纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Regulation of the NADH supply by nuoE deletion and pncB overexpression to enhance hydrogen production in Enterobacter aerogenes

In this study, seven mutants from E. aerogenes IAM1183 wildtype were constructed via different strategies including deletion of lactate dehydrogenase, disruption of NADH dehydrogenase gene nuoE, overexpression of pncB and a combination of both to regulate of the NADH supply to enhance hydrogen production. Compared with the parental strain, the hydrogen yields of the strains IAM1183-E, IAM1183-L and IAM1183-EL increased by 23.3, 81.7 and 97.9%, respectively. When the pncB gene was overexpressed, the hydrogen yield of IAM1183/P, IAM1183-E/P, IAM1183-L/P and IAM1183-EL/P increased by 39.0, 6.5, 5.9, and 5.1% compared with the respective original knockout strains. Among them, the total hydrogen yield of strain IAM1183-EL/P with highest production efficiency was 58% higher than IAM1183. Further metabolite analysis indicated that the knockout of nuoE and ldhA, combined with the overexpression of pncB, resulted in a redistribution of the metabolic fluxes in E. aerogenes, which led to an improvement of the hydrogen yield.     

Characteristic tryptic peptides and gelling properties of porcine skin gelatin affected by thermal action

Thermal action in extraction process had effects on characteristic tryptic peptides identification and gelling properties of porcine gelatin. SDS-PAGE, HPLC-LTQ/Orbitrap high-resolution mass spectrometry, texture analyser and rheometer were used to evaluate collagen depolymerisation degree, characteristic tryptic peptides and gelling properties of gelatins prepared in various thermal actions. Results showed that with increasing temperature and time, depolymerisation degree enlarged, while gel strength, gelling and melting temperature decreased. Mass spectra showed that 47 and 49 common characteristic tryptic peptides were identified in gelatins extracted at 50 °C and 100 °C with various times, respectively. Moreover, 34 common characteristic tryptic peptides were identified in all gelatin samples. Further comparison between this work and our previous investigations yielded 20 common characteristic tryptic peptides, which stably exist in various thermal actions. These common characteristic tryptic peptides may be very helpful for the accurate authentication of porcine gelatin.     

A novel method of shrimp blanching by CO2 heat pump: Quality,energy, and economy analysis

To reduce the energy consumption of the shrimp blanching process and improve the economic value of the blanched product, a transcritical CO₂ heat pump blanching system (THPB system) was designed in this paper. The trends of astaxanthin were investigated at atmospheric pressure near boiling temperature, combined with the color and structural properties of shrimp samples, and the optimal blanching times of 270 s and 240 s were obtained at 90°C and 95°C, respectively. In contrast to the fuel blanching system (FB system) at 100°C, the annual standard coal consumption of the THPB system with 90°C blanching is decreased by 79%, and the annual operating cost can be saved by CNY 63,800, with a payback period of about 3.13 years.Industrial relevanceBlanching is one of the effective ways to prolong the shelf life of shrimp. However, the research on the blanching time and temperature of shrimp is not comprehensive. In addition, the traditional fuel blanching process has high energy consumption and pollution, and can no longer meet the quality requirements of the modern food processing industry. Heat pump has been shown to have better performance in food drying, but it is less used in blanching. The information presented in this study may provide other insights into food processing.     

一株产羧酸酯酶菌的鉴定及酯酶特征的研究

目的:鉴定中国白酒发酵过程中的微生物种类，研究关键酶的特征与作用机制有利于提高白酒的优质品率。方法:本研究用形态学和生理学、16S rRNA、gyr B基因和antiSMASH分析的方法对酒曲中的一株微生物进行了验证；对该菌株的特性进行了研究，采用分子建模的方法获得了羧酸酯酶的3D模型，用分子对接的方法探讨了该菌株的羧酸酯酶的机理。结果:该菌株为产羧酸酯酶的革兰氏阴性菌Pb1（MW580690）；该菌株呈现典型的S型生长曲线，产物曲线为S型，羧酸酯酶活化最优pH范围为5.0~9.0。分子对接结果显示Phe21A为该酶具有催化活性的主要氨基酸，水解三丁酸甘油酯为丁酸和甘油。分子对接结果显示三丁酸甘油酯经过构象变化被转移到催化中心后，进一步被加工；酶的亲水性和疏水性的相互作用表面有利于配体向下转移，进而从疏水性通道释放产物到的酶表面。结论:产羧酸酯酶的菌株为贝莱斯芽胞杆菌，并为羧酸酯酶水解三丁酸甘油酯类物质的底物识别、转移和催化机理提供了新的见解。     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

The effect of particle size distribution on the microstructure and properties of Al2O3 ceramics formed by stereolithography

Stereolithography (SL) shows advantages for preparing alumina-based ceramics with complex structures. The effects of the particle size distribution, which strongly influence the sintering properties in ceramic SL, have not been systematically explored until now. Herein, the influence of the particle size distribution on SL-manufactured alumina ceramics was investigated, including bending strength at room temperature, post-sintering shrinkage, porosity, and microstructural morphology. Seven particle size distributions of alumina ceramics were studied (in μm/μm: 30/5, 20/3, 10/2, 5/2, 5/0.8, 3/0.5, and 2/0.3); a coarse:fine particle ratio of 6:4 was maintained. At the same sintering temperature, the degree of sintering was greater for finer particle sizes. The particle size distribution had a larger influence on flexural strength, porosity and shrinkage than sintering temperature when the particle size distribution difference reached 10-fold but was weaker for 10 μm/2 μm, 5 μm/2 μm and 5 μm/0.8 μm. The sintering shrinkage characteristics of cuboid samples with different particle sizes were studied. The use of coarse particles influenced the accuracy of small-scale samples. When the particle size was comparable to the sample width, such as 30 μm/5 μm and 5 mm, the width shrinkage was consistent with the height shrinkage. When the particle size was much smaller than the sample width, such as 2 μm/0.3 μm and 5 mm, the width shrinkage was consistent with the length shrinkage. The results of this study provide meaningful guidance for future research on applications of SL and precise control of alumina ceramics through particle gradation.     

A robust method for axis identification

The present paper proposes a new method for axis identification in discrete axially symmetrical geometric models. This method is based on-a-never-used-before property of the axially symmetrical surfaces for which the symmetry line of any section curve of the surface (or of a portion of it in the case of an incomplete axially symmetrical surface) always intersects the axis of symmetry of the surface. Thus the working principle of the method makes it very robust to local defectiveness, measurement noise and outliers.In order to compare it with the most cited methods presented in literature, several types of tests have been designed and performed. The robustness of those methods, on the one hand, has been evaluated by defining the Statistical Confidence Boundary at 1σ confidence level. The trueness of the method, on the other hand, has been evaluated on geometric models obtained by measuring real objects. The high robustness, which characterizes the proposed method, makes it particularly suitable for product geometric inspection where high accuracy is required.