A modern pollen record from the central Gulf of California

As one facet of an effort to tie the pollen record of central Gulf of California deep cores to modern analogs, pollen was analyzed in the uppermost 150-200 years of varved core 7807-1410 taken nearby. Sampling at 2- to 8-year resolution yielded a noncomplacent record, suggesting pollen in these sediments may be a potential high resolution proxy record of short-term climatic events. The pollen spectrum as a whole matches that of upper-most DSDP Site 480 (means of all samples). Lack of a ratio or influx shift following damming of local rivers and a surplus of low-spine Compositae pollen relative to mainland sites support Baumgartner's theory that terrigenous influx to the site is largely aeolian and also suggest that a significant fraction of the pollen influx may come from Baja California.

Stable isotopes in paleosols and origins of the Asian monsoon

The stable isotopic composition of buried soil carbonate and organic matter from northern Pakistan and Nepal can be used to reconstruct aspects of the paleoecology of riverine floodplain ecosystems over the past 17 Myr. Probable dry woodland dominated the floodplain biomass of large rivers ancestral to the modern Indus and Ganges up to 7.3 Myr. Between 7.3 and about 6 Myr, tropical grasses gradually displaced woodland and have dominated floodplain biomasses to the present. The paleovegetational transition beginning about 7.3 Myr likely signals the onset of the strongly seasonal precipitation pattern that typifies the monsoonal climate of the region today. One possible analog to the dry woodland soils of the Miocene are found under the Sal woodlands of the northern Indian subcontinent, while undisturbed modern analogs to the Plio-Pleistocene floodplain grasslands can still be found in the Chitwan area of southern Nepal.

Anti HIV-1 agents 5: Synthesis and anti-HIV-1 activity of some N-arylsulfonyl-3-acetylindoles in vitro

In continuation of our program aimed at the discovery and development of compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 21N-arylsulfonyl-3-acetylindole analogs (2a-u) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro. Among of all the analogs, several compounds exhibited significant anti-HIV-1 activity, especially N-phenylsulfonyl-3-acetyl-6-methylindole (2j) and N-(p-ethyl)phenylsulfonyl-3-acetyl-6-methylindole (2n) showed the most potent anti-HIV-1 activity with EC50 values of 0.36 and 0.13 mu g/mL, and TI values of >555.55 and 791.85, respectively. It demonstrated that introduction of the acetyl group at the 3-position of N-arylsulfonyl-6-methylindoles could generally lead to the more potent analogs. (C) 2010 Elsevier Ltd. All rights reserved.

PNA(T).DNA(AT) triplexes with Hoogsteen base pairing are more favorable

Peptide nucleic acids (PNAs) are nucleic acid analogs with the deoxyribose phosphate backbone replaced by pseudo-peptide polymers to which the nucleobases are linked. The achiral, uncharged and rather flexible properties of the peptide backbone permit peptide nucleic acids more potential than oligonucleotides in application to antisence and antigenic reagents. The process of PNA binding to DNA duplex and forming triplex is the first step of PNA interacting with PNA. But there are no PNA.2DNA triplex crystal data up to date and little has been reported on the structure features and the force of the PNA.2DNA triplex. In this work, PNA(T).DNA(AT) triplexes are successfully built and the structures and forces to stabilize the triplex after optimizations and molecule dynamics are systematically examined, which are expected to aid in the application of PNAs as anticense and antigene agents.

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues.

Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function.

