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Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Acta Pharmaceutica Sinica B 2021年第1期11卷 181-202页

作者： Shun Zhang Yan Zhao Shuyuan Wang Min Li Yue Xu Jianhua Ran xiaoqiang Geng Jinzhao He Jia Meng Guangying Shao hong Zhou Zemei Ge Guangping Chen Runtao Li Baoxue Yang Department of Pharmacology School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China Key Laboratory of Molecular Cardiovascular Sciences Ministry of EducationBeijing 100191China School of Pharmaceutical Sciences Peking UniversityBeijing 100191China College of Pharmacy Inner Mongolia Medical UniversityHohhot 010110China Department of Anatomy and Neuroscience Center Chongqing Medical UniversityChongqing 400016China Department of Physiology Emory University School of MedicineAtlantaGA 30322USA

Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing ***,UT inhibitors are promising for development as novel *** the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput *** of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar *** half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,*** investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell *** interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in ***,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.

关键词： Urea transporter inhibitor Diuretic Structure optimization Oral administration

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Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

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Traditional Medicine Research 2025年第2期10卷 16-29页

作者： Xia-Jie Quan Hao Liang Yong-hong Tang Li Jiang Xiong-Ying Ji Feng-Ying Zhang Ping Zhang Bo Ouyang Department of Information The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Neurology The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Gastroscopy The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Traditional Chinese Medicine The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of ***,the specific mechanism of action of SXLJF remains ***:The mouse model of insomnia was established by intraperitoneal injection of ***-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive *** open field test and pentobarbital-induced sleeping test were ***-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating ***,key targets were validated using ***:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep *** and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of ***,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,***-qPCR results supported the role of TH in the mechanism of SXLJF in treating ***:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

关键词： Shangxia Liangji formula insomnia metabolomics network pharmacology tyrosine hydroxylase tyrosine metabolism

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陕西关中东部棉花抗旱品种农艺节水综合技术研究

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中国农学通报 2006年第10期22卷 141-143页

作者：王俊峰杜健洪晓强赵俊兴刘漫道张兴亮夏志明王成贾涛张月丽胡森西北农林科技大学农学院棉花所陕西杨凌712100 西北农林科技大学资环学院陕西杨凌712100

按照生态农业理论和抗旱节水技术要求,对棉花抗旱品种、不同密度、不同基肥N、P的施用量进行田间综合试验,采用正交设计法。3年试验研究结果表明:密度以每公顷种植7.5万株比4.5万株、6万株平均增产671.85kg、483.30kg,增产57.49%和41.36... 详细信息

按照生态农业理论和抗旱节水技术要求,对棉花抗旱品种、不同密度、不同基肥N、P的施用量进行田间综合试验,采用正交设计法。3年试验研究结果表明:密度以每公顷种植7.5万株比4.5万株、6万株平均增产671.85kg、483.30kg,增产57.49%和41.36%。品种陕402(早熟)、陕576(中早熟)分别比中棉所19(中熟)增产16.62%和16.17%,具有较强抗旱性。磷酸二铵比尿素增产作用明显,每公顷施150、225kg分别增产11.35%和10.53%。

关键词：棉花抗旱品种节水技术关中东部

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Reliability model of organization management chain of South-to-North Water Diversion Project during construction period

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Water Science and Engineering 2008年第4期1卷 107-113页

作者： Feng Jingchun Zhou Yang hong Yuzhen Zhao Shixin Ren xiaoqiang Business School Hohai University Nanjing 210098 P. R. China Office of the South-to-North Water Diversion Project Construction Committee under the State Council Beijing 100053 P. R. China

In order to analyze the indispensability of the organization management chain of the South-to-North Water Diversion Project （SNWDP）, two basic forms （series connection state and mixed state of both series connection and parallel connection） of the organization management chain can be abstracted. The indispensability of each form has been studied and is described in this paper. Through analysis of the reliability of the two basic forms, reliability models of the organization management chain in the series connection state and the mixed state of both series connection and parallel connection have been set up.

关键词： South-to-North Water Diversion Project reliability model management chain parallel connection series connection

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Toxic marine diatoms of hong Kong:A paleoecological study

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Journal of Environmental Sciences 1997年第1期9卷 1-10页

作者： Mike Dickman Tom Glenwright Ecology and Biodiversity Department,The University of hong Kong,hong Kong Ecology Department University of Hong Kong Hong Kong Hong Kong

To determine whether toxic diatoms in hong Kong's Victoria Harbour have become more common during the last four decades,a gravity core was taken from the anaerobic sediments of Kowloon Bay in the harbour. Analysis of these sediments from a depth of 0-1cm,4-5cm and 9-10cm indicated that 6.4%,2.4% and 1.5% of the diatoms observed at each of these three respective depths belonged to the genus Pseudonitzschia. The abundance of Pseudonitzschia frustules in the surface sediments of Victoria Harbour was significantly higher(phong Kong's coastal waters as a re- sult of man's activities.

