Roles of flanking sequences in the binding between unimolecular parallel-stranded G-quadruplexes and ligands

G-quadruplexes attract more and more attention in recent years.Numerous small molecules which can induce or stabilize the formation of G-quadruplexes have been investigated on the purpose of anticancer drug development.As a motif existed in physiological condition,flanking sequences are an important part of G-quadruplexes but the study on the impact of flanking sequences on (G-quadruplex)-ligand binding is rarely reported.In this paper,the effects of flanking sequences on binding affinity between a series of unimolecular parallel-stranded G-quadruplex sequences derived from c-myc oncogene promoter (termed as c-myc G-quadruplexes) and their ligands are discussed in detail.The results showed that the flanking sequences on c-myc G-quadruplexes play key roles in (G-quadruplex)-ligand interaction.When a c-myc G-quadruplex is bound to its ligands,the flanking sequences might form a binding cavity above the terminal G-quartet,which could provide a suitable site for ligands to dock in.Moreover,the bases on flanking sequences could interact with ligand through π-π stacking,and finally form a sandwich-stacking mode (terminal G-quartet,ligand and bases on the flanking sequence).This mode could stabilize the (G-quadruplex)-ligand complex effectively and enhance the binding affinity dramatically.However,flanking sequences are also found to exhibit steric hindrance effect which could impede the (G-quadruplex)-ligand binding.     

Kinetic studies on the irreversible inhibition of restriction endonucleasePst I by site-specific inhibitors

The irreversible modifying effects onPst I of several inhibitors have been studied with the irreversible inhibition kinetic theory of single substrate reaction provided by Tsou, C. L. Pyridoxal phosphate (PLP), p-chloromercuribenzoic acid (PCMB), diisopropyl fluorophosphate (DEP), 2,3-diacetyl (DAC) and N-ethyl-5-phenylisoxazoliun-3′-sulfonate (woodward's reagent K, WRK) modify the lysine, cysine, serteine, arginine and carboxyl groups of the protein molecule respectively. These five inhibitors have been found to inhibit both the prime activity and star activity ofPst I. Used with the irreversible inhibition theory, the apparent inhibition rate constant,A and the microcosmic inhibition rate constants,k ₊₀ andk′ ₊₀ of every inhibitor were calculated. We also found that their inhibition effects belong to the noncompetitive irreversible inhibition. Results show that among the groups to be modified, some have nothing to do with the combination with the substrate, and some may have, but any of them isn't the only factor involved in the specific binding. Despite all this, they may take part in the catalysis of enzyme or have important effects on maintaining the active structure of enzyme molecules. Furthermore, serine and arginine residues are related to the alteration ofPst I conformation and then influence the ability ofPst I recognizing and incising DNA specifically. Foundation item: Supported by the Research Fund for the Doctoral Program of Higher Education (1999048601) Biography: Zou Guo-lin (1947-), male, Professor, research direction: enzymology.     

Quantum chemical studies on tuning the second-order nonlinear optical molecular switching of triarylborane derivatives

In this work, density functional theory (DFT) combined with the finite field (FF) method has been adopted to analyze the second-order nonlinear optical (NLO) properties of the triarylborane (TAB) derivatives obtained by introducing different inductive electron groups into the phenylene ring of the TAB (RTAB, where R=2-C6H5-C2B10H10(1),R=F(2), R=Me(3),R=NO2(4),R=NH2(5)). The static first hyperpolarizabilities (βtot) of the RTAB molecules can be switched by binding one F- to the boron center (RTAB′) or one-electron reduction (RTAB"). The DFT-FF calculations show that the βtot values of 2′, 3′ and 5′ decrease while those of 1′ and 4′ increase compared with the values of their neutral molecules, which was attributed to the fact that the charge transfers of 2, 3 and 5 become smaller and those of 1 and 4 become larger by binding one F- ion to the boron center, according to time-domain DFT (TD-DFT) analysis. However, the incorporation of one electron enhances the second-order NLO properties of the RTAB molecules remarkably, especially for system 1. It is notable that the βtot value of reduced form 1″ is 508.69×10-30 esu, i.e. about 578 times larger than that of system 1. Frontier molecular orbital (FMO) and natural bond orbital (NBO) analyses suggest that the reversal of the charge distribution between the neutral molecules and their reduced forms leads to low HOMO-LUMO energy gaps (E0) and thus large βtot values for the reduced forms.     

博落回生物碱成分及其抗菌活性的研究

为研究罂粟科植物博落回的生物碱成分,采用硅胶柱层析、重结晶等方法对其进行了分离纯化,结果获得了5个生物碱,分别经波谱分析鉴定为:原阿片碱(I),pancorine(II),去甲基白屈菜红碱(III),6-丙酮基二氢血根碱(IV),6-丙酮基二氢白屈菜红碱(V),其中化合物(II)为首次从该植物中分离得到.抗菌圈检测发现博落回总生物碱抗菌作用较强,对金黄色葡萄球菌的抑制作用尤为显著.     

