Smart Nanodrug with Nuclear Localization Sequences in the Presence of MMP-2 To Overcome Biobarriers and Drug Resistance

A series of physiological barriers have impeded nanoparticle-based drug formulations (NDFs) from reaching their targeted sites and achieving therapeutic outcomes. In this study, we develop size-controllable stealth doxorubicin-loaded nanodrug coated with CD47 peptides (DOX/sNDF-CD47) based on supramolecular chemistry to overcome multiple biological barriers. The smart DOX/sNDF-CD47 can efficiently decrease sequestration by macrophages and disassemble into poly(amidoamine) dendrimers with nuclear localization sequences (DOX/PAMAM-NLS) in the presence of matrix metalloproteinase-2 (MMP-2). Such structure transformation endows DOX/sNDF-CD47 with the ability of deep penetration in multicellular tumor spheroid, lysosomal escape, and nucleus localization, resulting in excellent cytotoxicity and drug resistance combating. In vivo experiments further confirmed that DOX/sNDF-CD47 has good tumor-targeting ability and can significantly improve therapeutic efficacy of DOX on xenograft tumor model. The ability to overcome multiple biological barriers makes sNDF-CD47 a promising NDFs to treat cancer expressing MMP-2 and combating drug resistance.     

Fully discrete dynamic mesh discontinuous Galerkin methods for the Cahn-Hilliard equation of phase transition

Fully discrete discontinuous Galerkin methods with variable mesh- es in time are developed for the fourth order Cahn-Hilliard equation arising from phase transition in materials science. The methods are formulated and analyzed in both two and three dimensions, and are proved to give optimal order error bounds. This coupled with the flexibility of the methods demonstrates that the proposed discontinuous Galerkin methods indeed provide an efficient and viable alternative to the mixed finite element methods and nonconforming (plate) finite element methods for solving fourth order partial differential equations.

     

用于高超音速推进的反循环发动机热力性能分析

符号表fIkg空气对应的燃料流量ISP燃料比冲Ti后燃烧室出口温度马比推力，燃料空气当量比WT涡轮输出功MT飞行马赫数＄前登燃烧室出口温度。T涡轮膨胀比H飞行高度T4＊热交换器出口温度7TC压气机压比1引言八十年代以来，美、俄、德、法、英、日等主要空间大国均提出了各自的高超音速计划，如NASP、Sanger、HOTOL、STAR等。各国的方案在Ma＞6．5均采用火箭发动机或超燃冲压发动机，对于Ma＜6．5采用何种方案则分歧较大，有涡轮一冲压组合发动机方案、ATR方案、LACE方案等。本文对反循环发动机（InverseCgcleEngine）方案作了进…     