关键词： paleoecology sediment cores marine diatoms toxic diatoms Pseudonitzschia.

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Effects of ultraviolet radiation B (UV-B) on photosynthesis of natural phytoplankton assemblages in a marine bay in Southern China

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Chinese Science Bulletin 2007年第4期52卷 545-552页

作者： YUAN XiangCheng YIN KeDong ZHOU WeiHua CAO WenXi XU xiaoqiang ZHAO Di Key Laboratory of Tropical Marine Environmental Dynamics South China Sea Institute of Oceanology Chinese Academy of Sciences Guangzhou 510301 China Atmospheric Marine & Coastal Environment (AMCE) Program Hong Kong University of Science & Technology Kowloon Hong Kong SAR China

Solar ultraviolet radiation B (UVB) is known to have inhibitive effects on phytoplankton photosynthesis. UVB light decreases rapidly with increasing depth in the water column and exerts different degrees of UVB inhibitive effects on phytoplankton photosynthesis. In this study, the objectives were to quantify effects of UVB on phytoplankton photosynthesis and quantum yield, and to examine UVB effects on phytoplankton photosynthesis when light varies. The insitu experiments were conducted in Da Ya Bay, which is a semienclosed area in the subtropical South China. The results showed a significant reduction of photosynthetic rates and quantum yield in the presence of UVB. Maximum photosynthetic rates (Pmax) and maximum quantum yield (Φmax) were 11%-22% and 17%-49% less under solar radiation with UVB than without UVB. A simplified model was developed to describe the UVB biologically effective fluence rate (E*inh) as an exponential decay function of depth. Light-shift experiments, in which water samples from the surface and at depth of 4 m were divided into several subsamples, and each subsamples were then incubated at different depths with and without UVB in the water column, showed that phytoplankton from the deeper water (4 m) had more inhibitive rates by UVB than that from the surface when exposed to the same light condition.

关键词：中国南海海湾浮游植物群落光合作用紫外辐射碳吸收抑制作用

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Advances and perspectives in catalytic oxidation of hydrocarbons in liquid phase

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Progress in Natural Science:Materials International 2007年第9期17卷 1003-1011页

作者： Zhou Lipeng,Yang Guanyu,Zhang Wei,Sun Zhiqiang,Gao Jin,Miao hong,Chen Chen,Ma hong,Li xiaoqiang,Zhang Qiaohong,Wang Feng,Tong Xinli and Xu Jie(Laboratory of Fine Chemicals,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,China) Laboratory of Fine Chemicals， Dalian Institute of Chemical Physics， Chinese Academy of Sciences， Dalian 116023， China

This review article summarizes recent advances in catalytic oxidation of hydrocarbons,especially presents two strategies for activation of C-H bonds or molecular *** on our own research results,the applications of the two methods in the oxidation of cyclohexane,toluene and ethyl benzene,*** introduced,and the perspectives of the two methods are also discussed.

关键词： hydrocarbon oxidation molecular oxygen catalysis C-H bond

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Inferring the dynamics of “black-box” systems using a learning machine

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Science China(Physics,Mechanics & Astronomy) 2021年第7期64卷 72-81页

作者： hong Zhao Department of Physics Xiamen UniversityXiamen361005China Lanzhou Center for Theoretical Physics Lanzhou UniversityLanzhou730000China

Given a segment of a time series of a system at a particular set of parameter values, is it possible to infer the dynamic behavior of the system in its parameter space? Here, we show that this goal can be achieved to a certain extent using a self-evolution learning machine. It is found that following an appropriate training strategy that monotonously decreases the cost function, the learning machine in different training stages is just like the system at different parameter sets. Consequently, the dynamic properties of the system are, in turn, usually revealed in the simple-to-complex order. The underlying mechanism can be attributed to the training strategy, which results in the learning machine collapsing to a qualitatively equivalent system of the system behind the time series. Thus, the learning machine enables a novel way of probing the dynamic properties of a “black-box” system without artificially establishing the equations of motion. The given illustrative examples include a representative model of low-dimensional nonlinear dynamical systems and a spatiotemporal model of reaction-diffusion systems.

