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Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent,specific and orally active P-glycoprotein(P-gp)inhibitor

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3263-3280页

作者： sai-qi wang qiu-Xu Teng Shuai wang Zi-Ning Lei Hui-Hui Hu Hui-Fang Lv Bei-Bei Chen Jian-Zheng wang Xiao-Jing Shi Wei-Feng Xu Hong-Min Liu Xiao-Bing Chen Zhe-Sheng Chen Bin Yu Department of Oncology the Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalHenan Cancer InstituteZhengzhou 450008China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhou 450052China College of Pharmacy and Health Sciences St.John’s UniversityQueensNY 11439USA Laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450052China

Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft(PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

关键词： Multidrug resistance(MDR) ATP-Binding cassette P-gp inhibitors Triazolo[1,5-a]pyrimidine Drug combination Preclinical studies Cancer therapy

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2005—2015年我国移动医疗研究现况的文献计量学分析

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中国全科医学 2017年第20期20卷 2495-2499页

作者：王艺蓉张容瑜何志辉马淑雯刘尧赛刘尚琪王前何群南方医科大学珠江医院广东省广州市510280 广东省疾病预防控制中心广东省公共卫生研究院广东省广州市511430 广州达安临床检验中心广东省广州市510670 南方医科大学第五附属医院广东省广州市510900

目的掌握我国移动医疗的研究动态,了解国内移动医疗的发展现状。方法以中国知网为搜索平台,采用文献计量法从文献数量、关键词、来源期刊、研究机构4个方面对2005—2015年收录的国内移动医疗研究领域相关文献进行分析研究。结果461篇文... 详细信息

目的掌握我国移动医疗的研究动态,了解国内移动医疗的发展现状。方法以中国知网为搜索平台,采用文献计量法从文献数量、关键词、来源期刊、研究机构4个方面对2005—2015年收录的国内移动医疗研究领域相关文献进行分析研究。结果461篇文献纳入研究,文献数量呈逐年递增趋势,于2005—2009年保持在较低区间,从2010年开始呈快速增长态势;按照关键词出现频次从大到小进行排序,出现频次≥10次的关键词,共32个;根据关键词可将文献分为移动医疗技术研究、移动医疗应用研究和移动医疗评述类3个研究主题,根据趋势推断,3个研究主题的文献数量占比将逐渐趋于一致;来源期刊共197种,其中载文数量≥5篇的期刊15种,发表文献总计199篇,占文献总量的43.17%(199/461);移动医疗研究机构主要为高校和各大附属医院。结论移动医疗已经成为学术研究的热点问题,但是仍然存在研究机构较为分散、研究质量不高等问题。

关键词：移动医疗中国文献计量学

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Ultrafast Dynamics of Polythiophene with Phenyl Vinylene Branches Studied by Femtosecond Fluorescence Spectroscopy in Solution

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Chinese Physics Letters 2011年第11期28卷 228-231页

作者： CHU sai-sai GAO Chao wang Shu-Feng GONG qi-Huang State Key Laboratory for Mesoscopic Physics Department of PhysicsPeking UniversityBeijing 100871 Xi’an Modern Chemistry Research Institute Xi’an 710065

Two polythiophene based polymers,poly[(3-[2-[4-(2-ethyl-hexyloxy)-phenyl]-vinyl]-thiophene)-co-thiophene](PT1)and poly(3-[2-[4-(2-ethyl-hexyloxy)-phenyl]-vinyl]-thiophene)(PT2),are synthesized and investigated by static,picosecond fluorescence spectroscopies and the femtosecond up-conversion technique in *** with pristine poly(3-hexylthiophene)(P3HT),PT1 and PT2,in which the main chains are decorated with phenyl vinylene present a‘camel back’structure in the absorption *** vinylene side chains induce a new process of charge transfer,chain twisting motion and defect-induced fluorescence quenching at time scales of 1 ps,10 ps and 150 ps,respectively.

