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Pannexin 1 (Panx1) forms large-pore, single-membrane channels that connect the intracellular and extracellular environments, permitting the passage of ions and small molecules such as ATP. Panx1 channels are involved in diverse signaling pathways that contribute to various physiological processes, including sensory processing, although their precise mechanisms of action remain incompletely understood. This study reveals a Panx1-mediated mechanism regulating visual signal processing in the amphibian retina. Using immunolabeling and confocal imaging, we localized Panx1 channels in the cone-dominated On-bipolar cells, specifically at both somas and axon terminals. Whole-cell patch-clamp recordings showed that these channels have high permeability to Cl⁻ ions, which can be blocked by¹⁰Panx1 peptide, carbenoxolone, and mefloquine, all recognized as Panx1 inhibitors. Blocking Panx1 channels or reducing external Cl⁻ concentrations significantly increased bright light-induced delayed spontaneous excitatory responses in ganglion cells, indicating an inhibitory role of Panx1 channels at the bipolar cell synaptic release. These delayed spontaneous responses in ganglion cells, known as rebound currents, are associated with afterimage signals in the retina. Our findings suggest that Panx1 channels help prevent over-excitation associated with bright light-induced afterimage phenomena. 

Abstract Ferroptosis has been shown to play a crucial role in preventing cancer development, but the underlying mechanisms of dysregulated genes and genetic alternations driving cancer development by regulating ferroptosis remain unclear. Here, we showed that the synergistic role of ELF3 overexpression and PTEN deficiency in driving lung cancer development was highly dependent on the regulation of ferroptosis. HumanELF3(hELF3) overexpression in murine lung epithelial cells only caused hyperplasia with increased proliferation and ferroptosis. hELF3overexpression andPtengenetic disruption significantly induced lung tumor development with increased proliferation and inhibited ferroptosis. Mechanistically, we found it was due to the induction of SCL7A11, a typical ferroptosis inhibitor, and ELF3 directly and positively regulated SCL7A11 in the PTEN-deficient background. Erastin-mediated inhibition of SCL7A11 induced ferroptosis in cells with ELF3 overexpression and PTEN deficiency and thus inhibited cell colony formation and tumor development. Clinically, human lung tumors showed a negative correlation betweenELF3andPTENexpression and a positive correlation betweenELF3andSCL7A11in a subset of human lung tumors withPTEN-low expression.ELF3andSCL7A11expression levels were negatively associated with lung cancer patients’ survival rates. In summary, ferroptosis induction can effectively attenuate lung tumor development induced byELF3overexpression andPTENdownregulation or loss-of-function mutations. 

Abstract. Seasonal snowpack is an essential component in the hydrological cycle and plays a significant role in supplying water resources to downstream users. Yet the snow water equivalent (SWE) in seasonal snowpacks, and its space–time variation, remains highly uncertain, especially over mountainous areas with complex terrain and sparse observations, such as in High Mountain Asia (HMA). In this work, we assessed the spatiotemporal distribution of seasonal SWE, obtained from a new 18-year HMA Snow Reanalysis (HMASR) dataset, as part of the recent NASA High Mountain Asia Team (HiMAT) effort. A Bayesian snow reanalysis scheme previously developed to assimilate satellite-derived fractional snow-covered area (fSCA) products from Landsat and MODIS platforms has been applied to develop the HMASR dataset (at a spatial resolution of 16 arcsec (∼500 m) and daily temporal resolution) over the joint Landsat–MODIS period covering water years (WYs) 2000–2017. Based on the results, the HMA-wide total SWE volume is found to be around163 km3 on average and ranges from 114 km3 (WY2001) to 227 km3 (WY2005) when assessed over 18 WYs. The most abundant snowpacks are found in the northwestern basins (e.g., Indus, Syr Darya and Amu Darya) that are mainly affected by the westerlies, accounting for around 66 % of total seasonal SWE volume. Seasonal snowpack in HMA is depicted by snow accumulating through October to March and April, typically peaking around April and depleting in July–October, with variations across basins and WYs. When examining the elevational distribution over the HMA domain, seasonal SWE volume peaks at mid-elevations (around 3500 m), with over 50 % of the volume stored above 3500 m. Above-average amounts of precipitation causes significant overall increase in SWE volumes across all elevations, while an increase in air temperature (∼1.5 K) from cooler to normal conditions leads to an redistribution in snow storage from lower elevations to mid-elevations. This work brings new insight into understanding the climatology and variability of seasonal snowpack over HMA, with the regional snow reanalysis constrained by remote-sensing data, providing a new reference dataset for future studies of seasonal snow and how it contributes to the water cycle and climate over the HMA region. 

This work describes our discovery of the dominant role of highly charged interfaces on the electrothermal transport properties of PbS, along with a method to reduce the barrier potential for charge carriers by an order of magnitude. High temperature thermoelectrics such as PbS are inevitably exposed to elevated temperatures during postsynthesis treatment as well as operation. However, we observed that as the material was heated, large concentrations of sulfur vacancy (VS̈) sites were formed at temperatures as low as 266 °C. This loss of sulfur doped the PbS n-type and increased the carrier concentration, where these excess electrons were trapped and immobilized at interfacial defect sites in polycrystalline PbS with an abundance of grain boundaries. Sulfur deficient PbS0.81 exhibited a large barrier potential for charge carriers of 0.352 eV, whereas annealing the material under a sulfur-rich environment prevented VS̈ formation and lowered the barrier by an order of magnitude to 0.046 eV. Through ab initio calculations, the formation of VS̈ was found to be more favorable on the surface compared to the bulk of the material with a 1.72 times lower formation energy barrier. These observations underline the importance of controlling interface-vacancy effects in the preparation of bulk materials comprised of nanoscale constituents.