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Background: Lymphocyte antigen 9 (LY9) participates in the development of several tumors and diseases but has not been reported yet in lung adenocarcinoma (LUAD). Methods: First, we analyzed the expression and prognostic value of LY9 in pan-cancer, including LUAD. Additionally, we conducted a correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSORT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis (GSEA). Finally, validation of differential expression at the mRNA level was obtained from the GEO database. We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY9. Results: Results showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD strongly and positively correlates with multiple immune cell infiltration and immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, GSE68465 dataset confirmed differential expression of LY9 mRNA levels in LUAD and the qRT-PCR results verified LY9 had a strong and positive correlation with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein level in tumor tissues and WB experiments validated the protein expression of LY9 in the OCI-AML-2 cell line. Conclusions: Therefore, we hypothesized that LY9 could serve as a potential, novel prognostic biomarker for LUAD and could predict immunotherapy efficacy at the mRNA level.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Inmunoterapia , Neoplasias Pulmonares , Humanos , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Inmunoterapia/métodos , Regulación Neoplásica de la Expresión Génica , Antígenos Ly/genética , Antígenos Ly/metabolismo , Antígenos de Superficie , Proteínas Ligadas a GPIRESUMEN
Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.
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Bellamya purificata is an important medicinal value and economically farmed species in China. However, because little is known about the genetic characteristics of this species, the utilization of high-quality germplasm resources is hindered. The study examined the genetic differentiation between, and the structure of 12 B. purificata populations in Guangxi using 7 microsatellite DNA markers. High genetic diversity occurred in each population, with mean observed heterozygosity 0.655 and a mean expected heterozygosity 0.832. Analysis of molecular variance reveals genetic diversity to be greater within (95.2%) than among populations (4.8%). Genetic differentiation between populations is weak (Fst = 0.048, P < 0.001), with mixing of genetic clusters prevalent at the level of the individual. Genetic flow exists between populations (Nm = 3.084-11.778), with Longshui and Guilin populations exchanging frequently. A Mantel test reveals a low correlation between geographic and genetic distances (r = 0.2482, P < 0.071), suggesting that dispersal between neighboring populations facilitates population exchange. No significant heterozygosity excess was observed for any population (P > 0.05), indicating a lack of recent genetic bottlenecks. The results provide important genetic information for B. purificata, and data for potential germplasm discovery and aquaculture development.
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Variación Genética , Repeticiones de Microsatélite , China , Repeticiones de Microsatélite/genética , Genética de Población , Flujo Génico , FilogeniaRESUMEN
Increasing evidence has shown that homologous recombination (HR) and metabolic reprogramming are essential for cellular homeostasis. These two processes are independent as well as closely intertwined. Nevertheless, they have rarely been reported in lung adenocarcinoma (LUAD). We analysed the genomic, immune microenvironment and metabolic microenvironment features under different HR activity states. Using cell cycle, EDU and cell invasion assays, we determined the impacts of si-SHFM1 on the LUAD cell cycle, proliferation and invasion. The levels of isocitrate dehydrogenase (IDH) and α-ketoglutarate dehydrogenase (α-KGDH) were determined by ELISA in the NC and si-SHFM1 groups of A549 cells. Finally, cell samples were used to extract metabolites for HPIC-MS/MS to analyse central carbon metabolism. We found that high HR activity was associated with a poor prognosis in LUAD, and HR was an independent prognostic factor for TCGA-LUAD patients. Moreover, LUAD samples with a high HR activity presented low immune infiltration levels, a high degree of genomic instability, a good response status to immune checkpoint blockade therapy and a high degree of drug sensitivity. The si-SHFM1 group presented a significantly higher proportion of cells in the G0/G1 phase, lower levels of DNA replication, and significantly lower levels of cell migration and both TCA enzymes. Our current results indicated that there is a strong correlation between HR and the TCA cycle in LUAD. The TCA cycle can promote SHFM1-mediated HR in LUAD, raising their activities, which can finally result in a poor prognosis and impair immunotherapeutic efficacy.
