以柚皮素为结构骨架的拓扑异构酶抑制剂的设计与合成

以柚皮素为骨架,引入拓扑异构酶抑制剂药物的药效基团对其进行结构修饰,合成生物利用度较高、抗肿瘤活性较好的一系列柚皮素衍生物.中间体的合成采用温和的非亲核碱DIPEA,一锅法反应同时获得单双取代的溴化物,并通过核磁共振以及质谱确认产物的结构.获得一系列柚皮素衍生物,进一步推广一锅法反应同时获得单双取代的溴化物的方法和应用,为今后的这一系列柚皮素衍生物的细胞活性实验提供依据和保障,为药物修饰和新药开发提供有价值的信息和基础.     

吡嗪酰胺-2,5-二羟基苯甲酸共晶制备及过程在线研究

吡嗪酰胺(PZA)为最有效的抗结核药物之一,其水溶性差,通过形成共晶的方法可以改善其溶解度,提高药效.本文通过悬浮法制备了PZA和2,5-二羟基苯甲酸(2,5-DHBA)共晶,产品采用X-射线粉末衍射(PXRD)、差式扫描热分析(DSC)、傅里叶变换红外(FT-IR)和拉曼光谱(Raman)进行表征.结果表明,利用悬浮法可以制备出纯度较高的PZA-2,5-DHBA(1∶1)共晶.进一步采用衰减全反射傅里叶变换红外光谱仪(ATR-FTIR)和在线拉曼光谱等过程分析技术(PAT),监测并分析了该共晶的形成过程.结果表明,在30,℃下PZA-2,5-DHBA(1∶1)共晶在乙腈中的溶度积为9.4×10-4(mol/L)2;且该过程为PZA溶解-共晶生成的两步过程,存在成核介稳现象,过程控制步骤为共晶生长.     

基于网络药理学和分子对接探讨黄连温胆汤治疗幽门螺杆菌相关性胃炎的作用机制

运用网络药理学和分子对接方法探索黄连温胆汤治疗幽门螺杆菌相关性胃炎的分子机制。应用中药系统药理学数据库与分析平台对黄连温胆汤药物活性成分及药物作用靶点基因进行筛选。通过Genecards数据库、DisGENET数据库查找幽门螺杆菌相关性胃炎疾病相关靶点,利用维恩在线绘图工具获得疾病与药物的共同靶点基因。利用Cytoscape 3.8.2软件以及STRING数据库分别构建药物-化合物-靶点相互作用网络及蛋白质-蛋白质相互作用网络图。运用DAVID数据库进行基因本体功能和京都基因与基因组百科全书通路富集分析。选取度值排名前3的靶点蛋白和活性成分使用AutoDockTools 1.5.6软件进行分子对接。共筛选得到槲皮素、川皮苷、柚皮素等127种黄连温胆汤药物活性成分,并获得Akt1、JUN、TNF-α、STAT3等101个潜在靶点蛋白,涉及P53信号通路、NOD样受体信号通路、TNF信号通路等90条信号通路。分子对接结果显示关键靶点STAT3、TP53、Akt1与活性成分槲皮素、川皮苷、柚皮素的亲和力较好,其中以Akt1与柚皮素的结合能力最强。通过分析黄连温胆汤治疗幽门螺杆菌相关性胃炎的作...     

柚皮素-钴(Ⅱ)配合物的合成与表征

应用柚皮素和硝酸钴在乙醇溶液中反应成功合成了柚皮素-钴配合物.用红外光谱和紫外光谱对配合物进行了表征.探讨并优化了柚皮素与钴反应的最佳条件:物质的量之比为0.75(钴:柚皮素),反应温度为60℃,反应时间为6h,pH值为4.5.     

柚皮苷半合成N-苯亚甲基柚皮素腙及细胞活性

从丰富易得的柚皮苷(Naringin)1出发,通过酸水解得到了柚皮素2.以柚皮素为先导化合物,通过4-位羰基与水合肼作用合成了中间体柚皮素腙3,进而与各种不同类型的醛缩合,合成了14个新型N-苯亚甲基柚皮素腙及类似物(4a~4n).MTT蛋白染色法体外抑制肿瘤增值活性测试显示化合物4c、4d、4h、4j、4n对胃癌细胞SGC-7901有一定的抑制作用.     