关键词： solution spectra vinyl

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Recent Development of Bio-inspired Porous Materials for Catalytic Applications

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Chemical Research in Chinese Universities 2023年第1期39卷 13-18页

作者： TANG Yongquan qi Ganggang wang sai MENG Xiangju XIAO Feng-Shou Department of Chemistry Zhejiang UniversityHangzhou310028P.R.China Stomatology Hospital School of StomatologyZhejiang UniversityHangzhou310006P.R.China Key Lab of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological EngineeringZhejiang UniversityHangzhou310028P.R.China Department of Chemistry Zhengzhou UniversityZhengzhou450001P.R.China

Nature has served as a source of inspiration for chemists to design the catalysts with superior performance via mimicking their characteristics,such as active sites,reaction microenvironment and electron transfer *** a few decades,many different types of materials have been widely used to construct the biomimetic *** these materials,the porous materials have been demonstrated to be powerful platforms for constructing the biomimetic catalysts owing to their high surface area,controllable composition and easy *** this review,we briefly showed recent advances in the construction of various biomimetic porous catalysts using porous materials for the design of excellent *** addition,we also present the challenge and opportunities in this emerging field.

关键词： Bio-inspired Porous material Biomimetic catalyst

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Impact Force Magnitude and Location Recognition of Composite Materials

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Computers, Materials & Continua 2020年第9期64卷 1647-1656页

作者： Yajie Sun Yanqing Yuan qi wang sai Ji Lihua wang Shao’en Wu Jiangsu Engineering Centre of Network Monitoring Nanjing University of Information Science and TechnologyNanjing210044China School of Computer and Software Nanjing University of Information Science and TechnologyNanjing210044China School of Information and Control Nanjing University of Information Science and TechnologyNanjing210044China Department of Computer Science Ball State UniversityMuncieUSA

In order to identify the location and magnitude of the impact force accurately,determine the damage range of the structure and accelerate the health monitoring of key components of the composite,this paper studies the location and magnitude of the impact force of composite plates by an inverse ***,a PZT sensor mounted on the material plate is used to collect the response signal generated by the impact force,which is from several impact locations,and establish transfer functions between the impact location and the PZT ***,this paper applies several forces to any location on the material plate,and collects the corresponding response signals,and reconstructs the impact force of several locations in ***,according to the reconstruction result of each location,the correct impact location is ***,an improved regularization method is used to optimize the reconstructed impact force and accurate the magnitude of the impact *** comparison experiments prove that the recognition error of this method is smaller.

关键词： Impact force identification transfer function regularization

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Effects of Magnetic Pressure Constraint on Dynamic Deformation and Oscillation Behavior of Metal Free Surface

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Journal of Iron and Steel Research International 2016年第11期23卷 1134-1141页

作者： Yang LI An-yuan DENG Chuan-qi YIN sai-juan ZHANG En-gang wang Key Laboratory of Electromagnetic Processing of Materials(Ministry of Education) Northeastern University College of Metallurgy Northeastern University

A new method was presented to constrain deformation and oscillations of liquid metal free surface by using a high frequency magnetic field. A magnetic field generator was designed to investigate its feasibility using numerical simulation and physical simulation. The results indicate the feasibility of controlling bulge deformation of liquid metal surface using magnetic pressure. Sunken deformation with a slight fluctuation occurs on the surface when magnetic pressure acts on the static liquid metal surface. The largest amplitude remains within i0.8 mm even if current rea- ches 1400 A. In case of the bump-type deformation, the magnetic pressure strengthens gravity field by the superpo- sition effect, dissipates the kinetic energy of metal flow impacting on free surface in advance, reduces the velocity of free surface, and decreases the bulge height. On the region without magnetic field, the liquid metal surface rises and tends to be flat because of the significant damping effect on surface fluctuation. The constraint strength of the mag- netic pressure increases with the augment of current intensity. However, different heights of bulge deformation should have a corresponding reasonable coil current for achieving the best constraint effect.

