The transcription factor NRF2 (NFE2L2) is a pivotal activator of genes encoding cytoprotective and detoxifying enzymes that limit the action of cytotoxic therapies in cancer. NRF2 acts by binding antioxidant response elements (ARE) in its target genes, but there is relatively limited knowledge about how it is negatively controlled. Here, we report that retinoic X receptor alpha (RXRa) is a hitherto unrecognized repressor of NRF2. RNAi-mediated knockdown of RXRa increased basal ARE-driven gene expression and induction of ARE-driven genes by the NRF2 activator tert-butylhydroquinone (tBHQ). Conversely, overexpression of RXRa decreased ARE-driven gene expression. Biochemical investigations showed that RXRa interacts physically with NRF2 in cancer cells and in murine small intestine and liver tissues. Furthermore, RXRa bound to ARE sequences in the promoters of NRF2-regulated genes. RXRa loading onto AREs was concomitant with the presence of NRF2, supporting the hypothesis that a direct interaction between the two proteins on gene promoters accounts for the antagonism of ARE-driven gene expression. Mutation analyses revealed that interaction between the two transcription factors involves the DNA-binding domain of RXRa and a region comprising amino acids 209-316 in human NRF2 that had not been defined functionally, but that we now designate as the NRF2-ECH homology (Neh) 7 domain. In non-small cell lung cancer cells where NRF2 levels are elevated, RXRa expression downregulated NRF2 and sensitized cells to the cytotoxic effects of therapeutic drugs. In summary, our findings show that RXRa diminishes cytoprotection by NRF2 by binding directly to the newly defined Neh7 domain in NRF2. Cancer Res; 73(10);

Electrocatalytic CO2 reduction to fuels is considered a promising strategy for the sustainable carbon cycle. However, the improvement of the catalytic performance of CO2 electrocatalysts still poses many challenges, especially achieving the large partial current density of product and high faradaic efficiency simultaneously, which are essential for future applications of the electrochemical CO2 reduction reaction. In response, herein, an in situ porous Zn catalyst is prepared and exhibits high faradaic efficiency and large CO partial current density at the same time, benefiting from the porous architecture with increased exposure and accessibility of active sites. Furthermore, density functional theory calculations demonstrate that the high faradaic efficiency is attributed to the favorable adsorption energy of the key intermediate, which promotes CO2 electroreduction to CO.

BackgroundIntimate partner violence (IPV) is the most common form of violence against women worldwide. IPV during pregnancy is an important risk factor for adverse health outcomes for women and their offspring. However, the prevalence of IPV during pregnancy is not well understood in China. The objective of this study was to estimate the pooled prevalence of IPV during pregnancy in China using a systematic review and meta-analysis.MethodsSystematic literature searches were conducted in PubMed, Web of Science, CNKI, Wanfang, Weipu and CBM databases to identify relevant articles published from the inception of each database to January 31, 2016 that reported data on the prevalence of IPV during pregnancy in China. The Risk of Bias Tool for prevalence studies was used to assess the risk of bias in individual studies. Owing to significant between-study heterogeneity, a random-effects model was used to calculate the pooled prevalence and corresponding 95% confidence interval, and then univariate meta-regression analyses were performed to investigate the sources of heterogeneity. Subgroup analysis was conducted to explore the risk factors associated with IPV during pregnancy.ResultsThirteen studies with a total of 30,665 individuals were included in this study. The overall pooled prevalence of IPV during pregnancy was 7.7% (95% CI: 5.6–10.1%) with significant heterogeneity (I2 = 97.8%, p < 0.001). The results of the univariate meta-regression analyses showed that only the variable “sample source” explained part of the heterogeneity in this study (p < 0.05). The characteristics “number of children” and “unplanned pregnancy” were determined as risk factors for experiencing violence during pregnancy.ConclusionsThe prevalence of IPV during pregnancy in China is considerable and one of the highest reported in Asia, which suggests that issues of violence against women during pregnancy should be included in efforts to improve the health of pregnant women and their offspring. In addition, a nationwide epidemiological study is needed to confirm the prevalence estimates and identify more risk factors for IPV during pregnancy.

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The recent developments of metal–nitrogen–carbon catalysts for electrochemical water splitting have been comprehensively summarized.

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