新药研究的思路与策略

新药研究是一门新型的多学科交叉的边缘性学科。特别是创新药物的研究具有重大的社会效益和经济效益,分为发现和开发两个阶段,其中发现阶段的研究核心就是要发现先导化合物的分子结构并加以优化。同时,创新药物的研究涉及一系列重大的科学前沿问题,其中心就是药物作用的靶标生物大分子的结构、功能及其与药物的相互作用。这方面的研究必然会对生命科学的发展产生重大的影响。     

天然活性成分的生物转化与创新药物开发

生物转化和生物催化技术是现代生物技术中一个较活跃的研究和应用分支。本文作者结合自身的研究工作,重点介绍了生物转化和生物催化技术在天然药物研究与开发中的应用;并提出了生物组合化学（Ｂｉｏ－ｃｏｍｂｉｎａｔｏｒｉａｌ Ｃｈｅｍｉｓｔｒｙ）概念与研究路线,为探索快速、有效寻找新的复杂结构药物和天然活性先导化合物提供了新研究思路和实验方法。     

抗肿瘤单克隆抗体导向药物的研究进展

单克隆抗体（单抗）对相应的抗原有高度特异性。因此,利用单抗作为治疗剂或利用单抗作为特异性载体制成导向药物（免疫偶联物）,对于治疗肿瘤有巨大潜力和引人瞩目的前景。大量研究证明,单抗导向药物对肿瘤靶细胞有选择性杀伤作用,显示特异性结合和内化;在动物体内显示肿瘤特异性分布以及更高的疗效。单抗与单抗导向药物在人体应用面临一些免疫学和药理学的问题。当前研究的发展趋向是单抗人源化,偶联物小型化与偶联物高效化。     

国家微重力实验室百米落塔实验设施的几项关键技术

在国家863计划的支持和安排下于2003年建成的国家微重力实验室百米落塔是我国发展载人航天, 开发利用外层空间计划中进行微重力科学实验的重要地基设施. 与美、德、日等国的同类设施相比, 我国的这座落塔在技术性能上先进水平, 并具有我国自己的特色. 其主要组成部分: 实验舱组件、减速回收系统和释放系统都展现了其先进性和原始创新性, 显示了我国在这个领域内的实力.     

载药脂质体的开发和利用

脂质体作为药物载体,开创了一种全新的药物剂型。通过近三十年的研究,已有数种由脂质体包载的药物投放市场,还有更多的药物的研究之中。由于脂质体本身所具有的优点,以及在应用过程中所发现的问题的逐步解决,可以认为,脂质体在制药、保健品、化妆品和生物工程等领域有着十分广阔的应用前景。     

核受体LXRα靶基因研究进展

核受体的研究近几年已有飞速的发展。LXRα(Liver X Receptor α)是一种与脂类代谢有关的核受体。研究发现LXRa的靶基因具有调节脂类的吸收、运输、转化和生物合成的功能，此外，LXRα在糖类的代谢等方面也有重要的调控作用。研究结果表明LXRα与动脉粥样硬化的发生有非常密切的关系。目前利用LXRα为靶标进行抗动脉粥样硬化药物筛选已经成为一个重要的研究方法。     

信息技术给系统建模与仿真的发展带来的机遇

本文在描述了系统建模与仿真主要研究内容之后，阐述了近年由于信息技术的飞速发展，给系统建模与仿真研究领域带来的机遇和挑战。     

冠状病毒疫苗研究进展及专利分析

本文利用科睿唯安公司Cortellis药物研发平台、德温特创新平台(Derwent Innovation)分析了冠状病毒疫苗研究进展及相关专利情况,包括冠状病毒疫苗药物当前的研发阶段、活跃公司、药物类型、新型冠状病毒肺炎(COVID-19)疫苗在研药物的基本情况、冠状病毒疫苗专利的发展态势及研发热点等。分析结果表明:冠状病毒疫苗活跃药物大多处于研发早期阶段,新型冠状病毒肺炎(COVID-19)疫苗已成为其中最热门的研发类型,重组病毒载体疫苗、蛋白亚基疫苗、DNA疫苗、RNA疫苗等新技术路线的研发多管齐下。此外,从专利方面看,疫苗专利的申请量与疫情发展关系密切,预计2020年冠状病毒疫苗专利申请量将会暴发式增长,目前相关专利主要分布在美国、欧洲、澳大利亚和中国。     

蛋白质组学在药物及疾病标志物研究中的应用进展

蛋白质组学提供了整体水平研究蛋白质的表达、翻译后修饰,以及蛋白质的功能的思路,由此获得蛋白质水平上的关于疾病发生、细胞代谢等过程的全面认识,逐渐被广泛应用于药物及生物标志物研究中.本文介绍了蛋白质组学的经典技术路线和新策略,并综述了其在药物及疾病标志物研究中应用进展.     

大分子载5-氟尿嘧啶药物及其缓释性研究进展

5-氟尿嘧啶是一种不可取代的最有效抗肿瘤药物之一,为了克服其毒副作用较大的缺点,将5-FU连接在天然高分子、化学合成高分子和微生物产生的高分子载体上,制成前药,并进行抗癌活性、缓释性、靶向性研究已成为药物传输、载运和释放研究领域最前沿和热点课题之一.     

