Prognostic value and gene regulatory network of CMSS1 in hepatocellular carcinoma.

BACKGROUND: Cms1 ribosomal small subunit homolog (CMSS1) is an RNA-binding protein that may play an important role in tumorigenesis and development. OBJECTIVE: RNA-seq data from the GEPIA database and the UALCAN database were used to analyze the expression of CMSS1 in liver hepatocellular carcinoma (LIHC) and its relationship with the clinicopathological features of the patients. METHODS: LinkedOmics was used to identify genes associated with CMSS1 expression and to identify miRNAs and transcription factors significantly associated with CMSS1 by GSEA. RESULTS: The expression level of CMSS1 in hepatocellular carcinoma tissues was significantly higher than that in normal tissues. In addition, the expression level of CMSS1 in advanced tumors was significantly higher than that in early tumors. The expression level of CMSS1 was higher in TP53-mutated tumors than in non-TP53-mutated tumors. CMSS1 expression levels were strongly correlated with disease-free survival (DFS) and overall survival (OS) in patients with LIHC, and high CMSS1 expression predicted poorer OS (P< 0.01) and DFS (P< 0.01). Meanwhile, our results suggested that CMSS1 is associated with the composition of the immune microenvironment of LIHC. CONCLUSIONS: The present study suggests that CMSS1 is a potential molecular marker for the diagnosis and prognostic of LIHC.

Visible-Light-Induced 1,7-Enyne Dicyclization: Synthesis of Ester-Substituted Benzo[j]phenanthridines.

A novel alkoxycarbonyl-radical-triggered cascade cyclization of 1,7-enynes, with alkyloxalyl chlorides as the ester units, for the synthesis of benzo[j]phenanthridines is described. The reaction conditions exhibit excellent compatibility with a broad range of alkoxycarbonyl radical sources and realize the installation of an ester group in the polycyclic compound. This radical cascade cyclization reaction features excellent functional group tolerance, mild reaction conditions, and good to excellent yields.

A point-of-care chemiluminescence immunoassay for pepsinogen I enables large-scale community health screening.

Pepsinogen I (PGI) can reflect the morphology and function of the gastric mucosa. Accordingly, the large-scale community health screening of PGI can dramatically increase the early diagnosis rate of gastric cancer. However, PGI testing can only be carried out in comprehensive hospitals and health examination centers. To ameliorate this issue, a point-of-care chemiluminescent immunoassay for PGI was developed in a fully automated miniaturized instrument. This instrument was especially developed for health check-ups in the grassroots communities; its volume of which is only 0.18 m3. Critically, the entire detection process for a single sample only requires 20 min, and the samples can be loaded continuously, making the method suitable for high-throughput analysis. The assay displayed an excellent detection limit of 0.048 ng/mL with a broad detection range of 0-200 ng/mL. Furthermore, this assay exhibited high sensitivity and specificity, had low intra- and inter-assay coefficients of variation (<10%), and was not affected after storage at 37 °C for 7 days. The assay was used to detect PGI in 95 clinical serum samples, and the results were highly correlated with those that were clinically tested (correlation coefficient, R2 = 0.998). Hence, the method established in this work has great application value and can be broadly applied for the large-scale screening of gastric cancer in resource-limited areas.

ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway.

Hepatocellular carcinoma (HCC) is a common high-mortality cancer, mainly due to diagnostic difficulties during its early clinical stages. In this study, we aimed to identify genes that are important for HCC diagnosis and treatment, and we investigated the underlying mechanism of prognostic differences. Differentially expressed genes (DEGs) were identified by using the limma package, and receiver operating characteristic curve analysis was performed to identify diagnostic markers for HCC. Bioinformatics and clinical specimens were used to assess epithelial cell transforming 2 (ECT2) in terms of expression, prognostic value, pathways, and immune correlations. In vitro experiments were used to investigate the underlying mechanism and function of ECT2, and the results were confirmed through in vivo experiments. The integrated analysis revealed 53 upregulated DEGs, and one candidate biomarker for diagnosis (ECT2) was detected. High expression of ECT2 was found to be an independent prognostic risk factor for HCC. ECT2 expression showed a strong correlation with tumor-associated macrophages. We found that ECT2 overexpression increased the migration and proliferation of HCC cells. It also promoted the expression of PLK1, which subsequently interacted with PTEN and interfered with its nuclear translocation, ultimately enhancing aerobic glycolysis and promoting M2 macrophage polarization. M2 macrophages suppress the functions of NK cells and T cells, and this was confirmed in the in vivo experiments. Overall, ECT2 may promote the polarization of M2 macrophages by enhancing aerobic glycolysis and suppressing the functions of immune cells. ECT2 could serve as a candidate diagnostic and prognostic biomarker for HCC.

