Deep-Learning-Assisted multivariate curve resolution.

Gas chromatography-mass spectrometry (GC-MS) is one of the major platforms for analyzing volatile compounds in complex samples. However, automatic and accurate extraction of qualitative and quantitative information is still challenging when analyzing complex GC-MS data, especially for the components incompletely separated by chromatography. Deep-Learning-Assisted Multivariate Curve Resolution (DeepResolution) was proposed in this study. It essentially consists of convolutional neural networks (CNN) models to determine the number of components of each overlapped peak and the elution region of each compound. With the assistance of the predicted elution regions, the informative regions (such as selective region and zero-concentration region) of each compound can be located precisely. Then, full rank resolution (FRR), multivariate curve resolution-alternating least squares (MCR-ALS) or iterative target transformation factor analysis (ITTFA) can be chosen adaptively to resolve the overlapped components without manual intervention. The results showed that DeepResolution has superior compound identification capability and better quantitative performances when comparing with MS-DIAL, ADAP-GC and AMDIS. It was also found that baseline levels, interferents, component concentrations and peak tailing have little influences on resolution result. Besides, DeepResolution can be extended easily when encountering unknown component(s), due to the independence of each CNN model. All procedures of DeepResolution can be performed automatically, and adaptive selection of resolution methods ensures the balance between resolution power and consumed time. It is implemented in Python and available at https://github.com/XiaqiongFan/DeepResolution.

Long-term arsenite exposure decreases autophagy by increased release of Nrf2 in transformed human keratinocytes.

Autophagy dysfunction in arsenite toxicity plays critical roles in cancer development and progression. However, the precise mechanisms of arsenite-induced skin cancer by blocking autophagy remain uncertain. Herein, this study investigated molecular mechanisms of arsenite-induced autophagy dysfunction mediated by nuclear factor erythroid-2 related factor 2 (Nrf2) in human keratinocyte (HaCaT) cells. The effects of long-term arsenite exposure on Nrf2 activation and autophagy were established using a siRNA interference assay and western blots. A specific siRNA of Nrf2 was used to verify that autophagy induced by arsenite can be influenced by Nrf2. Specific inhibitors of PI3K (LY294002) and mTOR (Rapamycin) and siRNA of Nrf2 were employed to verify that upregulation of Nrf2 correlated with activating the PI3K/Akt pathway. Downstream mTOR and Bcl2 were upregulated by Nrf2 signaling, inhibiting autophagy initiation in arsenite-exposed HaCaT cells. In conclusion, our data suggest that long-term exposure to arsenite promotes Nrf2 upregulation via the PI3K/Akt pathway and, along with upregulation of downstream mTOR and Bcl2, contributes to autophagy dysfunction in transformed HaCaT cells. This work provides new insights into the mechanisms underlying arsenite-induced autophagy dysfunction in cancer promotion and malignancy progression.

Role of mitochondrial DNA in oxidative damage induced by sodium arsenite in human bronchial epithelial cells.

Long-term exposure to sodium arsenite was found to induce malignant transformation in human bronchial epithelial (HBE) cell line as evidenced by elevated ROS levels. Although chronic sodium arsenite-induced HBE cell line transformation was associated with elevated ROS generation, it was of interest to determine whether acute sodium arsenite exposure also initiated pulmonary damage. Thus, the aim of this study was to investigate oxidative-stress-related pulmonary damage using a human bronchial epithelial (HBE) cell line. Incubation of ρ+-HBE (in the presence of mitochondrial DNA) cells with various concentrations of sodium arsenite, significantly increased ROS and MDA levels accompanied by decreased SOD activity in a concentration-dependent manner. In contrast, treatment of ρ-HBE (without mitochondrial DNA) cells various concentrations of sodium arsenite a reduction in ROS and MDA levels were noted. However, the SOD activity remained decreased in ρ-HBE cells. This was accompanied by a significant rise in HO-1 protein expressions levels in both cell types with greater changes ρ-HBE cells at the lower sodium arsenite concentrations. Data indicate that acute sodium arsenite exposure exerted a greater effect ρ-HBE cells suggesting that absence of mitochondrial DNA appears to enhance sensitivity to the oxidant actions of inorganic As.

[Effect of low-dose exposure to sodium arsenite on proliferation of HBE and HaCaT cells].

OBJECTIVE: To investigate the effect of chronic exposure to sodium arsenite at a dose of 1. 0 µmol / L on proliferation of human bronchial epithelial cells( HBE) and human keratinocytes( HaCaT) and discuss the mechanism of arsenic carcinogenesis. METHODS: Malignant transformation model of HBE and HaCaT cells cultured in vitro were used in this study. MTT assay was used to detect the capacity of proliferation. Flow cytometry was used to detect cell cycle. The expression of cell cycle related protein like cyclin E, cyclin D1 and cyclin A protein were inspected by Western blot. RESULTS: The treated cells, including passage 36 and 43 of HBE cells and passage 28 and 35 of HaCaT cells grow faster than the control group( P < 0. 01 and P < 0. 05). The treated cells in the G1 phase were decreased( P < 0. 05), however cells in the S phase were increased( P <0. 05). In addition, the expression of cyclin E displayed a trend of up-regulation( P <0. 05), and it was maintained at a high level in advanced period. CONCLUSION: By increasing the expression of cyclin E in HBE and HaCaT cells, low dose of sodium arsenite made cells escaping from the G1 phase to S phase, accelerating cell cycle progression and proliferation, a way that may lead to malignant transformation.

Nonylphenol induces pancreatic damage in rats through mitochondrial dysfunction and oxidative stress.

The organic alkylphenol 4-nonylphenol (NP) is regarded to be an endocrine disrupting chemical (EDC), one of the widely diffused and stable environmental contaminants. Due to its hydrophobicity and long half-life, NP can easily accumulate in living organisms, including humans, where it displays a series of toxic effects. It has been widely reported that NP affects male reproduction. In addition, there is increasing evidence suggesting that NP is detrimental to various organs, including the pancreas. This study investigated the adverse effects of NP exposure on the pancreas. Sprague-Dawley rats were treated with different doses of NP for 90 consecutive days. The data suggested that the body weights of the rats treated with NP decreased, and the highest dose of NP treatment (180 mg kg-1) dramatically increased water consumption by rats. Meanwhile, H&E staining and immunohistochemistry indicated that islets in the pancreases shrunk when the rats were treated with the indicated doses of NP. TUNEL staining demonstrated that NP exposure up-regulated the level of apoptosis in the pancreases in a dose-dependent manner. Besides this, NP exposure inhibited the secretion of insulin and disrupted glucose tolerance. The levels of reactive oxygen species (ROS) and intracellular calcium ([Ca2+]i) in the islets were up-regulated in the groups of rats treated with NP, but the levels of Mitochondrial Membrane Potential (MMP) were down-regulated. These results suggest that NP-induced pancreatic damage in rats occurs through mitochondrial dysfunction and oxidative stress, which causes disruption of glucose tolerance and decrease in insulin secretion.