A Zinc-Rich Coating Fabricated on a Magnesium Alloy by Oxide Reduction

The corrosion resistance of magnesium alloys could be enhanced by covering metallic coatings on the surface. The zinc-rich coating is one of these metallic coatings. To fabricate a zinc-rich coating on magnesium alloys, the substrate should be pretreated carefully, and a protective atmosphere is usually required. In this research, a zinc-rich coating was successfully fabricated on the AZ91D magnesium alloy in air by a diffusion alloying method, with zinc oxide as the zinc source. At the same time, the pretreatment of the magnesium alloy matrix was greatly simplified. The as-diffusion-alloyed zinc-rich intermetallic layer was investigated, utilizing SEM, EDS, and XRD, respectively. It is inferred that zinc oxide was reduced into Zn atoms by the active Mg atoms, and the Mg atoms were coming from the magnesium alloy matrix. Then the Zn atoms passed through the oxide film and formed an intermetallic layer on the magnesium alloy surface. Thus, taking advantage of the activity of Mg atoms, magnesium alloys could be surface alloyed with oxides

The corrosion behavior of Mg–Nd binary alloys in the harsh marine environment

The corrosion behavior of Mg-Nd binary alloys in the harsh South China Sea environment was researched by scanning electron microscopy, energy-dispersive spectrometry and X-ray diffraction analysis. In order to explain the corrosion mechanism, corrosion resistance was analyzed by weight loss rate and electrochemical measurement in the laboratory. With a continuous enlargement of Nd-content, Mg12Nd phases increased and multiplied. The weight loss rate of Mg-0.5Nd alloy was 0.0436 mg•cm−2•y−1 (0.0837 mm•y−1), whereas that of Mg-1.5Nd alloy was 0.0294 mg•cm−2•y−1 (0.0517 mm•y−1) during the exposure corrosion in the South China Sea site. The mechanical strength of Mg-1.5Nd alloy was 148 MPa before the exposure in the harsh marine environment, while the residual mechanical strength was merely about 94 MPa after the exposure test. Both Mg-1.5Nd alloy and Mg-1.0Nd alloy occurred the brittle fracture, which resulted that the elongation was nearly equal to zero. The self-corrosion current density demonstrated that degradation rate of Mg-Nd binary alloys was as follows : Mg-0.5Nd>Mg-1.0Nd>Mg-1.5Nd. For the South China Sea corrosion site, a large amount of sea salts exited in the atmospheric environment. Due to the heavy rainfall and high humidity, sodium chloride in the atmospheric environment dissolved, more serious electrochemical corrosion occurred on the surface of Mg-Nd binary alloys

Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent

The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound <b>13n</b> displayed the highest cytotoxicity toward HeLa cells (IC₅₀ = 1.4 μM). Structure–activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that <b>13n</b> selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to <b>13n</b> insult, while knockdown of TrxR sensitizes cells to <b>13n</b> treatment, highlighting the physiological significance of targeting TrxR by <b>13n</b>. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development

Highly Selective Off–On Fluorescent Probe for Imaging Thioredoxin Reductase in Living Cells

The first fluorescent probe for mammalian thioredoxin reductase (TrxR), TRFS-green, was designed, synthesized, and fully evaluated. The probe features a 1,2-dithiolane scaffold with a quenched naphthalimide fluorophore. TRFS-green displays a green fluorescence off–on change induced by the TrxR-mediated disulfide cleavage and subsequent intramolecular cyclization to liberate the masked naphthalimide fluorophore. It was demonstrated in vitro that TRFS-green manifests high selectivity toward TrxR over other related enzymes and various small molecule thiols as well as biological reducing molecules. HPLC analyses indicated that TRFS-green was exclusively converted to naphthalimide catalyzed by TrxR. The ability in triggering on the fluorescence signal by cellular protein extracts correlates well with the endogenous TrxR activity in different cells. Furthermore, inhibition of TrxR by 2,4-dinitrochlorobenzene or depletion of TrxR by immunoprecipitation remarkably decreases the reduction of TRFS-green by cellular protein extracts. Finally, TRFS-green was successfully applied in imaging TrxR activity in living cells. The fluorescence signal of TRFS-green in living cells was inhibited by pretreating the cells with TrxR inhibitor in a dose-dependent manner, potentiating the development of living cell-based screening assay for identifying TrxR inhibitors. We expect the novel fluorescent probe TRFS-green would facilitate the discovery of TrxR-targeting small molecules for potential therapeutic agents and provide significant advances in understanding the physiological/pathophysiological functions of TrxR in vivo

Dithiaarsanes Induce Oxidative Stress-Mediated Apoptosis in HL-60 Cells by Selectively Targeting Thioredoxin Reductase

The selenoprotein thioredoxin reductase (TrxR) plays a pivotal role in regulating cellular redox homeostasis and has attracted increasing attention as a promising anticancer drug target. We report here that 2-(4-aminophenyl)-1,3,2-dithiarsinane (PAO–PDT, <b>4</b>), a potent and highly selective small molecule inhibitor of TrxR, stoichiometrically binds to the C-terminal selenocysteine/cysteine pair in the enzyme in vitro and induces oxidative stress-mediated apoptosis in HL-60 cells. The molecular action of <b>4</b> in cells involves inhibition of TrxR, elevation of reactive oxygen species, depletion of cellular thiols, and activation of caspase-3. Knockdown of TrxR sensitizes the cells to <b>4</b> treatment, whereas overexpression of the functional enzyme alleviates the cytotoxicity, providing physiological relevance for targeting TrxR by <b>4</b> in cells. The simplicity of the structure and the presence of an easily manipulated amine group will facilitate the further development of <b>4</b> as a potential cancer chemotherapeutic agent

Le Courrier

24 octobre 18271827/10/24 (A0,N297)