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Drug repositioning offers two main advantages in drug discovery - the process is less tedious and less costly. In the past, many drugs like thalidomide and sildenafil were successfully repositioned but the process was entirely serendipitous. These days drug repositioning is widely accepted as an alternate method of drug discovery and the process is based on building a strong hypothesis guided by systematic computational and experimental methods. One of the methods used in drug repositioning is based on shared side effects by drugs of different pharmacological categories. This method rests on the principle that drugs that share side effects might also share common biological targets and therefore same pharmacological indications. Old drugs can be repositioned for new uses by identifying the shared side effects of existing drugs and by modulating their chemical structure if required. Breast cancer is the most common type of cancer in women and the second leading cause of death worldwide after lung cancer in both men and women. Letrozole, an aromatase inhibitor, is used in the treatment of advanced, recurrent and metastatic breast cancer in post-menopausal women. Identification of drugs that share side effects with letrozole might help us to identify a potential drug for repositioning in the treatment of breast cancer. Ropinirole, a dopaminergic agonist was found to share the maximum number of side effects with letrozole. Studies have proposed that dopaminergic agonists induce apoptosis in breast, colon, ovarian cancer cells and leukemia neuroblastoma. This is consistent with our hypothesis that ropinirole that shares the maximum number of side effects with letrozole might be effective in the management of breast cancer. This hypothesis was further validated by preliminary molecular docking and in-vitro cell-line studies.17α-ethinylestradiol (EE2) is a synthetic estrogen that can cause harmful effects on animals, such as male feminization and infertility. However, the impact of the EE2 contamination on microbial communities and the potential role of bacterial strains as bioremediation agents are underexplored. The aim of this work was to evaluate the impact of EE2 on the microbial community dynamics of aerated submerged fixed-film reactors (ASFFR) simulating a polishing step downstream of a secondary sewage treatment. For this purpose, the reactors were fed with a synthetic medium with low COD content (around 50 mg l-1), supplemented (reactor H) or not (reactor C) with 1 μg l-1 of EE2. Sludge samples were periodically collected during the bioreactors operation to assess the bacterial profile over time by 16S rRNA gene amplicon sequencing or by bacterial isolation using culture-dependent approach. The results revealed that the most abundant phyla in both reactors were Proteobacteria and Bacteroidetes. At genus level, Chitinophagaceae, Nitrosomonas and Bdellovibrio predominated. Significant effects caused by EE2 treatment and bioreactors operating time were observed by non-metric multidimensional scaling. Therefore, even at low concentrations as 1 μg l-1, EE2 is capable of influencing the bioreactor microbiome. Culture-dependent methods showed that six bacterial isolates, closely related to Pseudomonas and Acinetobacter genera, could grow on EE2 as the sole carbon source under aerobic conditions. These organisms may potentially be used for the assembly of an EE2-degrading bacterial consortium and further exploited for bioremediation applications, including tertiary sewage treatment to remove hormone-related compounds not metabolized in secondary depuration stages.Acid rain is a serious threat to terrestrial ecosystems. To provide more accurate early warning information for acid rain prevention, urban planning, and travel planning, a novel air pollutant prediction model was proposed in this paper to predict NO2 and SO2. First, the data were decomposed into several sub-sequences by a complete ensemble empirical mode decomposition with adaptive noise. Second, the subsequences are reconstructed by variational mode decomposition and sample entropy. Then, the new subsequences are predicted by the extreme learning machine combined with the whale optimization algorithm. The empirical analysis was carried out through 8 data sets. According to the experimental results, three main conclusions can be drawn. First, the proposed model in this paper has excellent prediction performance and robustness. In all the comparison experiments, the R2 and RMSE of the proposed model are the best among all the models. Second, data preprocessing is very necessary. After adding the decomposition algorithm, the average improvement levels of R2 and RMSE were 897.57% and 50.78%, respectively. Third, the re-decomposition of IMF1 is an effective method to improve prediction accuracy. After the re-decomposition of IMF1, R2 can be improved by 13.64% on average on the original basis, and RMSE can be reduced by 31.99% on average. The results of this study can provide a valuable reference for the research of air pollutant prediction. In future work, the application of the proposed model in other air pollutants or other regions can be explored.Open burning of crop residue is an important source of air pollution which is poorly characterized in South Asia. Currently, the gridded inventory reported by Global Fire Emissions Database for biomass burning including open burning of crop residue are of coarse resolution (0.25° × 0.25°), and may not be appropriate for a simulation for Nepal. This study develops a comprehensive high resolution (1 km × 1 km) gridded model-ready emissions inventory for Nepal to understand the spatial characteristics of air pollutant emissions from open burning. We estimate the national air pollutant emissions from crop residue burned between the years 2003 and 2017. The best available data on agricultural production, residue consumption patterns, agricultural burning parameters and emission factors were derived from secondary sources. The Monte Carlo method was used to estimate uncertainties. learn more The mass of crop residue burned in 2016/17 was 2908 Gg (61-139%), which was 22% of the dry matter generated that year. By multiplying the burned crop residue mass by emission factors, the air pollutant emissions were estimated as 4140 for CO2 (56-144%), 154 for CO (4-196%), 6.
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