21 research outputs found

    TAGAP expression influences CD4+ T cell differentiation, immune infiltration, and cytotoxicity in LUAD through the STAT pathway: implications for immunotherapy

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    BackgroundT-cell Activation GTPase Activating Protein (TAGAP) plays a role in immune cell regulation. This study aimed to investigate TAGAP’s expression and its potential impact on CD4+ T cell function and prognosis in lung adenocarcinoma (LUAD).MethodsWe analyzed TAGAP expression and its correlation with immune infiltration and clinical data in LUAD patients using multiple datasets, including The Cancer Genome Atlas (TCGA-LUAD), Gene Expression Omnibus (GEO), and scRNA-seq datasets. In vitro and in vivo experiments were conducted to explore the role of TAGAP in CD4+ T cell function, chemotaxis, and cytotoxicity.ResultsTAGAP expression was significantly lower in LUAD tissues compared to normal tissues, and high TAGAP expression correlated with better prognosis in LUAD patients. TAGAP was positively correlated with immune/stromal/ESTIMATE scores and immune cell infiltration in LUAD. Single-cell RNA sequencing revealed that TAGAP was primarily distributed in CD4+/CD8+ T cells. In vitro experiments showed that TAGAP overexpression enhanced CD4+ T cell cytotoxicity, proliferation, and chemotaxis. Gene Set Enrichment Analysis (GSEA) indicated that TAGAP was enriched in the JAK-STAT signaling pathway. In vivo experiments in a xenograft tumor model demonstrated that TAGAP overexpression suppressed tumor growth and promoted CD4+ T cell cytotoxicity.ConclusionsTAGAP influences CD4+ T cell differentiation and function in LUAD through the STAT pathway, promoting immune infiltration and cytotoxicity. This study provides a scientific basis for developing novel LUAD immunotherapy strategies and exploring new therapeutic targets

    Supercritical Carbon Dioxide Extraction of Bioactive Compounds from Ampelopsis grossedentata Stems: Process Optimization and Antioxidant Activity

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    Supercritical carbon dioxide (SC-CO2) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L9 (34), and antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and ferrous ion chelating (FIC) assay. The best conditions obtained for SC-CO2 extraction of flavonoids was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:3, v/v), and that for phenolics extraction was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:1, v/v). Meantime, flavonoids and phenolics were found to be mainly responsible for the DPPH scavenging activity of the extracts, but not for the chelating activity on ferrous ion according to Pearson correlation analysis. Furthermore, several unreported flavonoids such as apigenin, vitexin, luteolin, etc., have been detected in the extracts from A. grossedentata stems

    Structural variation and introgression from wild populations in East Asian cattle genomes confer adaptation to local environment

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    BACKGROUND: Structural variations (SVs) in individual genomes are major determinants of complex traits, including adaptability to environmental variables. The Mongolian and Hainan cattle breeds in East Asia are of taurine and indicine origins that have evolved to adapt to cold and hot environments, respectively. However, few studies have investigated SVs in East Asian cattle genomes and their roles in environmental adaptation, and little is known about adaptively introgressed SVs in East Asian cattle. RESULTS: In this study, we examine the roles of SVs in the climate adaptation of these two cattle lineages by generating highly contiguous chromosome-scale genome assemblies. Comparison of the two assemblies along with 18 Mongolian and Hainan cattle genomes obtained by long-read sequencing data provides a catalog of 123,898 nonredundant SVs. Several SVs detected from long reads are in exons of genes associated with epidermal differentiation, skin barrier, and bovine tuberculosis resistance. Functional investigations show that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages, which might contribute to the low susceptibility of Hainan cattle to bovine tuberculosis. Genotyping of 373 whole genomes from 39 breeds identifies 2610 SVs that are differentiated along a "north-south" gradient in China and overlap with 862 related genes that are enriched in pathways related to environmental adaptation. We identify 1457 Chinese indicine-stratified SVs that possibly originate from banteng and are frequent in Chinese indicine cattle. CONCLUSIONS: Our findings highlight the unique contribution of SVs in East Asian cattle to environmental adaptation and disease resistance

    Expression of RASGRP2 in Lung Adenocarcinoma and Its Effect 
on Immune Microenvironment

