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BACKGROUND: Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. METHODS: We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. RESULTS: We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.
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Biología Computacional , Citomegalovirus , Neoplasias , Microambiente Tumoral , Humanos , Citomegalovirus/genética , Citomegalovirus/patogenicidad , Biología Computacional/métodos , Neoplasias/genética , Neoplasias/virología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Regulación Neoplásica de la Expresión Génica/genética , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Pronóstico , Redes Reguladoras de Genes/genética , Perfilación de la Expresión Génica , Bases de Datos GenéticasRESUMEN
OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.
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Enfermedad Coronaria , Infecciones por VIH , Aprendizaje Automático , Humanos , Persona de Mediana Edad , Masculino , Femenino , Medición de Riesgo/métodos , Adulto , Registros Electrónicos de Salud , AncianoRESUMEN
BACKGROUND: Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. METHODS: In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs. RESULTS: Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were identified under erastin exposure and significantly enriched in several pathways, including DNA replication and cell cycle. The percentage of LNCaP and PC3 cells in G1 phase was markedly increased in response to erastin treatment. For four hub FRGs, TMEFF2 was higher in PCa tissue and the expression levels of NRXN3, CLU, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in androgen-dependent cell lines (LNCaP and VCaP) but not in androgen-independent cell lines (PC3 and C4-2). The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP and VCaP cells. CONCLUSION: TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells.
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Ferroptosis , Piperazinas , Neoplasias de la Próstata , Masculino , Humanos , Andrógenos , Ferroptosis/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Próstata/metabolismo , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Receptores de NetrinaRESUMEN
Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer.
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Neoplasias de la Mama , Retrovirus Endógenos , Humanos , Femenino , Neoplasias de la Mama/genética , Retrovirus Endógenos/genética , Genoma Humano , Expresión Génica , Pronóstico , Microambiente Tumoral/genética , Proteínas de la Membrana/genéticaRESUMEN
Colored-leaf poplar is increasingly popular due to its great ornamental values and application prospects. However, the photosynthetic characteristics of these colored-leaf cultivars have not been well understood. In this study, the photosynthetic differences between green-leaf poplar Populus deltoids Linn. "2025" (L2025) and colored-leaf cultivars 'Zhonghong poplar' (ZHP), 'Quanhong poplar' (QHP), and 'Caihong poplar' (CHP) were investigated on several levels, including chloroplast ultrastructure observation, photosynthetic physiological characteristics, and expression analysis of key genes. The results showed that the photosynthetic performance of ZHP was basically consistent with that of L2025, while the ranges of light energy absorption and efficiency of light energy utilization decreased to different degrees in CHP and QHP. A relatively low water use efficiency and high dark respiration rate were observed in QHP, suggesting a relatively weak environmental adaptability. The differences in chloroplast structure in different colored-leaf poplars were further observed by transmission electron microscopy. The disorganization of thylakoid in CHP was considered an important reason, resulting in a significant decrease in chlorophyll content compared with other poplar cultivars. Interestingly, CHP exhibited extremely high photosynthetic electron transport activity and photochemical efficiency, which were conductive to maintaining its relatively high photosynthetic performance. The actual quantum yield of PSII photochemistry of ZHP was basically the same as that of QHP, while the relatively high photosynthetic performance indexes in ZHP suggested a more optimized photosynthetic apparatus, which was crucial for the improvement of photosynthetic efficiency. The differential expressions of a series of key genes in different colored-leaf poplars provided a reasonable explanation for anthocyanin accumulation and specific photosynthetic processes.
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Populus , Populus/metabolismo , Fotosíntesis/fisiología , Clorofila/metabolismo , Cloroplastos/metabolismo , Hojas de la Planta/metabolismoRESUMEN
BACKGROUND: Human adenoviruses (HAdV) have been known to cause a range of diseases, including respiratory tract infections (RTIs). However, there is limited information available regarding the genotype diversity and epidemiology of HAdV associated with RTIs in Nanning. METHODS: Between June 2019 and December 2021, throat swab, nasal swab, or nasopharyngeal swab samples were obtained from individuals hospitalized with respiratory tract infections (RTIs). Statistical software was used to analyze the epidemiological data. The highly conserved 132-bp gene region of the HAdV hexon was targeted for the detection of HAdV using a qPCR assay. An 875-bp hexon gene fragment was subjected to phylogenetic analysis. RESULTS: Significant variations were observed in the age and gender distribution of HAdV-positive patients (P = 0.004 and P = 0.025, respectively). The age distribution of HAdV-positive patients showed that 67.89% of those who tested positive were the age group of 0-6 years. Furthermore, the prevalence of HAdV detection was highest during spring and autumn, with a peak in February. Additionally, genotyping of the 36 HAdV-positive samples with 875-bp fragments identified the presence of circulating HAdV species B, C, and E in Nanning between 2019 and 2021. CONCLUSIONS: This study identified an association between HAdV prevalence and age as well as season. Among hospitalized patients with RTIs in Nanning, HAdV-B, HAdV-C, and HAdV-E were found to be co-circulating. The most commonly detected genotypes were HAdV-C1, HAdV-C6, and HAdV-E4.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Gripe Humana , Infecciones del Sistema Respiratorio , Humanos , Lactante , Recién Nacido , Preescolar , Niño , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Adenovirus Humanos/genética , Filogenia , Infecciones por Adenovirus Humanos/epidemiología , Análisis de Secuencia de ADN , Infecciones del Sistema Respiratorio/epidemiología , China/epidemiología , GenotipoRESUMEN
Cadmium (Cd) pollution has attracted global attention because it not only jeopardizes soil microbial ecology and crop production, but also threatens human health. As of now, microbe-assisted phytoremediation has proven to be a promising approach for the revegetation of Cd-contaminated soil. Therefore, it is important to find such tolerant microorganisms. In the present study, we inoculated a bacteria strain tolerant to Cd, Cdb8-1, to Cd-contaminated soils and then explored the effects of Cdb8-1 inoculation on the performance of the Chinese milk vetch. The results showed plant height, root length, and fresh and dry weight of Chinese milk vetch grown in Cdb8-1-inoculated soils increased compared to the non-inoculated control group. The inoculation of Cd-contaminated soils with Cdb8-1 also enhanced their antioxidant defense system and decreased the H2O2 and malondialdehyde (MDA) contents, which alleviated the phytotoxicity of Cd. The inoculation of Cdb8-1 in Cd-contaminated soils attenuated the contents of total and available Cd in the soil and augmented the BCF and TF of Chinese milk vetch, indicating that the combined application of Cd-tolerant bacteria Cdb8-1 and Chinese milk vetch is a potential solution to Cd-contaminated soils.