关键词： alpha-Glucosidase   Flavonol   Flavone   Isoflavone   Molecular docking  

摘要： Diabetes mellitus is a major, global public health problem. alpha-Glucosidase inhibitors are one of the most widely used classes of oral antidiabetics. In addition to other pharmaceutical benefits, flavonoids are known as potent alpha-glucosidase inhibitors. In the last two decades, the latter property of flavonoids has attracted a great interest. In the current review, the literature on flavonoids as inhibitors of alpha-glucosidase enzyme, their mechanism of action along with in silico studies and structure-activity relationships is discussed. The main outcomes show that a double bond between C-2 and C-3, and free hydroxyl groups at C-3 and C-4 ' are crucial. Whereas sugar substitution at any position on the aglycon reduced the inhibitory effect, a phenolic group like gallic acid, coumaric acid, etc. substituted at different positions of sugar units increased it. Hydroxylation of flavonoids generally enhanced the effect due to possible electrostatic interactions with the enzyme, making flavonols stronger inhibitors than their flavone analogues. Hydroxyl groups at C-3, C-7, ring B, and the carbonyl oxygen at C-4 are considered to be key modifications to enhance binding through hydrogen bonds. With this overview we intend to motivate and challenge researchers to design novel flavonoids a find new hits.

关键词： alpha-Quartz   Molecular Dynamics   Mechanical Properties   Thermal Conductivity  

摘要： Silicon dioxide or quartz is one of the most important natural resources, and silicates are the prominent content of more than 90% of the earth's minerals. This research investigates the mechanical properties and thermal conductivity of alpha-quartz by using non-equilibrium molecular dynamics (NEMD) simulation method. The Beest, Kramer, and van Santen (BKS) pairwise interatomic potential suitable for quartz crystal was chosen to describe the interatomic interactions. The radial distribution function (RDF) of alpha-quartz was calculated and plotted. The stress-strain behavior of alpha-quartz under uniaxial tensile loading in different temperatures and strain rates was also studied using classical molecular dynamics. It was found that the thermal conductivity of alpha-quartz depends on the temperature, mostly in lower temperatures, and decreases with increasing the temperature. Stress-Strain curves show that the mechanical properties of alpha-quartz vary meaningfully with temperature and strain rate.

关键词： Grand canonical Monte Carlo   Solid oxide fuel cells   Carbon deposition   Thermal expansion coefficient   Nickle carbide  

摘要： Carbon deposition of solid oxide fuel cell (SOFC) anode is a key factor to understand the risk of structural cracking due to mechanical stress. In this study, Grand Canonical Monte Carlo (GCMC) was used under ReaxFF to construct the corresponding carbon deposition model and migration law of carbon atoms. The law of heat generation, diffusion coefficient of volume expansion and mechanical behavior of the nickel carbide composition in the simulation are close to the experimental and theoretically results, which validates the model built by ReaxFF. During analysis, the change in structural characteristics and mechanical properties of the anode caused by the carbon deposition were observed. The variation in volume of carbon deposition during diffusion process was detected, and the structure of the carbon deposition process was studied by combining ohmic loss and radial distribution function (RDF). Influence of carbon deposition on the mechanical properties of the uniaxial tensile process using different models was compared and the behavior of carbon content, expansion/compression rate, poison ratio and nickel carbide formation was obtained. The relationship between Young's modulus and carbon deposition of mechanical properties such as yield stress is clarified.

关键词： SARS-CoV-1   SARS-CoV-2   COVID-19   Fusion peptide   Fusion protein   Cell fusion  

摘要： The emerging and re-emerging viral diseases are continuous threats to the wellbeing of human life. Previous outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS had evidenced potential threats of coronaviruses in human health. The recent pandemic due to SARS-CoV-2 is overwhelming and has been going beyond control. Vaccines and antiviral drugs are ungently required to mitigate the pandemic. Therefore, it is important to comprehend the mechanistic details of viral infection process. The fusion between host cell and virus being the first step of infection, understanding the fusion mechanism could provide crucial information to intervene the infection process. Interestingly, all enveloped viruses contain fusion protein on their envelope that acts as fusion machine. For coronaviruses, the spike or S glycoprotein mediates successful infection through receptor binding and cell fusion. The cell fusion process requires merging of virus and host cell membranes, and that is essentially performed by the S2 domain of the S glycoprotein. In this review, we have discussed cell fusion mechanism of SARS-CoV-1 from available atomic resolution structures and membrane binding of fusion peptides. We have further discussed about the cell fusion of SARS-CoV-2 in the context of present pandemic situation.

