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The purpose of this paper is to attain the existence of coincidences and common fixed points in four mappings satisfying (ψ , β , L) -generalized contractive conditions in the framework of partially ordered b-metric spaces. The main results presented in this paper generalize some recent results in the existing literature. Furthermore, a nontrivial example is presented to support the obtained results. [ABSTRACT FROM AUTHOR]

Yang X, Ji Y, Ke D, Li F. Research on the methods and means of action strength training in aerobics training. Lu S. Scientific research and training satisfaction evaluation analysis of postgraduates in science and engineering colleges based on big data. Pang J, Li Y, Jin X, Xu L. Detection and analysis of typical vibration load of grain harvester based on short-time Fourier method. [Extracted from the article]

Simple Summary: Epigenetic modification plays an important regulatory role in breast cancer progression. However, the relationship between epigenetic modification with tumor metabolism has not yet been fully elucidated. PDK1, as a key enzyme in glucose metabolism, mediates multiple tumors development. But, the mechanism of epigenetic modification in regulating PDK1 remains unclear in breast cancer. Here, we demonstrated that HDAC2 and EZH2 upregulated PDK1 expression through inhibiting miR-148a. Importantly, miR-148a targeting PDK1 regulated breast cancer cells glycolysis, invasion, epithelial-mesenchymal transition (EMT) and Adriamycin resistance. Our results suggested that the HDAC2/EZH2/miR-148a/PDK1 axis may be a promising potential therapeutic strategy. Background: Breast cancer has one of highest morbidity and mortality rates for women. Abnormalities regarding epigenetics modification and pyruvate dehydrogenase kinase 1 (PDK1)-induced unusual metabolism contribute to breast cancer progression and chemotherapy resistance. However, the role and mechanism of epigenetic change in regulating PDK1 in breast cancer remains to be elucidated. Methods: Gene set enrichment analysis (GSEA) and Pearson's correlation analysis were performed to analyze the relationship between histone deacetylase 2 (HDAC2), enhancer of zeste homologue 2 (EZH2), and PDK1 in database and human breast cancer tissues. Dual luciferase reporters were used to test the regulation between PDK1 and miR-148a. HDAC2 and EZH2 were found to regulate miR-148a expression through Western blotting assays, qRT-PCR and co-immunoprecipitation assays. The effects of PDK1 and miR-148a in breast cancer were investigated by immunofluorescence (IF) assay, Transwell assay and flow cytometry assay. The roles of miR-148a/PDK1 in tumor growth were investigated in vivo. Results: We found that PDK1 expression was upregulated by epigenetic alterations mediated by HDAC2 and EZH2. At the post-transcriptional level, PDK1 was a new direct target of miR-148a and was upregulated in breast cancer cells due to miR-148a suppression. PDK1 overexpression partly reversed the biological function of miR-148a—including miR-148a's ability to increase cell sensitivity to Adriamycin (ADR) treatment—inhibiting cell glycolysis, invasion and epithelial–mesenchymal transition (EMT), and inducing apoptosis and repressing tumor growth. Furthermore, we identified a novel mechanism: DNMT1 directly bound to EZH2 and recruited EZH2 and HDAC2 complexes to the promoter region of miR-148a, leading to miR-148a downregulation. In breast cancer tissues, HDAC2 and EZH2 protein expression levels also were inversely correlated with levels of miR-148a expression. Conclusion: Our study found a new regulatory mechanism in which EZH2 and HDAC2 mediate PDK1 upregulation by silencing miR-148a expression to regulate cancer development and Adriamycin resistance. These new findings suggest that the HDAC2/EZH2/miR-148a/PDK1 axis is a novel mechanism for regulating cancer development and is a potentially promising target for therapeutic options in the future. [ABSTRACT FROM AUTHOR]

Selective separation and enrichment of phosphoproteins are essential for understanding their important functions in almost all cellular processes. Here, taking advantage of the feature that cadmium ion (Cd2+) has an overwhelming preference for phosphates, we developed a robust and simple Cd2+ co‐precipitation strategy for the selective isolation of intact phosphoproteins. After evaluating the feasibility of Cd2+ in phosphoprotein precipitation, we compared the washing protocols for the removal of non‐specific binding proteins and then used the best‐performing protocol for the isolation of phosphoproteins from different complex samples. It was found that phosphoproteins can be specifically enriched from artificial protein mixtures containing α‐casein, β‐casein, and bovine serum albumin or plasma, in which bovine serum albumin or plasma were served as interferences with very high molar ratios. Applying this method to enrich phosphoproteins from complex cell lysates, a high specificity was confirmed by western blotting analysis with a phosphoprotein‐specific kit. Finally, we successfully applied this method to the purification of caseins from drinking milk, highlighting its potential application in the studies where purified phosphoproteins were required. In a word, this Cd2+ co‐precipitation method enables universal and effective capture, enrichment, and detection of intact phosphoproteins, making it a powerful tool for the comprehensive analysis of the phosphoproteome. [ABSTRACT FROM AUTHOR]

