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Loss‐of‐function mutations in SDH and FH, which have been detected in “hereditary paraganglioma” and “hereditary leiomyomatosis and renal cell cancer”, were shown to cause abnormal accumulation of succinate and fumarate, respectively.23, 24 The accumulated metabolites inhibited PHD through product inhibition, whereby the product of an enzymatic reaction directly binds to the enzyme and inhibits its activity for negative feedback regulation, and eventually leads to the stabilization of HIF‐1α23, 24 (Table 2)

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The 2.9 million particles were subjected to ab initio reconstruction to generate three classes