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Safety-critical systems, such as the railway signal system, are subject to potentially high costs from failures, including loss of life and property damage. The use of new technology, including communication-based train control (CBTC) systems with software and computers, has changed the types of accidents that occur. Software-related issues and dysfunctional interactions between system components controlled by the software are increasingly the cause of incidents. Developing a "safe" safety-critical system requires accurate and complete safety requirements, which are the foundation of system development. Traditional hazard analysis techniques are insufficient for identifying the causes of accidents in modern railway signaling systems. Systems-Theoretic Process Analysis (STPA) is a powerful new hazard analysis method designed to address these limitations. Building upon this foundation, a hierarchical approach to safety requirement development has been further developed. This approach combines STPA analysis with a hierarchical modeling approach to establish traceability links from safety requirements to specific architectures, refine and allocate system-level safety requirements to relevant subsystems, and abstract safety requirements at higher hierarchical levels to enable easy changes to lower-level implementations. This paper employs the aforementioned methodology within the context of the CBTC system, thereby enhancing risk management and hazard analysis, enabling early insights, and facilitating the generation of safety requirements of CBTC System.
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The superconducting gap symmetry is crucial in understanding the underlying superconductivity mechanism. Angle-resolved photoemission spectroscopy (ARPES) has played a key role in determining the gap symmetry in unconventional superconductors. However, it has been considered so far that ARPES can only measure the magnitude of the superconducting gap but not its phase; the phase has to be detected by other phase-sensitive techniques. Here we propose a method to directly detect the superconducting gap sign by ARPES. This method is successfully validated in a cuprate superconductor Bi2Sr2CaCu2O8+δ with a well-known d-wave gap symmetry. When two bands have a strong interband interaction, the resulted electronic structures in the superconducting state are sensitive to the relative gap sign between the two bands. Our present work provides an approach to detect the gap sign and can be applied to various superconductors, particularly those with multiple orbitals like the iron-based superconductors.
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Killer cell lectin-like receptor B1 (KLRB1) is implicated in cancer progression and immunity. In this study, we aimed to evaluate the expression levels of KLRB1 in lung adenocarcinoma (LUAD) and analyze the relationship between KLRB1 expression levels, LUAD progression, and the tumor immune microenvironment. KLRB1 levels in LUAD were analyzed using data from the TCGA and XENA databases. Additionally, the diagnostic values of KLRB1 were analyzed in patients with LUAD. Survival and meta-analyses were employed to investigate the relationship between KLRB1 levels and other prognostic factors in patients with LUAD. Bioinformatics and cellular experiments were used to understand the functions and mechanisms of KLRB1. In addition, correlation analysis was used to investigate the relationship between KLRB1 levels and the immune microenvironment in LUAD. Reduced KLRB1 expression in LUAD was found to positively correlate with tumor size, distant metastasis, pathological stage, age, overall survival, diagnostic value, and disease-specific survival in patients with LUAD (P < 0.05). Conversely, increased KLRB1 expression was found to positively correlate with the overall survival and disease-specific survival in patients with LUAD (P < 0.05). We also found that the overexpression of KLRB1 can inhibit the proliferation, migration, and invasion of LUAD cells and promote apoptosis. KLRB1 was involved in immune cell differentiation, NF-kB, PD-L1, and PD-1 checkpoint pathways and others. Additionally, KLRB1 expression was linked to tumor purity, stromal, immune, and estimate scores, the levels of immune cells including B cells, CD8+ T cells, and CD4+ T cells, and immune cell markers in LUAD. Reduced KLRB1 expression has a significant positive correlation with diagnosis, poor prognosis, and immunity to cancer in patients with LUAD. KLRB1 inhibited cell proliferation and migration in patients with LUAD. These results suggest that KLRB1 may serve as a potential therapeutic target in patients with LUAD.
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Adenocarcinoma del Pulmón , Proliferación Celular , Neoplasias Pulmonares , Microambiente Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Metástasis de la Neoplasia , Pronóstico , Microambiente Tumoral/inmunologíaRESUMEN
As a cutting-edge technology, animal robots based on living organisms are being extensively studied, with potential for diverse applications in the fields of neuroscience, national security, and civil rescue. However, it remains a significant challenge to reliably control the animal robots with the objective of protecting their long-term survival, and this has seriously hindered their practical implementation. To address this issue, this work explored the use of a bio-friendly neurostimulation system that includes integrated stimulation electrodes together with a remote wireless stimulation circuit to control the moving behavior of rat robots. The integrated electrodes were implanted simultaneously in four stimulation sites, including the medial forebrain bundle (MFB) and primary somatosensory cortex, barrel field (S1BF). The control system was able to provide flexibility in adjusting the following four stimulation parameters: waveform, amplitude, frequency, and duration time. The optimized parameters facilitated the successful control of the rat's locomotion, including forward movement and left and right turns. After training for a few cycles, the rat robots could be guided along a designated route to complete the given mission in a maze. Moreover, it was found that the rat robots could survive for more than 20 days with the control system implanted. These findings will ensure the sustained and reliable operation of the rat robots, laying a robust foundation for advances in animal robot regulation technology.
