20:T4a5,Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers for tumor treatment are limited. This study proposes biodegradable K₃ZrF₇:Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy. ZrNPs, which are similar to ion reservoirs, can be dissolved inside cancer cells and release high amounts of K⁺ and [ZrF₇]^3- ions, resulting a surge in intracellular osmolarity and homeostasis imbalance. This further induces an increase in reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, and interleukin-1β (IL-1β) maturity, and results in cytolysis. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity confirmed by enhanced dendritic cells (DCs) maturity and frequency of effector-memory T cells, as well as observably inhibiting tumor growth and pulmonary metastasis. This work is believed to extend the biomedical applications of upconversion nanomaterials and deepen the understanding of intrinsic immunomodulatory activity of nanomaterials.21:T52f,ETS variant 4 (ETV4), together with ETV1 and ETV5, constitute the PEA3 subfamily of ETS transcription factors, which are implicated in the progression of many cancers. However, the clinicopathologic significance and molecular events regulated by ETV4 in lung cancer are still poorly understood, especially in squamous cell carcinoma of the lung. Here, we aimed to identify functional targets involved in ETV4-driven lung tumorigenesis. Microarray analysis and validation data revealed that ETV4 was the most preponderant PEA3 factor, which was significantly related to the advanced stage, lymph node metastasis, and poor prognosis of non-small cell lung cancers (NSCLCs; all P < .001). Reduced ETV4 expression suppressed the growth and metastasis of NSCLC both in vivo and in vitro. Microarray, gain, or loss of function and luciferase report assays revealed the direct regulatory effect of ETV4 on the expression of focal adhesion gene PXN and matrix metalloproteinase 1 (MMP1), and PXN and/or MMP1 inhibition partially abolished cell proliferation and migration induced by ETV4. Kaplan-Meier analysis indicated that ETV4 and PXN or MMP1 co-overexpression is associated with poor prognosis in human NSCLCs. In conclusion, the ETV4-PXN and ETV4-MMP1 axes are useful biomarkers of tumor progression and worse outcomes in NSCLCs.22:T6a3,

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