The synthesis and investigation of Silica/Lipid related nanohybrid for anti-cancer drug delivery

化学治疗法是肿瘤学中最广泛应用的方法，但传统的化疗药给药方式存在靶向性低，毒副作用大，容易出现肿瘤耐药性等多重障碍，严重影响了癌症的治疗。现如今，随着纳米科技的发展，设计出一种纳米载药系统应用于化疗药物的传递，从而降低给药剂量、降低毒副作用、提高细胞吸收具有明显的临床意义。在诸多纳米粒材料的选择中，硅纳米粒由于其具有诸多良好的物理化学性质被广泛应用于药物传递及生物成像，然而普通二氧化硅纳米粒性质较为单一且载药量较小；介孔二氧化硅药物容易渗漏，靶向释放性能较差，这些都限制了二氧化硅纳米粒的进一步发展和应用。除此之外相对于脂质体，二氧化硅纳米粒的生物相容性、流动性和长循环性均存在一定劣势，值得进一...Nanoparticle-based therapeutics are poised to become a leading delivery strategy for cancer treatment because they potentially offer higher selectivity, reduced toxicity, longer clearance times in the body, and increased therapeutic efficacy compared to conventional systemic therapeutic approaches. Among all the materials, silica based nanoparticles drawing an increasing number of attention for it...学位：医学硕士院系专业：药学院_药剂学学号：3232012115308

ANCA相关性血管炎肾损害的中医证候及与临床相关性研究

目的:观察抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AAV)肾损害患者中医证候特征及分布规律,探讨其与临床、实验室指标的关系,为AAV肾损害的中医诊断和辨证施治提供线索。方法:收集AAV肾损害患者中医症状体征,进行证候判定,采空腹静脉血查Hb、白蛋白(Alb)、补体C3、C-反应蛋白(CRP)、BUN、Scr、血浆D-二聚体(D-D)等指标,进行肾损害程度及BVAS活动性评分,探讨各中医证候与临床实验指标间的关系及规律。结果:AAV肾损害的中医证候分布情况为:脾肾两虚型52例(41. 6%)、气阴两虚型38例(30. 4%)、湿热内蕴型19例(15. 2%)、肺脾气虚型16例(12. 8%)。冬、春季以脾肾两虚及气阴两虚型多见,夏季以气阴两虚型多见(P <0. 05)。各证型组的Hb、Alb、C3水平按气阴两虚型、脾肾两虚型、湿热内蕴型依次降低,D-D、Scr、BVAS评分值依次增高。与湿热内蕴证比较,气阴两虚、脾肾两虚Hb升高(P <0. 05)、Scr降低(P <0. 05),气阴两虚、脾肾两虚D-D、BVAS评分降低(P <0. 05)。结论:AAV肾损害的中医证型以脾肾两虚型最多见,湿热内蕴型的肾损害更重、BVAS评分更高。福建省自然科学基金资助项目(No.2014J01430

血清高迁移率族蛋白B1在ANCA相关性小血管炎肾损害血瘀证患者的表达及意义

目的:探讨血清高迁移率族蛋白B1(HMGB1)在抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AASV)肾损害瘀血阻滞证患者的表达及意义。方法:采取前瞻性研究,中医辨证就诊的AASV肾损害患者血瘀证的分布情况;采用酶联免疫吸附法(ELISA)检测AASV肾损害血瘀患者血清HMGB1水平,并与24 h尿蛋白定量、血Hb、Alb、CRP、D-二聚体、BUN、Scr、GFR、肾损害程度、ANCA、伯明翰血管炎活动积分(BVAS)等因素进行相关性分析,探讨HMGB1在AASV肾损害瘀血阻滞型患者中的意义。结果:AASV肾损害中医证候分布以脾肾两虚证(42.85%)、气阴两虚证(30.95%)多见,其中57.14%兼有瘀证。AASV肾损害血瘀证患者血清HMGB1水平明显升高(P0.05)。结论:血清HMGB1可能与AASV肾损害瘀血阻滞的发病有一定关系。福建省自然科学基金资助项目(No.2014J01430

