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discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USp28 inhibitors

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Acta pharmaceutica Sinica B 2020年第8期10卷 1476-1491页

作者： Zhenzhen Liu Taoqian Zhao Zhonghua Li Kai sun Yundong Fu Ting Cheng Jimin Guo Bin Yu Xiaojing Shi Hongmin Liu School of pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 China

Ubiquitin specific peptidase 28(USp28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date,only few USp28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USp28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USp28 inhibitors. Especially, compound 19 potently inhibited USp28(IC50=1.10 ± 0.02 μmol/L, Kd=40 nmol/L), showing selectivity over USp7 and LSd1(IC50> 100 μmol/L). Compound 19 was cellularly engaged to USp28 in gastric cancer cells. Compound 19 reversibly bound to USp28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition(EMT) progression in gastric cancer cell lines. docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USp28 inhibitors for exploring the roles of deubiquitinase in cancers.

关键词： inhibited 1,2 compound

A star-based method for precise wavelength calibration of the Chinese Space Station Telescope(CSST) slitless spectroscopic survey

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Research in Astronomy and Astrophysics 2021年第3期21卷 235-242页

作者： Hai-Bo Yuan ding-Shan deng Yang sun department of Astronomy Beijing Normal UniversityBeijing 100875China

The Chinese Space Station Telescope(CSST)spectroscopic survey aims to deliver high-quality low-resolution(R>200)slitless spectra for hundreds of millions of targets down to a limiting magnitude of about 21 mag,distributed within a large survey area(17500 deg2)and covering a wide wavelength range(255-1000 nm by three bands GU,GV,and GI).As slitless spectroscopy precludes the usage of wavelength calibration lamps,wavelength calibration is one of the most challenging issues in the reduction of slitless spectra,yet it plays a key role in measuring precise radial velocities of stars and redshifts of *** this work,we propose a star-based method that can monitor and correct for possible errors in the CSST wavelength calibration using normal scientific observations,taking advantage of the facts that(ⅰ)there are about ten million stars with reliable radial velocities now available thanks to spectroscopic surveys like LAMOST,(ⅱ)the large field of view of CSST enables efficient observations of such stars in a short period of time,and(ⅲ)radial velocities of such stars can be reliably measured using only a narrow segment of CSST *** demonstrate that it is possible to achieve a wavelength calibration precision of a few km s^(-1) for the GU band,and about 10 to 20 kms^(-1) for the GV and GI bands,with only a few hundred velocity standard *** of the method to other surveys are also discussed.

关键词： methods:data analysis methods:statistical techniques:spectroscopic techniques:radial velocities stars:fundamental parameters stars:kinematics and dynamics

Joint Resource Allocation and Admission Control in Sliced Fog Radio Access Networks

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China Communications 2020年第8期17卷 14-30页

作者： Yuan Ai Gang Qiu Chenxi Liu Yaohua sun State Key Laboratory of Network and Switching Technology Beijing University of Posts and TelecommunicationsBeijing 100876China LTE&5G Wireless product R&d Institute ZTE CorporationShenzhen 518057China

Network slicing based fog radio access network(F-RAN) has emerged as a promising architecture to support various novel applications in 5 G-and-beyond wireless networks. However, the co-existence of multiple network slices in F-RANs may lead to significant performance degradation due to the resource competitions among different network slices. In this paper, the downlink F-RANs with a hotspot slice and an Internet of Things(Io T) slice are considered, in which the user equipments(UEs) of different slices share the same spectrum. A novel joint resource allocation and admission control scheme is developed to maximize the number of UEs in the hotspot slice that can be supported with desired quality-of-service, while satisfying the interference constraint of the UEs in the Io T slice. Specifically, the admission control and beamforming vector optimization are performed in the hotspot slice to maximize the number of admitted UEs, while the joint sub-channel and power allocation is performed in the Io T slice to maximize the capability of the UEs in the Io T slice tolerating the interference from the hotspot slice. Numerical results show that our proposed scheme can effectively boost the number of UEs in the hotspot slice compared to the existing baselines.