求解场问题的一种新算法

基于文（１）（２），本文给出了一种计算场问题的新算法－拓扑有限元Ｇｉｖｅｎｓ算法，该方法利用了拓扑有限元的特性及快速Ｇｉｖｅｎｓ变换。算例结果与实验吻合很好。     

新型肼桥联共价三嗪聚合物在二氧化碳捕集和催化转化方面的应用（英文）

二氧化碳的捕集和催化转化是近年来二氧化碳利用方面的研究热点.其原因,一方面二氧化碳是储量丰富、廉价易得的可再生碳资源,另一方面它又是带来环境问题的温室气体.以金属有机框架、沸石和多孔聚合物材料为代表的同时具有规则孔道和活性催化位点的双功能材料为实践这一新概念创造了条件.但是,金属有机框架和沸石的应用面临由其自身结构所带来的热稳定性和/或水稳定性较低等问题.多孔聚合物材料则由于其高稳定性、低密度以及非金属等优点,逐渐成为该领域的研究重点.然而,当前关于利用多孔聚合物类材料作为有机催化剂以实现二氧化碳固定的报道,其反应过程一般需要较高温度、有机溶剂和/或过渡金属催化组分,仍有较大改进余地.本文设计合成了新型肼桥联共价三嗪聚合物(HB-CTP),意图在利用其富氮三嗪结构单元促进二氧化碳捕集的同时,以大量肼官能团通过氢键作用活化环氧化物,进而将二氧化碳在无溶剂和非金属的温和条件下催化固定为环状碳酸酯.HB-CTP材料的合成方法简便易行,由2,4,6-三肼基-1,3,5-三嗪与三聚氯氰发生的亲核取代反应制得.采用多种表征手段分析了该类新材料的结构和形态:红外光谱表明三聚氯氰的C–Cl键在聚合过程中反应完全,其位于850 cm.1处的吸收信号彻底消失;固体核磁谱图仅在168.1 ppm处显示三嗪环的单峰信号,表明了该材料结构的完整性;X射线粉末衍射测试并未发现特征峰,表明HB-CTP呈无定形态;透射电镜和扫描电镜的观测结果则进一步证实了该材料的团聚形态;最后,热重分析显示HB-CTP具有良好的热稳定性,250 ℃以上才开始分解.然后,通过氮气吸附测定了HB-CTP比表面积(51.2 m~2/g)和总孔容(0.28 cm3/g),其吸附等温线呈Ⅱ型,表明材料结构以大孔为主,通过层间吸附.随后的二氧化碳吸附测试发现,HB-CTP在0°C、0.1 MPa条件下显示出较高的二氧化碳捕集容量(8.2 wt%),并且经过连续吸附脱附循环五次,仍能保持较好的二氧化碳捕集能力.在HB-CTP材料良好的二氧化碳捕集容量基础上,本文考察了其催化活性,发现带有多种取代基的环氧化物均能在无溶剂、非金属的温和条件下,以较高的收率被转化为环状碳酸酯类产物;并且底物结构中的卤素、羟基、炔基、烯丙基和苄基等官能团均未发生副反应,显示出良好的底物适用范围.此外,HB-CTP材料可通过简单的离心操作实现分离回收,且经连续使用五次,其催化活性也没有明显降低.综上所述,该类新型肼桥联共价三嗪聚合物不仅能够高效捕集二氧化碳,而且还可以将其在温和条件下催化转化为环状碳酸酯类产物,具有一定理论研究意义和实际应用价值     

Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy

Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411, and a replaceable anti-biomarker probe (ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.     

尿毒症患者与血清八种元素含量关系的研究

检测了３７例尿毒症患者血清微量元素Ｆｅ、Ｃｕ、Ｚｎ和常量元素Ｋ、Ｎａ、Ｃａ、Ｍｇ、Ｐ的含量，并进行比较，探讨其相互关系，以期为尿毒症的发生发展及防治措施提供依据．结果发现尿毒症患者血清Ｋ、Ｐ、Ｍｇ极显著高于对照组（均Ｐ＜０．０１），而Ｎａ、Ｃａ、Ｚｎ、Ｃｕ、Ｆｅ及Ｎａ／Ｋ、Ｃａ／Ｍｇ则极显著低于对照组（均Ｐ＜０．０１），且Ｎａ／Ｋ、Ｃａ／Ｍｇ与肾实质受损程度呈负相关，提示Ｎａ／Ｋ、Ｃａ／Ｍｇ降低与尿毒症的发生发展过程有密切的关系．     

Dynamics and energetics of single-step hole transport in DNA hairpins

The dynamics of single-step hole transport processes have been investigated in a number of DNA conjugates possessing a stilbenedicarboxamide electron acceptor, a guanine primary donor, and several secondary donors. Rate constants for both forward and return hole transport between the primary and secondary donor are obtained from kinetic modeling of the nanosecond transient absorption decay profiles of the stilbene anion radical. The kinetic model requires that the hole be localized on either the primary or the secondary donor and not delocalized over both the primary and the secondary donor. Rate constants for hole transport are found to be dependent upon the identity of the secondary donor, the intervening bases, and the location of the secondary donor in the same strand as the primary donor or in the complementary strand. Rate constants for hole transport are much slower than those for the superexchange process used to inject the hole on the primary donor. This difference is attributed to the larger solvent reorganization energy for charge transport versus charge separation. The hole transport rate constants obtained in these experiments are consistent with experimental data for single-step hole transport from other transient absorption studies. Their relevance to long-distance hole migration over tens of base pairs remains to be determined. The forward and return hole transport rate constants provide equilibrium constants and free energies for hole transport equilibria. Secondary GG and GGG donors are found to form very shallow hole traps, whereas the nucleobase deazaguanine forms a relatively deep hole trap. This conclusion is in accord with selected strand cleavage data and thus appears to be representative of the behavior of holes in duplex DNA. Our results are discussed in the context of current theoretical models of hole transport in DNA.     

Microwave assisted DIC-promoted intramolecular cyclization for solid phase synthesis of trisubstituted imidazolidinones and pyrimidinones

A convenient solid phase synthesis of trisubstituted imidazolidinones and pyrimidinones via microwave assisted DIC-promoted intramolecular cyclization is described. Intramolecular cyclization of a resin-bound thiourea prepared by acylation of a dipeptide with an aryl isothiocyanate was rapidly promoted with DIC under microwave to afford imidazolidinones and tetrahydropyrimidinones in good yield and purity.