酮康唑相关杂质国家标准物质的研制

目的:研制酮康唑相关杂质标准物质,提升国内酮康唑品种的质控标准。方法:对酮康唑杂质B、C、D、E进行合成与结构确证,并采用中国药典2010年版二部酮康唑有关物质检查方法测定各杂质的纯度,再根据各杂质的水分和炽灼残渣结果用质量平衡法确定首批各杂质国家标准物质的含量。最后采用标准曲线法测定了酮康唑诸杂质对酮康唑在220 nm检测波长下的相对校正因子。结果:研制的酮康唑杂质B、C、D、E标准物质与欧洲药典(EP 8.0版)中规定的结构一致。中国药典2010年版二部中酮康唑有关物质检查项下规定的色谱系统对酮康唑及其各杂质均能有效分离。以质量平衡法表示,本研究标定的酮康唑各杂质B、C、D、E的含量分别为95.2%、97.9%、98.5%和99.4%。各杂质对酮康唑的相对校正因子分别为1.13、1.08、0.94、1.01。结论:建立了首批酮康唑杂质B、C、D、E国家标准物质。     

Bisphenol A promotes X‐linked inhibitor of apoptosis protein‐dependent angiogenesis via G protein‐coupled estrogen receptor pathway

Bisphenol A (BPA), one of the high‐volume chemicals worldwide, has a core structure resembling that of natural estradiol. Recent evidence has demonstrated that exposure to BPA has a relationship with the risk of cancer. The objective of our study is to investigate the mechanisms underlying the pro‐angiogenic effects of BPA. We demonstrated that BPA markedly induces endothelial cell proliferation, migration and tube formation by activating endothelial nitric oxide synthase. BPA‐induced nitric oxide generation appeared to be associated with the X‐linked inhibitor of apoptosis protein (XIAP), which competes with endothelial nitric oxide synthase for caveolin‐1. BPA was shown to exert its pro‐angiogenic effect by upregulating XIAP expression via G protein‐coupled estrogen receptor (ER) activation but not via ERα or ERβ. Our data suggest that 100 nM BPA promote angiogenesis in a G protein‐coupled ER‐dependent genomic pathway, and provide a novel insight into the potential role of XIAP in mediating the pro‐angiogenic effects of BPA in endothelial cells. Copyright © 2015 John Wiley & Sons, Ltd.     

上海市闵行区2013年HIV-1分子流行病学研究

目的了解上海市闵行区艾滋病病毒(HIV)感染者特征和HIV基因亚型情况。方法上海市闵行区2013年首次确诊为HIV阳性的感染者血清,应用巢氏PCR扩增pol基因,使用HIV-Blast软件判定亚型;Mega 5.1软件将待分析序列与国际参考株序列比对,采用Neighbor-Joining(N-J)法构建系统进化树。应用SPSS 17.0软件,对计数数据采用χ2检验和Fisher′s精确概率计算法进行比较,P0.05为差异有统计学意义。结果有101例感染者纳入研究,成功扩增86例(85.15%)患者的pol基因。共发现6种亚型:CRF01_AE、CRF07_BC、RF08_BC、B、CC和CRF01_AE/B。CRF01_AE是最主要的亚型(60.47%,52/86),其次是CRF07_BC(27.91%,24/86)。感染者均由性途径传播,其中同性传播占63.95%(55/86),异性传播占36.05%(31/86)。结论同性传播是闵行区HIV感染的主要传播途径。流动人口聚集,带来的流行毒株多样化已经成为闵行区HIV的流行特点,应加强对HIV亚型变异的监测。     

Engineering substrate promiscuity in 2,4-dichlorophenol hydroxylase by in silico design

2,4-Dichlorophenol hydroxylase (2,4-DCP hydroxylase) is a key enzyme in the degradation of 2,4-dichlorophenoxyacetic acid in the hydroxylation step in many bacteria. Our previous study demonstrated that a 2,4-DCP hydroxylase (TfdB-JLU) exhibits broad substrate specificity for chlorophenols (CPs) and their homologues. In this study, TfdB-JLU has been engineered by rational design to further broaden its substrate scope towards CPs. We dissect the architectures of enzymes from oxidoreductase families to discover their underlying structural sources of substrate promiscuity. A homology model of TfdB-JLU has been built and docking experiments of this homology model with its natural substrate 2,4-DCP reveal that the phenyl rings of 2,4-DCP form strong interactions with residues His47, Ile48, Trp222, Pro316, and Phe424. These residues are found to be important for substrate binding in the active site. Then, the site-directed mutagenesis strategy has been applied for redesigning substrate promiscuity in TfdB-JLU. The TfdB-JLU-P316Q variant obtained shows a significant enhancement of activity (up to 3.4-fold) toward 10 CP congeners compared to wild-type TfdB-JLU. Interestingly, the active improvements of TfdB-JLU-P316Q toward CP congeners show significant difference, especially for active improvements of positional congeners such as 3-CP (1.1-fold) compared to 4-CP (3.0-fold), as well as 2,3-DCP (1.2-fold) compared to 2,5-DCP (3.4-fold). Structural analysis results indicate that the improvement in substrate promiscuity of the variant enzyme compared to the wild-type enzyme is possibly due to the increase of non-bonding interaction. The results suggest that exploiting enzyme–substrate promiscuity is promising, which would provide a starting point for designing and engineering novel biological catalysts for pollution removal.

In silico designed 2,4-DCP hydroxylase exhibits broader substrate promiscuity for chlorophenols than that of the wild-type enzyme.     

