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M1 microglial activation is crucial for the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and there is growing evidence that glucose metabolism is frequently involved in microglial activation. However, the molecular mechanism of glycolysis and its role in M1 microglial activation in context of EBI are not yet fully understood. In this study, rstly, the relationship between aerobic glycolysis and M1 microglial activation as well as SAH-induced EBI was researched in vivo. Then, intervention on mammalian target of rapamycin (mTOR) was performed to investigate the effects on glycolysis-dependent M1 microglial activation and EBI, and its relationship with hypoxia-inducible factor-1α (HIF-1α) in vivo. Next, Hif-1α was inhibited to analyze its role in aerobic glycolysis, M1 microglial activation and EBI in vivo. Lastly, both in vivo and in vitro, mTOR inhibition and Hif-1α enhancement were administered simultaneously, and the combined effects were further con rmed again. The results showed that aerobic glycolysis and M1 microglial polarization were increased after SAH, and glycolytic inhibition could attenuate M1 microglial activation and EBI. Inhibition of mTOR reduced glycolysis-dependent M1 microglial polarization and EBI severity by down-regulating HIF-1α expression, while enhancement had the opposite effects. Blockading HIF-1α had the similar effects as suppressing mTOR, while HIF-1α agonist worked against mTOR antagonist when administered simultaneously. In conclusion, the present study showed new evidence that aerobic glycolysis induced by mTOR/HIF-1α might promote EBI after SAH by activating M1 microglia. This nding provided new insights for the treatment of EBI.

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M1 microglial activation is crucial for the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and there is growing evidence that glucose metabolism is frequently involved in microglial activation. However, the molecular mechanism of glycolysis and its role in M1 microglial activation in context of EBI are not yet fully understood. In this study, firstly, the relationship between aerobic glycolysis and M1 microglial activation as well as SAH-induced EBI was researched in vivo. Then, intervention on mammalian target of rapamycin (mTOR) was performed to investigate the effects on glycolysis-dependent M1 microglial activation and EBI, and its relationship with hypoxia-inducible factor-1α (HIF-1α) in vivo. Next, Hif-1α was inhibited to analyze its role in aerobic glycolysis, M1 microglial activation and EBI in vivo. Lastly, both in vivo and in vitro, mTOR inhibition and Hif-1α enhancement were administered simultaneously, and the combined effects were further confirmed again. The results showed that aerobic glycolysis and M1 microglial polarization were increased after SAH, and glycolytic inhibition could attenuate M1 microglial activation and EBI. Inhibition of mTOR reduced glycolysis-dependent M1 microglial polarization and EBI severity by down-regulating HIF-1α expression, while enhancement had the opposite effects. Blockading HIF-1α had the similar effects as suppressing mTOR, while HIF-1α agonist worked against mTOR antagonist when administered simultaneously. In conclusion, the present study showed new evidence that aerobic glycolysis induced by mTOR/HIF-1α might promote EBI after SAH by activating M1 microglia. This finding provided new insights for the treatment of EBI.

Objective: This study aims to explore the role of aniline-actin binding protein (ANLN) in the prognosis of lung adenocarcinoma (LUAD) and its role in immune infiltration, and to provide new ideas for clinical diagnosis and treatment.Methods: In this study, we applied bioinformatics methods to analyze the expression pattern and prognostic value of ANLN in LUAD ,and confirmed its independent prognostic value through Cox analysis. TIMER was used to evaluate the correlation between ANLN and tumor infiltrating immunity. LinkedOmics was used to study the co-expressed genes and functional networks related to ANLN.The TIMER database was used to analyze the correlation between ANLN co-expressed genes and tumor infiltrating immune cells. Results: ANLN is highly expressed in most cancers. In the TCGA-LUAD cohort, ANLN was highly expressed in LUAD. ANLN was significantly related to the grade , T stage and N stage of patients with LUAD. It was verified in multiple independent queues. The high expression and highly mutation of ANLN predicts poor survival .Multivariate COX analysis showed that ANLN was an independent risk factor for survival . GSEA analysis shows that ANLN regulates cell cycle, and other pathways. The expression of ANLN was significantly correlated with the level of B cell infiltration.Conclusions: ANLN is closely related to the prognosis of patients with LUAD and tumor immune cell infiltration suggesting that ANLN is a key factor regulating the recruitment of immune cells to LUAD and may play an important role in immune.