关键词： magnetic pressure high {requency magnetic field free surface fluctuation numerical simulation liquid metal

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Improved photocatalytic performance of acetaldehyde degradation via crystal plane regulation on truncated octahedral CeO_(2)

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Rare Metals 2024年第5期43卷 2026-2038页

作者： Bin Xu Lu Jia Hui Yang Yue wang Si-Yu Fan sai-sai Yuan qi-TaoZhang Ming Zhang Teruhisa Ohno School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225002China College of Environmental Science and Engineering Yangzhou UniversityYangzhou225127China Department of Applied Chemistry Faculty of EngineeringKyushu Institute of TechnologyKitakyushu804-8550Japan School of Environmental and Chemical Engineering Jiangsu University of Science and TechnologyZhenjiang 212000China National&Local Joint Engineering Research Center for Mineral Salt Deep Utilization Huaiyin Institute of TechnologyHuaian 223003China School of Materials Science and Engineering Henan University of Science and TechnologyLuoyang 471000China International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen 518060China

In this study,the truncated octahedral CeO_(2)(CeO_(2)-to)with special morphology was prepared by the solvothermal method with oleic acid(OA)and oleamine(OM)as the morphology-directing ***-resolution transmission electron microscopy(HRTEM)results show that CeO_(2)-to exposes composite{100}and{111}facets,while CeO_(2)cubic(CeO_(2)-c)and CeO_(2)octahedral(CeO_(2)-o)only expose single crystal facets of{100}plane and{111}plane,***,this CeO_(2)-to photocatalyst exhibits remarkable photooxidation performance of gaseous acetaldehyde(CH_(3)CHO)degradation,in which CO_(2)generation value reaches 1.78 and 7.97-times greater than that of CeO_(2)-c and CeO_(2)-o,*** addition,the active species trapping experiment signifies that superoxide(·O_(2)^(-))and holes(h^(+))are the main reactive substances during the CH_(3)CHO degradation process,and the electron paramagnetic resonance(EPR)spectra indicates that the former is the major ***,the electron transfer mechanism between CeO_(2)-to{100}and{111}facets and the surface oxygen adsorption ability are revealed via density functional theory(DFT)*** is also confirmed that{100}facets are more conducive to the absorption of acetaldehyde than{111}***,a reasonable mechanism for improved photocatalytic CH_(3)CHO degradation on CeO_(2)-to is proposed based on relevant experiments and DFT *** study demonstrates that the systematic development of surface homojunction structured photocatalysts can efficiently increase the degradation activity for volatile organic compounds(VOCs).It also offers additional direction for optimizing the photocatalytic activity of other ceriumbased photocatalysts.

关键词： Truncated octahedral CeO_(2)(CeO_(2)-to) Composite crystal faces Surface energy level Efficient electrontransfer

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A Label-Free Colorimetric Aptasensor Containing DNA Triplex Molecular Switch and AuNP Nanozyme for Highly Sensitive Detection of Saxitoxin

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Journal of Ocean University of China 2022年第5期21卷 1343-1350页

作者： qi Xiaoyan LI Ling YAN Xiaochen ZHAO Yinglin wang Lele MA Rui wang sai MAO Xiangzhao College of Food Science and Engineering Ocean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of qingdao National Laboratory for Marine Science and Technology Qingdao 266237China

Saxitoxin(STX),one of the most toxic paralytic shellfish poisons discovered to date,is listed as a required item of aquatic product safety inspection ***,conventional detection methods for STX are limited by various issues,such as low sensitivity,complicated operations,and ethical *** this study,an aptamer-triplex molecular switch(APT-TMS)and gold nanoparticle(AuNP)nanozyme were combined to develop a label-free colorimetric aptasensor for the rapid and highly sensitive de-tection of *** anti-STX aptamer designed with pyrimidine arms and a purine chain was fabricated to form an *** binding between the aptamer and STX triggered the opening of the switch,which causes the purine chains to adsorb onto the surface of the AuNPs and enhances the peroxidase-like activity of the AuNP nanozyme toward 3,3’,5,5’-*** optimized conditions,the proposed aptasensor showed high sensitivity and selectivity for STX,with a limit of detection of 335.6 pmol L^(−1) and a linear range of 0.59-150 nmol L^(−1).Moreover,good recoveries of 82.70%-92.66%for shellfish and 88.97%-106.5%for seawater were *** analysis could be completed within 1 *** proposed design also offers a robust strategy to achieve detection of other marine toxin targets by altering the corresponding aptamers.

