Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI. Graphical abstract

Background. Neuroblastoma is a common solid tumor originating from the sympathetic nervous system, commonly found in children, and it is one of the leading causes of tumor-related deaths in children. In addition to pathological features, molecular-level features, such as how much gene expression is present and the mutational profile, may provide useful information for the precise treatment of neuroblastoma. Transcription factors (TFs) play an important regulatory role in all aspects of cellular life activities. But there are currently no studies on transcription factor-based biomarkers of neuroblastoma prognosis, and this study is much needed. Methods. We downloaded RNA transcriptome data and clinical data from the TARGET database to construct a prognostic model. The prognostic model was constructed by using univariate Cox analysis, LASSO, and multivariate Cox regression. We divided the patients into low-risk and high-risk groups using the median value of the risk score as the cut-off. Then, we validated the prognostic model with the dataset GSE49710. Results. We constructed a prognostic model consisting of eight genes (SATB1, ZNF564, SOX14, EN1, IKZF2, SLC2A4RG, FOXJ2, and ZNF521). Patients in the high-risk group had a lower survival rate than those in the low-risk group. The area under the 3-year ROC curve of the model reached 0.825, suggesting a good predictive efficacy. We performed target gene prediction for the eight transcription factors in the model using six online databases and found that TUT1 may be a target gene for transcription factor EN1 and is associated with immune infiltration. Conclusion. This prognostic model consisting of eight transcription factor-associated genes demonstrated reliable predictive efficacy. This prediction model may provide new potential targets for the treatment of neuroblastoma and personalized monitoring of neuroblastoma patients with high and low risk.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease primarily affecting preterm infants, characterised by impaired alveolar development and persistent inflammation, particularly associated with ventilator‐induced lung injury due to mechanical ventilation. In this study, we performed an integrated bioinformatic analysis of multiple datasets (GSE108754 and GSE39840) and identified 203 differentially expressed genes (DEGs) between BPD and control samples. Functional enrichment analysis revealed significant involvement in cytokine‐mediated signalling, response to lipopolysaccharide and regulation of interferon‐beta production. Using machine learning algorithms (LASSO, SVM‐RFE and Random Forest), we identified three hub genes (IL6, TFRC and PIEZO1) with high diagnostic accuracy for BPD. Immune infiltration analysis indicated altered immune cell proportions in BPD, with PIEZO1 expression positively correlated with neutrophil infiltration. Experimental validation confirmed elevated NETosis markers (PADI4, MPO, dsDNA) in BPD patients and further demonstrated that PIEZO1 overexpression promotes NET formation via calcium overload, which was inhibited by verapamil. Additionally, using a co‐culture system, we showed that PIEZO1‐induced NETosis exacerbates pulmonary fibrosis in lung epithelial cells. These findings highlight PIEZO1 as a key regulator of NETosis in BPD and a promising therapeutic target for mitigating lung injury and fibrosis.

Osteosarcoma is widely concerned because it is a malignant tumor with a high incidence rate among teenagers. Although some chemical, physical, and synergetic technologies have been developed to treat malignant osteosarcoma, molecular mechanism of structural nanomechanics is indistinct, especially for inducement mechanism, malignant evaluation, and distant metastasis of osteosarcoma. We fabricated photo‐responsive biomaterials as the biofunctional UV‐mediated “cell adhesion” switch to construct the advanced microarrays on cell culture plates. The adhesion‐automatic microarrays were modified with fibronectin and osteosarcoma cells were micropatterned on the microarrays by microscopy and AFM observation. The focal adhesion (FA) was matured in microarrayed osteosarcoma cells by adhesion phase separation. The influence of phase‐separated FA‐induced cytoskeleton bias on spatial mechanical property and force heterogeneity is investigated to disclose its interaction with nuclear activity in microarrayed osteosarcoma cells. Heterogeneous force remodeling could monitor nuclear force–sensing mechanotransduction, based on nuclear ectopia configuration by the evaluation of LaminA/C, Ki67 and YAP analysis. This study will provide theoretical potential for understanding phase‐separated adhesion, heterogeneous mechanical remodeling, and nuclear force–sensing mechanotransduction of malignant osteosarcoma.