MTIF2 impairs 5 fluorouracil-mediated immunogenic cell death in hepatocellular carcinoma in vivo: Molecular mechanisms and therapeutic significance.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality; it has been reported that immune cell infiltration is a prognosis factor. Here we identified genes that associated with tumor immune cell infiltrate; the underlying mechanism was verified by in vivo and in vitro experiment. In this study, Weighted correlation network analysis (WGCNA) and CIBERSORT tool were used to identify MTIF2 as the hub tumor immune infiltrating gene in HCC. To investigate the underlying role played by MTIF2, MTIF2 was knocked down by transfection of shRNA targeting MTIF2, CCK8, and EdU incorporation assay was used to evaluate the effect of MTIF2 on proliferation, wound heal assay and transwell assay was used to confirm its effect on cell migration. Ecto-calreticulin on the cell surface was evaluated by flow cytometry, ATP, and HMGB1 secretion were tested to the investigated effect of MTIF2 on the immunogenic cell death (ICD) process. We found that down-regulation of MTIF2 impaired proliferation and migration capacity of HCC cells, chemoresistance to 5-Fluorouracil (5-FU) weakened after MTIF2 was knocked down. Reduced release of damage-associated molecular patterns (DAMP) was observed after MTIF2 was overexpressed, which subsequently impaired dendritic cell (DC) maturation and proliferation of CD8 + T cells. Mechanically, the co-IP experiment confirmed that MTIF2 could interact with AIFM1, prevents AIFM1 induced transcription of caspase3, and finally suppress apoptosis. In vivo experiment also used to confirm our previously conclusion, our result indicated that MTIF2 overexpression suppresses tumor apoptosis and immune cell activity in the 5-FU therapy in vivo model, by suppression maturation of tumor-infiltrated DC. Collectively, our study confirmed that MTIF2 impair drug-induced immunogenic cell death in hepatocellular carcinoma cells.

Improvement to the Carrier Transport Properties of CdZnTe Detector Using Sub-Band-Gap Light Radiation.

The effects of sub-band-gap light radiation on the performance of CdZnTe photon-counting X-ray detectors were studied using infrared light with different wavelengths in the region of 980⁻1550 nm. The performance of the detectors for X-ray detection was improved by the radiation of infrared light with the wavelengths of 1200 nm and 1300 nm. This was because the increase of the electron indirect transition, and the weakening of the built-in electric field induced by the trapped holes, reduced the drift time of the carrier, and increased the charge collection efficiency. To further analyze the intrinsic behavior of the trapped charge, the deep-level defects of CdZnTe crystal were measured by thermally stimulated current spectroscopy (TSC). The deep-level defect indicated by the trap named T4 in TSC spectra with the ionization energy of 0.43 eV should be responsible for the performance deterioration of CdZnTe detectors.

[Effects of family and peer support upon the stages of health-related behavior in adolescent].

OBJECTIVE: To investigate the stages of health-related behaviors, family and peer support situation about adolescent in Wuhan, and to provide evidence for health intervention and health promotion. METHODS: Based on the principle of multi-stage stratified cluster sampling, extracted two junior middle school and two high school in two cities in Wuhan from March 2012 to May. A total of 1 200 students, which were part of the first and second grade class in middle school and high school, toke as the investigation object. The study surveyed following content, including the demographic situation, adolescent health-related behavior (physical activity, sedentary behavior, high-fat diet behavior, fruit and vegetable intaking behavior), stages of adolescent health related behavior (precontemplation, contemplation, preparation, action, maintenance) and adolescent support got from family and peer. The questionnaire was distributed in 1 200 copies, the valid questionnaires were 1 052 and the effective rate was 87.67%. Using χ² test to compare the different stages of change in health related behavior, t test was used to compare different groups of social support and using analysis of variance and post test to analyze social support of the four types behavior. RESULTS: In 1 052 students, there was 555 (52.8%) middle school students, 497 (47.2%) high school students, and 553 (52.6%) boys, 499 (47.4%) girls. In physical exercise and sedentary behavior, numbers of precontemplation was respectively accounting for 42.2% (444/1 200) and 28.4% (299/1 200). In high-fat diet behavior, the stages of preparation and maintain was occupied 46.7% (492/1 200). In fruit and vegetable intake behavior, there was 32.9% (346/1200) students in contemplation. Numbers in action stage was both less in the above four behavior, accounting for 6.2% (65/1 200), 8.9% (94/1 200), 14.0% (147/1 200) and 6.3% (66/1 200) separately. Adolescent peer support score respectively (2.9 ± 0.7), (2.8 ± 0.8) and (2.9 ± 0.9), which was higher than the family support scores ((2.7 ± 1.1), (2.5 ± 1.2) and (2.9 ± 1.2)) (t values were -8.72, -11.22 and -2.59, respectively. All P values were < 0.001) in physical exercise, sedentary behavior and high fat diet, but in the intake of fruits and vegetables behavior, family support score was higher than peer support (score was respectively (3.3 ± 0.9) and (3.5 ± 1.2); t < 9.97, P < 0.001). ANOVA and post hoc comparison showed that the score of family and peer support in the after-action stage was significantly higher than that the before-action stage in physical exercise, high-fat diet and fruit and vegetable intake behavior, while the differences in sedentary behavior was not significant. CONCLUSION: Youth health-related behaviors remained in its infancy, there was a certain impact on its stages which showed that the higher social support the more advanced stages of behavior.