Expression of recombinant hARRG cDNA in E.coli and purification of hARRG protein

目的　构建含重组人类抗砷相关基因 (humanarsenicresistencerelatedgene ,hARRG)的表达载体 ,诱导其在转化菌表达 ,分离纯化表达蛋白 ,研究该蛋白质的理化性质、抗砷功能和免疫活性 ,深入研究人类对砷化物的抵抗作用。方法　将hARRGcDNA开放阅读框亚克隆到原核表达载体Pet11C中 ,用异丙基 - β -D -硫代半乳糖苷 (IPTG)诱导表达蛋白质 ,利用阴离子交换柱Sepharose纯化蛋白质 ,SDS -PAGE胶电泳观察结果。 结果　将hARRGcDNA成功亚克隆到原核表达载体Pet11C中 ,并成功在大肠杆菌中表达 ,表达的hARRG蛋白占菌体蛋白的 5 %左右 ,该蛋白质被分离纯化。结论　原核表达载体Pet11C可以在大肠杆菌中表达hARRGcDNA ,可用阴离子交换柱Sepharose纯化抗砷相关蛋白质Objective To construct expression vector of the recombinant human arsenic resistance related gene (hARRG),induce its expression in DE\-3 and isolate and purify expression product,for studying the physiochemistry characteristic,function and immune activity of the protein,and further researching the arsenic resistant effects of human.Methods hARRG cDNA was subcloned into prokaryotic expression vector Pet11C.The recombinant protein expression was induced by IPTG,then,the protein was purified by anions Ion-exchange column Sepharose and examined by SDS-PAGE gel.Results hARRG cDNA was successfully subcloned into prokaryotic expression vector Pet11C and expressed in E.coli and the protein was purified by anions Ion-exchange column successfully.Conclusion Pet11C excpression vector containing hARRG cDNA wassuccessfully constructed,the cell DE\-3 transformed with expression vector capable of expression the gene and a hARRG protein could be purified by anions Ion-exchange column Sepharose.国家自然科学基金资助项目 (30 0 60 0 74

产前滴滴涕或多氯联苯暴露与出生缺陷风险相关性的Meta分析

目的系统评价孕妇产前暴露于滴滴涕(DDT)或多氯联苯(PCBs)与新生儿出生缺陷风险之间的关系。方法计算机检索PubMed、EMbase、WanFang Data、VIP和CNKI数据库,搜集有关产前DDT或PCBs暴露与出生缺陷关系的病例-对照研究,检索时限均从建库至2017年2月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 13.0软件进行Meta分析。结果共纳入14个研究,包括2 238例出生缺陷新生儿和2 355例对照新生儿。Meta分析结果显示:产前暴露于高水平的DDT会导致新生儿隐睾发生率增加[OR=1.12,95%CI(1.09,1.15),P<0.001]。而DDT暴露与尿道下裂和神经管畸形发生没有相关性。产前暴露于高水平的PCBs与隐睾、尿道下裂、神经管畸形发生也没有相关性。结论孕妇产前暴露于高水平的DDT可能是隐睾发生的危险因素。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。厦门市科技计划项目(编号:3502Z20163006);;厦门市集美区科技计划项目(编号:20142C01

Theoretical Study of Substituent Effects on Bond Dissociation Enthalpies in Lignite Model Compounds

