Structural analysis and insight into novel MMP-13 inhibitors from natural chemiome as disease-modifying osteoarthritis drugs

Purpose: To identify natural chemiome that inhibits matrix-metalloproteinases (MMPs) with a view to discovering novel disease-modifying osteoarthritis drugs (DMOADs).Methods: Computer-aided drug design (CADD) with virtual screening, ADME/Tox, molecular docking, molecular dynamics simulation, and MM-PBSA calculations were used in search of novel natural compounds that inhibit MMPs.Results: From more than fifty thousand compounds, a single lead compound (IBS ID: 77312) was shortlisted using bias based on binding energy and drug-likeness. This lead compound synergistically bound to the S1 domain of MMP-13 protein through five hydrogen bonds. The interactions became stable within 100-nanosecond molecular dynamics simulation run. The in vitro data for the lead compound showed that its minimal non-lethal dose increased collagen content but decreased aggrecan level in chondrocytes.Conclusion: This study has identified a natural lead compound that may pave the way for a novel DMOAD of natural origin against OA.Keywords: Osteoarthritis, MMP-13, Natural chemiome, Disease-modifying osteoarthritis drug, Molecular dockin

PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients

Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics.Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 μg and 50 μg PB-119 once weekly and exenatide (5–10 μg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results.Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-β after 12 weeks of treatment.Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance

Development of carbon coated membrane for zinc/bromine flow battery with high power density

The zinc/bromine flow battery is considered as one of the most suitable candidates for the large-scale electrical energy storage attributed to its nature of high energy density and low cost However, the relatively low power density determined by the working current density of 20 mA cm(-2) limits its performance and application. The relatively low working current density is caused by the insufficient electrochemical activity of positive electrode and the high internal resistance of cell. The formation of Brads is the rate-determined step to the positive electrode reaction. Thus the activated carbon with the specific surface area of 2314 m(2) g(-1), compared with the carbon felt, is a much more suitable and competitive choice. The activated carbon coated membrane is first designed to decrease the internal resistance. Demonstrated by the cycle voltammetry, AC impedance and polarization distribution investigations, both the positive electrode overpotential and the cell internal resistance decrease obviously attributed to the high electrochemical activity layer closing to the membrane. Thus the energy efficiency of 75% is achieved at charge-discharge current density of 40 mA cm(-2), which means a nearly two-fold increase in power density. (C) 2012 Elsevier B.V. All rights reserved

Confined-Space-Assisted Preparation of Fe₃O₄‑Nanoparticle-Modified Fe–N–C Catalysts Derived from a Covalent Organic Polymer for Oxygen Reduction

Iron–nitrogen–carbon (Fe–N–C) has been considered as one of the most promising nonprecious metal catalysts for the oxygen reduction reaction (ORR) in fuel cells and metal–air batteries. Herein, we prepare a highly active Fe₃O₄/Fe–N–C catalyst (named COP@K10-Fe-900), for the ORR from a layered tetraphenylporphyrin-based (TPP-based) covalent organic polymer (COP) grown in nanoconfined space as precursors, followed by iron ion incorporation and a pyrolysis process. The nanoconfined space, i.e., montmorillonite (K10) template, contributes to the unique layered structure of designed precursors and enables Fe₃O₄ nanoparticles to disperse uniformly in the resulting layered Fe–N–C catalyst. The nanoconfined space reduces the iron-based particle size from ∼50–150 to ∼10 nm. An enhancement of 50 mV was obtained after using layer space confinement for half-wave potential. Moreover, the half-wave potential of the newly developed COP@K10-900 exceeds 20 mV as compared to the benchmark Pt/C in alkaline media. Therefore, we believe that this work can provide an important guideline for designing highly active M–N–C catalysts that can be widely used in energy conversion and storage devices

Shifted Legendre polynomials algorithm used for the dynamic analysis of PMMA viscoelastic beam with an improved fractional model

