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BACKGROUND: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. METHODS: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. RESULTS: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. CONCLUSIONS: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.
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PURPOSE: Previous studies have demonstrated that early adolescents residing in chaotic households experience adverse health and well-being outcomes. However, the potential protective factors that mitigate the relationship between household chaos and early adolescents' health and well-being remain unknown. Accordingly, this study aims to investigate whether perceived social support moderates the link between household chaos and the health and well-being among Chinese rural early adolescents. METHODS: Physical health difficulties were assessed using two measures: general health and allostatic load (AL). Mental health difficulties were measured by depression. Well-being was reflected by life satisfaction. Specifically, this study included early adolescents (N = 337; Mage = 10.88 ± 1.36 years) from rural counties in China who reported their household chaos, perceived social support, general health, depression, and life satisfaction. AL scores were determined based on six physiological indices. RESULTS: Household chaos exhibited a negative relationship with the general health and life satisfaction while a positive correlation with depression. Moreover, perceived social support was found to moderate the association between household chaos and these health and well-being indicators of early adolescents. Specifically, early adolescents who reported higher levels of perceived social support exhibited weaker negative connections among household chaos and their general health, depression, and life satisfaction. Furthermore, no significant relationships were observed between the adolescents' AL and household chaos, perceived social support, or their interactions. CONCLUSIONS: Household chaos poses a significant risk to health and well-being. Furthermore, the findings indicate that perceived social support can mitigate these negative effects.
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Características da Família , População Rural , Apoio Social , Adolescente , Criança , Humanos , ChinaRESUMO
PURPOSE: This study aims to combine deep learning features with radiomics features for the computer-assisted preoperative assessment of meningioma consistency. METHODS: 202 patients with surgery and pathological diagnosis of meningiomas at our institution between December 2016 and December 2018 were retrospectively included in the study. The T2-fluid attenuated inversion recovery (T2-Flair) images were evaluated to classify meningioma as soft or hard by professional neurosurgeons based on Zada's consistency grading system. All the patients were split randomly into a training cohort (n = 162) and a testing cohort (n = 40). A convolutional neural network (CNN) model was proposed to extract deep learning features. These deep learning features were combined with radiomics features. After multiple feature selections, selected features were used to construct classification models using four classifiers. AUC was used to evaluate the performance of each classifier. A signature was further constructed by using the least absolute shrinkage and selection operator (LASSO). A nomogram based on the signature was created for predicting meningioma consistency. RESULTS: The logistic regression classifier constructed using 17 radiomics features and 9 deep learning features provided the best performance with a precision of 0.855, a recall of 0.854, an F1-score of 0.852 and an AUC of 0.943 (95 % CI, 0.873-1.000) in the testing cohort. The C-index of the nomogram was 0.822 (95 % CI, 0.758-0.885) in the training cohort and 0.943 (95 % CI, 0.873-1.000) in the testing cohort with good calibration. Decision curve analysis further confirmed the clinical usefulness of the nomogram for predicting meningioma consistency. CONCLUSIONS: The proposed method for assessing meningioma consistency based on the fusion of deep learning features and radiomics features is potentially clinically valuable. It can be used to assist physicians in the preoperative determination of tumor consistency.
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Aprendizado Profundo , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Radiômica , Estudos Retrospectivos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgiaRESUMO
Household income predicts early adolescents' cognitive development. However, the mechanism underlying this association and protective factors are unclear. This study assessed one-year longitudinal data to examine whether perceived discrimination mediated the association between household income and executive function and the moderating role of shift-and-persist. 344 early adolescents in rural China were included in the study (mean = 10.88 years, SD = 1.32 years, girls: 51.74%). The latent variable model revealed that household income predicted early adolescents' cognitive flexibility and working memory in the subsequent year through perceived discrimination. Shift-and-persist moderated the negative effects of perceived discrimination on cognitive flexibility: perceived discrimination impeded cognitive flexibility only among early adolescents with low shift-and-persist. The findings highlight perceived discrimination in the relation between household income and early adolescents' executive function and underscore the protective role of shift-and-persist.
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Função Executiva , Discriminação Percebida , Feminino , Humanos , Adolescente , Cognição , Memória de Curto Prazo , ChinaRESUMO
This paper rationally designs the morphology and phase structure of carbon nanotube/polyaniline@MoS2 (CNT/PANI@MoS2) composites, with MoS2 conductive wrapping growing vertically on the outer layer of the composites via hydrothermal method. The crystalline nature and chemical properties are characterized by X-ray diffraction (XRD), Flourier transformation infrared spectroscopy (FT-IR), Raman spectroscopy (Raman), X-ray photoelectron spectroscopy (XPS). Morphology and microstructures are determined by Scanning electric microscopy (SEM), Transmission electron microscope (TEM) and Brunauer-Emmett-Teller (BET). The developed composites possess excellent electrochemical properties (the specific capacitance is substantially increased by ~119%, reaching 700.0 F g-1 after wrapping by MoS2) and good cycling stability (after over 5000 cycles retains 80.8% capacitance) in three-electrode systems, which indicating that the unique morphology of MoS2 shells endow the channels to composites for rapid charge transport and ionic diffusion. Furthermore, symmetric supercapacitors devices assembled with the CNT/PANI@MoS2 composites achieve specific capacitance of 459.7 F g-1 at 1 A g-1, capacitance retention is 97.4% after 10,000 cycles and reach superior energy density of 40.9 Wh kg-1 at the power density of 400 W kg-1. This strategy of three-dimensional wrapping method may open up a new potential to relieve the dilemma of degraded performance of supercapacitor, while improving the capacitance and stability for supercapacitors.
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The aim of the present study was to investigate the acute effect and mechanism of tumor necrosis factor (TNF) on basolateral 50 pS K channels in the thick ascending limb (TAL) of the rat kidney. The TAL tubules were isolated from the rat kidney, and the activity of the 50 pS K channels was recorded using the patchclamp technique. The results indicated that the application of TNF (10 nM) significantly activated the 50 pS K channels and the TNF effect was concentrationdependent. Inhibition of protein kinase A, phospholipase A2 and protein tyrosine kinase using pathway inhibitors (H89, AACOCF3 and Herbimycin A, respectively) did not abolish the stimulatory effect of TNF, indicating that none of these pathways mediated the TNF effect. By contrast, the phenylarsine oxide inhibitor against protein tyrosine phosphatase (PTP) decreased the activity of the 50 pS K channels and blocked the stimulatory effect of TNF on these channels. Furthermore, western blot analysis demonstrated that the application of TNF (10 nM) in the TAL increased the phosphorylation of PTP, an indication of PTP activity stimulation. Thus, it was concluded that the acute application of TNF may stimulate the basolateral 50 pS K channel in the TAL and the stimulatory effect of TNF may be mediated by the PTPdependent pathway.