Biocatalytic Gelation of Silica in the Presence of a Lipase

The effect of the lipase from Burkholderia cepacia (previously known as Pseudomonas cepacia) on the gelation kinetics and gel structure was examined on a type of silica aerogel made from a mixture of methyltrimethoxysilane and tetramethoxysilane. For this purpose, gels were made with increasing concentrations of lipase in otherwise constant other conditions (pH, water and Si precursors concentrations). It was found that the enzyme accelerated the gelation kinetics, hence was participating in some way to the hydrolysis of the silica precursor. The structure of the gel was simultaneously modified to produce an increasing proportion of Q⁴ silicon sites.     

Effect of Acridine Derivatives on the Dissolution of α-Brass

Acridine derivatives as inhibitors of diffusion- and diffusion–kinetic-controlled dissolution of -brass are studied. Inhibition coefficients of the dissolution and its steps correlate with parameters of a standard reaction series and wavelengths of the longest-wave absorption band of the electronic spectrum.     

β-CD衍生物的反胶束微型反应器模拟酶催化氧化研究

利用我们设计的反胶束微型反应器，对两种β-环糊精（β-Cyclodextrin,简写β-CD）衍生物，在不同溶剂中催化苯甲醇氧化成苯甲醛和苯甲酸的反应动力学进行了研究，结果表明，该反应器的催化效率均相催化反应高，反应的后处理较简单，且较少污染物产生。     

Miniaturization of solid-phase reactors for on-line post-column derivatization in narrow-bore liquid chromatography

Summary The use of solid-phase reactors for post-column derivatization in narrow-bore HPLC (1.0mm i.d. analytical columns) is evaluated. Two systems are described, viz. for the determination of N-methylcarbamate pesticides and for that of urea and ammonia. The solid-phase reactor is packed with a strong anion exchange resin and urease immobilized on silica, respectively, to effect the catalytic hydrolysis of the solutes eluting from the analytical column. In both systems, the hydrolysis product is reacted with o-phthalaldehyde followed by fluorescence monitoring. Analytical data are presented and band broadening from various parts of the reaction detector system is discussed. An on-line trace enrichment procedure via a micro precolumn is descried for the trace level determination of N-methylcaramates in surface water samples.     

Stability of Surface Mechanisms with Three Species and Mass-Action Kinetics

The linear stability problem for surface mechanisms with free sites and two adsorbed species is investigated under the assumptions of mass action (Langmuir) surface kinetics, fast mass transport to and from the surface, and a conservation condition. The results also apply to enzyme kinetics for systems with a single enzyme occurring in the free form and two combined forms, and with fast mass transport of the substrates and products. Mechanisms are classified according to their stability and the presence or absence of complex eigenvalues, and specific reactions with numerical values of the rate constants and surface concentrations are given to illustrate the results. Some mechanisms, e.g., proportionate reactions, are shown to be stable for all values of the rate constants and stoichiometric coefficients. The two most common types of mechanisms, namely sequential mechanisms and the simple Langmuir–Hinshelwood mechanism (one adsorbate per site), are always stable. The possibility of complex eigenvalues arises for sequential mechanisms (providing a counterexample to a condition for real eigenvalues given previously in the literature). More general Langmuir–Hinshelwood mechanisms can be unstable (e.g., those in which one adsorbate occupies two sites). Some results are generalized to mechanisms with three or more adsorbed species, and global stability is investigated using monotone dynamical systems theory.     

