Explorin gearth-abundant oxygen evolution reaction electrocatalysts is attracting tremendous attention but still remains challenging. In this study, we design and synthesize hierarchical iron-doped nickel selenides with hollow structure and tunable composition. Benefiting from the synergistic effects of high specific surface area and optimal heteroatom doping, 5% Fe doped NiSe 2 hollow spheres present excellent performances, exhibiting a 10 mA cm −2 current density at the overpotential as low as 231 mV and long-term stability for 20 h at 15 mA cm −2 in the basic medium.
Development of highly efficient non‐noble metal electrocatalysts to replace platinum for hydrogen evolution reaction (HER) has attracted tremendous attention in recent years. In this work, a kind of novel MoxW2−xC@C hollow spheres with tunable stoichiometry is successfully synthesized. The synergetic effect of appropriate W‐introducing and hollow structure enables the composites to have superior performance for electrocatalytic HER and long‐term stability in a wide pH range. The MoxW2−xC@C with an optimized Mo/W ratio of 1.26/0.74 exhibits an overpotential (η10) of 106, 127, and 152 mV at 10 mA cm−2 in 1 m KOH, 0.5 m H2SO4, and 1 m phosphate buffer saline (PBS), respectively, and its overpotential in high current density region (η300) is only 237 and 250 mV in alkaline and acidic electrolytes, which are significantly better than most of the previously reported electrocatalysts.
Therapeutic perturbation of cyclin-dependent kinase 12 (CDK12) is proposed to have pleiotropic effects in ovarian cancer, including direct cytotoxicity against tumor cells and indirect induction of immunogenicity that confer synthetic sensitivity to immune-based treatment. However, formal testing of this hypothesis has been hindered by an insufficient mechanistic understanding of CDK12 and its close homolog CDK13, as well as generally unfavorable pharmacokinetics of available CDK12/CDK13 covalent inhibitors. In this study, we employed an innovative arsenous warhead modality to develop an orally bioavailable CDK12/CDK13 covalent compound. The dual CDK12/CDK13 inhibitor ZSQ836 exerted potent anticancer activity in cell culture and mouse models and induced transcriptional reprogramming, including downregulation of DNA damage response genes. CDK12 and CDK13 were both ubiquitously expressed in primary and metastatic ovarian cancer, and the two kinases performed independent and synergistic functions to promote tumorigenicity. Unexpectedly, although ZSQ836 triggered genomic instability in malignant cells, it counterintuitively impaired lymphocytic infiltration in neoplastic lesions by interfering with T cell proliferation and activation. These findings highlight the Janus-faced effects of dual CDK12/CDK13 inhibitors by simultaneously suppressing tumor and immune cells, offering valuable insights into the future direction of drug discovery to pharmacologically target CDK12.
Although some progress on exploring non-noble-metal based materials with remarkable activity for electrocatalytic hydrogen or oxygen evolution reactions has been made, it still remains critical challenge especially for overall water...
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