scholarly journals Identification of cell cycle as the critical pathway modulated by exosome-derived microRNAs in gallbladder carcinoma

2021 ◽  
Vol 38 (12) ◽  
Author(s):  
Li Su ◽  
Jicheng Zhang ◽  
Xinglong Zhang ◽  
Lei Zheng ◽  
Zhifa Zhu
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Cell Cycle Checkpoints ◽  
Gene Set Enrichment Analysis ◽  
Clinical Samples ◽  
Critical Pathway ◽  
Cerna Network

AbstractGallbladder cancer (GBC), the most common malignancy in the biliary tract, is highly lethal malignant due to seldomly specific symptoms in the early stage of GBC. This study aimed to identify exosome-derived miRNAs mediated competing endogenous RNAs (ceRNA) participant in GBC tumorigenesis. A total of 159 differentially expressed miRNAs (DEMs) was identified as exosome-derived miRNAs, contains 34 upregulated exo-DEMs and 125 downregulated exo-DEMs based on the expression profiles in GBC clinical samples downloaded from the Gene Expression Omnibus database with the R package. Among them, 2 up-regulated exo-DEMs, hsa-miR-125a-3p and hsa-miR-4647, and 5 down-regulated exo-DEMs, including hsa-miR-29c-5p, hsa-miR-145a-5p, hsa-miR-192-5p, hsa-miR-194-5p, and hsa-miR-338-3p, were associated with the survival of GBC patients. Results of the gene set enrichment analysis showed that the cell cycle-related pathways were activated in GBC tumor tissues, mainly including cell cycle, M phase, and cell cycle checkpoints. Furthermore, the dysregulated ceRNA network was constructed based on the lncRNA-miRNA-mRNA interactions using miRDB, TargetScan, miRTarBase, miRcode, and starBase v2.0., consisting of 27 lncRNAs, 6 prognostic exo-DEMs, and 176 mRNAs. Together with prognostic exo-DEMs, the STEAP3-AS1/hsa-miR-192-5p/MAD2L1 axis was identified, suggesting lncRNA STEAP3-AS1, might as a sponge of exosome-derived hsa-miR-192-5p, modulates cell cycle progression via affecting MAD2L1 expression in GBC tumorigenesis. In addition, the biological functions of genes in the ceRNA network were also annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Our study promotes exploration of the molecular mechanisms associated with tumorigenesis and provide potential targets for GBC diagnosis and treatment.

The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation

2021 ◽  
Author(s):  
Shan Yang ◽  
Wei Gao ◽  
Haoqi Wang ◽  
Xi Zhang ◽  
Yunzhe Mi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Clinical Samples

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

scholarly journals Identification of IL10RA by Weighted Correlation Network Analysis and in vitro Validation of Its Association With Prognosis of Metastatic Melanoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Si Cheng ◽  
Zhe Li ◽  
Wenhao Zhang ◽  
Zhiqiang Sun ◽  
Zhigang Fan ◽  
...  
Keyword(s):  
Network Analysis ◽  
Metastatic Melanoma ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion

Skin cutaneous melanoma (SKCM) is the major cause of death for skin cancer patients, its high metastasis often leads to poor prognosis of patients with malignant melanoma. However, the molecular mechanisms underlying metastatic melanoma remain to be elucidated. In this study we aim to identify and validate prognostic biomarkers associated with metastatic melanoma. We first construct a co-expression network using large-scale public gene expression profiles from GEO, from which candidate genes are screened out using weighted gene co-expression network analysis (WGCNA). A total of eight modules are established via the average linkage hierarchical clustering, and 111 hub genes are identified from the clinically significant modules. Next, two other datasets from GEO and TCGA are used for further screening of biomarker genes related to prognosis of metastatic melanoma, and identified 11 key genes via survival analysis. We find that IL10RA has the highest correlation with clinically important modules among all identified biomarker genes. Further in vitro biochemical experiments, including CCK8 assays, wound-healing assays and transwell assays, have verified that IL10RA can significantly inhibit the proliferation, migration and invasion of melanoma cells. Furthermore, gene set enrichment analysis shows that PI3K-AKT signaling pathway is significantly enriched in metastatic melanoma with highly expressed IL10RA, indicating that IL10RA mediates in metastatic melanoma via PI3K-AKT pathway.

