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•Synthesis of benzoxazinyl modified polyhedral oligomeric silsesquioxane (BZPOSS).•Homogeneous nanocomposites were prepared using cyanate ester and BZPOSS.•Processibility of cyanate ...ester was optimized by BZPOSS.•Dielectric constant of 2.01 was obtained by incorporation of BZPOSS.•Polymerization chemistry of benzoxazine and cyanate ester was discussed in detail.
Benzoxazinyl modified polyhedral oligomeric silsesquioxane (BZPOSS) is successfully synthesized and used to prepare nanocomposites with bisphenol A cyanate ester (BADCy). The DSC results showed that the curing peak temperature of BZPOSS/BADCy blend decrease significantly from 317.1 °C to 160.3 °C, suggesting the high catalytic activity of BZPOSS to the polymerization of cyanate ester. The SEM micrographs of poly(BZPOSS/BADCy) and Silicon element distribution maps given by EDS both indicated that BZPOSS disperses evenly in BADCy. Dielectric properties tests showed that the dielectric constant can be reduced by the introduction of BZPOSS, which is attributed to the nano-pores from the cage structure of POSS. When 15 wt% BZPOSS was added, the dielectric constant decreased to 2.01 and the dielectric loss was also only 0.0070 at 1 MHz. Meanwhile, DMA and TGA result showed that the thermal stability and heat resistance of poly(BZPOSS/BADCy) at high temperature decreased with increasing BZPOSS, which is due to the change of crosslinking structure of the copolymers. The influences of the crosslinking structure and the nano-porous organic-inorganic hybrid particles on the dielectric and thermal property of poly(BZPOSS/BADCy) were also discussed.
The effects of key parameters on locked mode induced disruption (LMiD) are investigated in EAST experiments. The experimental data for locked mode are collected from 2015 to 2022 when the externally ...applied resonant magnetic perturbation is successfully employed in EAST. In this dataset, ∼42% of the total shots are LMiD, while the remaining 58% are LM without disruption. To better analyze the LMiD, an intuitive physical process is proposed. The LMiD process can be divided into two stages, the evolution of magnetic islands and the loss of plasma stored energy. The LMiD can also be related to the evolution of the other 8 physical quantities. On the basis of this physical process analysis, the time scale and the influencing factors for LMiD are investigated using statistical analysis. It is found that the density (ne), the distance from the magnetic island outer boundary to the plasma last closed surface (dedge), the loop-voltage (Vloop), and the plasma core electron temperature (Te), which are consistent with the intuitive physical model, are key parameters to LMiD. In addition, other potentially important parameters, the relevant reasons, and statistical analysis on the parameter intervals where rapid disruption with greater harmfulness occurred have also been investigated.
Creating high-density durable bifunctional active sites in an air electrode is essential but still challenging for a long-life rechargeable zinc–air battery with appealing power density. Herein, we ...discover a general strategy mediated by metastable rock salt oxides for achieving high-density well-defined transition-metal nanocrystals encapsulated in N-doped carbon shells (M@NC) which are anchored on a substrate by a porous carbon network as highly active and durable bifunctional catalytic sites. Small-size (15 ± 5 nm) well-dispersed Co2Fe1@NC in a high density (metal loading up to 54.0 wt %) offers the zinc–air battery a record power density of 423.7 mW cm–2. The dual protection from the complete graphitic carbon shells and the anchoring of the outer carbon network make Co2Fe1@NC chemically and mechanically durable, giving the battery a long cycling life. Systematic in-situ temperature-dependent characterizations as well as DFT modeling rationalize the rock salt oxide-mediated process and its indispensable role in achieving high-density nanosized M@NC. These findings open up opportunities for designing efficient electrocatalysts for high-performance Zn–air batteries and diverse energy devices.
