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Rheumatoid arthritis (RA) is a chronic immune-related condition, primarily of joints, and is highly disabling and painful. The inhibition of Janus kinase (JAK)-related cytokine signaling pathways using small molecules is prevalent nowadays. The JAK family belongs to nonreceptor cytoplasmic protein tyrosine kinases (PTKs), including JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase 2). JAK1 has received significant attention after being identified as a promising target for developing anti-RA therapeutics. Currently, no crystal structure is available for JAK1 in complex with the next-generation anti-RA drugs. In the current study, we investigated the mechanism of binding of baricitinib, filgotinib, itacitinib, and upadacitinib to JAK1 using a combined method of molecular docking, molecular dynamics simulation, and binding free energy calculation via the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) scheme. We found that the calculated binding affinity decreases in the order upadacitinib > itacitinib > rs with better affinity.Many industrial processes operate at elevated temperatures or within broad pH and salinity ranges. However, the utilization of enzymes to carry out biocatalysis in such processes is often impractical or even impossible. Laccases (EC 1.10.3.2), which constitute a large family of multicopper oxidases, have long been used in the industrial setting. Although fungal laccases are in many respects considered superior to their bacterial counterparts, the bacterial laccases have been receiving greater attention recently. Albeit lower in redox potential than fungal laccases, bacterial laccases are commonly thermally more stable, act within broader pH ranges, do not contain posttranslational modifications, and could therefore serve as a high potential scaffold for directed evolution for the production of enzymes with enhanced properties. Several examples focusing on the axial ligand mutations of the T1 copper site have been published in the past. However, structural evidence on the local and global changes induced by those mutations have thus far been of computational nature only. In this study, we set out to structurally and kinetically characterize a few of the most commonly reported axial ligand mutations of a bacterial small laccase (SLAC) from Streptomyces coelicolor. While one of the mutations (Met to Leu) equips the enzyme with better thermal stability, the other (Met to Phe) induces an opposite effect. These mutations cause local structural rearrangement of the T1 site as demonstrated by X-ray crystallography. Our analysis confirms past findings that for SLACs, single point mutations that change the identity of the axial ligand of the T1 copper are not enough to provide a substantial increase in the catalytic efficiency but can in some cases have a detrimental effect on the enzyme’s thermal stability parameters instead.The existing concepts of the ionic micelle structure were specified. It was noted that the composition of dispersed phase particles in a liquid dispersion medium should necessarily include adsorbed counterions rigidly bound to these particles. By numerical solution of the Poisson equation for the two most often used approximations, the Poisson-Boltzmann (PB) model and the Jellium-approximation (JA), the electric potential decay from the Stern potential of dispersed phase particles was defined. A new methodological approach to analyze the reaction of micelle potential decay based on small variability of the CMC value was proposed. It made possible to determine the dimension parameter, which in the presence of weak thermal effects approximately corresponds to the micelle hydrodynamic radius, and to calculate the electrokinetic potential of micelles. The results of theoretical calculations were compared with our previous experimental data on the thickness of the SDS micelle hydrophilic layer obtained by SAXS. A good agreement between the calculated and measured values was obtained, and it was noted that for low concentrations the experimental values are more correctly described by the PB model, but for concentrations greater than 100 mM the JA model is more preferable. It was found that the slipping plane is located near the outer Stern plane and is separated from it only by a few molecular layers of water. The influence stronger than the thermal one can shift the slipping plane closer to the micelle core. Accordingly, the smallest hydrodynamic micelle size is determined by the outer Stern plane. The results of our work allowed us to conclude that the micelle is not something soft and watery, but according to its specified structure, it is a more solid-like particle than was previously assumed. The proposed approach can be extended to investigate other effects of a physicochemical nature, in particular, those observed with the addition of an external electrolyte or nanoparticles.Dynamical simulations of molecules and materials have been the route to understand the rearrangement of atoms within them at different temperatures. Born-Oppenheimer molecular dynamical simulations have further helped to comprehend the reaction dynamics at various finite temperatures. We take a case study of Si6B and Si5B clusters and demonstrate that their finite-temperature behavior is rather mapped to the potential energy surface. The study further brings forth the fact that an accurate description of the dynamics is rather coupled with the accuracy of the method in defining the potential energy surface. A more precise potential energy surface generated through the coupled cluster method is finally used to identify the most accurate description of the potential energy surface and the interconnected finite-temperature behavior.Refined montan wax (RMW) is a lignite-based chemical product with wide application and high added value. However, research on its processing and performance is very limited. Currently, four parameters in