDE)enzyme family,PDE10A is in charge of the degradation of cyclic adenosine(cAMP)and guanosine monophosphates(cGMP).While PDE10A is primarily expressed in the medium spiny neurons of the striatum,it has been implicated in a variety of neurological disorders.Indeed,inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system(CNS)pathologies caused by dysfunction of the basal ganglia–of which the striatum constitutes the largest component.A PDE10A-targeted positron emission tomography(PET)radioligand would enable a better assessment of the pathophysiologic role of PDE10A,as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate,thus accelerating the development of effective PDE10A inhibitors.In this study,we designed and synthesized a novel ^(18)F-aryl PDE10A PET radioligand,codenamed[^(18)F]P10A-1910([^(18)F]9),in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination.[^(18)F]9 possessed good in vitro binding affinity(IC_(50)=2.1 nmol/L)and selectivity towards PDE10A.Further,[^(18)F]9 exhibited reasonable lipophilicity(logD=3.50)and brain permeability(P_(app)>10×10^(−6) cm/s in MDCK-MDR1 cells).PET imaging studies of[^(18)F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer kinetics.Preclinical studies in rodents revealed an improved plasma and brain stability of[^(18)F]9 when compared to the current reference standard for PDE10A-targeted PET,[^(18)F]MNI659.Further,dose–response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of[^(18)F]9 for evaluating target occupancy in vivo in higher species.In conclusion,our results indicated that[^(18)F]9 is a promising PDE10A PET radioligand for clinical translation.Zhiwei Xiao Huiyi Wei Yi Xu Ahmed Haider Junjie Wei Shiyu Yuan Jian Rong Chunyu Zhao Guocong Li Weibin Zhang Huangcan Chen Yuefeng Li Lingling Zhang Jiyun Sun Shaojuan Zhang Hai-Bin Luo Sen Yan Qijun Cai Lu Hou Chao Che Steven H.Liang Lu Wang 2022Acta Pharmaceutica Sinica B2022,12,4:0
7Measurements of the center-of-mass energies of e^(+)e^(-)collisions at BESIII显示文摘During the 2016-17 and 2018-19 running periods,the BESIII experiment collected 7.5 fb of e^(+)e^(-)collision data at center-of-mass energies ranging from 4.13 to 4.44 GeV.These data samples are primarily used for the study of excited charmonium and charmoniumlike states.By analyzing the di-muon process e^(+)e^(-)→(γISR=FSR)μ^(+)μ^(-),we measure the center-of-mass energies of the data samples with a precision of 0.6 MeV.Through a run-by-run study,we find that the center-of-mass energies were stable throughout most of the data-collection period.M.Ablikim M.N.Achasov P.Adlarson S.Ahmed M.Albrecht R.Aliberti A.Amoroso M.R.An Q.An X.H.Bai Y.Bai O.Bakina R.Baldini Ferroli I.Balossino Y.Ban K.Begzsuren N.Berger M.Bertani D.Bettoni F.Bianchi