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High fructose intake is a risk of glomerular podocyte dysfunction. Podocyte apoptosis has emerged as a major cause of podocyte loss, exacerbating proteinuria. Magnesium ...isoglycyrrhizinate (MgIG) is usually used as a hepatoprotective agent in clinic. Liver and kidney injury often occurs in human diseases. Recent report shows that MgIG improves kidney function. In this study, we found that MgIG significantly alleviated kidney dysfunction, proteinuria and podocyte injury in fructose-fed rats. It also restored fructose-induced podocyte apoptosis in rat glomeruli and cultured differentiated podocytes. Of note, high-expression of miR-193a, downregulation of Wilms’ tumor protein (WT1) and RelA, as well as upregulation of C-Maf inducing protein (C-mip) were observed in these animal and cell models. The data from the transfection of miR-193a mimic, miR-193a inhibitor, WT1 siRNA or LV5-WT1 in cultured differentiated podocytes showed that fructose increased miR-193a to down-regulate WT1, and subsequently activated C-mip to suppress RelA, causing podocyte apoptosis. These disturbances were significantly attenuated by MgIG. Taken together, these results provide the first evidence that MgIG restrains fructose-induced podocyte apoptosis at least partly through inhibiting miR-193a to upregulate WT1, supporting the application of MgIG with a novel mechanism-of-action against podocyte apoptosis associated with fructose-induced kidney dysfunction.
Metabolic coupling between oocytes and the surrounding somatic cells allows for normal two-way communication, and their interactions is necessary for generating developmentally competent eggs. ...However, the metabolic framework that support oocyte maturation in surrounding cumulus cells is still lacking. Herin, we established a temporal metabolome profile of porcine cumulus cells at three key stages during oocyte maturation, illustrating the picture of global metabolic network in cumulus cells. Importantly, we discovered the novel metabolic signature in cumulus cells during meiotic maturation, in specific, significant consumption of fatty acids, elevated activity of hexosamine biosynthetic pathway (HBP), and enhanced polyamine biosynthesis. Meanwhile, we observed the different utilization of tryptophan, active biosynthesis of progesterone, and progressive decrease in purine and pyrimidine metabolism as the oocytes progress through meiosis. Collectively, our metabolomic data serves an entree to elaborate on the dynamic changes in these metabolic pathways, which not only reveals the metabolic networks controlling oocyte development, but also lays a foundation for the discovery of biomarkers in the improvement in porcine oocyte culture system.
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•Analyzed the temporal metabolome profiles of porcine cumulus cells.•Uncovered the metabolic networks regulating oocyte development.•Discovered the active biosynthesis of progesterone and polyamines in cumulus cells during maturation.•Several of the metabolites found in our study may be helpful for the prediction of biomarkers of higher oocyte quality.
Oxidative stress-mediated activation of inflammasome has a significant effect on the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Farnesoid X receptor (NR1H4, FXR) has been implicated in ...biological function and many diseases, including NAFLD. The regulatory effect of FXR on oxidative stress and whether this process is related with the activation of absent melanoma 2 (AIM2) inflammasome in NAFLD remain unclear. In the present research, we confirmed that FXR in the livers of steatosis patients is significantly reduced compared with normal liver tissue by using the Gene Expression Omnibus (GEO) database and a palmitic acid (PA) - mediated steatosis model in AML-12 cells. Under the premise of ensuring the same food intake as the control group, overexpression of FXR in mice attenuated HFD-mediated weight gain and liver steatosis, facilitated lipid metabolism, improved fatty acid β-oxidation, lipolysis, and reduced fatty acid synthesis and intake, which also inhibited the activation of AIM2 inflammasome. Overexpression of FXR alleviated PA-induced triglyceride (TG) accumulation, imbalance of lipid homeostasis, and the activation of AIM2 inflammasome in hepatic steatosis cells, while FXR knockdown appeared the opposite effects. FXR overexpression suppressed PA- and HFD-induced oxidative stress, but FXR siRNA demonstrated the opposite influence. The decreased ROS generation may be the reason why FXR weakens AIM2 activation when a fatty acid overload occurs. In conclusion, our results confirm that other than regulating lipid homeostasis and blocking NLRP3 inflammasome activation, FXR improves hepatic steatosis by a novel mechanism that inhibits oxidative stress and AIM2 inflammasome activation.
