茴拉西坦/介孔二氧化硅的制备及释药性能

为了提高难溶性药物的溶出速率,采用水热合成法制备了MCM-41和SBA-15两种介孔二氧化硅载体材料,利用浸渍法将模型药茴拉西坦负载于两种载体上.利用扫描电子显微镜(SEM)、高分辨透射电子显微镜(HRTEM)、小角X射线衍射(XRD)、N2吸附-脱附、红外光谱(IR)、差热-热重(DTA-TG)对载药前后载体材料的表面形貌、粒径、孔径、孔容、比表面积、晶胞参数、骨架结构等进行测试,结果表明MCM-41和SBA-15具有相同的二维六方孔道结构,孔径及孔容分别为3.49 nm和6.67 nm,载药后的载药量分别为17;和22;,药物以非晶态装载于介孔孔道中没有影响介孔二氧化硅的骨架结构,但使介孔孔容及比表面积都有所降低.通过在不同pH溶出介质中负载于载体上的茴拉西坦与原料药晶体的溶出比较发现,两种载体均能够显著提高茴拉西坦的溶出速率.结合材料表征、载药量及溶出度综合比较,SBA-15载体的载药及释药性能均优于MCM-41载体.     

Three-site and five-site fixed-charge water models compatible with AMOEBA force field

In a typical biomolecular simulation using Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field, the vast majority molecules in the simulation box consist of water, and these water molecules consume the most CPU power due to the explicit mutual induction effect. To improve the computational efficiency, we here develop two new nonpolarizable water models (with flexible bonds and fixed charges) that are compatible with AMOEBA solute: the 3-site AW3C and 5-site AW5C. To derive the force-field parameters for AW3C and AW5C, we fit to six experimental liquid thermodynamic properties: liquid density, enthalpy of vaporization, dielectric constant, isobaric heat capacity, isothermal compressibility and thermal expansion coefficient, at a broad range of temperatures from 261.15 to 353.15 K under 1.0 atm pressure. We further validate our AW3C and AW5C water models by showing that they can well reproduce the radial distribution function g(r), self-diffusion constant D, and hydration free energy from the AMOEBA03 water model and the experimental observations. Furthermore, we show that our AW3C and AW5C water models can greatly accelerate (>5 times) the bulk water as well as biomolecular simulations when compared to AMOEBA water. Specifically, we demonstrate that the applications of AW3C and AW5C water models to simulate a DNA duplex lead to a threefold acceleration, and in the meanwhile well maintain the structural properties as the fully polarizable AMOEBA water. We expect that our AW3C and AW5C water models hold great promise to be widely applied to simulate complex bio-molecules using the AMOEBA force field.     

Efficient Detection of Environmental Estrogens Bisphenol A and Estradiol By Sensing System Based on AuNP-AuNP-UCNP Triple Structure

A sensing system based on AuNP-AuNP-UCNP triple structure for efficient detection of dual targets bisphenol A and estradiol was constructed. In the preparation of triple structure, the gold nanoparticles (AuNPs) and upconversion nanoparticles (NaYF₄: Yb, Er, Gd, UCNPs) were synthesized and surface modified. Then, the two nanoparticles and their aptamers were connected to form two kinds of optical fluorescent probes. A nucleic acid sequence that matches with two aptamers was designed, rendering the probes to get close based on the principle of complementary base pairing. On the basis of this, a sensing system with triple structure was prepared, and its connecting effect was characterized by TEM. With this system, dual targets of bisphenol A and estradiol were detected efficiently and conveniently through quantitatively determination by fluorescence and UV spectrophotometer. At the reaction temperature 30 °C and pH 7.8, this method exhibited good linear range for determination of bisphenol A and estradiol from 2 ng mL^–1 to 200 ng mL^–1 and from 10 ng mL^–1 to 150 ng mL^–1, with the limits of detection of 0.2 ng mL^–1 and 0.5 ng mL^–1, respectively. This sensing system with triple structure owned better specificity to structural and functional analogues, showed good repeatability and stability. What's more, this sensing system could be applied to actual water detection, with the recoveries of 86.1%–107.4%, and the relative standard deviation below 6.8%. This method shows promising applications in other environmental estrogens in water sample.     

Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non‐human Primates

While dose dependencies in pharmacokinetics and clearance are often observed in clinically used small molecules, very few studies have been dedicated to the understandings of potential dose‐dependent in vivo transport of nanomedicines. Here we report that the pharmacokinetics and clearance of renal clearable gold nanoparticles (GS‐AuNPs) are strongly dose‐dependent once injection doses are above 15 mg kg^?1: high dose expedited the renal excretion and shortened the blood retention. As a result, the no‐observed‐adverse‐effect‐level (NOAEL) of GS‐AuNPs was >1000 mg kg^?1 in CD‐1 mice. The efficient renal clearance and high compatibility can be translated to the non‐human primates: no adverse effects were observed within 90 days after intravenous injection of 250 mg kg^?1 GS‐AuNPs. These fundamental understandings of dose effect on the in vivo transport of ultrasmall AuNPs open up a pathway to maximize their biomedical potentials and minimize their toxicity in the future clinical translation.     

液相色谱–大气压化学电离串联质谱法测定油脂中9种胆固醇氧化物

建立一种准确测定油脂中9种胆固醇氧化物含量的同位素稀释液相色谱-串联质谱测定方法。向油脂样品中加入无水乙醇和60%氢氧化钾溶液,在室温下避光皂化22 h,使用乙醚-石油醚混合液(1∶1)作为提取溶液,采用液-液萃取方式提取目标物,再使用硅胶柱进行净化,采用5 mmol/L乙酸铵溶液与甲醇-乙腈混合液(1∶1)为双流动相梯度淋洗,使用Agilent ZORBAX SB-C18色谱柱分离,在大气压化学电离(APCI)正离子模式下,采用多反应监测模式内标法定量测定。在10~500μg/L范围内,9种胆固醇氧化物的质量浓度与色谱峰面积线性良好,相关系数(r2)均大于0.995,检出限均为0.5 mg/kg,在1,5 mg/kg两个添加水平时,加标回收率为71.2%~94.4%,相对标准偏差小于10%(n=6)。该方法满足动植物油脂中胆固醇氧化物含量测定需要。     

Hybrid discrete-continuum model of tumor growth considering capillary points

A hybrid discrete-continuum model of tumor growth in the avascular phase considering capillary points is established. The influence of the position of capillary points on tumor growth is also studied by simulation. The results of the dynamic tumor growth and the distribution of oxygen, matrix-degrading enzymes, and extracellular matrixconcentration in the microenvironment with respect to time are shown by graphs. The relationships between different oxygenated environments and the numbers of surviving, dead, proliferative, and quiescent tumor cells are also investigated.     

Effect of BaO on mineral structure and hydration behavior of phosphoaluminate cement

Journal of Thermal Analysis and Calorimetry - Phosphoaluminate cement (PAC) clinker was one new type of special cement, which exhibits good mechanical properties and durability. In this paper, the...