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Adenocarcinoma del Pulmón , Ciclo del Ácido Cítrico , Recombinación Homóloga , Neoplasias Pulmonares , Femenino , Humanos , Masculino , Células A549 , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Reprogramación Celular/genética , Regulación Neoplásica de la Expresión Génica , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Complejo Cetoglutarato Deshidrogenasa/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Reprogramación Metabólica , Pronóstico , Microambiente Tumoral , Persona de Mediana Edad , AncianoRESUMEN
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.
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Adenocarcinoma , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Pronóstico , Algoritmos , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , PulmónRESUMEN
Background: T-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). Methods: We 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. Results: TAGAP 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. Conclusions: TAGAP 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.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Humanos , Linfocitos T CD4-Positivos , Diferenciación Celular/genética , Inmunoterapia , Modelos Animales de Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapiaRESUMEN
The highly malignant nature of lung adenocarcinoma (LUAD) makes its early diagnosis and prognostic assessment particularly important. However, whether the CXC subfamily of chemokine receptors (CXCR) is involved in the development and prognosis of LUAD remains unclear. Here, differentially expressed genes (DEGs) associated with overall survival (OS) were selected from the cancer genome atlas (TCGA) dataset using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognostic gene signature was constructed, which was evaluated using Kaplan-Meier curves, receiver operating characteristics curves, nomogram curves, and an external gene expression omnibus (GEO) dataset. Finally, we verified the functions of the genes comprising the signature using the gene expression profiling interactive analysis (GEPIA) and the immune system interaction database (TISIDB) web portals. We constructed a 7-gene signature (SHC1, PRKCD, VEGFC, RPS6KA1, CAT, CDC25C, and GPI) that stratified patients into high- and low-risk categories. Notably, the risk score of the signature was a separate and effective predictor for OS (P < .001). Patients in the low-risk category had a better prognosis than those in the high-risk category. The receiver operating characteristics and nomogram curves verified the predictive power of the signature. Moreover, in both categories, biological processes and pathways associated with cell migration were enriched. Immune infiltration statuses differed between the 2 risk categories. Critically, the results from the GEPIA and TISIDB web portals indicated that the expression of the 7-gene signature was associated with survival, clinical stage, and immune subtypes of LUAD patients. We identified a CXCR-related gene signature that could assess prognosis and provide a reference for the diagnosis and treatment of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Pronóstico , Receptores de QuimiocinaRESUMEN
Cipangopaludina chinensis is an economically important aquatic snail with high medicinal value. However, molecular biology research on C. chinensis is limited by the lack of a reference genome, so the analysis of its transcripts is an important step to study the regulatory genes of various substances in C. chinensis. Herein, we conducted the first full-length transcriptome analysis of C. chinensis using PacBio single-molecule real-time (SMRT) sequencing technology. We identified a total of 26,312 unigenes with an average length of 2,572 bp, of which the largest number of zf-c2h2 transcription factor families (120,18.24%) were found, and also observed that the majority of the 8,058 SSRs contained 4-7 repeat units, which provided data for subsequent work on snail genetics Subsequently, 91.86% (24,169) of the genes were successfully annotated to the four major databases, while the highest homology was observed with Pomacea canaliculata. Functional annotation revealed that the majority of transcripts were enriched in metabolism, signal transduction and Immune-related pathways, and several candidate genes involved in drug metabolism and immune response were identified (e.g., CYP1A1, CYP2J, CYP2U1, GST, ,PIK3, PDE3A, PRKAG). This study lays a foundation for future molecular biology research and provides a reference for studying genes associated with the medicinal value of C. chinensis.
