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Mulberry has been widely studied for its capacity to tolerate heavy metals. However, the anatomical and molecular response mechanisms of Cd detoxification and transportation in mulberry have not been fully elucidated. In this study, the anatomical characteristics, Cd and mineral element uptake and transport, and transcriptome profiling of mulberry were studied under Cd stress. The results showed that mulberry possessed strong detoxification and self-protection abilities against Cd stress. The growth and photosynthetic pigment contents of