Acid-sensing ion channels (ASICs) are emerging as fundamental players in the regulation of neural plasticity and in pathological conditions. Here we showed that lead (Pb2+), a well known neurotoxic metal ion, reversibly and concentration-dependently inhibited ASIC currents in the acutely dissociated spinal dorsal horn and hippocampal CA1 neurons of rats. In vitro expression of ASIC subunits in combination demonstrated that both ASIC1 and -3 subunits were sensitive to Pb2+. Mechanistically, Pb2+ reduced the pH sensitivity of ASICs independent of membrane voltage change. Moreover, Pb2+ inhibited the ASIC-mediated membrane depolarization and the elevation of intracellular Ca2+ concentration. In addition, we compared the effect of Pb2+ with that of Ca2+ or amiloride to explore the possible interactions of Pb2+ and Ca2+ in regulating ASICs, and we found that Pb2+ inhibited ASIC currents independent of the amiloride/Ca2+ blockade. Because ASIC1b and -3 subunits are mainly expressed in peripheral neurons, our data identified ASIC1a-containing Ca2+-permeable ASIC as a novel central target of Pb2+ action, which may contribute to Pb2+ neurotoxicity.
We investigate the Ti-doping effect on the charge density wave (CDW) of 1T-TaS2 by combining scanning tunneling microscopy (STM) measurements and first-principle calculations.Although the Ti-doping induced phase evolution seems regular with increasing of the doping concentration (x), an unexpected chiral CDW phase is observed in the sample with x = 0.08, in which Ti atoms almost fully occupy the central Ta atoms in the CDW clusters. The emergence of the chiral CDW is proposed to be from the doping-enhanced orbital order. Only when x = 0.08, the possible long-range orbital order can trigger the chiral CDW phase. Compared with other 3d-elements doped 1T-TaS2, the Ti-doping retains the electronic flat band and the corresponding CDW phase, which is a prerequisite for the emergence of chirality. We expect that introducing elements with a strong orbital character may induce a chiral charge order in a broad class of CDW systems. The present results open up another avenue for further exploring the chiral CDW materials.
We report the superconductivity of PbTaS2 single crystals with the centrosymmetric structure. The systematic measurements of magnetization, electric transport and specific heat indicate that PbTaS2 is a weakly coupled type-II superconductor with transition temperature Tc ~ 2.6 K. Furthermore, the band structure calculations predicted four nodal lines near the Fermi energy with 'drumhead-like' surface states, suggesting centrosymmetric PbTaS2 is a candidate of topological nodal line semimetals. These results demonstrate that PbTaS2 may open up another avenue for further exploring the properties of superconductivity and topological nodal-line states.
Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.
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