JAK3 differs from other JAK family members in terms of tissue distribution and functional properties, making it a promising target for autoimmune disease treatment. However, due to the high homology ...of these family members, targeting JAK3 selectively is difficult. As a result, exploiting small changes or selectively boosting affinity within the ATP binding region to produce new tailored inhibitors of JAK3 is extremely beneficial. PubChem CID 137321159 was used as the lead inhibitor in this study to preserve the characteristic structure and to collocate it with the redesigned new parent core structure, from which a series of 1,7-dihydro-dipyrrolo 2,3-b:3′,2′-e pyridine derivatives were obtained using the backbone growth method. From the proposed compounds, 14 inhibitors of JAK3 were found based on the docking scoring evaluation. The RMSD and MM/PBSA methods of molecular dynamics simulations were also used to confirm the stable nature of this series of complex systems, and the weak protein−ligand interactions during the dynamics were graphically evaluated and further investigated. The results demonstrated that the new parent core structure fully occupied the hydrophobic cavity, enhanced the interactions of residues LEU828, VAL836, LYS855, GLU903, LEU905 and LEU956, and maintained the structural stability. Apart from this, the results of the analysis show that the binding efficiency of the designed inhibitors of JAK3 is mainly achieved by electrostatic and VDW interactions and the order of the binding free energy with JAK3 is: 8 (−70.286 kJ/mol) > 11 (−64.523 kJ/mol) > 6 (−51.225 kJ/mol) > 17 (−42.822 kJ/mol) > 10 (−40.975 kJ/mol) > 19 (−39.754 kJ/mol). This study may provide a valuable reference for the discovery of novel JAK3 inhibitors for those patients with immune diseases.
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Abstract Symmetry-protected band degeneracy, coupled with a magnetic order, is the key to realizing novel magnetoelectric phenomena in topological magnets. While the spin-polarized nodal states have ...been identified to introduce extremely-sensitive electronic responses to the magnetic states, their possible role in determining magnetic ground states has remained elusive. Here, taking external pressure as a control knob, we show that a metal-insulator transition, a spin-reorientation transition, and a structural modification occur concomitantly when the nodal-line state crosses the Fermi level in a ferrimagnetic semiconductor Mn 3 Si 2 Te 6 . These unique pressure-driven magnetic and electronic transitions, associated with the dome-shaped T c variation up to nearly room temperature, originate from the interplay between the spin-orbit coupling of the nodal-line state and magnetic frustration of localized spins. Our findings highlight that the nodal-line states, isolated from other trivial states, can facilitate strongly tunable magnetic properties in topological magnets.
Polymer nanocomposites, which combine the advantages of polymers and fillers, are widely used in the field of automobile and aviation. Polyimine (PI) is an emerging thermoset material with remarkable ...properties, such as malleability, recyclability, and self-healing. Silicon carbide nano-whiskers (SiCw), as a cheap and high-hardness filler material, are chosen to enhance the properties of polyimine matrix. Silicon carbide nano-whisker-reinforced polyimine (PI-SiCw) nanocomposites were successfully fabricated by heat pressing, which was confirmed by FTIR and XPS tests. According to the results of mechanical tests, the mechanical properties of PI-SiCw nanocomposites were obviously improved. For example, with the addition of 0.5% SiCw, bending strength and bending elongation at break can be simultaneously increased by 33% and 148%, respectively. Surprisingly, the impact strength of PI-SiCw nanocomposites with 2% SiCw was increased by 154% compared to the matrix. SEM and EDS tests showed that the evenly distributed SiCw in the polyimine matrix enhanced the mechanical properties of PI-SiCw nanocomposites according to the mechanism of whiskers pulling out and the bridging principle. According to the TGA test results, the PI composites with SiCw retain a higher weight percentage at 800 °C. The reason was the combined effect of the good thermal stability of SiCw and their strong interactions with the PI matrix. As a result, introducing SiCw into the PI matrix imparts a slight improvement in thermal stability. This article presents an avenue of cost-effective research to enhance the mechanical properties of polyimine composites.
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Representing art using a robotic system is part of artificial intelligence in our lives, especially in the realm of emotional expression. Developing a painting robot involves addressing how to enable ...the robot to emulate human artistic processes, which often include imprecise techniques or errors akin to those made by human artists. This paper discusses our development of an innovative painting robot utilizing the sim-to-real approach within learning technology. Specifically, this pipeline operates under a deep reinforcement learning (DRL) framework designed to learn drawing strategies from training data derived from real-world settings, aiming for the robot’s proficiency in emulating human artistic expressions. Accordingly, the framework comprises two modules when given a target drawing image: the first module trains in a simulated environment to break down the target image into individual strokes; the second module then learns how to execute these strokes in a real environment. Our experiments have shown that this system can meet our objectives effectively.
