Image2_A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy.TIF

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear.Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan–Meier method (univariate Cox regression analysis and Kaplan–Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman’s rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal–Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level.Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman’s rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways.Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.</p

Image3_A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy.TIF

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear.Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan–Meier method (univariate Cox regression analysis and Kaplan–Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman’s rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal–Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level.Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman’s rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways.Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.</p

Image1_A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy.TIF

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear.Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan–Meier method (univariate Cox regression analysis and Kaplan–Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman’s rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal–Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level.Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman’s rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways.Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.</p

Data_Sheet_4_Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.docx

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.</p

Data_Sheet_2_Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.DOCX

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.</p

Data_Sheet_1_Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.DOCX

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.</p

Data_Sheet_3_Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.docx

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.</p

Table_1_Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.docx

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.</p

Additional file 1 of Molecular characterization of metallo-β-lactamase- producing carbapenem-resistant Enterobacter cloacae complex isolated in Heilongjiang Province of China

Additional file 1. The plasmid sequence with ND

Data_Sheet_1_Molecular antibiotic resistance mechanisms and co-transmission of the mcr-9 and metallo-β-lactamase genes in carbapenem-resistant Enterobacter cloacae complex.docx

Carbapenem-resistant Enterobacter cloacae complex (CRECC) has increasingly emerged as a major cause of healthcare-associated infections, with colistin being one of the last-resort antibiotics of treatment. Mobile colistin resistance (mcr)-9 is a member of a growing family of mcr genes and has been reported to be an inducible gene encoding an acquired phosphoethanolamine transferase. Here, we collected 24 ECC strains from Chongqing, China from 2018 to 2021. Subsequently, antibiotic resistance genes and the transmission dynamics of the strains were determined by PCR, whole-genome sequencing, and bioinformatic analysis. The mcr-9 was identified in IncHI2/2A or IncHI2/2A + IncN plasmids from six CRECC strains and was co-located with blaNDM-1 or blaIMP-4 in 2/6 plasmids. The genetic environment of mcr-9.1 was composed of IS903B-mcr-9.1-wbuC-IS26 in the five mcr-9.1-harboring-plasmid, but IS1B was located downstream of mcr-9.2 in the pECL414-1 sequence. We also found that the pNDM-068001 plasmid carrying mcr-9.1 could be a hybrid plasmid, formed by a Tn6360-like blaNDM-1 region inserted into an mcr-9.1-positive IncHI2/2A plasmid. A conjugation assay showed that plasmids mediated the co-dissemination of mcr-9 and metallo-β-lactamase (MBL) genes. In addition, we performed induction assays with sub-inhibitory concentrations of colistin and found an increase in the relative expression levels of the mcr-9.2, qseC, and qseB genes, as well as an increase in the minimum inhibitory concentration values of colistin in the CRECC414 strain. These findings provide a basis for studying the regulatory mechanisms of mcr-9 expression and highlight the importance of effective monitoring to assess the prevalence of MBL and mcr-9 co-existing plasmids.</p