为了探究褐煤热解过程中氧桥键C—O均裂这一重要反应,选取α-O-4和β-O-4类结构单元作为褐煤模型化合物,运用不同密度泛函计算了部分模型化合物中C—O的离解焓,并以CbS-Qb3作为理论基准值进行比较,最后选取M05-2X进行离解焓计算.结果显示,对于选定的α-O-4和β-O-4类模型化合物,其平均离解焓分别为51.0 kCAl/MOl和66.1 kCAl/MOl.周围取代环境能显著影响C—O离解焓,芳环上存在给电子基团(OH,OCH3和CH3)能降低C—O离解焓,而吸电子基团COOH则能增加其离解焓.然后深层次分析了取代基效应对C—O离解焓的影响.此外,分子内氢键的形成对离解焓也有很大的影响.C—O的离解焓与其键长没有特定的相关性,不能简单的通过C—O键长来预测其离解焓.Lignite is an abundant natural resource that is a potential source of clean fuel and value-added chemicals.The mechanisms by which thermal and catalytic treatments deconstruct lignite remain elusive,which is where quantum mechani-cal calculations can offer fundamental insights.In order to investigate the cleavage of C—O bridge bond,which is the critical step in the thermal decomposition of lignite,the α-O-4 and β-O-4 types of structural units are selected as lignite model com-pounds to calculate the C—O bond dissociation enthalpies using several kinds of density functional theory methods(B3PW91,B3P86,PBE1PBE,BMK,M06-2X and M05-2X) at 6-31+G(d,p) level.By the comparison between the results and the theoretical benchmark values provided by CBS-QB3 method,M05-2X functional was applied for the calculations on C—O bond dissociation enthalpies.The present results indicate that the C—O average bond dissociation enthalpies are 51.0 kcal/mol and 66.1 kcal/mol for the α-O-4 and β-O-4 types of model compounds,respectively.Local substituents have a great withdrawing groups such as carboxyl group.Then the substituent effects are deeply analyzed on the basis of the ground-state effect on the C—O bond dissociation enthalpies,the C—O bond dissociation enthalpies will decrease when the adjacent arene rings are substituted by electron donating groups(OH,OCH3 and CH3),while the results are opposite for the electron effect and radical effect.An electron donating group can stabilize the phenoxy radicals(radical effect),however,an electron withdrawing group has the opposite effect.In most cases,the radical effect is more important than the ground-state effect.Furthermore,there is a negligible correlation between the C—O bond distances and strengths,and the C—O bond dissocia-tion enthalpies cannot be predicted so easily.Interestingly,the C—O bond dissociation enthalpies can be significantly influ-enced by the intramolecular hydrogen bond,if the intramolecular hydrogen bond still exists after the cleavage of the C—O bond,the bond dissociation enthalpies will be lower.国家重点基础研究发展计划(No.2012CB214901); 国家自然科学基金(No.51274197)资助~

武夷山自然保护区生物多样性研究 1.小叶黄杨矮曲林物种多样性

本文为武夷山自然保护区生物多样性GEF项目内容之一 ,调查了保护区内不同海拔高度的代表性森林生态系统的物种多样性 .小叶黄杨 (Buxussinicavar .parvifolia)林是中山矮曲林的代表性类型之一 .应用Shannon Wiener多样性指数、Pielou均匀度、Simpson指数和PIE对武夷山小叶黄杨群落高等植物进行了物种多样性研究 .结果表明前两者是较好的多样性指标 ,该群落的Shannon Wiener指数值为 1.80 6 8,Pielou均匀度为 49.6 7% ,Simpson指数值为 2 .9146 ,PIE为 0 .6 5 6 9.群落乔木层与藤本植物的物种多样性较高 ,前者各项指数值分别为 2 .2 312 ,71.16 % ,5 .0 783,0 .80 31;后者各项指数值分别为 1.3371,83.0 8% ,3.5 32 7,0 .716 9

中国海洋生物研究70年

随着中国"海洋强国"战略的提出,加快建设海洋类学科的发展成为历史必然,海洋生物是海洋不可分割的一部分,海洋环境和生物相互依存,相互作用,海洋生物研究重要性日益凸显。为纪念中国科学家在海洋生物领域的突出贡献,本文回顾了建国以来中国海洋生物相关的重要研究进展,梳理了中国科学家在海洋生物领域的突出贡献,系统总结并讨论了未来研究方向,抛砖引玉,希望籍此助推中国海洋生物研究的新高潮。国家自然科学基金项目(41876134,41876171)中国大洋矿产资源研究开发协会专项项目(DY135-E2-5-03)教育部长江学者特聘教授项目(T2014253

Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation

厦门大学医学院、神经科学研究所张杰教授团队发现了抑郁症新的致病基因MEN1，并阐明了MEN1调控星形胶质细胞炎症导致抑郁发生发展的新机制，为抑郁症的诊治提供了新靶点和方向。抑郁症是严重威胁人类健康的重大神经系统疾病，危及全球30%的人口。但对其发病机制并不清楚。张杰教授团队发现，在慢性不可预测以及LPS处理的模拟抑郁小鼠模型中，多发性内分泌肿瘤蛋白(menin)在大脑中的表达显著降低，并且在星形胶质细胞中降低最明显。为了研究menin是否参与了小鼠抑郁表型的产生，研究团队制作了多种神经系统menin条件性敲除小鼠。通过对这些小鼠行为学的检测，锁定了只有在星形胶质细胞中敲除menin后，小鼠才会表现出抑郁样表型。证实了menin可能是通过调控星形胶质细胞的功能促进了抑郁的发生。 MEN1基因的突变会导致多发性内分泌肿瘤，而内分泌的紊乱和抑郁等精神疾病有着密切的联系。下丘脑-垂体-肾上腺轴（HPA轴）的功能紊乱直接参与了抑郁的产生。基于此研究团队推测MEN1的基因突变是否也会导致抑郁的发生。通过和中国医学科学院基础所的许琪教授合作，研究团队对1000多例重度抑郁患者和800多例对照人群进行了MEN1基因的外显子测序。通过测序发现MEN1的一个SNP s375804228和抑郁的发生有着显著关联。该SNP导致menin第503位的氨基酸由G突变成D。通过功能研究进一步证实该突变可以阻断menin和p65的结合，从而过度激活NF-κB-IL-1β通路，导致神经炎症的发生。 张杰，厦门大学特聘教授、博士生导师。国家优秀青年科学基金；教育部新世纪优秀人才；福建省杰出青年科学基金；厦门市五四青年奖章等获得者。2011年8月加入厦门大学医学院神经科学研究所担任教授至今。张杰博士主要从事重大神经系统疾病（老年痴呆、帕金森、抑郁症、自闭症、术后认知障碍、胶质瘤）等的发病机制和药物开发研究。至今以第一作者或者通讯作者在国际知名期刊发表研究论文21篇。其中回国独立开展研究工作以后，作为通讯作者在 Neuron，Cell Reports, PNAS, The Journal of Neuroscience, Clinical Cancer Research，Cell Death and Disease, JBC, Chemistry，Chem. Biol. Drug Des.等杂志上发表多篇研究论文。【Abstract】Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.We thank Prof. Guanghui Jin (Xiamen University) and Prof. Xianxin Hua (University of Pennsylvania) for providing the Men1-floxp mice. This work was supported by the National Natural Science Foundation of China (grants 81522016, 81271421, and 31571055 to J.Z.; 81625008 and 31430048 to Q.X.; 81630026 to Z.Y.; 81771163 and U1405222 to H.X.; U1505227 to G.B.; 81472725 to W.M.), the Natural Science Foundation of Fujian Province of China (grant 2013J01147 and 2014J06019 to J.Z.), the Fundamental Research Funds for the Central Universities (grants 20720150062 and 20720180049 to J.Z.), the National Key Research and Development Program of China (2016YFC1305903), and CAMS Innovation Fund for Medical Sciences (grant 2016I2M1004 to Q.X.).研究工作得到国家自然科学基金项目（81522016、81271421、31571055）以及厦门大学校长基金等资助

