Synthesis and biodistribution of ~(18)F-labeled pyridyl pyridaben analogues

目的设计并合成一种氟-18标记的哒螨灵类似物:4-氯-2-叔丁基-5-[[6-[[4-[2-[2-[2-氟[18f]乙氧基]乙氧基]乙氧基]-1H-1,2,3-三唑-1-基]甲基]-2-吡啶基]甲氧基]-3(2H)-哒嗪酮([18f]fPTP-P3),并评价其用于心肌灌注显像的可能性。方法采用[18f]f-取代OTS前体的方法进行标记,通过稳定性研究、脂水分配系数测定、生物分布实验等手段对标记物进行评价。结果 [18f]fPTP-P3的总制备时间为70~90 MIn,校正后的放化产率为36±5.6%,放化纯>98%。[18f]fPTP-P3为脂溶性化合物,在水溶液中可稳定放置3 H以上。生物分布实验结果显示,[18f]fPTP-P3在小鼠心肌具有一定的初始摄取,且肝部清除较快,但其心肌滞留较差。结论 [18f]fPTP-P3不具有用于心肌显像的潜力。Objective A fluorine-18 labeled pyridazinone derivative: 4-chloro-2-tert-butyl-5-[[6-[[4-[2-[2-[2-[18F]fluroethoxy] ethoxy]ethoxy]-1H-1,2,3-triazol-1-yl]methyl]-2-pyridinyl]methoxy]-3(2H)-pyridazinone([18F]FPTP-P3) was designed and prepared,and its potential as a myocardial perfusion imaging agent was evaluated.Methods [18F]FPTP-P3 was prepared by substituting tosyl of precursor with 18 F.The tracer was evaluated by stability study,octanol/water partition coefficient and biodistribution study.Results The total radio-synthesis time was 70-90 min,typical decay-corrected radiochemical yield was 36 ± 5.6%,and the radiochemical purity(RCP) was >98% after purification.It is a lipophilic compound,and stable in water for 3 h.The results of biodistribution study in mice showed that [18F]FPTP-P3 had certain initial heart uptake and the clearance of liver was very fast as well.However the retention of heart uptake was not ideal.Conclusion [18F]FPTP-P3 is not suitable for heart imaging in vivo.国家自然科学基金(20871020;81271613;21271030); 北京市自然科学基金(2092018)资助项目~

新时代一流本科教育的重建(笔会)

继\"双一流\"建设正式实施,建设一流本科教育成为我国高等教育发展的又一重要任务。一流本科教育的概念具有历史性、时代性、国别性和普遍性。\"以本为本\"的提出重在强调本科教育的最基础地位、本科教学的最基本职能、本科教育的最基本特质。建设一流的本科教育首先需要有先进的教育理念,明确其基本定位、指导思想、主要内涵与实施路径。提高本科教育质量的关键在于结构化育人模式,而通过学生课程学习经历调查可以评估本科教与学的质量。在建设一流本科教育中,还要重视学业考核制度建设,推进教育评价改革,构建良好的师生关系。对于一流研究型大学,要凸显一流本科的特色,处理好本科教育与学科发展的关系。国家社科基金“十三五”规划2017年度教育学重大招标课题“‘双一流’建设背景下高校学科调整与建设研究”(项目编号:VIA170003)的阶段性研究成果;;教育部人文社科重点研究基地重大项目“中国特色的大学内部治理结构与质量保障机制建设研究”(项目编号:18JJD880005)的阶段性研究成果;;国家社科基金(管理学)一般项目“管办评分离背景下大学社会评价体系和机制研究”(项目编号:16BGL172)的阶段性研究成果;;中国高教学会“中国高等教育改革发展重大理论实践问题研究”之“一流大学建设与一流本科教育的研究”(项目编号:2017ZD02)的阶段性研究成果

中国式学科评估:问题与出路

今年四月份,教育部学位与研究生教育发展中心(以下简称"教育部学位中心")邀请全国学位授予单位参加全国第四轮一级学科整体水平评估。随之,各个高校展开了一场大规模、高级别的学科评估申报及材料提交总动员。第四轮学科评估自发布起也引发了学界的广泛关注和热烈讨论。高等教育是中国崛起的思想发动机,关涉民族复兴的未来,而学科评估是近年来中国高等教育学科建设成就的集中展示,其意义和影响可谓深远。为了更好推进学科评估科学进行,特别是促进高等教育健康发展,《探索与争鸣》编辑部邀请全国

Synthesis and Biodistribution of 2-tert-butyl-4-chloro-5-(2-[~(18)F]fluroethoxy)-2H-pyridazin-3-one