虎眼万年青化学成分及抗癌药与DNA相互作用的电喷雾质谱研究

首先，对虎眼万年青中化学成分进行了分离提取研究，采用柱层析和薄层层析等方法，并利用电喷雾质谱技术跟踪洗脱流分，首次从虎眼万年青氯仿提取物中分离得到两个新化合物。其一为单菇内酷loliolide，通过FT－ICRMS高分辨质谱、IR和NMR等手段对其结构进行了确定，并通过IHNMR和旋光法确定了其绝对构型。此外，还利用电喷雾多级串联质谱（ESI一MSn）技术对其质谱裂解规律进行了系统研究，其分析结果与NMR解析结果完全一致，建立了该类化合物结构解析的简便、快速的质谱新方法；另一化合物为生物碱类化合物，采用电喷雾多级串联质谱技术对其质谱裂解规律进行了详细研究，并对其结构进行了初步推断，进一步的NMR结构确定正在进行中。其次，对虎眼万年青多糖成分进行了分离提取研究，并结合体外抑瘤活性评价实验，确定了两种具有抑瘤生物活性的多糖成分OC一2一1一c和OC一2一卜d。并通过SDS凝胶电泳和糖基组成分析，初步证明了虎眼万年青中的活性多糖成分为阿拉伯半乳糖蛋白（AGPs），为进一步研究虎眼万年青抗肿瘤活性提供了基础数据和理论指导。此外，还对虎眼万年青中的微量元素及其溶出率进行了初步的研究，研究结果表明，其水煎液中Cu/Zn比值明显低于癌症患者血清中的Cu/Zn比值，因此，虎眼万年青可能有助于调节癌症患者体内的Cu、Zn平衡，从而达到抗癌目的；而虎眼万年青中Se、Ge含量很低，不能作为两种微量元素的药用来源。为了进一步研究抗癌药物的作用机理，我们采用电喷雾质谱技术，对三种临床疗效较好的抗癌药物与DNA相互作用进行了系统的研究，确定了复合物的化学计量比及其结合的特异性，并利用竞争实验方法，研究了抗癌药物的相对结合强度。质谱实验结果与液相行为完全一致，其中抗癌药物米托葱醒为首次利用质谱进行研究。最后，采用电喷雾质谱技术，对硝酸盐离子簇合物进行了详细研究，发现了双电荷簇合物离子，并且在离子簇合物中还发现了魔数规律的存在。利用电喷雾多级串联质谱技术，研究了双电荷簇合物离子的质谱裂解规律，并对其稳定性进行了分析。此外，还讨论了溶液浓度和毛细管温度对离子簇合物形成的影响规律。

