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Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 697-712页

作者： Canyu Yang Shumin Fan Xing wang Wei Liu Long Yang Bing He Wenbing Dai Hua Zhang xueqing wang Qiang Zhang Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencePeking UniversityBeijing 100191China Beijing Key Laboratory of Molecular Pharmaceutics New Drug Delivery SystemsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China Department of Pharmacy Peking University Third HospitalBeijing100083China

The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)***,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors ***-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination ***,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor *** the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low ***,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was *** with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics.

关键词： Caveolin-1 Nab-paclitaxel Trastuzumab Combination regimen optimization

A magnetism/laser-auxiliary cascaded drug delivery to pulmonary carcinoma

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1549-1562页

作者： Jialiang Lin Qingqing Yin Binlong Chen Haoran Zhang Dong Mei Jijun Fu Bing He Hua Zhang Wenbing Dai xueqing wang Yiguang wang Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and *** ultrasmall superparamagnetic iron oxide nanoparticles(USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin(Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed in vivo that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

关键词： auxiliary overcome delivery

Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver

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Cancer Biology & Medicine 2021年第4期18卷 1092-1108页

作者： Xiangdong Ye xueqing wang Wenhui Yu Qing Yang Yan Li Yanxia Jin Yanting Su Jiaqi Song Bo Xu Hui Sun College of Life Sciences Wuhan UniversityWuhan 430071China Department of Biochemistry and Molecular Biology Institute of Biomedical researchCollege of Basic MedicineHubei University of MedicineShiyan 442000China Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization Hubei Normal UniversityHuangshi 435002China Hubei Province key Laboratory of Allergy and Immunology Wuhan UniversityWuhan 430071China

Objective:Therapy for hepatocellular carcinoma(HCC)is a major challenge,and targeted therapies provide only a modest benefit in terms of overall *** with antibodies to programmed cell death protein 1(PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20%of patients with advanced *** approaches are urgently needed to treat HCC and to augment the efficacy of ***:Tumor-bearing mice were treated with Agrocybe aegerita galectin(AAGL)alone or in combination with anti-PD-1,and the tumor sizes and lifespans of mice were *** analysis,cytokine analysis,flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen,and molecular and cellular analyses of tumors were used to define the underlying ***:AAGL significantly inhibited the growth of liver tumors in a dose-dependent ***,AAGL increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers;this effect was associated with the activation and migration of T cells and macrophages,in agreement with the in vitro ***,the aggregation of T cells and macrophages induced by AAGL in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade ***:The results showed that AAGL induced the activation and migration of lymphocytes to the liver,and that the combination of AAGL and anti-PD-1 may be a promising strategy for HCC treatment.

关键词： Hepatocellular carcinoma AAGL anti-PD-1 immunotherapy lymphocyte infiltration

Two RING-Finger Ubiquitin E3 Ligases Regulate the Degradation of SPX4, An Internal Phosphate Sensor, for Phosphate Homeostasis and Signaling in Rice

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Molecular Plant 2019年第8期12卷 1060-1074页

作者： Wenyuan Ruan Meina Guo xueqing wang Zhenhui Guo Zhuang Xu Lei Xu Hongyu Zhao Haiji Sun Chengqi Yan Keke Yi Key Laboratory of Plant Nutrition and Fertilizer Ministry of AgricultureInstitute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081China College of Life Science Shandong Normal UniversityJinan 250014China Ningbo Academy of Agriculture Sciences 19 Dehou StreetNingbo City 315000China

