Designing N-doped graphene-like supported highly dispersed bimetallic NiCoP NPs as an efficient electrocatalyst for water oxidation.

Electrocatalysts with a high oxygen evolution reaction (OER) activity are very important for electrochemical water oxidation, but they are also challenging. In this study, N-doped graphene-like supported highly dispersed bimetallic NiCoP NPs as an efficient electrocatalyst for water oxidation were prepared by using cation exchange resin as a carbon source and by loading cobalt and nickel on D001 by a high-temperature calcination method. The designed electrocatalyst with bimetallic phosphide as the active center shows excellent OER catalytic performance, with an overpotential of 324 mV at 10 mA cm-2 and a corresponding Tafel slope of 97.28 mV dec-1. The increase in NiCoP-3@GL activity may be due to the increase in surface area (933.49 m2 g-1) caused by the irregular morphology, rich interface contact, and porous structure. In addition, the strong combination of NiCoP and GL improves the structural stability and durability of the electrocatalyst. After 5000 cyclic voltammetry tests, the performance of the catalyst decreased by 16.9 %. This work provides a new idea for designing efficient bimetallic phosphide electrocatalysts.

Nursing Students' Perceptions of Menstrual Distress during Clinical Practice: A Q-Methodology Study.

This study aimed to explore the cluster patterns of female nursing students' perceptions of the effects of menstrual distress during clinical practice. This study adopted the Q-methodology study design. We recruited female nursing students from a college in northern Taiwan. Forty-seven Q-statements were constructed to explore participants' experiences of the impact of menstrual distress on clinical learning. In total, 58 participants subjectively ranked Q-statements concerning menstrual distress experiences during clinical practice and were classified. After Q-sorting, the subjective ranking process PQ Method (version 2.35, Schmolck, Emmendingen, Germany) was employed for factor analysis. Four patterns of shared perspectives, accounting for 46.6% of the total variance, were identified: (a) influencing clinical learning and making good use of painkillers; (b) responsible attitudes and diversified relief of discomfort; (c) seeking peer support and effect on mood; (d) negative impact on learning ability and conservative self-care. Clinical practice is a major component of nursing education; menstrual distress affects female nursing students' clinical learning and performance. The exploration of clustering different nursing students' perceptions may facilitate customized strategies to enable more appropriate assistance.

Curcumin inhibits proteasome activity in triple-negative breast cancer cells through regulating p300/miR-142-3p/PSMB5 axis.

BACKGROUND: Curcumin functions as a proteasome inhibitor. However, the molecular mechanisms behind this action need more detailed explanations. PURPOSE: This study aimed to investigate the inhibitory effect of curcumin on 20S proteasome activity and to elucidate its exact mechanism in triple-negative breast cancer (TNBC) MDA-MB-231 cells. METHODS: Proteasomal peptidase activities were assayed using synthetic fluorogenic peptide substrates. Knockdown or overexpression of microRNA (miRNA or miR) or protein was used to investigate its functional effect on downstream cellular processes. BrdU (5­bromo­2'-deoxyuridine) assay was performed to identify cell proliferation. Western blot and quantitative real-time PCR(qRT-PCR) were carried out to determine protein abundance and miRNA expression, respectively. Correlations between protein expressions, miRNA levels, and proteasome activities were analyzed in TNBC tissues. Xenograft tumor model was performed to observe the in vivo effect of curcumin on 20S proteasome activity. RESULTS: Curcumin significantly reduced PSMB5 protein levels, accompanied with a reduction in the chymotrypsin-like (CT-l) activity of proteasome 20S core. Loss of PSMB5 markedly inhibited the CT-l activity of 20S proteasome. Furthermore, curcumin treatment significantly elevated miR-142-3p expression. PSMB5 was a direct target of miR-142-3p and its protein levels were negatively regulated by miR-142-3p. Moreover, histone acetyltransferase p300 suppressed miR-142-3p expression. Overexpression of p300 mitigated the promotive effect of curcumin on miR-142-3p expression. The correlations among p300 abundances, miR-142-3p levels, PSMB5 expressions, and the CT-l activities of 20S proteasome were evidenced in TNBC tissues. In addition, loss of p300 and PSMB5 reduced cell proliferation. Inhibition of miR-142-3p significantly attenuated the inhibitory impact of curcumin on cell proliferation. These curcumin-induced changes on p300, miR-142-3p, PSMB5, and 20S proteasome activity were further confirmed in in vivo solid tumor model. CONCLUSION: These findings demonstrated that curcumin suppressed p300/miR-142-3p/PSMB5 axis leading to the inhibition of the CT-l activity of 20S proteasome. These results provide a novel and alternative explanation for the inhibitory effect of curcumin on proteasome activity and also raised potential therapeutic targets for TNBC treatment.