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    Background and objective Lung cancer still has the highest incidence rate and mortality rate nowadays. In recent years, with the emergence of new drugs and the optimization of treatment mode, especially the clinical application of immunotherapy, the prognosis of lung cancer patients has been improved. However, the benefits of immunotherapy are still limited. Therefore, it is necessary to find new biomarkers to predict the prognosis of lung adenocarcinoma patients and explore its impact on the immune microenvironment. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the gene sequencing and clinical data of patients with lung adenocarcinoma. The distribution of RASGRP2 in lung adenocarcinoma was determined by using the human protein mapping database. The Kaplan-Meier plotter database was used to explore the relationship between the expression of RASGRP2 and the prognosis of patients with lung adenocarcinoma. KEGG and GO gene enrichment analysis was performed in patients with high and low expression of RASGRP2. TCGA database was used to analyze the co-expression genes of RASGRP2 and TIMER database was used to calculate the immune related lymphoid infiltration of RASGRP2 and its coexpression genes. The relationship between RASGRP2 expression and immune checkpoint expression was analyzed by using TIMER 2.0 database. Results We found that RASGRP2 was low expressed in lung adenocarcinoma, and its expression level was related to the prognosis of patients. The high expression of RASGRP2 was involved in the process of hematopoietic cell formation and cell adhesion, and RASGRP2 played an important role in the process of T cell activation. Through TCGA database analysis, ZAP70, TBC1D10C, RASAL3, FGD2, CD37 and ACAP1 were significantly correlated with RASGRP2. The high expression of these genes leaded to the increase of the proportion of CD8+ T cells, memory CD4+ T cells, and the decrease of the proportion of neutrophils and Treg cells. Finally, we found that the expression of RASGRP2 was significantly correlated with the expression of CD274, CTLA4, LAG3 and TIGIT. Conclusion RASGRP2 was abnormally expressed in lung adenocarcinoma and correlated with the infiltration level of immune related cells, which might influence the efficacy of immunotherapy

    Quantification of the urbanization impacts on solar dimming and brightening over China

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    Metropolis’ contribution (anthropogenic aerosols) to solar dimming and brightening remains a hot topic of special concern over the past several decades. However, urbanization effects on surface incident solar radiation ( R _s ) have not been comprehensively investigated. In this study, the urbanization effects on solar dimming and brightening were addressed using the densely distributed reconstructed R _s data at 375 stations and 92 urban–rural station pairs over the time period of 1960–2019 in China. The results indicate that the impacts of urbanization on the monthly mean R _s is 0.86 ± 7.99 W m ^−2 during the study period, while the impact is 0.90 ± 8.30 W m ^−2 and 0.82 ± 8.26 W m ^−2 for the solar dimming (1960–1992) and brightening (1992–2019) phase, respectively. The urbanization effects on the trend of R _s is −0.39 and 0.16 W m ^−2 per decade during dimming and brightening, respectively. It also found that urbanization effects on R _s trend differs strikingly in magnitudes for specific regions in China. Generally, urbanization speeds up China’s dimming in the dimming phase and slows down China’s brightening in the brightening phase

    Construction of 11 metabolic-related lncRNAs to predict the prognosis in lung adenocarcinoma

