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To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress, short-term transverse aortic constriction (TAC) was performed in mice and then withdrawn for several days by aortic debanding, followed by subsequent myocardial exposure to ischemia/reperfusion (I/R). Following I/R injury, the myocardial infarct size and apoptosis were markedly reduced, and contractile function was significantly improved in the TAC preconditioning group compared with the control group. Mechanistically, hypertrophic preconditioning remarkably alleviated I/R-induced oxidative stress, as evidenced by the increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP) ratio, increase in the reduced glutathione (GSH)/oxidized glutathione (GSSH) ratio, and reduced mitochondrial reactive oxygen species (ROS) production. Moreover, TAC preconditioning inhibited caspase-3 activation and mitigated the mitochondrial impairment by deacetylating isocitrate dehydrogenase 2 (IDH2) via a sirtuin 3 (SIRT3)-dependent mechanism. In addition, the expression of a genetic deacetylation mimetic IDH2 mutant (IDH2 K413R) in cardiomyocytes, which increased IDH2 enzymatic activity and decreased mitochondrial ROS production, and ameliorated I/R injury, whereas the expression of a genetic acetylation mimetic (IDH2 K413Q) in cardiomyocytes abolished these protective effects of hypertrophic preconditioning. Furthermore, both the activity and expression of the SIRT3 protein were markedly increased in preconditioned mice exposed to I/R. Treatment with an adenovirus encoding SIRT3 partially emulated the actions of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. The present study identifies hypertrophic preconditioning as a novel endogenous self-defensive and cardioprotective strategy for cardiac I/R injury that induces IDH2 deacetylation through a SIRT3-dependent mechanism. A therapeutic strategy targeting IDH2 may be a promising treatment for cardiac ischemic injury., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

This research designs an intelligent parking system including service application layer, perception layer, data analysis layer, and management layer. The network system adopts opm15 system, and the parking space recognition adopts improved convolution neural networks (CNNs) algorithm and image recognition technology. Firstly, the parking space is occupied and located, and the shortest path (Dynamic Programming, DP) is selected. In order to describe the path algorithm, the parking system model is established. Aiming at the problems of DP low power and adjacent path interference in the path detection system, a method of combining interference elimination technology with enhanced detector technology is proposed to effectively eliminate the interference path signal and improve the performance of the intelligent parking system. In order to verify whether the CNNs system designed in this study has advantages, the simulation experiments of CNNs, ZigBee, and manual parking are carried out. The results show that the parking system designed in this study can control the parking error, has smaller parking error than ZigBee, and has more than 25.64% less parking time than ZigBee, and more than 34.83% less time than manual parking. In terms of parking energy consumption, when there are less free parking spaces, CNNs have lower energy consumption., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Yucheng Guo and Hongtao Shi.)

Cardiomyocyte hypertrophy is a fatal factor in heart disease resulting in heart failure and even mortality. Although many studies have been focusing on the pathogenesis of cardiomyocyte hypertrophy, the exact molecular mechanisms are still unexclusive. In this study, we first found that the expression level of lncRNA Tincr was significantly decreased in the myocardial tissues of TAC mouse models of cardiomyocyte hypertrophy, and this result was further confirmed in H9C2 cells, a widely used rat myoblast cell lines. More intriguingly, we demonstrated that the aberration of Tincr is essential to the pathogenesis of cardiomyocyte hypertrophy, indicated by the re-induction of Tincr improving the heart functions of hypertrophic mice. In mechanism, we identified miR-31-5p as a direct target of Tincr using a widely used online bioinformatics tool StarBase, and this result was further experimentally validated using dual-luciferase reporter assay and real-time PCR. Also, we identified PRKCE as a direct target of miR-31-5p, and loss function of miR-31-5p significantly blocks the positive regulatory effect of Tincr on PRKCE expression in H9C2 cells. The knockdown of Tincr resulted in increased cardiomyocyte size, and, however, inhibition of miR-31-5p or overexpression of PRKCE significantly reversed the increased cardiomyocyte size. Taken together, our study showed that a novel Tincr-miR-31-5p axis targeting PRKCE was involved in cardiomyocyte hypertrophy, indicating that it may provide potential therapy in cardiomyocyte hypertrophy.