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Cipangopaludina chinensis is an important economic value snail species with high medicinal value. The gut microbes of aquatic animals plays a vital role in food digestion and nutrient absorption. Herein, we aimed at high-throughput sequencing of 16S rRNA to further investigate whether there were differences in the composition and function of gut microbes of adult and juvenile C. chinensis snails, as well as sediments. This study found that the microbial diversity of the sediment was significantly higher than that of the snails gut (P < 0.001), but there was no significant difference between the gut flora of adult and juvenile snails (P > 0.05). A total of 47 phyla and 644 genera were identified from all samples. Proteobacteria and Verrucomicrobia were the two dominant phyla in all samples, and overall relative abundances was 48.2% and 14.2%, respectively. Moreover, the relative abundances of Aeromonas and Luteolibacter in the gut of juvenile snails (30.8%, 11.8%) were higher than those of adults (27.7%, 10.6%) at the genus level (P > 0.05). Then, four indicator genera were found, namely Flavobacterium, Silanimonas, Geobacter and Zavarzinella, and they abundance in the gut of juvenile snails was significantly higher than that of adults (P < 0.05). This results imply the potential development of Silanimonas as a bait for juvenile snail openings. We observed that Aeromonas was the primary biomarker of the snail gut and sediments (P < 0.001), and it may be a cellulose-degrading bacteria. Function prediction revealed significantly better biochemical function in the snail gut than sediments (P < 0.001), but no significant differences in adult and juvenile snail (P > 0.05). In conclusion, studies show that the snail gut and sediment microbial composition differ, but the two were very similar. The microbial composition of the snail gut was relatively stable and has similar biological functions. These findings provide valuable information for in-depth understanding of the relationship between snails and environmental microorganisms.
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Microbioma Gastrointestinal , Oryza , Animales , Microbioma Gastrointestinal/genética , Oryza/genética , ARN Ribosómico 16S/genética , Caracoles/genética , AlimentosRESUMEN
Growth mechanism of economically important aquaculture species has aroused widespread interest among scholars. Rice flower carp (Cyprinus carpio), commonly cultured in rice-fish farming systems, shows wide variation in body mass at the same age, which limits the development of commercial aquaculture. In this study, muscle tissues from 20-month-old fish of different sizes were used for transcriptome analysis and muscle histological studies. The muscle histological analysis showed the muscle growth in rice flower carp main depends on the hypertrophic growth of muscle fibers. A total of 30,590 unigenes were generated by muscle trancriptome analysis, including 403 differentially expressed genes (DEGs). Of these, 157 DEGs were upregulated and 246 DEGs were downregulated. Nine unigenes related to the ubiquitin-proteasome pathway were identified using differential expression analysis. This study initially revealed that the differences in growth of rice flower carp could be due to hypertrophic growth of muscle fibers caused by higher protein deposition, and the ubiquitin-proteasome pathway was an important factor affecting the growth rate of rice flower carp. E3 ubiquitin-protein ligase ari7, g2e3, Neurl1 and rnf144ab were upregulated in the slow-growing fish, indicating the binding of ubiquitin to target protein was enhanced. Foxo3 was upregulated in the slow-growing fish, which could promote the muscle loss. Eif4a2 was upregulated in the fast-growing fish, increasing protein translation efficiency. Some genes related to active muscle contraction such as actb, actg, camk2a, and camk2b were upregulated in the fast-growing rice flower carp muscle. In summary, these results provide valuable information about the key genes for use as biomarkers of growth in selective breeding programs for rice flower carp and provide novel insights into the regulatory mechanisms of muscle growth.
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Carpas , Oryza , Animales , Carpas/genética , Carpas/metabolismo , Flores/metabolismo , Perfilación de la Expresión Génica , Músculos/metabolismo , Oryza/genética , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Transcriptoma , Ubiquitina/genéticaRESUMEN
BACKGROUND: Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated. METHOD AND MATERIALS: The angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed. RESULTS: A total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival). CONCLUSION: Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.
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Carcinoma de Células Escamosas , MicroARNs , Antígenos CD , Antígenos B7 , Carcinoma de Células Escamosas/genética , Humanos , Pronóstico , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico , Análisis de Supervivencia , Microambiente TumoralRESUMEN
BACKGROUND: The epidermal growth factor receptor (EGFR) is a primary target of molecular targeted therapy for lung adenocarcinoma (LUAD). The mechanisms that lead to epigenetic abnormalities of EGFR in LUAD are still unclear. The purpose of our study was to evaluate the abnormal methylation of EGFR CpG sites as potential biomarkers for LUAD. METHODS: To assess the differentially methylation CpG sites of EGFR in LUAD, we used an integrative study of Illumina HumanMethylation450K and RNA-seq data from The Cancer Genome Atlas (TCGA). We evaluated and compared EGFR multiple-omics data to explore the role of CpG sites located in EGFR promoter regions and gene body regions and the association with transcripts, protein expression levels, mutations, and somatic copy number variation. We calculated the correlation coefficients between CpG sites of EGFR and immune infiltration fraction (by MCPcounter and ESTIMATE) and immune-related pathways in LUAD. Finally, we validated the differential methylation of clinically and prognostically relevant CpG sites using quantitative methylation-specific PCR (qMSP). RESULTS: We found that the methylation level of many EGFR CpGs in the promoter region was negatively correlated with the transcription level, protein expression, and SCNV, while the methylation at the gene body region was positively correlated with these features. The methylation level of EGFR CpGs in the promoter region was positively correlated with the level of immune infiltration and IFN-γ signature, while the opposite was found for methylation of the gene body region. The qMSP results showed that cg02316066 had a high methylation level, while cg02166842 had a low methylation level in LUAD. There was a high degree of co-methylation between cg02316066 and cg03046247. CONCLUSION: Our data indicate that EGFR is an epigenetic regulator in LUAD acting through DNA methylation. Our research provides a theoretical basis for the further detection of EGFR DNA methylation as a predictive biomarker for LUAD survival and immunotherapy.
