Charge Dynamics Engineering Sparks Hetero-Interfacial Polarization for an Ultra-Efficient Microwave Absorber with Mechanical Robustness.

Microwave absorbers with high efficiency and mechanical robustness are urgently desired to cope with more complex and harsh application scenarios. However, manipulating the trade-off between microwave absorption performance and mechanical properties is seldom realized in microwave absorbers. Here, a chemistry-tailored charge dynamic engineering strategy is proposed for sparking hetero-interfacial polarization and thus coordinating microwave attenuation ability with the interfacial bonding, endowing polymer-based composites with microwave absorption efficiency and mechanical toughness. The absorber designed by this new conceptual approach exhibits remarkable Ku-band microwave absorption efficiency (-55.3 dB at a thickness of 1.5 mm) and satisfactory effective absorption bandwidth (5.0 GHz) as well as desirable interfacial shear strength (97.5 MPa). The calculated differential charge density depicts the uneven distribution of space charge and the intense hetero-interfacial polarization, clarifying the structure-performance relationship from a theoretical perspective. This work breaks through traditional single performance-oriented design methods and ushers a new direction for next-generation microwave absorbers.

SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer.

BACKGROUND: Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. METHODS: The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-κB was determined by luciferase assay and qRT-PCR. AKT, IKK, IκB and their phosphorylation level were verified by western blot. RESULTS: We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation to confer oxaliplatin resistance. CONCLUSIONS: Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-κB pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment.

Development and validation of a hypoxia-related gene pair signature to predict overall survival in head and neck squamous cell carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC. METHODS: Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model. RESULTS: A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, T cells CD8, etc. were significantly higher in the low-risk group. CONCLUSION: In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

SOX9 drives the epithelial-mesenchymal transition in non-small-cell lung cancer through the Wnt/ß-catenin pathway.

BACKGROUND: The distant metastasis of cancer cells is a risk factor for tumor lethality and poor prognosis in non-small-cell lung carcinoma (NSCLC). Increased SOX9 expression has been associated with clinical stage and poor prognosis in NSCLC, but the molecular mechanisms by which SOX9 promotes metastasis in NSCLC are still unknown. METHODS: The relationship between SOX9 expression and T, N, M classification was assessed using the χ2 test and Spearman's analysis in 142 immunohistochemically diagnosed specimens of NSCLC. We also generated SOX9-overexpression and SOX9-knockdown cells lines and their corresponding control cell lines by transfection with lentiviral constructs. In vivo assay, SOX9-overexpressing and SOX9-knockdown NSCLC cells were injected in zebrafish to examine distance metastasis. Gene set enrichment analysis (GSEA) was applied to analysis the correlation between SOX9 overexpression and Wnt/ß-catenin pathway. Luciferase assay was used to check transcriptional activity of TCF/LEF and western blot and immunofluorescence was employed to detect ß-catenin translocation in SOX9-overexpression, SOX9-knockdown and their corresponding control cell lines. RESULTS: We found that SOX9 overexpression correlates with the T, N and M stage significantly (p = 0.03, 0.000, and 0.032 respectively) in 142 immunohistochemically diagnosed specimens of NSCLC. SOX9 overexpression was found to decrease the expression of the epithelial cell markers E-cadherin and γ-catenin and increase the expression of the mesenchymal cell markers N-cadherin and vimentin. An in vivo assay showed distant metastasis of the SOX9-overexpressing cells, which was not observed in the SOX9-knockdown cells. These findings indicate that SOX9 promotes distant metastasis by promoting EMT in NSCLC cells. GSEA showed that SOX9 overexpression was significantly correlated with the Wnt/ß-catenin pathway which was corroborated by the expression of EMT-associated proteins in this pathway and its downstream target genes. SOX9 overexpression was also found to enhance the transcriptional activity of TCF/LEF, promote the nuclear translocation of ß-catenin and increase the phosphorylation of GSK3ß at Ser9. Further, inhibition of ß-catenin suppressed the metastasis-promoting effects of SOX9 overexpression. CONCLUSIONS: This study is the first to report that SOX9 is associated with clinical TNM stage and indicates that SOX9 promotes migration, invasion and the EMT process through the Wnt/ß-catenin pathway.