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OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis. METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting. RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC. CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Resistencia a Antineoplásicos/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Emerging evidence suggested a significant association between optic atrophy 1 (OPA1) polymorphisms and primary open angle glaucoma (POAG) risk. However, the current data are inconsistent or even contradictory. Given these, we conducted a meta-analysis to examine the precise association between OPA1 polymorphisms and POAG risk. MATERIALS AND METHODS: Online databases were retrieved, and the related studies were reviewed from inception to December 1, 2022. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of each genetic model. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. RESULT: Overall, 14 studies within 11 publications (involving 2,413 POAG patients and 1,904 controls) were included and some significant association between OPA1 rs166850 C/T (T vs. C: OR = 1.24, 95%CI = 1.06-1.45, P = 0.01, I2 = 39.0%; CT vs. CC: OR = 1.37, 95%CI = 1.05-1.79, P = 0.02, I2 = 41.6%; CT + TT vs. CC: 1.37, 95%CI = 1.06-1.77, P = 0.02, I2 = 41.6%), rs10451941T/C (TC + CC vs. TT: OR = 1.79, 95%CI = 1.41-2.28, P < 0.01, I2 = 71.9%) polymorphisms and POAG susceptibility. In addition, further significant associations were also observed in the stratified analysis, especially in normal tension glaucoma groups and Caucasian descendants. CONCLUSION: The observed evidences suggest that OPA1 polymorphisms may be associate with POAG susceptibility significantly.
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In conventional superconductors, electron-phonon coupling plays a dominant role in generating superconductivity. In high-temperature cuprate superconductors, the existence of electron coupling with phonons and other boson modes and its role in producing high-temperature superconductivity remain unclear. The evidence of electron-boson coupling mainly comes from angle-resolved photoemission (ARPES) observations of [Formula: see text]70-meV nodal dispersion kink and [Formula: see text]40-meV antinodal kink. However, the reported results are sporadic and the nature of the involved bosons is still under debate. Here we report findings of ubiquitous two coexisting electron-mode couplings in cuprate superconductors. By taking ultrahigh-resolution laser-based ARPES measurements, we found that the electrons are coupled simultaneously with two sharp modes at [Formula: see text]70meV and [Formula: see text]40meV in different superconductors with different dopings, over the entire momentum space and at different temperatures above and below the superconducting transition temperature. These observations favor phonons as the origin of the modes coupled with electrons and the observed electron-mode couplings are unusual because the associated energy scales do not exhibit an obvious energy shift across the superconducting transition. We further find that the well-known "peak-dip-hump" structure, which has long been considered a hallmark of superconductivity, is also omnipresent and consists of "peak-double dip-double hump" finer structures that originate from electron coupling with two sharp modes. These results provide a unified picture for the [Formula: see text]70-meV and [Formula: see text]40-meV energy scales and their evolutions with momentum, doping and temperature. They provide key information to understand the origin of these energy scales and their role in generating anomalous normal state and high-temperature superconductivity.
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Common ragweed is an invasive alien species causing severe allergies in urban residents. Understanding its urban invasion pathways is crucial for effective control. However, knowledge is limited, with most studies focusing on agricultural and natural areas, and occurrence record-based studies exhibiting uncertainties. We address this gap through a study in East China cities, combining population genetics and occurrence records. Leaf samples from 37 urban common ragweed populations across 15 cities are collected. Genomic and chloroplast DNA extraction facilitate analysis of spatial genetic patterns and gene flows. Additionally, international grain trade data is examined to trace invasion sources. Results indicate spatial genetic patterns impacted by multiple introductions over time. We infer the modern grain trade between the United States and China as the primary invasion pathway. Also, cities act as transportation hubs and ports of grain importation might disperse common ragweed to urban areas. Invasive species control should account for cities as potential landing and spread hubs of common ragweed.
