ABSTRACT
We report the isolation of Helicobacter cholecystus from a positive blood culture from a 58-year-old man in China who had bacteremia and acute cholecystitis. The patient's condition improved after symptomatic support treatment and subtotal cholecystectomy. This finding suggests that H. cholecystus should be considered as potential human pathogens.
ABSTRACT
Nephroblastoma, colloquially known as Wilms' tumour (WT), is the predominant malignant renal neoplasm arising in the paediatric population. Modern therapeutic approaches for WT incorporate a synergistic combination of surgical intervention, radiotherapy, and chemotherapy, which substantially ameliorate the overall patient survival rate. Despite this, the optimal sequence of chemotherapy and surgical intervention remains a matter of contention, with each strategy presenting its own strengths and weaknesses that could influence clinical decision-making. To make some headway on this clinical dilemma, we deployed a multidimensional transcriptomics integration approach by analysing bulk RNA sequencing data with 136 samples, as well as single-nucleus RNA sequencing (snRNA-seq) and paired spatial transcriptome sequencing (stRNA) data from 32 WT specimens. Our findings identified a distinct elevation of RNF34 expression within WT samples, which correlated with unfavourable prognostic outcomes. Leveraging the Genomics of Drug Sensitivity in Cancer (GDSC), we simultaneously revealed that patients with high expression of RNF34 have higher sensitivity to commonly used chemotherapy drugs for WT. Furthermore, our analysis of snRNA and stRNA data unveiled a reduced proportion of RNF34 expression in neoplastic cells after chemotherapy. Moreover, stRNA data delineated a significant association between a higher proportion of RNF34 expression in cancer cells and adverse features such as anaplastic histology and tumour recurrence. Intriguingly, we also observed a close association between elevated RNF34 expression and a characteristic exhausted tumour immune microenvironment. Collectively, our findings underscore the pivotal role of RNF34 in the prognostic prediction potential and treatment sensitivity of WT. This comprehensive analysis can potentially inform and refine clinical decision-making for WT patients and guide future studies towards the development of optimized, rational therapeutic strategies.
Subject(s)
Biomarkers, Tumor , Kidney Neoplasms , Wilms Tumor , Child, Preschool , Female , Humans , Male , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Drug Resistance, Neoplasm/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis , Transcriptome , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Wilms Tumor/genetics , Wilms Tumor/drug therapy , Wilms Tumor/pathology , Wilms Tumor/metabolism , Carrier Proteins/analysis , Carrier Proteins/geneticsABSTRACT
Background: Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant. Methods: We comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments. Results: Our analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation. Conclusions: Our research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , DNA Copy Number Variations , Neoplasm Recurrence, Local , Lymphoma, Large B-Cell, Diffuse/pathology , B-Lymphocytes/metabolism , Tumor MicroenvironmentABSTRACT
Background: Nephroblastoma, also known as Wilms' tumor (WT), remains one of the major causes of tumor-related deaths worldwide in children. Cancer stem cells (CSCs) are considered to be the main culprits in cancer resistance and disease recurrence, which are reported in multiple types of tumors. However, the research on CSCs in WT is limited. Therefore, our study aimed to identify the key genes related to CSCs in WT to provide new ideas for treating WT. Methods: The RNA-seq and clinical data of WT samples were obtained from the University of California Santa Cruz (UCSC) Xena database, which included 120 WT and six para-cancerous tissues. The mRNA stemness index (mRNAsi) based on mRNA expression was calculated to evaluate tumor stem cell characteristics in WT patients. A Kaplan-Meier (KM) analysis was performed to explore the clinical characteristics of the mRNAsi in WT. A weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and genes related to the mRNAsi. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to explore the signaling pathways based on the key genes. The expression levels of the key genes were validated by the Gene Expression Omnibus (GEO) database. Further, the important upstream genes were identified by DisNor and gene co-expression analyses. Results: The mRNAsi was significantly upregulated in WT (P=7.2e-05) and showed an upward trend in line with the pathological stage. Patients with lower mRNAsi scores had better overall survival (OS) than those with higher mRNAsi scores (P=0.0087). Eleven genes were defined as the key genes associated with the mRNAsi based on our WGCNA analysis [cor.MM (correlation. Module membership) >0.8 and cor.GS (correlation. Gene significance) >0.45] and were closely related to cell proliferation-related signaling pathways (P<0.05). Moreover, using protein interaction analysis, we identified ATM and CDKN1A as the key upstream regulatory genes of the 11 key genes. Conclusions: Our study showed that the mRNAsi score was a potential prognostic factors in WT and identified the upstream genes ATM and CDKN1A and 11 genes closely related to the mRNAsi, which may provide new insights for CSC-targeted therapy in WT and improve clinical outcomes for WT patients.
ABSTRACT
Innovation has been a major growing driver of sustainability. The topic addressed in this study is a much-required transition to environmental and social sustainability considering the role of innovation in pacing up those changes. Digital evolution has greatly helped in dealing with climatic changes and promoting sustainability. This has helped the entrepreneurial organizations to adopt innovative approaches to tackle the inflexible challenges. Few developed and developing countries are at the forefront regarding technological innovation that encounter significant challenges in terms of innovation and adoption of new technologies and there is still a study vacuum as to whether the influence of technical innovation on achieving social and environmental sustainability differs depending on the stage of sustainability. This quantitative study has explored these effects collecting data from the SME's (small and medium enterprises). The findings of the study show that attitude toward technological innovation has a strong role to play in organizational innovation, digital entrepreneurship, environmental and social sustainability. Organizational innovation has been found a strong mediator between technological innovation and sustainability while digital entrepreneurship could not find significant results as mediator. This study will be useful for the countries and organizations involved in adopting new technologies considering their organization's role in achieving an overall eco-friendly and social sustainability.
Subject(s)
Entrepreneurship , InventionsABSTRACT
As a consequence of the COVID-19 pandemic outbreak, most commodities experienced significant price drops, which were expected to continue well into 2020. As a result, the Markov switching model is used to study the influence of policy uncertainty and the COVID-19 pandemic on commodity prices in the USA. Commodity markets are stimulated by economic policy uncertainty, according to results from a two-state Markov switching model. In both high and low regimes, economic policy uncertainty (EPU) influences the commodity market, according to the study's findings. However, in the high regime, EPU has a greater influence on the energy and metal sectors. EPU has different influences on commodity markets in high- and low-volatility regimes, according to this study. There is a wide range of correlations between COVID-19 outcomes and EPU and how the prices of natural gas, oil, corn, silver, soybean, copper, gold, and steel respond to these tremors, in both high- and low-volatility tenure. Oil and natural gas, on the other hand, are unaffected by shifts in COVID-19 death rates under either regime. Results show that in both high- and low-volatility regimes, the demand and supply for most commodities are responsive to historical prices.
Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Natural Gas , Pandemics , UncertaintyABSTRACT
The coronavirus (COVID-19) outbreak in the China has exposed small- and medium-sized enterprises (SMEs) to a variety of challenges, some of which are potentially life-threatening to their sustainability. Therefore, this study aims to investigate the macroeconomic lockdown effects of COVID-19 on small business in China. A survey questionnaire with 313 participants was used to collect the data. In this study, the SEM technique was used to analyse model. The data have been gathered for the study from the managers and employees of Chinese SMEs. The findings of the study show that COVID-19 has a significant negative impact on financial performance, operational performance, profitability, access to finance, and customer satisfaction. According to the study's findings, external support aids have a greater impact on SMEs' ability to survive and thrive through innovation than on their actual performance. The findings of this study have a number of important practical consequences for small- and medium-sized business owners, governments, and policymakers.