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Discovery of a highly specific ^(18)F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1963-1975页

作者： 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 Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI Centerthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital&Department of RadiologyHarvard Medical SchoolBostonMA 02114USA Department of Cardiology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhen 518055China Guangdong Landau Biotechnology Co.Ltd. Guangzhou 510555China Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570228China Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhou 510632China

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 ***,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 *** 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 ***,[^(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 *** 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]***,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 *** conclusion,our results indicated that[^(18)F]9 is a promising PDE10A PET radioligand for clinical translation.

关键词： Phosphodiesterase 10A PET radioligand 18F Spirocyclic iodonium ylide Nonhuman primate Target occupancy

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Processable Rylene Diimides up to 4 nm in length: Synthesis and STM Visualization

Processable Rylene Diimides up to 4 nm in length: Synthesis ...

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2015年第十四届全国应用化学年会

作者： YUAN Zhongyi LEE Shern-Long chen,Long LI chen MALI Kunal S. MUELLEN Klaus DE FEYTER steven Max Planck Institute for Polymer Research Department of Chemistry KU Leuven-University

Our group has reported the syntheses of terrylene, quaterrylene,pentarylene, and hexarylene diimides over the past two decades. To achieve good solubility, four bulk alkylphenoxy groups were introduced at the bay positions. However, this method has two limitations: 1) the steric repulsion between the substituents at the bay positions causes a serious twist of the conjugated core and thus obstructs the intermolecular interactions;2) electron-rich phenoxy groups greatly raise the LUMO energy level, and hamper the role of RDIs as n-type semiconductors. To overcome these drawbacks, we designed and synthesized soluble hexarylene diimides(HDI) and octarylene diimides(ODI) with planar conjugated cores which are as long as 2.87 and 3.74 nm respectively. HDI(λ = 908 nm, ε = 256000 M)cm) shows intense NIR absorption in the range of 700-1000 nm. The absorption of ODI(λ = 1007 nm, ε = 79800 Mcm) is the range of 400-1400 nm. Electrochemical properties of HDI and ODI were investigated by cyclic voltammetry, and the LUMO energy is-3.95 eV and-3.94 eV respectively, which indicates strong electron accepting ability of the two compounds. Scanning tunneling microscopy(STM) reveals that HDI, after deposition from solution, forms a unique herringbone bilayer or stable multilayers depending on the concentration at the liquid–solid interface. We also found a simple and efficient method to fabricate well-aligned thin films of HDI over a few millimeter squares. The strategy involves use of capillary force in a two-step flow method to induce large area alignment of multilayers of molecules at the organic liquid-solid interface.

关键词： Rylene Diimides Organic semiconductors Scanning tunneling microscopy

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Sources of organic matter and paleo-environmental implications inferred from carbon isotope compositions of lacustrine sediments at Inexpressible Island, Ross Sea, Antarctica

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Advances in Polar Science 2016年第4期27卷 233-244页

作者： WEI Yangyang JIN Jing NIE Yaguang chen Xin WU Libin FU Pingqing LIU Xiaodong steven D.Emslie Institute of Polar Environment School of Earth and Space Sciences University of Science and Technology of China Key Laboratory of Ion Beam Bioengineering Hefei Institutes of Physical Science Chinese Academy of SciencesKey Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province LAPC Institute of Atmospheric Physics Chinese Academy of Sciences Department of Biology and Marine Biology University of North Carolina Wilmington

The carbon isotopic composition of organic matter （δ^13Corg） was determined in two sediment cores （IIL1 and IIL9） recovered from Inexpressible Island, Ross Sea, Antarctica, and analyzed to identify the sources of that organic matter. The δ^13Corg values of sediments of IIL9 were found to vary between -14.6‰ and -11.6‰, with a mean of-13.4‰ （n=48）. These values were significantly higher than those of IIL1 sediments which varied between -23.2‰ and -20.4‰, with a mean of-21.8%o （n=55）. The variation in δ^13Corg values in these two sediment cores indicate different sources of organic matter, The relatively high 6~3Corg values in IIL9 are in accordance with a source from algae, while the low δ^13Corg values in IIL1 evince significant influence from penguin guano with algae as the secondary source. Compared with the reference data from other high-latitude lake sediments and plants, the δ^13Corg values in IIL9 were extremely high, a result likely related to intense competition for CO2 assimilation among algal species during the growing season in this relatively shallow pond. These results indicate that sedimentary δ^13Corg is a reliable proxy for paleo-primary productivity in ponds at Inexpressible Island.

