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

Value of C-ROSE During EBUS-TBNA to Obtain the Tissue Sample in the Diagnosis of Lung Cancer

Background and objective Most of the patients with lung and (or) mediastinal occupying lesions are considered to be primary lung cancer clinically, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly useful operation to obtain the tissue sample and get definitive diagnosis of pathological tissues. In the EBUS-TBNA process, cytological rapid on-site evaluation (C-ROSE) is a useful technology. The purpose of our study is to discuss the value of C-ROSE in the diagnosis of lung cancer by EBUS-TBNA sampling. Methods Retrospective analysis of 141 cases clinical data who were performed with EBUS-TBNA and suspected diagnosis primary lung cancer, which were found have mediastinal and (or) lung lesions (including the enlargement of the lymph nodes/mass) by computed tomography (CT). Among these patients, 81 patients were in the C-ROSE group and 60 patients were in the No C-ROSE group. The message of puncture and complication of EBUS-TBNA with or without C-ROSE were compared. At the same time, we analysis the sensitivity and specificity, positive predictive value, negative predictive value of C-ROSE combined with EBUS-TBNA in that of the diagnosis of lung cancer. Results We found no statistical difference of the needle passes between C-ROSE group and No C-ROSE group. But in C-ROSE group, specimen qualified rate and diagnostic yields were signicantly higher than No C-ROSE group (98.77% vs 90.00%, 88.89% vs 75.00%, P<0.05), the incidence of complications in the C-ROSE group was signicantly lower than that in the No C-ROSE group (1.23% vs 11.67%, P<0.05). The sensitivity, specificity, positive predictive value and negative predictive value of C-ROSE combined with EBUS-TBNA in the diagnosis of lung cancer are 92.21%, 100.00%, 100.00% and 40.00%. Conclusion EBUS-TBNA combined with C-ROSE can improve the specimen qualified rate and diagnostic rate, also can reduce the complications thus worthy of further promotion

Porous Copper/Zinc Bimetallic Oxides Derived from MOFs for Efficient Photocatalytic Reduction of CO2 to Methanol

A novel metal organic framework (MOF)-derived porous copper/zinc bimetallic oxide catalyst was developed for the photoreduction of CO2 to methanol at a very fast rate of 3.71 mmol gcat&minus;1 h&minus;1. This kind of photocatalyst with high activity, selectivity and a simple preparation catalyst provides promising photocatalyst candidates for reducing CO2 to methanol

Ultrathin Photonic Polymer Gel Films Templated by Non-Close-Packed Monolayer Colloidal Crystals to Enhance Colorimetric Sensing

Responsive polymer-based sensors have attracted considerable attention due to their ability to detect the presence of analytes and convert the detected signal into a physical and/or chemical change. High responsiveness, fast response speed, good linearity, strong stability, and small hysteresis are ideal, but to gain these properties at the same time remains challenging. This paper presents a facile and efficient method to improve the photonic sensing properties of polymeric gels by using non-close-packed monolayer colloidal crystals (ncp MCCs) as the template. Poly-(2-vinyl pyridine) (P2VP), a weak electrolyte, was selected to form the pH-responsive gel material, which was deposited onto ncp MCCs obtained by controlled O2 plasma etching of close-packed (cp) MCCs. The resultant ultrathin photonic polymer gel film (UPPGF) exhibited significant improvement in responsiveness and linearity towards pH sensing compared to those prepared using cp MCCs template, achieving fast visualized monitoring of pH changes with excellent cyclic stability and small hysteresis loop. The responsiveness and linearity were found to depend on the volume and filling fraction of the polymer gel. Based on a simple geometric model, we established that the volume increased first and then decreased with the decrease of template size, but the filling fraction increased all the time, which was verified by microscopy observations. Therefore, the responsiveness and linearity of UPPGF to pH can be improved by simply adjusting the etching time of oxygen plasma. The well-designed UPPGF is reliable for visualized monitoring of analytes and their concentrations, and can easily be combined in sensor arrays for more accurate detection

Early acquired resistance to EGFR-TKIs in lung adenocarcinomas before radiographic advanced identified by CT radiomic delta model based on two central studies