动物中天然抗癌产物研究

抗癌动物资源包括两栖动物、肠腔动物、苔虫动物、被囊动物、棘皮动物、软体动物、鱼类等。其天然产物主要是脂溶性甾族类、大环内酯类、肽类、聚醚类、多糖类、生物碱类及必需脂肪酸（EFAS）类等。重点介绍了对蟾蜍、医蛭及海洋生物中的海鞘、沙群海葵、海绵、苔藓虫、鱼类等抗癌动物资源与天然产物的研究开发，并对这些领域开发前景进行了展望。     

Atmospheric heterogeneous reaction of acetone: Adsorption and desorption kinetics and mechanisms on SiO2 particles

Acetone plays an important role in photooxidation processes in the atmosphere. Up to date, little is known regarding the heterogeneous fate of acetone. In this study, the adsorption and desorption processes of acetone on SiO2 particles, which are the major constituent of mineral dust in the atmos-phere, have been investigated for the first time under the simulated atmospheric conditions, using in situ transmission Fourier transform infrared spectroscopy. It is found that acetone molecules are adsorbed on the surfaces of SiO2 particles by van der Waals forces and hydrogen bonding forces in a nonreactive and reversible state. The rates of initial adsorption and initial desorption, initial uptake coefficients and adsorption concentrations at equilibrium have been determined at different relative humidity. The presence of water vapor cannot result in the formation of new substances, but can decrease the adsorption ability by consuming or overlapping the isolated OH groups on the surfaces of SiO2 particles. In the desorption process, a considerable amount of acetone molecules will remain on SiO2 particles in dry air, whereas acetone molecules are almost completely desorbed at a high relative humidity. In order to evaluate the role of heterogeneous reactions of acetone and other carbonyl compounds in the atmosphere, a new model fitting the atmospheric conditions is needed.     

钆基无机纳米粒子磁共振造影剂设计的研究进展

磁共振成像（MRI）技术是常见的临床医学影像学的检测手段之一.在临床诊断中使用最多的是纵向弛豫（T₁）造影剂：马根维显（Gd-DTPA）.自其正式商用化后,人们对钆基造影剂进行了大量研究.文章介绍了钆基无机纳米粒子（Gd IONPs）造影剂的作用原理,阐述了无机纳米粒子的形貌、尺寸、表面修饰、氧空位等因素的影响,并对Gd IONPs造影剂的设计做了展望.     

Label-free selective sensing of Pb2+ lead(II) sensors based on the aggregation of a pyrene fluorescent probe

In the present work, we report a label-free fluorescence turn-on approach for the sensitive and selective sensing of Pb²⁺. Pyrene with one positive charge was used as the fluorescent probe, and thrombin aptamer (TBA), which was a G-rich oligonucleotide, was employed to form G-quadruplex with lead(II). When TBA and Pb²⁺ were mixed with lead(II) in an aqueous solution, it was folded into a stable G-quadruplex. Subsequently, a single-stranded nucleic acid-specific nuclease S1 was added. The G-quadruplex stabilized by Pb²⁺ lead(II) had markedly a significant resistant ability to nuclease S1 digestion. However, in the absence of Pb²⁺ lead(II), no quadruplex or less stable quadruplex was formed and TBA was digested by nuclease S1 in 3 min under the optimized experimental conditions. Finally, pyrene probe was mixed with oligonucleotide in Pb²⁺ lead(II). Electrostatic interactions between oligonucleotide (a polyanion) and the probe induced the aggregation of the probe, which in turn produced strong emission of the strong pyrene excimer emission. The intensity of the induced excimer emission was directly proportional to the amount of Pb²⁺ added. Our approach shows good selectivity and sensitivity for the detection of Pb²⁺ with a limit of detection limit as low as 800 nmol/L.     

钩藤的药理作用及临床应用研究进展

钩藤(Uncaria rhynchophylla)是广西区域特色药材品种之一,具有息风定惊、清热平肝的功效,药用历史悠久。钩藤生物碱是钩藤的主要药效成分,对缓解药物成瘾、阿尔茨海默症、高血压等疾病具有显著功效,其方药天麻钩藤饮、复方钩藤降压片等在临床上广泛应用。随着现代医学研究技术的进步,钩藤生物碱及其方药的治病机理正在不断被发现。本文收集近十年钩藤相关研究文献,以钩藤的药效物质为基础,总结钩藤生物碱及其方药的药理研究成果,分析钩藤的临床应用情况,以期为钩藤的新药研发或新应用提供理论借鉴。     

The ring-substituted phthalo-cyanines and its metal com-plexes: Crystal structure of 1,4, 8,11,15,18,22,25-octa-butoxyphthalocyani-natocopper(Ⅱ)