J.Bloms A.Bortone I.Boyko R.A.Briere H.Cai X.Cai A.Calcaterra G.F.Cao N.Cao S.A.Cetin J.F.Chang W.L.Chang G.Chelkov D.Y.Chen G.Chen H.S.Chen M.L.Chen S.J.Chen X.R.Chen Y.B.Chen Z.J.Chen W.S.Cheng G.Cibinetto F.Cossio X.F.Cui H.L.Dai X.C.Dai A.Dbeyssi R.E.de Boer D.Dedovich Z.Y.Deng A.Denig I.Denysenko M.Destefanis F.De Mori Y.Ding C.Dong J.Dong L.Y.Dong M.Y.Dong X.Dong S.X.Du Y.L.Fan J.Fang S.S.Fang Y.Fang R.Farinelli L.Fava F.Feldbauer G.Felici C.Q.Feng J.H.Feng M.Fritsch C.D.Fu Y.Gao Y.Gao Y.Gao Y.G.Gao I.Garzia P.T.Ge C.Geng E.M.Gersabeck A Gilman K.Goetzen L.Gong W.X.Gong W.Gradl M.Greco L.M.Gu M.H.Gu Y.T.Gu C.Y Guan A.Q.Guo L.B.Guo R.P.Guo Y.P.Guo A.Guskov T.T.Han W.Y.Han X.Q.Hao F.A.Harris K.L.He F.H.Heinsius C.H.Heinz T.Held Y.K.Heng C.Herold M.Himmelreich T.Holtmann G.Y.Hou Y.R.Hou Z.L.Hou H.M.Hu J.F.Hu T.Hu Y.Hu G.S.Huang L.Q.Huang X.T.Huang Y.P.Huang Z.Huang T.Hussain N Husken W.Ikegami Andersson W.Imoehl M.Irshad S.Jaeger S.Janchiv Q.Ji Q.P.Ji X.B.Ji X.L.Ji Y.Y.Ji H.B.Jiang X.S.Jiang J.B.Jiao Z.Jiao S.Jin Y.Jin M.Q.Jing T.Johansson N.Kalantar-Nayestanaki X.S.Kang R.Kappert M.Kavatsyuk B.C.Ke I.K.Keshk A.Khoukaz P.Kiese R.Kiuchi R.Kliemt L.Koch O.B.Kolcu B.Kopf M.Kuemmel M.Kuessner A.Kupsc M.G.Kurth W.Kuhn J.J.Lane J.S.Lange P.Larin A.Lavania L.Lavezzi Z.H.Lei H.Leithoff M.Lellmann T.Lenz C.Li C.H.Li Cheng Li D.M.Li F.Li G.Li H.Li H.Li H.B.Li H.J.Li J.L.Li J.Q.Li J.S.Li Ke Li L.K.Li Lei Li P.R.Li S.Y.Li W.D.Li W.G.Li X.H.Li X.L.Li Xiaoyu Li Z.Y.Li H.Liang H.Liang H.Liang Y.F.Liang Y.T.Liang G.R.Liao 廖龙洲 J.Libby C.X.Lin B.J.Liu C.X.Liu D.Liu F.H.Liu Fang Liu Feng Liu H.B.Liu H.M.Liu Huanhuan Liu Huihui Liu J.B.Liu J.L.Liu J.Y.Liu K.Liu K.Y.Liu L.Liu M.H.Liu P.L.Liu Q.Liu Q.Liu S.B.Liu Shuai Liu T.Liu W.M.Liu X.Liu Y.Liu Y.B.Liu Z.A.Liu Z.Q.Liu X.C.Lou F.X.Lu H.J.Lu J.D.Lu J.G.Lu X.L.Lu Y.Lu Y.P.Lu C.L.Luo M.X.Luo P.W.Luo T.Luo X.L.Luo X.R.Lyu F.C.Ma H.L.Ma L.L.Ma M.M.Ma Q.M.Ma R.Q.Ma R.T.Ma X.X.Ma X.Y.Ma F.E.Maas M.Maggiora S.Maldaner S.Malde Q.A.Malik A.Mangoni Y.J.Mao Z.P.Mao S.Marcello Z.X.Meng J.G.Messchendorp G.Mezzadri T.J.Min R.E.Mitchell X.H.Mo N.Yu.Muchnoi H.Muramatsu S.Nakhoul Y.Nefedov F.Nerling I.B.Nikolaev Z.Ning S.Nisar S.L.Olsen Q.Ouyang S.Pacetti X.Pan Y.Pan A.Pathak A.Pathak P.Patteri M.Pelizaeus H.P.Peng K.Peters J.Pettersson J.L.Ping R.G.Ping S.Pogodin R.Poling V.Prasad H.Qi H.R.Qi K.H.Qi M.Qi T.Y.Qi S.Qian W.B.Qian Z.Qian C.F.Qiao L.Q.Qin X.P.Qin X.S.Qin Z.H.Qin J.F.Qiu S.Q.Qu K.H.Rashid K.Ravindran C.F.Redmer A.Rivetti V.Rodin M.Rolo G.Rong Ch.Rosner M.Rump H.S.Sang A.Sarantsev Y.Schelhaas C.Schnier K.Schoenning M.Scodeggio D.C.Shan W.Shan X.Y.Shan J.F.Shangguan M.Shao C.P.Shen H.F.Shen P.X.Shen X.Y.Shen H.C.Shi R.S.Shi X.Shi X.D Shi J.J.Song W.M.Song Y.X.Song S.Sosio S.Spataro