Endoplasmic reticulum stress (ERS) has been implicated in obesity-associated cardiac remodeling and dysfunction. Inactive rhomboid protein 2 (iRhom2), also known as Rhbdf2, is an inactive member of ...the rhomboid intramembrane proteinase family, playing an essential role in regulating inflammation. Nevertheless, the role of ERS-meditated iRhom2 pathway in metabolic stress-induced cardiomyopathy remains unknown. In the study, we showed that 4-PBA, as an essential ERS inhibitor, significantly alleviated high fat diet (HFD)-induced metabolic disorder and cardiac dysfunction in mice. Additionally, lipid deposition in heart tissues was prevented by 4-PBA in HFD-challenged mice. Moreover, 4-PBA blunted the expression of iRhom2, TACE, TNFR2 and phosphorylated NF-κB to prevent HFD-induced expression of inflammatory factors. Further, 4-PBA restrained HFD-triggered oxidative stress by promoting Nrf-2 signaling. Importantly, 4-PBA markedly suppressed cardiac ERS in HFD mice. The anti-inflammation, anti-ERS and anti-oxidant effects of 4-PBA were verified in palmitate (PAL)-incubated macrophages and cardiomyocytes. In addition, promoting ERS could obviously enhance iRhom2 signaling in vitro. Intriguingly, our data demonstrated that PAL-induced iRhom2 up-regulation apparently promoted macrophage to generate inflammatory factors that could promote cardiomyocyte inflammation and lipid accumulation. Finally, interventions by adding fisetin or metformin significantly abrogated metabolic stress-induced cardiomyopathy through the mechanisms mentioned above. In conclusion, this study provided a novel mechanism for metabolic stress-induced cardiomyopathy pathogenesis. Therapeutic strategy to restrain ROS/ERS/iRhom2 signaling pathway could be developed to prevent myocardial inflammation and lipid deposition, consequently alleviating obesity-induced cardiomyopathy.
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•High fat diet ingestion promotes ER-stress associated iRhom2 activation.•iRhom2 influences inflammatory response in macrophage and is stimulated by ER-stress.•iRhom2 enables macrophage to produce inflammatory factors to promote cardiomyocyte inflammation and lipid accumulation.
Many variants with various strategies have been proposed to improve the efficiency of Particle Swarm Optimization (PSO) algorithm. These strategies are a precious resource waiting to be exploited. We ...conjecture that some new combinations of strategies selected from different PSO variants may better improve the performance of PSO. Inspired by this idea, this paper proposes a strategy learning framework to learn an optimal combination of strategies and thus derive a new PSO variant based on this combination. In this framework, a strategy pool with strategies selected from existing PSO variants is first constructed. Then, a training engine, implemented by an adaptive differential evolutionary algorithm, is employed to evaluate the performance of strategy combinations on training benchmark functions. Furthermore, a new PSO variant, named SLFPSO, is created based on the strategies learned from training results. This framework provides a novel method to design PSO variants by learning from existing algorithms through a learning mechanism. The performance and scalability of SLFPSO are compared with ten state-of-the-art PSO variants on 10/30/50/100-dimensional CEC2013/2014/2017 benchmark functions. The results verify that SLFPSO performs significantly better than the compared algorithms in most test scenarios.
Background
Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m5C) is an important posttranscriptional widespread modification ...involved in many biological processes. However, the association between genetic variations of m5C modification genes and the prognostic value of colorectal cancer remains unclear.
Methods
We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m5C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression‐free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis.
Results
We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose–response effect between NRA and OS after chemotherapy was found (ptrend = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3–4 NRA group was markedly reduced in comparison to that in the 0–2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p < 0.05) in the TCGA database, and eQTL analysis demonstrated that the two SNPs were associated with YBX1 (p = 0.003 for rs10890208 and p = 0.024 for rs3862218).
Conclusion
Our study indicates that genetic variants in m5C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients.
We identified that rs10890208 and rs3862218 in YBX1 were associated with colorectal cancer overall survival after chemotherapy. Our study indicates that genetic variants in m5C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients.
