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Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essential. Here, we identified that an underappreciated serine/threonine kinase, cyclin-dependent kinase-like 3 (CDKL3), crucially drives rapid cell cycle progression and cell growth in cancers. With regard to mechanism, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of cyclin-dependent kinase 4 (CDK4) by direct phosphorylation on T172 to sustain [G.sub.1] phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized, and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes acquired resistance to CDK4/6 inhibitor. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presents an integrated paradigm of cancer cell cycle regulation and suggests CDKL3 targeting as a feasible approach in cancer treatment., Introduction The cell cycle consists of multiple modules and machineries to regulate cell division in a precise manner (1, 2). A complete cell cycle is composed of [G.sub.1], S, [G.sub.2], [...]

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The quantum confinement effect is an effective strategy to broaden the bandgaps of quasi-2D perovskites for achieving efficient blue perovskite light-emitting diodes (PeLEDs). However, reducing the quantum well (QW) width in quasi-2D PEA2Csn−1PbnBr3n+1 perovskites always induces a disordered QW distribution, which is detrimental to its electroluminescent performance. We disclose that low-n quasi-2D perovskites tend to freely distort octahedra forming γ-phase perovskites due to the lattice mismatch brought by small-size Cs+ ions. The short-chain ligand ethylammonium (EA) is then used to suppress the distortion of [PbBr6]4− octahedra by partially entering the A-site interspace as a larger cation. The quasi-2D perovskites prepared with the mixed EA/PEA ligands exhibit a narrow diffraction peak with little octahedral distortion, uniform QW distribution and efficient energy transfer process. The sky-blue PeLEDs prepared with the proposed strategy of mixed EA/PEA ligands achieve a remarkable external quantum efficiency of 14.14%. [ABSTRACT FROM AUTHOR]

The electrochemical N2 reduction reaction (ENRR), driven by renewable electricity and run under ambient conditions, offers a promising sustainable avenue for carbon‐neutral NH3 production. Yet, to efficiently bind and activate the inert N2 remains challenge. Herein, effective and stable electrochemical NH3 synthesis on Sm(OH)3 via enhanced adsorption of hydrogen and dinitrogen by dual integration of sulfur dopants and oxygen vacancies (VO) is reported. The resulting S‐doped lanthanide electrocatalyst attains both a good NH3 yield rate, exceeding 21 μgNH3 h−1 mgcat.−1, and an NH3 faradaic efficiency of over 29% at −0.3 V (vs reversible hydrogen electrode) in an H‐type cell using a neutral electrolyte, figures of merit that are largely maintained after 2 days of consecutive polarization. Density functional theory calculations show that the adsorption energy barrier of N2 on S‐Sm(OH)3(VO) is greatly lowered by the introduction of VO. In addition, the S sites improve the adsorption of hydrogen produced via the Volmer reaction, which is conducive to the formation of the *N–NH intermediate (i.e., the potential determining step, PDS) on adjacent Sm sites, and thereby significantly promotes the reaction kinetics of ENRR. The PDS free energy for the catalyst is comparable with the values at the peak of the ENRR volcano plots of leading transition metal catalyst surfaces. [ABSTRACT FROM AUTHOR]

The electrochemical N2 reduction reaction (ENRR), driven by renewable electricity and run under ambient conditions, offers a promising sustainable avenue for carbon‐neutral NH3 production. Yet, to efficiently bind and activate the inert N2 remains challenge. Herein, effective and stable electrochemical NH3 synthesis on Sm(OH)3 via enhanced adsorption of hydrogen and dinitrogen by dual integration of sulfur dopants and oxygen vacancies (VO) is reported. The resulting S‐doped lanthanide electrocatalyst attains both a good NH3 yield rate, exceeding 21 μgNH3 h−1 mgcat.−1, and an NH3 faradaic efficiency of over 29% at −0.3 V (vs reversible hydrogen electrode) in an H‐type cell using a neutral electrolyte, figures of merit that are largely maintained after 2 days of consecutive polarization. Density functional theory calculations show that the adsorption energy barrier of N2 on S‐Sm(OH)3(VO) is greatly lowered by the introduction of VO. In addition, the S sites improve the adsorption of hydrogen produced via the Volmer reaction, which is conducive to the formation of the *N–NH intermediate (i.e., the potential determining step, PDS) on adjacent Sm sites, and thereby significantly promotes the reaction kinetics of ENRR. The PDS free energy for the catalyst is comparable with the values at the peak of the ENRR volcano plots of leading transition metal catalyst surfaces. [ABSTRACT FROM AUTHOR]

Development of low‐cost and high‐efficiency electrocatalysts for overall water splitting is of great significance in the sustainable hydrogen economy. Herein, Fe1.2(CoNi)1.8Sex medium‐entropy metal selenides (MESes) nanoparticles are prepared via the selenylation of metal‐organic frameworks (MOFs) precursors. The optimal Fe1.2(CoNi)1.8Se6 MESe exhibits an outstanding electrocatalytic performance in alkaline media, offering low overpotentials of 66 and 216 mV at 10 mA cm−2 for the hydrogen evolution reaction and oxygen evolution reaction, respectively. A full electrolysis apparatus with Fe1.2(CoNi)1.8Se6 MESe as both cathode and anode displays an excellent performance, achieving 10 mA cm−2 at a potential of 1.55 V. Furthermore, density functional theory calculations demonstrate that the formation of MESe enhances the surface charge density and brings the d‐band center closer to Fermi level, as compared with that of the MOF precursor. Overall, the proposed strategy of medium‐entropy materials presents a low‐cost approach to fabricate energy storage and conversion devices. [ABSTRACT FROM AUTHOR]