恩替卡韦4′-氨基酸酯化衍生物的合成及生物活性评价

恩替卡韦是一种常用的治疗乙型肝炎病毒的拟核苷类药物,可以显著的抑制病毒HBV-DNA在人体内的复制水平,降低HBV-DNA在人体血浆中的含量;但临床实验表明恩替卡韦在人体中的口服生物利用度偏低,稳定性不好。选择性的合成了8种恩替卡韦4'-氨基酸酯化衍生物,以期提高其在体内的吸收效率;并保留其抗HBV活性。所有的化合物之前均未见报道,其结构经ESI-MS和1HNMR确证,同时其对于Caco-2细胞的膜渗透活性及其在HepG 2.2.15细胞中的抗HBV活性都在体外进行了进一步的评价。结果表明与恩替卡韦相比,所有的4'-氨基酸酯化衍生物的膜渗透活性都有一定程度的提高,同时化合物5c还表现出了与恩替卡韦相接近的抗HBV活性。     

苯乙酰异谷氨酰胺类化合物合成及抗肿瘤活性

苯乙酰异谷酰胺作为抗癌酮（Antineoplaston A10）在体内的一种降解产物，具有一定程度的抗肿瘤活性。为此设计并合成了一些新的苯乙酰异谷氨酰胺类化合物以测试其抗肿瘤活性。合成中采用在酸性条件下，先选择性地对L－谷氨酸γ位羧基进行酯化，再进一步合成目标化合物，反应条件温和，收率好。所合成化合物结构经IR、^1HNMR及元素分析鉴定，对所合成的目标化合物的抗肿瘤活性采用MTT法对体外培养的乳腺癌细胞成活率进行了测试，初步结果显示有一定抑制肿瘤细胞存活的作用。     

抗癌药物放线菌素D及其新类似物体外DNA结合特性研究

以 CD及 UV光谱研究了放线菌素 D及新合成的两个新类似物体外与小牛胸腺 DNA的结合特性 ,并与以往报道的 3种化合物抗肿瘤活性研究结果进行了比较 .结果显示 ,测试的 3种化合物体外与 DNA结合能力的大小与体内抗肿瘤活性之间存在平行关系 .     

植物液泡膜Na~+/H~+逆向转运蛋白的研究与应用

液泡膜Na~+/H~+逆向转运蛋白是植物体内广泛存在的一种跨膜转运蛋白,负责植物体内Na~+、H~+的交换。本文对Na~+/H~+逆向转运蛋白的克隆、分子结构、功能及应用等方面展开论述,旨在为研究者系统的理解Na~+/H~+逆向转运蛋白的研究进展,为调控该蛋白的表达来改进植物的生长发育及抗盐胁迫能力等方面的应用提供参考。     

benztropine类多巴胺转运蛋白配体的QSAR研究

利用Hansch方法，研究了37种benztropine类化合物diphenylmethoxy部位苯环取代基结构与其活性的定量关系，结果表明：苯环取代基的电性和体积等均是影响该类化合物与多巴胺转运蛋白亲和力的重要因素，所得到的benztropine类化合物diphenylmethoxy部位取代基的综合结构效应，对进一步研究该部位与多巴胺转运蛋白相互作用的电性和立体性质及设计新的多巴胺转运蛋白配体具有指导意义。     

转运葡萄糖苷类化合物的Caco-2细胞模型建立

建立转运葡萄糖苷类化合物的Caco-2细胞模型,为葡萄糖及葡萄糖苷类化合物肠道吸收研究提供基础。通过对Caco-2细胞最适培养基的选择、单层致密性的测定、单层通透性和细胞两侧碱性磷酸酶活性比的测定、单层亚显微结构的观察、细胞葡萄糖转运蛋白SGLT1和GLUT2的mRNA及蛋白表达水平的分析,建立可靠的细胞模型。研究表明:Caco-2细胞的最适培养基为添加体积分数15%血清的DMEM低糖培养基;Caco-2细胞在14～17d的跨膜电阻趋于稳定,苯酚红的表观渗透系数达到0.49×10-6~0.51×10-6cm·s-1,微绒毛分化成熟,细胞两侧碱性磷酸酶比值达到2.0以上。葡萄糖转运载体SGLT1的mRNA表达在14d时显著高于17d和21d,葡萄糖转运载体SGLT1和GLUT2的蛋白表达在14、17、21d无显著差异(P<0.05)。Caco-2细胞培养14～17d即可建立可靠的肠细胞吸收模型,用于葡萄糖及葡萄糖苷类化合物吸收的体外研究。     

拟南芥中一个镍离子转运蛋白的亚细胞定位

离子的跨膜转运是细胞获取养分的重要环节,亦是植物在组织和器官水平上进行养分吸收运移的基础．在植物中镍（Ni）元素主要以Ni^2＋的形式存在,并通过Ni^2＋转运蛋白将其跨膜转运至相应的组织器官,参与氢酶和脲酶的合成．生物信息学分析表明,拟南芥中一个Ni^2＋转运蛋白AT2G16800含有叶绿体定位信息．克隆该基因5’端编码转运肽的272bp片段,与绿色荧光蛋白（GFP）基因融合后,在拟南芥中高效表达,对其进行了亚细胞定位的研究．转基因植株通过共聚焦扫描显微镜的观察,发现GFP荧光信号只存在于叶绿体中,该结果表明A他G16800为叶绿体蛋白．     