Hypertrophic Adipocyte-Derived Exosomal miR-802-5p Contributes to Insulin Resistance in Cardiac Myocytes Through Targeting HSP60.

OBJECTIVE: This study aimed to elucidate the mechanism by which hypertrophic adipocytes regulate insulin signaling in cardiac myocytes. METHODS: Palmitate was used to induce hypertrophic 3T3-L1 adipocytes. Exosomes were purified from normal control or hypertrophic 3T3-L1 adipocyte-associated conditioned medium. Exosome-exposed neonatal rat ventricular myocytes were stimulated with insulin to investigate the effects of exosomes on insulin signaling. Small interfering RNA techniques were used to downregulate protein levels, and their efficiency was evaluated by Western blot. RESULTS: Hypertrophic adipocyte-derived exosomes highly expressed miR-802-5p. Insulin sensitivity of neonatal rat ventricular myocytes was negatively regulated by miR-802-5p. TargetScan and luciferase reporter assays revealed that heat shock protein 60 (HSP60) was a direct target of miR-802-5p. HSP60 silencing was found to induce insulin resistance and to mitigate the insulin-sensitizing effects of adiponectin. In addition, HSP60 depletion significantly increased the expression levels of C/EBP-homologous protein and enhanced oxidative stress, accompanied by the increases in the phosphorylation of JNK and IRS-1 Ser307. Moreover, the effects of HSP60 knockdown on C/EBP-homologous protein and oxidative stress were abolished by the inhibition of either miR-802-5p or endocytosis. CONCLUSIONS: Hypertrophic adipocyte-derived exosomal miR-802-5p caused cardiac insulin resistance through downregulating HSP60. These findings provide a novel mechanism by which epicardial adipose tissue impairs cardiac function.

Identification of differentially expressed mRNA and the Hub mRNAs modulated by lncRNA Meg3 as a competing endogenous RNA in brown adipose tissue of mice on a high-fat diet.

Obesity is associated with insulin resistance, diabetes, and obesity-related metabolic disorders. Brown adipocytes have emerged as potential targets for the treatment of obesity and obesity-related diseases. However, changes that occur in brown adipose tissue during various stages of high fat diet (HFD)-induced obesity remain poorly understood. The present study aimed to determine the changes occurring in brown adipose tissue during various stages of an HFD by analyzing two microarray expression profiles. A total of 1,337 differentially expressed RNAs (DE RNAs) were identified between the HFD and ND groups, using the limma package in R. The DE RNAs included 1,249 mRNAs, 74 long non coding RNAs (lncRNAs), and 14 pseudogenes. Functional annotation of the DE mRNAs, including GO terms and KEGG pathways were identified using the Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction network was constructed using STRING and clusters were obtained through the Molecular Complex Detection plug-in. In the present study, the lncRNA,maternally expressed gene 3 (Meg3), was identified as the DE lncRNA with a significant fold change. The network of Meg3 as a ceRNA was constructed, which demonstrated that Meg3 modulated five hub DE mRNAs via competitive binding to microRNAs.

Icariin Attenuates Amyloid-ß (Aß)-Induced Neuronal Insulin Resistance Through PTEN Downregulation.

