Discovery of small molecular inhibitors for interleukin-33/ST2 protein–protein interaction: a virtual screening,molecular dynamics simulations and binding free energy calculations

The interleukin-1 receptor like ST2 has emerged as a potential drug discovery target since it was identified as the receptor of the novel cytokine IL-33, which is involved in many inflammatory and autoimmune diseases. For the treatment of such IL-33-related disorders, efforts have been made to discover molecules that can inhibit the protein–protein interactions (PPIs) between IL-33 and ST2, but to date no drug has been approved. Although several anti-ST2 antibodies have entered clinical trials, the exploration of small molecular inhibitors is highly sought-after because of its advantages in terms of oral bioavailability and manufacturing cost. The aim of this study was to discover ST2 receptor inhibitors based on its PPIs with IL-33 in crystal structure (PDB ID: 4KC3) using virtual screening tools with pharmacophore modeling and molecular docking. From an enormous chemical space ZINC, a potential series of compounds has been discovered with stronger binding affinities than the control compound from a previous study. Among them, four compounds strongly interacted with the key residues of the receptor and had a binding free energy?<????20 kcal/mol. By intensive calculations using data from molecular dynamics simulations, ZINC59514725 was identified as the most potential candidate for ST2 receptor inhibitor in this study.

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On a Nonlinear Heat Equation Associated with Dirichlet–Robin Conditions

This article is devoted to the study a nonlinear heat equation associated with Dirichlet-Robin conditions. At first, we use the Faedo–Galerkin and the compactness method to prove existence and uniqueness results. Next, we consider the properties of solutions. We obtain that if the initial condition is bounded then so is the solution and we also get asymptotic behavior of solutions as t → + ∞. Finally, we give numerical results.     

Sol-gel microextraction phases for sample preconcentration in chromatographic analysis

Sol-gel technology provides a simple and reliable method for solid-phase microextraction (SPME) fiber preparation through in situ creation of surface-bonded organic-inorganic hybrid coatings characterized by enhanced thermal stability and solvent-resistance properties that are important for the coupling of SPME with GC and HPLC, respectively. The sol-gel coating technology has led to the development of an extensive array of sol-gel sorbent coatings for SPME. In this article, sol-gel microextraction coatings are reviewed, with particular attention on their synthesis, characterization, and applications in conjunction with GC and HPLC analyses. In addition, the development of sol-gel-coated stir bars, their inherent advantages, and applications are discussed. Next, the development and applications of sol-gel capillary microextraction (CME) in hyphenation with GC and HPLC is extensively reviewed. The newly emerging germania- and titania-based sol-gel microextraction phases look promising, especially in terms of pH and hot solvent stability. Finally, sol-gel monolithic beds for CME are reviewed. Such monolithic beds are in a position to greatly improve the extracting capabilities and enhanced sensitivity in CME.     

Symmetry factors of Feynman diagrams for scalar fields

We calculate the symmetry factors of diagrams for real and complex scalar fields in general form using an analysis of the Wick expansion for Green’s functions. We separate two classes of symmetry factors: factors corresponding to connected diagrams and factors corresponding to vacuum diagrams. The symmetry factors of vacuum diagrams play an important role in constructing the effective action and phase transitions in cosmology. In the complex scalar field theory, diagrams with different topologies can contribute the same, and the inverse symmetry factor for the total contribution is therefore the sum of the inverse symmetry factors.     

The regularity and exponential decay of solution for a linear wave equation associated with two-point boundary conditions

This paper is concerned with the existence and the regularity of global solutions to the linear wave equation associated the boundary conditions of two-point type. We also investigate the decay properties of the global solutions to this problem by the construction of a suitable Lyapunov functional. Finally, we present some numerical results.     

Interaction curves for vibration and buckling of thin-walled composite box beams under axial loads and end moments

Interaction curves for vibration and buckling of thin-walled composite box beams with arbitrary lay-ups under constant axial loads and equal end moments are presented. This model is based on the classical lamination theory, and accounts for all the structural coupling coming from material anisotropy. The governing differential equations are derived from the Hamilton’s principle. The resulting coupling is referred to as triply flexural–torsional coupled vibration and buckling. A displacement-based one-dimensional finite element model with seven degrees of freedoms per node is developed to solve the problem. Numerical results are obtained for thin-walled composite box beams to investigate the effects of axial force, bending moment, fiber orientation on the buckling loads, buckling moments, natural frequencies and corresponding vibration mode shapes as well as axial-moment–frequency interaction curves.     

An extension of Krasnoselskii’s fixed point theorem and its application to nonlocal problems for implicit fractional differential systems with uncertainty

The traditional Krasnoselskii’s fixed point theorem in Banach spaces does not reproduce the rich and varied forms of operator equations in abstract spaces which are not linear structure. Consequently, its applications to integral equations and differential equations have met many obstacles. The present alternative Krasnoselskii’s fixed point theorem in generalized semilinear Banach spaces overcomes this deficiency and opens up for profitable investigation such as differential systems with uncertainty. An application to the existence of solutions of nonlocal problems for fuzzy implicit fractional differential systems under Caputo generalized Hukuhara differentiability with demonstrated example is given to validate the effectiveness of our theoretical results.     

Determination of 4-nonylphenol in water samples using 4-(2,6-dimethylhept-3-yl)phenol as new internal standard

A new method for determining the endocrine disrupting substance 4-nonylphenol (technical grade = mixture of isomers, 4-NP) from water samples has been developed by using 4-(2,6-dimethylhept-3-yl)phenol (4-sec-NP) as model compound. This branched monoalkylphenol is shown to serve as internal standard (IS) for the determination of technical 4-nonylphenol. To the best of our knowledge, 4-(2,6-dimethylhept-3-yl)phenol (racemic mixture) is a newly synthesized 4-nonylphenol isomer and has not been described elsewhere. Recoveries have been determined by analyzing spiked water samples from distilled water, river water and wastewater. Following acetylation, the compounds were enriched via solid phase extraction (SPE). Analyses of the compounds were performed by capillary column gas chromatography/mass spectrometry (GC/MS), operating in selected ion-monitoring (SIM) mode. The recovery of technical 4-NP using either the newly prepared 4-sec-NP or 4-n-nonylphenol (4-n-NP) as IS have been compared. 4-sec-NP showed slightly better results. However, in the first series of experiments using wastewater, the yields for the derivatization of the two standard compounds were remarkably different. The yield for derivatization of 4-n-NP was approximately 20%, probably due to the difficult matrix of the wastewater. In contrast, the yield for the derivatization of 4-sec-NP was considerably higher (approximately 63%). This problem can be solved by increasing the concentration of the reagent used for derivatization. For better control of the clean-up process, we recommend application of 4-sec-NP as internal standard, at least in water samples with complex matrices (e.g., high content of hydroxylated compounds).