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Generally, the development of novel TCIs entails the introduction of a warhead onto a potent noncovalent scaffold [1,21,32,33,34], or high-throughput screening (HTS) of small molecule covalent ligands [35,36,37] or covalent fragment libraries [31,36,38,39,40,41,42,43], with structure-based lead optimization supported by in silico approaches (e.g., covalent docking, virtual screening [32,44,45,46])

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Otherwise, without therapy, these syndromes were commonly presented in rats with the permanent occlusion of major vessels (veins and/or arteries [18,19,20,22,23,24,25,26,27,28,29,30], peripherally and centrally), major intoxication (lithium, alcohol) [39,40], acute pancreatitis [37], myocardial infarction [37], and maintained intra-abdominal hypertension [31]

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Symptoms associated with vitamin B12 deficiency include fatigue and lack of energy (due to anemia), and depression, psychosis and even dementia

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