CPLX2 Regulates Ferroptosis and Apoptosis Through NRF2 Pathway in Human Hepatocellular Carcinoma Cells.

Understanding the principle of regulated cell death (RCD) such as ferroptosis and apoptosis provides opportunities to overcome sorafenib resistance of HCC. Complexin II (CPLX2) is involved in calcium-dependent fusion of vesicles and plasma membrane, and recent studies showed CPLX2 is involved in cancer progression. However, the expression and function of CPLX2 are unclear in hepatocellular carcinoma (HCC). qPCR and western blotting assays were used to detect the levels of CPLX2. MTT and colony formation assays were used to detect cell viability. The contents of iron, ROS, MDA, and GSH were used to evaluate the function of CPLX2 on ferroptosis, while the flow cytometry and TUNEL assays were used to evaluate the role of CPLX2 on apoptosis. Our analysis showed CPLX2 is significantly upregulated in HCC, which predicts poor overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and disease-specific survival (DSS) for patients with HCC. Further function enrichment analysis of genes related to CPLX2 showed CPLX2 is involved in the NRF2 pathway. Downregulation of CPLX2 can inhibit NRF2 expression and the transcription of its downstream genes, which confirms that CPLX2 is involved in NRF2 pathway. Cell viability assay showed that ferroptosis and apoptosis inhibitors can reverse the inhibition effect of CPLX2-knockdown on cell survival, respectively. And downregulation of CPLX2 significantly promotes the contents of iron, ROS, and MDA, while inhibiting the GSH level of HCC cell lysate, suggesting CPLX2 involved in ferroptosis. Moreover, downregulation of CPLX2 promotes the apoptosis of HCC cells by flow cytometry and TUNEL assay. And upregulation of NRF2 can partly reverse the inhibitory effect of CPLX2-downregulation on ferroptosis and apoptosis. Finally, we found downregulation of CPLX2 aggravates cell death induced by sorafenib. CPXL2 regulates ferroptosis and apoptosis through NRF2 pathway, and CPLX2 knockdown promotes cell death induced by sorafenib. CPLX2 might be an effective target for therapy patients with HCC.

Neighboring sp-Hybridized Carbon Participated Molecular Oxygen Activation on the Interface of Sub-nanocluster CuO/Graphdiyne.

Activation of O2 is a crucial step in oxidation processes. Here, the concept of sp-hybridized C≡C triple bonds as an electron donor is adopted to develop highly active and stable catalysts for molecular oxygen activation. We demonstrate that the neighboring sp-hybridized C and Cu sites on the interface of the sub-nanocluster CuO/graphdiyne are the key structures to effectively modulate the O2 activation process in the bridging adsorption mode. The as-prepared sub-nanocluster CuO/graphdiyne catalyst exhibited the highest CO oxidation activity and readily converted 50% CO at around 133 °C, which is 34 and 94 °C lower than that for CuO/graphene and CuO/active carbon catalysts, respectively. In situ diffused reflectance infrared Fourier transform spectroscopy and density functional theory calculation results proved that the neighboring sp-hybridized C is more favorable to promote the rapid dissociation of carbonate than sp2-hybridized C without overcoming any energy barrier. The gaseous CO directly reacts with the active molecular oxygen and tends to proceed through the E-R mechanism with a relatively low energy barrier (0.20 eV). This work revealed that sp-hybridized C of graphdiyne-based materials could effectively improve the O2 activation efficiency, which could facilitate the low-temperature oxidation processes.

Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation.

BACKGROUND: Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3'UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date. METHODS: In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-time PCR (qRT-PCR); protein levels of MAD1 and BUB3 were analysed by Western blotting. RESULTS: statistical analysis (p < 0.05) showed that miR-125b and BUB3 were significantly down-regulated in the aneuploidy group compared to the control group and that MAD1 was significantly up-regulated. Additionally, the MAD1 protein level was significantly higher in aneuploidy abortion villus, but BUB3 protein was only mildly increased. Correlation analysis revealed that expression of MAD1 correlated negatively with miR-125b. CONCLUSION: These results suggest that aneuploid abortion correlates positively with MAD1 overexpression, which might be caused by insufficient levels of miR-125b. Taken together, our findings first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion.

Rechargeable Zinc-Air Battery with Ultrahigh Power Density Based on Uniform N, Co Codoped Carbon Nanospheres.

Highly efficient catalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are key to the commercialization of rechargeable zinc-air batteries (ZABs). In this work, a catalyst with uniform nanospherical morphology was prepared from cobalt nitrate, acetylacetone, and hydrazine hydrate. The final catalyst possesses high ORR and OER performances, with a half-wave potential of 0.911 V [vs reversible hydrogen electrode (RHE)] for ORR and a low potential of 1.57 V (vs RHE) at 10 mA cm-2 for OER in 0.1 M KOH solution. Specially, a ZAB based on the catalyst demonstrates an ultrahigh power density of 479.1 mW cm-2, as well as excellent stability, and potential in practical applications.