关键词： prediction learning machine inverse problems “black-box”system nonlinear dynamics

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纤维桩联合不同冠部修复方式修复穿髓型非龋性颈部缺损牙体的力学分析

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中国组织工程研究 2025年第4期29卷 866-871页

作者：陈倚珑张旭李红首都医科大学附属北京口腔医院北京市100050 北京市房山区良乡医院北京市102401

背景:使用纤维桩修复穿髓型非龋性颈部缺损可以改变牙齿的应力分布,显著降低患牙折裂风险,但关于纤维桩改善牙体抗折性的力学机制及穿髓型非龋性颈部缺损的最佳冠部修复方式尚有争论。目的:综述纤维桩修复穿髓型非龋性颈部缺损后的应力... 详细信息

背景:使用纤维桩修复穿髓型非龋性颈部缺损可以改变牙齿的应力分布,显著降低患牙折裂风险,但关于纤维桩改善牙体抗折性的力学机制及穿髓型非龋性颈部缺损的最佳冠部修复方式尚有争论。目的:综述纤维桩修复穿髓型非龋性颈部缺损后的应力分布模式,在各种受力状态下的抗折能力与断裂模式,以及纤维桩联合不同冠部修复方式的最新研究进展。方法:应用计算机在PubMed和中国知网数据库中检索2008年9月至2023年9月发表的相关文献,英文检索词为“non-carious cervical lesions,endodontically treated teeth restoration,endodontically treated teeth stress distribution”,中文检索词为“非龋性颈部缺损,根管治疗后牙体修复,根管治疗后牙齿应力分布”,最终纳入56篇文献进行分析。结果与结论:穿髓型非龋性颈部缺损根管治疗后,应用纤维桩修复可部分改善牙齿颈部应力,同时不会增加牙根纵裂的风险;使应力分布更加均匀,提高牙齿的抗折性。使用纤维桩修复的非龋性颈部缺损牙齿若折断,其断裂模式显示出有利的、可恢复的或可修复的断裂模式。纤维桩联合瓷贴面或贴面式嵌体可能会成为修复穿髓型非龋性颈部缺损的一种较理想微创修复方法。

关键词：非龋性颈部缺损穿髓型三维有限元分析纤维桩冠部修复应力分布抗折性折断模式

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肝静脉剥夺术与门静脉栓塞治疗剩余肝体积不足肝癌效果比较的Meta分析

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临床肝胆病杂志 2025年第12期40卷 2464-2472页

作者：闫凯峰胡小杰刘宏山西医科大学第一临床医学院太原 030001 山西医科大学第一医院肝胆胰外科及肝脏移植中心太原 030001

目的系统性评价肝静脉剥夺术（LVD）与门静脉栓塞（PVE）治疗剩余肝体积（FLR）不足的肝脏恶性肿瘤的效果及预后。方法本研究根据PRISMA指南完成，PROSPERO注册号：CRD42024533292。检索PubMed、Embase、Cochrane Library、Web of Scie... 详细信息

目的系统性评价肝静脉剥夺术（LVD）与门静脉栓塞（PVE）治疗剩余肝体积（FLR）不足的肝脏恶性肿瘤的效果及预后。方法本研究根据PRISMA指南完成，PROSPERO注册号：CRD42024533292。检索PubMed、Embase、Cochrane Library、Web of Science、知网、万方、维普等数据库中关于LVD与PVE效果比较的所有文献。根据制定的纳入和排除文献标准，筛选相关文献，评估文献质量，提取相关LVD与PVE的临床对比资料，整理并分析数据。使用RevMan 5.3软件进行Meta分析。结果共纳入12篇文献（均为队列研究），含644例患者（LVD组245例，PVE组399例）。Meta分析结果显示，在栓塞后FLR增长率（SMD=0.84，95%CI：0.59～1.09）、栓塞后FLR每日增长体积（SMD=1.19，95%CI：0.64～1.73）、栓塞后并发症发病率（RR=1.59，95%CI：1.06～2.38）、栓塞与二期手术间隔时间（SMD=-0.81，95%CI：-1.32～-0.29）和二期手术完成率（RR=1.09，95%CI：1.01～1.18）两组间差异均有统计学意义（P值均<0.05）。结论LVD相较于PVE能够使患者在相对较短的时间内获得达到手术指征的FLR，从而降低疾病进展的发生率以及解决肥大不足的问题，达到更高的二期手术切除率，从而使更多的肝癌患者受益。并且，LVD在二期手术中具有和PVE相似的安全性。

关键词：肝肿瘤肝静脉剥夺门静脉栓塞 Meta分析

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