关键词： Inexpressible Island Ross Sea pond sediments lake algae carbon isotopic composition paleo-environment

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碳纳米纤维与环氧树脂单体相互作用的分子动力学模拟

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高分子学报 2015年第10期25卷 1158-1164页

作者：陈生辉孙霜青 steven R Gwaltney 李春玲王秀民胡松青中国石油大学(华东)理学院青岛266580 密西西比州立大学化学系美国密西西比州39762 中国石油大学(华东)山东省高校新能源物理与材料科学重点实验室青岛266580

利用分子动力学模拟方法,以双酚A型环氧树脂(DGEBA)和异佛尔酮二胺(IPD)分子为研究对象,对环氧树脂单体体系与碳纳米纤维表面之间的相互作用进行了分析.研究结果表明,环氧树脂单体分子受到碳纳米纤维的吸引作用,能够在碳纳米纤维表面形... 详细信息

利用分子动力学模拟方法,以双酚A型环氧树脂(DGEBA)和异佛尔酮二胺(IPD)分子为研究对象,对环氧树脂单体体系与碳纳米纤维表面之间的相互作用进行了分析.研究结果表明,环氧树脂单体分子受到碳纳米纤维的吸引作用,能够在碳纳米纤维表面形成了浓度较高的界面相,且在界面相内IPD分子浓度高于其体相浓度,而DGEBA分子浓度低于其体相浓度;界面相内,DGEBA的分子结构更加伸展,而IPD分子结构未发生明显变化;碳纳米纤维表面能够抑制界面相内单体分子的运动,其中在垂直于表面方向上的抑制作用最强.通过分析单体分子的结合能密度可知,碳纳米纤维与IPD分子的结合强度大于其与DGEBA分子的结合强度,这与前面的结果相吻合.

关键词：分子动力学模拟环氧树脂碳纳米纤维界面相相互作用

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后电影情动

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文化艺术研究 2021年第1期14卷 105-110,116页

作者： steven Shaviro 陈瑜(译) 韦恩州立大学底特律上海大学上海电影学院上海200072

何谓后电影情动(affect)?“后电影”(post-cinematic)是一种不同于20世纪的新的媒体制度和生产模式,是新自由主义的经济关系和数字技术所产生的一种全新的生活体验生产方式和表达方式;作者依据布莱思·马苏米对“情动”的理解,提出电影... 详细信息

何谓后电影情动(affect)?“后电影”(post-cinematic)是一种不同于20世纪的新的媒体制度和生产模式,是新自由主义的经济关系和数字技术所产生的一种全新的生活体验生产方式和表达方式;作者依据布莱思·马苏米对“情动”的理解,提出电影和音乐视频可被视为后电影情动的地图,并结合当代社会领域,绘制了情动流动的四个维度:一是德勒兹的“控制社会”;二是当代资本主义疯狂的资金流动;三是当代数字和后电影“媒体生态”;四是麦肯锡·沃克所谓的“游戏空间”。由此出发,还可以进一步认识后电影流行明星的特点以及他们是如何吸引观众的。

关键词：后电影情动情动流动情动映射美学后电影明星

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Large optical nonlinearity enabled by coupled metallic quantum wells

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Light(Science & Applications) 2019年第1期8卷 1069-1075页

作者： Haoliang Qian Shilong Li Ching-Fu chen Su-Wen Hsu steven Edward Bopp Qian Ma Andrea R.Tao Zhaowei Liu Department of Electrical and Computer Engineering University of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA Department of NanoEngineering University of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA Materials Science and Engineering University of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA Center for Memory and Recording Research University of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA

New materials that exhibit strong second-order optical nonlinearities at a desired operational frequency are of paramount importance for nonlinear *** second-order susceptibility χ^((2)) has been obtained in semiconductor quantum wells(QWs).Unfortunately,the limited confining potential in semiconductor QWs causes formidable challenges in scaling such a scheme to the visible/near-infrared(NIR)frequencies for more vital nonlinear-optic ***,we introduce a metal/dielectric heterostructured platform,i.e.,TiN/Al_(2)O_(3) epitaxial multilayers,to overcome that *** platform has an extremely high χ^((2)) of approximately 1500 pm/V at NIR *** combining the aforementioned heterostructure with the large electric field enhancement afforded by a nanostructured metasurface,the power efficiency of second harmonic generation(SHG)achieved 10^(−4) at an incident pulse intensity of 10 GW/cm^(2),which is an improvement of several orders of magnitude compared to that of previous demonstrations from nonlinear surfaces at similar *** proposed quantum-engineered heterostructures enable efficient wave mixing at visible/NIR frequencies into ultracompact nonlinear optical devices.

