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Bioinformatics analysis Hierarchical clustering analyzes were performed using the GenePattern software ( Raw RNA-Seq reads were pre-processed with Trimmomatic software ( Homo sapiens reference transcriptome (Gencode, release 36) and the total number of reads mapped per transcript and the number of transcripts per million were calculated with Salmon software ( summarizeToGene function of the R Tximeta package ( P value less than 0.05 obtained in the False Discovery Rate (FDR) analysis were considered differentially expressed (DEG) and submitted to functional enrichment analysis with Ingenuity Pathways Analysis software (IPA, Qiagen) using default parameters

These results, which suggest that D-Nle-Tyr-Ile-NH(CH 2 ) 5 CONH 2 is likely to be relatively hydrophobic, are in agreement with the outcome of QSAR modeling estimates generated by ADMET Predictor that calculated an octanol:water partition coefficient of 28.18 for D-Nle-Tyr-Ile-NH(CH 2 ) 5 CONH 2 (Table 6)

E.HendersonD

To verify whether MeCbl directly engages GSDME at Cys180 in vivo, WT (GSDME WT ), C180A (GSDME C180A ) and D270A (GSDME D270A ) GSDME plasmids constructed in adenovirus vector were injected into Gsdme -/- mice via tail vein (Fig