PM2.5 is one of the most important pollutants related to air quality, and the increase of its concentration will aggravate the threat to people's health. Therefore, the prediction of surface PM2.5 concentration is of great significance to human health protection. In this study, A hybrid CNN-LSTM model is developed by combining the convolutional neural network (CNN) with the long short-term memory (LSTM) neural network for forecasting the next 24h PM2.5 concentration in Beijing, which makes full use of their advantages that CNN can effectively extract the features related to air quality and the LSTM can reflect the long term historical process of input time series data. The air quality data of the last 7days and the PM2.5 concentration of the next day are first set as the input and output of the model due to the periodicity, respectively. Subsequently four models namely univariate LSTM model, multivariate LSTM model, univariate CNN-LSTM model and multivariate CNN-LSTM model, are established for PM2.5 concentration prediction. Finally, mean absolute error (MAE) and root mean square error (RMSE) are employed to evaluate the performance of these models and results show that the proposed multivariate CNN-LSTM model performs the best results due to low error and short training time.
The transcriptional factors nuclear factor-κB (NF-κB) and NF-E2-related factor 2 (Nrf2) have been recently reported to have critical roles in protecting various tissues against inflammation and colitis-associated colorectal cancer (aberrant crypt foci). Our previous studies showed that wogonin (5,7-dihydroxy-8-methoxyflavone) possessed anti-neoplastic and anti-inflammatory activities. The present study extended these important earlier findings by exploring the effect of wogonin on the initiation and development of colitis-associated cancer. Wogonin lowered tumor incidence and inhibited the development of colorectal adenomas in azoxymethane- or dextran sulfate sodium-induced mice. We found that wogonin significantly decreased the secretion and expression of IL-6 and IL-1β, reduced cell proliferation and nuclear expression of NF-κB in adenomas and surrounding tissues and promoted Nrf2 nuclear translocation in surrounding tissues, although overexpressed Nrf2 in tumor tissues was independent of wogonin administration. Furthermore, wogonin inhibited the interaction between human monocytic THP-1 cells and human colon cancer HCT116 cells, and significantly downregulated lipopolysaccharide-induced secretion of prototypical pro-inflammatory cytokines IL-6 and IL-1β in THP-1 cells. Further mechanism research revealed that wogonin inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β, and promoted Nrf2 signaling pathway in HCT116 cells and THP-1 cells. Taken together, the present results indicated that wogonin effectively suppressed inflammation-associated colon carcinogenesis and cancer development, suggesting its potential as a chemopreventive agent against colitis-associated colon cancer.
Imatinib (IM) is highly effective in treatment of chronic myeloid leukemia (CML) but does not eliminate minimal residual disease (MRD), which remains a potential source of relapse. IM treatment effectively inhibits BCR-ABL kinase activity in CML cells, suggesting that additional kinase-independent mechanisms contribute to the presence of MRD. Bone marrow (BM) microenvironment protecting CML cells from IM treatment was investigated. Culturing CML cell line K562 in human stromal cell line HS-5-derived conditioned medium significantly inhibited apoptosis induced by IM, which was soluble factor-mediated drug resistance (SFM-DR). The BM stroma-derived soluble factors could enhance the resistance of K562 cells to IM by increasing Stat3 phosphorylation on tyrosine 705 and subsequently increasing the expression of anti-apoptotic proteins and P-glycoprotein (P-gp) in K562 cells. Furthermore, the reversal effect of oroxylin A, a naturally monoflavonoid isolated from the root of Scutellaria baicalensis Georgi, in K562 cells within the SFM-DR model was detected. After treatment of weakly toxic concentration of oroxylin A, the apoptosis of K562 cells induced by IM was increased dramatically through suppressing Stat3 pathway. In addition, the in vivo study showed that oroxylin A potentiates the inhibitory effects of IM on leukemia development by suppressing Stat3 pathway in the K562 xenograft model. In conclusion, IM-induced resistance in K562 cells within the SFM-DR model correlated with increasing Stat3 signaling and upregulating P-gp expression through Stat3 pathway. Additionally, oroxylin A improved the sensitivity of K562 cells to IM in SFM-DR model and in vivo, and the underlying mechanism attributed to the suppression of Stat3 pathway, which suggested oroxylin A might be a promising agent for treatment designed to eradicate MRD in CML patients.
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