K.X.Su P.P.Su F.F.Sui G.X.Sun H.K.Sun J.F.Sun L.Sun S.S.Sun T.Sun W.Y.Sun W.Y.Sun X Sun Y.J.Sun Y.K.Sun Y.Z.Sun Z.T.Sun Y.H.Tan Y.X.Tan C.J.Tang G.Y.Tang J.Tang J.X.Teng V.Thoren W.H.Tian Y.T.Tian I.Uman B.Wang C.W.Wang D.Y.Wang H.J.Wang H.P.Wang K.Wang L.L.Wang M.Wang M.Z.Wang Meng Wang W.Wang W.H.Wang W.P.Wang X.Wang X.F.Wang X.L.Wang Y.Wang Y.Wang Y.D.Wang Y.F.Wang Y.Q.Wang Y.Y.Wang Z.Wang Z.Y.Wang Ziyi Wang Zongyuan Wang D.H.Wei F.Weidner S.P.Wen D.J.White U.Wiedner G.Wilkinson M.Wolke L.Wollenberg J.F.Wu L.H.Wu L.J.Wu X.Wu Z.Wu L.Xia H.Xiao S.Y.Xiao Z.J.Xiao X.H.Xie Y.G.Xie Y.H.Xie T.Y.Xing G.F.Xu Q.J.Xu W.Xu X.P.Xu Y.C.Xu F.Yan L.Yan W.B.Yan W.C.Yan Xu Yan H.J.Yang H.X.Yang L.Yang S.L.Yang Y.X.Yang Yifan Yang Zhi Yang M.Ye M.H.Ye J.H.Yin Z.Y.You B.X.Yu C.X.Yu G.Yu J.S.Yu T.Yu 苑长征 L.Yuan X.Q.Yuan Y.Yuan Z.Y.Yuan C.X.Yue A.A.Zafar X.Zeng Zeng Y.Zeng A.Q.Zhang B.X.Zhang Guangyi Zhang H.Zhang H.H.Zhang H.H.Zhang H.Y.Zhang J.J.Zhang J.L.Zhang J.Q.Zhang J.W.Zhang J.Y.Zhang J.Z.Zhang Jianyu Zhang Jiawei Zhang L.M.Zhang L.Q.Zhang Lei Zhang S.Zhang S.F.Zhang Shulei Zhang X.D.Zhang X.Y.Zhang Y.Zhang Y.T.Zhang Y.H.Zhang Yan Zhang Yao Zhang Z.Y.Zhang G.Zhao J.Zhao J.Y.Zhao J.Z.Zhao Lei Zhao Ling Zhao M.G.Zhao Q.Zhao S.J.Zhao Y.B.Zhao Y.X.Zhao Z.G.Zhao A.Zhemchugov B.Zheng J.P.Zheng Y.H.Zheng B.Zhong C.Zhong L.P.Zhou Q.Zhou X.Zhou X.K.Zhou X.R.Zhou X.Y.Zhou A.N.Zhu J.Zhu K.Zhu K.J.Zhu S.H.Zhu T.J.Zhu W.J.Zhu W.J.Zhu Y.C.Zhu Z.A.Zhu B.S.Zou J.H.Zou 2021Chinese Physics C2021,45,10:0
8STCF conceptual design report (Volume 1): Physics & detector显示文摘The superτ-charm facility(STCF)is an electron–positron collider proposed by the Chinese particle physics community.It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with a peak luminosity of 0.5×1035 cm–2·s–1 or higher.The STCF will produce a data sample about a factor of 100 larger than that of the presentτ-charm factory—the BEPCII,providing a unique platform for exploring the asymmetry of matter-antimatter(charge-parity violation),in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions,as well as searching for exotic hadrons and physics beyond the Standard Model.The STCF project in China is under development with an extensive R&D program.This document presents the physics opportunities at the STCF,describes conceptual designs of the STCF detector system,and discusses future plans for detector R&D and physics case studies.M.Achasov X.C.Ai L.P.An R.Aliberti Q.An X.Z.Bai Y.Bai O.Bakina A.Barnyakov V.Blinov V.Bobrovnikov D.Bodrov A.Bogomyagkov A.Bondar I.Boyko Z.H.Bu F.M.Cai H.Cai J.J.Cao Q.H.Cao X.Cao Z.Cao Q.Chang K.T.Chao D.Y.Chen H.Chen H.X.Chen J.F.Chen K.Chen L.L.Chen P.Chen S.L.Chen S.M.Chen S.Chen S.P.Chen W.Chen X.Chen X.F.Chen X.R.Chen Y.Chen Y.Q.Chen