Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Corrosion inhibition of carbon steel in hydrochloric acid by cationic arylthiophenes as new eco-friendly inhibitors: Experimental and quantum chemical study

This study describes the adsorption behavior of three arylthiophene derivatives namely: 2-(4-amidino-3-fluorophenyl)-5-[4-methoxy phenyl] thiophene dihydrochloride salt (MA-1217), 2-(4-amidinophenyl)-5-[4-chlorophenyl] thiophene dihydrochloride salt (MA-1316) and 2-(4-amidino-3-fluorophenyl)-5-[4-chlorophenyl]thiophene dihydrochloride salt (MA-1312) at C-steel in 1.0 mol·L^-1 HCl interface using experimental and theoretical studies. Electrochemical and mass loss measurements showed that the inhibition efficiency (IE) of the arylthiophene derivatives increases with increasing concentrations and exhibited maximum efficiency 89% at 21×10^-6 mol·L^-1 (MA-1217) by mass loss method. The investigated arylthiophene derivatives obey the Langmuir adsorption isotherm. From polarization studies the arylthiophene derivatives act as mixed-type inhibitors. Surface analysis were carried out and discussed. The mode of orientation and adsorption of inhibitor molecules on C-steel surface was studied using molecular dynamics (MD) simulations. Quantum chemical parameters as well as the radial distribution function indices and binding energies confirm the experimental results.     

Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE₂) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.     

Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

An Autophagy-Disrupting Small Molecule Promotes Cancer Cell Death via Caspase Activation

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.     

Effects of annealing at high pressure on structure and mechanical properties of Al87Ni7Gd6 metallic glass

The effects of annealing and annealing with a superimposed pressure of 940 MPa on the primary crystallization behaviour of α-Al and the resulting micro-hardness have been studied for as-quenched Al₈₇Ni₇Gd₆ metallic glass. Isothermal annealing experiments were conducted for 30 min at 188 °C, 191 °C, and 205 °C in silicone oil maintained either at atmospheric pressure (i.e. 0.1 MPa) or at 940 MPa. XRD analyses detected the evolution of structure with annealing at 0.1 MPa, while specimens annealed with 940 MPa pressure exhibited sharper diffraction peaks than those annealed at 0.1 MPa. DSC measurements were conducted on the as-received amorphous ribbons as well as ribbons annealed at different temperatures at either 0.1. MPa or with 940 MPa superimposed pressure. Specimens annealed with 940 MPa pressure exhibited higher onset temperatures (i.e. T_x1) and temperatures for the first exothermic peak (i.e. T_p1) for primary crystallization. TEM measurements revealed an increase in the volume fraction of α-Al with increases in annealing temperature, while micro-hardness measurements revealed an increase in hardness with increasing amounts of α-Al. Specimens annealed with 940 MPa pressure exhibited further increases in both the volume fraction of α-Al and resulting micro-hardness.     

MECHANISM OF NON-EQUILIBRIUM SEGREGATION OF SOLUTE TO GRAIN BOUNDARIES

本文以空位-溶质原子拖曳机制为基础,并考虑了空位、溶质原子和复合体三者的反应平衡及晶界平衡偏聚的作用,得到了溶质原子的非平衡晶界偏聚动力学方程。对硼在奥氏体中等温及连续冷却时所产生的非平衡晶界偏聚现象进行了理论计算,得到了与实验较为一致的结果。     

A study of the cu clusters using gray-coded genetic algorithms and differential evolution

Energy minimization studies were carried out for a number of Cu clusters using binary and Gray-coded genetic algorithms along with real coded differential evolution, and their optimized ground state geometries are presented. The potential energy function is constructed using a two-body interaction methodology, involving both attractive and repulsive pair-potential terms. The results obtained through the evolutionary algorithms are compared against those obtained earlier using a Monte Carlo technique.