Heat shock factor 1-mediated transcription activation of Omi/HtrA2 induces myocardial mitochondrial apoptosis in the aging heart.

BACKGROUND: Increased cardiac apoptosis is a hallmark of the elderly, which in turn increases the risk for developing cardiac disease. The overexpression of Omi/HtrA2 mRNA and protein contributes to apoptosis in the aged heart. Heat shock factor 1 (HSF1) is a transcription factor that binds to the promoter of Omi/HtrA2 in the aging myocardium. However, whether HSF1 participates in cardiomyocyte apoptosis via transcriptional regulation of Omi/HtrA2 remains unclear. The present study was designed to investigate whether HSF1 plays a role in Omi/HtrA2 transcriptional regulation and myocardial apoptosis. METHODS AND RESULTS: Assessment of the hearts of mice of different ages was performed, which indicated a decrease in cardiac function reserve and an increase in mitochondrial apoptosis. Omi/HtrA2 overexpression in the elderly was negatively correlated with left ventricular function after exercise overload and positively correlated with myocardial Caspase-9 apoptosis. Chromatin immunoprecipitation (ChIP) of aging hearts and plasmid transfection/RNA interference of H9C2 cells revealed that enhancement of HSF1 expression promotes Omi/HtrA2 expression by inducing the promoter activity of Omi/HtrA2 while also increasing mitochondrial apoptosis by upregulating Omi/HtrA2 expression. CONCLUSIONS: HSF1 acts as a transcriptional factor that induces Omi/HtrA2 expression and Caspase-9 apoptosis in aged cardiomyocytes, while also decreasing cardiac function reserve

Analysis of necroptosis-related prognostic genes and immune infiltration in idiopathic pulmonary fibrosis

BackgroundIPF is an undetermined, progressive lung disease. Necroptosis is a type of programmed apoptosis, which involved in the pathogenesis of lung diseases like COPD and ARDS. However, necroptosis in IPF have not been adequately studied. This study aimed to investigate the necroptosis in IPF and the relationship between necroptosis and immune infiltration, to construct a prognostic prediction model of IPF based on necroptosis-related genes.MethodsGSE110147 was downloaded from the GEO database and utilized to analyze the expression of necroptosis-related differentially expressed genes (NRDEGs). Then NRDEGs were used to construct protein-protein interaction (PPI) networks in the STRING database, and Cytoscape software was used to identify and visualize hub genes. Necroptosis-related prognosticgenes were explored in GSE70866, and a prognostic prediction model was constructed. The ImmuCellAI algorithm was utilized to analyze the landscape of immune infiltration in GSE110147. The single-cell RNA sequencing dataset GSE122960 was used to explore the association between necroptosis and type II alveolar epithelial cells (AT II) in IPF. The GSE213001 and GSE93606 were used for external validation. The expression of prognostic genes was quantified using RT-qPCRin the IPF A549 cell model, and was further verified by western blotting in the bleomycin-induced pulmonary fibrosis mouse model.ResultsIt was observed that necroptosis-related signaling pathways were abundantly enriched in IPF. 29 NRDEGs were screened, of which 12 showed consistent expression trends in GSE213001. Spearman correlation analysis showed that the expression of NRDEGs was positively correlated with the infiltration of proinflammatory immune cells, and negatively correlated with the infiltration of anti-inflammatory immune cells. NRDEGs, including MLKL, were highly expressed in AT II of fibrotic lung tissue. A necroptosis-related prediction model was constructed based on 4 NRDEGsby the cox stepwise regression. In the validation dataset GSE93606, the prognostic prediction model showed good applicability. The verification results of RT-qPCR and western blotting showed the reliability of most of the conclusions.ConclusionsThis study revealed that necroptosis existed in IPF and might occur in AT II. Necroptosis was associated with immune infiltration, suggesting that necroptosis of AT II might involve in IPF by activating immune infiltration and immune response

Basic Simulation Environment for Highly Customized Connected and Autonomous Vehicle Kinematic Scenarios

To enhance the reality of Connected and Autonomous Vehicles (CAVs) kinematic simulation scenarios and to guarantee the accuracy and reliability of the verification, a four-layer CAVs kinematic simulation framework, which is composed with road network layer, vehicle operating layer, uncertainties modelling layer and demonstrating layer, is proposed in this paper. Properties of the intersections are defined to describe the road network. A target position based vehicle position updating method is designed to simulate such vehicle behaviors as lane changing and turning. Vehicle kinematic models are implemented to maintain the status of the vehicles when they are moving towards the target position. Priorities for individual vehicle control are authorized for different layers. Operation mechanisms of CAVs uncertainties, which are defined as position error and communication delay in this paper, are implemented in the simulation to enhance the reality of the simulation. A simulation platform is developed based on the proposed methodology. A comparison of simulated and theoretical vehicle delay has been analyzed to prove the validity and the creditability of the platform. The scenario of rear-end collision avoidance is conducted to verify the uncertainties operating mechanisms, and a slot-based intersections (SIs) control strategy is realized and verified in the simulation platform to show the supports of the platform to CAVs kinematic simulation and verification

