The relationship between serum uric acid within the normal range and β-cell function in Chinese patients with type 2 diabetes: differences by body mass index and gender

Background Elevated serum uric acid (SUA) has a positive correlation with insulin secretion and insulin resistance indexes. However, whether weight- and gender-specific differences regarding the relationship between SUA within the normal range and β-cell function and insulin resistance exist is unknown in type 2 diabetes mellitus (T2DM) patients. Methods A total of 380 patients with type 2 diabetes were divided into two groups as overweight/obesity (n = 268) and normal weight (n = 112). Each group were again divided into low (LSUA) and high normal SUA (HSUA). The HbA1c, C-peptide, SUA, creatinine, and lipids profiles were measured. HOMA2IR and HOMA%2B were estimated using fasting glucose and C-peptide by homeostasis model assessment (HOMA). Pearson’s correlations and multiple linear regression analyses were conducted to assess the associations between SUA levels and islet function indexes. Results In overweight/obesity subgroup, the levels of body mass index, fasting C-peptide (FCP), P2hCP, fasting CPI (FCPI), postprandial CPI (PPCPI), ΔC-peptide, HOMA2%B, and HOMA2IR were higher in HSUA group than in LSUA group. In contrast, the HbA1c, FBS, and P2hBS were lower in HSUA than in LSUA. In normal weight subgroup, there were no differences between the HSUA than LSUA group in terms of clinical characteristics. Pearson’s correlations indicated that there were no significant correlations between SUA and insulin secretory capacity in normal weight group, but in overweight/obesity group, SUA had positive significant correlations with P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. In the female group, there were no significant correlations between SUA and insulin secretory capacity. However, in the male group, SUA had positive significant correlations with insulin secretory capacity include P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. Multiple linear regression showed that SUA was significantly associated with HOMA2%B, but not with HOMA2IR in overweight/obesity and male group. Conclusions Our study shows that SUA levels within normal range were associated with β-cell function in T2DM patients with overweight/obesity or male. This finding supports that the association between SUA within normal range and insulin secretion ability differs by weight and sex

Irisin attenuates pyroptosis in high glucose-induced pancreatic beta cells via the miR-133a-3p/FOXO1 axis

Introduction: Irisin is closely related to type 2 diabetes mellitus (T2DM) and other metabolic diseases. It can improve the homeostasis of T2DM. MiR-133a-3p is decreased in the peripheral blood of patients with T2DM. Forkhead box protein O1 (FOXO1) is widely expressed in beta-cells and affects the occurrence of diabetes through transcriptional regulation and signalling pathway regulation. Material and methods: The miR-133a-3p inhibitor was constructed to verify the effect of irisin on pyroptosis through miR-133a-3p. Next, we predicted the presence of targeted binding sequences between FOXO1 and miR-133a-3p by bioinformatics software, which was then confirmed with a double fluorescence assay. Finally, the FOXO1 overexpression vector was used to further verify the effect of irisin through the miR-133a-3p/FOXO1 axis. Results: We first observed that irisin inhibited the protein levels of N-terminal gasdermin D (GSDMD-N) and cleaved caspase-1 and the secretion of interleukins (IL): IL-1beta and IL-18 in Min6 cells treated with high glucoes (HG). Irisin inhibited pyroptosis of Min6 cells treated with HG by reinforcing miR-133a-3p. Then, FOXO1 was validated to be the target gene of miR-133a. Both miR-133a-3p inhibitor and overexpression of FOXO1 restrained the force of irisin on pyroptosis in HG-induced Min6 cells. Conclusion: We explored the protective effect of irisin on HG-induced pyroptosis of islet b-cells in vitro and explained its mechanism of inhibiting pyroptosis through the miR-133a-3p/FOXO1 axis, to provide a theoretical basis for finding new molecular targets to delay beta-cell failure and the treatment of T2DM

Solid polymer electrolytes: Ion conduction mechanisms and enhancement strategies

Solid polymer electrolytes (SPEs) possess comprehensive advantages such as high flexibility, low interfacial resistance with the electrodes, excellent film-forming ability, and low price, however, their applications in solid-state batteries are mainly hindered by the insufficient ionic conductivity especially below the melting temperatures, etc. To improve the ion conduction capability and other properties, a variety of modification strategies have been exploited. In this review article, we scrutinize the structure characteristics and the ion transfer behaviors of the SPEs (and their composites) and then disclose the ion conduction mechanisms. The ion transport involves the ion hopping and the polymer segmental motion, and the improvement in the ionic conductivity is mainly attributed to the increase of the concentration and mobility of the charge carriers and the construction of fast-ion pathways. Furthermore, the recent advances on the modification strategies of the SPEs to enhance the ion conduction from copolymer structure design to lithium salt exploitation, additive engineering, and electrolyte micromorphology adjustion are summarized. This article intends to give a comprehensive, systemic, and profound understanding of the ion conduction and enhancement mechanisms of the SPEs for their viable applications in solid-state batteries with high safety and energy density

Comparative experimental study on reactive crystallization of Ni(OH)(2) in an airlift-loop reactor and a stirred reactor