Plasticizer dibutyl phthalate (DBP) pollution has received more and more attention. In this study, a DBP degrading bacteria Enterobacter sp. DNB-S2 was found to suffer membrane damage and oxidative stress during DBP degradation. Physiological and transcriptome analysis showed that 100 μmol L -1 anthraquinone-2,6-disulfonate (AQDS) could enhance the ability of strain DNB-S2 for biodegradation of DBP. AQDS adjusted the cell surface structure, including increase levels of hydrophobic and unsaturated fatty acids. These changes increased the chemotactic ability of the strain DNB-S2 to the hydrophobic pollutant DBP and the fluidity of the cell membrane. The expression of methyl chemotactic protein and genes associated with cell membrane-fixed components were up-regulated. AQDS also improved the scavenging ability of ·OH and H 2 O 2 of DNB-S2 by promoting expression genes related to glutathione metabolism, thereby reducing oxidative stress. These results will provide new insights into the biodegradation of DBP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rationale : Hyperlipidemia is a major risk factor of atherosclerosis and cardiovascular diseases (CVD). As a standard-of-care approach for hyperlipidemia, statins only reduce the risk of coronary artery disease by 20-40%, underscoring the importance of identifying molecular pathways for the design of drugs against this disorder. Alterations in microRNA (miRNA) expression have been reported in patients with hyperlipidemia and CVD. This study was designed to determine the mechanism of dysregulated miR-378a-3p under the status of hyperlipidemia and evaluate how miR-378a-3p regulates hepatic secretion of VLDL. Methods : Wild-type mice kept on a high fat diet were injected with miR-378a-3p inhibitor or a mini-circle expression system containing miR-378a precursor to study loss and gain-of functions of miR-378a-3p. Mice were treated with Triton WR1339 and 35 S-methionine/cysteine to determine the effect of miR-378a-3p on hepatic secretion of VLDL. Database mining, luciferase assay, and ChIP (chromatin immunoprecipitation) were used to study the mechanism of dysregulated miR-378a-3p biogenesis. Results : miR-378a-3p expression is significantly increased in livers of hyperlipidemic mice. Sort1 (sortilin 1) was identified as a direct target of miR-378a-3p. By inhibiting the function of sortilin 1 as a transmembrane trafficking receptor, miR-378a-3p stabilized ApoB100 and promoted ApoB100 secretion in vitro . Liver-specific expression of miR-378a-3p stabilized ApoB100 and facilitated hepatic secretion of VLDL, which subsequently increased levels of VLDL/LDL cholesterol as well as triglycerides. In contrast, antagonizing miR-378a-3p using its inhibitor increased hepatic expression of Sort1 and reduced hepatic export of VLDL with its consequent effects of serum lipid levels. Additional knockdown of up-regulated Sort1 in livers of mice offset the effects of miR-378a-3p inhibitor, suggesting that Sort1 was indispensable for miR-378a-3p to promote secretion of VLDL and thereby high levels of circulating VLDL/LDL cholesterol and triglycerides. Furthermore, oncogenic E2F1 (E2F transcription factor 1) was identified as a transcriptional activator of miR-378a-3p. E2f1 knockdown, through reducing miR-378a-3p, impaired secretion of VLDL and reduced levels of VLDL/LDL cholesterol and triglycerides. Conclusions : This study defines a novel pathway of E2F1-miR-378a-3p-SORT1-ApoB100 that controls levels of circulating VLDL/LDL cholesterol and triglycerides by modulating degradation and secretion of ApoB100, and suggests the use of miR-378a-3p as a potential therapeutic target for dyslipidemia., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The role of M1 macrophages (M1M)-derived exosomes in the progression of neointimal hyperplasia remains unclear now. Using a transwell co-culture system, we demonstrated that M1M contributed to functional change of vascular smooth muscle cell (VSMC). We further stimulated VSMCs with exosomes isolated from M1M. Our results demonstrated that these exosomes could be taken up by VSMCs through macropinocytosis. Using a microRNA array assay, we identified that miR-222 originated from M1M-derived exosomes triggered the functional changes of VSMCs. In addition, we confirmed that miR-222 played a key role in promoting VSMCs proliferation and migration by targeting Cyclin Dependent Kinase Inhibitor 1B (CDKN1B) and Cyclin Dependent Kinase Inhibitor 1C (CDKN1C) in vitro. In vivo, M1M-derived exosomes significantly aggravated neointima formation following carotid artery ligation injury and wire injury and these effects were partly abolished by miR-222 inhibitor 2'OMe-miR-222. Our findings thus suggest that exosomes derived from M1M could aggravate neointimal hyperplasia through delivering miR-222 into VSMCs. Future studies are warranted to validate if the post-injury vascular neointimal hyperplasia and restenosis could be attenuated by inhibiting miR-222.

