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Efficient and robust platinum-carbon electrocatalysts are of great significance for the long-term service of high-performance fuel cells. Here, we report a Pt alloy integrated in a cobalt-nitrogen-nanocarbon matrix by a multiscale design principle for efficient oxygen reduction reaction. This Pt integrated catalyst demonstrates an increased mass activity, 11.7 times higher than that of commercial Pt catalyst, and retains a stability of 98.7% after 30,000 potential cycles. Additionally, this integrated catalyst delivers a current density of 1.50 A cm −2 at 0.6 V in the hydrogen-air fuel cell and achieves a power density of 980 mW cm −2 . Comprehensive investigations demonstrate that the synergistic contribution of components and structure in the platinum-carbon integrated catalyst is responsible for the high-efficiency ORR in fuel cells. Improving fuel cell technologies based on Pt-based alloys is important for efficient fuel cells. Here, the authors report a hybrid PtCo alloy electrocatalyst for acidic oxygen reduction at high current densities and H 2 /air fuel cell power densities.

Introduction Traditionally, dental students learn the skills for dentist-patient interaction and communication via on-site contact with patients, when they start clinical training. However, preclinical students (who have not started clinical practice) have fewer chances to realize the context of dentist-patient interaction. It has remained unclear if a gamification approach via digital media, i.e., a computer role-playing game, can help to learn clinical communication skills. The intervention-based study investigates the effectiveness of the clinical dentist-patient communication (CDPC) game on students’ motivation, beliefs, and self-efficacy to learn behavioral issues of clinical communication. Methods Fifty-two dental students (Preclinical group) and 18 dental interns and dentists (Clinical group) played the CDPC game, which consists of 16 scenes of clinical context about dentist-patient communication (less than 40 min for playing), via web browsers. Pre-test and post-test questionnaires were used to assess their motivation, beliefs, and self-efficacy to learn behavioral issues of clinical communication. The effectiveness was examined by comparing pre-test and post-test scores within-subject and between-group difference was compared between Preclinical and Clinical groups, via non-parametric statistical tests. Results (A) In the Preclinical group, participants showed a significant increase in motivation and self-efficacy in learning after playing the CDPC game ( p  < 0.05, adjusted of multiple comparison). (B) In contrast, the Clinical group did not show a significant difference before vs. after playing the game. (C) After playing the game, the Preclinical group showed a significant association between motivation and beliefs ( p  = 0.024) and between motivation and self-efficacy ( p  = 0.001); the Clinical group showed a significant association between motivation and beliefs ( p  = 0.033). Conclusions The current evidence suggests that gamification of learning helps preclinical students to understand the context of clinical dentist-patient interaction and increase their motivation and self-efficacy to learn behavioral issues of clinical communication.

The hilum (a transitional region) of the mouse ovary is identified as a stem cell niche of the ovarian surface epithelium, and its cells are prone to malignant transformation after inactivation of common tumour suppressor genes, suggesting that they may be the origin of ovarian carcinoma. Stem cell niche linked to ovarian cancer The recent publication of integrated genomic analyses of ovarian carcinoma has provided an extensive catalogue of molecular aberrations of this deadly disease, but uncertainty about which epithelial cells the cancer originates in has complicated the application of such results. This study identifies a stem cell population in the hilum region of the mouse ovary as the origin of ovarian cancers induced by the loss of the RB1 and TRP53 tumour suppressors, whose pathways are altered frequently in the most aggressive and common types of human epithelial ovarian cancers. Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood 1 , 2 , 3 . Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells 4 , 5 , 6 . The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B. These cells display long-term stem cell properties ex vivo and in vivo , as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma 7 , 8 . Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.

Eicosanoids are bioactive lipids that play crucial roles in various pathophysiological conditions, including inflammation and cancer. They include both the COX-derived prostaglandins and the LOX-derived leukotrienes. Furthermore, the epidermal growth factor receptor (EGFR) pathways family of receptor tyrosine kinases also are known to play a central role in the tumorigenesis. Various antitumor modalities have been approved cancer treatments that target therapeutically the COX-2 and EGFR pathways; these include selective COX-2 inhibitors and EGFR monoclonal antibodies. Research has shown that the COX-2 and epidermal growth factor receptor pathways actively interact with each other in order to orchestrate carcinogenesis. This has been used to justify a targeted combinatorial approach aimed at these two pathways. Although combined therapies have been found to have a greater antitumor effect than the administration of single agent, this does not exempt them from the possible fatal cardiac effects that are associated with COX-2 inhibition. In this review, we delineate the contribution of HB-EGF, an important EGFR ligand, to the cardiac dysfunction related to decreased shedding of HB-EGF after COX-2/PGE2 inhibition. A better understanding of the molecular mechanisms underlying these cardiac side effects will make possible more effective regimens that use the dual-targeting approach.

Background Manual dexterity is key to clinical skill training. The networking between sensorimotor and visual-attention functions may be associated with the expertise of dental students. The study aims to investigate the pattern of networking between sensorimotor and visual-attention functions and related resting-state (rs) functional connectivity (FC). Methods Twenty-six dental and 19 non-dental students completed visual-attention tests and psychomotor tests for manual dexterity and steadiness. Thirty participants also received structural and rs-functional magnetic resonance imaging. Results Compared to non-dental students, dental students showed increased networking in performance between visual-attention tests and manual dexterity, increased rsFC between bilateral sensorimotor network (SMN) and the left middle frontal gyrus, and decreased rsFC between bilateral SMN and the left posterior insula. Better performance of manual dexterity was associated with increased rsFC between the left SMN and the right supramarginal gyrus. Conclusions Dental skill training is associated with the networking of sensorimotor and visual-attention functions and coupled with increased rsFC of the SMN. In dental students, better manual dexterity is associated with the functional connectivity of the SMN. Clinical trial number Not applicable.

MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial to tumorigenesis. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. Up-regulation of miR-146 has been identified in OSCC tissues. However, the roles of miR-146 in carcinogenesis are controversial as it is suppressive in many other malignancies. The present study investigated the pathogenic implications of miR-146a in oral carcinogenesis. Microdissected OSCC exhibits higher levels of miR-146a expression than matched adjacent mucosal cells. The plasma miR-146a levels of patients are significantly higher than those of control subjects; these levels decrease drastically after tumor resection. miR-146a levels in tumors and in patients' plasma can be used to classify OSCC and non-disease status (sensitivity: >0.72). Exogenous miR-146a expression is significantly increased in vitro oncogenic phenotypes as well as during xenograft tumorigenesis and OSCC metastasis. The plasma miR-146a levels of these mice parallel the xenograft tumor burdens of the mice. A miR-146a blocker abrogates the growth of xenograft tumors. miR-146a oncogenic activity is associated with down-regulation of IRAK1, TRAF6 and NUMB expression. Furthermore, miR-146a directly targets the 3'UTR of NUMB and a region within the NUMB coding sequence when suppressing NUMB expression. Exogenous NUMB expression attenuates OSCC oncogenicity. Double knockdown of IRAK1 and TRAF6, and of TRAF6 and NUMB, enhance the oncogenic phenotypes of OSCC cells. Oncogenic enhancement modulated by miR-146a expression is attenuated by exogenous IRAK1 or NUMB expression. This study shows that miR-146a expression contributes to oral carcinogenesis by targeting the IRAK1, TRAF6 and NUMB genes.

The Polycomb group protein EZH2 promotes trimethylation of histone H3K27 and gene silencing. Cdk1 is found to phosphorylate EZH2 to inhibit its methyltransferase activity, affecting EZH2-target genes involved in osteogenic differentiation. Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyses the trimethylation of histone H3 on Lys 27 (H3K27), which represses gene transcription. EZH2 enhances cancer-cell invasiveness and regulates stem cell differentiation. Here, we demonstrate that EZH2 can be phosphorylated at Thr 487 through activation of cyclin-dependent kinase 1 (CDK1). The phosphorylation of EZH2 at Thr 487 disrupted EZH2 binding with the other PRC2 components SUZ12 and EED, and thereby inhibited EZH2 methyltransferase activity, resulting in inhibition of cancer-cell invasion. In human mesenchymal stem cells, activation of CDK1 promoted mesenchymal stem cell differentiation into osteoblasts through phosphorylation of EZH2 at Thr 487. These findings define a signalling link between CDK1 and EZH2 that may have an important role in diverse biological processes, including cancer-cell invasion and osteogenic differentiation of mesenchymal stem cells.

Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROS Low cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings. Herein, we first showed CICs mainly relying on glycolysis that was important for the maintenance of stemness properties. Next, we revealed that NRF2, a master regulator of antioxidants, was able to maintain low intracellular ROS levels of CICs, even though in the absence of oxidative stress. We further characterized that NRF2 activation was required for the maintenance of CICs properties. Of ROS Low cells, NRF2 activation not only directly activates the transcription of genes encoding glycolytic enzymes but also inhibited the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1) to lead to inhibition of tricarboxylic acid (TCA) cycle; therefore, to promote Warburg effect. A positive regulatory ROS-independent ER stress pathway (GRP78/p-PERK/NRF2 signaling) was identified to mediate the metabolic shift (Warburg effect) and stemness of CICs. Lastly, co-expression of p-PERK and p-NRF2 was significantly associated with the clinical outcome. Our data show that NRF2 acting as a central node in the maintenance of low ROS levels and stemness associated properties of the CICs, which is significantly associated with the clinical outcome, but independent from ROS stress. Future treatments by inhibiting NRF2 activation may exhibit great potential in targeting CICs.

Oral squamous cell carcinoma (OSCC) is a cancerous disease with poor prognosis. According to the statistics, the 5-year survival rate has not improved significantly over the past 20 years. The platelet-derived growth factor (PDGF) and its signaling pathway is a key regulator of angiogenesis and tumorigenesis. High level of PDGF and its receptor (PDGFR) have been reported in several types of malignancies. In this study, we investigated the relationship of the molecular expression levels of PDGF and PDGFR with clinicopathological parameters in OSCC. To this end, we measured the mRNA and protein levels of PDGF and PDGFR by real-time quantitative PCR (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. We found positive correlations of the mRNA levels of PDGFA, PDGFB, and PDGFRB with lymph node metastasis and poor overall survival (OS). High expression of PDGF, PDGFRA, and PDGFRB were remarkably associated with lymph node metastasis and poor OS, as determined by immunohistochemistry. Preoperative serum levels of PDGF-AA and PDGF-BB had a positive correlation with preoperative platelet count. Elevated serum levels of PDGF-AA. PDGF-BB, and platelet count correlated with lymph node metastasis and an unfavorable outcome. In multivariate Cox regression analysis, PDGFA mRNA, PDGFB mRNA, PDGFRB mRNA, PDGF immunoexpression, PDGFRB immunoexpression, serum PDGF-AA, serum PDGF-BB, and platelet count emerged as significant independent prognostic factors for OS. In vitro, we found that elevated PDGF promotes colony formation, migration, and invasiveness of SAS and OECM-1 cancer cell lines. Our results suggest that the expression level of serum PDGF has the potential to become a useful diagnostic marker for the prognosis of OSCC. In addition, PDGFR should be considered as a potential therapeutic target for OSCC. Furthermore, research should be undertaken to elucidate the role of PDGF and PDGFR regarding the behavior of tumor cells in OSCC.

Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions.