Circulating RNAs as predictive markers for the progression of type 2 diabetes

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.     

Sodium (±)‐5‐bromo‐2‐(α‐hydroxypentyl) benzoate ameliorates pressure overload‐induced cardiac hypertrophy and dysfunction through inhibiting autophagy

Sodium (±)‐5‐bromo‐2‐(a‐hydroxypentyl) benzoate (generic name: brozopine, BZP) has been reported to protect against stroke‐induced brain injury and was approved for Phase II clinical trials for treatment of stroke‐related brain damage by the China Food and Drug Administration (CFDA). However, the role of BZP in cardiac diseases, especially in pressure overload‐induced cardiac hypertrophy and heart failure, remains to be investigated. In the present study, angiotensin II stimulation and transverse aortic constriction were employed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial cell autophagy. We observed that BZP administration ameliorated cardiomyocyte hypertrophy and excessive autophagic activity. Further results indicated that AMP‐activated protein kinase (AMPK)‐mediated activation of the mammalian target of rapamycin (mTOR) pathway likely played a role in regulation of autophagy by BZP after Ang II stimulation. The activation of AMPK with metformin reversed the BZP‐induced suppression of autophagy. Finally, for the first time, we demonstrated that BZP could protect the heart from pressure overload‐induced hypertrophy and dysfunction, and this effect is associated with its inhibition of maladaptive cardiomyocyte autophagy through the AMPK‐mTOR signalling pathway. These findings indicated that BZP may serve as a promising compound for treatment of pressure overload‐induced cardiac remodelling and heart failure.     

TSG101 promotes the proliferation,migration and invasion of hepatocellular carcinoma cells by regulating the PEG10

The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.     

The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury

Inflammatory response plays an important role in ischaemia reperfusion injury (IRI) through a variety of inflammatory cells. Apart from neutrophils, macrophages and lymphocytes, the role of dendritic cells (DCs) in IRI has been noticed. The study was aimed at investigating whether the high‐mobility group protein box‐1/toll like receptor 4 (HMGB1/TLR4) signalling pathway regulate the migration, adhesion and aggregation of DCs to the myocardium, induce DCs activation and maturation, stimulate the expression of surface costimulatory molecules and participate in myocardial IRI. In vivo, migration, adhesion, and aggregation of DCs was enhanced; the expression of peripheral blood DCs CD80 and CD86, myocardial adhesion molecules were increased; and the infarct size was increased during myocardial ischaemia reperfusion injury myocardial ischemic/reperfusion injury (MI/RI). These responses induced by MI/RI were significantly inhibited by HMGB1 specific neutralizing antibody treatment. Cellular experiments confirmed that HMGB1 promoted the release of inflammatory cytokines through TLR4/MyD88/NF‐κB, upregulated CD80 and CD86 expression, mediated the damage of cardiomyocytes and accelerated the apoptosis. Our results indicate that DCs activation and maturation, stimulate the expression of surface costimulatory molecules by promoting the release of inflammatory factors through NF‐κB pathway and participate in myocardial IRI.     

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

Cardiac hypertrophy is a common pathological change frequently accompanied by chronic hypertension and myocardial infarction. Nevertheless, the pathophysiological mechanisms of cardiac hypertrophy have never been elucidated. Recent studies indicated that miR‐103 expression was significantly decreased in heart failure patients. However, less is known about the role of miR‐103 in cardiac hypertrophy. The present study was designed to investigate the relationship between miR‐103 and the mechanism of pressure overload‐induced cardiac hypertrophy. TRPV3 protein, cardiac hypertrophy marker proteins (BNP and β‐MHC) and autophagy associated proteins (Beclin‐1 and LC3‐II) were up‐regulated, as well as, miR‐103 expression and autophagy associated proteins (p62) were down‐regulated in cardiac hypertrophy models in vivo and in vitro respectively. Further results indicated that silencing TRPV3 or forcing overexpression of miR‐103 could dramatically inhibit cell surface area, relative fluorescence intensity of Ca²⁺ signal and the expressions of BNP, β‐MHC, Beclin‐1 and LC3‐II, but promote p62 expression. Moreover, TRPV3 protein was decreased in neonatal rat ventricular myocyte transfected with miR‐103, but increased by AMO‐103. Co‐transfection of the miR‐103 with the luciferase reporter vector into HEK293 cells caused a sharp decrease in luciferase activity compared with transfection of the luciferase vector alone. The miR‐103‐induced depression of luciferase activity was rescued by an AMO‐103. These findings suggested that TRPV3 was a direct target of miR‐103. In conclusion, miR‐103 could attenuate cardiomyocyte hypertrophy partly by reducing cardiac autophagy activity through the targeted inhibition of TRPV3 signalling in the pressure‐overloaded rat hearts.     