Crystal structure of 1, 4, 8, 11, 15, 18, 22, 25-octa-butoxyphthalocyaninato- copper (Ⅱ) (1) was determined by X-ray diffraction methods. The crystal system is mono-clinic, space group is P2₁/c, Z = 4, a = 1.3741(1) nm, b = 2.6737(1) nm, c = 1.6690(1) nm, β= 101.278(1)°. The steric congestion between the neighbouring butoxyl groups causes the distortion of the ring core of phthalocyanine (Pc) into a saddle shape conformation. In the crystal structure, molecules stack along a axis forming one-dimensional packing structure and there are two molecular overlap types which appear in turn with different distances between molecules, overlap area and angle.     

UPLC-QQQ-MS/MS法用于粉防己根双苄基异喹啉生物碱合成途径中12种化合物的定量检测

超高效液相色谱-三重四极杆串联质谱(UPLC-QQQ-MS/MS)法用于粉防己(Stephania tetrandra S.Moore)中的有机酸和生物碱类化合物的同时定性、定量检测具有重要的研究意义，可为汉防己甲素等双苄基异喹啉类生物碱的代谢合成机理解析提供数据参考。本研究采用Poroshell 120 CS-C18色谱柱进行分离，以含0.1%甲酸的10 mmol/L甲酸铵水溶液(A)-乙腈(B)为流动相进行梯度洗脱，在喷射流技术离子源(AJS-ESI)，正、负离子多反应监测(MRM)模式下进行检测，通过一级和二级质谱数据对不同采集批次的粉防己根部代谢物进行定性和定量分析。结果显示：12种被测化合物在线性范围内都呈现出良好的线性关系，相关系数均大于0.99；粉防己根部中12种被测化合物的含量存在显著差异，同一化合物的含量在不同的采集月份也有着明显的差异；L-酪氨酸、汉防己甲素和汉防己乙素在粉防己根部的含量相对较高。本研究实现了粉防己根部中12种被测化合物的同时定性和精确定量分析。     

Inductive transfer learning for unlabeled target-domain via hybrid regularization

Recent years have witnessed an increasing interest in transfer learning. This paper deals with the classification problem that the target-domain with a different distribution from the source-domain is totally unlabeled, and aims to build an inductive model for unseen data. Firstly, we analyze the problem of class ratio drift in the previous work of transductive transfer learning, and propose to use a normalization method to move towards the desired class ratio. Furthermore, we develop a hybrid regularization framework for inductive transfer learning. It considers three factors, including the distribution geometry of the target-domain by manifold regularization, the entropy value of prediction probability by entropy regularization, and the class prior by expectation regularization. This framework is used to adapt the inductive model learnt from the source-domain to the target-domain. Finally, the experiments on the real-world text data show the effectiveness of our inductive method of transfer learning. Meanwhile, it can handle unseen test points.     

Spectroscopic studies of the interaction between methylene blue and G-quadruplex

The telomere is a complex of simple guanine-rich repeating sequences of single-stranded DNA and pro-tein at the ends of eukaryotic chromosomes[1―3]. Hu-man telomere consists of the sequence, 5′-TTAGGG-3′, with the length ranging from 5 to 15 kb. The gu…     

新型咪唑并邻菲罗啉衍生物对人端粒G-四链体相对于双螺旋DNA的选择性识别

G-四链体DNA是抗肿瘤药物研究开发的重要靶点,选择性识别并稳定G-四链体DNA的化合物是潜在的抗肿瘤药物.文章利用紫外可见吸收滴定,荧光滴定,CD光谱以及荧光共振能量转移熔点实验(FRET-melring)研究了三个基于邻菲罗啉的新型衍生物(A,B和C)与人端粒G-四链体DNA的相互作用.结果表明三个化合物通过末端堆积方式与G四链体DNA相互作用,结合常数(K)约为106 mol-1·L.当浓度为3 μmol·L-1时,化合物A,B和C分别使G四链体DNA熔点温度增加(△Tm)16.2,10.5和10.9℃.而且在10倍过量双螺旋DNA存在下均能选择性识别并稳定G-四链体结构.     