关键词： NOMA fog radio access networks resource allocation admission control

胸外侧动脉彩色多普勒超声血流参数及血清VEGF、HAS2水平联合检测对乳腺癌术后患者复发转移的预测价值

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中国民康医学 2024年第20期36卷 123-125页

作者：袁梅孙改艳刘芳开封市祥符区第一人民医院超声科河南开封475100 开封市中心医院超声科河南开封475000

目的:探讨胸外侧动脉(LTA)彩色多普勒超声血流参数及血清血管内皮生长因子(VEGF)、透明质酸合成酶2(HAS2)水平联合检测对乳腺癌术后患者复发转移的预测价值。方法:回顾性分析2022年5月至2023年6月该院收治的63例行根治术的乳腺癌患者的... 详细信息

目的:探讨胸外侧动脉(LTA)彩色多普勒超声血流参数及血清血管内皮生长因子(VEGF)、透明质酸合成酶2(HAS2)水平联合检测对乳腺癌术后患者复发转移的预测价值。方法:回顾性分析2022年5月至2023年6月该院收治的63例行根治术的乳腺癌患者的临床资料,根据出院后随访6个月是否出现复发转移分为预后良好组(n=50)和预后不良组(n=13),比较两组LTA彩色多普勒超声血流参数及VEGF、HAS2水平,并绘制受试者工作特征(ROC)曲线分析其对乳腺癌术后患者复发转移的预测价值。结果:预后不良组阻力指数(RI)、搏动指数(pI)和收缩末期峰值/舒张末期峰值(S/d)均低于预后良好组,差异有统计学意义(pppI、S/d及血清VEGF、HAS2水平单项及联合检测预测乳腺癌术后患者复发转移的曲线下面积分别为0.746、0.797、0.818、0.758、0.738、0.932,联合检测预测价值高于各指标单项检测。结论:LTA彩色多普勒超声血流参数及血清VEGF、HAS2水平联合检测预测乳腺癌术后患者复发转移的价值高于各指标单项检测。

关键词：胸外侧动脉彩色多普勒超声透明质酸合成酶2 血管内皮生长因子乳腺癌根治术复发转移

Assessing the Connectivity of a Regional Fractured Aquifer Based on a Hydraulic Conductivity Field Reversed by Multi-Well pumping Tests and Numerical Groundwater Flow Modeling

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Journal of Earth Science 2023年第6期34卷 1926-1939页

作者： Jingjing Lin Rui Ma Ziyong sun Liansong Tang School of Environmental Studies State Key Laboratory of Biogeology and Environmental GeologyChina University of GeosciencesWuhan 430078China Yangtze River Basin Ecological Environment Monitoring and Scientific Research Center Yangtze River Basin Ecological Environment Supervision and Administration BureauMinistry of Ecological EnvironmentWuhan 430010China

Aquifer connectivity could greatly affect groundwater flow and further control the contaminant transport in fractured ***,assessing connectivity of fractured aquifer at regional scales is still a challenge because such connectivity is difficult to be measured *** study proposes a framework for assessing connectivity of a fractured aquifer,with Qitaihe area,Heilongjiang province,northeastern China as an illustrating study *** 3-d finite difference numerical models were established to interpret the results of three multi-well pumping tests and inversely estimate the distribution of hydraulic conductivity(K)in the fractured aquifer.A static connectivity metric of the minimum hydraulic resistance(MHR)was calculated,based on the optimized K-field,to evaluate the hydraulic connectivity in the aquifer,and the corresponding least resistance paths(LRps)were *** results indicate a better horizontal connectivity in the fractured aquifer in the northeastern and middle parts than in the southwestern part of the study *** identified LRp indicated that the preferential flow channels at regional scales were controlled mainly by aquifer connectivity instead of local high-K *** results of this study can provide a method for aquifer connectivity estimation at regional scales.