H.Y.Cheng J.Cheng S.Cheng T.G.Cheng J.P.Dai L.Y.Dai X.C.Dai D.Dedovich A.Denig I.Denisenko J.M.Dias D.Z.Ding L.Y.Dong W.H.Dong V.Druzhinin D.S.Du Y.J.Du Z.G.Du L.M.Duan D.Epifanov Y.L.Fan S.S.Fang Z.J.Fang G.Fedotovich C.Q.Feng X.Feng Y.T.Feng J.L.Fu J.Gao Y.N.Gao P.S.Ge C.Q.Geng L.S.Geng A.Gilman L.Gong T.Gong B.Gou W.Gradl J.L.Gu A.Guevara L.C.Gui A.Q.Guo F.K.Guo J.C.Guo J.Guo Y.P.Guo Z.H.Guo A.Guskov K.L.Han L.Han M.Han X.Q.Hao J.B.He S.Q.He X.G.He Y.L.He Z.B.He Z.X.Heng B.L.Hou T.J.Hou Y.R.Hou C.Y.Hu H.M.Hu K.Hu R.J.Hu W.H.Hu X.H.Hu Y.C.Hu J.Hua G.S.Huang J.S.Huang M.Huang Q.Y.Huang W.Q.Huang X.T.Huang X.J.Huang Y.B.Huang Y.S.Huang N.Hüsken V.Ivanov Q.P.Ji J.J.Jia S.Jia Z.K.Jia H.B.Jiang J.Jiang S.Z.Jiang J.B.Jiao Z.Jiao H.J.Jing X.L.Kang X.S.Kang B.C.Ke M.Kenzie A.Khoukaz I.Koop E.Kravchenko A.Kuzmin Y.Lei E.Levichev C.H.Li C.Li D.Y.Li F.Li G.Li G.Li H.B.Li H.Li H.N.Li H.J.Li H.L.Li J.M.Li J.Li L.Li L.Li L.Y.Li N.Li P.R.Li R.H.Li S.Li T.Li W.J.Li X.Li X.H.Li X.Q.Li X.H.Li Y.Li Y.Y.Li Z.J.Li H.Liang J.H.Liang Y.T.Liang G.R.Liao L.Z.Liao Y.Liao C.X.Lin D.X.Lin X.S.Lin B.J.Liu C.W.Liu D.Liu F.Liu G.M.Liu H.B.Liu J.Liu J.J.Liu J.B.Liu K.Liu K.Y.Liu K.Liu L.Liu Q.Liu S.B.Liu T.Liu X.Liu Y.W.Liu Y.Liu Y.L.Liu Z.Q.Liu Z.Y.Liu Z.W.Liu I.Logashenko Y.Long C.G.Lu J.X.Lu N.Lu Q.F.Lü Y.Lu Y.Lu Z.Lu P.Lukin F.J.Luo T.Luo X.F.Luo Y.H.Luo H.J.Lyu X.R.Lyu J.P.Ma P.Ma Y.Ma Y.M.Ma F.Maas S.Malde D.Matvienko Z.X.Meng R.Mitchell A.Nefediev Y.Nefedov S.L.Olsen Q.Ouyang P.Pakhlov G.Pakhlova X.Pan Y.Pan E.Passemar Y.P.Pei H.P.Peng L.Peng X.Y.Peng X.J.Peng K.Peters S.Pivovarov E.Pyata B.B.Qi Y.Q.Qi W.B.Qian Y.Qian C.F.Qiao J.J.Qin J.J.Qin L.Q.Qin X.S.Qin T.L.Qiu J.Rademacker C.F.Redmer H.Y.Sang M.Saur W.Shan X.Y.Shan L.L.Shang M.Shao L.Shekhtman C.P.Shen J.M.Shen Z.T.Shen H.C.Shi X.D.Shi B.Shwartz A.Sokolov J.J.Song W.M.Song Y.Song Y.X.Song A.Sukharev J.F.Sun L.Sun X.M.Sun Y.J.Sun Z.P.Sun J.Tang S.S.Tang Z.B.Tang C.H.Tian J.S.Tian Y.Tian Y.Tikhonov K.Todyshev T.Uglov V.Vorobyev B.D.Wan B.L.Wang B.Wang D.Y.Wang G.Y.Wang G.L.Wang H.L.Wang J.Wang J.H.Wang J.C.Wang M.L.Wang R.Wang R.Wang S.B.Wang W.Wang W.P.Wang X.C.Wang X.D.Wang X.L.Wang X.L.Wang X.P.Wang X.F.Wang Y.D.Wang Y.P.Wang Y.Q.Wang Y.L.Wang Y.G.Wang Z.Y.Wang Z.Y.Wang Z.L.Wang Z.G.Wang D.H.Wei X.L.Wei X.M.Wei Q.G.Wen X.J.Wen G.Wilkinson B.Wu J.J.Wu L.Wu P.Wu T.W.Wu Y.S.Wu L.Xia T.Xiang C.W.Xiao D.Xiao M.Xiao K.P.Xie Y.H.Xie Y.Xing Z.Z.Xing X.N.Xiong F.R.Xu J.Xu L.L.Xu Q.N.Xu X.C.Xu X.P.Xu Y.C.Xu Y.P.Xu Y.Xu Z.Z.Xu D.W.Xuan F.F.Xue L.Yan M.J.Yan W.B.Yan W.C.Yan X.S.Yan B.F.Yang C.Yang H.J.Yang H.R.Yang H.T.Yang J.F.Yang S.L.Yang Y.D.Yang Y.H.Yang Y.S.Yang Y.L.Yang Z.W.Yang Z.Y.Yang D.L.Yao H.Yin X.H.Yin N.Yokozaki S.Y.You Z.Y.You C.X.Yu F.S.Yu G.L.Yu H.L.Yu J.S.Yu J.Q.Yu L.Yuan