摘要： Purpose Determine the hemodynamic and autonomic response to implantation of durable continuous-flow (CF) left ventricular assist device (LVAD) among individuals with advanced heart failure (AHF). Background HF leads to neurohormonal activation with exaggerated increases in sympathetic tone. This hyperadrenergic environment is positively correlated with HF severity and mortality. Previous investigations have demonstrated that non-physiologic reductions in pulsatility associated with CF-LVADs, contributes to elevated levels of sympathetic nerve activity. Therefore, it is thought that CF-LVAD implantation leads to heightened sympathetic tone. However, there are no data examining longitudinal changes in hemodynamics and/or sympathetic tone prior to and following device implantation. Methods Nine individuals (59 ± 9 yrs, 8 males) scheduled for CF-LVAD implantation underwent hemodynamic assessment ∼two weeks prior to, and ∼three months following surgery. At those dates participants completed a graded head-up tilt (HUT) at supine, 30 and 60 degrees, with assessment of heart rate (HR), blood pressure (BP) by arterial catheter, and plasma catecholamines at each position. Results Hemodynamic and catecholamine responses to HUT are displayed in Figure 1. HR and MAP were similar prior to and following CF-LVAD implantation (Supine MAP 78.9 ± 7.5 v. 87.8 ± 14 mmHg, for pre- and post-LVAD respectively, P=0.76). However, pulse pressure was significantly reduced following device implantation (47.3 ± 18, 23.7 ± 12 mmHg for supine pre- and post-LVAD, respectively, P=0.009). Despite the reduction in pulsatility, plasma norepinephrine levels were significantly reduced following device implantation (pre-LVAD 712 ± 374, post- LVAD 319 ± 156 pg/ml, both supine, P =0.016). Notably, pre-LVAD supine norepinephrine levels were significantly greater than post-LVAD levels at a 60-degree HUT (712 ± 374 v. 481 ± 234 pg/ml, P=0.25), indicating a marked reduction in autonomic tone following de

关键词： BixSb2-xTe3   Young's modulus   Thermal conductivity   Non-equilibrium molecular dynamics  

摘要： In this decade, BixSb2-xTe3 of Bi2Te3-based thermoelectric (TE) materials has been proven effective in improving the TE properties and figure of merit (ZT) at room temperature of these materials. In this work, the mechanical and thermal properties of quintuple layers of the BixSb2-xTe3 nanofilms are studied by using non-equilibrium molecular dynamics simulation. The effects of different proportions of Sb content on deformation mechanism and thermal conductivity are determined. Results indicate that the mechanical and thermal properties of the BixSb2-xTe3 nanofilms are significantly affected by Sb content and differ greatly from those of pure Bi2Te3 nanofilms. Furthermore, the BixSb2-xTe3 nanofilms exhibit better tensile strength than pure Bi2Te3 nanofilms. Changes in Sb content strongly affect the concentration of SbTe antisite defects and alter thermal conductivity. The results of this investigation should benefit the potential application of the BixSb2-xTe3 nanofilms to TE devices and energy generation.

关键词： Cu2+   ab initio   HF   liquid ammonia   MP2   NBO   QMCF MD  

摘要： The impact of solvent flexibility and electron correlation on the simulation results ofCu(2+)in liquid ammonia has been investigated via an ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulation approach. To achieve this, three different simulation systems were considered in this study, namelyCu(2+)in rigid and flexible ammonia at Hartree-Fock (HF) level of theory, as well as resolution of identity second order Moller-Plesset (MP2) perturbation theory in the rigid body case. In all cases, a stable octahedral[Cu(NH3)(6)](2+)complex subject to dynamic Jahn-Teller distortions without the occurrence of ligand exchange was observed. TheCu(2+) - NH(3)distance in the first shell agrees well with the experimental and other theoretical data. In all three cases, the structural data shows that the rigid-body ammonia model in conjunction with the HF level of theory provides accurate data for the first solvation shell, while at the same time, the computational demand and thus the achievable simulation time are much more beneficial. The vibrational analysis of theCu(2+) - NH(3)interaction yields similar force constants in the three investigated systems indicating that there is no distinct difference on the dynamical properties of the first solvation shell. In addition to the QMCF MD simulations, a number of natural bond orbital (NBO) analyses were carried out, confirming the strong electrostatic character of theCu(2+) - NH(3)interaction.