一个用于有机物生物活(毒)性研究的新拓扑指数

提出一个新的拓扑指数Yx,即隐氢图中的所有相邻边的一阶分子连接性指数的乘积之和占分子中有效碳原子的分率,用Yx研究取代苯,甲基苯、卤代苯、卤代烃、氯苯、含氮杂环化合物和直链伯醇的生物活（毒）性,建立相应的相关方程（r=0.9203-0.9914),计算出部分取代苯类化合物对发光菌（Photobacterium phosphoreum)、呆鲦鱼（Piumephales promelass)、大型蚤（Daphnia magua strau)、酵母菌（Saccharomyces cerevisiae)和绿藻Green algae的毒性数据,新的拓扑指数易于计算,有较高的结构区分能力,新方法计算方便,物理意义明确。     

Distribution and characterization of C31 sterane from cretaceous sediments and oils, Songliao Basin, China

Relatively high abundance of C₃₁ steranes has been identified from cretaceous source rocks and crude oils in the Songliao Basin, China. C₃₁ steranes which occur as ten isomers were tentatively identified as 4, 22, 23, 24-tetrametyhlcholestane based on their retention time and mass spectrum. They bear a lower thermal stability and occur as important components in the immature oils of Chaochang region because they have three-methyl groups in their side chain. The relatively high abundance of C₃₁ steranes in the samples can indicate the source input of some special algae in the brackish and saline environment. Therefore they can be used as very useful bimarkers for organic facies analysis and oil correlation. Their biological source perhaps related to the dinoflagellate such asG. foliaceum andP. foliaceum. The gorgostanol are considered as possible precursors for the putative C₃₁4-methyl sterane which formed in the stage of diagenesis.     

龙血竭抗癌成分的虚拟筛选及体外抗癌活性检测验证

应用计算机辅助虚拟筛选技术研究龙血竭抗癌活性成分. 以HER2为靶蛋白受体，对龙血竭149种已知化合物进行了虚拟筛选，对其中具有潜在活性的成分进行了体外HER2影响测定以及SK-Br-3抗癌活性检测验证. 结果表明， HER2靶蛋白分子对接模型具有较强的活性分子富集能力，与HER2受体有效对接、具有抗癌潜力的活性分子主要为二氢查耳酮、黄烷、甾体以及芪类成分，与HER2胞外域和胞内域结合的4种成分及能与HER2胞内域结合的3种成分均能显著的抑制体外HER2活性，其中反式3-甲氧基-4′,5-二羟基二苯乙烯、反式3,4′,5-三羟基二苯乙烯能够抑制SK-Br-3癌细胞增殖、改变细胞周期，引发SK-Br-3极显著凋亡，具有良好的体外抗癌活性，可为龙血竭抗癌药物的研发提供基础数据.      

田七药材重金属及微量元素含量分析

【目的】测定不同产地田七（Panax notoginseng）主根及田七不同部位的重金属和微量元素含量,为广西建立田七规范化生产基地提供实验依据.【方法】采用原子荧光光谱法、原子吸收分光光谱法及电感耦合等离子体发射光谱法进行测定分析.【结果】除镉（Cd）含量偏高外,其它重金属含量均符合绿色行业标准.另Cd含量在根茎中最高,其他测定的铅（Pb）、铜（Cu）、汞（Hg）和砷（As）等重金属及微量元素都以须根中含量最高,主根中最低.【结论】不同产地的田七主根重金属元素含量存在差异,但没有明显变化规律;田七不同部位富集重金属及微量元素的能力有差异.     

Anisotropic effect on the vibronic reduction factors

The reduction factors p and q defined by Ham in the Ee JT system and their relation 2q-p=1 have been well accepted and the concept of reduction factors is widely used in the studies of vibronic coupling. However, when the system is under the anisotropic conditions, the reduction factors and their relation will change accordingly. The first-order reduction factors p and q of Ee system were further studied using the method of unitary transformation here. The relation between p and q proposed by Ham was investigated under both conditions of the linear coupling and the anisotropic effects. The result demonstrated that the relation of 2q-p=1 was only correct for the linear vibronic coupling, but not correct when the anisotropic effect was considered. This result suggested that the anisotropic effect influence considerably the reduction factors, and hence the physical properties of materials. Our method could be also applied to other JT systems, especially the highly symmetric JT systems involving C60 molecules.     

两株氧化葡萄糖酸杆菌静息细胞的催化性能比较

【目的】氧化葡萄糖酸杆菌是一种严格好氧的革兰氏阴性菌,能够立体选择性氧化多种羟基化合物生成相应的醛、酮或酸。【方法】本文将比较两株氧化葡萄糖酸杆菌DSM 2003和621H的静息细胞对甘油、乙二醇及乙醇的催化能力,并研究了溶氧对催化反应的影响。【结果】两株氧化葡萄糖酸杆菌氧化甘油的能力较相似,溶氧对这两株菌的甘油催化能力都有较大影响;氧化葡萄糖酸杆菌DSM 2003能够将乙二醇几乎全部氧化为羟基乙酸,副产物少,而621H转化相同量的底物只生成较少量的羟基乙酸,副产物多。氧化葡萄糖酸杆菌621H生产乙酸的能力也很低。【结论】两株氧化葡萄糖酸杆菌催化甘油生成二羟基丙酮的能力相当,但在催化醇生成酸的反应中,氧化葡萄糖酸杆菌DSM 2003更具优势。