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Summary Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg⁻¹; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF‐04859989 (30 mg kg⁻¹; s.c.); or (iv) PF‐04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non‐rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non‐rapid eye movement sleep delta power and sleep spindles. PF‐04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non‐rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics. 

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers. Vast efforts have been dedicated to small molecular, macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation, including local facial amphiphilicity and global amphiphilicity. This work conceptualizes Facial Amphiphilicity Index (FAI) as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy. FAI is a ratio of numbers of charges to rings, representing both compositions of hydrophilicity and hydrophobicity. Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria. Both monocyclic and bicyclic compounds are nonantimicrobial regardless of FAIs. Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid. While low and high FAIs respectively lead to higher and lower antimicrobial efficacy, in consideration of cytotoxicity, the sweet spot is typically suited with intermediate FAIs for each specific system. This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes. The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.