Identification of immune-related signature with prognosis in children with stage 4 and 4S neuroblastoma.

OBJECTIVE: Spontaneous regression of tumors is an attractive phenomenon that most commonly occurs in stage 4S neuroblastoma (NB). However, the mechanism underlying this phenomenon remains unclear. METHODS: Datasets correlated with NB were downloaded from online public databases, the differentially expressed genes (DEGs) between stage 4 and 4S associated with immunity were identified, and functional enrichment analysis was utilized to explore the potential functions and signaling pathways of these DEGs. In addition, based on these DEGs, a prognostic signature was constructed and validated, and differences in immune cell infiltration were analyzed. RESULTS: A total of 13 DEGs were finally identified, and functional enrichment analysis revealed that these DEGs were primarily enriched in the positive regulation of neuron differentiation and TGF-ß signaling pathway. The signature successfully stratifies patients into two risk score groups and performs well in judging prognosis and predicting overall survival time. In addition, the prognostic value of the risk score calculated by the signature was independent of clinical factors. The results of immune cell infiltration showed that patients with a high infiltration of resting CD4 + memory T cells had a better prognosis, while plasma cells had a worse prognosis. CONCLUSION: The results of the functional enrichment analysis of these identified DEGs suggested that these DEGs may be related to spontaneous regression of NB. In addition, the prognostic signature has the potential to create new risk stratification in patients with NB.

The direct catalytic synthesis of ultrasmall Cu2O-coordinated carbon nitrides on ceria for multimodal antitumor therapy.

Engineering chem-/sono-/photo-multimodal antitumor therapies has become an efficient strategy to combat malignant tumors. However, the existence of hypoxia in the tumor microenvironment (TME) leads to limited sonodynamic or photodynamic efficiency because O2 is the key reactant during the process of generation of reactive oxygen species (ROS). Here, to design a desirable platform that can simultaneously convert H2O2 in the TME into ROS and O2 for efficient chem-/sono-/photo-multimodal tumor therapies, we have created ultrasmall Cu2O-coordinated carbon nitride on a biocompatible ceria substrate (denoted as Cu2O-CNx@CeO2) via a self-assisted catalytic growth strategy. The chemical and morphological structures, ROS and O2 generation activities, and chemo-/photo-/sono-dynamic specificities of Cu2O-CNx@CeO2 when serving as multifunctional biocatalytic agents were systematically disclosed. The experimental studies validated that Cu2O-CNx@CeO2 presents state-of-the-art peroxidase-like and catalase-like activities. Moreover, the light excitation and ultrasound irradiation were also demonstrated to boost ROS production. The in vitro and in vivo experiments suggest that Cu2O-CNx@CeO2 can efficiently inhibit the growth of malignant melanoma via chem-/sono-/photo-multimodal antitumor ability. We believe that applying these new biocatalysts with dual catalytic activities of producing ROS and O2 will offer a new path for engineering multimodal nanoagents to combat malignant tumors.

Expression of ADRB2 in children with neuroblastoma and its influence on prognosis.

Objective: Neuroblastoma (NB), originating from sympathetic spinal tissue, is a serious threat to the life of children. Especially in the high-risk group, an overall five-year survival rate less than 50% indicates an extremely poor clinical outcome. Here, the expression the of ß-2 adrenergic (ADRB2) receptor gene in tumor tissues of children with NB was detected and the correlation between its expression and clinical characteristics and prognosis was analyzed. Methods: Forty-five tumor tissue samples and forty-eight paraffin sections of NB were obtained from Children's Hospital of Chongqing Medical University from 2015 to 2021. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to detect the expression of ADRB2 at the mRNA level and immunohistochemistry (IHC) at the protein level. Results: For the RT-qPCR, the analysis showed that the expression of ADRB2 in the high-risk group was significantly lower (P = 0.0003); in addition, there were also statistically significant differences in Shimada classification (P = 0.0025) and N-MYC amplification (P = 0.0011). Survival prognosis analysis showed that the prognosis was better with high ADRB2 expression (P = 0.0125), and the ROC curve showed that ADRB2 has a certain accuracy in predicting prognosis (AUC = 0.707, CI: 0.530-0.884). Moreover, the expression of ADRB2, N-MYC amplification and bone marrow metastasis were the factors that independently affected prognosis, and at the protein level, the results showed that the differential expression of ADRB2 was conspicuous in risk (P = 0.0041), Shimada classification (P = 0.0220) and N-MYC amplification (P = 0.0166). In addition, Kaplan-Meier curves showed that the prognosis in the group with high expression of ADRB2 was better (P = 0.0287), and the ROC curve showed that the score of ADRB2 had poor accuracy in predicting prognosis (AUC = 0.662, CI: 0.505-0.820). Conclusion: ADRB2 is a protective potential biomarker and is expected to become a new prognostic biomolecular marker of NB.

Single-cell landscape analysis reveals distinct regression trajectories and novel prognostic biomarkers in primary neuroblastoma.

Neuroblastoma (NB), which is the most common pediatric extracranial solid tumor, varies widely in its clinical presentation and outcome. NB has a unique ability to spontaneously differentiate and regress, suggesting a potential direction for therapeutic intervention. However, the underlying mechanisms of regression remain largely unknown, and more reliable prognostic biomarkers are needed for predicting trajectories for NB. We performed scRNA-seq analysis on 17 NB clinical samples and three peritumoral adrenal tissues. Primary NB displayed varied cell constitution, even among tumors of the same pathological subtype. Copy number variation patterns suggested that neuroendocrine cells represent the malignant cell type. Based on the differential expression of sets of related marker genes, a subgroup of neuroendocrine cells was identified and projected to differentiate into a subcluster of benign fibroblasts with highly expressed CCL2 and ZFP36, supporting a progressive pathway of spontaneous NB regression. We also identified prognostic markers (STMN2, TUBA1A, PAGE5, and ETV1) by evaluating intra-tumoral heterogeneity. Lastly, we determined that ITGB1 in M2-like macrophages was associated with favorable prognosis and may serve as a potential diagnostic marker and therapeutic target. In conclusion, our findings reveal novel mechanisms underlying regression and potential prognostic markers and therapeutic targets of NB.

Multifaceted Catalytic ROS-Scavenging via Electronic Modulated Metal Oxides for Regulating Stem Cell Fate.

Developing reactive oxygen species (ROS)-scavenging nanostructures to protect and regulate stem cells has emerged as an intriguing strategy for promoting tissue regeneration, especially in trauma microenvironments or refractory wounds. Here, an electronic modulated metal oxide is developed via Mn atom substitutions in Co3 O4 nanocrystalline (Mn-Co3 O4 ) for highly efficient and multifaceted catalytic ROS-scavenging to reverse the fates of mesenchymal stem cells (MSCs) in oxidative-stress microenvironments. Benefiting from the atomic Mn-substitution and charge transfer from Mn to Co, the Co site in Mn-Co3 O4 displays an increased ratio of Co2+ /Co3+ and improved redox properties, thus enhancing its intrinsic and broad-spectrum catalytic ROS-scavenging activities, which surpasses most of the currently reported metal oxides. Consequently, the Mn-Co3 O4 can efficiently protect the MSCs from ROS attack and rescue their functions, including adhesion, spreading, proliferation, and osteogenic differentiation. This work not only establishes an efficient material for catalytic ROS-scavenging in stem-cell-based therapeutics but also provides a new avenue to design biocatalytic metal oxides via modulation of electronic structure.