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    Abstract Objective To explore the metabolism-related lncRNAs in the tumorigenesis of lung adenocarcinoma. Methods The transcriptome data and clinical information about lung adenocarcinoma patients were acquired in TCGA (The Cancer Genome Atlas). Metabolism-related genes were from the GSEA (Gene Set Enrichment Analysis) database. Through differential expression analysis and Pearson correlation analysis, lncRNAs about lung adenocarcinoma metabolism were identified. The samples were separated into the training and validation sets in the proportion of 2:1. The prognostic lncRNAs were determined by univariate Cox regression analysis and LASSO (Least absolute shrinkage and selection operator) regression. A risk model was built using Multivariate Cox regression analysis, evaluated by the internal validation data. The model prediction ability was assessed by subgroup analysis. The Nomogram was constructed by combining clinical indicators with independent prognostic significance and risk scores. C-index, calibration curve, DCA (Decision Curve Analysis) clinical decision and ROC (Receiver Operating Characteristic Curve) curves were obtained to assess the prediction ability of the model. Based on the CIBERSORT analysis, the correlation between lncRNAs and tumor infiltrating lymphocytes was obtained. Results From 497 lung adenocarcinoma and 54 paracancerous samples, 233 metabolic-related and 11 prognostic-related lncRNAs were further screened. According to the findings of the survival study, the low-risk group had a greater OS (Overall survival) than the high-risk group. ROC analysis indicated AUC (Area Under Curve) value was 0.726. Then, a nomogram with T, N stage and risk ratings was developed according to COX regression analysis. The C-index was 0.743, and the AUC values of 3- and 5-year survival were 0.741 and 0.775, respectively. The above results suggested the nomogram had a good prediction ability. The results based on the CIBERSORT algorithm demonstrated the lncRNAs used to construct the model had a strong correlation with the polarization of immune cells. Conclusions The study identified 11 metabolic-related lncRNAs for lung adenocarcinoma prognosis, on which basis a prognostic risk scoring model was created. This model may have a good predictive potential for lung adenocarcinoma

    Evaluation of Surface Upward Longwave Radiation in the CMIP6 Models with Ground and Satellite Observations

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    Surface upward longwave radiation (SULR) is an indicator of thermal conditions over the Earth’s surface. In this study, we validated the simulated SULR from 51 Coupled Model Intercomparison Project (CMIP6) general circulation models (GCMs) through a comparison with ground measurements and satellite-retrieved SULR from the Clouds and the Earth’s Radiant Energy System, Energy Balanced and Filled (CERES EBAF). Moreover, we improved the SULR estimations by a fusion of multiple CMIP6 GCMs using multimodel ensemble (MME) methods. Large variations were found in the monthly mean SULR among the 51 CMIP6 GCMs; the bias and root mean squared error (RMSE) of the individual CMIP6 GCMs at 133 sites ranged from −3 to 24 W m−2 and 22 to 38 W m−2, respectively, which were higher than those found between the CERES EBAF and GCMs. The CMIP6 GCMs did not improve the overestimation of SULR compared to the CMIP5 GCMs. The Bayesian model averaging (BMA) method showed better performance in simulating SULR than the individual GCMs and simple model averaging (SMA) method, with a bias of 0 W m−2 and an RMSE of 19.29 W m−2 for the 133 sites. In terms of the global annual mean SULR, our best estimation for the CMIP6 GCMs using the BMA method was 392 W m−2 during 2000–2014. We found that the SULR varied between 386 and 393 W m−2 from 1850 to 2014, exhibiting an increasing tendency of 0.2 W m−2 per decade (p < 0.05)

    Structural variation and introgression from wild populations in East Asian cattle genomes confer adaptation to local environment

    No full text
    Background Structural variations (SVs) in individual genomes are major determinants of complex traits, including adaptability to environmental variables. The Mongolian and Hainan cattle breeds in East Asia are of taurine and indicine origins that have evolved to adapt to cold and hot environments, respectively. However, few studies have investigated SVs in East Asian cattle genomes and their roles in environmental adaptation, and little is known about adaptively introgressed SVs in East Asian cattle. Results In this study, we examine the roles of SVs in the climate adaptation of these two cattle lineages by generating highly contiguous chromosome-scale genome assemblies. Comparison of the two assemblies along with 18 Mongolian and Hainan cattle genomes obtained by long-read sequencing data provides a catalog of 123,898 nonredundant SVs. Several SVs detected from long reads are in exons of genes associated with epidermal differentiation, skin barrier, and bovine tuberculosis resistance. Functional investigations show that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages, which might contribute to the low susceptibility of Hainan cattle to bovine tuberculosis. Genotyping of 373 whole genomes from 39 breeds identifies 2610 SVs that are differentiated along a “north–south” gradient in China and overlap with 862 related genes that are enriched in pathways related to environmental adaptation. We identify 1457 Chinese indicine-stratified SVs that possibly originate from banteng and are frequent in Chinese indicine cattle. Conclusions Our findings highlight the unique contribution of SVs in East Asian cattle to environmental adaptation and disease resistance.ISSN:1474-760
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