scholarly journals Gene expression profiles of inflammatory breast cancer reveal high heterogeneity across the epithelial-hybrid-mesenchymal spectrum

2020 ◽  
Author(s):  
Priyanka Chakraborty ◽  
Jason T George ◽  
Wendy A Woodward ◽  
Herbert Levine ◽  
Mohit Kumar Jolly
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Inflammatory Breast Cancer ◽  
Predictive Accuracy ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Clinical Samples ◽  
Intratumor Heterogeneity ◽  
Training Algorithms

AbstractInflammatory breast cancer (IBC) is a highly aggressive breast cancer that metastasizes largely via tumor emboli, and has a 5-year survival rate of less than 30%. No unique genomic signature has yet been identified for IBC nor has any specific molecular therapeutic been developed to manage the disease. Thus, identifying gene expression signatures specific to IBC remains crucial. Here, we compare various gene lists that have been proposed as molecular footprints of IBC using different clinical samples as training and validation sets and using independent training algorithms, and determine their accuracy in identifying IBC samples in three independent datasets. We show that these gene lists have little to no mutual overlap, and have limited predictive accuracy in identifying IBC samples. Despite this inconsistency, single-sample gene set enrichment analysis (ssGSEA) of IBC samples correlate with their position on the epithelial-hybrid-mesenchymal spectrum. This positioning, together with ssGSEA scores, improves the accuracy of IBC identification across the three independent datasets. Finally, we observed that IBC samples robustly displayed a higher coefficient of variation in terms of EMT scores, as compared to non-IBC samples. Pending verification that this patient-to-patient variability extends to intratumor heterogeneity within a single patient, these results suggest that higher heterogeneity along the epithelial-hybrid-mesenchymal spectrum can be regarded to be a hallmark of IBC and a possibly useful biomarker.

scholarly journals Combined Analysis of ceRNA Regulatory Network and DNA Methylation in CAD

2021 ◽  
Author(s):  
Yue Zhao ◽  
Chen Wang ◽  
Wangxia Li ◽  
Bingyu Jin ◽  
Yang Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Gene Expressions ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Differentially Methylated Genes

Abstract BackgroundThe mobidity and mortality of coronary artery disease (CAD) is increasing year by year. Hence it is urgent to probe into the molecular mechanism of CAD and seek new therapeutic strategies. The purpose of our study was to screen genes associated with the development of CAD by using bioinformatics tools and clinical samples. MethodsMicroarray datasets from the Gene Expression Omnibus (GEO) database of peripheral blood cells (PBLs) were chosen for this study, and candidate differentially expressed microRNAs (DEMs) were screened using the limma and weighted co-expression network analysis (WGCNA) packages in R (v4.0). Subsequently, we construct a competitive endogenous RNAs (ceRNA) network and perform enrichment analysis of genes in the network. Meanwhile, differentially methylated genes (DMGs) in PBLs were identified using the "ChAMP" package in a DNA methylation chip. We then constructed the methylation-associated ceRNA network in CAD. Eventually, the methylation levels of genes and the relationship with the expression of genes in ceRNA were validated in PBLs samples using the Illumina Methylation 850K chip and transcriptome sequencing, while gene expressions were verified by qRT-PCR. And the regulation of DNA methylation on gene expression was verified in the THP-1 cells treated with 5-Aza-2'-deoxycytidine (5-AZA). ResultsA total of 71 differentially expressed miRNAs were screened by both WGCNA and limma. Then the ceRNA network in CAD was constructed with 269 nodes and 705 edges, which were significantly enriched in the chemokine-mediated signaling pathway and so on. Furthermore, from 4354 identified DMGs in a methylation data, 34 methylation-associated differentially expressed genes (DEGs) and 1 differentially expressed lncRNA (DEL) were obtained. After verification of methylation experiments in study population A, three genes were found to have altered methylation consistent with the bioinformatics results. And these genes were correlated in terms of methylation and expression levels. Corresponding with the bioinformatics results, qRT-PCR results in validation set B also showed that the expression of AGPAT4 and FAM169A were significantly lower in CAD. In addition, 5-AZA treatment could increase the expression of AGPAT4 and FAM169A in THP-1 cells. ConclusionsOur study deepens the understanding of the molecular mechanisms underlying the pathogenesis of CAD and provides new ideas for its treatment.