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There are few studies on the role of iron metabolism genes in predicting the prognosis of lung adenocarcinoma (LUAD). Therefore, our research aims to screen key genes and to establish a prognostic signature that can predict the overall survival rate of lung adenocarcinoma patients. RNA-Seq data and corresponding clinical materials of 594 adenocarcinoma patients from The Cancer Genome Atlas(TCGA) were downloaded. GSE42127 of Gene Expression Omnibus (GEO) database was further verified. The multi-gene prognostic signature was constructed by the Cox regression model of the Least Absolute Shrinkage and Selection Operator (LASSO). We constructed a prediction signature with 12 genes (HAVCR1, SPN, GAPDH, ANGPTL4, PRSS3, KRT8, LDHA, HMMR, SLC2A1, CYP24A1, LOXL2, TIMP1), and patients were split into high and low-risk groups. The survival graph results revealed that the survival prognosis between the high and low-risk groups was significantly different (TCGA: P < 0.001, GEO: P = 0.001). Univariate and multivariate Cox regression analysis confirmed that the risk value is a predictor of patient OS (P < 0.001). The area under the time-dependent ROC curve (AUC) indicated that our signature had a relatively high true positive rate when predicting the 1-year, 3-year, and 5-year OS of the TCGA cohort, which was 0.735, 0.711, and 0.601, respectively. In addition, immune-related pathways were highlighted in the functional enrichment analysis. In conclusion, we developed and verified a 12-gene prognostic signature, which may be help predict the prognosis of lung adenocarcinoma and offer a variety of targeted options for the precise treatment of lung cancer.
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Adenocarcinoma del Pulmón , Hierro/metabolismo , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Transcriptoma/genéticaRESUMEN
AIMS: Defective components resulting from DNA damage and repair mechanisms have been found to be underlying causes that affect the development and progression of different types of cancers, including squamous cell carcinoma (SCC). A more detailed classification of SCC is necessary for better application of DNA damage repair therapies. MATERIALS AND METHODS: We aimed to characterize the molecular profile of SCC by developing a classification system based on DNA damage repair gene expression profiles. An integrative analysis was performed using a metadata set of 1374 SCC human samples from the UCSC Genome Browser. We then analyzed genomic alterations and mutations, and genes-TF-microRNA regulatory relationships and conducted enrichment, survival, and immune infiltration analyses. KEY FINDINGS: This study was conducted on a total of 1374 SCC patients and 402 DNA damage repair genes. Two subtypes were established using consensus clustering, with 1143 patients being of the Non DDR subtype and 231 patients being of the DDR subtype. MATH, mutation burden, and heterogeneity were significantly higher in Non-DDR subtype than in DDR subtype. Next, a total of 1081 differentially expressed genes and 21 microRNAs were identified between the two subtypes and a genes-TF-microRNA regulatory network was constructed. In addition, stromal score, immune score and ESTIMATE score were significantly lower for the Non-DDR subtype, while tumor purity was significantly lower for the DDR subtype. In addition, five pathways associated with DNA damage repair were all enriched in the DDR subtype. SIGNIFICANCE: Our study established two subtypes of SCC based on DNA damage repair, which may help to predict prognosis and determine the most suitable treatment for SCC patients.