Adult hippocampal neurogenesis: regulation by HIV and drugs of abuse

New dentate granule cells are continuously generated from neural progenitor cells and integrated into the existing hippocampal circuitry in the adult mammalian brain through an orchestrated process termed adult neurogenesis. While the exact function remains elusive, adult neurogenesis has been suggested to play important roles in specific cognitive functions. Adult hippocampal neurogenesis is regulated by a variety of physiological and pathological stimulations. Here we review emerging evidence showing that HIV infection and several drugs of abuse result in molecular changes that may affect different aspects of adult hippocampal neurogenesis. These new findings raise the possibility that cognitive dysfunction in the setting of HIV infection or drug abuse may, in part, be related to alterations in hippocampal neurogenesis. A better understanding of how HIV and drugs of abuse affect both molecular and cellular aspects of adult neurogenesis may lead to development of more effective therapeutic interventions for these interlinked epidemics. Received 6 February 2007; received after revision 26 March 2007; accepted 25 April 2007     

Colloidal drug carriers: achievements and perspectives

Colloidal drug carriers such as liposomes and nanoparticles are able to modify the distribution of an associated substance. They can therefore be used to improve the therapeutic index of drugs by increasing their efficacy and/or reducing their toxicity. If these delivery systems are carefully designed with respect to the target and route of administration, they may provide one solution to some of the delivery problems posed by new classes of active molecules such as peptides, proteins, genes, and oligonucleotides. They may also extend the therapeutic potential of established drugs such as doxorubicin and amphotericin B. This article discusses the use of colloidal, particulate carrier systems (25 nm to 1 μm in diameter) in such applications. In particular, systems which show diminished uptake by mononuclear phagocytes are described. Specific targeting of carriers to particular tissues or cells is also considered. Received 8 April 2002; received after revision 25 June 2002; accepted 26 June 2002     

Deep levels,transport and THz emission properties of SiGe/Si quantum-well structures

In coal mines in such countries as China and Russia,most of the coal mine methane(CMM) generated during mining is emitted to the atmosphere without any effective usage,because the methane concentration of CMM is relatively low and not allowed to be used as fuel for safety reasons.Methane is one of the greenhouse gases.Therefore,if it becomes possible to concentrate CMM to an acceptable level for use as fuel,this will greatly contribute to reduction of greenhouse gas emissions.With the aim of gaining approva...     

微动力系统的若干研究动态和进展

本文介绍了微动力系统的研究意义，简要地描述了当前微动力系统的若干研究动态和进展。开发并展示了我们研究小组的一种全新的无运动部件、不需高制造、装配精度的微TPV系统，介绍了我们实验和分析的最新研究结果。     

Know your enemy: understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics

The prevention and treatment of malaria is heavily dependent on antimalarial drugs. However, beginning with the emergence of chloroquine (CQ)-resistant Plasmodium falciparum parasites 50 years ago, efforts to control the disease have been thwarted by failed or failing drugs. Mutations in the parasite's 'chloroquine resistance transporter' (PfCRT) are the primary cause of CQ resistance. Furthermore, changes in PfCRT (and in several other transport proteins) are associated with decreases or increases in the parasite's susceptibility to a number of other antimalarial drugs. Here, we review recent advances in our understanding of CQ resistance and discuss these in the broader context of the parasite's susceptibilities to other quinolines and related drugs. We suggest that PfCRT can be viewed both as a 'multidrug-resistance carrier' and as a drug target, and that the quinoline-resistance mechanism is a potential 'Achilles' heel' of the parasite. We examine a number of the antimalarial strategies currently undergoing development that are designed to exploit the resistance mechanism, including relatively simple measures, such as alternative CQ dosages, as well as new drugs that either circumvent the resistance mechanism or target it directly.     

复杂能源系统结构演化和评价的新模型

能源系统作为开放的有机整体，是一个无确定边界的、与环境耦合的实体。定义了描述该实体的新物理量，由此建立了能源系统演化和评价的新模型，对“参考情景”、“可选择情景”以及“高经济增长情景”三种模式下的中国能源系统结构演化进行了案例分析，得到了合理的结果。该模型也为一般的社会经济系统发展提供了比笛卡尔一牛顿式的机械模型和熵增的热寂模型更合理的图景。     

Targeted polymeric micelles for delivery of poorly soluble drugs

Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.     

Partition coefficients of drugs in bilayer lipid membranes

The oil/water partition coefficient of drugs is widely accepted as a key parameter in drug design. The coefficients are usually determined using a bulk octanol phase to represent the lipid. The physiologically and pharmacologically relevant structure is, of course, the bilayer lipid membrane, but until now there has been no convenient means of measuring the partition coefficients of small molecules into a single bilayer. This paper demonstrates that the partition coefficient may be calculated from the change in membrane refractive index which occurs when a drug molecule partitions into the membrane. The refractive index is determined by an integratedoptics technique ideally suited to an ultra-thin structure such as a lipid bilayer.     

An overview of cancer multidrug resistance: a still unsolved problem

Although various mechanisms involved in anticancer multidrug resistance (MDR) can be identified, it remains a major problem in oncology. Beyond that, the introduction of new “targeted” drugs have not solved the problem. On the contrary, it has been demonstrated that the “classical” MDR-associated mechanisms are similar or identical to those causing resistance to these novel agents. These mechanisms include the enhanced activity of drug pumps, i.e. ABC or alternative transporters; modulation of cellular death pathways; alteration and repair of target molecules; and various less common mechanisms. Together they build a complex network of cellular pathways and molecular mechanisms mediating an individual MDR phenotype. Although the application of new high throughput “-omics” technologies have identified multiple new gene-/protein expression signatures or factors associated with drug resistance, so far none of these findings has been useful for creating improved diagnostic assays, for prediction of individual therapy response, or for development of updated chemosensitizers. Received 05 March 2008; received after revision 21 May 2008; accepted 23 May 2008