两种银莲花属植物的化学成分研究

本学位论文由5 章组成。第1 章报道了两头尖中三萜皂苷类化合物的全扫描电喷雾多级质谱分析及银莲花素A 的电喷雾质谱裂解规律；第2 和3 章报道了两种银莲花属药用植物化学成分的研究结果；第4 章报道了银莲花素A 的化学结构修饰及其对一种蛋白酪氨酸磷酸酯酶（PTP-1B）的抑制活性；第5 章综述了电喷雾质谱在皂苷类化合物结构鉴定中的应用进展。 第1 章报道了运用全扫描电喷雾多级质谱对两头尖中三萜皂苷类化合物的快速定性检测，共检测出18 个准分子离子峰，根据多级质谱数据并结合文献报道，对其中的15 个准分子离子峰进行了归属，并区分了一些同分异构体；更有意思的是，发现了3 个未见文献报道的三萜皂苷类化合物。根据它们的多级质谱数据，对其结构分别进行了初步解析。本章同时对银莲花素A 特殊的质谱裂解途径通过衍生物制备及其质谱分析进行了确认。 第2 和3 章，分别报道了两头尖和打破碗花花中水溶性多糖苷的分离纯化和结构鉴定。采用D101 大孔树脂和反复硅胶柱层析等分离手段，从两头尖水溶性部分分离得到8 个三萜皂苷类化合物，通过红外、电喷雾质谱和核磁共振等现代谱学方法，并结合传统的化学手段鉴定了它们的结构，其中4 个化合物为新化合物，分别命名为多被银莲花皂苷19、多被银莲花皂苷20、多被银莲花皂苷21和多被银莲花皂苷22。从打破碗花花水溶性部位分离得到6 个三萜皂苷类化合物，通过现代谱学手段，并结合传统的化学方法对它们进行了鉴定，其中1 个为新化合物，命名为打破碗花花苷H。 第4 章报道了以银莲花素A 及其同系物为先导化合物，进行化学结构修饰并对修饰产物进行广泛的生物活性筛选，发现在银莲花素A 及其同系物的结构中引入一些酸性基团后，其生物活性发生了变化，一些修饰产物显示出很强的PTP-1B 抑制作用，提示这些化合物有可能用于治疗II 型糖尿病。 第5 章综述了电喷雾多级质谱用于皂苷类化合物结构鉴定的研究进展。 This dissertation composes of five chapters. The first chapter elaborates the detection and qualification of the triterpenoidal saponins in Anemone raddeana by positive and negative full scan ESI-MSn. This part also reports the special fragmentation pathway of Raddeanin A by ESI-MS/MS. The second and third chapters present the phytochemical investigation of two medicinal plants from Anemone. The fourth part dwells on the structure modification of Raddeanin A and their inhibitory activity against PTP-1B. The last part is a review on the progress in the application of ESI-MSn in the structure identification of saponins. The first chapter reports the application of full scan ESI-MSn for fast analysis of triterpenoid saponins in Anemone raddeana. Eighteen quasi- molecular ion peaks were detected in the positive full scan ESI-MS and fifteen of them were identified by analysis of their tandem mass spectral data in the negative ion mode. Several isomers were differentiated. More interesting, three unreported triterpenoid saponins in this medicinal plant were detected and their structures were deduced according to the dissociation pathway of the known triterpenoidal saponins. This chapter also confirms the special fragmentation pathway of Raddeanin A by its derivative and the mass spectral analysis. The second and third chapters expatiate on the isolation and identification of the chemical constituents from A. raddeana and A. hupehensis. Eight compounds were isolated from the roots and stems of A. raddeana by methanol extraction and repeated column chromatography (including D101 and silica gel), and their structures were determined on the basis of IR, ESI-MS, NMR and chemical methods (including acid hydrolysis and alkaline saponification). Among them, four are new triterpenoid saponins and named as Raddeanoside R19, Raddeanoside R20, Raddeanoside R21 and Raddeanoside R22. Six compounds were isolated from the whole plants of A. hupehensis by the same methods as above, and their structures were also determined with the same way. One of them was confirmed to be new triterpenoid saponins and named as hupehensis saponin H. In the fourth chapter, in order to look for new active compounds, the structure of Raddeanin A and its analogs were modified. It was found that the modified products exhibited obvious inhibitory activity against PTP-1B when several acid groups were introduced. The fifth chapter summarizes the progress on the application of ESI-MSn in the structure identification of saponins.

Direct characterization of bitter acids in a crude hop extract by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry

The applicability of on-line coupling of reversed-phase high-performance liquid chromatography to atmospheric pressure ionization tandem mass spectrometry for the separation and characterization of hop acids mixture from the crude extract of Humulus lupulus was investigated. The solvent system consisting of acetonitrile-aqueous formic acid was used to give proper separation of the six main hop bitter acids within 30 min. Further structural information about the components was acquired by collision-induced dissociation (CID). On the basis of analyses of the fragmentation patterns of the major alpha- and beta-bitter acids respectively, identification of the minor ones was performed using selected reaction monitoring (SRM) with a group of qualitatively relevant selected precursor-product ion transitions for each bitter acid in a single high performance liquid chromatography (HPLC) run. Using this technique, six minor hop acids, including "adprelupulone" observed for the first time in natural resources, were detected along with the six major acids. This hyphenated techniques provides potency for rapid qualitative determination of analogs and homologs in mixtures. (C) 2004 American Society for Mass Spectrometry.

On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles

We describe here the chemical synthesis and in vitro drug delivery response of polyethylene glycol (PEG)-functionalized magnetite (Fe3O4) nanoparticles, which were activated with a stable ligand, folic acid, and conjugated with an anticancer drug, doxorubicin. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared spectroscopy. The drug-release behavior of PEG-functionalized and folic acid-doxorubicin-conjugated magnetic nanoparticles was characterized by two stages involving an initial rapid release, followed by a controlled release. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning

The release behavior of a water-soluble small molecule drug from the drug-loaded nanofibers prepared by emulsion-electrospinning was investigated. Doxorubicin hydrochloride (Dox), a water-soluble anticancer agent, was used as the model drug. The laser scanning confocal microscopic images indicated that the drug was well incorporated into amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA) diblock copolymer nanofibers, forming "core-sheath" structured drug-loaded nanofibers.

