Assessment of the combined vulnerability to droughts and heatwaves in Shandong Province in summer from 2000 to 2018.

Droughts and heat waves exhibit synergistic effects and are among the world's most costly disasters. To explore the spatiotemporal differences and formation mechanisms of the combined vulnerability to droughts and heat waves in Shandong Province over the past 20 years, a vulnerability scoping diagram (VSD) model with three dimensions-exposure, sensitivity, and adaptability-was constructed to assess and compare the combined vulnerability to high-temperature and drought events, considering economic and social conditions. The results showed that (1) over the past 20 years, heat waves and droughts have increased in Shandong Province. The number of high-temperature events significantly increased in the west and decreased along the eastern coast, and drought change was characterized by an increase in the south and a decrease in the north. (2) The combined exposure to summer droughts and heat waves in Shandong Province showed a significant increasing trend (P < 0.05) at a rate of approximately 0.072/10a; the combined sensitivity significantly decreased (P < 0.05) at a rate of approximately 0.137/10a, and the combined adaptability continued to increase at a rate of approximately 0.481/10a. (3) The combined vulnerability to summer droughts and heat waves in the western inland area of Shandong Province was high and gradually decreased toward the southeastern coast. The overall decrease trend was nonsignificant with a decrease of approximately 0.126/10a, and the decline rate decreased from northwest to southeast, in which Laiwu, Yantai, Jinan, and Zibo cities exhibited a significant decreasing trend (P < 0.05). Although the compound vulnerability of Shandong Province has decreased insignificantly, the frequency of combined drought and heat wave events has increased, and the combined vulnerability will increase in the future.

Mechanical activation opens a lipid-lined pore in OSCA ion channels.

OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.

MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels.

Piezo channels are critical cellular sensors of mechanical forces. Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few Piezo channel-binding proteins have emerged. In this work, we found that MyoD (myoblast determination)-family inhibitor proteins (MDFIC and MDFI) are PIEZO1/2 interacting partners. These transcriptional regulators bind to PIEZO1/2 channels, regulating channel inactivation. Using single-particle cryogenic electron microscopy, we mapped the interaction site in MDFIC to a lipidated, C-terminal helix that inserts laterally into the PIEZO1 pore module. These Piezo-interacting proteins fit all the criteria for auxiliary subunits, contribute to explaining the vastly different gating kinetics of endogenous Piezo channels observed in many cell types, and elucidate mechanisms potentially involved in human lymphatic vascular disease.