Neuronal insulin resistance is implicated in neurodegenerative diseases. Icariin has been reported to improve insulin resistance in skeletal muscle cells and to restore impaired hypothalamic insulin signaling in the rats with chronic unpredictable mild stress. In addition, icariin can exert the neuroprotective effects in the mouse models of neurodegenerative diseases. However, the molecular mechanisms by which icariin affects neuronal insulin resistance are poorly understood. In the present study, amyloid-ß (Aß) was used to induce insulin resistance in human neuroblastoma SK-N-MC cells. Insulin sensitivity was evaluated by measuring insulin-stimulated Akt T308 phosphorylation and glucose uptake. We found that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mediated Aß-induced insulin resistance. Icariin treatment markedly reduced Aß-enhanced PTEN protein levels, leading to an improvement in Aß-induced insulin resistance. Accordingly, PTEN overexpression obviously abolished the protective effects of icariin on Aß-induced insulin resistance. Furthermore, icariin activated proteasome activity. The proteasome inhibitor MG132 attenuated the effects of icariin on PTEN protein levels. Taken together, these results suggest that icariin protects SK-N-MC cells against Aß-induced insulin resistance by activating the proteasome-dependent degradation of PTEN. These findings provide an experimental background for the identification of novel molecular targets of icariin, which may help in the development of alternative therapeutic approaches for neurodegenerative diseases.

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor.

Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action. Video abstract.

APPL1 knockdown blocks adipogenic differentiation and promotes adipocyte lipolysis.

Adipocyte dysfunction is closely associated with the development of obesity, insulin resistance, and type 2 diabetes. In addition to having a positive effect on adiponectin pathway and insulin signaling through direct and/or indirect mechanisms, adapter protein APPL1 has also been reported to regulate body weight, brown fat tissues thermogenesis, and body fat distribution in diabetic individuals. However, there is dearth of data on the specific role of APPL1 on adipogenic differentiation and adipocyte lipolysis. In this study, APPL1's function in adipocyte differentiation and adipocyte lipolysis was evaluated, and the possible mechanisms were investigated. We found that APPL1 knockdown (KD) impeded differentiation of 3T3-L1 preadipocytes into mature 3T3-L1 adipocytes and enhanced basal and insulin-suppressed lipolysis in mature 3T3-L1 adipocytes. APPL1 KD cells presented a reduced autophagic activity in 3T3-L1 preadipocytes and mature 3T3-L1 adipocytes. In 3T3-L1 preadipocytes, APPL1 KD reduced PPARγ protein levels, which was prevented by administration with proteasome inhibitor MG132. Furthermore, APPL1 KD-reduced autophagic activity in mature 3T3-L1 adipocytes was markedly restored by inhibition of PKA, accompanied with prevention of APPL1-induced lipolysis. In addition, APPL1 KD caused insulin resistance in mature 3T3-L1 adipocytes. Unexpectedly, we found that APPL1 overexpression did not appear to play a role in adipogenic differentiation and adipocyte lipolysis. Our results confirmed that APPL1 KD inhibits adipogenic differentiation by suppressing autophagy and enhances adipocyte lipolysis through activating PKA respectively. These findings may deepen our understanding of APPL1 function, especially its regulation on adipocyte biology.

Does "hospital loyalty" matter? Factors related to the intention of using a mobile app.

PURPOSE: This study aimed to explore the association between hospital loyalty, perceived usefulness of a mobile app, perceived ease of use of that mobile app, and satisfaction with the app's use as well as predicting patients' intended use of the app. PATIENTS AND METHODS: Purposive sampling was adopted in a cross-sectional survey. The participants were outpatients at the traditional Chinese medicine departments of three hospitals in northern Taiwan (n=125). The self-report questionnaire comprised information about sociodemographics and scales related to hospital loyalty, perceived usefulness of the mobile app, its perceived ease of use, satisfaction with its use, and its usage intention. The data were analyzed using structural equation modeling. RESULTS: The four factors explained 70% variance in usage intention. The perceived usefulness of the mobile app directly and indirectly affects their usage intention, but its perceived ease of use had only indirect effects on the usage intention. Perceived usefulness and perceived ease of use influence the usage intention through satisfaction. The women's hospital loyalty does not directly affect the usage intention of the mobile app, but indirectly affects it through perceived usefulness and perceived ease of use of the mobile app. CONCLUSION: Intended use of the app by women is mainly related to their experience of which is usefulness, ease of use and satisfaction of service are the most important factors contributing to continuous use. Hospital loyalty does not directly affect intention to use as expected. The influence of loyalty must be related to the patients' perception of the product, in terms of usefulness, ease to use, and satisfaction. The finding is helpful to understand patients' preference and support their behavioral adherence.