The abuse of agricultural antibiotics has led to the emergence of drug-resistant phytopathogens. Rifampicin and streptomycin and streptomycin resistance Pectobacterium carotovorum subsp. carotovorum ...(PccS1) was obtained from pathological plants in a previous experiment. Rheum tanguticum, derived from the Chinese plateau area, exhibits excellent antibacterial activity against PccS1, yet the action mode has not been fully understood. In present text, the cell wall integrity of the PccS1 was tested by the variation of the cellular proteins, SDS polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM) and Fourier transform infrared spectrophotometer (FTIR) characteristics. Label-free quantitative proteomics was further used to identify the DEPs in the pathogen response to treatment with Rheum tanguticum Maxim. ex Balf. extract (abbreviated as RTMBE). Based on the bioinformatics analysis of these different expressed proteins (DEPs), RTMBE mainly inhibited some key protein expressions of beta-Lactam resistance, a two-component system and phosphotransferase system. Most of these membrane proteins were extraordinarily suppressed, which was also consistent with the morphological tests. In addition, from the downregulated flagellar motility related proteins, it was also speculated that RTMBE played an essential antibacterial role by affecting the swimming motility of the cells. The results indicated that Rheum tanguticum can be used to attenuate the virulence of the drug-resistant phytopathogenic bacteria.
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Abstract
Drilling along the coal seam is an effective method for large-scale gas control. The distribution law of the stress field is determined by the parameters affecting the drilling along the ...coal seam, thereby affecting the drainage effect of the drilling along the coal seam. In order to study the distribution law and drilling parameters of the borehole stress field along the coal seam, the residual plastic zone, the radius of the plastic softening zone, the radius of The radial displacement of the coal body on the hole wall and the axial plastic range are used to construct the calculation model of the sealing length; the calculation model of the sealing strength is established through the micro-element analysis of the packer rubber cylinder. The research finally determined that the most suitable drilling position is the original rock stress area; the reasonable sealing length and sealing strength were determined.
The high temperature oxidation resistance is crucial to assure the reliability of nickel-based superalloy parts serving at elevated temperature. Hastelloy X is a solid solution strengthening ...superalloy featured by decent mechanical properties and excellent high temperature oxidation resistance, having the potential to replace the commonly used nickel-based superalloy Inconel 718 in appropriate high-end manufacturing fields. In this work, a comparative study on mechanical properties and high temperature oxidation behaviour of Hastelloy X and Inconel 718 fabricated by laser directed energy deposition was carried out. Under the same processing parameters, the as-built Hastelloy X consisted of columnar and cellular γ phase with dispersed carbides, but Inconel 718 contained columnar γ phase with dispersed carbides and γ′ phase. At ambient temperature, Hastelloy X showed better ductility but inferior strength and hardness. Additionally, the isothermal oxidation tests at 1000 and 1100 °C demonstrated that the oxidation kinetics curves of both as-built superalloys followed the parabolic law. Hastelloy X owned a better high temperature oxidation resistance, which could be attributed to the uniformly distributed dense Cr2O3 and the relatively slight exfoliation of oxides in the oxide scales.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colloidal solutions of surfactants that form micelles or vesicles are useful for solubilizing and stabilizing hydrophobic molecules that are otherwise sparingly soluble in aqueous solutions. In this ...paper we investigate the use of micelles and vesicles prepared from ionic surfactants for solubilizing and stabilizing curcumin, a medicinal natural product that undergoes alkaline hydrolysis in water. We identify spectroscopic signatures to evaluate curcumin partitioning and deprotonation in surfactant mixtures containing micelles or vesicles. These spectroscopic signatures allow us to monitor the interaction of curcumin with charged surfactants over a wide range of pH values. Titration data are presented to show the pH dependence of curcumin interactions with negatively and positively charged micelles and vesicles. In solutions of cationic micelles or positively charged vesicles, strong interaction between the Cur−1 phenoxide ion and the positively charged surfactants results in a change in the acidity of the phenolic hydrogen and a lowering of the apparent lowest pK a value for curcumin. In the microenvironments formed by anionic micelles or negatively charged bilayers, our data indicates that curcumin partitions as the Cur0 species, which is stabilized by interactions with the respective surfactant aggregates, and this leads to an increase in the apparent pK a values. Our results may explain some of the discrepancies within the literature with respect to reported pK a values and the acidity of the enolic versus phenolic protons. Hydrolysis rates, quantum yields, and molar absorption coefficients are reported for curcumin in a variety of solutions.
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Corrosion resistance is a critical consideration in the selection of materials for various applications. In this study, we employed a data-driven approach using machine learning techniques and a ...large dataset of corrosion data to design and test four different low-alloy steels with varying amounts of tin (Sn) microalloying (0.1 wt%, 0.2 wt%, 0.3 wt% and Sn-free) for improved corrosion resistance in Beijing outdoor atmosphere. Using experimental methods such as corrosion morphology and rust layer analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and potentiodynamic polarization measurements, we verified that the 0.2 wt% Sn microalloying steel exhibited the best corrosion resistance. Our findings demonstrate the potential of data-driven approaches and machine learning techniques, such as the use of corrosion big data, in the identification and optimization of optimal alloy compositions of corrosion-resistant materials for outdoor environments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