列车通信网络实时调度技术研究

未来铁路技术日趋关注高速化、智能化、信息化和高运行密度，高速铁路成为推动国家和地区经济发展的强大动力。由于起步较晚，与国外相比，我国列车通信网络（TCN）相关理论的研究相对比较落后。尽管我国铁路经过多次提速，相继成功开通武广、郑西高铁，实现了跨越式的发展；但研究多关注于应用开发，依赖于现有的TCN设备进口，实现集成并构建列车通信网络，实时调度理论等底层关键技术和方法的研究明显滞后于实际应用。鉴于列车通信网络的特殊地位，高速列车通信网络相关理论的研究迫在眉睫，本文定位于列车通信网络实时调度技术的研究。本文在分析国内外研究现状的基础上，结合列车通信网络实时调度相关理论，从多功能车辆总线（MVB）调度技术、绞线式列车总线（WTB）调度技术和TCN性能优化三个方面展开研究；并依据硬实时系统指标，结合列车的实际应用，利用OPNET构建了精确的仿真平台，以对MVB调度算法、WTB调度算法和TCN性能优化进行仿真论证。（1）在深入研究MVB周期任务和非周期任务通信机制的基础上，对MVB任务调度问题进行了抽象，建立了MVB周期任务和非周期任务调度问题的数学模型；提出了一种MVB实时调度表构建算法，并基于最长响应时间分析了MVB实时调度算法的可调度性；仿真实验表明，MVB周期任务调度满足可预测性和时间约束性特征。鉴于CSMA/CD和时隙的介质访问冲突方法各自的优势和不足，提出了一种基于令牌传递的二分查找MVB非周期任务调度算法；仿真实验表明，MVB非周期任务调度中高优先级任务具有较好的实时特性。（2）在深入研究了WTB周期任务和非周期任务通信机制的基础上，建立了WTB周期任务和非周期任务调度问题的数学模型；利用MVB实时调度表构建算法，设计了一种同时满足周期任务和非周期任务的WTB调度算法；并进行了相应的仿真实验，验证了算法的正确性，有效评估了极端情况下WTB周期任务和非周期任务的最长响应时间。（3）针对TCN中固定带宽分配机制易导致带宽资源浪费，提出了一种动态带宽分配策略。仿真实验表明，采用动态带宽分配机制，在实现开销可接受的范围内，非周期任务的最长响应时间降低效果明显，TCN实时性能提升显著。Future railway technology will focus more on high-speed, intelligence, information and high-density operation. High-speed railway has become a strong driving force for economic development of countries and regions.&nbsp; Compared to other countries, the Train Communication Network (TCN) of our country is relatively backward as a later start. With the raising of train speed for several times and the operation of high speed railway from Beijing to Shanghai and from Zhengzhou to Xian, the railway has developed in a spanning way. However, the research on TCN of China focuses more on application development; the integration and implementation of TCN relies on foreign imports of existing equipment; The underlying key technologies, such as real-time scheduling theory and methods in practical applications has lagged far behind. Considering the special status of TCN, the research of theory and methods of TCN is imminent. This thesis pays more attention on the real-time scheduling technology of TCN.Based on the analysis of TCN at home and abroad and the real-time scheduling theories of TCN, The scheduling theory of Multifunction Vehicle Bus (MVB), the scheduling theory of Wire Train Bus (WTB) and the performance optimization of TCN are studied in this thesis. Considering the target of hard real time system, the TCN simulation system based OPNET is founded on the basis of actual train application to validate all of the three aspects.After researching of the periodic data and non-periodic data communication mechanism of MVB, the various elements of scheduling problem are abstracted, and the mathematics scheduling models of periodic task and non-periodic task are built. Then, a real-time building algorithm of scheduling table is presented with the worse response time to judge the validity of the built scheduling table. Finally, the predictability and time constraints of periodic task of MVB are demonstrated by the simulation. Considering the advantage and the disadvantage of media access methods based CSMA/CD and time slots, a binary search non-periodic task scheduling algorithm of MVB based token is proposed, and the simulation results show that the algorithm is real-time of the non-periodic tasks with high priority.Similar to MVB, both the mathematics scheduling models of periodic tasks and non-periodic tasks of WTB are built. Based the real-time building algorithm of scheduling table of MVB, this thesis designed a task scheduling algorithm of WTB which satisfy both periodic tasks and non-periodic tasks. Finally, simulation results show that the algorithm is valid with an effective assessment of worse response time of the periodic tasks and non-periodic tasks.To solve the problem of the fixed bandwidth allocation mechanism which leads to the waste of the bandwidth resources, a dynamic bandwidth allocation scheme is presented. Finally, the result of the longest response time of non-periodic task is dropped obvious with good real-time performances and less cost through simulation.</p