RESUMO
Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.
Assuntos
Movimento Celular , Endometriose , Endométrio , Fator 6 Semelhante a Kruppel , Células Estromais , beta Catenina , Humanos , Feminino , Endometriose/metabolismo , Endometriose/patologia , Endometriose/genética , Fator 6 Semelhante a Kruppel/metabolismo , Fator 6 Semelhante a Kruppel/genética , beta Catenina/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia , Endométrio/metabolismo , Endométrio/patologia , Adulto , Apoptose/genética , Proliferação de Células , Progressão da DoençaRESUMO
N-nitrosodiethylamine (NDEA), which is the most toxic nitrosamine among the 9 detected species, has been widely detected in drinking water. Amines containing diethylamine (DEA) groups in the structure would generate NDEA during the disinfection processes. The aim of this study was to evaluate the feasibility of reducing NDEA formation from a commonly used dithiocarbamate pesticide sodium diethyldithiocarbamate (DEDTC) in subsequent chlorination and chloramination by pre-ozonation. The results demonstrated that NDEA could be generated directly during ozonation, its amounts increased from 0 to 14.34 µg/L with increasing ozone dosages (0-4 mg/L), which was higher than that chlorination (2.68 µg/L) and chloramination (4.91 µg/L) when the initial concentration of DEDTC was 20 µM. Pre-ozonation significantly raised NDEA formation from 2.68 to15.32 µg/L in subsequent chlorination; and that from 4.91 to 9.54 µg/L during subsequent chloramination processes. The addition of â¢OH scavenger tert-butanol (tBA) increased the production of NDEA from 8.14 to 20.80 µg/L during ozonation, and that from 6.76 to17.98 µg/L in O3/HClO process, 8.74 to 17.33 µg/L in O3/NH2Cl process. Except for NO3- and CO32-, most of the co-existing substances promoted NDEA generation from DEDTC under disinfection conditions. Based on the results of Gaussian theory calculations, GC/MS and UPLC-Q-TOFMS analysis, the influencing mechanisms of pre-ozonation on NDEA generation in the subsequent disinfection process were proposed. In addition, not only acute/chronic toxicity calculation but also luminescent bacteria test was performed to assess the possibility of pre-ozonation on the risk control of DEDTC. The research results fill a gap in the control of NDEA pollution and help to develop a safer ozone oxidation technology.
Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Halogenação , Dietilnitrosamina , Estudos de Viabilidade , Desinfecção/métodos , Ozônio/análise , Purificação da Água/métodos , Poluentes Químicos da Água/análiseRESUMO
Based on the automatic identification system (AIS) data and large field survey datasets for Xiamen port, the activity-based approach was used to calculate the emissions from each sailing ship in the Xiamen Emission Control Area (XECA), and to obtain the 2018 air emissions inventory for the XECA. This study subsequently analyzed the emission characteristics and spatiotemporal distribution characteristics of pollutants. The results showed that in 2018, the total amount of pollutants discharged from ships in the XECA was 16413 t, of which 82.2% were from ships entering and leaving the port and 17.8% were from ships outside of the port. NOx emissions were the highest among all of the pollutants and accounted for 64.2% of the total. Comparing the results of the five modes, emissions at berth were the highest, which was followed by the cruise mode, reduced speed-zone mode and maneuvering mode, and finally, the hoteling mode. In addition, the analysis indicated that the main source of pollutant emissions in Xiamen Port was cargo ships, of which, container ships contributed the most. The peak period of pollutant emissions from ships was between 09:00 and 16:00. The emission value during February was the lowest over the year, whereas the highest emission values occurred mostly during March and May. In terms of the spatial distribution, this study revealed that the main channel and port coastline had the highest emission values.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Navios , Emissões de Veículos/análiseRESUMO
While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.