cNPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. AIM: To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. METHODS: Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. RESULTS: We found that NPAS2 was significantly up-regulated in islet ß cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. CONCLUSION: This study demonstrated that NPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.

Constructing sulfur and oxygen super-coordinated main-group electrocatalysts for selective and cumulative H2O2 production.

Direct electrosynthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction presents a burgeoning alternative to the conventional energy-intensive anthraquinone process for on-site applications. Nevertheless, its adoption is currently hindered by inferior H2O2 selectivity and diminished H2O2 yield induced by consecutive H2O2 reduction or Fenton reactions. Herein, guided by theoretical calculations, we endeavor to overcome this challenge by activating a main-group Pb single-atom catalyst via a local micro-environment engineering strategy employing a sulfur and oxygen super-coordinated structure. The main-group catalyst, synthesized using a carbon dot-assisted pyrolysis technique, displays an industrial current density reaching 400 mA cm-2 and elevated accumulated H2O2 concentrations (1358 mM) with remarkable Faradaic efficiencies. Both experimental results and theoretical simulations elucidate that S and O super-coordination directs a fraction of electrons from the main-group Pb sites to the coordinated oxygen atoms, consequently optimizing the *OOH binding energy and augmenting the 2e- oxygen reduction activity. This work unveils novel avenues for mitigating the production-depletion challenge in H2O2 electrosynthesis through the rational design of main-group catalysts.

Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid cancer (TC) is the most common endocrine system tumour. Several studies had revealed the potential of circulating microRNAs (miRNAs) as novel biomarkers for the diagnosis of TC. The purpose of this meta-analysis is to summarize published studies and evaluate the diagnostic accuracy of circulating miRNAs in TC detection. METHODS: In this meta-analysis, we systematically searched three databases: PubMed, EMBASE and Cochrane Library. We used the bivariate mixed-effects regression model to calculate the pooled diagnostic parameters and conduct the summary receiver operator characteristic curve (SROC). All calculations were performed using stata software. RESULTS: Thirty-five studies from 9 articles, including 663 TC patients, 519 patients with benign thyroid nodules (BTNs), and 84 healthy controls were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were 0.81 (95% CI 0.75-0.86), 0.81 (95% CI 0.75-0.86), 4.3 (95% CI 3.2-5.6), 0.24 (95% CI 0.18-0.31), 18 (95% CI 12-28) and 0.88 (95% CI 0.85-0.90), respectively in BTN controls, and 0.81 (95% CI 0.75-0.86), 0.85 (95% CI 0.75-0.91), 5.3 (95% CI 3.3-8.7), 0.23 (95% CI 0.18-0.29), 24 (95% CI 14-39), 0.89 (95% CI 0.86-0.91) in healthy controls. The subgroup analysis found that multiple miRNA assays had higher diagnostic accuracy than single miRNA assays with sensitivity of 0.88, specificity of 0.89 and AUC of 0.94. CONCLUSION: Circulating miRNAs have good values to diagnose TC and distinguish TC patients from BTN patients. MiRNAs can assist in the diagnosis of malignancy and avoid unnecessary surgery. In summary, circulating miRNAs should be added to our current clinical tools.

[Effect of RYBP Gene Silencing on Sensitivity of HL-60 Cells to Chemotherapeutic Drugs].

OBJECTIVE: To investigate the effect of RYBP gene on sensitivity of HL-60 cells to chemotherapy drugs by using RNA interference. METHODS: Plasmid expressing RYBP specific shRNA was constructed and then was used to establish the RYBP knockdown stable HL-60 cell line. Q-PCR and Western blot were used to confirm the efficacy of RYBP gene silencing at mRNA and protein level respectively; then the DNA ladder and Annexin V labeled flow cytometry were used to detect cell apoptosis; CCK-8 was used detect the sensitivity of HL-60 cells to the chemotherapeutic drug cytarabine or daunorubicin. RESULTS: The lentiviral-RYBP-shRNA vector was succesfully and effectively inhibit the expression of RYBP at mRNA and protein in HL-60 cells. It was found that without chemotherapy drug treatment the apoptosis rate of RYBP shRNA group was lower than that of the empty vector control group (NC group). When treated with cytarabine, the apoptosis rate and inhibitive rate of RYBP shRNA group were lower than those of NC group. Besides, when treated with daunorubicin, the apoptosis rate of RYBP shRNA group was lower than that of NC group, while the inhibitive rate had no significant difference. CONCLUSIONS: RYBP gene silencing can inhibitive the apoptosis of HL-60 cells and significantly reduce the sensitivity to cytarabine, but this gene silencing can't affect the sensitivity to daunorubicin.

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese.

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95% confidence intervals (95%CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR = 1.13, 95%CI 1.01-1.25, P = 0.029; GlnGln vs. ArArg: OR = 1.41, 95%CI 1.07-1.84, P = 0.013; GlnGln vs. ArArg/ArgGln: OR = 1.37, 95%CI 1.07-1.76, P = 0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.