Acid-sensing ion channels (ASICs) have long been considered as extracellular proton (H(+))-gated cation channels, and peripheral ASIC3 channels seem to be a natural sensor of acidic pain. Here, we report the identification of a nonproton sensor on ASIC3. We show first that 2-guanidine-4-methylquinazoline (GMQ) causes persistent ASIC3 channel activation at the normal pH. Using GMQ as a probe and combining mutagenesis and covalent modification analysis, we then uncovered a ligand sensor lined by residues around E423 and E79 of the extracellular "palm" domain of the ASIC3 channel that is crucial for activation by nonproton activators. Furthermore, we show that GMQ activates sensory neurons and causes pain-related behaviors in an ASIC3-dependent manner, indicating the functional significance of ASIC activation by nonproton ligands. Thus, natural ligands beyond protons may activate ASICs under physiological and pathological conditions through the nonproton ligand sensor, serving for channel activation independent of abrupt and marked acidosis.

Background Since SARS‐CoV‐2 infection was first identified in December 2019, the novel coronavirus‐induced pneumonia COVID‐19 spread rapidly and triggered a global pandemic. Recent bioinformatics evidence suggests that angiotensin converting enzyme 2—the main cell entry target of SARS‐CoV‐2—is predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS‐CoV‐2 infection. Objectives To identify SARS‐CoV‐2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection. Methods From February 26 to April 2, 2020, 23 male patients with COVID‐19 were recruited. The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail. We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS‐CoV‐2 infection using approved methods. Results The age range of the 23 patients was 20–62 years. All patients tested negative for SARS‐CoV‐2 RNA in semen specimens. Among them, the virus had been cleared in 11 patients, as they tested negative. The remaining 12 patients tested negative for SARS‐CoV‐2 RNA in semen samples, but were positive in sputum and fecal specimens. The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts and sperm morphology of the patients were within normal ranges. Discussion and Conclusion In this cohort of patients with a recent infection or recovering from COVID‐19, there was no SARS‐CoV‐2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection.

We report results of quantum mechanics (QM) mechanistic studies of Nafion membrane degradation in a polymer electrolyte membrane (PEM) fuel cell. Experiments suggest that Nafion degradation is caused by generation of trace radical species (such as OH(●), H(●)) only when in the presence of H(2), O(2), and Pt. We use density functional theory (DFT) to construct the potential energy surfaces for various plausible reactions involving intermediates that might be formed when Nafion is exposed to H(2) (or H(+)) and O(2) in the presence of the Pt catalyst. We find a barrier of 0.53 eV for OH radical formation from HOOH chemisorbed on Pt(111) and of 0.76 eV from chemisorbed OOH(ad), suggesting that OH might be present during the ORR, particularly when the fuel cell is turned on and off. Based on the QM, we propose two chemical mechanisms for OH radical attack on the Nafion polymer: (1) OH attack on the S-C bond to form H(2)SO(4) plus a carbon radical (barrier: 0.96 eV) followed by decomposition of the carbon radical to form an epoxide (barrier: 1.40 eV). (2) OH attack on H(2) crossover gas to form hydrogen radical (barrier: 0.04 eV), which subsequently attacks a C-F bond to form HF plus carbon radicals (barrier as low as 1.00 eV). This carbon radical can then decompose to form a ketone plus a carbon radical with a barrier of 0.86 eV. The products (HF, OCF(2), SCF(2)) of these proposed mechanisms have all been observed by F NMR in the fuel cell exit gases along with the decrease in pH expected from our mechanism.