The present study was performed to investigate the effects of dietary supplementation with Lactobacillus plantarum (CGMCC1.557) on egg production and fecal microbiota composition in laying hens. Sixty Hy-Line Brown laying hens (18 weeks old) were randomly divided into two groups. The control group was fed a basal diet only, and the test group was fed basal diet supplemented with a final concentration of 1.0 × 10 9 CFU/mL during the 10-week experimental period. Egg production and fecal microbiota composition were both assessed in 28-week-old hens using high-throughput sequencing technology. The results showed that, compared with the control group, the test group exhibited increased laying and feed intake rates ( p < 0.05). At the genus level, Lactobacillus was more abundant in the test group compared with the control group ( p < 0.05). Conversely, Romboutsia was more abundant in the control group compared with the test group ( p < 0.05). This study provides us with an insight into the potential use of L. plantarum as a food supplement in the laying hen industry. the study also provides us with a better understanding of the interplay between L. plantarum and the fecal microbiota of laying hens., Competing Interests: Conflict of interest Authors state no conflict of interest, (© 2019 Hongxing Qiao et al., published by De Gruyter.)

The immune inflammatory response plays a crucial role in many cardiac pathophysiological processes, including ischaemic cardiac injury and the post-infarction repair process. MicroRNAs (miRNAs) regulate the development and function of dendritic cells (DCs), which are key players in the initiation and regulation of immune responses; however, the underlying regulatory mechanisms remain unclear. Here, we used the supernatants of necrotic primary cardiomyocytes (Necrotic-S) to mimic the myocardial infarction (MI) microenvironment to investigate the role of miRNAs in the regulation of DC-mediated inflammatory responses. Our results showed that Necrotic-S up-regulated the DC maturation markers CD40, CD83 and CD86 and increased the production of inflammatory cytokines, concomitant with the up-regulation of miR-181a and down-regulation of miR-150. Necrotic-S stimulation activated the JAK/STAT pathway and promoted the nuclear translocation of c-Fos and NF-κB p65, and silencing of STAT1 or c-Fos suppressed Necrotic-S-induced DC maturation and inflammatory cytokine production. The effects of Necrotic-S on DC maturation and inflammatory responses, its activation of the JAK/STAT pathway and the induction of cardiomyocyte apoptosis under conditions of hypoxia were suppressed by miR-181a or miR-150 overexpression. Taken together, these data indicate that miR-181a and miR-150 attenuate DC immune inflammatory responses via JAK1-STAT1/c-Fos signalling and protect cardiomyocytes from cell death under conditions of hypoxia., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aims: Inflammation plays an important role in the neointima formation of grafted veins. However, the initiation of inflammation in grafted veins is still unclear. Here, we investigated the role and underlying mechanism of an innate immunity signalling protein, caspase-associated recruitment domain 9 (CARD9) in vein grafts in mice., Methods and Results: In early murine vein grafts, we observed robust death of smooth muscle cells (SMCs), which was accompanied by infiltration of macrophages and expression of pro-inflammatory cytokines. Meanwhile, SMC necrosis was associated with the expression of pro-inflammatory cytokines in macrophages in vitro. To explore the mediators of necrotic SMC-induced inflammation in grafted veins from mice, we examined the expression of CARD family proteins and found CARD9 highly expressed in infiltrated macrophages of