体外消化对大豆多肽性质和ACE抑制活性的影响

为了验证大豆多肽血管紧张素转换酶(ACE)抑制活性的生物可获得性,采用Alcalase蛋白酶催化大豆蛋白水解获得了3种水解程度不同的大豆多肽,再应用摸拟体外消化方法处理大豆蛋白及其水解产物,并进一步分析了摸拟消化前后大豆多肽结构、性质和ACE抑制活性的变化.结果显示:3个大豆多肽的相对分子质量均小于16000,且水解度越高,TCA可溶性蛋白含量就越高;经过摸拟体外消化,大豆蛋白出现降解,其分子大小和性质与大豆多肽趋于一致,大豆多肽则进一步降解;3种大豆多肽的ACE抑制活性在经过摸拟体外消化后显著下降,大豆蛋白的ACE抑制活性则显著上升,两者之间没有显著差异,表明虽然Alcalase对大豆蛋白的酶促处理能够释放降血压肽,但经过模拟体外消化后其ACE抑制活性又会下降,而直接口服大豆蛋白有可能获得同样的降血压效果.     

凋亡素融合蛋白的基因克隆、表达与体外活性分析

来源于HIV-1病毒(47~57位氨基酸)的TAT小肽具有跨膜功能,可以将外源蛋白进行跨膜转运。通过聚合酶链反应(PCR)的方法扩增了TAT-凋亡蛋白序列,与载体pET-28b连接后在大肠杆菌BL21(DE3)中获得了高表达,以包涵体形式表达的TAT-凋亡蛋白在变性条件下进行了Ni-NTA纯化,纯化的蛋白经MTT法证明具有诱导HeLa细胞凋亡的能力。     

肽树枝状化合物在生物学中的应用

肽树枝状化合物是一类含有肽键或表面接枝肽的树枝状化合物,在生物技术及生物化学领域具有广泛的应用。作者就该类化合物在基因转运、作为蛋白质类似物及在催化剂载体方面的研究进展进行讨论。     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Features of Women's language

Language is a means of verbal communication. People use language to communicate with each other. In the society, no two speakers are exactly alike in the way of speaking. Some differences are due to age, gender, statue and personality. Above all, gender is one of the obvious reasons. The writer of this paper tries to describe the features of women＇s language from these perspectives： pronunciation, intonation, diction, subjects, grammar and discourse. From the discussion of the features of women＇s language, more attention should be paid to language use in social context. What＇s more, the linguistic phenomena in a speaking community can be understood more thoroughly.     

An Analysis of Catherine＇s Character——Wuthering Heights

Wuthering Heights, Emily Bronte＇s only novel, was published in December of 1847 under the pseudonym Ellis Bell. The book did not gain immediate success, but it is now thought one of the finest novels in the English language. Catherine is the key character of this masterpiece, because everybody and everything center on her though she had a short life. We can understand this masterpiece better if we know Catherine well.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower Ordovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as "oil families", although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any "oil family". Despite their close stratigraphic proximity, it is evident that the oils of the Lower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new "oil family" within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

Achieving Unusual States of Matter Under High Pressure

正The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry,rooted in the atomic shell structure.Within compounds,Group I elements,for example,invariably assume the+1 oxidation state,and their chemical properties differ completely from those of the p-block elements.These general rules govern our understanding of chemical structures and reactions.Using first principles calcula-     

Exchange-Correlation and Electronic Excitation Energies from Pairing Matrix Fluctuations

We have developed an adiabatic connection to formulate the ground-state exchange-correlation energy in terms of pairing matrix linear fluctuations.This formulation of the exchange-correlation energy opens a new channel for density functional approximations based on the many-body perturbation theory.We illustrate the potential of such approaches with an approximation based on the particle-particle Random Phase Approximation(pp-RPA).This re-     

Density Functional Theory for the Response of Periodic Systems to Electric Fields Based on the Vector Potential Approach

正The electronic and nuclear(structural/vibrational)response of 1D-3D nanoscale systems to electric fields gives rise to a host of optical,mechanical,spectral,etc.properties that are of high theoretical and applied interest.Due to the computational difficulty of treating such large systems it is convenient to model them as infinite and periodic(at least,in first approximation).The fundamental theoretical/computational problem in doing so is that     

On the Thermodynamic Limit for Responses to Static Electromagnetic Fields

For molecular systems,the quantum-mechanical treatment of their responses to static electromagnetic fields usually employs a scalar-potential treatment of the electric field and a vector-potential treatment of the magnetic field.Although the potential for each field separately is associated with the choice of an(unphysical)origin,the precise choice of the origin for the electrostatic field has little consequences for the results.This is different for the