Abstract Background Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles. Results Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine particles. Western-blot analysis showed an activation of proapoptotic factors including Fas (CD95), Fas-associated protein with death domain (FADD), caspase-8, death receptor 3 (DR3) and BID in apoptotic cells induced by metallic nickel particles. Immunoprecipitation (IP) western blot analysis demonstrated the formation of the Fas-related death-inducing signaling complex (DISC) in the apoptotic process. Furthermore, lamin A and beta-actin were cleaved. Moreover, we found that apoptosis-inducing factor (AIF) was up-regulated and released from mitochondria to cytoplasm. Interestingly, although an up-regulation of cytochrome c was detected in the mitochondria of metallic nickel particle-treated cells, no cytochrome c release from mitochondria to cytoplasm was found. In addition, activation of antiapoptotic factors including phospho-Akt (protein kinase B) and Bcl-2 was detected. Further studies demonstrated that metallic nickel particles caused no significant changes in the mitochondrial membrane permeability after 24 h treatment. Conclusion In this study, metallic nickel nanoparticles caused higher cytotoxicity and apoptotic induction than fine particles in JB6 cells. Apoptotic cell death induced by metallic nickel particles in JB6 cells is through a caspase-8/AIF mediated cytochrome c-independent pathway. Lamin A and beta-actin are involved in the process of apoptosis. Activation of Akt and Bcl-2 may play an important role in preventing cytochrome c release from mitochondria to the cytoplasm and may also be important in the carcinogenicity of metallic nickel particles. In addition, the results may be useful as an important reference when comparing the toxicities of different nickel compounds.

We demonstrate for the first time the integration of a dumbbell probe with dual signal amplification for the simultaneous detection of multiple DNA methyltransferases (MTases). This method is very sensitive with a detection limit of 2.15 × 10−5 U mL−1 for DNA adenine methyltransferase (Dam) and 3.23 × 10−6 U mL−1 for CpG Methyltransferase (M.SssI), and it can be used to screen the enzyme inhibitors and simultaneously measure Dam and M.SssI in complex biological samples. [ABSTRACT FROM AUTHOR]

We develop a new fluorescence method for the sensitive detection of protein tyrosine phosphatase 1B (PTP1B) based on dephosphorylation-directed tricyclic DNA amplification cascades. This method exhibits good specificity and high sensitivity with a detection limit of 0.24 pM. Moreover, it can be applied for kinetics analysis, inhibitor screening, and the accurate detection of PTP1B in a variety of cancer cells. [ABSTRACT FROM AUTHOR]

Nucleases play a crucial role in DNA replication, recombination and repair which are associated with cancers. Herein, we develop a four-color fluorescent probe for ratiometric detection of multiple nucleases. This four-color fluorescent probe consists of four fluorescent dyes connected by a DNA tetrahedral nanostructure with the involvement of multistep fluorescence resonance energy transfer (FRET). Based on the principle of self-assembly, the four-color fluorescent probe is constructed by integrating one acceptor with three spatially and spectrally distinct acceptors. A DNA tetrahedral nanostructure functions as a scaffold to link the acceptor dyes (i.e., diethylaminocoumarin (DEA), carboxyfluorescein (FAM), Texas Red, and Cy5). The fluorescence emissions of DEA, FAM, Texas Red and Cy5 can be observed through efficient multi-step energy transfer. This four-color fluorescent probe enables single excitation/four emissions, and it can be used for ratiometric detection of nucleases (i.e., XhoI, HindIII and KpnI) and the screening of nuclease inhibitors. Importantly, this four-color fluorescent probe can be further applied to discriminate multiple biomolecule targets by simply integrating the recognition sites of various biomolecules into the DNA tetrahedral nanostructure. [ABSTRACT FROM AUTHOR]

Recently, Qiao [8] investigated the distributive laws of uninorms over overlap and grouping functions when the uninorms were one of the usual classes (e.g., U min , U max , the family of idempotent uninorms, representable uninorms or uninorms continuous on ] 0, 1 [2) and obtained some characterizations. As an addendum to [8], in this paper, we investigate the distributive laws of overlap and grouping functions over uninorms. In addition, we show some characterizations when the uninorm U belongs to one certain class. [ABSTRACT FROM AUTHOR]