Identification of biomarkers, pathways and potential therapeutic agents for white adipocyte insulin resistance using bioinformatics analysis.

For the better understanding of insulin resistance (IR), the molecular biomarkers in IR white adipocytes and its potential mechanism, we downloaded two mRNA expression profiles from Gene Expression Omnibus (GEO). The white adipocyte samples in two databases were collected from the human omental adipose tissue of IR obese (IRO) subjects and insulin-sensitive obese (ISO) subjects, respectively. We identified 86 differentially expressed genes (DEGs) between the IRO and ISO subjects using limma package in R software. Gene Set Enrichment Analysis (GSEA) provided evidence that the most gene sets enriched in kidney mesenchyme development in the ISO subjects, as compared with the IRO subjects. The Gene Ontology (GO) analysis indicated that the most significantly enriched in cellular response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were most significantly enriched in cytokine-cytokine receptor interaction. Protein-Protein Interaction (PPI) network was performed with the STRING, and the top 10 hub genes were identified with the Cytohubba. CMap analysis found several small molecular compounds to reverse the altered DEGs, including dropropizine, aceclofenac, melatonin, and so on. Our outputs could empower the novel potential targets to treat omental white adipocyte insulin resistance, diabetes, and diabetes-related diseases.

Primary idiopathic chylopericardium: a case report.

Primary idiopathic chylopericardium is a rare disease, particularly in children. We report the case of a 5-year-old male child who presented with cough and dyspnoea. Bulging of the chest wall and distant heart sounds suggested the diagnosis of a pericardial effusion, which was confirmed on a chest computed tomography. Pericardial drainage confirmed the diagnosis of a chylopericardium. After the failure of continuous catheter drainage, surgical ligation of the thoracic duct and the creation of a pericardial window were performed under thoracoscopy.

The fixed combination of fortified vancomycin and amikacin ophthalmic solution--VA solution: in vitro study of the potency and stability.

PURPOSE: We compared the in vitro potency and stability of a fixed combination of vancomycin and amikacin solution (VA solution) with amikacin or vancomycin solution. METHODS: Solutions of 2% amikacin (20 mg/mL) and of 5% vancomycin (50 mg/mL) and VA solution (each 1 mL contained 20 mg of amikacin and 50 mg of vancomycin) were prepared from parenteral antibiotics by reconstituting them with sterile injection water and refrigerated (4 degrees C) in the dark. Triplicate 5-mL portions of each solution were tested before storage and 7 and 14 days after preparation for potency of antimicrobial activity by the disk diffusion method and for stability. RESULTS: There were no significant differences in the diameter of zones of inhibition of VA solution compared with amikacin or vancomycin solution within a 2-week period. Visual inspection revealed that all solutions remained clear, colorless, and particle-free at 4 degrees C throughout the study period. For osmolarity, the VA solution was much higher than that of either amikacin or vancomycin solution at all tested times and more near the well-tolerated range of human eyes. There were no significant differences at days 0, 7, or 14 for either vancomycin, amikacin, or VA solution. For pH, the VA solution was higher than that of vancomycin solution (nearly equal to that of amikacin solution) at each time and more near the level of normal tear film. The pH did not differ significantly for either vancomycin, amikacin, or VA solution at all tested times. CONCLUSIONS: The vancomycin and amikacin ophthalmic solutions can be mixed together with the same potency and stable physical properties. It may be useful in the treatment of bacterial keratitis pending clinical trials to determine its effectiveness and safety.