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Neuroblastoma (NB) is the most common extracranial solid tumor in children, and the AURKA gene encodes a protein kinase involved in cell cycle regulation that plays an oncogenic role in a variety of human cancers. The aim of this study was to validate the biological function and prognostic significance of AURKA in NB using basic experiments and bioinformatics. Data obtained from Target and GEO databases were analyzed using various bioinformatic techniques. The expression of AURKA in 77 NB samples was detected by immunohistochemistry (IHC) method. The lentiviral RNA interference technique was employed to downregulate AURKA gene expression in NB cell lines. Additionally, cell counting kit-8 and flow cytometry analysis were conducted to investigate the impact of AURKA expression on cell proliferation, cell cycle progression, and apoptosis. A bioinformatic analysis showed that patients with NB in the AURKA-high-expression group had shorter OS (Overall Survival). Immune cell infiltration analysis showed that only activated CD4 T cell and type 2 T helper cell infiltration levels were higher in the AURKA-high-expression group than in the AURKA-low-expression group, with the infiltration levels of most other immune cells and cytokines lower in the high-expression group. Furthermore, the enhanced infiltration of activated CD4 T cells was associated with worse OS in patients with NB. IHC results showed that the AURKA expression was correlated with MYCN status and INSS stage. Log-rank test showed that pathological type, MYCN status, INSS stage, COG risk group, and AURKA expression was related to PFS (Progression-free survival) of NB patients, but COX regression analysis showed that none of the above factors were independently prognostic for PFS. In vitro, shRNA delivered via an AURKA-specific lentivirus significantly and consistently silenced endogenous AURKA expression in the human NB cell line SK-N-AS. This inhibited tumor cell proliferation, induced apoptosis, and caused G2/M-phase cell cycle arrest. Moreover, western blot assay showed significant reductions in the levels of mTOR, p70S6K, and 4E-BP1 phosphorylation in the AURKA-knockdown group. I found in subsequent experiments that NFYB can bind to the AURKA promoter and thus promote AURKA expression. High-level AURKA expression in NB is associated with poor patient prognosis. Silencing AURKA inhibited tumor cell proliferation, induced tumor cell apoptosis, and led to cell cycle arrest in the G2/M phase. Mechanistically, AURKA knockdown inhibited the phosphorylation and the activation of the mTOR1/p70S6K/4E-BP1 signaling pathway. In addition, AURKA was observed to regulate the infiltration levels of various immune cells in the NB tumor microenvironment, resulting in remodeling of the immunosuppressive tumor microenvironment.

Neuroblastoma (NB) is an embryonic tumour that originates in the sympathetic nervous system and occurs most often in infants and children under 2 years of age. Moreover, it is the most common extracranial solid tumour in children. Increasing studies suggest that intercellular communication within the tumour microenvironment is closely related to tumour development. This study aimed to construct a prognosis-related intercellular communication-associated genes model by single-cell sequencing and transcriptome sequencing to predict the prognosis of patients with NB for precise management. Single-cell data from patients with NB were downloaded from the gene expression omnibus database for comprehensive analysis. Furthermore, prognosis-related genes were screened in the TARGET database based on epithelial cell marker genes through a combination of Cox regression and Lasso regression analyses, using GSE62564 and GSE85047 for external validation. The patients’ risk scores were calculated, followed by immune infiltration analysis, drug sensitivity analysis, and enrichment analysis of risk scores, which were conducted for the prognostic model. I used the Lasso regression feature selection algorithm to screen characteristic genes in NB and developed a 21-gene prognostic model. The risk scores were highly correlated with multiple immune cells and common anti-tumour drugs. Furthermore, the risk score was identified as an independent prognostic factor for NB. In this study, I constructed and validated a prognostic signature based on epithelial marker genes, which may provide useful information on the development and prognosis of NB.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population 1 . Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies 2 – 10 , the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants. The replication and pathogenicity of the Omicron variant of SARS-CoV-2 is attenuated compared with the original strain and other variants.