X.B.Yuan Z.Y.Yuan Y.F.Yue M.Zeng S.Zeng A.L.Zhang B.W.Zhang G.Y.Zhang G.Q.Zhang H.J.Zhang H.B.Zhang J.Y.Zhang J.L.Zhang J.Zhang L.Zhang L.M.Zhang Q.A.Zhang R.Zhang S.L.Zhang T.Zhang X.Zhang Y.Zhang Y.J.Zhang Y.X.Zhang Y.T.Zhang Y.F.Zhang Y.C.Zhang Y.Zhang Y.Zhang Y.M.Zhang Y.L.Zhang Z.H.Zhang Z.Y.Zhang Z.Y.Zhang H.Y.Zhao J.Zhao L.Zhao M.G.Zhao Q.Zhao R.G.Zhao R.P.Zhao Y.X.Zhao Z.G.Zhao Z.X.Zhao A.Zhemchugov B.Zheng L.Zheng Q.B.Zheng R.Zheng Y.H.Zheng X.H.Zhong H.J.Zhou H.Q.Zhou H.Zhou S.H.Zhou X.Zhou X.K.Zhou X.P.Zhou X.R.Zhou Y.L.Zhou Y.Zhou Y.X.Zhou Z.Y.Zhou J.Y.Zhu K.Zhu R.D.Zhu R.L.Zhu S.H.Zhu Y.C.Zhu Z.A.Zhu V.Zhukova V.Zhulanov B.S.Zou Y.B.Zuo 2024Frontiers of physics2024,19,1:0
9机械振动对热作模具钢显微组织和热疲劳性能的影响显示文摘振动能量已被用于冶金和工程领域的许多方面。凝固过程中可用不同的方法提供振动,资料介绍了机械式、电磁式、声波式及超声波式振动对细化晶粒,增加密度,脱气,补缩,第二相形态、尺寸、分布都具有显著影响。然而,也有报导电磁和超声波振动成本高,必须有巨大的能量才有效,相对的机械振动(MV)由于其简单及成本低而应用较普遍。Y. H.LIANG 2009现代冶金(内蒙古)2009,,1:0
10Development of a highly-specific ^(18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping显示文摘As a serine hydrolase,monoacylglycerol lipase(MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol(2-AG) in the central nervous system(CNS),leading to the formation of arachidonic acid(AA).Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms,including neuroinflammation,cognitive impairment,epileptogenesis,nociception and neurodegenerative diseases.Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions,and a MAGL positron emission tomography(PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors.Herein,we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates.Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound,which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[^(18)F]fluoropyridine scaffold.Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [^(18)F]14(also named as [^(18)F]MAGL-1902).This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers.Zhen Chen Wakana Mori Jian Rong Michael A.Schafroth Tuo Shao Richard S.Van Daisuke Ogasawara Tomoteru Yamasaki Atsuto Hiraishi Akiko Hatori Jiahui Chen Yiding Zhang Kuan Hu Masayuki Fujinaga Jiyun Sun Qingzhen Yu Thomas L.Collier Yihan Shao Benjamin F.Cravatt Lee Josephson Ming-Rong Zhang Steven H.Liang 2021Acta Pharmaceutica Sinica B2021,11,6:0
11Biomass-derived carbon doping to enhance the current carrying capacity and flux pinning of an isotopic Mg^(11)B_(2)superconductor显示文摘Low activation isotopic boron(11B)based magnesium diboride(Mg^(11)B_(2))superconductors doped with biomass-derived activated carbon were synthesized using11B and magnesium powder via solid-state reaction.The effect of carbon doping on the lattice structure and superconducting properties of Mg^(11)B_(2)bulks were evaluated using X-ray powder diffraction,high resolution