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Ambrosia , Genética de Población , Estados Unidos , Ciudades , Ambrosia/genética , Especies Introducidas , AgriculturaRESUMEN
As the number of CuO2 layers, n, in each unit cell of a cuprate family increases, the maximum transition temperature (Tc,max) exhibits a universal bell-shaped curve with a peak at n = 3. The microscopic mechanism of this trend remains elusive. In this study, we used advanced electron microscopy to image the atomic structure of cuprates in the Bi2Sr2Can-1CunO2n+4+δ family with 1 ≤ n ≤ 9; the evolution of the charge-transfer gap size (Δ) with n can be measured simultaneously. We determined that the n dependence of Δ follows an inverted bell-shaped curve with the minimum Δ value at n = 3. The correlation between Δ, n, and Tc,max may clarify the origin of superconductivity in cuprates.
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Background: Lymph node metastasis is one of the important factors affecting the prognosis of lung adenocarcinoma (LUAD) patients. The key molecules in lymph node metastasis have not yet been fully revealed. Therefore, we aimed to construct a prognostic model based on lymph node metastasis-related genes to evaluate the prognosis of LUAD patients. Methods: The differentially expressed genes (DEGs) in the process of LUAD metastasis were identified in The Cancer Genome Atlas (TCGA) database, and the biological roles of the DEGs were depicted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a protein-protein interaction (PPI) network. Survival analysis and Cox regression analysis were used to identify the genes related to the prognosis of patients with LUAD, and a nomogram and a prognostic model were constructed. The potential prognostic value, immune escape, and regulatory mechanisms of the prognostic model in LUAD progression were explored through survival analysis and gene set enrichment analysis (GSEA). Results: A total of 75 genes were upregulated, and 138 genes were downregulated in tissues of lymph node metastasis. The expression levels of STC1, CYP17A1, RHOV, GUCA2B, TM4SF20, DEFB1, CRHR2, ABCC2, CYP4B1, KRT16, and NTS were revealed as risk factors for a poor prognosis in LUAD patients. High-risk LUAD patients had a poor prognosis in the prognostic model based on RHOV, ABCC2, and CYP4B1. The clinical stage and the risk score were found to be independent risk factors for a poor prognosis in LUAD patients, and the risk score was associated with the tumor purity, T cell, natural killer (NK) cell, and other immune cells. The prognostic model might affect the progression of LUAD using DNA replication, the cell cycle, P53, and other signaling pathways. Conclusions: Lymph node metastasis-related genes RHOV, ABCC2, and CYP4B1 are associated with a poor prognosis in LUAD. A prognostic model based on RHOV, ABCC2, and CYP4B1 might predict the prognosis of LUAD patients and be associated with immune infiltration.
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This article presents a novel parallel path detection algorithm for identifying suspicious fraudulent accounts in large-scale banking transaction graphs. The proposed algorithm is based on a three-step approach that involves constructing a directed graph, shrinking strongly connected components, and using a parallel depth-first search algorithm to mark potentially fraudulent accounts. The algorithm is designed to fully exploit CPU resources and handle large-scale graphs with exponential growth. The performance of the algorithm is evaluated on various datasets and compared with serial time baselines. The results demonstrate that our approach achieves high performance and scalability on multi-core processors, making it a promising solution for detecting suspicious accounts and preventing money laundering schemes in the banking industry. Overall, our work contributes to the ongoing efforts to combat financial fraud and promote financial stability in the banking sector.
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As the leading cause of cancer-related death worldwide, non-small-cell lung cancer (NSCLC) is still in need of improved therapeutic strategies. CircKIF4A has been found to be involved in the progression of multiple cancers while its role in NSCLC remains unclear. To investigate the functions of circKIF4A, we assessed the expression of circKIF4A in NSCLC cells and tissues and performed experiments to determine the detailed functions of circKIF4A in NSCLC, including migration and proliferation. We found CircKIF4A expressed more heavily in the cells and tissues of NSCLC patients, and functional studies showed that inhibition of circKIF4A reduced NSCLC cells metastasis and proliferation. Furthermore, we seek to identify the underlying regulatory effect of circKIF4A in NSCLC. Studies revealed that circKIF4A sponged miR-1238 to promote NSCLC progression by up-regulating claudin14 (CLDN14) expression. In conclusion, circKIF4A is a potential diagnostic and therapeutic target in the circKIF4A/miR-1238/CLDN14 axis that plays an important role in NSCLC progression.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Claudinas , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
China implemented the first phase of its National Healthy Cities pilot program from 2016-20. Along with related urban health governmental initiatives, the program has helped put health on the agenda of local governments while raising public awareness. Healthy City actions taken at the municipal scale also prepared cities to deal with the COVID-19 pandemic. However, after intermittent trials spanning the past two decades, the Healthy Cities initiative in China has reached a crucial juncture. It risks becoming inconsequential given its overlap with other health promotion efforts, changing public health priorities in response to the pandemic, and the partial adoption of the Healthy Cities approach advanced by the World Health Organization (WHO). We recommend aligning the Healthy Cities initiative in China with strategic national and global level agendas such as Healthy China 2030 and the Sustainable Development Goals (SDGs) by providing an integrative governance framework to facilitate a coherent intersectoral program to systemically improve population health. Achieving this alignment will require leveraging the full spectrum of best practices in Healthy Cities actions and expanding assessment efforts. Funding: Tsinghua-Toyota Joint Research Fund "Healthy city systems for smart cities" program.
