Hypoxia-induced GPR4 suppresses trophoblast cell migration and proliferation through the MAPK signaling pathway.

Pre-eclampsia (PE), a common pregnancy-systemic syndrome, is characterized by proteinuria and hypertension and is the leading cause of maternal and fetal mortality. Thus, we aim to investigate the role of G-Protein Coupled Receptor 4 (GPR4) in PE and the underlying molecular mechanism. In this study, GSE66273 microarray data were obtained from the Gene Expression Omnibus(GEO) database of the National Center for Biotechnology Information, and Gene set enrichment analysis (GSEA) was performed by GSEA software. qRT-PCR and Immunohistochemistry (IHC) or western blotting were used to assay for the expression of GPR4 in PE placentas and HTR8/SVneo cells. The influence of acidosis and hypoxia environments on the expression of GPR4 was explored using western blotting. Cell proliferation and migration of HTR8/SVneo cells were measured using EdU and MTT assays and migration assay, respectively. Moreover, expressions of MEK1/2, p-MEK1/2, ERK1/2, and p-ERK1/2 in HTR8/SVneo cells were assayed by western blotting. Our data demonstrated that the expression of GPR4 was up regulated in PE placentas. Increase in acidic pH and hypoxic levels increased the expression of GPR4 in HTR8/SVneo cells. GPR4 inhibited cell proliferation and migration in the HTR8/SVneo cells. GPR4 silencing enhanced the phosphorylation of p-MEK1/2and p-ERK1/2 in HTR8/SVneo cells. Additionally, we found that pathway inhibitor partially reversed the effects of GPR4 on proliferation and migration of HTR8/SVneo cells. In conclusions, these results show that GPR4 suppressed cell proliferation and migration by inhibiting MAPK signaling pathway in PE.

Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861-0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.

Underground coal fire emission of spontaneous combustion, Sandaoba coalfield in Xinjiang, China: Investigation and analysis.

Long-term spontaneous combustion of coal has caused serious ecological and environmental problems. Only in recent years has it received growing popularity to undertake relevant researches. In order to study the impact of combustion by-products on atmosphere in the Sandaoba fire field, Xinjiang, a region-scale field survey was firstly conducted to investigate the gaseous-solid emissions in separated fire sections. The evaluation method and model have been proposed to describe the underground combustion and the related air pollution. Every year, the total estimates of the gaseous emission are approximately 4030 t of CO2, 113.6 t of SO2 and 57.3 t of CO. The emission pollution varies considerably from regions, and is substantially attenuated with the advancement of fire control. Principal component analysis (PCA) refines the thermophysical parameters into three attributions: the intrinsic thermophysical property, atmospheric dynamics, and combustion degree. PCA score distribution shows that thermophysical parameter is dominated by the combustion condition at severely polluted areas. Factor Analysis is used to extract four contaminant indicators, which suggests the local air suffers sulfur oxides pollution the most. The air quality index of the eight study sections calculated are all below 60, ranging from 24 to 58. It indicates that coal fire air pollution is in the medium-to-severe stage. By Canonical Correlation Analysis, it is noted that thermophysical indicator performs outstanding explanatory for contaminant variates. On the whole, the higher the level of thermophysical properties in the fire area, the greater the intensity of pollutant emission. Underground coalfield fire is dominated by smoldering, and the overall combustion efficiency is lower than 0.8 which generally declines as the excess air coefficient increasing.

Clean Power Generation from the Intractable Natural Coalfield Fires: Turn Harm into Benefit.

The coal fires, a global catastrophe for hundreds of years, have been proved extremely difficult to control, and hit almost every coal-bearing area globally. Meanwhile, underground coal fires contain tremendous reservoir of geothermal energy. Approximately one billion tons of coal burns underground annually in the world, which could generate ~1000 GW per annum. A game-changing approach, environmentally sound thermal energy extraction from the intractable natural coalfield fires, is being developed by utilizing the waste energy and reducing the temperature of coalfield fires at the same time. Based on the Seebeck effect of thermoelectric materials, the temperature difference between the heat medium and cooling medium was employed to directly convert thermal energy into clean electrical energy. By the time of December 2016, the power generation from a single borehole at Daquan Lake fire district in Xinjiang has been exceeded 174.6 W. The field trial demonstrates that it is possible to exploit and utilize the waste heat resources in the treated coal fire areas. It promises a significant impact on the structure of global energy generation and can also promote progress in thermoelectric conversion materials, geothermal exploration, underground coal fires control and other energy related areas.

Changes of cardiac structure and function in pediatric patients with high altitude pulmonary hypertension in Tibet.

This study was performed to evaluate the structural and functional cardiac changes in pediatric high altitude pulmonary hypertension (HAPH) using magnetic resonance imaging (MRI) and Doppler echocardiography (Echo). Ten patients with infantile HAPH (aged 12 to 24 months) and eight healthy age-matched children (control group) underwent MRI and Echo studies. All participants were born and living in the Qinghai-Tibetan Plateau (3600 to 4600 m). The studies were performed at the Children's Hospital located in Xining, Qinghai (2260 m). The right and left ventricular end-systolic (RVEST and LVEST, respectively) and end-diastolic (RVEDT and LVEDT, respectively) wall thicknesses were calculated directly from the MRI scans. The mean pulmonary arterial pressure (mPAP) was measured using Echo. RVEST was significantly higher in the HAPH group than in the control group (6.8 +/- 0.6 and 3.7 +/- 0.5 mm, respectively; p < 0.001). RVEDT was significantly higher in the HAPH patients when compared with the control group (4.9 +/- 1.1 and 2.1 +/- 0.3 mm, respectively; p < 0.05). Mean PAP in the HAPH group was significantly higher than in the control group (66.8 +/- 6.7 and 33.8 +/- 3.6 mmHg, respectively; p < 0.001) and was positively correlated with RVEDT (r(2) = 0.562, p < 0.001). Right ventricular ejection fraction was significantly lower in the HAPH group when compared with the control group (29.8 +/- 11.8 and 55.5 +/- 9.9%, respectively; p < 0.001); however, left ventricular ejection fraction was similar in both groups. These results indicate that hypoxia-induced infantile HAPH leads to right ventricular hypertrophy in these patients. These structural cardiac changes may lead to right ventricular dysfunction and right heart failure; however, left ventricular function is preserved.