SPX-domain-containing proteins (SPXs) play an important role in inorganic phosphate (Pi) sensing,signaling,and transport in *** plants,SPXs are known to integrate cellular Pi status and negatively regulate the activity of Pi central regulators,the PHOSPATE STARVATION RESPONSE proteins (PHRs).The stability of SPXs,such as SPX4,is reduced under Pi-deficient ***,the mechanisms by which SPXs are degraded remain *** this study,using a yeast-twhybrid screen we *** two RING-finger ubiquitin E3 ligases regulating SPX4 degradation,designated SDEL1 and SDEL2,which were post-transcriptionally induced by Pi *** found that both SDELs were located in the nucleus and cytoplasm,had ubiquitin E3 ligase activity,and directly ubiquitinated the K^213 and K^299 lysine residues in SPX4 to regulate its ***,we found that PHR2,a Pi central regulator in rice,could compete with SDELs by interacting with SPX4 under Pi-sufficient conditions,which protected SPX4 from ubiquitination and *** with the biochemical function of SDEL1 and SDEL2,overexpression of SDEL1 or SDEL2 resulted in Pi overaccumulation and induced Pi-starvation signaling even under Pi-sufficient ***,their loss-of-function mutants displayed decreased Pi accumulation and reduced Pi-starvation ***,our study revealed that SDEL1 and SDEL2 facilitate the degradation of SPX4 to modulate PHR2 activity and regulate Pi homeostasis and Pi signaling in response to external Pi availability in rice.

关键词： rice SPX4 PHR2 ubiquitination Pi signaling Pi homeostasis phosphate regulation network

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超高压处理对赤霞珠葡萄挥发性物质的影响

中国农业科技导报 2024年第9期26卷 146-158页

作者：王学庆张波韩丽婷吕转转陈建军张竹林张军强杜建梅甘肃农业大学食品科学与工程学院甘肃省葡萄与葡萄酒工程学重点实验室甘肃省葡萄酒产业技术研发中心兰州730030 甘肃张掖国风葡萄酒业有限责任公司甘肃张掖734000

为改善酿酒葡萄原料的香气品质,研究不同超高压处理条件对赤霞珠葡萄果实挥发性物质的影响,利用顶空固相微萃取(headspace-solid phase microextraction,HS-SPME)与气相色谱-质谱联用技术(gas chromatography-mass spectrometry,GC-MS),对不同超高压条件处理的葡萄果实挥发性物质进行测定,结合主成分分析与香气轮廓描述对其特征香气进行分析。结果表明,不同处理条件下的果实挥发性物质与对照相比均发生显著变化(P<0.05);主成分分析发现,400 MPa压力操作及25 min的处理时间均与果实中具有草本、果香气味的醛、酮类物质有较高的相关性;香气轮廓分析发现,一定的压力与时间处理可显著提高赤霞珠葡萄的气味强度。以上研究结果为超高压技术在葡萄酒生产中的应用与推广提供了一定的数据参考和技术支持。

关键词：超高压挥发性物质主成分分析香气轮廓分析

Small GTPases:Structure,biological function and its interaction with nanoparticles

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Asian Journal of Pharmaceutical Sciences 2019年第1期14卷 30-39页

作者： Siyang Song Wenshu Cong Shurong Zhou Yujie Shi Wenbing Dai Hua Zhang xueqing wang Bing He Qiang Zhang Shenyang Pharmaceutical University No.103Wenhua RoadShenyang 110016China Peking University No.38Xueyuan RoadBeijing 100191China

Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic *** plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign ***,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical ***,there is no review in this *** review summarizes the small GTPases in terms of the structure,biological function and its interaction with *** briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different *** current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases *** will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research *** is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.

关键词： Small GTPase Nanoparticles Ras Rab Rho

POLLUTION, GOVERNMENT EXPENDITURE, TAXES AND STOCHASTIC GROWTH

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Applied Mathematics(A Journal of Chinese Universities) 2005年第4期20卷 384-392页

作者： Zhang xueqing Hu Shigeng wang Haijun Dept. of Math. Huazhong Univ. of Science and TechnologyWuhan 430074China.

This paper studies a stochastic endogenous growth model with pollution. It introduces government expenditure and exogenous pollution abatement technology to eliminate pollution and proves that under appropriate equilibrium conditions the main economic indexes （including economic growth rate, the optimal government expenditure rate） in the centrally planned economy and decentralized economy can be expressed by the parameters of the model uniquely. The optimal tax policy is analyzed ,and the optimal pollution is derived.