transmission electron microscopy,scanning electron microscopy and magnetization measurements.Precise refinement of structural parameters indicates successful substitution of carbon in Mg^(11)B_(2)bulks.The critical current density(Jc)of carbon doped Mg^(11)B_(2)synthesized at 650℃was enhanced more than two times compared with the pure Mg^(11)B_(2)bulk.Similar improvement was observed for the Mg^(11)B_(2)bulks heat-treated at 800℃.This enhancement is due to successful substitution of biomass-derived carbon with high surface area into Mg^(11)B_(2)lattice.The flux pinning mechanism of pure and doped Mg^(11)B_(2)bulks were investigated using the Dew-Hughes model.This study provides information regarding enhancement of the Jc of low activation Mg^(11)B_(2)superconductors suitable for next-generation fusion magnets.M.Shahbazi Y.Hao D.Patel H.Liang Y.Yamauchi M.S.A.Hossain 2022Journal of Magnesium and Alloys2022,10,7:0
12Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4显示文摘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 lacking.As such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the brain.Structure-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 striatum.However,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 site.Remarkably,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 species.These 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 cortex.In conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising attributes.The availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.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 2023Acta Pharmaceutica Sinica B2023,13,1:0
13[^(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models显示文摘Monoacylglycerol lipase(MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol(2-AG) into the proinflammatory eicosanoid precursor arachidonic acid(AA). MAGL and other endogenous cannabinoid(EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell(HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an;F-labeled MAGL inhibitor([18F]MAGL-4-11)for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation(BDL) and carbon tetrachloride(CCl_(4)) models of liver cirrhosis;we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models;[18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosisseverity, while its levels in normal liver tissue are high;in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that[18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.Tuo Shao Zhen Chen Jian Rong Vasily Belov Jiahui Chen Andre Jeyarajan Xiaoyun Deng Hualong Fu Qingzhen Yu Steve H.Rwema Wenyu Lin Mikhail Papisov Lee Josephson Raymond T.Chung Steven H.Liang 2022Acta Pharmaceutica Sinica B2022,12,1:0
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