scholarly journals Alterations in the host transcriptome in vitro and in vivo following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

2020 ◽  
Author(s):  
Xiaomei Lei ◽  
Zhijun Feng ◽  
Xiaojun Wang ◽  
Xiaodong He
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Microarray Data ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set ◽  
Gene Sets ◽  
Core Genes

Abstract Background. Exploring alterations in the host transcriptome following SARS-CoV-2 infection is not only highly warranted to help us understand molecular mechanisms of the disease, but also provide new prospective for screening effective antiviral drugs, finding new therapeutic targets, and evaluating the risk of systemic inflammatory response syndrome (SIRS) early.Methods. We downloaded three gene expression matrix files from the Gene Expression Omnibus (GEO) database, and extracted the gene expression data of the SARS-CoV-2 infection and non-infection in human samples and different cell line samples, and then performed gene set enrichment analysis (GSEA), respectively. Thereafter, we integrated the results of GSEA and obtained co-enriched gene sets and co-core genes in three various microarray data. Finally, we also constructed a protein-protein interaction (PPI) network and molecular modules for co-core genes and performed Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for the genes from modules to clarify their possible biological processes and underlying signaling pathway. Results. A total of 11 co-enriched gene sets were identified from the three various microarray data. Among them, 10 gene sets were activated, and involved in immune response and inflammatory reaction. 1 gene set was suppressed, and participated in cell cycle. The analysis of molecular modules showed that 2 modules might play a vital role in the pathogenic process of SARS-CoV-2 infection. The KEGG enrichment analysis showed that genes from module one enriched in signaling pathways related to inflammation, but genes from module two enriched in signaling of cell cycle and DNA replication. Particularly, necroptosis signaling, a newly identified type of programmed cell death that differed from apoptosis, was also determined in our findings. Additionally, for patients with SARS-CoV-2 infection, genes from module one showed a relatively high-level expression while genes from module two showed low-level. Conclusions. We identified two molecular modules were used to assess severity and predict the prognosis of the patients with SARS-CoV-2 infection. In addition, these results provide a unique opportunity to explore more molecular pathways as new potential targets on therapy in COVID 19.

scholarly journals Bioinformatic Analysis of Gene Expression Profile in Plasma of Hypertensive Patients

2020 ◽  
Vol 33 (6) ◽  
pp. 581-581
Author(s):  
Yan-zhen Li ◽  
Hao-jie Xu ◽  
Jia-min Hu ◽  
Shi-zhu Lin ◽  
Na Zhang ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Interventions ◽  
Total Rna ◽  
Hormone Synthesis ◽  
Public Data

Abstract Background To analyze expression profiles of long noncoding RNA (lncRNA) and messenger RNA (mRNA) in patients with essential hypertension (EH) and normotensive adults. Methods The gene chip dataset GSE76845, which was generated from 5 plasma samples from patients with EH and 5 normotensives, was downloaded from the National Biotechnology Information Center Public Data Platform. Each sample (total RNA) was pooled from the total RNA of 3 age- and gender-matched subjects (EH patients or healthy controls). A ClusterProfiler package including gene set enrichment analysis (GSEA) was used to identify differentially expressed genes. The target microRNA and mRNA were predicted by microcode, microDB, microTarBase, and TargetScan databases. Finally, a competing endogenous RNAs (ceRNA) regulatory network was constructed. Results Compared with the healthy control adults, 191 differential lncRNAs (90 upregulated and 101 downregulated) and 1,187 differential mRNAs (533 upregulated and 654 downregulated) were identified in EH patients. GSEA analysis showed that 17 pathways, including ubiquinone and terpenoid-quinone biosynthesis, parathyroid hormone synthesis secretion and action, fatty acid metabolism, and steroid hormone biosynthesis are involved in hypertension. A ceRNA network consisting of 150 nodes and 488 interactive pairs was constructed. Conclusions lncRNA and mRNA profile analysis provides new insight into molecular mechanisms of EH pathogenesis and potential targets for therapeutic interventions.