International audienceIn this paper, a fractional viscoelastic model is proposed to describe the physical behaviour of polymeric material. The material parameters in the model are characterized by the experimental data obtained in the dynamical mechanical analysis. The proposed model is integrated into the fractional governing equation of polymethyl methacrylate (PMMA) above its glass transition temperature. The numerical algorithm based on the shifted Legendre polynomials is retained to solve the fractional governing equations in the time-domain. The accuracy and effectiveness of the algorithm are verified according to the mathematical examples. The advantage of this method is that Laplace transform and the inverse Laplace transform commonly used in fractional calculus are avoided. The dynamical response of the viscoelastic PMMA beam is determined with several loading conditions (uniformly distributed load and harmonic load). The effects of the loading condition and the temperature on the dynamic response of the beam are investigated in the results. The proposed approach shows great potentials for the high-precision calculation in solving the fractional equations in the science and engineering

Holey Graphitic Carbon Derived from Covalent Organic Polymers Impregnated with Nonprecious Metals for CO2 Capture from Natural Gas

Natural gas (NG), as a renewable and clean energy gas, is considered to be one of the most attractive energy carriers owing to its high calorific value, low price, and less pollution. Efficiently capturing CO2 from NG is a very important issue since CO2 reduces energy density of natural gas and corrodes equipment in the presence of water. In this study, the authors use holey graphene-like carbon derived from covalent organic polymers (COP) impregnated with nonprecious metals, i.e., COP graphene, as highly efficient separation materials. The dual-site LangmuirFreundlich adsorption model based ideal absorbed solution theory is applied to explore the adsorption selectivity. The experimental results along with first principles calculations show Mn-impregnated COP graphene exhibits greater CO2/CH4 selectivity than Fe and Co impregnated materials. Particularly, the selectivity of CCOPPMn reaches 11.4 at 298 K and 12 bars, which are much higher than those in many reported conventional porous materials and can be compared to the highest separation performance under similar condition. Importantly, all the three COP graphene show remarkably high regenerability (R &gt; 77%), which are much better than many reported promising zeolites, active carbon, and metal organic frameworks. Accordingly, COP graphene are promising cyclic adsorbents with high selectivity for separation and purification of CO2 from natural gas.</p

A Bifunctional Liquid Fuel Cell Coupling Power Generation and V3.5+ Electrolytes Production for All Vanadium Flow Batteries

Abstract All vanadium flow batteries (VFBs) are considered one of the most promising large‐scale energy storage technology, but restricts by the high manufacturing cost of V3.5+ electrolytes using the current electrolysis method. Here, a bifunctional liquid fuel cell is designed and proposed to produce V3.5+ electrolytes and generate power energy by using formic acid as fuels and V4+ as oxidants. Compared with the traditional electrolysis method, this method not only does not consume additional electric energy, but also can output electric energy. Therefore, the process cost of producing V3.5+ electrolytes is reduced by 16.3%. This fuel cell has a maximum power of 0.276 mW cm−2 at an operating current of 1.75 mA cm−2. Ultraviolet–visible spectrum and potentiometric titration identify the oxidation state of prepared vanadium electrolytes is 3.48 ± 0.06, close to the ideal 3.5. VFBs with prepared V3.5+ electrolytes deliver similar energy conversion efficiency and superior capacity retention to that with commercial V3.5+ electrolytes. This work proposes a simple and practical strategy to prepare V3.5+ electrolytes

Numerical analysis of fractional viscoelastic column based on shifted Chebyshev wavelet function

International audienceAn innovative nuAn innovative numerical procedure for solving the viscoelastic column problem based on fractional rheological models, directly in the time domain, is investigated. Firstly, the governing equation is established according to the fractional constitutive relation. Secondly, the resulting equation is transformed into algebraic equation and solved by using the shifted Chebyshev wavelet function. Furthermore, the convergence analysis and the retained numerical benchmarks are carried out to validate the performance of the proposed method. A small value of the absolute error between numerical and accurate solution is obtained. Finally, the dynamic analysis of viscoelastic beam-column problems is investigated with different cross-section shape (circular and square) under various loading conditions (axial compressive force and harmonic load). The displacement, strain and stress of the viscoelastic column at different time and position are determined. The deformation and stress of the viscoelastic column of different materials under the same loading condition are compared. The results in the paper show the highly accuracy and efficiency of the proposed numerical algorithm in the dynamical stability analysis of the viscoelastic colum

Number of compensatory switches in 5S rRNAs.

<p>Number of compensatory switches in 5S rRNAs.</p