Surface-immobilized cross-linked cationic polyelectrolyte enables CO2 reduction with metal cation-free acidic electrolyte.

Electrochemical CO2 reduction in acidic electrolytes is a promising strategy to achieve high utilization efficiency of CO2. Although alkali cations in acidic electrolytes play a vital role in suppressing hydrogen evolution and promoting CO2 reduction, they also cause precipitation of bicarbonate on the gas diffusion electrode (GDE), flooding of electrolyte through the GDE, and drift of the electrolyte pH. In this work, we realize the electroreduction of CO2 in a metal cation-free acidic electrolyte by covering the catalyst with cross-linked poly-diallyldimethylammonium chloride. This polyelectrolyte provides a high density of cationic sites immobilized on the surface of the catalyst, which suppresses the mass transport of H+ and modulates the interfacial field strength. By adopting this strategy, the Faradaic efficiency (FE) of CO reaches 95 ± 3% with the Ag catalyst and the FE of formic acid reaches 76 ± 3% with the In catalyst in a 1.0 pH electrolyte in a flow cell. More importantly, with the metal cation-free acidic electrolyte the amount of electrolyte flooding through the GDE is decreased to 2.5 ± 0.6% of that with alkali cation-containing acidic electrolyte, and the FE of CO maintains above 80% over 36 h of operation at -200 mA·cm-2.

ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation.

Rho family mechano-signaling through the actin cytoskeleton positively regulates physiological TEAD/YAP transcription, while the evolutionarily conserved Hippo tumor suppressor pathway antagonizes this transcription through YAP cytoplasmic localization/degradation. The mechanisms responsible for oncogenic dysregulation of these pathways, their prevalence in tumors, as well as how such dysregulation can be therapeutically targeted are not resolved. We demonstrate that p53 DNA contact mutants in human tumors, indirectly hyperactivate RhoA/ROCK1/actomyosin signaling, which is both necessary and sufficient to drive oncogenic TEAD/YAP transcription. Moreover, we demonstrate that recurrent lesions in the Hippo pathway depend on physiological levels of ROCK1/actomyosin signaling for oncogenic TEAD/YAP transcription. Finally, we show that ROCK inhibitors selectively antagonize proliferation and motility of human tumors with either mechanism. Thus, we identify a cancer driver paradigm and a precision medicine approach for selective targeting of human malignancies driven by TEAD/YAP transcription through mechanisms that either upregulate or depend on homeostatic RhoA mechano-signaling.

Effective Heterogeneous Oxidative Desulfurization Catalyzed by H3 PMo9 W3 O40 @rht-MOF-1.

With the increasingly strict standard for sulfur content in fuel, it is necessary to develop high-efficiency catalyst for extractive and catalytic oxidative desulfurization systems (ECODS). Herein, a series of three remarkable complexes H3 PMo(12-n) Wn O40 @rht-MOF-1 (1 a, n=1; 2 a, n=2; 3 a, n=3) have been designed and prepared. Complexes 1 a, 2 a and 3 a were characterized by single-crystal X-ray diffraction and FT-IR, PXRD, SEM, N2 adsorption-desorption isotherms, etc. Upon complex 3 a was applied as catalyst, it exhibited remarkably high catalytic activity in the ECODS reactions of aromatic sulfur compounds under optimal conditions. On the basis of its excellent heterogeneity, the catalyst could be recycled for nine consecutive cycles without significant losing of activity centers. Then, the reaction kinetics and mechanism were investigated and the activation energy have been calculated and discussed. Further, the complex 3 a is employed to catalyze the ODS of commercial diesel oil. As a result, the desulfurization efficiency reached 90%. These results provided important structure data for study the structure-property relationship and potential heterogeneous catalyst applied in ODS in industry.

Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.

Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.

Circ_0000218 plays a carcinogenic role in laryngeal cancer through regulating microRNA-139-3p/Smad3 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) accounts for about 85%-90% of all cases of laryngeal cancer. So far, the role and molecular mechanism of circular RNA 0,000,218 (circ_0000218)/microRNA (miR)-139-3p in laryngeal cancer are not clear. The present study aimed to investigate the role and regulatory mechanism of circ_0000218/miR-139-3p in laryngeal cancerin vitro and in vivo. METHODS: quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0000218/miR-139-3p in LSCC cells. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm binding sites between miR-139-3p and smad family member 3 (Smad3), and circ_0000218 and miR-139-3p. Cell Counting Kit-8 (CCK-8) and cell apoptosis analysis were used to detect cell viability and apoptosis. Xenograft experiment was performed to show in vivo effect of circ_0000218/miR-139-3p on the growth of LSCC. RESULTS: Circ_0000218 was highly expressed in LSCC cells. miR-139-3p, lower expressed in LSCC cells, was negatively regulated by circ_0000218 in LSCC cells. Besides, the findings suggested that circ_0000218 silencing inhibited the LSCC cell viability and promoted apoptosis by negatively regulating miR-139-3p expression. Furthermore, the data indicated that miR-139-3p inhibited the viability of LSCC cells and promoted apoptosis, and these effects were reversed by Smad3 over-expression. In addition, the in vivo effects of circ_0000218/miR-139-3p on LSCC were consistent with the in vitro study. CONCLUSIONS: circ_0000218 inhibition inhibited the growth of LSCC by targeting miR-139-3p/Smad3 axis. Our present study provided a new target for laryngeal cancer treatment.