Photoluminescence mechanism and applications of Zn-doped carbon dots

Heteroatom-doped carbon dots (CDs) with excellent optical characteristics and negligible toxicity have emerged in many applications including bioimaging, biosensing, photocatalysis, and photothermal therapy. The metal-doping of CDs using various heteroatoms results in an enhancement of the photophysics but also imparts them with multifunctionality. However, unlike nonmetal doping, typical metal doping results in low fluorescence quantum yields (QYs), and an unclear photoluminescence mechanism. In this contribution, we detail results concerning zinc doped CDs (Zn-CDs) with QYs of up to 35%. The zinc ion charges serve as a surface passivating agent and prevent the aggregation of graphene π–π stacking, leading to an increase in the QY of the Zn-CDs. Structural and chemical investigations using spectroscopic and first principle simulations further revealed the effects of zinc doping on the CDs. The robust Zn-CDs were used for the ultra-trace detection of Hg²⁺ with a detection limit of 0.1 μM, and a quench mechanism was proposed. The unique optical properties of the Zn-CDs have promise for use in applications such as in vivo sensing and future phototherapy applications.

Zinc ions, acting as a surface passivating agent, prevented the aggregation of graphene π–π stacking and increased the quantum yield of Zn-carbon dots.     

Mechanical properties of epoxy nanocomposites filled with melamine functionalized molybdenum disulfide

In this work, a melamine functionalized molybdenum disulfide (M-MoS₂) was prepared and used as fillers to form epoxy (EP)/MoS₂ nanocomposites. The effects of molybdenum disulfide (MoS₂) and melamine functionalized molybdenum disulfide (M-MoS₂) loading on the mechanical properties of epoxy composites were investigated and compared. With only addition of 0.8 wt% M-MoS₂, the tensile strength and modulus of EP/M-MoS₂ nanocomposites showed 4.5 and 4.0 times increase over the neat epoxy. Interestingly, the elongation at break value of EP was also increased with the introduction of M-MoS₂ fillers. These properties could result from the good dispersion and strong interfacial adhesion of M-MoS₂ fillers and the EP matrix. Therefore, this work provides a facile way to produce of high-performance EP nanocomposites.

In this work, a melamine functionalized molybdenum disulfide (M-MoS₂) was prepared and used as fillers to form epoxy (EP)/MoS₂ nanocomposites. The mechanical properties of EP were significantly improved, even with very low M-MoS₂ addition.     

Improving microalgal growth by strengthening the flashing light effect simulated with computational fluid dynamics in a panel bioreactor with horizontal baffles

Biological CO₂ elimination by photosynthetic microalgae is a sustainable way to mitigate CO₂ from flue gas and other sources. Computational fluid dynamics was used to simulate algal cell movement with an enhanced flashing light effect in a novel panel bioreactor with horizontal baffles. Calculation results showed that the light/dark (L/D) cycle period decreased by 17.5% from 17.1 s to 14.1 s and that the horizontal fluid velocity increased by 95% while horizontal baffles were used under a 0.02 vvm air aeration rate and a microalgal concentration of 0.85 g L⁻¹. The probability of the L/D cycle period within 5–10 s increased from 27.9% to 43.6%, indicating a 56% increase when horizontal baffles existed. It was proved by experiments that the mass-transfer coefficient increased by 31% and the mixing time decreased by 13% under a 0.06 vvm air aeration rate when horizontal baffles were used, and the algal biomass yield increased by ∼51% along with the decrease in the L/D cycle period when horizontal baffles were used.

Biological CO₂ elimination by photosynthetic microalgae is a sustainable way to mitigate CO₂ from flue gas and other sources.     

In vivo detection of salicylic acid in sunflower seedlings under salt stress

Salicylic acid (SA) is an important phytohormone. It plays an essential role in regulating many physiological processes of plants. Most of the conventional methods for SA detection are based on in vitro processes. More attention should be paid to develop in vivo methods for SA detection. In this work, Pt nanoflowers and GO were simultaneously electrodeposited and reduced on a Pt wire microelectrode in one step. The Pt nanoflowers/ERGO modified Pt microsensor demonstrated high sensitivity and selectivity for SA. SA could be detected from 100 pM to 1 μM with a detection limit of 48.11 pM. Then this microsensor was used to detect SA in the stem of sunflower seedlings under different salt stresses in vivo. The result showed that with the increasing concentration of salt, SA levels decreased. Our result was also confirmed by UPLC-MS and gene expression analysis. To the best of our knowledge, this is the first report of in vivo detection of SA in plants using the Pt nanoflowers/ERGO modified Pt microelectrode. It is foreseeable that our strategy could pave the way for the in vivo detection of phytohormones in plants.

A Pt nanoflowers/ERGO modified Pt microelectrode was proposed to detect salicylic acid in plants under salt stress in vivo.     

纳米铜对微生物杀灭效果的试验观察

目的观察纳米铜粒子杀灭微生物效果。方法采用悬液定量杀菌试验方法,对纳米铜粒子进行了杀菌效果观察。结果浓度为2.0g/L纳米铜胶体分别作用5min和20min,对大肠杆菌和金黄色葡萄球菌杀灭率均大于99%;作用20min,对白色念珠菌杀灭率仅大于50%。浓度为5.0g/L纳米铜胶体作用2min,对大肠杆菌杀灭率大于99%;作用20min,对金黄色葡萄球菌和白色念珠菌杀灭率均大于99%。结论纳米铜粒子有良好的杀菌效果。