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MOTIVATION: Spatial transcriptomic techniques can profile gene expressions while retaining the spatial information, thus offering unprecedented opportunities to explore the relationship between gene expression and spatial locations. The spatial relationship may vary across cell types, but there is a lack of statistical methods to identify cell-type-specific spatially variable (SV) genes by simultaneously modeling excess zeros and cell-type proportions. RESULTS: We develop a statistical approach CTSV to detect cell-type-specific SV genes. CTSV directly models spatial raw count data and considers zero-inflation as well as overdispersion using a zero-inflated negative binomial distribution. It then incorporates cell-type proportions and spatial effect functions in the zero-inflated negative binomial regression framework. The R package pscl is employed to fit the model. For robustness, a Cauchy combination rule is applied to integrate P-values from multiple choices of spatial effect functions. Simulation studies show that CTSV not only outperforms competing methods at the aggregated level but also achieves more power at the cell-type level. By analyzing pancreatic ductal adenocarcinoma spatial transcriptomic data, SV genes identified by CTSV reveal biological insights at the cell-type level. AVAILABILITY AND IMPLEMENTATION: The R package of CTSV is available at https://bioconductor.org/packages/devel/bioc/html/CTSV.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Programas Informáticos , TranscriptomaRESUMEN
Background: Oxidative stress plays a role in carcinogenesis. This study explores the roles of oxidative stress-related genes (OSRGs) in lung adenocarcinoma (LAC). Besides, we construct a risk score model of OSRGs that evaluates the prognosis of LAC patients. Methods: OSRGs were downloaded from the Gene Set Enrichment Analysis (GSEA) website. The expression levels of OSRGs were confirmed in LAC tissues of the TCGA database. GO and KEGG analyses were used to evaluate the roles and mechanisms of oxidative stress-related differentially expressed genes (DEGs). Survival, ROC, Cox analysis, and AIC method were used to screen the prognostic DEGs in LAC patients. Subsequently, we constructed a risk score model of OSRGs and a nomogram. Further, this work investigated the values of the risk score model in LAC progression and the relationship between the risk score model and immune infiltration. Results: We discovered 163 oxidative stress-related DEGs in LAC, involving cellular response to oxidative stress and reactive oxygen species. Besides, the areas under the curve of CCNA2, CDC25C, ERO1A, CDK1, PLK1, ITGB4, and GJB2 were 0.970, 0.984, 0.984, 0.945, 0.984, 0.771, and 0.959, respectively. This indicates that these OSRGs have diagnosis values of LAC and are significantly related to the overall survival of LAC patients. ERO1A, CDC25C, and ITGB4 overexpressions were independent risk factors for the poor prognosis of LAC patients and were associated with risk scores in the risk model. High-risk score levels affected the poor prognosis of LAC patients. Notably, a high-risk score may be implicated in LAC progression via cell cycle, DNA replication, mismatch repair, and other mechanisms. Further, ERO1A, CDC25C, and ITGB4 expression levels were related to the immune infiltrating cells of LAC, including mast cells, NK cells, and CD8 T cells. Conclusion: In summary, ERO1A, CDC25C, and ITGB4 of OSRGs are associated with poor prognosis of LAC patients. We confirmed that the risk model based on the ERO1A, CDC25C, and ITGB4 is expected to assess the prognosis of LAC patients.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Carcinogénesis , Ciclo Celular , Humanos , Neoplasias Pulmonares/patología , Estrés Oxidativo/genéticaRESUMEN
We experimentally demonstrated a high-efficiency grating coupler by combining an interleaved etch and apodized structure for fiber-to-chip coupling. The grating coupler was optimized using the fast directional optimization method to achieve apodization. The grating coupler utilized a layout strategy involving an extended mask to avoid alignment errors for a multi-etch structure. The coupling efficiency was measured to be -2.2â dB at a wavelength of 1549â nm with a 3â dB bandwidth of 47â nm. The grating coupler, having no gold reflector, subwavelength index matching structure, or additional material layers, was fabricated using a commercial silicon photonics process with a minimum feature size of 140â nm. This grating coupler design provides a robust and effective coupling scheme and the proposed method can be employed to adopt the design in accordance with standard foundry design rules.