The present study aimed to select anti‐tumor‐associated antigen (TAA) autoantibodies as biomarkers in the immunodiagnosis of gastric adenocarcinoma (GAC) by the recursive partitioning approach (RPA) and further construct and evaluate a predictive model. A case‐control study was designed including 407 GAC patients as the case group and 407 normal controls. In addition, 67 serial serum samples from 25 GAC patients were collected at different time points before and after gastrectomy treatment. Autoantibodies against 14 TAA were measured in sera from all subjects by enzyme immunoassay. Finally, RPA resulted in the selection of nine‐panel TAA (c‐Myc, p16, HSPD1, PTEN, p53, NPM1, ENO1, p62, HCC1.4) from all detected TAA in the case‐control study; the classification tree based on this nine‐TAA panel had area under curve (AUC) of 0.857, sensitivity of 71.5% and specificity of 71.3%; The optimal panel also can identify GAC patients at an early stage from normal individuals, with AUC of 0.737, sensitivity of 64.9% and specificity of 70.5%. However, frequencies of the nine autoantibodies showed no correlation with GAC stage, tumor size, lymphatic metastasis or differentiation. GAC patients positive for more than two autoantibodies in the nine‐TAA panel had a worse prognosis than that of the GAC patients positive for no or one antibody. Titers of 10 autoantibodies in serial serum samples were significantly higher in GAC patients after surgical resection than before. In conclusion, this study showed that the panel of nine multiple TAAs could enhance the detection of anti‐TAA antibodies in GAC, and may be potential prognostic biomarkers in GAC. [ABSTRACT FROM AUTHOR]

Fluoride is an environmental toxicant and induces dental fluorosis and oxidative stress. Lycopene (LYC) is an effective antioxidant that is reported to attenuate fluoride toxicity. To determine the effects of LYC on sodium fluoride (NaF) -induced teeth and ameloblasts toxicity, rats were treated with NaF (10 mg/kg) and/or LYC (10 mg/kg) by orally administration for 5 weeks; ameloblasts were treated with NaF (5 mM) and/or LYC (2 μM) for 6 h. We found that the concentrations of fluoride, malondialdehyde (MDA) and reactive oxygen species (ROS), gene expressions and activities of Caspase-9 and Caspase-3, and the gene expressions of Bax were significantly decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX), the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated rats group; concentrations of MDA and ROS, gene expressions and activities of Caspase-9 and Caspase-3, and the gene expression of Bax, and ameloblasts apoptosis rate were significantly decreased, while the activities of SOD and GPX, the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated ameloblasts group. These results suggest that LYC significantly combated NaF-induced ameloblasts apoptosis and dental fluorosis by attenuation oxidative stress and down-regulation Caspase pathway. [ABSTRACT FROM AUTHOR]

Background & Aims We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. Methods We collected data from the Surveillance, Epidemiology, and End Results–Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan–Meier method and the Cox proportional hazards model. Results After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) ( P < .0001); this value decreased significantly, to 5.0% ( P < .0001), after patients were matched for tumor presentation, and decreased to 4.9% ( P < .0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% ( P = .0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% ( P = .090) after tumor presentation match, but was not reduced further after treatment match. Conclusions We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer. [ABSTRACT FROM AUTHOR]

Resistance to TKI treatment is a major obstacle in effective treatment of NSCLC. Besides EGFR mutation status, the mechanisms involved are largely unknown. Some evidence supports a role for microRNA 21 in modulating drug sensitivity of chemotherapy but its role in NSCLC TKI resistance still remains unexplored. This study aimed to investigate whether NSCLC miR-21 mediated resistance to TKIs also results from Pten targeting. Here, we show miR-21 promotes cancer by negatively regulating Pten expression in human NSCLC tissues: high miR-21 expression levels were associated with shorter DFS in 47 NSCLC patients; high miR-21/low Pten expression levels indicated a poor TKI clinical response and shorter overall survival in another 46 NSCLC patients undergoing TKI treatment. In vitro assays showed that miR-21 was up-regulated concomitantly to down-regulation of Pten in pc-9/GR cells in comparison with pc-9 cells. Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. We propose alteration of miR-21/Pten expression as a novel mechanism for TKI resistance in NSCLC cancer. Our findings provide a new basis for using miR 21/Pten-based therapeutic strategies to reverse gefitinib resistance in NSCLC. [ABSTRACT FROM AUTHOR]

In this paper, we present some new generalizations of Mizoguchi-Takahashi's fixed point theorem which also improve and extend Du-Hung's fixed point theorem. Some new examples illustrating our results are also given. By applying our new results, some new fixed point theorems for essential distances and e0-metrics were established. [ABSTRACT FROM AUTHOR]