Enhancement for phonon-mediated superconductivity up to 37 K in few-hydrogen metal-bonded layered magnesium hydride under atmospheric pressure.

The discovery of superconductivity in layered MgB2 has renewed interest in the search for high-temperature conventional superconductors, leading to the synthesis of numerous hydrogen-dominated materials with high critical temperatures (Tc) under high pressures. However, achieving a high-Tc superconductor under ambient pressure remains a challenging goal. In this study, we propose a novel approach to realize a high-temperature superconductor under ambient pressure by introducing a hexagonal H monolayer into the hexagonal close-packed magnesium lattice, resulting in a new and stable few-hydrogen metal-bonded layered magnesium hydride (Mg4)2H1. This compound exhibits superior ductility compared to multi-hydrogen, cuprate, and iron-based superconductors due to its metallic bonding. Our unconventional strategy diverges from the conventional design principles used in hydrogen-dominated covalent high-temperature superconductors. Using anisotropic Migdal-Eliashberg equations, we demonstrate that the stable (Mg4)2H1 compound is a typical phonon-mediated superconductor, characterized by strong electron-phonon coupling and an excellent Tc of 37 K under ambient conditions, comparable to that of MgB2. Our findings not only present a new pathway for exploring high-temperature superconductors but also provide valuable insights for future experimental synthesis endeavors.

Computational and experimental prediction of molecules involved in the anti-melanoma action of berberine.

ETHNOPHARMACOLOGIC RELEVANCE: Berberine (BBR) is a naturally occurring alkaloid compound that can be found in Chinese medicinal herbs such as Rhizoma Coptidis and Phellodendri Cortex. These BBR containing herbs are commonly used by Chinese medicine doctors to treat cancers including melanoma. In this study, we explored proteins potentially involved in the anti-melanoma effects of BBR using computational and experimental approaches. MATERIALS AND METHODS: Target proteins of BBR were predicted using the reverse pharmacophore screening, molecular docking and molecular dynamics. Anti-melanoma activities of BBR in melanoma cells were examined by MTT and EdU proliferation assays. Effects of BBR on activities of target proteins in melanoma cells were examined by Western blotting or fluorescence assay. RESULTS: Ten proteins implicated in cancer and with high fit-score in the reverse pharmacophore screening were selected as potential targets of BBR. Molecular docking and molecular dynamics revealed that BBR could stably bind to four of the ten proteins, namely 3-phosphoinositide-dependent protein kinase 1 (PDK1), glucocorticoid receptor (GR), p38 mitogen-activated protein kinase (p38) and dihydroorotate dehydrogenase (DHODH). Cellular experiments showed that BBR inhibited cell proliferation, increased the phosphorylation of GR and p38, and inhibited the activity of DHODH in A375 human melanoma cells. CONCLUSIONS: These findings suggest that p38, GR and DHODH are potentially involved in the anti-melanoma action of BBR. This study provided a chemical and pharmacological justification for the clinical use of BBR-containing herbs in melanoma treatment.

Sonic hedgehog improves delayed wound healing via enhancing cutaneous nitric oxide function in diabetes.

Sonic hedgehog (SHH) plays an important role in postnatal tissue repair. The present study tested the hypothesis that impaired SHH pathway results in delayed wound healing by suppressing cutaneous nitric oxide (NO) function in type 1 diabetes. Adult male C57/B6 mice and streptozotocin (STZ)-induced type 1 diabetic mice were used. Although cutaneous SHH and Patched-1 (Ptc-1 encoded by PTCH, PTCH 1) proteins were increased significantly on day 4 after wounding compared with day 0 in normal mice, both were decreased significantly in STZ-induced diabetic mice. Topical application of SHH restored wound healing delay in STZ-induced diabetic mice, with a concomitant augmentation of both cutaneous constitutive nitric oxide synthase (NOS) activity and nitrite level. The effects of SHH on wound healing and cutaneous NO function were markedly inhibited by SHH receptor inhibitor cyclopamine. After 24-h treatment in vitro, SHH (5-20 microg/ml) significantly increased cutaneous endothelial NOS protein expression, NOS activity and NO level in normal mice and STZ-induced diabetic mice in a concentration-dependent manner, an effect that was blunted by cyclopamine and NOS inhibitor N(omega)-nitro-L-arginine methyl ester. The phosphatidylinositol 3-kinase inhibitor LY-294002 significantly blunted the increase of NOS activity and NO level induced by SHH treatment in human umbilican vein endothelial cells. These results demonstrate that the SHH pathway is activated in a normal wound, and its reduction results in impaired NO function and wound healing in diabetes. Strategies aimed at augmenting the endogenous SHH pathway may provide an effective means in ameliorating delayed diabetic wound healing.