设计并合成了一种18 f标记哒嗪酮类似物:2-特丁基-4-氯-5-(2-氟[18 f]乙氧基)-2H-3-哒嗪酮(18 f-fP2),通过生物分布实验评价了其用于心肌灌注显像的可行性。18 f-fP2的总制备时间为70~90MIn,校正后的放化产率为53.0%±5.2%,放化纯度>98%;18f-fP2为脂溶性化合物,在水溶液中可稳定放置3H以上。生物分布实验结果显示,18f-fP2在肝、肺中初期摄取高,注射后2MIn分别为(14.53±2.36)%Id/g和(33.69±10.79)%Id/g,但清除很快,注射后15MIn,其肝、肺的清除率已分别达57.7%和86.2%。18 f-fP2的心肌摄取较低,最高摄取值为(4.09±0.53)%Id/g(注射后2MIn)。这可能因标记侧链上未带苯环造成的,说明哒嗪酮侧链的芳环结构对心肌的摄取与滞留有较大影响。A fluorine-18labeled pyridazinone derivative:2-tert-butyl-4-chloro-5-(2-[18F]fluroethoxy)-2H-pyridazin-3-one(18F-FP2)was designed and prepared as a potential myocar- dial perfusion imaging agent.The total radio-synthesis time was 70-90min,typical decay-corrected radiochemical yield was 53.0%±5.2%,and the radiochemical purities were> 98%after purification.It is a lipophilic compound,and stable in water for 3h.The results of biodistribution studies in mice showed that 18F-FP2had high liver and lung uptake at initial post-injection time,the uptake was(14.53±2.36)%ID/g and(33.69±10.79)%ID/g at 2min post-injection,respectively.Radioactivity was washed out very fast from liver and lung,the rate of clearance was 57.7%and 86.2%at 15min post-injection,respectively.However the heart uptake of 18F-FP2was very low,the highest heart uptake was(4.09± 0.53)%ID/g at 2min post-injection.This may due to the removing of phenyl group in the labeling sidechain of pyridazinone,indicating that the aromatic ring has strong influence on the heart uptake and retention.国家自然科学基金资助项目(20871020;21271030); 北京市自然科学基金资助项目(2092018

Preparation and Biological Evaluation of Novel ~(18)F-labeled Phosphonuim Cation for Myocardial Perfusion Imaging with PET

为研制新型的PET心肌灌注显像剂,设计合成了18 f标记的鏻正阳离子:3-氟-18 f-甲基苄基-三-(2,6-二甲氧基苯基)鏻盐(18f-2),并进行了小鼠生物分布研究。18f-2采用一锅法制备得到,总的标记时间小于60MIn,校正后的产率为(31±3)%,放化纯度>95%;小鼠生物分布结果表明,18 f-2在小鼠心肌中有很高的初始摄取和良好的滞留,给药后2MIn和60MIn的心肌摄取分别为(53.88±7.45)%Id/g和(23.93±3.28)%Id/g;其在肝、肺、血等非靶组织中的摄取低,且清除快,给药后60MIn心与肝、心与肺、心与血放射性摄取比分别为3.99、3.80和9.17。值得进一步深入研究。In order to develop new PET myocardial perfusion imaging agent,a novel 18 F labeled phosphonium cation:(3-([18 F]fluoromethyl)benzyl)tris(2,6-dimethoxyphenyl)phosphonium salt,18F-2,had been designed and prepared.Biological evaluation of18F-2had been performed in Kunming normal mice.18F-2was obtained by a simple onepot method and the radiochemical yield was(31±3)%.The total radio-synthesis time was less than 60 min and the radiochemical purity of final radiotracer was more than95%.The biodistribution of 18F-2displayed a high heart uptake and good retention.The heart uptake of 18F-2at 5and 60 min post-injection were(53.88±7.45)%ID/g and(23.93±3.28)%ID/g,respectively.18F-2exhibited low radio-accumulation in nontarget tissues and rapid clearance in liver,lung and blood.The heart to liver,heart to lungs and heart to blood ratio values were 3.99,3.80 and 9.17,respectively.The results indicated that 18F-2could be as a promising myocardial perfusion imaging agent for PET imaging.国家自然科学基金项目(20871020;21271030;81471707

干旱内陆河灌区节水农业综合技术体系研究与集成

本课题从工程节水、农艺节水、管理节水三个方面,集成了农业高效节水、水肥盐调控、生态保护、监测与管理等关键技术,提出了干旱内陆河灌区农业节水技术集成体系与应用模式。提出了仅需根据水流推进过程确定土壤入渗参数和田面糙率系数的新方法,简化了地面灌溉设计。提出了根据土壤剖面含水率变化估算柽柳生长条件下潜水蒸发的理论方法与数学模型,为解决天然植被实际生态耗水问题提供了简易可行的方法

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies