Mutations and altered expression of deubiquitinating enzymes (DUBs) have been found associated with many human diseases including cancers. In this study, Ubiquitin specific protease 1 (USP1) expression was found significantly increased in some colorectal cancers (CRC). The elevated USP1 level was associated with short overall survival of patients and with advanced stages of cancers. In cultured CRC cells, knockdown of USP1 induced growth arrest at G 2 /M of cell cycle and reduced the expression of anti-apoptotic proteins Bcl-2 and Mcl-1. Its knockdown also led to reduction of DNA-repair related substrates FANCD2 and ID1. Further investigations found that small molecular inhibitor of USP1 ML323 sensitized CRC cells to DNA-targeting chemotherapeutics, including doxorubicin, TOPI/II inhibitors, and PARP inhibitor, but not to 5-Fu. These results indicate that USP1 plays a critical in colorectal cancer cell survival and is a promising target for anti-colorectal cancer chemotherapy. Targeting USP1 may represent an effective strategy to regulate the DNA-repairing system.

This work reports a facile and effective approach for preparing graphene quantum dots co-doped with nitrogen and sulfur (N-S/GQDs). The proposed method comprised pyrolysis of citric acid with glutathione and dialysis treatment. The fabricated N-S/GQDs exhibited blue luminescence and a high fluorescence quantum yield of 36.3%. N-S/GQDs can be sensitively quenched by Fe 3+ , which was absorbed on the edge of N-S/GQDs through the coordination interaction between Fe 3+ and N, S elements. The subsequent introduction of pyrophosphate ion (PPi) resulted in the recovery of the fluorescence of Fe 3+-quenched N-S/GQDs. The stronger coordination reactivity between Fe 3+ and PPi induced changes in fluorescence. PPi concentration was facilely quantified through the recovered amplitudes of the fluorescence intensities of N-S/GQDs. Under the optimized experimental condition, increased fluorescence intensity showed a linear relationship to PPi concentration (1 μM to 1000μM) in serum samples. Additionally, the proposed method featured sensitive and selectivity for the detection of PPi in synovial fluid, suggesting the potential application for simple and accurate clinical diagnosis of arthritic diseases.

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