MicroRNA‐488 inhibits endometrial glandular epithelial cell proliferation,migration, and invasion in endometriosis mice via Wnt by inhibiting FZD7

Endometriosis is a chronic inflammatory syndrome and nearly 6%‐10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR‐488 would effectively inhibit the development of endometriosis. The microarray‐based data analysis was performed to screen endometriosis‐related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR‐488 in mice with endometriosis, we measured miR‐488 expression and expression levels of Frizzled‐7 (FZD7), cyclinD1, β‐catenin, and c‐Myc in vivo and in vitro. Finally, we detected the effect of miR‐488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, β‐catenin, c‐Myc and cyclinD1, and lower miR‐488 expression in mouse endometrial tissues. FZD7 was the target gene of miR‐488. Furthermore, elevated miR‐488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of β‐catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up‐regulated miR‐488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down‐regulating FZD7.     

3D Printing of Tunable Energy Storage Devices with Both High Areal and Volumetric Energy Densities

Developing advanced supercapacitors with both high areal and volumetric energy densities remains challenging. In this work, self‐supported, compact carbon composite electrodes are designed with tunable thickness using 3D printing technology for high‐energy‐density supercapacitors. The 3D carbon composite electrodes are composed of the closely stacked and aligned active carbon/carbon nanotube/reduced graphene oxide (AC/CNT/rGO) composite filaments. The AC microparticles are uniformly embedded in the wrinkled CNT/rGO conductive networks without using polymer binders, which contributes to the formation of abundant open and hierarchical pores. The 3D‐printed ultrathick AC/CNT/rGO composite electrode (ten layers) features high areal and volumetric mass loadings of 56.9 mg cm^?2 and 256.3 mg cm^?3, respectively. The symmetric cell assembled with the 3D‐printed thin GO separator and ultrathick AC/CNT/rGO electrodes can possess both high areal and volumetric capacitances of 4.56 F cm^?2 and 10.28 F cm^?3, respectively. Correspondingly, the assembled ultrathick and compact symmetric cell achieves high areal and volumetric energy densities of 0.63 mWh cm^?2 and 1.43 mWh cm^?3, respectively. The all‐component extrusion‐based 3D printing offers a promising strategy for the fabrication of multiscale and multidimensional structures of various high‐energy‐density electrochemical energy storage devices.     

Low‐Temperature Growth of Hard Carbon with Graphite Crystal for Sodium‐Ion Storage with High Initial Coulombic Efficiency: A General Method

Practical application of hard carbon materials in sodium‐ion batteries (SIBs) is largely limited by their low initial coulombic efficiency (ICE), which may be improved by increasing the graphitization degree. However, biomass‐derived hard carbon is usually nongraphitizable and extremely difficult to graphitize by direct heating even at 3000 °C. Herein, a general strategy is reported for fabricating hard carbon materials with graphite crystals at 1300 °C promoted by external graphite that serves as a crystal template for the growth of graphite crystals. The graphite crystals enable the contacted pseudographitic domains with a high‐level ordered structure, large domain size, and low defects, leading to an enhanced ICE. The obtained hard carbon materials with graphite crystals, using the carbonized eggshell membranes, and sucrose‐derived microsphere as precursors, achieve very high ICE of 89% and 91% with reversible capacity of 310 and 301 mA h g^?1, respectively. Therefore, using external graphite to promote high‐level ordering pseudographitic domains at low temperature is quite useful to improve ICE for SIB applications.     

Na3V2(PO4)3 as the Sole Solid Energy Storage Material for Redox Flow Sodium‐Ion Battery

Redox flow batteries have considerable advantages of system scalability and operation flexibility over other battery technologies, which makes them promising for large‐scale energy storage application. However, they suffer from low energy density and consequently relatively high cost for a nominal energy output. Redox targeting–based flow batteries are employed by incorporating solid energy storage materials in the tank and present energy density far beyond the solubility limit of the electrolytes. The success of this concept relies on paring suitable redox mediators with solid materials for facilitated reaction kinetics and lean electrolyte composition. Here, a redox targeting‐based flow battery system using the NASICON‐type Na₃V₂(PO₄)₃ as a capacity booster for both the catholyte and anolyte is reported. With 10‐methylphenothiazine as the cathodic redox mediator and 9‐fluorenone as anodic redox mediator, an all‐organic single molecule redox targeting–based flow battery is developed. The anodic and cathodic capacity are 3 and 17 times higher than the solubility limit of respective electrolyte, with which a full cell can achieve an energy density up to 88 Wh L^?1. The reaction mechanism is scrutinized by operando and in‐situ X‐ray and UV–vis absorption spectroscopy. The reaction kinetics are analysed in terms of Butler–Volmer formalism.