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Carcinoma de Células Escamosas/genética , Daño del ADN , Reparación del ADN , Adulto , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/diagnóstico , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Masculino , MicroARNs/genética , Mutación , Pronóstico , TranscriptomaRESUMEN
Aim: To establish a signature based on hypoxia-related alternative splicing (AS) events for lung adenocarcinoma. Materials & methods: The least absolute shrinkage and selection operator Cox approach was used to construct a prognostic model. A nomogram that integrates the final AS predictor and stage was created. The network of the key AS events and splicing factors was created. Results: We created a prognostic signature of 11 AS events. Moreover, a nomogram that constitutes the pathological stage and risk was exhibited to be greatly effective in estimating the survival likelihood of lung adenocarcinoma patients. Conclusion: Herein we developed the first-ever signature based on hypoxia-related AS events with both prognostic predictive power and diagnostic efficacy.
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Adenocarcinoma del Pulmón/genética , Empalme Alternativo , Hipoxia/complicaciones , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/patología , Nomogramas , PronósticoRESUMEN
To investigate the physiological responses of Oreochromis aureus to salinity fluctuations at the molecular level. We used RNA-seq to explore the differentially expressed genes (DEGs) in the liver and spleen of O. aureus at 0, 3, 7 and 11 ppt (parts per thousand) salinity levels. Herein, De novo assembly generated 71,009 O. aureus unigenes, of which 34,607 were successfully mapped to the four major databases. A total of 120 shared DEGs were identified in liver and spleen transcripts, of which 83 were up-regulated and 37 were down-regulated. GO and KEGG analysis found a total of 26 significant pathways, mainly including energy metabolism, immune response, ion transporters and signal transduction. The trend module category of DEGs showed that the genes (e.g., FASN, ODC1, CD22, MRC, TRAV and SLC7 family) involved in the change-stable-change (1) and the constant-change categories (2) were highly sensitive to salinity fluctuations, which were of great value for further study. Based on these results, it would help provide basic data for fish salinity acclimation, and provide new insights into evolutionary response of fish to various aquatic environments in the long-term stress adaptation mechanism.
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Cíclidos/fisiología , Metabolismo Energético , Inmunidad , Hígado/metabolismo , Estrés Salino/fisiología , Bazo/metabolismo , Transcriptoma/fisiología , Animales , Cíclidos/genética , Cíclidos/inmunología , Estrés Salino/inmunología , Transcriptoma/inmunologíaRESUMEN
Snapping shrimp produces a high-speed jet through the rapid closure of the snapper claw, which stimulates the formation of cavitation bubbles of various shapes. In order to explore the fast motion characteristics of snapper claw, the formation and change process of cavitation, and the physical principles underlying the biological phenomena, the equivalent model of snapper claw was constructed through CT scanning technology. A high-speed camera was used to capture the claw's motion characteristics, thereby simulating the production of cavitation bubbles by snapping shrimp. The results show that the rotation speeds of different species of snapping shrimps are different, as well as their motion characteristics. Cavitation is formed by the interaction of the pressure drop caused by the vortex at the nozzle with the inertia of the liquid inside the socket. Under the influence of the jet, the shapes of bubbles change from ring to cone, and eventually collapse into bubble clouds.
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A new microporous MIL-100(Fe)/Ti3C2 MXene composite was constructed as a non-noble metal-based Schottky junction photocatalyst with improved nitrogen fixation ability. Ti3C2 MXene nanosheets exhibited excellent metal conductivity and were employed as two-dimensional support to optimize the composite's energy band structure. MIL-100(Fe) with a large specific surface area was used as an adsorbent and a photocatalytic oxidation center. The MIL-100(Fe)/Ti3C2 MXene composite not only exhibited higher thermal stability but also showed significantly increased nitrogen fixation activity under visible light. The NO conversion rate of the composite catalyst was about four and three times higher than that of the pure Ti3C2 MXene and the pure MIL-100(Fe) samples, respectively. Although adsorption plays an important role in the nitrogen fixation process, the synergistic effects of the Schottky junctions are the main cause of the enhanced photocatalytic activity. The built-in electric field can be generated to form charge-transfer channels, which help to achieve a desirable photocatalytic activity.