关键词： saxitoxin colorimetric aptasensor aptamer triplex molecular switch AuNP nanozyme

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Development of a Label-Free Colorimetric Aptasensor with Rationally Utilized Aptamer for Rapid Detection of Okadaic Acid

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Journal of Ocean University of China 2022年第2期21卷 400-408页

作者： YAN Xiaochen qi Xiaoyan ZHAO Yinglin LI Ling MA Rui wang Lele wang sai MAO Xiangzhao College of Food Science and Engineering Ocean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of qingdao National Laboratory for Marine Science and Technology Qingdao 266237China

Okadaic acid(OA)is a typical marine toxin with strong toxicity causing diarrheic shellfish poisoning(DSP).Aptamers show great advantages in toxin detection and attract increasing attentions in the field of food *** this study,a label-free col-orimetric aptasensor was constructed for visual and rapid detection of OA in *** exploit the binding capability of the anti-OA aptamer,the inherent molecular recognition mechanism of aptamer and OA was studied,based on molecular docking,fluorescent assay,and biolayer *** results showed that the stem-loop near the 3’terminal of the aptamer exhibit dominate binding *** on the revealed recognition information,the aptamer was thus rationally utilized and combined with AuNPs and cationic polymer polydiallyl dimethyl ammonium chloride(PDDA)for the development of the label-free colorimetric aptasensor,in which the 3’terminal was thoroughly exposed to *** aptasensor provided robust performance with a linear detection range of 100-1200 nmol L-1,a limit of detection of 41.30 nmol L-1,recovery rates of 91.6%-106.2%,as well as a high selectivity towards OA in shellfish *** whole detection process can be completed within 1 *** our best knowledge,this is the first time that the anti-OA aptamer was thoroughly studied,and a label-free colorimetric aptasensor was rationally designed in this *** study not only provides a rapid detection method for highly sensitive and specific detection of OA,but also serves as a reference for the design of efficient aptasensors in the future.

关键词： aptamer okadaic acid colorimetric aptasensor molecular docking fluorescent assay biolayer interferometry

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Transient interactions between bubbles and a high-speed cylinder in underwater launches: An experimental and numerical study

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Journal of Hydrodynamics 2023年第1期35卷 36-45页

作者： sai Zhang qi-Hang Chen Chang Liu A-Man Zhang Shuai Li College of Shipbuilding Engineering Harbin Engineering UniversityHarbin150001China

The underwater launch of high-speed vehicles involves complex bubble-structure interactions,which are not currently well *** this study,two small-scale experiments are carried out involving transient bubble-cylinder *** adopt the underwater electric discharge method to generate a high-pressure bubble that drives a cylinder to a maximum velocity of∼25 m/s within 1 ms.A tail bubble forms as the cylinder is ejected from the launch ***,we observe a shoulder cavity around the head of the cylinder due to the pressure reduction in the *** better understand the complex interaction between bubbles and the high-speed cylinder,we use the boundary element method to establish a bubble—structure interaction *** numerical model reproduces the experimental observations quite well,including the cylinder motion and the transient evolution of the ***,a systematic study is carried out to reveal the dependence of the bubble-cylinder interactions on the initial pressure of the tail bubble *** obtain a scaling law for the maximum velocity of the cylinder v_(m) with respect to p_(0),namely,v_(m) ∝ p_(0)^(0.45).The findings from this study may provide a reference for subsequent research into underwater launches.

关键词： Bubble dynamics underwater launch cavitation boundary element method

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