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Lett."},{"key":"10.1016\/j.bioorg.2026.110502_bb0390","first-page":"179","article-title":"Tetrazolium (MTT) assay for cellular viability and activity","volume":"79","author":"Morgan","year":"1998","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.bioorg.2026.110502_bb0395","doi-asserted-by":"crossref","unstructured":"I. Lakshmanan, S.K. Batra, Protocol for apoptosis assay by flow cytometry using annexin V Staining Method, 3 (6) (2013) e374-e374. http:\/\/www.bio-protocol.org\/e374.","DOI":"10.21769\/BioProtoc.374"},{"key":"10.1016\/j.bioorg.2026.110502_bb0400","series-title":"Assay Guidance Manual [Internet]","author":"Glickman","year":"2012"},{"key":"10.1016\/j.bioorg.2026.110502_bb0405","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","article-title":"Merck molecular force field. I. 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