the key preparation procedure for the oxidation bleaching of RMW, including the concentration of two oxidants (H2SO4 (P1) and CrO3 (P2)), oxidation time (P3), and the mass ratio of CrO3 used in two oxidation steps (P4), were systematically evaluated in regard to their impact on the properties and chemistry of RMW. Selleckchem GW5074 The results showed that the four tested parameters visibly affected RMW, and each parameter had a different impact on the properties of RMW by range analysis, of which P1 showed a greater influence on its acid value; P2 influenced its friability, specific surface area, and aperture; P3 affected its color, initial melting point, and saponification value; and P4 had a higher impact on its final melting point, melting range, and hardness. Gas chromatography with flame ionization detection-mass spectrometry analysis revealed that the compounds found in RMW samples (RMWs) under different oxidation conditions differed significantly, with major differences in the content and amount of these components. Among the compounds in RMWs, 16 different compounds (variable importance of projection > 1) were found by the orthogonal projections to latent structures discriminant analysis method, nine of which have a strong relationship to the different performances of RMWs. This work provided a basis for the development of performance-oriented preparation processing technology for RMW.Addition of melamine formaldehyde (MF) as a crosslinker containing hydroxymethyl to partially hydrolyzed poly(acrylamide) (HPAM) generated covalently crosslinked in situ gels through chemically nucleophilic attack by hydroxymethyl groups to amide in an HPAM backbone, which was demonstrated by FTIR spectrum analysis and rheological studies. NH4Cl could act as a catalyst to reduce the gelation time from 7 days in dilute water to 8 h in the presence of 0.8 wt % NH4Cl. Compared to high-temperature HPAM/phenol/formaldehyde and HPAM/Cr3+ gel systems, this gel has better adhesion and higher strength over a broad range of temperature from 60 to 100 °C under reservoir conditions with a denser and hook-like three-dimensional microstructure. Pressure-bearing capacity experiments demonstrated that the gel could efficiently plug high pressure from underneath to seal the wellbore, attributing to its high strength and good adhesion. This study could aid petroleum engineers in applying soft materials on controlling the pressure via polymer gels.A combined steady-state and transient approach is employed to investigate the corrosion behavior of X80 pipeline steel in carbon dioxide-saturated brines. Continuous bubbling of carbon dioxide into a test vessel with 1 liter capacity is performed to simulate the flowing condition. The measurement of time-dependent open-circuit potential, polarization resistance, and electrochemical impedance spectroscopy (EIS) is conducted to interpret the evolution of dissolution processes at the corroding interface. Three distinguishing stages are observed at a temperature of 60 °C during a whole exposure of 144 h. Analyses mainly based on the consecutive mechanism show that after the first stage of the active-adsorption state, the anodic reaction is significantly retarded by the accumulation of (FeOH)ads on the iron surface, causing a sharp increase in the polarization resistance and the open-circuit potential, as well as the disappearance of the inductive loop in EIS. At the third stage, the formation of the corrosion pro exposed in carbon dioxide aqueous environments is dominant by water adsorption on the iron surface, and further investigation should be performed on the role that carbon dioxide plays in the evolution of corrosion products and the formation of a protective film on the steel surface by taking into account local water chemistry.Density functional calculations at the B3LYP-D3+IDSCRF/TZP-DKH(-dfg) level of theory have been performed to understand the mechanism of ruthenium-catalyzed C-H allylation reported in the literature in depth. The plausible pathway consisted of four sequential processes, including C-H activation, migratory insertion, amide extrusion, and recovery of the catalyst, in which C-H activation was identified as the rate-determining step. The amide extrusion step could be promoted kinetically by trifluoroacetic acid since its mediation lowered the free-energy barrier from 32.1 to 12.2 kcal/mol. Additional calculations have been performed to explore other common pathways between arenes and alkenes, such as C-H alkenylation and hydroarylation. A comparison of the amide extrusion and β-H elimination steps established the following reactivity sequence of the leaving groups protonated amide group > β-H group > unprotonated amide group. The suppression of hydroarylation was attributed to the sluggishness of the Ru-C protonation step as compared to the amide extrusion step. This study can unveil factors favoring the C-H allylation reaction.The objective of this work is to explore the effect and potential mechanism of Punicalagin (Pun) in managing Alzheimer’s disease (AD) based on computer-aided drug technology. The following methods were used the intersection genes of Pun and AD were retrieved from the database and subjected to PPI analysis, GO, and KEGG enrichment analyses. Preliminary verification was performed by molecular docking, molecular dynamics (MD) simulation, and combined free energy calculation. The motor coordination and balance ability, anxiety degree, spatial learning, and memory ability of mice were measured by a rotating rod fatigue instrument, elevated cross maze, and Y maze, respectively. The amyloid β protein (Aβ) in the hippocampus was examined by immunohistochemistry, and the phosphorylation of serine at position 404 of the tau protein (Tau-pS404) was examined by western blot in the mouse brain. The PPI network of Pun showed that the intersection genes were closely related and enriched in muscle cell proliferation and the response to lipopolysaccharide.