Abstract Early acquired resistance (EAR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinomas before radiographic advance cannot be perceived by the naked eye. This study aimed to discover and validate a CT radiomic model to precisely identify the EAR. Training cohort (n = 67) and internal test cohort (n = 29) were from the First Affiliated Hospital of Fujian Medical University, and external test cohort (n = 29) was from the Second Affiliated Hospital of Xiamen Medical College. Follow-up CT images at three different times of each patient were collected: (1) baseline images before EGFR-TKIs therapy; (2) first follow-up images after EGFR-TKIs therapy (FFT); (3) EAR images, which were the last follow-up images before radiographic advance. The features extracted from FFT and EAR were used to construct the classic radiomic model. The delta features which were calculated by subtracting the baseline from either FFT or EAR were used to construct the delta radiomic model. The classic radiomic model achieved AUC 0.682 and 0.641 in training and internal test cohorts, respectively. The delta radiomic model achieved AUC 0.730 and 0.704 in training and internal test cohorts, respectively. Over the external test cohort, the delta radiomic model achieved AUC 0.661. The decision curve analysis showed that when threshold of the probability of the EAR to the EGFR-TKIs was between 0.3 and 0.82, the proposed model was more benefit than treating all patients. Based on two central studies, the delta radiomic model derived from the follow-up non-enhanced CT images can help clinicians to identify the EAR to EGFR-TKIs in lung adenocarcinomas before radiographic advance and optimize clinical outcomes

One-Step Asymmetric Growth of Continuous Metal–Organic Framework Thin Films on Two-Dimensional Colloidal Crystal Arrays: A Facile Approach toward Multifunctional Superstructures

In this work, we present a facile approach toward producing multifunctional metal–organic framework (MOF) superstructures by asymmetric growth of continuous MOFs thin films on two-dimensional colloidal crystal arrays anchored at the air–solution interfaces, in which the control over spatial configuration, structural hierarchy, and overall dimensionality of MOF superstructures can be realized all at once. This interfacial growth method also endows MOF superstructures with an unprecedented transferability, which greatly facilitates the interfacing of MOF materials with other functional surfaces. We have demonstrated this by the construction of layered structures (including hybrid ones) that are promising for device applications. Taking advantage of the resultant periodic and hierarchical porous structures, the as-grown MOF superstructures lend themselves to efficient vapor sensing, size-screening of nanoparticles, and removal of dye molecules from aqueous solutions, and have exhibited a superior performance as compared to their unstructured counterparts. Therefore, this work not only presents an efficient route in well-organizing MOF nanocrystals at the meso-/macroscopic scale but also provides an inspiring example of enriching the material performance of MOFs by shaping their physical forms

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)

Application value of CT radiomic nomogram in predicting T790M mutation of lung adenocarcinoma

Abstract Background The purpose of this study was to develop a radiomic nomogram to predict T790M mutation of lung adenocarcinoma base on non-enhanced CT lung images. Methods This retrospective study reviewed demographic data and lung CT images of 215 lung adenocarcinoma patients with T790M gene test results. 215 patients (including 52 positive) were divided into a training set (n = 150, 36 positive) and an independent test set (n = 65, 16 positive). Multivariate logistic regression was used to select demographic data and CT semantic features to build clinical model. We extracted quantitative features from the volume of interest (VOI) of the lesion, and developed the radiomic model with different feature selection algorithms and classifiers. The models were trained by a 5-fold cross validation strategy on the training set and assessed on the test set. ROC was used to estimate the performance of the clinical model, radiomic model, and merged nomogram. Results Three demographic features (gender, smoking, emphysema) and ten radiomic features (Kruskal-Wallis as selection algorithm, LASSO Logistic Regression as classifier) were determined to build the models. The AUC of the clinical model, radiomic model, and nomogram in the test set were 0.742(95%CI, 0.619–0.843), 0.810(95%CI, 0.696–0.907), 0.841(95%CI, 0.743–0.938), respectively. The predictive efficacy of the nomogram was better than the clinical model (p = 0.042). The nomogram predicted T790M mutation with cutoff value was 0.69 and the score was above 130. Conclusion The nomogram developed in this study is a non-invasive, convenient, and economical method for predicting T790M mutation of lung adenocarcinoma, which has a good prospect for clinical application