CRAC ion channel inhibitors / Roche, Madrigal Pharma - LARVOL DELTA

Scalable and hardness-tolerant H2O2 electrosynthesis in tap-water-based electrolytes enabled by electrode architecture and reactor engineering. (PubMed, Water Res) - "Operando electrochemical reflection-absorption imaging elucidates a unique tolerance mechanism wherein the crack channels retain their hydrophobicity and gas permeability to support sustained reaction despite the severe deactivation of catalyst islands by scaling. Leveraging this design, we engineer a scaled-up, membrane-free electrolyzer that, operating directly with tap water at 100 mA cm-2, achieves high-throughput H2O2 production (600 mL min-1) for >200 h. This work resolves the critical hardness tolerance bottleneck, establishing a robust foundation for the deployment of on-site H2O2 electrosynthesis in diverse real-world water matrices."

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Identifying hydrogeochemistry evolution mechanism in high-sulfur non-ferrous metal mining areas via hydrochemical characteristics and isotopic evidence. (PubMed, J Contam Hydrol) - "Although the fissure water flowing from the closed mine to the mining mine is neutral, considering the fact that the fissure water will aggravate the mine drainage and the water quality will deteriorate, active measures should be taken to identify crack channels as far as possible to reduce the risk of acid mine drainage diffusion through minimizing the hydraulic connection between them. These findings could understand the hydrogeochemical characteristics of high‑sulfur non-ferrous metal mines, thus effectively prevent groundwater pollution in the mining regions."

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A multiple-oscillator mechanism underlies antigen-induced Ca oscillations in Jurkat T-cells. (PubMed, J Biol Chem) - "The loss of both STIM proteins abrogates CRAC channel activity, drastically reduces ER Ca content, severely hampers cell proliferation and enhances cell death. These results clarify the mechanism and the contribution of STIM proteins to Ca oscillations in T-cells."

Journal • NFATC1 • STIM1

The Mitochondrial Ca Uniporter is a Central Regulator of Interorganellar Ca Transfer and NFAT Activation. (PubMed, J Biol Chem) - "MCU activity sustains cytosolic Ca signaling by preventing Ca-dependent inactivation (CDI) of store-operated Ca release-activated Ca (CRAC) channels and by inhibiting Ca extrusion...Our data show that MCU has dual counterbalancing functions at the cytosol-mitochondria interface, whereby the cell-specific MCU-dependent cytosolic Ca clearance and buffering capacity of mitochondria reciprocally regulate inter-organellar Ca transfer and NFAT nuclear translocation during receptor-evoked signaling. These findings highlight the critical dual function of the MCU not only in the acute Ca buffering by mitochondria but also in shaping ER and cytosolic Ca signals that regulate cellular transcription and function."

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