The evolutionally conserved DNA damage response (DDR) and cell cycle checkpoints preserve genome integrity. Central to these genome surveillance pathways is a protein kinase, Chk1. DNA damage induces activation of Chk1, which then transduces the checkpoint signal and facilitates cell cycle arrest and DNA damage repair. Significant progress has been made recently towards our understanding of Chk1 regulation and its implications in cancer etiology and therapy. Specifically, a model that involves both spatiotemporal and conformational changes of proteins has been proposed for Chk1 activation. Further, emerging evidence suggests that Chk1 does not appear to be a tumor suppressor; instead, it promotes tumor growth and may contribute to anticancer therapy resistance. Recent data from our laboratory suggest that activating, but not inhibiting, Chk1 in the absence of chemotherapy might represent an innovative approach to suppress tumor growth. These findings suggest unique regulation of Chk1 in cell biology and cancer etiology, pointing to novel strategies for targeting Chk1 in cancer therapy.

Background: Epigenetic alterations are involved in various aspects of colorectal carcinogenesis. N 6methyladenosine (m 6 A) modifications of RNAs are emerging as a new layer of epigenetic regulation. As the most abundant chemical modification of eukaryotic mRNA, m 6 A is essential for the regulation of mRNA stability, splicing, and translation. Alterations of m 6 A regulatory genes play important roles in the pathogenesis of a variety of human diseases. However, whether this mRNA modification participates in the glucose metabolism of colorectal cancer (CRC) remains uncharacterized. Methods: Transcriptome-sequencing and liquid chromatography-tandem mass spectrometry (LC-MS) were performed to evaluate the correlation between m 6 A modifications and glucose metabolism in CRC. Mass spectrometric metabolomics analysis, in vitro and in vivo experiments were conducted to investigate the effects of METTL3 on CRC glycolysis and tumorigenesis. RNA MeRIP-sequencing, immunoprecipitation and RNA stability assay were used to explore the molecular mechanism of METTL3 in CRC. Results: A strong correlation between METTL3 and 18 F-FDG uptake was observed in CRC patients from Xuzhou Central Hospital. METTL3 induced-CRC tumorigenesis depends on cell glycolysis in multiple CRC models. Mechanistically, METTL3 directly interacted with the 5′/3'UTR regions of HK2, and the 3'UTR region of SLC2A1 (GLUT1), then further stabilized these two genes and activated the glycolysis pathway. M 6 A-mediated HK2 and SLC2A1 (GLUT1) stabilization relied on the m 6 A reader IGF2BP2 or IGF2BP2/3, respectively. Conclusions: METTL3 is a functional and clinical oncogene in CRC. METTL3 stabilizes HK2 and SLC2A1 (GLUT1) expression in CRC through an m 6 A-IGF2BP2/3-dependent mechanism. Targeting METTL3 and its pathway offer alternative rational therapeutic targets in CRC patients with high glucose metabolism.

† Electronic supplementary information (ESI) available: Experimental preparation and instrumentation, XRD patterns and Raman spectra of graphite and GO, full XPS spectra of GO and ED-RGO, photographs of filtrates after adsorptions, and SEM-EDX images of ED-RGO before and after Cr(VI) adsorption. See

We demonstrate a facile and environmentally friendly approach to prepare well-dispersed graphene sheets by g-ray induced reduction of a graphene oxide (GO) suspension in N,N-dimethyl formamide (DMF) at room temperature. GO is reduced by the electrons generated from the radiolysis of DMF under g-ray irradiation. The reduced GO by g-ray irradiation (G-RGO) can be re-dispersed in many organic solvents, and the resulting suspensions are stable for two weeks due to the stabilization of N(CH 3 ) 2 + groups on G-RGO. Additionally, G-RGO is efficient in improving the conductivity of polystyrene (PS). Its PS nanocomposites exhibit a sharp transition from electrically insulating to conducting with a low percolation threshold of 0.24 vol% and a high electrical conductivity of 45 S m À1 is obtained with only 2.3 vol% of G-RGO. The superior electrical conductivity is attributed to the uniform dispersion of the G-RGO sheets in the PS matrix.

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High-quality homogeneous junctions are of great significance for developing transition metal dichalcogenides (TMDs) based electronic and optoelectronic devices. Here, we demonstrate a lateral p-type/intrinsic/n-type (p-i-n) homojunction based multilayer WSe2 diode. The photodiode is formed through selective doping, more specifically by utilizing self-aligning surface plasma treatment at the contact regions, while keeping the WSe2 channel intrinsic. Electrical measurements of such a diode reveal an ideal rectifying behavior with a current on/off ratio as high as 1.2 × 106 and an ideality factor of 1.14. While operating in the photovoltaic mode, the diode presents an excellent photodetecting performance under 450 nm light illumination, including an open-circuit voltage of 340 mV, a responsivity of 0.1 A W–1, and a specific detectivity of 2.2 × 1013 Jones. Furthermore, benefiting from the lateral p-i-n configuration, the slow photoresponse dynamics including the photocarrier diffusion in undepleted regions and photocarrier trapping/detrapping due to dopants or doping process induced defect states are significantly suppressed. Consequently, a record-breaking response time of 264 ns and a 3 dB bandwidth of 1.9 MHz are realized, compared with the previously reported TMDs based photodetectors. The above-mentioned desirable properties, together with CMOS compatible processes, make this WSe2 p-i-n junction diode promising for future applications in self-powered high-frequency weak signal photodetection.

Electrochemical water splitting requires efficient, low‐cost water oxidation catalysts to accelerate the sluggish kinetics of the water oxidation reaction. A rapid photocorrosion method is now used to synthesize the homogeneous amorphous nanocages of Cu‐Ni‐Fe hydr(oxy)oxide as a highly efficient electrocatalyst for the oxygen evolution reaction (OER). The as‐fabricated product exhibits a low overpotential of 224 mV on a glassy carbon electrode at 10 mA cm−2 (even lower down to 181 mV when supported on Ni foam) with a Tafel slope of 44 mV dec−1 for OER in an alkaline solution. The obtained catalyst shows an extraordinarily large mass activity of 1464.5 A g−1 at overpotential of 300 mV, which is the highest mass activity for OER. This synthetic strategy may open a brand new pathway to prepare copper‐based ternary amorphous nanocages for greatly enhanced oxygen evolution.