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Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. However, little is known about the MACB metabolism in vivo. Here, we determined the metabolism of MACB in zebrafish and microglia cell model. We found that MACB mainly disrupted the metabolism of branched-chain amino acids (Leu, Ile and Val) in zebrafish model and gamma-aminobutyric acid (GABA) pathway-related amino acids in microglia model. Additionally, we demonstrated that MACB can be metabolized by the mixed-function oxidase CYP1A2 enzyme which could be inhibited by estrogen causing the gender-difference in the accumulation of MACB in vivo. These results indicated that MACB perturbed metabolism and induced neurological disorders, particularly in the female zebrafish. The 7-membered ring of DZPs can be easily opened and generate MACB during chlorine disinfection. MACB induced metabolic perturbation and neurological disorders. Note: DZP, diazepam; MACB, 2-methylamino-5-chlorobenzophenone; ACB, 2-amino-5-chlorobenzophenone; BCAAs, branched-chain amino acids. [Display omitted] • The emerging MACB disturbed the amino acids metabolism in zebrafish model. • MACB disrupted the GABA pathway-related amino acids homeostasis in microglia model • Gender difference in metabolism of MACB owed much to CYP1A2 activity. [ABSTRACT FROM AUTHOR]

The P300 event-related potential (ERP) varies across individuals, and exploring this variability deepens our knowledge of the event, and scope for its potential applications. Previous studies exploring the P300 have relied on either electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). We applied simultaneous event-related EEG-fMRI to investigate how the network structure is updated from rest to the P300 task so as to guarantee information processing in the oddball task. We first identified 14 widely distributed regions of interest (ROIs) that were task-associated, including the inferior frontal gyrus and the middle frontal gyrus, etc. The task-activated network was found to closely relate to the concurrent P300 amplitude, and moreover, the individuals with optimized resting-state brain architectures experienced the pruning of network architecture, i.e. decreasing connectivity, when the brain switched from rest to P300 task. Our present simultaneous EEG-fMRI study explored the brain reconfigurations governing the variability in P300 across individuals, which provided the possibility to uncover new biomarkers to predict the potential for personalized control of brain-computer interfaces. • Simultaneous EEG-fMRI is used to study P300 variability during the oddball task. • Network reconfiguration helps to uncover the P300 variability. • Low P300 group shows enhanced connectivity deviating from resting state. • The smaller the network updates, the larger the P300 amplitude. [ABSTRACT FROM AUTHOR]