grafted veins. CARD9-knockout (KO) inhibited necrotic SMC-induced pro-inflammatory cytokine expression and NF-κB activation. Furthermore, CARD9-KO suppressed necrotic SMC-induced expression of VEGF in macrophages. Finally, CARD9-KO decreased neointima formation of grafted veins in mice., Conclusion: The innate immune protein CARD9 in macrophages may mediate necrotic SMC-induced inflammation by activating NF-κB and contributed to neointima formation in the vein grafts., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Sustained inflammation is associated with pulmonary vascular remodeling and arterial hypertension (PAH). Serum-glucocorticoid regulated kinase 1 (SGK1) has been shown to participate in vascular remodeling, but its role in inflammation-associated PAH remains unknown. In this study, the importance of SGK1 expression and activation was investigated on monocrotaline (MCT)-induced PAH, an inflammation-associated experimental model of PAH used in mice and rats. The expression of SGK1 in the lungs of rats with MCT-induced PAH was significantly increased. Furthermore, SGK1 knockout mice were resistant to MCT-induced PAH and showed less elevation of right ventricular systolic pressure and right ventricular hypertrophy and showed reduced pulmonary vascular remodeling in response to MCT injection. Administering the SGK1 inhibitor, EMD638683, to rats also prevented the development of MCT-induced PAH. The expression of SGK1 was shown to take place primarily in alveolar macrophages. EMD638683 treatment suppressed macrophage infiltration and inhibited the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in the lungs of rats with MCT-induced PAH. Co-culture of bone marrow-derived macrophages (BMDMs) from wild-type (WT) mice promoted proliferation of PASMC in vitro, whereas BMDMs from either SGK1 knockout mice or WT mice with EMD638683 treatment failed to induce this response. Collectively, the present results demonstrated that SGK1 is important to the regulation of macrophage activation that contributes to the development of PAH; thus, SGK1 may be a potential therapeutic target for the treatment of PAH.

The formation of penniform BaWO4 nanostructures made of nanowires or nanobelts under the direction of a block copolymer in catanionic reverse micelles has been studied in detail. On the basis of the experimental results obtained from the BaWO4 crystallization in aqueous polymer solutions and careful transmission electron microscopy (TEM) observations of BaWO4 nanostructures formed in reverse micelles containing polymers, a detailed two-stage growth mechanism has been proposed for the formation of the penniform nanostructures in reverse micelles, which involves the polymer-controlled shaft formation (Stage 1) and the mixed surfactants-controlled barb growth (Stage 2). During Stage 1, poly(ethylene glycol)-block-poly(methacrylic acid) (PEG-b-PMAA) induced the formation of c-axis-oriented shuttle-like nanocrystals and the subsequent oriented attachment of these shuttle-like nanocrystals resulted in the formation of [100]-oriented shafts with many parallel [001]-oriented pricks. During Stage 2, [001]-oriented nanowires or nanobelts grew gradually from the pricks into barbs, leading to the formation of well-defined penniform BaWO4 nanostructures with the barb morphology essentially determined by the mixing ratio r of the anionic to cationic surfactants (i.e., nanowires were formed at r=1 while nanobelts were formed at r deviating from 1). The current understanding of the growth mechanism of penniform BaWO4 nanostructures in catanionic reverse micelles involving polymers may be potentially applied for designing a new synthesis system for the controlled synthesis of other hierarchical 1D nanostructures with desired architectures.