甲烷单加氧酶化学模拟研究进展

本文综述了近年来对甲烷单加氧酶进行结构模拟和催化功能模拟研究工作的进展情况。就结构模拟而言，已合成和表征了很多模型化合物，并与天然酶进行了比较，获得了一些能较好地再现天然酶活性中心结构特征和诺学特征的模型化合物。在催化功能模拟方面，少数体系能将环己烷等经类转化为醇类或酮类。而真正能把甲烷转化成甲醇的体系仅有一例报道，这方面的工作比较薄弱，尚待加强。     

Beneficial Effects of Laurel (Laurus nobilis L.) and Myrtle (Myrtus communis L.) Extract on Rat Health

Polyphenols of Laurel and Myrtle exhibit structural diversity, which affects bioavailability, metabolism, and bioactivity. The gut microbiota plays a key role in modulating the production, bioavailability and, thus the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. The aim of this study was to investigate whether the polyphenolic components of Laurel and Myrtle aqueous extract have beneficial effects on rat health. The growth of lactic acid bacteria (LAB), β-glucuronidase, β-glucosidase, β-galactosidase activity, pH value, body weight change and food efficacy ratio after intragastric treatment of rats with Laurel and Myrtle extract at doses of 50 and 100 mg/kg for two weeks were investigated. The endogenous populations of colonic probiotic bacteria (Lactobacilli and Bifidobacteria) were counted on selective media. According to the obtained data, Laurel extract in the applied dose of 50 and 100 and Myrtle extract (100 mg/kg) positively affects the rats health by increasing the number of colonies of Lactobacilli and Bifidobacteria compared to the control group, causes changes in glycolytic enzymatic activity and minor change in antioxidative tissue activity. In addition, high doses of Laurel increase food efficiency ratio, while Myrtle has the same effect at a lower dose.     

Nek2 Kinase Signaling in Malaria,Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development

Cell cycle kinases represent an important component of the cell machinery that controls signal transduction involved in cell proliferation, growth, and differentiation. Nek2 is a mitotic Ser/Thr kinase that localizes predominantly to centrosomes and kinetochores and orchestrates centrosome disjunction and faithful chromosomal segregation. Its activity is tightly regulated during the cell cycle with the help of other kinases and phosphatases and via proteasomal degradation. Increased levels of Nek2 kinase can promote centrosome amplification (CA), mitotic defects, chromosome instability (CIN), tumor growth, and cancer metastasis. While it remains a highly attractive target for the development of anti-cancer therapeutics, several new roles of the Nek2 enzyme have recently emerged: these include drug resistance, bone, ciliopathies, immune and kidney diseases, and parasitic diseases such as malaria. Therefore, Nek2 is at the interface of multiple cellular processes and can influence numerous cellular signaling networks. Herein, we provide a critical overview of Nek2 kinase biology and discuss the signaling roles it plays in both normal and diseased human physiology. While the majority of research efforts over the last two decades have focused on the roles of Nek2 kinase in tumor development and cancer metastasis, the signaling mechanisms involving the key players associated with several other notable human diseases are highlighted here. We summarize the efforts made so far to develop Nek2 inhibitory small molecules, illustrate their action modalities, and provide our opinion on the future of Nek2-targeted therapeutics. It is anticipated that the functional inhibition of Nek2 kinase will be a key strategy going forward in drug development, with applications across multiple human diseases.     

Approach for the Design of Covalent Protein Kinase Inhibitors via Focused Deep Generative Modeling

Deep machine learning is expanding the conceptual framework and capacity of computational compound design, enabling new applications through generative modeling. We have explored the systematic design of covalent protein kinase inhibitors by learning from kinome-relevant chemical space, followed by focusing on an exemplary kinase of interest. Covalent inhibitors experience a renaissance in drug discovery, especially for targeting protein kinases. However, computational design of this class of inhibitors has thus far only been little investigated. To this end, we have devised a computational approach combining fragment-based design and deep generative modeling augmented by three-dimensional pharmacophore screening. This approach is thought to be particularly relevant for medicinal chemistry applications because it combines knowledge-based elements with deep learning and is chemically intuitive. As an exemplary application, we report for Bruton’s tyrosine kinase (BTK), a major drug target for the treatment of inflammatory diseases and leukemia, the generation of novel candidate inhibitors with a specific chemically reactive group for covalent modification, requiring only little target-specific compound information to guide the design efforts. Newly generated compounds include known inhibitors and characteristic substructures and many novel candidates, thus lending credence to the computational approach, which is readily applicable to other targets.