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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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Space Observation Data Processing of XPNAV-01

Space Observation Data Processing of XPNAV-01

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第十四届中国卫星导航年会

作者： Linli Yan Qingyong Zhou shaojuan Fan Xiao-long Hao Kun Jiang Xiwei Chong School of Mathematics and Physics Anhui Jianzhu University Key Laboratory of Architectural Acoustics Environment of Anhui High Education Institutes Beijing Institute of communication and Tracking technology Space Engineering University

The pulsar navigation test satellite 01(XPNAV-01) is the first space test platform dedicated to exploring the verification of X-ray pulsar navigation technology in China. It has collected a large amount of scientific observation data in orbit, which can be used for scientific research and timing navigation analysis. In this work, more than three years of observations of the Crab pulsar of XPNAV-01 are analyzed, and the pulse profiles of the Crab pulsar each orbit, day and year are obtained. The experimental goal of the satellite being able to accurately "see" the pulsar was achieved. The pulse profiles of four energy bands based on the observation data of XPNAV-01 are reported for the first time in China, and their variation trends with energy are in good agreement with the observation results abroad. A variety of parameters are used to comprehensively evaluate the change of the Crab pulsar's pulse profile shape over time. It is found that the distribution of each parameter is relatively uniform, and the standard deviation of each parameter is small. The estimated single pulse arrival time accuracy is about 83 μs. All these results indicate that the X-ray detector independently developed in China has a good in-orbit operation status in its first four years.

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广西某高硫低品位碳酸锰矿选矿试验研究

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有色金属（选矿部分） 2017年第5期 51-54页

作者：汤振宏阙绍娟广西柳州钢铁集团有限公司矿业分公司广西柳州545001 广西冶金研究院有限公司南宁530023

广西某低品位锰矿石含锰7.34%、含硫6.47%,锰主要以碳酸锰形式存在。针对矿石性质,对锰的回收进行了浮选、跳汰重选、摇床重选、湿式强磁选探索试验,试验结果表明,湿式强磁选是处理该矿合理的工艺流程。通过一次粗选、两次精选、一次扫... 详细信息

广西某低品位锰矿石含锰7.34%、含硫6.47%,锰主要以碳酸锰形式存在。针对矿石性质,对锰的回收进行了浮选、跳汰重选、摇床重选、湿式强磁选探索试验,试验结果表明,湿式强磁选是处理该矿合理的工艺流程。通过一次粗选、两次精选、一次扫选强磁选、中矿返回再选的试验流程,获得锰品位17.2.%、硫品位4.81%、锰回收率81.11%的磁精矿,将磁精矿磨矿至-74μm占90%,进行一次粗选一次扫选脱硫,最终获得锰品位19.72.、硫品位0.78%、锰回收率80.2.%的锰精矿。

关键词：高硫低品位碳酸锰矿强磁选浮选脱硫锰精矿

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Comparison of spatial-temporal distribution characteristics of water temperatures between Lancang River and Mekong River

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Science Bulletin 2007年第S2期 141-147页

作者： ZHANG YiPing~(1+) GAO Fu~(1,2.4) HE DaMing~3 LI shaojuan~3 1 Xishuangbanna Tropical Botanical Garden,Chinese Academy of Sciences,Kunming 6502.3,China 2.Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 6502.4,China 3 Asian International Rivers Center,Yunnan University,Kunming 650014,China 4 Graduate University of the Chinese Academy of Sciences,Beijing 100049,China

Water temperature(WT)is one of the important indicators of water body physical ***- standing the characteristics of spatial-temporal variation on WT in the river continuum will help to de- velop the rational river-water-resource utilization plan,to avoid the possible ecology crisis,and to take full advantages of the natural resources in the involved *** the biggest international river con- tinuum in Asia,the Lancang-Mekong river subregion(known as Greater Mekong Subregion,GMS)has become a famous economic,political,and ecological natural *** study examined the spa- tial-temporal distribution characteristics of the Lancang River water temperature,using the observa- tional data of WT values from 11 hydrological stations in ***,the WT differences be- tween Yunjinghong hydrological station(one representative station in China)and Chiang Saen hydro- logical station(one representative station in Thailand)were *** indicated that:1)Water temperature was higher in the lower part of the river continuum than the upper *** variation is the main influencing *** effect is more obvious in dry season than in rainy season,more obvious in winter than in summer,and more obvious of the average minimum WT than the average maximum WT;2.WT difference between the upper and the lower parts of the river continuum was de- creasing due to little increase of WT in the upper part(Yunjinghong hydrological station)and obvious decrease of the WT in the lower part(Chiang Saen hydrological station)during the research period. Therefore,the parameters of WT are affected by the latitude,and the Lancang-Mekong river continuum lies in the north-south direction,so the tropical aquatic creatures,such as the tropical aquatic fishes, cannot survive in the upper part of this river continuum in winter season,while in summer season,the tropical aquatic creatures properly swim to the upper *** water temperature in the lower Me- kong R