关键词： numerical modeling aquifer connectivity groundwater flow hydraulic conductivity minimum hydraulic resistance least resistance paths

Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults

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Science China(Life Sciences) 2009年第7期52卷 643-650页

作者： JIAO Yang1,QIU ZhiFeng1,XIE Jing1,LI dongJing2 & LI TaiSheng1 1 department of Infectious disease,peking Union Medical College Hospital,peking Union Medical College & Chinese Academy of Medical Sciences,Beijing,China 2 department of Special Care Unit,peking Union Medical College Hospital,peking Union Medical College & Chinese Academy of Medical Sciences,Beijing,China department of Infectious disease Peking Union Medical College Hospital Peking Union Medical College & Chinese Academy of Medical Sciences Beijing China department of Special Care Unit Peking Union Medical College Hospital Peking Union Medical College & Chinese Academy of Medical Sciences Beijing China

This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values.151 healthy adults aged 19-86 were recruited based on the SENIEUR *** sets of reference ranges were finally built applicable for the healthy young(19-44 years),middle-aged(45-64 years) and elder adults(≥65).Comparisons in parameters among the three cohorts showed that a statistically significant increase in Cd16Cd56+ NK cell was observed between the middle-aged and elder cohorts,whereas for the majority of the parameters,a significant decline was observed between the young and the middle-aged *** results showed that inverse correlations were observed between the age and Cd19+ B,Cd3+ T,Cd3+Cd4+ T,Cd4+Cd45RA+Cd62L+ nave T cell and Cd4+Cd28+/Cd4+,while the positive one was identified between the age and the NK *** significant changes of the most of immune parameters provided evidence for ***,T cell activation markers of Cd8+Cd38+ and Cd8+HLA-dR+ showed reverse trends of association with age,which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.

关键词： lymphocyte subsets age reference range immunosenescence

二氢麦角碱治疗脑小血管病性认知障碍对患者神经功能、认知功能及炎症因子水平的影响

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中国医学创新 2024年第24期21卷 60-64页

作者：孙文强王洪亮南通市第六人民医院神经内科江苏南通226011

目的:探讨二氢麦角碱治疗脑小血管病性认知障碍的效果及对炎症因子的影响。方法:选择2022年4月—2023年7月南通市第六人民医院收治的脑小血管病性认知障碍患者73例,按照随机数字表法分为观察组(n=37)、对照组(n=36)。两组患者均应用标... 详细信息

目的:探讨二氢麦角碱治疗脑小血管病性认知障碍的效果及对炎症因子的影响。方法:选择2022年4月—2023年7月南通市第六人民医院收治的脑小血管病性认知障碍患者73例,按照随机数字表法分为观察组(n=37)、对照组(n=36)。两组患者均应用标准的脑小血管病治疗方案,对照组给予盐酸多奈哌齐片,观察组给予甲磺酸二氢麦角碱缓释片。对比两组治疗前后神经功能[美国国立卫生研究院卒中量表(NIHSS)]、简易智力状态检查量表(MMSE)评分、日常生活活动能力量表(AdL)评分、炎症因子,评估两组治疗效果及不良反应发生率。结果:治疗90 d后,两组NIHSS均降低,观察组低于对照组,MMSE、AdL评分均升高,观察组均高于对照组,差异均有统计学意义(ppd后,两组超敏C反应蛋白、同型半胱氨酸、白细胞介素-6均降低,且观察组均低于对照组(pp>0.05)。结论:对于脑小血管病性认知障碍,采用二氢麦角碱治疗的效果满意,可显著改善患者神经功能及认知功能,提高日常生活能力,降低血清炎症因子水平,且安全性高。

关键词：脑小血管病认知障碍二氢麦角碱超敏C反应蛋白

New methyl formate synthesis method:Coal to methyl formate

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Journal of Energy Chemistry 2018年第1期27卷 238-242页

作者： Lingyun Rong Zhongning Xu Jing sun Guocong Guo State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou 350002FujianChina Key Laboratory of Coal to Ethylene Glycol and Its Related Technology Chinese Academy of SciencesFuzhou 350002FujianChina

