Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.
Tungsten carbides, featured by their Pt-like electronic structure, have long been advocated as potential replacements for the benchmark Pt-group catalysts in hydrogen evolution reaction. However, tungsten-carbide catalysts usually exhibit poor alkaline HER performance because of the sluggish hydrogen desorption behavior and possible corrosion problem of tungsten atoms by the produced hydroxyl intermediates. Herein, we report the synthesis of tungsten atomic clusters anchored on P-doped carbon materials via a thermal-migration strategy using tungsten single atoms as the parent material, which is evidenced to have the most favorable Pt-like electronic structure by in-situ variable-temperature near ambient pressure X-ray photoelectron spectroscopy measurements. Accordingly, tungsten atomic clusters show markedly enhanced alkaline HER activity with an ultralow overpotential of 53 mV at 10 mA/cm2 and a Tafel slope as low as 38 mV/dec. These findings may provide a feasible route towards the rational design of atomic-cluster catalysts with high alkaline hydrogen evolution activity.
Some gamma-ray bursts (GRBs) have a tera–electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory of the bright GRB 221009A, which serendipitously occurred within the instrument field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger, then rose to a peak about 10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
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