scholarly journals Host transcriptome alterations in vitro and in vivo following severe acute respiratory syndrome coronavirus 2 infection

2021 ◽  
Author(s):  
Yannian Luo ◽  
Juan Xu ◽  
Mingzhen Zhou ◽  
Xiaomei Lei ◽  
Wen Cao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Microarray Data ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set ◽  
Gene Sets ◽  
Core Genes

Abstract Background. Exploring alterations in the host transcriptome following SARS-CoV-2 infection is not only highly warranted to help us understand molecular mechanisms of the disease, but also provide new prospective for screening effective antiviral drugs, finding new therapeutic targets, and evaluating the risk of systemic inflammatory response syndrome (SIRS) early.Methods. We downloaded three gene expression matrix files from the Gene Expression Omnibus (GEO) database, and extracted the gene expression data of the SARS-CoV-2 infection and non-infection in human samples and different cell line samples, and then performed gene set enrichment analysis (GSEA), respectively. Thereafter, we integrated the results of GSEA and obtained co-enriched gene sets and co-core genes in three various microarray data. Finally, we also constructed a protein-protein interaction (PPI) network and molecular modules for co-core genes and performed Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for the genes from modules to clarify their possible biological processes and underlying signaling pathway. Results. A total of 11 co-enriched gene sets were identified from the three various microarray data. Among them, 10 gene sets were activated, and involved in immune response and inflammatory reaction. 1 gene set was suppressed, and participated in cell cycle. The analysis of molecular modules showed that 2 modules might play a vital role in the pathogenic process of SARS-CoV-2 infection. The KEGG enrichment analysis showed that genes from module one enriched in signaling pathways related to inflammation, but genes from module two enriched in signaling of cell cycle and DNA replication. Particularly, necroptosis signaling, a newly identified type of programmed cell death that differed from apoptosis, was also determined in our findings. Additionally, for patients with SARS-CoV-2 infection, genes from module one showed a relatively high-level expression while genes from module two showed low-level. Conclusions. We identified two molecular modules were used to assess severity and predict the prognosis of the patients with SARS-CoV-2 infection. In addition, these results provide a unique opportunity to explore more molecular pathways as new potential targets on therapy in COVID 19.

scholarly journals Intrinsic Activation of β-catenin Signaling by CRISPR/Cas9-mediated Exon Skipping Contributes to Immune Evasion in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Masafumi Akasu ◽  
Shu Shimada ◽  
Ayano Kabashima ◽  
Yoshimitsu Akiyama ◽  
Masahiro Shimokawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Clinical Samples ◽  
Engineering System ◽  
Human And Mouse ◽  
Hcc Cells

Abstract Comprehensive analysis of clinical samples has recently identified molecular and immunological classification of hepatocellular carcinoma (HCC), and the CTNNB1 (β-catenin)-mutated subtype exhibits distinctive characteristics of immunosuppressive tumor microenvironment. For clarifying the molecular mechanisms, we first established human and mouse HCC cells with exon 3 skipping of β-catenin, which promoted nuclear translocation and activated the Wnt/β-catenin signaling pathway, by using newly developed multiplex CRISPR/Cas9-based genome engineering system. Gene set enrichment analysis indicated downregulation of immune-associated gene sets in the HCC cells with activated β-catenin signaling. T cell killing assays demonstrated that the mouse Ctnnb1Δex3 HCC cells evaded immune surveillance. Comparative analysis of gene expression profiles between HCC cells harboring wild-type and exon 3 skipping β-catenin elucidated that the expression levels of eight cytokines were commonly decreased in human and mouse β-catenin-mutated HCC cells. Public exome and transcriptome data of 373 human HCC samples showed significant downregulation of five candidate cytokine genes, CCL20, CXCL1, CXCL2, NAMPT and VEGFA, in HCC tumors with β-catenin hotspot mutations. Taken together, this study discovered that cytokine controlled by β-catenin signaling activation could contribute to immune evasion, and provided novel insights into cancer immunotherapy for the β-catenin-mutated HCC subtype.