关键词： stochastic optimization Bellman equation eliminate pollution stochastic growth.

基于中医体质探求寒冷地区老年人失眠的影响因素

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现代中西医结合杂志 2024年第3期33卷 335-340,346页

作者：王雪晴程光宇王超杰赵慧怡纪青灼李巧彤程为平黑龙江中医药大学黑龙江哈尔滨150040 黑龙江中医药大学附属第一医院黑龙江哈尔滨150040

目的基于中医体质探求寒冷地区老年人失眠的相关影响因素及临床预测作用。方法采用横断面调查,对2021年9月-2022年12月至黑龙江中医药大学附属第一医院就诊的老年患者进行问卷调查及体质判定,根据阿森斯失眠量表(AIS)评分将入组者分为... 详细信息

目的基于中医体质探求寒冷地区老年人失眠的相关影响因素及临床预测作用。方法采用横断面调查,对2021年9月-2022年12月至黑龙江中医药大学附属第一医院就诊的老年患者进行问卷调查及体质判定,根据阿森斯失眠量表(AIS)评分将入组者分为正常组(AIS评分0.05)。寒冷地区失眠老年人体质以偏颇体质为主;单因素分析中,学历、不良嗜好史与部分中医体质组间差异有统计学意义(P均<0.05);多因素Logistic回归显示,学历、不良嗜好史、阳虚质、气虚质、气郁质、痰湿质与寒冷地区老年人失眠显著相关(P均<0.05),不良嗜好史、中高学历水平、阳虚质、气虚质、气郁质、痰湿质为影响老年人睡眠的危险因素。ROC曲线分析显示,ROC曲线下面积(AUC)为0.808(95%CI:0.765~0.851,P<0.001)。结论中医体质、不良嗜好史及学历水平与寒冷地区老年人失眠存在关联,且具有一定的临床预测价值,临证时可依据相关风险因素对老年人失眠风险进行预测,结合“辨体施治”为其提供个性化诊治方案。

关键词：寒冷地区失眠老年人体质 Logistic回归分析

Biomimetic Lightweight Design of Legged Robot Hydraulic Drive Unit Shell Inspired by Geometric Shape of Fish Bone Rib Structure

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Journal of Bionic Engineering 2024年第3期21卷 1238-1252页

作者： Zhipeng Huang Xinjie Li Xikang Guan xueqing Sun Chenxu wang Yuepeng Xu Bin Yu Xiangdong Kong School of Mechanical Engineering Yanshan UniversityQinhuangdao066004China School of Arts and Design Yanshan UniversityQinhuangdao066004China Hebei Provincial Key Laboratory of Heavy Machinery Fluid Power Transmission and Control Qinhuangdao066004China

The lightweight design of hydraulic quadruped robots,especially the lightweight design of the leg joint Hydraulic Drive Unit(HDU),can improve the robot's response speed,motion speed,endurance,and load ***,the lightweight design of HDU is a huge challenge due to the need for structural *** paper is inspired by the geometric shape of fish bones and biomimetic reinforcing ribs on the surface of the HDU shell are designed to increase its strength and reduce its ***,a HDU shell with biomimetic fish bone reinforcing ribs structure is ***,the MATLAB toolbox and ANSYS finite element analysis module are used to optimize the parameters of the biomimetic reinforcing ribs structure and the overall layout of the ***,the HDU shell is manufactured using additive manufacturing technology,and a performance testing platform is built to conduct dynamic and static performance tests on the designed *** experimental results show that the HDU with biomimetic fish bone reinforcing ribs has excellent dynamic performance and better static performance than the prototype model,and the weight of the shell is reduced by 20%compared to the prototype *** work has broad application prospects in the lightweight and high-strength design of closed-pressure vessel components.

关键词： Hydraulic drive unit Lightweight design of shell Biomimetic fish bone structure design Dynamic and static performance testing