基于“标准-3”动能拦截弹的顺轨拦截方法研究

提出了针对大气层外机动目标的顺轨拦截方法,能够大幅度降低目标与拦截器之间的相对速度,缓和拦截器的过载需求,避免脱靶现象。采用“标准-3”拦截弹的公开参数建立数学模型,对大气层外机动弹头的顺轨拦截过程进行了仿真研究,仿真综合考虑了助推器和拦截器的质量变化、末制导初始对准误差、导引头的测量误差和盲区、动力学系统的响应延迟和过载约束。结果表明,在处于速度劣势的情况下,拦截器能够对机动目标进行精准碰撞,验证了顺轨拦截方法的工程实践意义。     

Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors

The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like (β5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the β5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure–activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors.     

Modulating Protein–Protein Interactions by Cyclic and Macrocyclic Peptides. Prominent Strategies and Examples

Cyclic and macrocyclic peptides constitute advanced molecules for modulating protein–protein interactions (PPIs). Although still peptide derivatives, they are metabolically more stable than linear counterparts, and should have a lower degree of flexibility, with more defined secondary structure conformations that can be adapted to imitate protein interfaces. In this review, we analyze recent progress on the main methods to access cyclic/macrocyclic peptide derivatives, with emphasis in a few selected examples designed to interfere within PPIs. These types of peptides can be from natural origin, or prepared by biochemical or synthetic methodologies, and their design could be aided by computational approaches. Some advances to facilitate the permeability of these quite big molecules by conjugation with cell penetrating peptides, and the incorporation of β-amino acid and peptoid structures to improve metabolic stability, are also commented. It is predicted that this field of research could have an important future mission, running in parallel to the discovery of new, relevant PPIs involved in pathological processes.     

Positively charged liposomes consisting of the KTTKS pentapeptide conjugated with rhodamine increase rhodamine toxicity in E. coli and zebrafish embryo

Liposomes composed of cell‐penetrating peptide derivatives increased transport across the cell membrane. Conjugating rhodamine to a cell‐penetrating peptide increased the toxicity of rhodamine in E. coli and zebrafish embryos. A similar total protein inhibition pattern with different intensities, indicating that the interaction pathways of the rho‐KTTKS‐CONH₂ monomer and liposomes were the same. It suggests that the rho‐KTTKS‐CONH₂ liposomes showed higher toxicity because better transport across the cell membrane increased the effective concentration inside cells. The staining of zebrafish embryos using rho‐KTTKS‐CONH₂ liposomes showed a longer retention time, suggesting that it can penetrate deeper tissues or organs in zebrafish.     

The progress and perspective of strategies to improve tumor penetration of nanomedicines

Tumor penetration is important fo r effectively tumor targeting drug delivery.Recently,many researches are published to overcome the barriers that restrict tumor penetration and improve drug delivery efficiency.In the mini review,we first analyzed the barriers influence the tumor penetration,including tumor microenvironment barriers,nanoparticle properties,and interaction barriers between tumor and nanoparticles.To overcome the barrier,several strategies are developed,including modulating tumor microenvironment,changing particle size,transcytosis enabled tumor penetration,cell penetrating peptide modification and overcoming binding site barrier,which could effectively improve tumor penetration,and finally enhance tumor treatment outcome.     

球形钨合金破片空气阻力系数实验研究

 实验研究了理想球形钨合金破片和经历爆轰驱动的球形钨合金破片长距离飞行时的速度衰减规律。实验结果表明：（1）对于理想球形钨合金破片,在同一初始速度条件下,衰减系数为常数,空气阻力系数与初始速度有关,两者成线性关系;（2）对于经历爆轰驱动的球形钨合金破片,由于有轻微的质量损失和变形,速度衰减规律与理想球形钨合金破片有明显的区别,空气阻力系数与飞行速度有关,两者成线性关系。     

柱状装药预制破片缩比战斗部爆炸冲击波和破片的作用时序

针对柱状装药的周向预制破片战斗部,结合无量纲分析方法和爆炸驱动理论,确定了影响破片和冲击波相遇位置的关键参数,给出了由缩比战斗部推广预测原型战斗部爆炸产生的破片冲击波作用时序的方法。采用ANSYS/LS-DYNA有限元软件进行数值模拟,对比验证了理论分析和数值试验结果,分析了战斗部缩比比例对冲击波和破片作用时序的影响。结果表明:缩比模型与原型战斗部爆炸产生的破片和冲击波的相遇位置之比和相遇时间之比主要取决于两模型的质量比,在不考虑破片速度衰减时,两模型中载荷相遇位置之比和相遇时间之比等于其质量比的0.33次方。受破片速度衰减影响,该方法仅适用于质量缩比不小于0.2的模型。     

不同类型细胞穿膜肽二级结构特征研究

细胞穿膜肽是一类能以受体依赖或非受体依赖方式介导胞吞作用的小分子短肽,能够携带不同分子穿过细胞膜,这一特性使细胞穿膜肽成为一种有效的运输载体,为药物靶向治疗提供了新希望.本文从生物信息角度针对不同长度区间、运输不同类型分子细胞穿膜肽之间的异同二级结构特征进行了系统研究,同时进一步对不同穿膜方式对应的细胞穿膜肽二级结构特征进行了对比研究,结果表明不同类型细胞穿膜肽之间在二级结构组成上具有不同程度差异特征,为今后揭示细胞穿膜肽相关分子结构机制奠定可靠的理论基础.