Valproic Acid Enhances Sensitivity Of Triple-Negative Breast Cancer Cells to Paclitaxel

第一部分丙戊酸诱导人三阴性乳腺癌细胞凋亡及其机制研究 目的： 丙戊酸（VPA）系一临床广谱抗癫痫药；作为一组蛋白去乙酰化酶抑制剂，近年来诸多研究还表明其对多种肿瘤均具有较强的抗癌活性，但其确切的作用机制尚未完全阐明。鉴于目前临床上对三阴性乳腺癌的治疗手段尚有限，现有的治疗方案的临床疗效也比较局限，因此本研究第一部分的主要目的在于从体外细胞水平探讨VPA对三阴性乳腺癌可能的治疗作用，并初步探索相关的分子机制。 方法： 1、MTS方法检测不同浓度的VPA（0、0.125、0.25、0.5、1、2mmol/L）作用于人三阴性乳腺癌细胞MDA-MB-231和BT2072h后细胞的存活情况，绘制...Part one: Valproic Acid induces the apoptosis of Triple-Negative Breast Cancer cells and its underlying mechanism Objective: Valproic acid (VPA), a broad-spectrum anti-seizure drugs, also defined as one of the histone deacetylase inhibitors, was showed to have anti-cancer ability by many studies in recent years but the underlying mechanism of which has not been fully elucidated yet. Currently, t...学位：医学硕士院系专业：医学院_肿瘤学学号：2452014115357

Promotion of proliferation of luminal B breast cancer cells by mesenchymal stem cells and its underlying molecular mechanisms

目的分析人脐带间充质干细胞(hUC-MSCs)对Luminal B型乳腺癌细胞生长增殖的影响,并初步探讨其可能的分子机理。方法绿色荧光蛋白(GFP)和荧光素酶共表达慢病毒感染人Luminal B型乳腺癌细胞BT474,并经嘌呤霉素筛选两周后,于荧光显微镜下观察GFP的表达情况,IVIS Kinetic成像系统拍照以观察和记录慢病毒感染后BT474细胞荧光素酶的表达情况;荧光显微镜下直接观察,结合MTS实验分析hUC-MSCs共培养或其浓缩上清处理对GFP和荧光素酶共表达BT474细胞生长增殖的影响;Western blot法检测hUC-MSCs浓缩上清处理对BT474细胞Akt和MAPK信号通路激活情况以及下游细胞周期调控蛋白Cyclin D1表达的影响;常规RT-PCR法检测hUC-MSCs中NRG-1、NRG-2、IGF-Ⅰ、IGF-Ⅱ和EGF等配体的表达。荧光素酶表达强度与细胞数量的相关性经由Excel软件行统计学分析,MTS实验数据则经由SPSS13.0统计软件行统计学分析。结果荧光显微镜和IVIS Kinetic成像系统的观察结果分别证实,GFP和荧光素酶经慢病毒载体系统的介导可在BT474细胞中成功地共表达,且荧光素酶的表达强度与细胞数量呈直线相关。MSCs共培养或其浓缩上清处理均可显著促进Luminal B型乳腺癌细胞BT474的生长增殖,其细胞存活比例分别为各自对照组的148.06%(P<0.005)和147.99%(P<0.001);MSCs浓缩上清处理同时激活BT474细胞内Akt和MAPK信号通路,并上调细胞周期调控蛋白Cyclin D1表达。此外,RT-PCR结果显示,hUC-MSCs中NRG-1和EGF的mRNAs水平呈高表达,而NRG-2、IGF-Ⅰ和IGF-Ⅱ等配体的mRNAs表达也可见。结论 MSCs可通过表达并分泌NRG-1等配体,从而激活Luminal B型乳腺癌细胞BT474的下游Akt和MAPK信号转导通路以上调细胞周期调控蛋白Cyclin D1的表达,进而促进其生长增殖。Objective To investigate the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs) on proliferation of luminal B breast cancer cells and its underlying molecular mechanisms. Methods Human luminal B breast cancer cells BT474 were infected with GFP and luciferase co-expressing lentiviruses and then subjected for selection with Puromycin for 2 weeks. The expression of GFP and luciferase was detected by fluorescent microscopy and IVIS Kinetic image system, respectively. The effect of coculture or treatment with conditioned medium of hUCMSCs on proliferation of BT474 was analyzed with MTS assay. Western blot was carried out to detect the effect of treatment with conditioned medium of hUC-MSCs on the activation of both Akt and MAPK signalings in BT474, as well as the expression of downstream cell cycle regulator Cyclin D1. Regular RT-PCR was applied to analyze the mRNAs expression of ligands such as NRG-1, NRG-2, IGF-Ⅰ, IGF-Ⅱ, and EGF in hUC-MSCs. The correlation between relative luciferase activity and cell number was analyzed with Excel software, while MTS assay data was statistically analyzed with SPSS 13.0 software. Results The co-expression of GFP and luciferase in BT474 via lentiviral expression system was visualized by fluorescent microscopy and IVIS Kinetic image system. The linear correlation between relative luciferase activity and cell number was determined by curve fitting analysis. Coculture or treatment with conditioned medium of hUC-MSC significantly promoted the proliferation of BT474, with survival rates being 148.06 %(P < 0.005)and 147.99 %(P < 0.001)of control, respectively. In addition, treatment with conditioned medium of hUC-MSC was shown to induce activation of both Akt and MAPK signalings, which further upregulated the expression of Cyclin D1. Moreover, high mRNAs expression levels of both NRG-1 and EGF, as well as moderate mRNAs expression levels NRG-2, IGF-Ⅰ, and IGF-Ⅱ were showed by RT-PCR. Conclusion Our results here demonstrated that MSCs may promote the proliferation of luminal B breast cancer cells through paracrine of ligands such as NRG-1, which in turn results in the activation of both Akt and MAPK signalings and upregulation of the expression of Cyclin D1.国家自然科学基金面上项目(81272922);; 福建省自然科学基金面上项目(2016J01577);; 福州总医院院内课题国际合作研究专项(2015G01

