Abstract. The climatological variation of aerosol properties and the planetary boundary layer (PBL) during 2013-2015 over the Yangtze River Delta (YRD) region were investigated by employing ground-based Micro Pulse Lidar (MPL) and CE-318 sun-photometer observations. Combining Moderate Resolution Imaging Spectroradiometer (MODIS) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite products, enhanced haze pollution events affected by different types of aerosol over the YRD region were analyzed through vertical structures, spatial distributions, backward trajectories, and the potential source contribution function (PSCF) model. The results show that aerosols in the YRD are dominated by fine-mode par-
This study aims to investigate the potential mechanisms and identify core biomarkers of Hepatocellular carcinoma (HCC). The profile GSE113850 was downloaded to analyze the differentially expressed genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network analysis were used to reveal the main signal pathways of the differentially expressed genes (DEGs) and hub genes. The correlation between core gene expression and pathological stages, the disease-free survival analysis, the overall survival analysis were analyzed by Gene Expression Profiling Interactive Analysis. Furthermore, we reidentified the expression level of core genes of carcinoma tissues and para-carcinoma tissues from 14 HCC patients with real-time reverse transcription-polymerase chain reaction analysis (RT-PCR) and western blotting. After SK-Hep1 cell was treated with cyclin-dependent kinase 1 (CDK1) siRNA for 72 h, we detected the expression of the core genes and fluorescence-activated cell sorting analysis. A total of 378 DEGs were found. GO and KEGG analysis revealed that the DEGs were mainly enriched in the cell cycle. There were positive correlations among CDK1, polo-like kinase 1, shugoshin2 and anillin actin-binding protein. Moreover, the expression levels of four core genes were related to the HCC occurrence, pathological stages, and survivorship curve. The clinical HCC specimens verified the higher expression level of core genes by real-time RT-PCR. The transfection of siCDK1 in SK-Hep1 resulted in a disordered cell cycle. Furthermore, CDK1 knockdown suppressed the expression of PLK1, ANLN, and SGOL2. The CDK1-PLK1/SGOL2/ANLN pathway mediating abnormal cell division in the cell cycle might be a critical process in HCC.
34Aerosol particles influence Earth's radiation budget and play a significant role in global and regional climate change 35 (Hansen et al., 1997;Che et al., 2015a;Zhang et al., 1998;Li et al., 2016). Despite numerous studies on aerosols, there is still 36 much uncertainty surrounding aerosol optical properties in relation to current assessments and predictions of global climatic 37 change (Ipcc, 2007;Stocker et al., 2013). The frequent occurrence of regional pollution demands worldwide attention 38 because of the serious consequences it can have on visibility and human health (Wu et al., 2012;Sun et al., 2016;Chan and 39 Yao, 2008). 40The planetary boundary layer (PBL) is a critical component of Earth's climate system (Medeiros et al., 2005). The PBL 41is directly coupled with the land surface, and its height (PBLH) plays a significant role in determining the vertical 42 distributions of aerosol particles (Deardorff, 1972). The higher the accumulation of ambient aerosols, the less solar radiation 43 reaches the surface, which will further restrict the development of the PBL, thus compounding the air pollution near the 44 surface during prolonged stagnant weather conditions (Gao et al., 2015;Petä jä et al., 2016;Leng et al., 2015). Lidar measures 47Micro Pulse Lidar (MPL) observations to ascertain seasonal variations (Ku et al.; Lewis et al., 2013). 48To analyze the spatiotemporal distribution of aerosol optical properties, multiple measurements from diverse angles 58Monitoring Instrument (OMI) products, to detail an integrated observation of an agricultural biomass burning episode in 59 Nanjing, China. Along with the observations, trajectory models (e.g. HYSPLIT) for air mass tracking and potential source 60apportionment have been applied to analyze the origins of aerosols (Wang et al., 2006b). 61The Yangtze River Delta (YRD) region is a key economic and cultural hub in China, with progressive development 62 resulting in further particle emissions from industry and other anthropogenic activities. Many studies have been conducted 63 on the aerosol optical properties and their variations in the cities of the YRD, such as Shanghai, Nanjing, Lin'an, and Taihu (Xia et al., 2007;Pan et al., 2010;He et al., 2012;Ding et al., 2013;Liu et al., 2015). Particularly in Hangzhou, the capital city 64 65of Zhejiang province, some researches have focused on determining the seasonal variation of aerosol properties, chemical 66 compositions, and PM concentrations (Qi, 2016;Ming et al., 2017;Xiao et al., 2011), or single-case analyses on features of 67 one pollution process (Chen et al., 2012;Fu et al., 2014;Li et al., 2015). However, research into the sources of pollutants in 68 the YRD region is still needed to understand the mechanisms underlying haze pollution. Among these studies, there is a lack 69of long-term analysis of aerosols and their sources. In addition, single-case analysis is insufficiently representative for a site 70 that experiences frequent haze occurrence. There is a lack of comprehensive studies in proc...
