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Background: Accumulating evidence shows that high expression of casein kinase 2 (CK2) and phosphorylated acetyl CoA carboxylase (pACC) in patients with squamous cell carcinoma of the head and neck (SCCHN) correlates with decreased survival rates. Computational analysis has shown that ACC is a potential substrate for CK2, and its inhibition can suppress ACC phosphorylation in vitro. CX-4945, also known as silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2 and is under clinical investigation as a treatment for malignancies. We hypothesize that inhibition of CK2 by CX-4945 can reduce CK2-downstream phosphorylation of ACC as a therapeutic strategy against SCCHN.Methods: Three aggressive SCCHN cell lines (OSC-19, FaDu and HN31) were cultured to investigate the anticancer mechanism of the CK2 inhibitor, CX-4945. Cell cycle analysis, Annexin V/PI staining, and cleavage of PARP were performed to detect apoptosis. Western blot, electron microscopy and analysis of acidic vesicular organelle development were used to detect autophagy. Interference with cellular metabolism by CX-4945 treatment was determined by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry.Results: Cellular metabolism was impeded by CX-4945 in aggressive SCCHN cells by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry, and consequently time- and dose-dependent lipid droplet accumulation and non-apoptotic cell death were observed. The lipogenic enzyme ACC was demonstrated to be associated with CK2, and its repressive phosphorylation could be removed by the CK2 inhibitor CX-4945. Overexpression of ACC resulted in impaired cell survival following transient transfection.Conclusion: The findings demonstrate that CK2 inhibition impairs normal cellular energy metabolism and may be an attractive therapy for treating aggressive SCCHN. [ABSTRACT FROM AUTHOR]

Auxin and auxin‐mediated signaling pathways are known to regulate lateral root development. Although exocytic vesicle trafficking plays an important role in recycling the PIN‐FORMED (PIN) auxin efflux carriers and in polar auxin transport during lateral root formation, the mechanistic details of these processes are not well understood. Here, we demonstrate that BYPASS1‐LIKE (B1L) regulates lateral root initiation via exocytic vesicular trafficking‐mediated PIN recycling in Arabidopsis thaliana. b1l mutants contained significantly more lateral roots than the wild type, primarily due to increased lateral root primordium initiation. Furthermore, the auxin signal was stronger in stage I lateral root primordia of b1l than in those of the wild type. Treatment with exogenous auxin and an auxin transport inhibitor indicated that the lateral root phenotype of b1l could be attributed to higher auxin levels and that B1L regulates auxin efflux. Indeed, compared to the wild type, C‐terminally green fluorescent protein‐tagged PIN1 and PIN3 accumulated at higher levels in b1l lateral root primordia. B1L interacted with the exocyst, and b1l showed defective PIN exocytosis. These observations indicate that B1L interacts with the exocyst to regulate PIN‐mediated polar auxin transport and lateral root initiation in Arabidopsis. [ABSTRACT FROM AUTHOR]

Photochemical dehydrogenation of N-heterocyclic amines to corresponding N-heteroaromatics paired with hydrogen (H 2) production represents a promising route for the green and sustainable organic synthesis and clean fuel generation. Herein, metal-organic frameworks (MOFs)-supported CdS nanoparticles are gingerly fabricated for the visible light-initiated acceptorless dehydrogenation of diverse N-heterocycles at ambient conditions. With further nickel cocatalysts modification via a simple photodeposition method, the optimized MIL-101 @CdS-Ni composite exhibits remarkably enhanced activities, which are 8 folds higher than that of binary MIL-101 @CdS and 2.8 times higher than that of MOF-removed CdS-Ni counterparts, along with high selectivity and good stability. Mechanism studies reveal that active nickel species plays a key role in accelerating the separation of photogenerated charge carries and the cleavage of C−H and N−H bonds in the scaffold of N-heterocycles on the catalyst surface. This work is expected to guide the rational catalysts design of MOF-based multifunctional materials for photochemical coupling of concurrent organic synthesis with H 2 production. [Display omitted] • Ternary MOFs-supported CdS-Ni composites have been well prepared. • Photochemical dehydrogenation of a series of N-heterocycles is conducted mildly. • Supported effect of MOFs and Ni modification contributes to the boosted performance. • Carbon radicals as primary active intermediates are detected in reaction conditions. • Ni species plays a key role in accelerating the separation of photogenerated charge carries. [ABSTRACT FROM AUTHOR]

Incorporating different materials, such as metal sulfides, with metal-organic frameworks (MOFs) to develop MOF-based multifunctional composites with enhanced performance is an important area of research. However, the intrinsically high interfacial energy barrier significantly restricts the heterogeneous nucleation and nanoassembly of metal sulfides onto MOFs during the wet chemistry synthesis process. Herein, taking advantage of the natural tailorability of MOFs, the precise and controllable growth of metal sulfide nanoparticles (NPs) (CdS, ZnS, CuS and Ag2S) at the coordinatively unsaturated metal sites (CUSs) of MOFs to form MOF@metal sulfide composites under mild conditions is achieved via a cysteamine-assisted coordination-driven route. During the process, the molecular linker of cysteamine, possessing one amino group for chelating with the CUSs of the MOF and one thiol group as a docking site to anchor metal ions, plays a prominent role in enhancing interfacial interactions between the MOF and metal ions. The subsequent S2- anion exchange process leads to intimate surface-attached nucleation and epitaxial growth of metal sulfide NPs on the surface of the MOF. The as-formed composites exhibit enhanced charge separation and transfer capability, and thus boost photocatalytic performance. This general and simple approach provides a new avenue for the design of MOF-metal sulfide hybrids.