关键词： quantum nonlinear visible

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中国管理教育报告

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经理人 2006年第6期 50-57页

作者： John chen steven Wheelwright Carin-Isabel Knoop 哈佛商学院出版公司哈佛商学院

本文系哈佛商学院三位知名专家学者针对中国管理教育论题多年的研究成果，经三位作者授权，《经理人》杂志在中国大陆地区独家刊发。

关键词：中国大陆地区管理教育教育报告《经理人》杂志哈佛商学院研究成果专家学者授权

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Profiling of immune features to predict immunotherapy efficacy

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The Innovation 2022年第1期3卷 71-82页

作者： Youqiong Ye Yongchang Zhang Nong Yang Qian Gao Xinyu Ding Xinwei Kuang Rujuan Bao Zhao Zhang Chaoyang Sun Bingying Zhou Li Wang Qingsong Hu Chunru Lin Jianjun Gao Yanyan Lou steven HLin Lixia Diao Hong Liu Xiang chen Gordon B.Mills Leng Han Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical SchoolHoustonTX 77030USA Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunan 410008China Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Molecular and Cellular Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Division of Hematology and Oncology Mayo ClinicJacksonvilleFL 32224USA Department of Radiation Oncology Division of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Knight Cancer Institute Oregon Health and Science UniversityPortlandOR 97239USA Center for Epigenetics and Disease Prevention Institute of Biosciences and TechnologyTexas A&M UniversityHoustonTX 77030USA Department of Translational Medical Sciences College of MedicineTexas A&M UniversityHoustonTX 77030 USA

Immune checkpoint blockade(ICB)therapies exhibit substantial clinical benefit in different cancers,but relatively low response rates in the majority of patients highlight the need to understand mutual relationships among immune ***,we reveal overall positive correlations among immune checkpoints and immune cell ***,patients benefiting from ICB exhibited increases for both immune stimulatory and inhibitory features after initiation of therapy,suggesting that the activation of the immune microenvironment might serve as the biomarker to predict immune *** proof-of-concept,we demonstrated that the immune activation score(ISD)based on dynamic alteration of interleukins in patient plasma as early as two cycles(4-6 weeks)after starting immunotherapy can accurately predict immunotherapy *** results reveal a systematic landscape of associations among immune features and provide a noninvasive,cost-effective,and time-efficient approach based on dynamic profiling of pre-and on-treatment plasma to predict immunotherapy efficacy.

关键词： immunotherapy features mutual

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Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China

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National Science Review 2021年第2期8卷 51-59页

作者： Xin Huang Aijun Ding Jian Gao Bo Zheng Derong Zhou Ximeng Qi Rong Tang Jiaping Wang Chuanhua Ren Wei Nie Xuguang Chi Zheng Xu Liangduo chen Yuanyuan Li Fei Che Nini Pang Haikun Wang Dan Tong Wei Qin Wei cheng Weijing Liu Qingyan Fu Baoxian Liu Fahe Chai steven J.Davis Qiang Zhang Kebin He School of Atmospheric Sciences Nanjing University Chinese Research Academy of Environmental Sciences Department of Earth System Science Tsinghua University State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua University Department of Earth System Science University of California Jiangsu Environmental Monitoring Center Jiangsu Provincial Academy of Environment Science Shanghai Environmental Monitoring Center Beijing Key Laboratory of Airborne Particulate Matter Monitoring Technology Beijing Municipal Environmental Monitoring Center

To control the spread of the 2019 novel coronavirus(COVID-19), China imposed nationwide restrictions on the movement of its population(lockdown) after the Chinese New Year of 2020, leading to large reductions in economic activities and associated emissions. Despite such large decreases in primary pollution, there were nonetheless several periods of heavy haze pollution in eastern China, raising questions about the well-established relationship between human activities and air quality. Here, using comprehensive measurements and modeling, we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution. In particular, large decreases in NOx emissions from transportation increased ozone and nighttime NO3radical formation, and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter. Our results, afforded by the tragic natural experiment of the COVID-19 pandemic, indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants.

关键词： COVID-19 haze pollution ozone emission reduction secondary pollution

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Energy constraints modulate honest signaling in Xenopus

Energy constraints modulate honest signaling in Xenopus

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第十三届全国野生动物生态与资源保护学术研讨会暨第六届中国西部动物学学术研讨会

作者： Xiaocui Wang Zhijun Zhao Yan Cao steven E.Brauth Jianguo Cui Jingfeng chen Yezhong Tang chengdu Institute of Biology Chinese Academy of Sciences College of Life and Environmental Sciences Wenzhou University Department of Psychology University of Maryland

The handicap principle predicts that secondary sexual ornamentation provides honest information to opponents and/or potential mates because only high-quality individuals can afford the costs of producing attractive ***,variations in the costs or benefits of signaling may result in variations in signaling strategies and

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