The objective of this work is to study the reactive crystallization in an airlift-loop reactor (ALR) using the precipitation of Ni(OH)(2) as a model reaction. The growth of Ni(OH)(2) particles in an ALR and a stirred tank was quantified by scanning electronic microscope (SEM), X-ray diffraction (XRD), laser particle analyzer, tap densitometer and optical microscope, and the growth process of Ni(OH)(2) particles is analyzed. It is found that the Ni(OH)(2) particles prepared in an ALR have a better sphericity than those in a stirred tank and the growth of Ni(OH)(2) particle tap density mainly depends on the size of crystallites: the bigger the size of crystallites, the bigger the tap density is. Based on these, the growth process of Ni(OH)(2) particles in ALR is elaborated. Crystallites precipitated from solution aggregate to form large particles with much void. These constituting crystallites continue to grow up, that takes up the void inside particles and makes the tap density increase. (C) 2017 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.</p

Irisin suppresses pancreatic β cell pyroptosis in T2DM by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis

Abstract Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown. Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results. Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets. Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis

Comparative experimental study on reactive crystallization of Ni(OH)_2 in an airlift-loop reactor and a stirred reactor

The objective of this work is to study the reactive crystallization in an airlift-loop reactor (ALR) using the precipitation of Ni(OH) 2 as a model reaction. The growth of Ni(OH) 2 particles in an ALR and a stirred tank was quantified by scanning electronic microscope (SEM), X-ray diffraction (XRD), laser particle analyzer, tap densitometer and optical microscope, and the growth process of Ni(OH) 2 particles is analyzed. It is found that the Ni(OH) 2 particles prepared in an ALR have a better sphericity than those in a stirred tank and the growth of Ni(OH) 2 particle tap density mainly depends on the size of crystallites: the bigger the size of crystallites, the bigger the tap density is. Based on these, the growth process of Ni(OH) 2 particles in ALR is elaborated. Crystallites precipitated from solution aggregate to form large particles with much void. These constituting crystallites continue to grow up, that takes up the void inside particles and makes the tap density increase

The Primary Complete Mitochondrial Genome of the Lappet Moth Brahmophthalma hearseyi (Lepidoptera: Brahmaeidae) and Related Phylogenetic Analysis

Background: Brahmophthalma hearseyi (Lepidoptera: Brahmaeidae) is widely distributed across China. Its larvae damage the leaves of many plants such as those belonging to the Oleaceae family, causing significant economic losses and seriously affecting the survival and reproduction of Cervus nippon; however, genetic data for this species are scarce. Methods: The complete mitochondrial genome (mitogenome) of B. hearseyi was sequenced using long-PCR and primer-walking methods. Phylogenetic analysis that was based on 13 PCGs and two rRNAs was carried out using the neighbor-joining and Bayesian interference methods. Results: The mitogenome is a typical circular molecule that is made up of 15,442 bp, which includes 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and an A + T-rich region (456 bp). All of the PCGs, except for COX1 and COX2, start with ATN codons. COX2 and ND5 use the incomplete termination codon T, and 11 other PCGs use the typical stop codon TAA. All tRNA genes, except for trnS1 and trnS2, display a typical cloverleaf structure; trnS1 lacks the “DHU” arm, whereas trnS2 exhibits two mismatched base pairs in the anticodon stem. Phylogenetic analysis showed that B. hearseyi is clustered into Brahmaeidae, and the phylogenetic relationships are (Brahmaeidae + Lasiocampidae) + (Bombycidae + (Sphingidae + Saturniidae)). Conclusions: This study provides the first mitogenomic resources for the Brahmaeidae

NARFL deficiency caused mitochondrial dysfunction in lung cancer cells by HIF-1α–DNMT1 axis

Abstract NARFL was reported to be a component of cytosolic iron–sulfur cluster assembly pathway and a causative gene of the diffused pulmonary arteriovenous malformations (dPAVMs). NARFL knockout dramatically impaired mitochondrial integrity in mice, which might promote mitochondrial dysfunction and lead to worse survival rate of lung cancer. However, the underlying molecular mechanism of NARFL deficiency in non-small cell lung cancer (NSCLC) is unknown. Knockdown assay was performed in A549 and H1299 cells. The protein levels of HIF-1α and DNMT1 were measured, and then Complex I activity, mtDNA copy numbers and mRNA levels of mtND genes were determined. Cisplatin resistance and cell proliferation were conducted using CCK8 assay. Cell migration and invasion were detected using wound heal assay and transwell assay. Survival analysis of lung cancer patients and KM plotter database were used for evaluating the potential value of NARFL deficiency. NARFL protein was expressed in two cell lines and knockdown assay significantly reduced its levels. Knockdown NARFL increased the protein levels of HIF-1α and DNMT1, and downregulated the mRNA levels of ND genes, mitochondrial Complex I activity, mtDNA copy number, and ATP levels. The mitochondrial dysfunction caused by NARFL deficiency were ameliorated by siHIF-1α and DNMT1 inhibitor. Knockdown NARFL increased the drug resistance and cell migration, and siHIF-1α reversed this effect. Moreover, NSCLC patients with NARFL deficiency had a poor survival rate using a tissue array and KM plotter database, and it would be a target for cancer prognosis and treatment. NARFL deficiency caused dysregulation of energy metabolism in lung cancer cells via HIF-1α–DNMT1 axis, which promoted drug resistance and cell migration. It provided a potential target for treatment and prognosis of lung cancer