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A series of binuclear ruthenium vinyl complexes [RuCl(CO)(PMe 3 ) 3 ] 2 (µ-CHdCH-Ar-CHdCH) (Ar 6l), and C 6 H 3 CF 3 (6m)) have been prepared. The respective products have been characterized by elemental analyses, NMR spectrometry, and UV/vis spectrophotometry. The structures of 6h, 6i, and 6j have been established by X-ray crystallography. Electrochemical studies have revealed that intermetallic electron communication between the two Ru centers may be fine-tuned by modification of the bridging spacers, that is, by introducing one or two substituent groups on the 1,4-diethenylphenylene bridge. Electron-releasing substituents have been found to facilitate electron communication between the two metal centers.

Objectives To determine the prognostic significance of preoperative prognostic nutritional index (PNI) in patients with primary oral squamous cell carcinoma (OSCC) after ablative surgery. Materials and Methods A total of 333 patients from two tertiary referral centers were enrolled as training and validation cohorts. The PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte number (per mm3), and its optimal cutoff value for patient stratification was identified by X‐tile software. Cox's proportional regression analyses and receiver operating characteristic (ROC) curves were employed to identify prognostic factors and their predictive performance. Results The optimal cutoff value of PNI was 47.4. Patients with low PNI had significantly shorter overall (OS) and disease‐free survival than those with high PNI. Moreover, multivariate regression analyses indicated that PNI was an independent prognostic factor for OS in the training (hazard ratio [HR], 2.267; 95% confidence interval [CI]:1.335–3.849; p = .002) and validation (HR, 2.247; 95% CI: 1.352–3.735; p = .002) cohorts. ROC analyses revealed similar or superior predictive performance of PNI as compared to other prognostic parameters. Conclusions Our findings reveal that decreased preoperative PNI significantly associates with worse prognosis for patients with OSCC, which serves as a novel prognostic biomarker for OSCC.

HOX genes are transcription factors that control morphogenesis, organogenesis and differentiation. Increasing evidence suggests that HOX genes play a role in hepatocellular carcinoma (HCC) progression; however few studies have defined the functional roles and mechanisms of action. In the present study, we used siRNA and forced-expression in multiple cell lines to define the role of HOXA7 in the regulation of proliferation of HCC in vitro and in vivo. Knockdown of endogenous HOXA7 decreased the proliferation of HepG2 and QGY-7703 cells. These changes were not associated with significant changes in cyclin D1 and CDK4. However, downregulation of HOXA7 significantly reduced cyclin E1 and CDK2 protein levels. Conversely, overexpression of HOXA7 in QSG-7701 cells stimulated proliferation and increased cyclin E1 and CDK2 protein levels. Our results confirmed that HOXA7 promoted cell proliferation, and these changes were mediated by cyclin E1/CDK2. These observations contribute to our understanding of the important roles of HOXA7 in HCC development and progression and HOXA7 could be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.

h-R3 in combination with irradiation or chemoradiation was safe and tolerable, and yielded encouraging OS, PFS and LC.

Alternative splicing (AS) is critically associated with tumorigenesis and patient's prognosis.Here, we systematically analyzed survival-associated AS signatures in oral squamous cell carcinoma (OSCC) and evaluated their prognostic predictive values. Survival-related AS events were identified by univariate and multivariate Cox regression analyses using OSCC data from the TCGA head neck squamous cell carcinoma data set. The Percent Spliced In calculated by SpliceSeq from 0 to 1 was used to quantify seven types of AS events. A predictive model based on AS events was constructed by least absolute shrinkage and selection operator Cox regression assay and further validated using a training-testing cohort design. Patient survival was estimated using the Kaplan-Meier method and compared with Log-rank test. The receiver operating characteristics curve area under the curves was used to evaluate the predictive abilities of these predictive models.Furthermore, gene-gene interaction networks and the splicing factors (SFs)-AS regulatory network was generated by Cytoscape. A total of 825 survival-related AS events within 719 genes were identified in OSCC samples. The integrative predictive model was better at predicting outcomes of patients as compared to those models built with the individual AS event. The predictive model based on three AS-related genes also effectively predicted patients' survival. Moreover, seven survival-related SFs were detected in OSCC including RBM4, HNRNPD, and HNRNPC, which have been linked to tumorigenesis. The SF-AS network revealed a significant correlation between survival-related AS genes and these SFs. Our findings revealed a systemic portrait of survival-associated AS events and the splicing network in OSCC, suggesting that AS events might serve as novel prognostic biomarkers and therapeutic targets for OSCC. K E Y W O R D Salternative splicing, oral squamous cell carcinoma, prognosis, splicing factor

Aim: Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro. Methods: Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit. Results: SFN (0.1-5 μmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 μmol/L) blocked the SFN-induced cardioprotective effects. Conclusion: SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.