Selective methylation of toluene using CO2 and H2 to para-xylene

二甲苯（PX）是石化工业的基本有机化工原料之一，主要用于生产三大合成材料—合成树脂、合成纤维和合成橡胶。随着我国下游产业的快速发展，PX的需求量迅猛增长，进口依存度大于50%。袁友珠教授课题组提出使用CO2和H2替代甲醇作为甲苯烷基化试剂，利用CO2和H2在相对较低温度下生成的甲氧基中间体（无需经甲醇）直接与甲苯烷基化。化学化工学院2018级博士生左佳昌为论文第一作者，博士生陈伟坤、硕士生刘佳以及醇醚酯化工清洁生产国家工程实验室（厦门大学）段新平博士和叶林敏博士等参与了论文的部分研究。该研究结果已分别申请了中国发明专利（申请号201911149539.2, 2019）和国际专利（申请号PCT/CN2020/077412, 2020）。【Abstract】Toluene methylation with methanol to produce xylene has been widely investigated. A simultaneous side reaction of methanol-to-olefin over zeolites is hard to avoid, resulting in an unsatisfactory methylation efficiency. Here, CO2 and H2 replace methanol in toluene methylation over a class of ZnZrOx–ZSM-5 (ZZO-Z5) dual-functional catalysts. Results demonstrate that the reactive methylation species (H3CO*; * represents a surface species) are generated more easily by CO2 hydrogenation than by methanol dehydrogenation. Catalytic performance tests on a fixed-bed reactor show that 92.4% xylene selectivity in CO-free products and 70.8% para-xylene selectivity in xylene are obtained on each optimized catalyst. Isotope effects of H2/D2 and CO2/13CO2 indicate that xylene product is substantially generated from toluene methylation rather than disproportionation. A mechanism involving generation of reactive methylation species on ZZO by CO2 hydrogenation and migration of the methylation species to Z5 pore for the toluene methylation to form xylene is proposed.This work was supported by the National Key Research and Development Program of China (2017YFA0206801), the National Natural Science Foundation of China (21972113), and the Program for Innovative Research Team in Chinese Universities (IRT_14R31).该工作得到了国家重点研发计划（2017YFA0206801）、国家自然科学基金（21972113、91545115）和教育部创新团队（IRT_14R31）的资助

一种磁场施加装置

本实用新型提供一种磁场施加装置。该装置包括永磁体、软磁体以及线圈；软磁体与永磁体构成磁回路，用于将永磁体产生的直流磁场进行导磁；线圈绕行在软磁体上，用于产生交流磁场；工作状态时，永磁体产生的直流磁场经软磁体导磁，形成导磁后的直流磁场，将样品置于该导磁后的直流磁场中，样品受到直流磁场作用；向线圈施加交变电流，样品受到交流磁场作用。该装置结构简单、功能灵活，使用方便，具有良好的应用前景，可用于纳米多参量耦合原位探测系统，能够原位、同步、实时地探测样品在直流或交流磁场作用下的磁学性质等