scholarly journals Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

2021 ◽  
Vol 9 ◽  
Author(s):  
Shengnan Cong ◽  
Jinlong Li ◽  
Jingjing Zhang ◽  
Jingyi Feng ◽  
Aixia Zhang ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Control Group ◽  
Sodium Reabsorption ◽  
Cerna Network ◽  
Reporter Assays

Lubrication disorder is a common health issue that manifests as insufficient sexual arousal at the beginning of sex. It often causes physical and psychological distress. However, there are few studies on lubrication disorder, and the complexity of circular RNA (circRNA) and the related competing endogenous RNA (ceRNA) network in lubrication disorder is still poorly known. Therefore, this study aims to build a regulatory circRNA-micro (mi)RNA-mRNA network and explore potential molecular markers of lubrication disorder. In the study, 12 subjects were recruited, including 6 in the lubrication disorder group and 6 in the normal control group. RNA sequencing was exploited to identify the expression profiles of circRNA, miRNA and mRNA between two groups, and then to construct the circRNA-miRNA-mRNA networks. The enrichment analyses of the differentially expressed (DE)-mRNAs were examined via Gene Set Enrichment Analysis (GSEA). Furthermore, the expression level and interactions among circRNA, miRNA, and mRNA were validated using real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assays. In the results, 73 circRNAs, 287 miRNAs, and 354 target mRNAs were differentially expressed between two groups when taking | Log2 (fold change)| > 1 and P-value < 0.05 as criteria, and then the results of GSEA revealed that DE-mRNAs were linked with “vascular smooth muscle contraction,” “aldosterone regulated sodium reabsorption,” “calcium signaling pathway,” etc. 19 target relationships among 5 circRNAs, 4 miRNAs, and 7 mRNAs were found and constructed the ceRNA network. Among them, hsa-miR-212-5p and hsa-miR-874-3p were demonstrated to be related to the occurrence of lubrication disorder. Eventually, consistent with sequencing, RT-qPCR showed that hsa_circ_0026782 and ASB2 were upregulated while hsa-miR-874-3p was downregulated, and dual-luciferase reporter assays confirmed the interactions among them. In summary, the findings indicate that the circRNA-miRNA-mRNA regulatory network is presented in lubrication disorder, and ulteriorly provide a deeper understanding of the specific regulatory mechanism of lubrication disorder from the perspective of the circRNA-miRNA-mRNA network.

scholarly journals Predictive Value of CCNB1, BUB1B and TTK in the Progression and Prognosis of Lung Adenocarcinoma

2020 ◽  
Author(s):  
Lecai Xiong ◽  
Yuquan Bai ◽  
Minglin Zhu ◽  
Zetian Yang ◽  
Jinping Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Lung Cancer Patients

Lung cancer predominates in cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) being a common histological subtype of lung cancer. The aim at this study was to search for biomarkers associated with the progression and prognosis of LUAD. We have integrated the expression profiles of 1174 lung cancer patients from five GEO datasets (GSE18842, GSE19804, GSE30219, GSE40791 and GSE68465) and identified a set of differentially expressed genes. Functional enrichment analysis showed that these genes are closely related to the progression of LUAD, such as cell cycle, mitosis and adhesion. Cytoscape software was used to establish a protein-protein interaction (PPI) network to analyze important modules using Molecular Complex Detection (MCODE), and finally CCNB1, BUB1B and TTK were selected for further study. The study found that compared with non-tumor lung tissue, CCNB1, BUB1B and TTK are highly expressed in LUAD. Kaplan-Meier analysis showed that CCNB1, BUB1B and TTK were negatively correlated with the overall survival and disease-free survival of patients. Gene set enrichment analysis (GSEA) demonstrated that for the samples of any hub gene highly expressed, most of the functional gene sets enriched in cell cycle. In summary, CCNB1, BUB1B and TTK can be used as biomarkers of poor prognosis of LUAD. The high expression of CCNB1, BUB1B and TTK can accelerate the progression of LUAD and lead to shorter survival, suggesting that they may be potential targets for treatment in LUAD.

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