关键词： DNA polymerase   RNA polymerase   enzyme kinetics   dNTP   rNTP   inhibitors   DNA polymerase   nucleoside   nucleotide metabolism   enzyme inhibitor  

摘要： Enzyme kinetic analysis reveals a dynamic relationship between enzymes and their substrates. Overall enzyme activity can be controlled by both protein expression and various cellular regulatory systems. Interestingly, the availability and concentrations of intracellular substrates can constantly change, depending on conditions and cell types. Here, we review previously reported enzyme kinetic parameters of cellular and viral DNA and RNA polymerases with respect to cellular levels of their nucleotide substrates. This broad perspective exposes a remarkable co-evolution scenario of DNA polymerase enzyme kinetics with dNTP levels that can vastly change, depending on cell proliferation profiles. Similarly, RNA polymerases display much higherK(m)values than DNA polymerases, possibly due to millimolar range rNTP concentrations found in cells (compared with micromolar range dNTP levels). Polymerases are commonly targeted by nucleotide analog inhibitors for the treatments of various human diseases, such as cancers and viral pathogens. Because these inhibitors compete against natural cellular nucleotides, the efficacy of each inhibitor can be affected by varying cellular nucleotide levels in their target cells. Overall, both kinetic discrepancy between DNA and RNA polymerases and cellular concentration discrepancy between dNTPs and rNTPs present pharmacological and mechanistic considerations for therapeutic discovery.

关键词： Oligomers  

摘要： The clinical signature of Alzheimer's disease (AD) is the deposition of aggregated A beta fibrils that are neurotoxic to the brain. It is the major form of dementia affecting older people worldwide, impeding their normal function. Finding and testing various natural compounds to target and disrupt stable A beta fibrils seems to be a promising and attractive therapeutic approach. Four phenolic compounds from plant sources were taken into consideration for the present work, and were initially screened by docking. Ellagic acid (REF) came out to be the best binder of the A beta oligomer from docking studies. To test the destabilization effect of REF on the A beta oligomer, MD simulation was conducted. The simulation outcome obtained clearly indicates a drift of terminal chains from the A beta oligomer, leading to the disorganization of the characteristically organized cross beta structure of the A beta fibrils. Increased values of RMSD,R-g, RMSF, and SASA are indicative of the destabilization of the A beta fibril in the presence of REF. The disruption of salt bridges and a notable decline in the number of hydrogen bonds and beta-sheet content explain the conformational changes in the A beta fibril structure, ceasing their neurotoxicity. The MM-PBSA results revealed the binding of REF to chain A of the A beta oligomer. The destabilization potential of ellagic acid, as explained by the MD simulation study, establishes it as a promising drug for curing AD. The molecular-level details about the destabilization mechanism of ellagic acid encourage the intensive mining of other natural compounds for therapeutic intervention for AD.

关键词： Oxidation reactions   Antimicrobial agents   Ionic strength   Oxidation   Kinetics  

摘要： The kinetics and mechanistic aspects of the oxidation of two beta-lactam antibiotics (A), ampicillin and flucloxacillin, by alkaline hexacyanoferrate(III) (HCF(III)) were examined using spectrophotometry at a fixed temperature. The oxidation reactions showed a 1:4 (A: HCF(III)) stoichiometry. The reaction kinetics were found to follow first-order dependence for the oxidant and fractional first-order dependence for [A] and [OH-]. The enhancement of the ionic strength and dielectric constant was found to increase the oxidation rates. Free radical tests of the reactions showed positive results. The addition of HCF(II) as a predicted oxidation product did not considerably change the oxidation rates. Under the same experimental conditions, the oxidation rate of ampicillin was found to be slightly lower than that of flucloxacillin. The acquired oxidation products were recognized using spot testing and Fourier transform infrared spectra. A conceivable oxidation mechanism was suggested. A derived rate law expression was found to be consistent with the experimental results. The activation parameters were assessed and discussed.