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Lung cancer is the most common cause of cancer-related death worldwide. The occurrence of multidrug resistance (MDR) affects the therapeutic efficacy of chemotherapeutics. Therefore, to develop new anticarcinogen which can overcome MDR is urgent. Here, the novel microtubule inhibitor 5-(4-ethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-3-amine (YAN) exhibited strong cytotoxicity towards A549 and MDR-phenotype A549/Taxol cells. We demonstrated that YAN was a poor substrate of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) which were over-expressed in A549/Taxol cells, and YAN inhibited their expression and function. Moreover, YAN arrested cells at mitosis phase by inhibiting microtubule polymerization. Further, YAN induced caspase-dependent apoptosis in A549 cells via mitochondria-mediated intrinsic pathway. In contrast, the multinucleation of A549/Taxol cells after YAN-treatment indicated the occurrence of mitotic catastrophe, and the subsequent apoptosis was mediated by apoptosis-inducing factor (AIF) nuclear translocation instead of p53- and caspase-dependent manner. Moreover, the inhibitory effect of YAN on PI3K/Akt activity was involved in the regulation of P-gp, MRP1 and AIF in A549/Taxol cells. Taken together, our finding indicates that YAN is a novel microtubule inhibitor and overcomes MDR by suppressing P-gp and MRP1 function and inducing cell death independent of p53 and caspase in A549/Taxol cells. Therefore, YAN possesses great potential for future development into an effective anticarcinogen especially for drug-resistant cancer.

Lightning serves as the dominant source of nitrogen oxides (NOx=NO+NO2) in the upper troposphere (UT), with a strong impact on ozone chemistry and the hydroxyl radical production. However, the production efficiency (PE) of lightning nitrogen oxides (LNOx) is still quite uncertain (32–1100 mol NO per flash). Satellite measurements are a powerful tool to estimate LNOx directly compared to conventional platforms. To apply satellite data in both clean and polluted regions, a new algorithm for calculating LNOx has been developed that uses the Berkeley High-Resolution (BEHR) v3.0B NO2 retrieval algorithm and the Weather Research and Forecasting model coupled with chemistry (WRF-Chem). LNOx PE over the continental US is estimated using the NO2 product of the Ozone Monitoring Instrument (OMI) data and the Earth Networks Total Lightning Network (ENTLN) data. Focusing on the summer season during 2014, we find that the lightning NO2 (LNO2) PE is 32±15 mol NO2 per flash and 6±3 mol NO2 per stroke while LNOx PE is 90±50 mol NOx per flash and 17±10 mol NOx per stroke. Results reveal that our method reduces the sensitivity to the background NO2 and includes much of the below-cloud LNO2. As the LNOx parameterization varies in studies, the sensitivity of our calculations to the setting of the amount of lightning NO (LNO) is evaluated. Careful consideration of the ratio of LNO2 to NO2 is also needed, given its large influence on the estimation of LNO2 PE.

Lightning serves as the dominant source of nitrogen oxides (NOx = NO + NO2) in the upper troposphere (UT), with strong impact on ozone chemistry and the hydroxyl radical production. However, the production efficiency (PE) of lightning nitrogen oxides (LNOx) is still quite uncertain (32–1100 mol NO per flash). Satellites measurements are a powerful tool to estimate LNOx directly as compared to conventional platforms. To apply satellite data in both clean and polluted regions, a new algorithm for calculating LNOx has been developed based on the program of new Berkeley High Resolution (BEHR) v3.0B NO2 product and the Weather Research and Forecasting-Chemistry (WRF-Chem) model. LNOx PE over the continental US is estimated using the NO2 product of the Ozone Monitoring Instrument (OMI) satellite and the Earth Networks Total Lightning Network (ENTLN) data. Focusing on the summer season during 2014, we find that the lightning NO2 (LNO2) PE is 44 ± 16 mol NO2 flash-1 and 8 ± 3 mol NO2 stroke-1 while LNOx PE is 120 ± 52 mol NOx flash-1 and 22 ± 9 mol NOx stroke-1. Results reveal that former methods are more sensitive to background NO2 and neglect much of the below-cloud LNO2. As the LNOx parameterization varies in studies, the sensitivity of our calculations to the setting of the amount of lightning NO (LNO) is evaluated. Careful consideration of the ratio of LNO2 to NO2 is also needed, given its large influence on the estimation of LNO2 PE.

Chunlan Xu, Lei Qiao, Li Ma, Yu Guo, Xina Dou, Shuqi Yan, Baohua Zhang, Alexandra RomanThe Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, People’s Republic of ChinaBackground: Selenium (Se) can exert antioxidative activity and prevent the body from experiencing oxidative injury. Biogenic Se nanoparticles (SeNPs) synthesized by probiotics possess relatively strong chemical stability, high bioavailability, and low toxicity, this makes them potential Se supplements. Previously, we demonstrated that SeNPs synthesized by Lactobacillus casei ATCC 393 can alleviate hydrogen peroxide (H2O2)-induced human and porcine intestinal epithelial cells’ oxidative damage. However, the antioxidant mechanism remains unclear.Methods: The possible antioxidant mechanism and protective effect of SeNPs on intestinal epithelial permeability and mitochondrial function were evaluated by establishing an H2O2-induced oxidative damage model of human colon mucosal epithelial cells (NCM460) and conducting Nrf2 inhibitor interference experiments. Mitochondrial membrane potential (MMP), mitochondrial DNA content, adenosine triphosphate (ATP), ROS, and protein expression levels of Nrf2-related genes were determined. Mitochondrial ultrastructure was visualized by transmission electron microscopy.Results: An amount of 4 μg Se/mL of SeNPs synthesized by L. casei ATCC 393 alleviated increase of ROS, reduced ATP and MMP, and maintained intestinal epithelial permeability in NCM460 cells challenged by H2O2. In addition, SeNPs improved the protein levels of Nrf2, HO-1, and NQO-1. Moreover, SeNPs attenuated the damage of mitochondrial ultrastructure caused by oxidative stress. Nrf2 inhibitor (ML385) abolished the regulatory effect of SeNPs on intracellular ROS production.Conclusion: Data suggest that biogenic SeNPs synthesized by L. casei ATCC 393 can protect the intestinal epithelial barrier function against oxidative damage by alleviating ROS-mediated mitochondrial dysfunction via Nrf2 signaling pathway. Biogenic SeNPs are an attractive candidate for potential Se supplement agent in preventing oxidative stress-related intestinal disease by targeting mitochondria.Keywords: Lactobacillus casei, selenium nanoparticles, mitochondrial, antioxidant, reactive oxygen species, intestinal barrier