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Isotopically labeled FT-ICR-MS combined with multiple post-analyses, including interpretable machine learning (IML) and a paired mass distance (PMD) network, was employed to unravel the reactivity and transformation of natural organic matter (NOM) during ultraviolet (UV) irradiation. FT-ICR-MS analysis was used to assign formulas, which were classified on the basis of their molecular compositions and structural categories. Isotope (deuterium, D) labeling was utilized to unequivocally determine the photochemical products and examine the development of OD radical-mediated NOM transformation. With regard to the reactive molecular formulas, CHOS formulas exhibited the highest reactivity (86.5% of precursors disappeared) followed by CHON (53.4%) and CHO (24.6%) formulas. With regard to structural categories, the degree of reactivity decreased in the following order: tannins > condensed aromatics > lignin/CRAMs. The IML algorithm demonstrated that the crucial features governing the reactivity of formulas were the molecular weight, DBE-O, NOSC, and the presence of heteroatoms (i.e., N and S), suggesting that the large and unsaturated compounds containing S and N are more prone to photodegradation. The reactomics approach using the PMD network further indicated that 11 specific molecular formulas in the CHOS and CHO class served as hubs, implying a higher photoreactivity and participation in a range of transformations. The isotope labeling analyses also found that, among the reactions observed, hydroxylation (i.e., +OD) is dominant for lignin/CRAMs and condensed aromatics, and formulas containing ≤10 D atoms were developed. Overall, this study, by adopting rigorous and interpretable techniques, could provide in-depth insights into the molecular-level dynamics of NOM under UV irradiation.
Assuntos
Lignina , Raios Ultravioleta , FotóliseRESUMO
In order to identify emerging per- and polyfluoroalkyl substances (PFASs) and their alternatives in the environment or population, we need to perform extensive profiling of PFASs to determine their distribution in samples. The sequential window acquisition of all theoretical fragment-ion spectra (SWATH mode) is capable of obtaining a wide range of MS2 spectra but is difficult for direct identification of PFASs due to its complex MS2 spectra, and the nontarget screening method is difficult to identify due to its lack of a priori information. In this study, we demonstrated the great potential of SWATH-F, a nontarget fragment-based homologue screening method in combination with the SWATH-MS deconvolution, for detecting PFASs. We evaluated the application of SWATH-F to gradient spiked samples and real population serum samples, compared it with nontarget homologue screening in the information-dependent acquisition mode (IDA mode), and obtained better results for SWATH-F with 276% improvement (IDA:17 PFASs, SWATH-F: 64 PFASs) in identification. In addition, we automated the screening and identification process of SWATH-F to facilitate its use by researchers. SWATH-F is freely available on GitHub (https://github.com/njuIrene/SWATH-F) under an MIT license.
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Potential adverse effects of microcystin-LR (MC-LR) on soil invertebrates have not been studied. Here we investigated the mechanism of MC-LR toxicity to earthworm (Eisenia fetida) intestine at the individual level and at the cellular level. The results showed an inverse relationship between the bodyweight and survival rate of earthworms over exposure time- and MC-LR doses in soil. Dose-dependent intestinal lesions and disturbances of enzymatic activities (e.g., cellulase, Na+/K+-ATPase, and AChE) were observed, which resulted in intestinal dysfunction. Excessive reactive oxygen species generation led to DNA damage and lipid peroxidation of intestinal cells. The oxidative damage to DNA prolonged cell cycle arrest at the G2/M-phase transition in mitosis, thus stimulating and accelerating apoptosis in earthworm intestine. MC-LR target earthworm intestine tissue. MC-LR at low concentrations can damage earthworm intestine regardless of exposure routes (oral or contact). High toxicity of MC-LR to earthworms delineates its ecological risks to terrestrial ecosystems.