关键词： Lancang-Mekong river river channel water temperature trends of variation Longitudinal Range-Gorge Region

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大数据情境下创新创业生态系统路径研究

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无线互联科技 2021年第11期18卷 99-100页

作者：赵绍娟徐州市高新技术创业服务中心江苏徐州221000

大数据技术的发展改变了传统意义上的创新创业生态系统。创新资源获取更加便捷高效,创业主体增多,创业门槛降低,创业竞争加剧,创业主体之间、创业主体与所处群落和支持环境之间的联系更加紧密频繁,生态系统内部交互作用增加、外部边界... 详细信息

大数据技术的发展改变了传统意义上的创新创业生态系统。创新资源获取更加便捷高效,创业主体增多,创业门槛降低,创业竞争加剧,创业主体之间、创业主体与所处群落和支持环境之间的联系更加紧密频繁,生态系统内部交互作用增加、外部边界拓宽。在大数据情境下如何构建新型创新创业生态系统成为当下亟待研究和解决的问题。文章具体分析了大数据及其技术对创新创业生态系统的影响,并就如何培育新型创新创业系统提出了相关意见建议。

关键词：大数据创新创业生态系统

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数字经济赋能农产品供应链管理转型升级

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商业经济研究 2021年第19期 137-140页

作者：白世贞黄绍娟哈尔滨商业大学管理学院黑龙江哈尔滨150028

数字经济是国民经济发展的新经济形态,为我国经济发展提供了新的发展动力,如何利用数字经济实现产业增值成为实体产业发展的重点。本文从数字经济对农产品供应链的影响入手,分析了我国农产品供应链管理的实践现状,探究了数字经济赋能农... 详细信息

数字经济是国民经济发展的新经济形态,为我国经济发展提供了新的发展动力,如何利用数字经济实现产业增值成为实体产业发展的重点。本文从数字经济对农产品供应链的影响入手,分析了我国农产品供应链管理的实践现状,探究了数字经济赋能农产品供应链管理的内在机理,构建了数字经济背景下农产品供应链的新运作模式,并提出优化当前农产品供应链管理模式的对策,为农业经济数字化发展提供参照,促进农业数字经济快速发展,进而提升我国数字经济整体竞争实力。

关键词：数字经济农产品供应链管理优化路径信息平台

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An addition of medium-dose ATG to conditioning regimens favours the long-term survival of patients with allogeneic hematopoietic stem cell transplantation

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Stem Cell Discovery 2013年第1期3卷 22-31页

作者： Bingyi Wu Chaoyan Song Zhigang Lu Kunyuan Guo Yingzhi He Sanfan Tu shaojuan Pan Can Sun Junyong Fang Department of Haematology Zhujiang Hospital Southern Medical University Guangzhou China

Long-term survival of 116 leukemia/MDS patients received allo-SCT conditioned by a regimen with ATG-F or without ATG-F was analysed, together with the impact of ATG-F on the long-term survival, GVHD and disease relapse. Seventy patients received an ATG-F containing conditioning regimen FBCA, and 46 patients received a non-ATG-F FBC regimen. The FBCA regimen was associated with a 5-year survival of 65.4% in the complete HLA-matched group and 39.3% in the HLA-mismatched group. The difference between the two groups was significant (P = 0.012.. For the FBC conditioning regimen, the 5-year overall survival of HLA-matched patients and the HLA-mismatched patients was 34.2. and 2..2. respectively (P = 0.2.6). The incidence of cGVHD was 32.9% and 83.6% in the FBCA and FBC condition regimen group respectively. Only 2.9% of the cases showed extensive cGVHD in the FBCA group while it was 69.4% in the FBC group (P = 0.00). Multivariate analysis indicated that relapse was related to the disease status and HLA typing, but unrelated to the conditioning regimens whether or not ATG-F was used (HR 0.54, P = 0.109). We conclude that the addition of ATG-F to conditioning regimen favours the longterm survival of allo-SCT.