Recent research highlights the pivotal role of N6-methyladenosine (m 6 A) modification and ferroptosis in the evolution of various cancers. This study aimed to establish a prognostic framework centered on genes associated with m 6 A and ferroptosis to enhance the accuracy of prognosis predictions for neuroblastoma (NB) patients, thereby improving targeted therapeutic strategies. Patient data, including expression profiles and clinical information from NB cases, were acquired from The Cancer Genome Atlas. Genes related to m 6 A modification and ferroptosis were identified, and those significant for prognosis were pinpointed using a combination of Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression. For further validation, the study utilized external datasets GSE62564 and GSE85047. A prognostic index was computed for each NB patient, followed by analyses of immune cell infiltration and potential drug responsiveness based on the prognostic model. Additionally, enrichment analysis was conducted on the prognostic scores. These scores showed a strong association with the tumor immune environment and the efficacy of prevalent cancer therapies. Moreover, the model’s prognostic score emerged as an independent predictive marker for NB. This research succeeded in creating and confirming a prognostic model rooted in m 6 A and ferroptosis-linked genes, promising to enrich the prognostic understanding and treatment approaches for NB.

The toxic effect of excessive manganese (Mn) on photosystem II (PSII) of woody species remains largely unexplored. In this study, five Mn concentrations (0, 12, 24, 36, and 48 mM) were used, and the toxicity of Mn on PSII behavior in leaves of Ligustrum lucidum was investigated using in vivo chlorophyll fluorescence transients. Results showed that excessive Mn levels induced positive L- and K- bands. Variable fluorescence at 2 ms (V J ) and 30 ms (V I ), absorption flux (ABS/RC), trapped energy flux (TR o /RC), and dissipated energy flux (DI o /RC) increased in Mn-treated leaves, whereas the performance index (PI ABS ), electron transport flux (ET o /RC), maximum quantum yield (φ Po ), quantum yield of electron transport (φ Eo ), and probability that an electron moves further than Q A − (ψ o ) decreased. Also, excessive Mn significantly decreased the net photosynthesis rate and increased intercellular CO 2 concentration. The results indicated that Mn blocked the electron transfer from the donor side to the acceptor side in PSII, which might be associated with the accumulation of Q A − , hence limiting the net photosynthetic rate.

Although the CoSb 3 -based skutterudite thermoelectric devices have been highly expected for wide uses such as waste heat recovery and space power supply, the limited long-term service stability majorly determined by the degradation of electrode interface obstructs its applications. Here, we built up an effective criterion for screening barrier layer based on the combination of negative interfacial reaction energy and high activation energy barrier of Sb migration through the formed interfacial reaction layer. Accordingly, we predicted niobium as a promising barrier layer. The experimental results show the skutterudite/Nb joint has the slowest interfacial reaction layer growth rate and smallest interfacial electrical resistivity. The fabricated 8-pair skutterudite module using Nb as barrier layer achieves a recorded conversion efficiency of 10.2% at hot-side temperature of 872 K and shows excellent stability during long-time aging. This simple criterion provides an effective guidance on screening barrier layer with bonding-blocking-conducting synergetic functions for thermoelectric device integration. Long-term service stability of thermoelectric devices is one of the major obstacles for their application. Here, the authors combine interfacial reaction energy and Sb migration activation energy barrier as a criterion to determine the interfacial reliability for skutterudite thermoelectric devices.

While robust interferon (IFN) responses in fish are critical for viral clearance, dysregulated signalling can trigger detrimental hyperinflammation, necessitating precise immunoregulatory mechanisms. This study identified Toll-interacting protein (TOLLIP) as a pivotal negative regulator of IFN production in grass carp (Ctenopharyngodon idella) . Upon grass carp reovirus (GCRV) infection, TOLLIP expression increases significantly in tissues and cells. Furthermore, TOLLIP overexpression reduced GCRV- and polyinosinic-polycytidylic acid (poly I:C)-induced IFN expression, whereas tollip knockdown increased the cellular IFN production capacity. TOLLIP subsequently binds and degrades STING. Further mechanistic studies revealed that TOLLIP degrades STING in a dose-dependent manner via an autophagy-lysosome-dependent pathway. Interestingly, autophagy-related protein 5 (ATG5) was found to interact with TOLLIP and reduce TOLLIP-mediated STING degradation after atg5 knockdown. In addition, TOLLIP attenuated STING-driven IFN activation and compromised antiviral efficacy. These findings demonstrate that fish TOLLIP plays a specialized regulatory role in antiviral innate immunity, balancing immune defence with homeostasis maintenance.