BackgroundTacrolimus (FK506)-induced diabetes mellitus is one of the most important factors of post-transplant diabetes mellitus (PTDM). However, the detailed mechanisms underlying PTDM are still unclear. Farnesoid X receptor (FXR) regulates glycolipid metabolism. The objective of this study was to explore whether FXR is involved in the development of tacrolimus-induced diabetes mellitus.MethodsAfter C57BL/6J mice were treated with tacrolimus (FK506) for 3 months, the fasting blood glucose levels, body weights, renal morphological alterations, and mRNA expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2) among the control group, the FK506 group and the FK506 + GW4064 (a FXR agonist) group (n = 7) were measured. The intracellular location of peroxisome proliferator activated receptor γ coactivator-1α (PGC1α) and forkhead box O1 (FOXO1) was detected by immunofluorescence. Human renal cortex proximal tubule epithelial cells (HK-2) were treated with 15 μM FK506 or 4 μM FXR agonist (GW4064) for 24, 48 and 72 h, and the expression levels of FXR, gluconeogenesis and glucose uptake, representing the enzymes PEPCK and GLUT2, were detected with real-time PCR and western blot analyses. Finally, the mRNA levels of PEPCK and GLUT2 in HK-2 cells were measured after FXR was upregulated.ResultsFK506 significantly inhibited the mRNA and protein levels of FXR at 48 h and 72 h in HK-2 cells (P < 0.05). Meanwhile, FK506 promoted gluconeogenesis and inhibited glucose uptake in HK-2 cells (P < 0.05). However, overexpression of FXR in transfected HK-2 cell lines significantly inhibited gluconeogenesis and promoted glucose uptake (P < 0.05). The FXR agonist GW4064 significantly decreased the fasting blood glucose in mice challenged with FK506 for 3 months (P < 0.05), inhibited gluconeogenesis (P < 0.05) and significantly promoted glucose uptake (P < 0.05). Immunofluorescence staining and western blot analyses further revealed that FXR activation may affect the translocation of PGC1α and FOXO1 from the nucleus to the cytoplasm.ConclusionsFXR activation may mitigate tacrolimus-induced diabetes mellitus by regulating gluconeogenesis as well as glucose uptake of renal cortex proximal tubule epithelial cells in a PGC1α/FOXO1-dependent manner, which may be a potential therapeutic strategy for the prevention and treatment of PTDM.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality globally. Despite the remarkable improvements in comprehensive HCC treatment, the underlying mechanistic details of HCC remain elusive. We screened HCC patients for differentially expressed genes (DEGs) using the Gene Expression Omnibus (GSE113850) and The Cancer Genome Atlas (TCGA) datasets. LINC01554 expression in 40 paired samples was determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and its clinical significance was assessed. LINC01554 was found to have a gain-of-function role in HCC in vitro. Additionally, the bioinformatics analysis of the genes co-expressed with LINC01554 was performed using the Co-LncRNA website, and potential molecular mechanisms were investigated using the Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes resources and validated by in vitro experiments. A total of 229 DEGs were identified from the GSE113850 dataset. Among the identified DEGs, three long non-coding RNAs (lncRNAs) (DIO3OS, LINC01554, and LINC01093) with |logFC| ≥2 and P<0.05 were screened. A total of 148 lncRNAs with |logFC| ≥1 and P<0.05 were identified from TCGA dataset. Low LINC01554 expression levels were significantly correlated with overall survival, pathological stage, hepatitis B infection, tumour size, portal vein tumour thrombus, and TNM stage. Using gain-of-function assays, we further showed that LINC01554 inhibited the proliferation, migration, and invasion of the HCCLM9 and SK-Hep1 cells and promoted G0/G1 arrest, but it did not significantly affect apoptosis. Western blotting revealed that LINC01554 overexpression resulted in increased ZO-1 and E-cadherin expression levels, but decreased N-cadherin and vimentin expression levels. Moreover, LINC01554 overexpression inhibited Akt, p-Akt, β-catenin, and p-Gsk3β expression. Our results showed that LINC01554 repressed HCC cell invasiveness and epithelial-to-mesenchymal transition partly by inhibiting Wnt and PI3K-Akt signalling in vitro. Taken together, our findings provide new insights into the molecular mechanisms underlying HCC tumourigenesis and implicate LINC01554 as a potential target for HCC therapy.
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