Interferon Consensus Sequence-Binding Protein 8, a Tumor Suppressor, Suppresses Tumor Growth and Invasion of Non-Small Cell Lung Cancer by Interacting with the Wnt/β-Catenin Pathway

Background/Aims: Interferon consensus sequence-binding protein 8 (IRF8) belongs to a family of interferon (IFN) regulatory factors that modulates various important physiological processes including carcinogenesis. As reported by others and our group, IRF8 expression is silenced by DNA methylation in both human solid tumors and hematological malignancies. However, the role of IRF8 in lung carcinoma remains elusive. In this study, we determined IRF8 epigenetic regulation, biological functions, and the signaling pathway involved in non-small cell lung cancer (NSCLC). Methods: IRF8 expression were determined by Q- PCR. MSP and A+T determined promotor methylation. MTS, clonogenic, Transwell assay, Flow cytometry, three-dimensional culture and AO/EB stain verified cell function. In vivo tumorigenesis examed the in vivo effects. By Chip-QPCR, RT-PCR, Western blot and Immunofluorescence staining, the mechanisms were studied. Results: IRF8 was significantly downregulated in lung tumor tissues compared with adjacent non-cancerous tissues. Furthermore, methylation-specific PCR analyses revealed that IRF8 methylation in NSCLC was a common event, and demethylation reagent treatment proved that downregulation of IRF8 was due to its promoter CpG hypermethylation. Clinical data showed that the IRF8 methylation was associated with tumor stage, lymph node metastasis status, patient outcome, and tumor histology. Exogenous expression of IRF8 in the silenced or downregulated lung cancer cell lines A549 and H1299 at least partially restored the sensitivity of lung cancer cells to apoptosis, and arrested cells at the G0/G1 phase. Cell viability, clonogenicity, and cell migration and invasive abilities were strongly inhibited by restored expression of IRF8. A three-dimensional culture system demonstrated that IRF8 changed the cells to a more spherical phenotype. Moreover, ectopic expression of IRF8 enhanced NSCLC chemosensitivity to cisplatin. Furthermore, as verified by Chip-qPCR, immunofluorescence staining, and western blotting, IRF8 bound to the T-cell factor/lymphoid enhancer factor (TCF /LEF) promoter, thus repressing β-catenin nuclear translocation and its activation. IRF8 significantly disrupted the effects of Wnt agonist, bml284, further suggesting its involvement in the Wnt/β-catenin pathway. Conclusion: IRF8 acted as a tumor suppressor gene through the transcriptional repression of β-catenin-TCF/LEF in NSCLC. IRF8 methylation may serve as a potential biomarker in NSCLC prognosis

Outlier Detection for Spotting Micro-expressions

Facial expression, as a basic communication method, is an important way of emotion expression and cognition. Facial emotional expression impairment seriously affects interpersonal communication and social life. Micro-expressions (MEs) are involuntary and instant facial dynamics that occurs when the subject failed to suppress their genuine emotions, especially in high-stake situations. Psychological research has shown that MEs can reflect people&rsquo;s true emotions, which is of great help to the treatment of Facial emotional expression impairment. ME spotting aims to locate the apex frame positions of MEs from long videos, which is the first step in ME analysis. Unlike previous researches that used binary classification or maximum feature difference for analysis, in this paper, we apply the idea of outlier detection to spot ME for the first time. MEs are unusual facial dynamics whose movement patterns diverge from others, so they can be regarded as outliers in the feature space of long videos. Our proposed method uses Gaussian model to estimate the probability density function and locates outliers by analyzing the statistical features of long videos to achieve ME spotting. This method was evaluated on CASME I, CASME II and SAMM datasets that only include spontaneous MEs in long videos. The results show that this method can efficiently locate apex frames of ME efficiently in long videos and also provide a new perspective for ME spotting.</p

Petrologic characteristics and genesis of dolostone from the Campanian of the SK-I Well Core in the Songliao Basin, China

The well SK-I in the Songliao Basin is the first scientific borehole targeting the continental Cretaceous strata in China. Oval concretions, thin laminae and beds of dolostone are found intercalated within mudstone and organic-rich black shale in the Nenjiang Formation of Campanian age. Low ordered ferruginous dolomite is composed of euhedral–subhedral rhombs with cloudy nucleus and light rims formed during the diagenesis, which are typical features of replacement. The heavy carbon isotopes (δ13CPDB – 1.16–16.0) are results of both the fermentation of organic matter by microbes and degassing of carbon dioxide during the period of diagenesis, and the presence of light oxygen isotopes (δ18OPDB – 18.53∼−5.1) is a characteristic feature of fresh water influence which means the carbonate may have been altered by ground water or rainwater in the late diagenesis. Marine water incursions into the normally lacustrine basin have been proved by both the salinity of Z value and the occurrence of foraminifera in the same strata where dolomite occurs. Pyrite framboids observed by SEM are usually enclosed in the dolomite crystals or in the mudstones, supporting the sulfate reducing bacteria (SRB). The formation of both dolomite and pyrite are associated with marine water incursions, which not only supply magnesium ion for dolomite, but also result in limited carbonate precipitation in the basin. The presence of pyrite framboids indicates the development of an anoxic environment associated with salinity stratification in the lake. The dolomite in the Nenjiang Formation is the results of marine water incursions, diagenetic replacement of calcareous carbonate and sulfate reducing bacteria (SRB)

Distinct lipidomic profiles between people living with HIV treated with E/C/F/TAF or B/F/TAF: An open-label prospective cohort study

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