Methyl formate is one of the most important intermediates in C1 chemistry, which has been employed in a wide range of industrial applications. Current synthesis methods for methyl formate mainly include esterification of methanol and formic acid, liquid-phase methanol carbonylation, oxidative dehydrogenation of methanol, one-step syngas synthesis, and carbon dioxide hydrogenation and condensation with methanol, Liquid-phase methanol carbonylation is currently a main commercially viable process devel- oped by BASF Corp, for the industrial production of methyl formate. Recently, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences has developed a new synthesis method to con- vert coal to methyl formate （denoted as CTMF）, different from the liquid-phase methanol carbonylation using homogeneous catalysts, CTMF method features with vapor-phase methanol carbonylation using het- erogeneous nanocatalysts, which can effectively utilize the coal-based syngas and produce value-added fine chemicals （i.e., methyl formate）. The newly developed method not only provides a new methyl for- mate synthesis technology but also contributes to the development of strategies for synthesizing valuable chemicals from coal. In this review, we firstly provide introduction on the development of existing methyl formate synthesis methods and then highlight the research progress of CTMF method. Finally, a perspec- tive on the future of CTMF is given,

关键词： Methyl formate Coal to methyl formate Vapor-phase methanol carbonylation Nanocatalyst

极端干旱与食草昆虫对草原群落的交互作用受干旱模式的影响

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Journal of plant Ecology 2024年第3期17卷 128-140页

作者： Ye Luo Yuguang Ke Hongqiang Wang Chong Xu Qian Gu Qiang Yu Melinda d.Smith Rajabboy Madrimov Nuriddin Samatov Wei Yang Honghui Wu State Key Laboratory of Effcient Utilization of Arid and Semi-arid Arable Land in Northern China Institute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Arable Land Quality Monitoring and Evaluation Ministry of Agriculture and Rural AffairsInstitute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081China School of Grassland Science Beijing Forestry UniversityBeijing 100083China department of Biology and Graduate degree program in Ecology Colorado State UniversityFort CollinsCO 80523USA Research Institute of Environment and Nature Conservation Technologies of the Ministry of Ecology Environmental Protectionand Climate Change of the Republic of UzbekistanTashkent 100043Uzbekistan Institute of Microbiology of the Academy of Sciences Tashkent 100128Uzbekistan Institute of Environment and Sustainable development in Agriculture Chinese Academy of Agricultural SciencesBeijing 100081China

极端干旱和食草昆虫可以共同影响植物群落,并且它们的交互作用可能受到干旱模式的影响。然而,目前尚缺乏相关的观测证据。本研究以半干旱草原为研究对象,通过控制实验探讨了不同极端干旱模式与食草昆虫的交互作用对植物群落的影响。实... 详细信息

极端干旱和食草昆虫可以共同影响植物群落,并且它们的交互作用可能受到干旱模式的影响。然而,目前尚缺乏相关的观测证据。本研究以半干旱草原为研究对象,通过控制实验探讨了不同极端干旱模式与食草昆虫的交互作用对植物群落的影响。实验设置了3种干旱处理,分别为对照(自然降雨量)、慢性干旱(生长季5–8月减少66%降雨量)和急性干旱(6–7月完全无降雨)。在各小区设置了两种食草昆虫处理,分别是有食草昆虫和无食草昆虫。结果表明,食草昆虫和极端干旱及二者的交互作用对物种丰富度无显著影响。食草昆虫缓解了慢性干旱对总盖度的负面影响,而这种缓解作用在急性干旱下较低。食草昆虫对慢性干旱带来的负面效应具有更强的缓解作用,这主要是因为食草昆虫导致慢性干旱下适口性较高的杂类草(具有较低叶片碳含量、叶片干物质含量,以及较低叶片淀粉、钙、镁、锰含量)的大幅降低,进而降低了禾草的负面效应。上述结果表明,干旱和食草昆虫的交互作用受干旱模式的影响。通过调节植物的适口性来控制食草昆虫的采食行为,可以减轻极端干旱对草原生态系统的影响。

关键词：急性干旱慢性干旱半干旱草原食草昆虫极端气候