Neuroblastoma (NB) is the most common extracranial solid tumor in early childhood and frequently presents with bone marrow (BM) metastasis, particularly in high-risk cases. Metastatic NB cells residing in the BM exhibit distinct biological behaviors and are closely associated with treatment resistance and poor prognosis. Emerging evidence suggests that metabolic reprogramming is a hallmark of NB progression; however, its regulatory landscape within the bone marrow microenvironment remains poorly understood. This study aimed to systematically elucidate the molecular mechanisms underlying metabolic reprogramming in bone marrow–infiltrating metastatic NB cells by integrating single-cell transcriptomic data, bulk RNA-sequencing profiles, and in vitro functional validation. Single-cell RNA-sequencing data from 17 bone marrow aspirates of NB patients—with and without marrow infiltration—were retrieved from the GEO database, while bulk RNA-seq data from 155 NB tumor samples were obtained from the TARGET database. A suite of bioinformatics tools, including Seurat, Harmony, CellChat, and SCENIC, was employed to perform multi-dimensional analyses such as cell subtype annotation, intercellular communication mapping, and transcription factor regulon construction. AUCell scoring, differential gene expression analysis, random survival forest modeling, and Kaplan–Meier survival analysis were conducted to identify key genes involved in metabolic reprogramming and to characterize their immune infiltration features. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and single-cell pathway scoring were applied to predict the metabolic and immune pathways associated with these candidate genes. Furthermore, co-expression network analysis was used to evaluate the relationships between candidate genes and known NB regulatory factors. Finally, in vitro experiments were carried out to validate the roles of selected genes in regulating NB cell proliferation, migration, invasion, and mitochondrial function. Single-cell transcriptomic analysis of bone marrow–derived NB samples identified nine distinct cell subpopulations with diverse intercellular communication networks. Among these, the ligand–receptor pair MDK–NCL emerged as a key mediator of cell–cell signaling. Regulatory network analysis revealed five critical regulons—JUND, JUNB, FOS, E2F1, and KLF16—closely associated with metabolic reprogramming in NB. The “Neuroblastoma cell” cluster displayed markedly elevated metabolic activity. Through integrated analyses, five core metabolic reprogramming genes (MRPL21, NHP2, RPL13, RPL18A, and RPL27A) were identified and shown to be significantly associated with poor prognosis. High expression of these genes correlated with an immunosuppressive tumor microenvironment, characterized by reduced infiltration of monocytes, M1 macrophages, and T cells. Functional enrichment analysis revealed that these genes were primarily enriched in oxidative phosphorylation, MYC targets, PI3K-Akt, and p53 signaling pathways. Co-expression network analysis further demonstrated that MRPL21 and NHP2 positively correlated with known NB regulatory genes TP53, NRAS, and NKIF1B. In vitro assays confirmed that MRPL21 knockdown significantly impaired NB cell proliferation, migration, invasion, and mitochondrial oxidative phosphorylation. This study identified five key genes involved in metabolic reprogramming of bone marrow–infiltrating NB cells, which are closely associated with immunosuppressive microenvironment formation and enrichment in tumor-associated metabolic pathways. Among these, MRPL21 plays a pivotal role in regulating NB cell proliferation and mitochondrial function, underscoring its potential as a promising therapeutic target. These findings suggest that integrated strategies targeting both tumor metabolism and the immune microenvironment may provide new avenues for the treatment of high-risk, metastatic NB.

In recent years, along with the rapid development in the domain of artificial intelligence and aerospace, aerospace combined with artificial intelligence is the future trend. As an important basic tool for Natural Language Processing, Named Entity Recognition technology can help obtain key relevant knowledge from a large number of aerospace data. In this paper, we produced an aerospace domain entity recognition dataset containing 30 k sentences in Chinese and developed a named entity recognition model that is Multi-Feature Fusion Transformer (MFT), which combines features such as words and radicals to enhance the semantic information of the sentences. In our model, the double Feed-forward Neural Network is exploited as well to ensure MFT better performance. We use our aerospace dataset to train MFT. The experimental results show that MFT has great entity recognition performance, and the F 1 score on aerospace dataset is 86.10%.