Clinicopathological and prognostic significance of pretreatment thrombocytosis in patients with endometrial cancer: a meta-analysis.

Background: The prognostic and clinicopathological role of pretreatment thrombocytosis in cancer has been widely studied, but conclusions in endometrial cancer (EnCa) remain controversial. Therefore, we conducted a meta-analysis to assess the pathologic and prognostic impacts of pretreatment thrombocytosis in patients with EnCa. Methods: We searched PubMed, Embase, SpringerLink, ScienceDirect and China National Knowledge Infrastructure databases. Pooled HR or OR with their 95% CIs were applied to assess the association of pretreatment thrombocytosis with survival outcomes and clinical parameters of EnCa patients. Results: In total, 10 studies containing 2,995 cases of EnCa met the criteria. The results suggested that pretreatment thrombocytosis was significantly associated with high International Federation of Gynecology and Obstetrics (FIGO) stage (pooled OR 3.45, 95% CI 1.68-7.08, P=0.001), poor tumor differentiation (pooled OR 2.00, 95% CI 1.22-3.29, P=0.006), lymph-vascular space invasion (pooled OR 2.04, 95% CI 1.35-3.07, P=0.001); myometrial invasion (pooled OR 2.14, 95% CI 1.39-3.32, P=0.001); cervical involvement (pooled OR 2.54, 95% CI 1.56-4.15, P=0.000) and lymph node metastasis (OR 3.15, 95% CI 1.71-5.80, P=0.001). No significant difference existed between pretreatment thrombocytosis and overall survival (P=0.012), cancer/disease-specific survival (P=0.07) or disease-free survival (P=0.25). Conclusion: pretreatment thrombocytosis was associated with advanced clinicopathological features in patients with EnCa, which may serve as a potential therapeutic target for EnCa.

Autophagy facilitates lung adenocarcinoma resistance to cisplatin treatment by activation of AMPK/mTOR signaling pathway.

Resistance to cisplatin-based therapy is a major challenge in the control of lung cancer progression. However, the underlying mechanisms remain largely unclear. Autophagy is closely associated with resistance to lung cancer therapy, but the function of autophagy in cisplatin treatment is still controversial. Here, we investigated whether autophagy was involved in lung adenocarcinoma resistance to cisplatin and further elucidated the underlying molecular mechanisms. Cisplatin-refractory lung adenocarcinoma cells increased autophagic vacuole formation detected by monodansylcadaverine staining. When exposed to cisplatin, lung adeno-carcinoma cells demonstrated increased levels of autophagy detected by MAP1A/1B LC3B and mammalian homologue of yeast Atg6 (Beclin-1) expression using Western blot analysis. Activation of cisplatin-induced autophagic flux was increased by using chloroquine (CQ), which can accumulate LC3B-II protein and increase punctate distribution of LC3B localization. The combination of cisplatin with CQ was more potent than cisplatin alone in inhibiting lung adenocarcinoma cell growth, which also increased cisplatin-induced apoptosis. Compared to cisplatin treatment alone, the combination of cisplatin and CQ decreased p-AMPK and increased p-mTOR protein expressions, in addition, the AMPK inhibitor Compound C plus cisplatin downregulated p-AMPK and upregulated p-mTOR as well as depressed LC3B cleavage. These findings demonstrate that activation of autophagy is a hallmark of cisplatin exposure in human lung adenocarcinoma cells, and that there is a cisplatin-induced autophagic response via activation of the AMPK/mTOR signaling pathway. We speculate that autophagy can be used as a novel therapeutic target to overcome cisplatin-resistant lung adenocarcinoma.

Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis.

Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS) was then reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17-1.83, P=0.0001). The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16-0.86, P=0.02) and tumor size >5 cm (OR 0.48, 95% CI 0.26-0.88, P=0.02). In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC.