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Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4748-4764页

作者： Yingqiang Liu Zhengsheng Zhan Zhuang Kang mengyuan Li Yongcong Lv Shenglan Li Linjiang Tong fang Feng Yan Li Mengge Zhang Yaping Xue Yi Chen Tao Zhang Peiran Song Yi Su Yanyan Shen Yiming Sun Xinying Yang Yi Chen Shanyan Yao Hanyu Yang Caixia Wang Meiyu Geng Wenbin Li Wenhu Duan Hua Xie Jian Ding Division of Antitumor Pharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Medicinal Chemistry Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Neuro-oncology Cancer CenterBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Shanghai Runshi Pharmaceutical Technology Co. Ltd.Shanghai 201218China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan 528400China University of Chinese Academy of Sciences Beijing 100049China Hangzhou Institute for Advanced Study University of Chinese Academy of SciencesHangzhou 310024China

Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380).

关键词： Small molecule inhibitor Glioblastoma VEGFR CSF1R Angiogenesis Macrophage Tumor microenvironment Immune-checkpoint inhibitor

2017-2019年中国基层医疗机构处方用药分析

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中国社会医学杂志 2024年第3期41卷 350-354页

作者：张宇晴巩志文余俊璇李灿朱玥桢于爱晨范平安胡琳王芳傅孟元管晓东史录文北京大学药学院药事管理与临床药学系北京100191 北京大学医药管理国际研究中心北京100191 北京市东城区社区卫生服务管理中心北京100010

目的分析2017-2019年中国基层医疗机构的处方用药现状,为进一步改善我国基层医疗机构合理用药提供依据。方法通过二阶段结构性抽样方法设计并实施全国基层医疗机构门诊处方调查。采用WHO/INRUD用药评价指标,应用描述性统计、Wilcoxon... 详细信息

目的分析2017-2019年中国基层医疗机构的处方用药现状,为进一步改善我国基层医疗机构合理用药提供依据。方法通过二阶段结构性抽样方法设计并实施全国基层医疗机构门诊处方调查。采用WHO/INRUD用药评价指标,应用描述性统计、Wilcoxon秩和检验、卡方检验分析方法,分析基层医疗机构用药现状和变化趋势。结果研究共纳入2017-2019年6个省、31个地市的269家基层医疗机构的64.2万张门诊处方。处方分析结果显示,2017-2019年,除每处方药物费用呈显著上升趋势外,每处方药品数、抗菌药物处方率、注射剂处方率和激素处方率均呈显著下降趋势;所有抗菌药物处方中包含共计25.6万个抗菌药物,其中82.2%为广谱抗菌药物;城乡间用药指标值差异较小。结论中国基层医疗机构用药整体情况持续改善、城乡差距缩小,但药物使用合理性和抗菌药物种类选择方面仍有待进一步改善。

关键词：基层医疗机构药物使用处方用药

航空集群机载网络Failure-Oblivious路由策略

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国防科技大学学报 2022年第1期44卷 156-168页

作者：吕娜潘颖朱梦圆陈坤方宇空军工程大学信息与导航学院陕西西安710077

航空集群机载网络作为集群成员间信息交互的纽带,其路由策略性能优劣直接影响信息传输实时性与可靠性,从而制约网络化集群作战效能发挥。考虑到航空集群机载网络具有诸多不确定性,为应对路由失效以及尽可能避免路由更新,从路由选择算法... 详细信息

航空集群机载网络作为集群成员间信息交互的纽带,其路由策略性能优劣直接影响信息传输实时性与可靠性,从而制约网络化集群作战效能发挥。考虑到航空集群机载网络具有诸多不确定性,为应对路由失效以及尽可能避免路由更新,从路由选择算法的角度,在软件定义网络架构下提出Failure-Oblivious路由策略。与传统路由策略不同的是,该策略利用随机算法生成多条路由,能够在不进行路由失效预测的情况下应对路由随机失效问题。理论推导与仿真验证表明,该策略能够在保证通信时效性代价可控的基础上,降低航空集群机载网络路由失效风险。

关键词：航空集群机载网络路由失效 Oblivious路由策略图嵌入

Phenotype,Physiology,and Gene Expression of Barley Seedlings in Response to Nano Zinc Oxide Stress

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Phyton-International Journal of Experimental Botany 2021年第6期90卷 1589-1598页

作者： mengyuan Dong Rong Sun Qianhui Yang Lantian Zhang Yangying Yong Yunxia fang Xian Zhang Xiaoqin Zhang Dawei Xue College of Life and Environmental Sciences Hangzhou Normal UniversityHangzhou310036China

In recent years,zinc oxide nanoparticles(ZnO NPs)have been widely used as zinc fertilizers and pesticides.The use of ZnO NPs in this way can provide benefits to humans,but also has potential risks.ZnO NPs inevitably enter the environment during their production and use,which affects the ecological environment and crop growth.In order to investigate the phenotype,physiology,and gene expression of barley(Hordeum vulgare L.)seedlings under ZnO NPs stress,the barely cultivars ZJU3(P21),Golden Promise(GP)and L23 were chosen for study.Different ZnO NPs concentrations were applied to compare the physiological and biochemical indexes of the barley seedlings and the responses of six stress-related genes,when seedlings were cultured to the two-leaf stage through hydroponics.The results showed that the density of brown spots on the leaf surface increased with increasing ZnO NPs concentration.ZnO NPs stress inhibited the root growth of barley seedlings,and P21 was the most sensitive.Furthermore,ZnO NPs stress could stimulate plants to produce a large number of reactive oxygen species(ROS),resulting in an imbalance between the production and removal of ROS and membrane lipid peroxidation in plants.This imbalance inhibited the growth and development of the barley seedlings.With increasing ZnO NPs concentration,the activity of superoxide dismutase was gradually increased,the activity of catalase was progressively decreased,and the contents of malondialdehyde and proline were increased.Compared with the control,among six stress-related genes,the expression levels of five genes were downregulated and one gene was upregulated in the experimental group.This study preliminarily revealed the toxic effect of ZnO NPs on seedlings and the effect on the expression of stress-related resistance genes in different barley varieties.

关键词： Antioxidant enzymes barley seedlings reactive oxygen species gene expression zinc oxide nanoparticles

Genome-Wide Identification of the F-box Gene Family and Expression Analysis under Drought and Salt Stress in Barley

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Phyton-International Journal of Experimental Botany 2020年第2期89卷 229-251页

作者： Lantian Zhang Siyi Wang Yuyu Chen mengyuan Dong Yunxia fang Xian Zhang Tao Tong Ziling Zhang Junjun Zheng Dawei Xue Xiaoqin Zhang College of Life and Environmental Sciences Hangzhou Normal UniversityHangzhou310036China

The F-box protein-encoding gene family plays an essential role in plant stress resistance.In present study,126 non-redundant F-box genes were identified in barley(Hordeum vulgare L.,Hv).The corresponding proteins contained 165–887 amino acid residues and all were amphiphilic,except 5 proteins.Phylogenetic analysis of F-box protein sequences in barley and stress-related F-box protein sequences in wheat and Arabidopsis thaliana(At)was used to classify barley F-box genes are divided into 9 subfamilies(A–I).A structure-based sequence alignment demonstrated that F-box proteins were highly conserved with a total of 10 conserved motifs.In total,124 F-box genes were unevenly distributed on 7 chromosomes;another 2 genes have not been anchored yet.The gene structure analysis revealed high variability in the number of exons and introns in F-box genes.Comprehensive analysis of expression profiles and phylogenetic tree analysis,a total of 12 F-box genes that may be related to stress tolerance in barley were screened.Of the 12 detected F-box genes,8 and 10 were upregulated after drought and salt stress treatments,respectively,using quantitative real-time polymerase chain reaction(qRT-PCR).This study is the first systematic analysis conducted on the F-box gene family in barley,which is of great importance for clarifying this family’s bioinformatic characteristics and elucidating its function in barley stress resistance.These results will serve as a theoretical reference for subsequent research on molecular regulation mechanisms,genetic breeding,and improvement.

关键词： Drought and salt stress barley expression analysis F-box gene family phylogenetic analysis

基于电压谐波注入算法的PMSM转矩脉动抑制研究

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机床与液压 2023年第24期51卷 54-59页

作者：沈梦圆谢芳张文雨安徽大学电气工程与自动化学院安徽合肥230601 安徽大学高节能电机及控制技术国家地方联合实验室安徽合肥230601

在永磁同步电机矢量控制系统中,受电流谐波的影响,电机产生转矩脉动。为了解决此问题,利用谐波注入原理设计一种电压谐波注入器。利用坐标变换提取待消除次数的电流谐波,考虑到基波会影响到谐波的提取精度,设计一种消去基波的电流谐波... 详细信息

在永磁同步电机矢量控制系统中,受电流谐波的影响,电机产生转矩脉动。为了解决此问题,利用谐波注入原理设计一种电压谐波注入器。利用坐标变换提取待消除次数的电流谐波,考虑到基波会影响到谐波的提取精度,设计一种消去基波的电流谐波提取结构。利用提取到的电流谐波,设计针对5、7次谐波的电压谐波注入器。最后通过实验对比,证明了所提方法能够明显抑制电机转矩脉动。

关键词：谐波注入永磁同步电机电流谐波转矩脉动

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多用户多边缘的公平卸载及优化策略研究

郑州大学学报（理学版） 2022年第5期54卷 16-21页

作者：赵梦远郝万明杨守义王芳郑州大学信息工程学院河南郑州450001 郑州大学电子材料与系统国家级国际联合研究中心河南郑州450001 郑州大学河南省电子材料与系统国际联合实验室河南郑州450001

针对物联网设备计算密集和时延敏感的特点,边缘云可为物联网设备提供计算资源,对多个物联网设备在多个边缘云中的计算卸载进行研究。通过优化细粒度的卸载决策,解决时延敏感设备的计算卸载问题,在降低时延的同时考虑用户公平性,即优化... 详细信息

针对物联网设备计算密集和时延敏感的特点,边缘云可为物联网设备提供计算资源,对多个物联网设备在多个边缘云中的计算卸载进行研究。通过优化细粒度的卸载决策,解决时延敏感设备的计算卸载问题,在降低时延的同时考虑用户公平性,即优化物联网设备的时延并最小化其最大用户的任务完成时间。该优化问题是一个混合整数非线性规划问题,为了解决这个NP-hard问题,提出了基于潜在博弈论的分布式算法来降低运算复杂度。仿真结果验证了所提算法的收敛性,而且对公平性有显著提升的同时,对物联网时延影响较小。

关键词：边缘云时延优化公平性潜在博弈

Optimization of Soundscape in Theme Park Based on Soundscape Comfortable Degree——A Case Study of China Dinosaur Land in Changzhou

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Journal of Landscape Research 2014年第2期6卷 34-38页

作者： WANG fang QIU mengyuan SHA Run QIN Jingwen School of Cultural Industry & Tourism Management Sanjiang University School of Geography Nanjing Normal University

Tourism soundscape is a new field of tourism landscape research, soundscape designs offer new concepts for the landscape research and development. Taking China Dinosaur Land in Changzhou City for example, visitors' perception about soundscape comfort in theme parks was studied. The researches found that acoustic comfort was infl uenced by objective parameters of sound and subjective perception of visitors, and when the soundscape volume stayed at a certain threshold value, visitors would gain the most satisfi ed acoustic comfort experience, and they were most sensitive to sound elements that able to convey cultural connotations of the theme park. On this basis, this paper adopted positive design, negative design, and zero design, and proposed the concepts of optimizing theme park soundscapes.

关键词： Acoustic comfort Theme park Tourism soundscape Optimization

基于Cesium的BIM与实景三维模型集成可视化研究

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测绘地理信息 2022年第2期47卷 111-114页

作者：方孟元罗年学许毅祁平利武汉大学测绘学院湖北武汉430079 中铁第五勘察设计院集团有限公司北京102600

建筑信息模型(building information model,BIM)是对建筑的物理和功能特性的全要素信息数字化表达,而建筑设计、施工中都需要周边环境信息作为参考,GIS作为地理空间信息的表达载体,正弥补了BIM的不足。将BIM与GIS进行有机融合可将建筑... 详细信息

建筑信息模型(building information model,BIM)是对建筑的物理和功能特性的全要素信息数字化表达,而建筑设计、施工中都需要周边环境信息作为参考,GIS作为地理空间信息的表达载体,正弥补了BIM的不足。将BIM与GIS进行有机融合可将建筑与环境融为一体,可以广泛应用于规划设计、城市管理等领域。实景三维模型是具备高精度、高真实性的GIS数据源。本文以某磁浮铁路项目为例,介绍BIM与GIS数据集成可视化思路,针对坐标基准统一、模型衔接处理等问题介绍在Cesium中的实现方法,为BIM+GIS在建筑设计、城市规划、路桥施工等领域的应用打下基础。

关键词： BIM+GIS 实景三维模型 Cesium 规划设计