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The Kagome superconductors AV3Sb5 (A = K, Rb, Cs) have received enormous attention due to their nontrivial topological electronic structure, anomalous physical properties and superconductivity. Unconventional charge density wave (CDW) has been detected in AV3Sb5. High-precision electronic structure determination is essential to understand its origin. Here we unveil electronic nature of the CDW phase in our high-resolution angle-resolved photoemission measurements on KV3Sb5. We have observed CDW-induced Fermi surface reconstruction and the associated band folding. The CDW-induced band splitting and the associated gap opening have been revealed at the boundary of the pristine and reconstructed Brillouin zones. The Fermi surface- and momentum-dependent CDW gap is measured and the strongly anisotropic CDW gap is observed for all the V-derived Fermi surface. In particular, we have observed signatures of the electron-phonon coupling in KV3Sb5. These results provide key insights in understanding the nature of the CDW state and its interplay with superconductivity in AV3Sb5 superconductors.
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Low temperature during the vegetative stage depresses rice tillering. Zinc (Zn) can promote rice tiller growth and improve plant resistance to abiotic stress. Consequently, Zn application after low temperature might be an effective approach to promote rice tiller recovery. A water culture experiment with treatments of two temperatures (12 °C and 20 °C) and three Zn concentrations (0.08 µM, 0.15 µM and 0.31 µM ZnSO4·7H2O) was conducted to determine by analyzing rice tiller growth, nutrient absorption and hormones metabolism. The results showed that low temperature reduced rice tiller numbers and leaf age, decreased as well. Increasing Zn application after low temperature could enhance not only rice tiller growth rate but also N metabolism and tillering recovery, and correlation analysis showed a significantly positive correlation between tiller increment and Zn and N accumulation after low temperature. In addition, higher cytokinin (CTK)/auxin (IAA) ratio was maintained by promoted synthesis of CTK and IAA as well as enhanced IAA transportation from tiller buds to other parts with increased Zn application after cold stress, which resulted in accelerated germination and growth of tiller buds. These results highlighted that Zn application after low temperature promoted rice tiller recovery by increasing N and Zn accumulation and maintaining hormones balance.
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Adaptación Fisiológica/efectos de los fármacos , Frío/efectos adversos , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Zinc/metabolismoRESUMEN
Background: The occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis. Methods: The expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA. Results: Expression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-ß, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients. Conclusions: LINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.
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Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Aminoácido Oxidorreductasas/genética , Proteína Morfogenética Ósea 2/genética , Proteína C-Reactiva/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/patología , Factores de Transcripción NFI/genética , Componente Amiloide P Sérico/genética , Transducción de Señal , Análisis de SupervivenciaRESUMEN
Recent advances in single-cell technologies enable spatial expression profiling at the cell level, making it possible to elucidate spatial changes of cell-specific genomic features. The gene co-expression network is an important feature that encodes the gene-gene marginal dependence structure and allows for the functional annotation of highly connected genes. In this paper, we design a simple and computationally efficient two-step algorithm to recover spatially-varying cell-specific gene co-expression networks for single-cell spatial expression data. The algorithm first estimates the gene expression covariance matrix for each cell type and then leverages the spatial locations of cells to construct cell-specific networks. The second step uses expression covariance matrices estimated in step one and label information from neighboring cells as an empirical prior to obtain thresholded Bayesian posterior estimates. After completing estimates for each cell, this algorithm can further predict or interpolate gene co-expression networks on tissue positions where cells are not captured. In the simulation study, the comparison against the traditional cell-type-specific network algorithms and the cell-specific network method but without incorporating spatial information highlights the advantages of the proposed algorithm in estimation accuracy. We also applied our algorithm to real-world datasets and found some meaningful biological results. The accompanied software is available on https://github.com/jingeyu/CSSN.