Aqueous Zn-ion batteries (ZIBs) are a potential electrochemical energy storage device because of their highly intrinsic safety, low cost, and large capacity. However, it is still in the primary stage ...because of the limited selection of cathode materials with high rate and long-life cycling stability. In addition, the energy storage mechanisms of ZIBs have not been well established. In this work, we report the synthesis of porous V2O3@C materials with high conductivity and further illustrate its application as the intercalation cathode for aqueous zinc-ion batteries. The unique channel and appropriate pore size distribution of corundum-type V2O3 are beneficial to the rapid zinc ion intercalation and removal, leading to a high rate capability. Also, the carbon framework structure achieves a high cyclic stability. The porous V2O3@C cathode delivers high capacities of 350 mA h g–1 at 100 mA g–1, an excellent rate capability (250 mA h g–1 at 2 A g–1), and an impressive long-life cycling stability with 90% capacity retention over 4000 cycles at 5 A g–1. The storage mechanism of zinc ions in the Zn/V2O3 system was studied by various analytical methods and first-principles calculation.
GTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase uncoupling in endothelial dysfunction. MicroRNAs (miRs) are a class of regulatory RNAs that negatively ...regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation.
Endothelial function was assessed by measuring acetylcholine-induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization.
We first demonstrated that GCH1 mRNA is a target of miR-133a. In endothelial cells, miR-133a was robustly induced by cytokines/oxidants and inhibited by lovastatin. Furthermore, lovastatin upregulated GCH1 and tetrahydrobiopterin, and recoupled endothelial nitric oxide synthase in stressed endothelial cells. These actions of lovastatin were abolished by enforced miR-133a expression and were mirrored by a miR-133a antagomir. In mice, hyperlipidemia- or hyperglycemia-induced ectopic miR-133a expression in the vascular endothelium, reduced GCH1 protein and tetrahydrobiopterin levels, and impaired endothelial function, which were reversed by lovastatin or miR-133a antagomir. These beneficial effects of lovastatin in mice were abrogated by in vivo miR-133a overexpression or GCH1 knockdown. In rats, multiple cardiovascular risk factors including hyperglycemia, dyslipidemia, and hyperhomocysteinemia resulted in increased miR-133a vascular expression, reduced GCH1 expression, uncoupled endothelial nitric oxide synthase function, and induced endothelial dysfunction, which were prevented by lovastatin.
Statin inhibits aberrant miR-133a expression in the vascular endothelium to prevent endothelial dysfunction by targeting GCH1. Therefore, miR-133a represents an important therapeutic target for preventing cardiovascular diseases.
Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and ...lipids. We have previously reported that activation of AMP‐activated protein kinase (AMPK) produces anti‐inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin‐1 beta (IL‐1β), IL‐6 and tumour necrosis factor alpha (TNF‐α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP‐activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose‐dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL‐1β, IL‐6 and TNF‐α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS‐induced macrophage activation if AMPK was in deficient through siRNA‐mediated approaches. Further, the anti‐inflammatory effects produced by VitB6 or AICAR in LPS‐treated macrophages were abolished in DOK3 gene knockout (DOK3−/−) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS‐induced both systemic inflammation and acute pneumonia in wild‐type mice, but not in DOK3−/− mice. VitB6 prevents LPS‐induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.
Reconfigurability of photonic integrated circuits (PICs) has become increasingly important due to the growing demands for electronic–photonic systems on a chip driven by emerging applications, ...including neuromorphic computing, quantum information, and microwave photonics. Success in these fields usually requires highly scalable photonic switching units as essential building blocks. Current photonic switches, however, mainly rely on materials with weak, volatile thermo‐optic or electro‐optic modulation effects, resulting in large footprints and high energy consumption. As a promising alternative, chalcogenide phase‐change materials (PCMs) exhibit strong optical modulation in a static, self‐holding fashion, but the scalability of present PCM‐integrated photonic applications is still limited by the poor optical or electrical actuation approaches. Here, with phase transitions actuated by in situ silicon PIN diode heaters, scalable nonvolatile electrically reconfigurable photonic switches using PCM‐clad silicon waveguides and microring resonators are demonstrated. As a result, intrinsically compact and energy‐efficient switching units operated with low driving voltages, near‐zero additional loss, and reversible switching with high endurance are obtained in a complementary metal‐oxide‐semiconductor (CMOS)‐compatible process. This work can potentially enable very large‐scale CMOS‐integrated programmable electronic–photonic systems such as optical neural networks and general‐purpose integrated photonic processors.
Nonvolatile electrically reconfigurable photonic switches based on phase‐change‐material‐clad silicon waveguides and microring resonators are demonstrated via in situ silicon PIN diode heaters. Low‐energy, compact, low‐loss, low‐voltage, and high‐cyclability operations at moderate speeds are obtained in a complementary metal‐oxide‐semiconductor‐compatible process, promising very large‐scale programmable electronic–photonic systems such as optical neural networks and general‐purpose integrated photonic processors.
Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of ...microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.
Aims
Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP‐1), as a gene regulator, initiates cytokine expression in response to ...environmental stimuli. In this study, we investigated the relationship between AP‐1 and neuroinflammation‐associated brain injury triggered by ICH.
Methods
Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP‐1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP‐1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro.
Results
AP‐1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α. Inhibition of AP‐1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL‐6 and TNF‐α production and brain‐infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin‐induced production of IL‐6 and TNF‐α in cultured microglia.
Conclusions
Inhibition of AP‐1 curbs neuroinflammation and reduces brain injury following ICH.
Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we ...focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 results in a marked reduction of the expression level of a large number of mature miRNAs and concomitant accumulation of unprocessed primary microRNAs (pri-miRNAs) in multiple human cells. Mechanistically, PUS10 directly binds to pri-miRNAs and interacts with the microprocessor to promote miRNA biogenesis. Unexpectedly, this process is independent of the catalytic activity of PUS10. Additionally, we develop a sequencing method to profile Ψ in the tRNAome and report PUS10-dependent Ψ sites in tRNA. Collectively, our findings reveal differential functions of PUS10 in nuclear miRNA processing and in cytoplasmic tRNA pseudouridylation.
Reliable and accurate daily runoff predictions are critical to water resource management and planning. Probability density predictions of daily runoff can provide decision-makers with comprehensive ...information by quantifying the uncertainty of forecasting. Models based on quantile regression (QR) have been proven to achieve good probabilistic prediction performance, but the predicted quantiles may crossover with each other, seriously reducing the reliability of the prediction. This paper proposes non-crossing quantile regression (NCQR), which guarantees that the intervals between adjacent quantiles are greater than 0, which avoids the occurrence of quantile crossing. In order to apply NCQR to the prediction of nonlinear runoff series, this paper combines NCQR with recurrent neural network (RNN) models. In order to reduce the model training time and further improve the model accuracy, this paper simplifies the minimal gated memory (MGM) model and proposes a new RNN model, called the simplified minimal gated memory (SMGM) model. Kernel density estimation (KDE) is used to transform the discrete quantiles predicted using SMGM-NCQR into a continuous probability density function (PDF). This paper proposes a novel daily density prediction model that combines SMGM-NCQR and KDE. Three daily runoff datasets in the Yangtze River Basin in China are taken as examples and compared with the advanced models in current research in terms of five aspects: point prediction evaluation, interval prediction evaluation, probability density prediction evaluation, the degree of quantile crossing and training time. The experimental results show that the model can provide high-quality and highly reliable runoff probability density predictions.
The impaired angiogenesis is the major cause of diabetic delayed wound healing. The molecular insight remains unknown. Previous study has shown that high glucose (HG) activates Na+/H+ exchanger 1 ...(NHE1) and induces intracellular alkalinization, resulting in endothelial dysfunction. The aim of this study is to investigate whether activation of NHE1 in endothelial cells by HG damages the angiogenesis in vitro and in vivo.
We used western blot to detect the phosphorylations of both Akt and Girdin, and pH-sensitive BCECF fluorescence to assay NHE1 activity and pHi value, respectively. The angiogenesis was evaluated by measuring the number of tube formation in vitro, and blood perfusion by laser doppler and neovascularization by staining CD31 in vivo. Our results indicated that induction of intracellular acidosis (IA) increased p-Akt and p-Girdin in human umbilical vein endothelial cells (HUVEC). HG activated NHE1 and increased pHi value in a time-dependent manner, associated with the decreased phosphorylations of both Akt and Gridin, while inhibition of NHE1 by amiloride abolished the HG-induced reductions of p-Akt and p-Girdin. However, silence of Akt by siRNA transfection or pharmacological inhibitors (wortmannin and LY294002) bypassed IA-induced Girdin phosphorylation. Overexpression of constitutively active Akt abolished HG-reduced Girdin phosphorylation. In addition, upregulation of Akt or inhibition of NHE1 remarkably attenuated HG-impaired tube formation in HUVEC. In vivo study revealed that amiloride dramatically rescued hyperglycemia-delayed blood perfusion and neovascularization by augmenting ischemia-induced angiogenesis.
IA promotes ischemia-induced angiogenesis via Akt-dependent Girdin phosphorylation in diabetic mice.
•Intracellular acidosis activated Akt in endothelial cells.•Hyperglycemia inhibits endothelial cell-mediated angiogenesis and the delayed recovery of blood perfusion in mice following hind limb ischemia through Akt dephosphorylation mediated by NHE1/pHi in vivo.
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