Synthesis and characterization of Prussian blue@platinum nanoparticle hybrids from a mixture solution of platinum nanocatalyst and ferric ferricyanide

In the present study, platinum nanoparticles modified with Prussian blue (PB) have been synthesized by a heterogeneous catalytic reaction. Transmission electronic microscopy (TEM) confirmed the deposition of nanoclusters around the Surfaces of platinum particles, and spectroscopic studies verified that the molecular composition of the nanoclusters was dominantly PB and a minority of platinum ferricyanide. Thus, it was shown that the platinum particles behaved not only as catalysts for the growth of PB, but also as a reactant to generate a PB analogue complex.

Monodisperse mesoporous superparamagnetic single-crystal magnetite nanoparticles for drug delivery

In this contribution, we report a facile, gram-scale, low-cost route to prepare monodisperse superparamagnetic single-crystal magnetite NPs with mesoporous structure (MSSMN) via a very simple solvothermal method. The formation mechanism of MSSMN is also discussed and we think that Ostwald ripening probably plays an important role in this synthesis process. It is also interestingly found that the size and morphology of mesoporous Fe3O4 NPs can be easily controlled by changing the amount of NaOH and 1,2-ethylenediamine (ETH). Most importantly, the MSSMN can be used as an effective drug delivery carrier. A typical anticancer drug, doxorubicin (Dox), is used for drug loading, and the release behaviors of Dox in two different pH solutions are studied. The results indicate that the MSSMN has a high drug loading capacity and favorable release property for Dox; thus, it is very promising for the application in drug delivery.

Gold nanoparticle probes

Depending on their size, shape. degree of aggregation and nature of the protecting organic shells on their surface, gold nanoparticles (AuNPs) can appear red, blue and other colors and emit bright resonance light scattering of various wavelengths. Because of this unique optical property. AuNPs have been extensively explored as probes for sensing/imaging a wide range of analytes/targets, such as heavy metallic cations, nucleic acids, proteins, cells, etc. Since their initial discovery, novel synthetic methods have led to precise control over particle size, shape and stability, thus allowing the modification of a wide variety of ligands on the AuNP surfaces to meet different experimental conditions. This review discusses the synthesis and applications of functionalized AuNPs in chemical sensing and imaging.

Interactions of Rare Earth-Amino Acid Complexes with Nucleic Acids

A number of metal-based anticancer drugs are designed to target nucleic acids. Therefore, the elucidation of their interactions with nucleic acids is important for rational design of new anticancer agents with high selectivity and low toxicity, which has been received much attention in this field. Lanthanide complexes have the potential to be therapeutic agents due to their unique magnetic, optical, electronic, and coordinate characteristics. However, lanthanide ions are easy to hydrolysis under physiological pH, which makes it difficult to study rare earth complexes nucleic acids selectivity. Recent studies have shown that natural amino acids can form stable complexes with rare earth ions under near physiological condition and the complexes have high solubility. This review summarizes the current progress in rare earth-amino acid complexes binding to nuclelic acids and their selectivity.

Folate-Conjugated Micelles and Their Folate-Receptor-Mediated Endocytosis

A folate-conjugated copolymer PEG-PLA-PLL/folate was synthesized and mixed with pure PEG-PLA-PLL and a fluorescent model drug mFITC to prepare folate-conjugated micelles. The distribution of micelles was studied on cancer-cell-bearing mice via frozen slicing. The results show that mFITC is successfully encapsulated into folate(+) and folate(-)micelles; PEG-PLA-PLL micelles the latter can be internalized by both HeLa and CHO cells without selectivity due to their cationic surface charges, while folate(+)micelles exhibit more preferential endocytosis by HeLa cells than by CHO cells. The folate(-)micelles showed retention in both organs and tumors. The folate(+)micelles are a promising active targeting drug delivery system for FR over-expressing cells and they accumulate in tumor beds.