Hyperosmotic stress-induced NLRP3 inflammasome activation via the mechanosensitive PIEZO1 channel in dry eye corneal epithelium.

Unlabelled: The activation of the NLRP3 inflammasome by hyperosmotic stress is a critical pathophysiological response in dry eye disease (DED), driving the chronic cycle of inflammation on the ocular surface. The specific mechanism underlying hyperosmotic mechanical stimulation activates the NLRP3 inflammasome remains unclear. This study provides evidence that PIEZO1, a mechanosensitive ion channel, functions as the primary receptor for corneal epithelial cells in sensing mechanical stimulation induced by tear hyperosmolarity.

A strategy for Cas13 miniaturization based on the structure and AlphaFold.

The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2.