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Abstract Caspase-4 (CASP4) is a member of the inflammatory caspase subfamily and promotes inflammation. Here, we report that CASP4 in lung adenocarcinoma cells contributes to both tumor progression via angiogenesis and tumor hyperkinesis and tumor cell killing in response to high interferon (IFN)-γ levels. We observe that elevated CASP4 expression in the primary tumor is associated with cancer progression in patients with lung adenocarcinoma. Further, CASP4 knockout attenuates tumor angiogenesis and metastasis in subcutaneous tumor mouse models. CASP4 enhances the expression of genes associated with angiogenesis and cell migration in lung adenocarcinoma cell lines through nuclear factor kappa-light chain-enhancer of activated B cell signaling without stimulation by lipopolysaccharide or tumor necrosis factor. CASP4 is induced by endoplasmic reticulum stress or IFN-γ via signal transducer and activator of transcription 1. Most notably, lung adenocarcinoma cells with high CASP4 expression are more prone to IFN-γ-induced pyroptosis than those with low CASP4 expression. Our findings indicate that the CASP4 level in primary lung adenocarcinoma can predict metastasis and responsiveness to high-dose IFN-γ therapy due to cancer cell pyroptosis.

The Weilasituo Li–polymetallic deposit, located on the western slope of the southern Great Xing’an Range in the eastern Central Asian Orogenic Belt, is hosted by quartz porphyry with crypto-explosive breccia-type Li mineralisation atop and vein-type Sn-Mo-W-Zn polymetallic mineralisation throughout the breccia pipe. This study introduces new data on multistage quartz and mica in situ trace elements; the study was conducted using laser ablation inductively coupled plasma mass spectrometry and 40Ar/39Ar dating of zinnwaldite to delineate the metallogenic age and genesis of Li mineralisation. Zinnwaldite yields a plateau age of 132.45 ± 1.3 Ma (MSWD = 0.77), representing Early Cretaceous Li mineralisation. Throughout the magmatic–hydrothermal process, quartz trace elements showed Ge enrichment. Li, Al, and Ti contents decreased, with Al/Ti and Ge/Ti ratios increasing, indicating increased magmatic differentiation, slight acidification, and cooling. Mica’s rising Li, Rb, Cs, Mg, and Ti contents and Nb/Ta ratio, alongside its falling K/Rb ratio, indicate the magma’s ongoing crystallisation differentiation. Fractional crystallisation primarily enriched Li, Rb, and Cs in the late melt. Mica’s high Sc, V, and W contents indicate a high fO2 setting, with a slightly lower fO2 during zinnwaldite formation. Greisenisation observed Zn, Mg, and Fe influx from the host rock, broadening zinnwaldite distribution and forming minor Zn vein orebodies later. Late-stage fluorite precipitation highlights a rise in F levels, with fluid Sn and W levels tied to magma evolution and F content. In summary, the Weilasituo Li–polymetallic deposit was formed in an Early Cretaceous extensional environment and is closely related to a nearby highly differentiated Li-F granite. During magma differentiation, rare metal elements such as Li and Rb were enriched in residual melts. The decrease in temperature and the acidic environment led to the precipitation of Li-, Rb-, and W-bearing minerals, and the increased F content in the late stage led to Sn enrichment and mineralisation. Fluid metasomatism causes Zn, Mg, and Fe in the surrounding rock to enter the fluid, and Zn is enriched and mineralised in the later period.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs’ histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.