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It chelated Cd in the cytosol and drove its secretion to extracellular spaces, promoting its loading into xylem vessels for root-to-shoot translocation and accumulation in leaves and straws, but not in rice grains ( NtCAL1 in tobacco functions as a positive factor in plant Cd accumulation and resistance ( NtCAL1 enhanced the content of ascorbic acid and the activities of antioxidant enzymes such as catalase (CAT) and ascorbate peroxidase (APX), helping to scavenge oxidative stress induced by Cd ( NtRAMP3, NtHMA, NtHMA ( AtPDF2.5 in Arabidopsis mediated Cd tolerance and accumulation (Luo et al., 2019), and its expression, which is induced by Cd, was primarily expressed in root xylem vascular bundles (Luo et al., 2020)

FDA review Applications of MIDD principles in FDA reviews started in early 1990 s and have continuously evolved to the transformative presence today [5]