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  • Snedker Thomson posted an update 4 days, 8 hours ago

    A recent research has identified chymase, a mast cell-specific protease as an exclusive novel therapeutic target to prevent Japanese encephalitis virus (JEV) induced encephalitis. Interestingly, JEV activates mast cell specific chymase during its penetration through blood brain barrier (BBB) which eventually guide to viral encephalitis. Hence, in this study, natural chemical entities (NCE) from multiple databases (MPD3, TIPDB and MTDP) were virtually screened for their binding affinity as chymase inhibitors, a promising negotiator for prolong survival against JEV tempted encephalitis. Merged computational programs, Maestro software, QikProp, ProTox and Gromacs were applied to screen the NCEs against target receptor (PDB 4KP0). Three hits (C00008437, C00014417 and 8141903) were identified after employing a series of sieves such as High Throughput Virtual Screening (HTVS), Standard precision (SP) and Xtra precision (XP) molecular docking simulations followed by desired pharmacokinetic-toxicity profile predictions and molecular dynamics (MD) examinations. Maestro simulations resulted in best three binding energy scores as -11.992 kcal/mol (first ranked; C00008437), -11.673 kcal/mol (second ranked; C00014417) and -11.456 kcal/mol (third ranked; 8141903), respectively. The top three hits revealed an ideal range of pharmacokinetic and toxicity descriptors values. In addition, MD simulations enabled us to confirm top hits higher selectivity toward chymase receptor. In conclusion, this might potentially represent remarkable novel classes with an effective chymase mediated treatment to combat JEV induced encephalitis, which need to justify with further detail studies.Malunion is a common complication of distal radius fracture and often causes a reduction in the range of motion. The measurement of the range of motion is a part of the process for evaluating the final motion after a malunion of a distal radius fracture is diagnosed. However, the amount of range of motion reduced due to the malunion often is calculated upon the assumption that the motion is equal in both forearms. Although this assumption has been questioned, not much work has been conducted which defines the difference in range of motion between the two forearms. In this work, a methodology has been proposed to measure the forearm range of motion using inertial measurement units. The motion was measured in both forearms of a control group. Afterwards, the motion was compared between both forearm sides; then, differences and relationships were drawn. Our results indicated that the forearm rotational motion is larger in the dominant forearm. Moreover, pronation and supination motions differ among the limbs, supination being always larger than pronation. In the dominant forearm, supination is much larger than pronation, while in the non-dominant their magnitudes are rather close. These results provide important data for a more accurate way to determine how the malunion of a fracture or another pathology affects the forearm motion.New monometallic platinum complex ([PtL2Cl2]Cl2) of pyrimidine and morpholine derivative ligand were synthesized and structurally elucidated by elemental analysis, molar conductance, 1H NMR, FT-IR, ESI-MS and UV-Visible spectroscopic techniques. Analytical and spectroscopic result suggests that platinum complex has octahedral geometry. In order to understand the molecular geometry and absorption spectra of the ligand and platinum complex, DFT and TDDFT calculations have been carried out. Catalytic reduction of platinum complex with p-nitrophenol (p-NP) was carried out by the spectrophotometric method. In vitro anticancer activity of ligand and platinum complex on human cancer cell lines (MCF-7, HepG2, HeLa and A549) as well as normal cell (NHDF) line was done by MTT assay. This result reveals that platinum complex has enhanced anticancer against MCF-7 (19.13 ± 0.96 µg/mL) cell line than HepG2 (32.82 ± 1.64 µg/mL), HeLa (29.2 ± 1.46 µg/mL) and A549 (34.21 ± 1.71, µg/mL) cell lines as compared to ligand. Antioxidant activity results sustained that platinum complex has better radical scavenging ability than ligand. Platinum complex has better antimicrobial activity toward E. coli bacteria and C. albicans fungi than other antimicrobial pathogens. DNA binding affinities of the ligand and platinum complex have been assessed by probing their ability to bind to calf thymus DNA (CT-DNA) with UV-Visible, fluorescence, viscometric measurements and cyclic voltammetric techniques. These results proved that ligand and platinum bind to CT-DNA by intercalative binding mode. Molecular docking analysis reveals that the platinum complex tends to show good binding affinity toward both DNA and BSA than ligand.Using a crude enzyme solution prepared from astigmatid mites, the conversion reaction to (Z,Z)-6,9-heptadecadiene (6,9-C17) using linoleyl aldehyde (LAld) as a substrate was successful. The mass spectrum of the reaction product using 13C-labeled LAld as a substrate could be assigned as 13C-labeled 6,9-C17. Unlike the findings in other species, the decarbonylase derived from mites did not require a coenzyme.End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.The wall motion of atherosclerotic plaque was analyzed using a computational method, and the effects of tissue viscoelasticity, fibrosis thickness, and lipid-core stiffness on wall displacement waveforms were examined. The viscoelasticity of plaque tissues was modeled using a time Prony series with four Maxwell elements. Computational simulation of tissue indentation tests showed the validity of the proposed viscoelastic constitutive models. Decreasing the relative moduli of the viscoelastic model reduced their viscous characteristics while enhancing the stiffness of the wall, which corresponded with the effects of decreased smooth muscle cells content. A finite-element analysis was conducted for atherosclerotic wall models and wall displacement waveforms were computed. The phase difference between the first harmonics of pressure and displacement waves was selected to represent the time delay of the wall motion. Elsubrutinib chemical structure As the relative modulus decreased, the wall displacement and phase lag decreased. A thinner wall and softer lipid core corresponded to a greater wall displacement and smaller phase lag.