Enrichment and Purification of Total Ginkgo Flavonoid O-Glycosides from Ginkgo Biloba Extract with Macroporous Resin and Evaluation of Anti-Inflammation Activities In Vitro

In the present study, the performance and separation characteristics of six macroporous resins for the enrichment and purification of total ginkgo flavonoid O-glycosides (TGFs) (quercetin (I), kaempferol (II), isorhamnetin (III)) from Ginkgo Biloba extracts (EGB) are evaluated. The adsorption and desorption properties of TGFs are studied on macroporous resins, including D101, D201, AB-8, HPD400, D301, and D311. Along with the results, AB-8 resin exhibits the best adsorption and desorption capacity for these three ginkgo flavonoid O-glycosides among the six resins. Adsorption isotherms are created on AB-8 resin and fit well to the Langmuir (R2 > 0.96) and Freundlich (R2 > 0.92, 0.3 < 1/n < 0.7) models. After the treatment with gradient elution on AB-8 resin packed chromatography column, the contents of the three main ginkgo flavonoid O-glycosides (I, II, and III) increase from 8.93%, 9.88%, and 6.11% in the extracts to 30.12%, 35.21%, and 14.14%, respectively, in the product. The recoveries of compounds I, II, and III are 88.76%, 93.78%, and 60.90%, respectively. Additionally, the anti-inflammatory effects of TGFs are evaluated in LPS-treated RAW 264.7 macrophages, and the result demonstrates that TGFs could significantly inhibit LPS-induced NO release in vitro in a dose-dependent manner compared with the control group. These findings suggest that TGFs could potentially be natural antioxidants and anti-inflammatory ingredients that could be used in pharmaceutical products and functional food additives

An Improved Frequency-Adaptive Virtual Variable Sampling-Based Repetitive Control for an Active Power Filter

To eliminate the harmonics caused by nonlinear loads, repetitive controllers are widely applied as current controllers for active power filters (APF). In practice, a variation in grid frequency leads to the appearance of a fractional-order delay filter. As a result, the resonant frequency of the repetitive controller will deviate from the fundamental frequency and the controller cannot compensate for harmonics accurately. To solve this problem, an improved frequency-adaptive repetitive controller based on virtual variable sampling (IMFA-VVS-RC) for APF is proposed in this paper. To enhance the system stability margin, the proposed RC introduces an infinite impulse response (IIR) low-pass filter. The proposed RC has a high stability margin at high frequencies due to the low gain of the IIR low-pass filter in the region above the cutoff frequency. In this way, the influence of model uncertainty and parameter uncertainty on system stability are reduced at high frequencies. At the same time, compared with the conventional repetitive controller (CRC), the proposed RC for APF has a better harmonic suppression ability when the frequency varies. Experiments have verified the effectiveness of the scheme adopted for APF

Using Deep Learning to Identify Circulation Patterns of Intense Rainfall in the Beijing–Tianjing–Hebei Region

The properties and distributions of precipitation are often determined by specific synoptic patterns. Hence, the objective identification of corresponding impact patterns is an important field of research for improving rain forecasting. However, the identification of the weather patterns producing intense rainfall is much more challenging. Since they are violent and local, impact patterns tend to be meso- or smaller-scale systems and are often incompletely presented or only presented in limited regions. In this paper, a deep learning network with a feature cross-fusion module, FConvNeXt, was proposed to address this difficulty and showed great potential. Four major patterns corresponding to intense rainfall in the Beijing–Tianjing–Hebei Region were studied. Statistical testing showed that FConvNeXt performed better than ConvNeXt and ResNet and that the model could identify the weak synoptic forcing type, the subtropical high-pressure type, and the low-vortex pattern with high accuracy. Furthermore, a strictly independent 2021 dataset was tested, and FConvNeXt maintained an equal if not even slightly better performance in spite of a decrease in the subtropical high-pressure type. Meanwhile, the study showed that the accuracy in identifying the upper-level trough type is the lowest for the three deep learning methods, which may be because the northeast vortex was intercepted in the limited region, making it difficult to distinguish from the shallow upper-level trough type. This study is useful for improving the fine objective of forecasting intense rainfall

An Improved Frequency-Adaptive Virtual Variable Sampling-Based Repetitive Control for an Active Power Filter

To eliminate the harmonics caused by nonlinear loads, repetitive controllers are widely applied as current controllers for active power filters (APF). In practice, a variation in grid frequency leads to the appearance of a fractional-order delay filter. As a result, the resonant frequency of the repetitive controller will deviate from the fundamental frequency and the controller cannot compensate for harmonics accurately. To solve this problem, an improved frequency-adaptive repetitive controller based on virtual variable sampling (IMFA-VVS-RC) for APF is proposed in this paper. To enhance the system stability margin, the proposed RC introduces an infinite impulse response (IIR) low-pass filter. The proposed RC has a high stability margin at high frequencies due to the low gain of the IIR low-pass filter in the region above the cutoff frequency. In this way, the influence of model uncertainty and parameter uncertainty on system stability are reduced at high frequencies. At the same time, compared with the conventional repetitive controller (CRC), the proposed RC for APF has a better harmonic suppression ability when the frequency varies. Experiments have verified the effectiveness of the scheme adopted for APF

