Atherosclerosis (AS) is a chronic inflammatory disease with a significant contributor to mortality worldwide. Regulatory T cells (Tregs) are atheroprotective. However, the potential pathways and genes associated with atherosclerotic plaque progression in Tregs remain largely unknown. Therefore, this study aimed to identify critical target genes and pathways of Tregs associated with the progression of AS. The gene expression data and single cell RNA-seq data of AS were downloaded from the Gene Expression Omnibus (GEO) database. Initially, we quantified CD4+ T cell proportions in non-plaque and plaque tissues using cell infiltration by estimation of RNA sequences (CIBERSORT) analysis, identifying pivotal transcription factors regulating the number of Tregs in atherosclerotic plaque. Subsequently, we identified significantly differential expressed genes of Tregs during the progression of atherosclerotic plaque and investigated the key pathways and transcription factors for these differentially expressed genes using gene ontology (GO) analysis and transcription factor enrichment analysis (TFEA), respectively. We also employed high dimensional weighted gene co-expression network analysis (hdWGCNA) and cell-cell communication analysis to elucidate the modules and cascade reaction of Tregs in the progression of AS. The key genes diagnostic potential was assessed via receiver operating characteristic (ROC) curve analysis. Finally, the target genes were validated in AS model using Ldlr-/- mice. We found that the proportion of Tregs significantly decreased, and Th2 cells showed a significant increase in atherosclerotic plaque compared to that in non-plaque arterial tissues. The five transcription factors (TEFC, IRF8, ZNF267, KLF2, and JUNB), identified as key targets associated with the function and the number of Tregs driving the progression of AS, primarily regulate immune response, ubiquitination, cytokine production, and T-cell differentiation pathways. ZNF267 may mainly involve in regulating ubiquitination, TGF-beta, and MAPK pathways of Tregs to regulate the function and the number of Tregs during the progress of AS. Interestingly, we found that IRF8 and ZNF267 as potential biomarkers were upregulated in circulating CD4+ T cells in patients with atherosclerotic coronary artery disease. Moreover, we also found that the changes of the function and the number of Tregs could modulate endothelial cell and smooth muscle cell functions to counteract AS through ligand-receptor pairs such as the MIF signaling pathway. Finally, we validated that two of the five transcription factors were also upregulated in mice atherosclerotic plaque through AS model using Ldlr-/- mice. Our results indicate that the transcription factors TEFC, IRF8, ZNF267, KLF2, and JUNB in Tregs could be potential targets for the clinical management of AS.
Cancer poses a significant public health challenge worldwide, and timely screening has the potential to mitigate cancer progression and reduce mortality rates. Currently, early identification of most tumors relies on imaging techniques and tissue biopsies. However, the use of low-cost, highly sensitive, non-invasive detection methods for early cancer screening has become more attractive. Extracellular Vesicles (EVs) released by all living cells contain distinctive biological components, such as nucleic acids, proteins, and lipids. These vesicles play crucial roles in the tumor microenvironment and intercellular communication during tumor progression, rendering liquid biopsy a particularly suitable method for diagnosis. Nevertheless, challenges related to purification methods and validation of efficacy currently hinder its widespread clinical implementation. These limitations underscore the importance of refining isolation techniques and conducting comprehensive investigations on EVs. This study seeks to evaluate the potential of liquid biopsy utilizing blood-derived EVs as a practical, cost-effective, and secure approach for early cancer detection.
Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model.The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT.In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection.NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.
Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. In recent decades, zebrafish has entered the field of CVD as an important model organism. HEG1, a heart development protein with EGF like domains 1, plays important roles in the development of vertebrate cardiovascular system. Loss of HEG1 will affect the stabilization of vascular endothelial cell connection and eventually lead to dilated cardiomyopathy (DCM). Here, we generated a heg1-specific knockout zebrafish line using CRISPR/Cas9 technology. Zebrafish heg1 mutant demonstrated severe cardiovascular malformations, including atrial ventricular enlargement, heart rate slowing, venous thrombosis and slow blood flow, which were similar to human heart failure and thrombosis phenotype. In addition, the expression of zebrafish cardiac and vascular markers was abnormal in heg1 mutants. In order to apply zebrafish heg1 mutant in cardiovascular drug screening, four Traditional Chinese Medicine (TCM) herbs and three Chinese herbal monomers were used to treat heg1 mutant. The pericardial area, the distance between sinus venosus and bulbus arteriosus (SV-BA), heart rate, red blood cells (RBCs) accumulation in posterior cardinal vein (PCV), and blood circulation in the tail vein were measured to evaluate the therapeutic effects of those drugs on DCM and thrombosis. Here, a new zebrafish model of DCM and thrombosis was established, which was verified to be suitable for drug screening of cardiovascular diseases. It provided an alternative method for traditional in vitro screening, and produced potential clinical related drugs in a rapid and cost-effective way.
In the paper a new method for the license plate character image matching is presented. There are many available methods for image matching, e.g., Hausdorff distance and wavelet transform based matching. We proposed an adaptive weighted Hausdorff (AWHD) distance matching algorithm, the results of our experiment showed that AWHD is time efficient, robust, and high recognition rate method.
Le travail de cette these a ete consacre au developpement d’une nouvelle methode de detection pour un systeme anticollision par la mesure de trajectographie, ce qui pourrait contribuer aux systemes d’aide a la conduite. Pour obtenir une haute probabilite de detection, nous avons choisi la solution de video stereoscopique cooperative : la cooperation entre vehicules rend la detection plus facile et fiable. Il y a deux participants dans le systeme : les vehicules « porteurs du systeme » aussi bien que les « suiveurs », sont equipes de cameras stereoscopiques, c’est a dire de deux capteurs d’image, appartenant a des familles technologique a haute cadence; les vehicules « cibles » sont equipes des feux a Leds modules, dont la frequence de modulation est deja connue par les vehicules « suiveurs ». Apres filtrage dans l’espace temporel, le systeme ne detecte que des signaux issus des feux modules, ce qui reduit fortement l’information a traiter par rapport aux calculs de trajectographie traditionnels. La detection de feux modules est donc realisee par le filtrage par traitement numerique des images, qui est adapte a la frequence de modulation recherchee. Pour cela, nous avons propose 3 types de filtres adaptes a la frequence de modulation et concus de facon a rejeter au mieux les signaux de fond.Pour evaluer les performances tant en detection qu’en rejection des fausses alarmes, nous avons d’abord effectue des simulations numeriques en prenant en compte des signaux artificiels, puis des calculs sur vrais signaux obtenus dans les experimentations avec vehicule d’essai statique, puis roulant. Les roulages etaient de differentes vitesses, de 30km/h jusqu’a 100km/h, ce qui nous a permis d’analyser le signal issu du feu ainsi que le comportement de nos filtres a des vitesses angulaires de feu nulles, faibles ou elevees. Le resultat de ces experimentations montre que le filtrage permet de detecter les feux a Leds de type DRL jusqu’a 140m sans aucune fausse detection sur le fond. Ces experimentations sont une etape essentielle pour definir de facon plus precise un tel systeme, en particulier dans le choix du seuil. Nous avons aussi evalue des technologies qui peuvent ameliorer la performance du systeme, mais qui ne sont pas encore pretes a industrialiser. Par exemple, les « retines » artificielles nous permettent d’utiliser les filtres analogiques integres, et ainsi de reduire leurs bandes passantes.
As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions ( p -value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including TRIM73 , FAM150A , EPB41L3 , SIX3 , MIR663 , MAPT , LOC100128977 , and LOC100130148 . In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)