Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
View Article and Find Full Text PDFDiapause is essential for insect survival under adverse environmental conditions and plays a crucial role in regulating reproduction. However, the role of long non-coding RNAs (lncRNAs) in this process remains unclear. In this study, we investigated the function of lncRNAs in the diapause of Aspongopus chinensis.
View Article and Find Full Text PDFIntense inflammatory responses and elevated levels of reactive oxygen species (ROS) extremely exacerbate the pathological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) can mitigate SCI-related inflammation but their production yield remains limited. Alternatively, MSC-extruded nanovesicles (NV) inherit the therapeutic potential from MSCs and have a markedly higher yield than EV.
View Article and Find Full Text PDFPurpose: This study aimed to explore symptom clusters and the inter-relationship of symptoms in esophageal cancer (EC) patients during the first week after surgery.
Methods: A cross-sectional survey across multiple centers was carried out using the EORTCQLQ-OES18. Patients with esophageal cancer within a week post-surgery were recruited from the "Be Resilient to Cancer" project in Guangdong, Hunan, and Sichuan provinces between January and September 2024.
Peracetic acid (PAA) is an emerging disinfectant known to be highly effective against various microorganisms. However, the capability of PAA to eliminate spores under different conditions and its application in liquid and gaseous forms remain unclear. Here, we aimed to develop a stabilized single-composite PAA and evaluate its disinfection efficacy in both liquid and gaseous form against suspended or surface-coated spores under varying temperature and humidity conditions.
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