Extraction and biodegradation of ginkgolic acids from Ginkgo biloba sarcotestae

Ginkgolic acids are unwanted constituents in standard Ginkgo biloba leaves extracts. Thus, for the quality control of ginkgo extracts, it is important to establish an effective degradation method, with high catalytic efficiency and safety, to remove ginkgolic acids. Laccases are oxidases with potential for application in elimination of hazardous phenolic compounds. In this study, single-factor and orthogonal experiments were used to optimize extraction of ginkgolic acid from G. biloba sarcotestae. The results showed that ethanol was the best solvent, with the highest extraction rate for ginkgolic acid at 85% ethanol. On this basis, we measured ethanol volume fraction, extraction time, temperature and solid-liquid ratio using an orthogonal experiment. By using absorbance of 310 nm as standard, the optimal extraction conditions were 85% ethanol with, solid-liquid ratio of 1:14 at 40°C for 12 h. These conditions gave a ginkgolic acid yield of 73.1 mg·g−1. Subsequently, recombinant laccase was used to degrade the ginkgolic acid in several laccase/mediator systems, of which LacC was the best. At 50°C, pH 4.5, enzyme concentration of 0.01 U·mL−1, 0.5 mmol·L−1 mediator ABTS and reaction time of 3 h, the degradation rate of ginkgolic acid reached 100%. These results lay the foundation for research on and application of biological enzymes for detoxification of G. biloba extracts

Corticosterone rather than ethanol epigenetic programmed testicular dysplasia caused by prenatal ethanol exposure in male offspring rats

Prenatal ethanol exposure (PEE) could affect offspring’s testicular development. This study aimed to illuminate its intrauterine origin and the programming mechanism caused by PEE. Pregnant Wistar rats were given ethanol (4 g/kg.d) by gavage administration during gestational days (GD) 9–20. Serum samples and testes of male offspring rats were collected on GD20, postnatal week (PW) 6, and PW12. We found that PEE induced testicular morphological abnormality, low serum testosterone levels, expressive suppression of 3β-hydroxysteroid dehydrogenase (3β-HSD), and low acetylation levels of histone 3 lysine 14 (H3K14ac) of 3β-HSD before and after birth. In utero, when fetal rats were overexposed to corticosterone by PEE, the expression levels of testicular glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) were increased, while that of steroidogenic factor 1 (SF1) was decreased. In vitro, corticosterone (rather than ethanol) at 500 to 2,000 nM concentration decreased testosterone production and 3β-HSD expression in a concentration-dependent manner. Moreover, corticosterone downregulated SF1 and upregulated HDAC2 via activating GR, accompanied by a low H3K14ac level of 3β-HSD; SF1 overexpression could reverse the increased HDAC2 expression, and knockdown of HDAC2 could partially reverse the inhibitory effects of corticosterone on H3K14ac level and 3β-HSD expression but not on SF1 expression. Taken together, PEE caused testicular dysplasia in male offspring rats, which was associated with corticosterone-induced low-functional programming of 3β-HSD through the GR/SF1/HDAC2/H3K14ac pathway. This study provides new academic perspectives to illuminate the theory of ‘Developmental Origins of Health and Disease.

Oriented Deep Eutectic Solvents as Efficient Approach for Selective Extraction of Bioactive Saponins from Husks of <i>Xanthoceras sorbifolia</i> Bunge

The husks of Xanthoceras sorbifolia Bunge (X. sorbifolia), as by-products of industrial production, have brought a severe burden to the environment and caused an enormous waste of resources. Bioactive triterpenoid saponins are rich in the husks. To reuse the husks and gain high-quality saponin products, saponin-oriented deep eutectic solvents (DESs), as an efficient and selective extraction strategy from X. sorbifolia husks, were designed for the first time. The enhancement of the extraction rate was investigated by screening solvents from acidic DESs and response surface methodology (RSM) optimization. As a result, the tetrapropylammonium bromide-lactic acid (TPMBr-La) was the most efficient DESs, with an extraction efficiency of up to 135% higher than 70% ethanol. A maximum extraction rate of 72.11 ± 0.61 mg Re/g dw was obtained under the optimized parameters. Scanning electron microscope graphs revealed that damage to the microstructure caused by DESs enhanced the extraction efficiency. Moreover, the recovery of total saponins with D101 macroporous resin was consistent with the pseudo-second-order kinetic model. Seven saponins were also identified by HPLC-MS analysis. Finally, TPMBr-La extracts exhibited 92.30 ± 1.10% DPPH radical scavenging rate at 100 μg/mL, and 92.20 ± 0.30% ABTS radical scavenging rate at 1200 μg/mL. Our current research proposes a selective and high-efficiency substitute for the extraction of saponins and might contribute to further DESs application in the recycling of by-products