柚皮素与过渡金属铜（Ⅱ）离子的配位反应

利用配体和配合物在配位反应前后紫外吸收的不同,采用单因素实验法探讨了柚皮素与过渡金属铜（Ⅱ）离子在乙醇溶液中的最佳反应条件,考察了碱、不同阴离子的铜盐、配位比及温度对配位反应的影响.在最佳反应条件下成功合成了柚皮素-铜配合物,并用红外光谱和紫外光谱对配合物进行了表征.结果表明,碱是影响柚皮素与铜离子配位反应活性最明显的因素.最终确定了柚皮素与铜盐配位反应的最佳条件为：碱选用无水碳酸钠,铜盐选用氯化铜,氯化铜与柚皮素的配位比为0.75∶1.0,温度为60℃.     

葛根素-吡乙酰胺共晶的制备与表征

药物共晶是改善难溶性药物葛根素溶解度的一种有效方法。以葛根素为药物活性成分(API),对共晶形成物(CCF)进行筛选。研究结果表明,当葛根素与吡乙酰胺的摩尔比为1∶2时,通过溶液结晶的方法可以制备得到共晶。共晶的熔点为163.78℃,处于葛根素与吡乙酰胺的熔点之间。共晶在溶解性上也有明显的改观,在纯水中的溶解度是葛根素溶解度的20倍。     

芒柄花素平衡溶解度和油水分配系数的测定

目的测定芒柄花素的平衡溶解度和油水分配系数,为设计芒柄花素新剂型提供理论基础与依据。方法采用高效液相色谱(HPLC)法测定芒柄花素在水、不同缓冲盐溶液中的质量浓度,并运用摇瓶法测定芒柄花素在正辛醇-水、缓冲液体系中的表观油水分配系数。结果 37℃下芒柄花素在水中的平衡溶解度为2.079±0.036μg·mL~(-1),随着pH值增大,芒柄花素的平衡溶解度增大。芒柄花素在正辛醇-水体系中的表观油水分配系数lg P_(app)=2.79±0.03,随着缓冲盐溶液的pH值增大,芒柄花素在正辛醇-缓冲盐溶液体系中的油水分配系数减小。结论建立的方法可以准确测定芒柄花素的平衡溶解度和表观油水分配系数,科学合理地预测药物在体内的吸收与分布情况。     

原创中药红珠胶囊基于RRLC-ESI-MS/MS技术的化学成分分析

采用快速液相-三重串联四极杆质谱(RRLC-ESI-MS/MS)技术,在电喷雾质谱正模式和负模式下,对红珠胶囊内容物进行分析鉴定。通过质谱中分子离子峰和碎片离子峰的精确相对分子质量匹配,保留时间,紫外光谱对比,与对照品比对并结合参考文献鉴定,确证和指认了红珠胶囊中的新北美圣草苷、樱桃苷、柚皮苷、忍冬苷、野漆树苷、橙皮内酯水合物、7-(2″-α-鼠李糖基-6″-(3″″-羟基-3″″-甲基戊二酰)-β-D-葡萄糖基)柚皮素、异橙皮内酯、柚皮素9个化学成分。研究揭示了红珠胶囊的化学物质基础,为控制该药质量提供了依据。     

HPLC-MS/MS法同时测定人血清中4种一线抗结核药物浓度及其临床应用

建立利用HPLC-MS/MS法同时测定人血清中4种一线抗结核药物(异烟肼、利福平、吡嗪酰胺及乙胺丁醇)浓度的方法,以苯海拉明为内标,利用蛋白沉淀法将分析物与生物基质分离,色谱柱:Gemini C18(50×4.6mm,3 μm),流动相:A: 2 mmol/L甲酸铵-0.2%甲酸水溶液,B: 0.1%甲酸-甲醇-异丙醇(90∶10,体积比)溶液,采用电喷雾离子源,正离子扫描模式,并应用于临床进行治疗药物监测,共监测316例.结果显示,该方法快速准确稳定,特异性、标准曲线与定量下限、准确度与精密度、基质效应与提取回收率及稳定性均满足药物浓度测定的要求,可用于抗结核药临床治疗药物浓度监测.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

海南岛地体及其毗邻陆缘晚中生代—新生代古地磁研究和构造演化

本文叙述了对海南岛及其毗邻大陆边缘白垩纪到第四纪地层岩石进行古地磁研究的全部工作过程。通过分析岩石中剩余磁矢量的磁偏角及磁倾角的变化,提出海南岛白垩纪以来经历的构造演化模式如下:早期伴随顺时针旋转而向南迁移,后期伴随逆时针转动并向北运移。联系该地区及邻区的地质、地球物理资料,对海南岛上述的构造地体运动提出以下认识:北部湾内早期有一拉张作用,主要是该作用使湾内地壳显著伸长减薄,形成北部湾盆地。从而导致了海南岛的早期构造运动,而海南岛后期的构造运动则主要是受南海海底扩张的影响。海南地体运动规律的阐明对于了解北部湾油气盆地的形成演化有重要的理论和实际意义。     

Exciton Seebeck in Molecular Systems

Various applications relevant to the exciton dynamics,such as the organic solar cell,the large-area organic light-emitting diodes and the thermoelectricity,are operating under temperature gradient.The potential abnormal behavior of the exicton dynamics driven by the temperature difference may affect the efficiency and performance of the corresponding devices.In the above situations,the exciton dynamics under temperature difference is mixed with     

Achieving Unusual States of Matter Under High Pressure

The elongation method,originally proposed by Imamura was further developed for many years in our group.As a method towards O(N)with high efficiency and high accuracy for any dimensional systems.This treatment designed for one-dimensional(ID)polymers is now available for three-dimensional(3D)systems,but geometry optimization is now possible only for 1D-systems.As an approach toward post-Hartree-Fock,it was also extended to     

《Chinese Science Bulletin》SUBJECT INDEX TO VOLUME 59(2014)

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An on-line scaling method for improving scalability of a database cluster

The explosive growth of the Internet and database applications has driven database to be more scalable and available, and able to support on-line scaling without interrupting service. To support more client's queries without downtime and degrading the response time, more nodes have to be scaled up while the database is running. This paper presents the overview of scalable and available database that satisfies the above characteristics. And we propose a novel on-line scaling method. Our method improves the existing on-line scaling method for fast response time and higher throughputs. Our proposed method reduces unnecessary network use, i.e. , we decrease the number of data copy by reusing the backup data. Also, our on-line scaling operation can be processed parallel by selecting adequate nodes as new node. Our performance study shows that our method results in significant reduction in data copy time.     

An improved R-tree based on childnode''s probability

R-Tree is a good structure for spatial searching. But in this indexing structure,either the sequence of nodes in the same level or sequence of traveling these nodes when queries are made is random. Since the possibility that the object appears in different MBR which have the same parents node is different, if we make the subnode who has the most possibility be traveled first, the time cost will be decreased in most of the cases. In some case, the possibility of a point belong to a rectangle will shows direct proportion with the size of the rectangle. But this conclusion is based on an assumption that the objects are symmetrically distributing in the area and this assumption is not always coming into existence. Now we found a more direct parameter to scale the possibility and made a little change on the structure of R-tree, to increase the possibility of founding the satisfying answer in the front sub trees. We names this structure probability based arranged R-tree (PBAR-tree).     

Integrating GIS Web services based on mediating architecture

The geographic information service is enabled by the advancements in general Web service technology and the focused efforts of the OGC in defining XML-based Web GIS service. Based on these models, this paper addresses the issue of services chaining,the process of combining or pipelining results from several interoperable GIS Web Services to create a customized solution. This paper presents a mediated chaining architecture in which a specific service takes responsibility for performing the process that describes a service chain. We designed the Spatial Information Process Language (SIPL) for dynamic modeling and describing the service chain, also a prototype of the Spatial Information Process Execution Engine (SIPEE) is implemented for executing processes written in SIPL. Discussion of measures to improve the functionality and performance of such system will be included.     

Tracking data management using topology of moving object database system for moving object constrained trajectory in LBS application

Advances in wireless technologies and positioning technologies and spread of wireless devices, an interest in LBS (Location Based Service) is arising. To provide location based service, tracking data should have been stored in moving object database management system (called MODBMS) with proper policies and managed efficiently. So the methods which acquire the location information at regular time intervals then, store and manage have been studied. In this paper, we suggest tracking data management techniques using topology that is corresponding to the moving path of moving object. In our techniques, we update the MODBMS when moving object arrived at a street intersection or a curved road which is represented as the node in topology and predict the location at past and future with attribute of topology and linear function. In this technique, location data that are corresponding to the node in topology are stored, thus reduce the number of update and amount of data. Also in case predicting the location,because topology are used as well as existing location information, accuracy for prediction is increased than applying linear function or spline function.