关键词： Hematopoietic Stem Cell Transplantation Long-Term Survival Anti-Human Lymphocyte Globulin

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不同端壁间隙下压气机平面叶栅角区流动的数值模拟和实验研究

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工程热物理学报 2015年第7期36卷 1428-1432页

作者：王子楠高磊耿少娟张宏武中国科学院先进能源动力重点实验室(工程热物理研究所) 北京100190 中国科学院大学北京100190

采用数值模拟和实验方法,对比分析了不同端壁间隙下平面叶栅攻角损失特性与角区流动结构的关联。各间隙情况下,当来流攻角大于某一数值时,角区失速的发生使得叶栅总压损失呈突跃式增加。小于该来流攻角时,无间隙叶栅损失最小。大于该来... 详细信息

采用数值模拟和实验方法,对比分析了不同端壁间隙下平面叶栅攻角损失特性与角区流动结构的关联。各间隙情况下,当来流攻角大于某一数值时,角区失速的发生使得叶栅总压损失呈突跃式增加。小于该来流攻角时,无间隙叶栅损失最小。大于该来流攻角时,无间隙叶栅损失最大。分析表明,间隙的存在可以抑制间隙侧角区分离,并同时推迟无间隙侧角区失速的发生。

关键词：压气机平面叶栅角区分离泄漏流

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Probing the dynamic structural changes of DNA using ultrafast laser pulse in graphene-based optofluidic device

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InfoMat 2021年第3期3卷 316-326页

作者： Bannur NShivananju Lu Zhou Yuefeng Yin Wenzhi Yu Babar Shabbir Haoran Mu Xiaozhi Bao Yiqiu Zhang Sun Tian Qingdong Ou shaojuan Li Mohammad MHossain Yupeng Zhang Huaiyu Shao Guichuan Xing Nikhil V.Medhekar Chang-Ming Li Jian Liu Qiaoliang Bao Institute of Advanced Cross-field Science College of Life ScienceQingdao UniversityQingdaoPeople's Republic of China Department of Materials Science and Engineering ARC Centre of Excellence in Future Low-Energy Electronics Technologies(FLEET)Monash UniversityClaytonVictoriaAustralia Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhouPeople's Republic of China College of Electronic Science and Technology and College of Optoelectronics Engineering Shenzhen UniversityShenzhenPeople's Republic of China Joint Key Laboratory of the Ministry of Education Institute of Applied Physics and Materials Engineering(IAPME)University of MacaoMacaoPeople's Republic of China Institute of Material Science and Devices Suzhou University of Science and TechnologySuzhouPeople's Republic of China

The ultrafast monitoring of deoxyribonucleic acid(DNA)dynamic structural changes is an emerging and rapidly growing research topic in *** existing optical spectroscopy used to identify different dynamical DNA structures lacks quick response while requiring large consumption of samples and bulky instrumental *** is highly demanded to develop an ultrafast technique that monitors DNA structural changes with the external stimulus or cancer-related disease ***,we demonstrate a novel photonic integrated graphene-optofluidic device to monitor DNA structural changes with the ultrafast response *** approach is featured with an effective and straightforward design of decoding the electronic structure change of graphene induced by its interactions with DNAs in different conformations using ultrafast nanosecond pulse laser and achieving refractive index sensitivity of~3×10^(−5) *** innovative technique for the first time allows us to perform ultrafast monitoring of the conformational changes of special DNA molecules structures,including G-quadruplex formation by K+ions and i-motif formation by the low pH *** graphene-optofluidic device as presented here provides a new class of label-free,ultrafast,ultrasensitive,compact,and cost-effective optical biosensors for medical and healthcare applications.

关键词： DNA optical biosensor graphene optofluidic device two-dimensional materials ultrafast fiber laser

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新型喹唑啉类化合物的合成研究

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四川师范大学学报（自然科学版） 2020年第3期43卷 357-363页

作者：孟令强杨绍娟张小博燕京理工学院教务处河北三河065201 燕京理工学院生命与健康学院河北三河065201 燕京理工学院工学院河北三河065201

以2.氨基-4-甲氧基-3-(3-氯丙氧基)苯甲酸甲酯为原料,经环合、氯代和取代等反应得到6种新型喹唑啉类化合物,总收率为45%左右;目标产物结构经GC-MS和核磁~1HNMR进行表征.与传统方法相比,该法具有原料廉价易得、路线简短、操作简便和反应... 详细信息

以2.氨基-4-甲氧基-3-(3-氯丙氧基)苯甲酸甲酯为原料,经环合、氯代和取代等反应得到6种新型喹唑啉类化合物,总收率为45%左右;目标产物结构经GC-MS和核磁~1HNMR进行表征.与传统方法相比,该法具有原料廉价易得、路线简短、操作简便和反应条件温和等优点,为后续的生物活性测试打下良好的基础.

关键词： 2.氨基-4-甲氧基-3-(3-氯丙氧基)苯甲酸甲酯合成新型喹唑啉类化合物

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