Intrinsically reactive hyperbranched interface governs graphene oxide dispersion and crosslinking in epoxy for enhanced flame retardancy.

Enhancing the flame retardancy of epoxy (EP) resins typically entailed a trade-off with other physical properties. Herein, hyperbranched poly(amidoamine) (HPAA) and phytic acid (PA) were used to functionalize graphene oxide (GO) via electrostatic self-assembly in water to prepare a phosphorus-nitrogen functionalized graphene oxide nanosheet (PN-GOs), which could be utilized as high efficient flame-retardant additive of epoxy resin without sacrificing other properties. The PN-GOs demonstrated improved dispersion and compatibility within the EP matrix, which resulted in significant concurrent enhancements in both the mechanical performance and flame-retardant properties of the PN-GOs/EP nanocomposites over virgin EP. Notably, the incorporation of just 1.0 wt% PN-GOs yielded a 20.4, 6.4 and 42.7 % increases in flexural strength, flexural modulus and impact strength for the PN-GOs/EP nanocomposites, respectively. Furthermore, simultaneous reductions were achieved in the peak heat release rate (pHRR) by 60.0 %, total smoke production (TSP) by 43.0 %, peak CO production rate (pCOP) by 57.9 %, and peak CO2 production rate (pCO2P) by 63.9 %. This study presented a facile method for the design of GO-based nano flame retardants, expanding their application potential in polymer-matrix composites.

Serine-arginine protein kinase 1 (SRPK1) promotes EGFR-TKI resistance by enhancing GSK3ß Ser9 autophosphorylation independent of its kinase activity in non-small-cell lung cancer.

Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major challenge for clinicians and patients with non-small cell lung cancer (NSCLC). Serine-arginine protein kinase 1 (SRPK1) is a key oncoprotein in the EGFR/AKT pathway that participates in tumorigenesis. We found that high SRPK1 expression was significantly associated with poor progression-free survival (PFS) in patients with advanced NSCLC undergoing gefitinib treatment. Both in vitro and in vivo assays suggested that SRPK1 reduced the ability of gefitinib to induce apoptosis in sensitive NSCLC cells independently of its kinase activity. Moreover, SRPK1 facilitated binding between LEF1, ß-catenin and the EGFR promoter region to increase EGFR expression and promote the accumulation and phosphorylation of membrane EGFR. Furthermore, we verified that the SRPK1 spacer domain bound to GSK3ß and enhanced its autophosphorylation at Ser9 to activate the Wnt pathway, thereby promoting the expression of Wnt target genes such as Bcl-X. The correlation between SRPK1 and EGFR expression was confirmed in patients. In brief, our research suggested that the SRPK1/GSK3ß axis promotes gefitinib resistance by activating the Wnt pathway and may serve as a potential therapeutic target for overcoming gefitinib resistance in NSCLC.

Prognostic Correlation of Glycolysis-Related Gene Signature in Patients with Laryngeal Cancer.

BACKGROUND: Aerobic glycolysis is one of the metabolic characteristics of tumor cells, which is regulated by many genes. The aim of our study was to construct glycolysis-related gene signature to accurately predict the prognosis of laryngeal cancer (LC) patients. METHODS: We analyzed the mRNA expression profiles of LC patients from The Cancer Genome Atlas (TCGA). Eleven glycolysis-related gene sets were analyzed by gene set enrichment analysis (GSEA). In order to acquire the gene signature related to prognosis, we used univariate and multivariate Cox regression analysis. RESULTS: We confirmed that a gene signature composed of two genes (STC2, LHPP) can predict the overall survival (OS) of patients with LC. Based on each patient's risk score, we found that the survival results of patients in the high-risk group were significantly lower than those in the low-risk group (log-rank test P-value=0.002). Multivariate Cox regression analysis confirmed that gene signature could independently predict OS in LC patients (HR = 1.981, 95% CI 1.446-2.714 P<0.001). In addition, a nomogram including the age, sex, grade and risk score was constructed. The nomogram demonstrated good accuracy for OS prediction, with a C-index of 0.752. CONCLUSION: The glycolysis-related two-gene risk score model could be used as a biomarker for LC prognosis.

Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study.

Marital status has long been recognized as an important prognostic factor for many cancers, however its' prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan-Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.