Assuntos
Oligoquetos , Animais , Ecossistema , Intestinos , SoloRESUMO
Thyroid cancer is derived from follicular or thyroid cells and has become the most prevalent malignant tumor of endocrine organs, with increased morbidity and mortality. Circular RNAs (circRNAs) are used as prognostic and predictive markers for different types of cancer. However, the role of circRNA_0000285 in thyroid cancer and its potential molecular mechanism remain unclear. The present study aimed to investigate the roles and underlying molecular mechanism of circRNA_0000285 in thyroid cancer to identify novel treatments for this disease. The target binding site of circRNA_0000285 and microRNA-654-3p (miR-654-3p) were predicted and confirmed via the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Thyroid cancer cell viability and apoptosis were determined via the MTT assay and flow cytometric analysis, respectively, whereas the expression levels of circRNA_0000285 and miR-654-3p were determined via reverse transcription-quantitative PCR analysis. In addition, the protein expression levels of the apoptosis-associated proteins, Bax and B-cell lymphoma 2 (Bcl-2), were detected via western blotting. The results of the dual-luciferase reporter and RIP assays demonstrated that miR-654-3p directly targeted circRNA_0000285. The expression levels of circRNA_0000285 and miR-654-3p in thyroid cancer cells (TPC-1 and FTC133) were upregulated and downregulated, respectively. Knockdown of circRNA_0000285 via small interfering (si)RNA inhibited circRNA_0000285 levels and increased miR-654-3p levels. In addition, miR-654-3p expression decreased following transfection with miR-654-3p inhibitor. Functional experiments demonstrated that circRNA_0000285-siRNA decreased thyroid cancer cell proliferation, promoted cell apoptosis, enhanced Bax expression and suppressed Bcl-2 expression. All these effects were reversed following transfection with miR-654-3p inhibitor. Taken together, the results of the present study suggest that circRNA_0000285 plays a vital role in thyroid cancer progression by regulating miR-654-3p, which provides a potential therapeutic target for this disease.
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Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Long non coding RNAs (lncRNAs) have been involved in regulating tumor progression including PTC. In the present study, we demonstrated that long non coding RNA LINC01186 was significantly downregulated in PTC tissue samples compared with adjacent normal tissue samples in patients. LINC01186 expression was also found to be higher in PTC cells. Lower LINC01186 expression was associated with lymph node metastasis of PTC patients. Functionally, LINC01186 overexpression significantly suppressed cell proliferation, cell colony formation and cell invasion ability in TPC-1 and IHH-4 cells. In addition, we demonstrated that LINC01186 overexpression inhibited large tumor suppressor kinase 1 (LATS1)/YY1 associated protein 1 (YAP) signaling by reducing YAP1 expression, while increasing LATS1 expression in TPC-1 and IHH-4 cells. Collectively, our data suggested that LINC01186 may serve as a potential target for therapy in thyroid carcinoma.
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BACKGROUND AND OBJECTIVE: Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug-food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA). METHODS: From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure. RESULTS: Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79). CONCLUSIONS: Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Ablação por Cateter , Rivaroxabana/uso terapêutico , Tromboembolia/prevenção & controle , Idoso , Albuminas/análise , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Feminino , Seguimentos , Globulinas/análise , Hemorragia/prevenção & controle , Humanos , Lipoproteínas HDL/sangue , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Prevalência , Estudos Prospectivos , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêuticoRESUMO
Through integrating multi-spectral sensor characteristics of ZY-3 satellite, a modified reflectance-based method is proposed and used to achieve ZY-3 satellite multispectral sensor in-flight radiometric calibration. This method chooses level 1A image as data source and establishes geometric model to get an accurate observation geometric parameters at calibration site according to the information provided in image auxiliary documentation, which can reduce the influences on the calibration accuracy from image resampling and observation geometry errors. We use two-point and multi-points methods to calculate the absolute radiometric calibration coefficients of ZY-3 satellite multispectral sensor based on the large campaign at Dongying city, Shan Dong province. Compared with ZY-3 official calibration coefficients, multi-points method has higher accuracy than two-point method. Through analyzing the dispersion between each calibration point and the fitting line, we find that the residual error of water calibration site is larger than others, which of green band is approximately 67.39%. Treating water calibration site as an error, we filter it out using 95.4% confidence level as standard and recalculate the calibration coefficients with multi-points method. The final calibration coefficients show that the relative differences of the first three bands are less than 2% and the last band is less than 5%, which manifests that the proposed radiometric calibration method can obtain accurate and reliable calibration coefficients and is useful for other similar satellites in future.