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Decreased ventrolateral PFC activity is another common feature of bipolar mania that differentiates it from depressed, euthymic state, and healthy controls (99, 105, 106, 137)

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In contrast, in macrophage-like cells, synthetic ICA derivatives (at concentrations of 10.8–21.6 μM) elicit a distinct response: within 4 hours of exposure, they activate endosomal TLR3 and surface TLR4 (164), triggering cascades of type I interferons (e.g., IFNB1) and proinflammatory cytokines (e.g., IL6, IL12A/B) that amplify innate antiviral immunity—underscoring ICA’s context-dependent functional plasticity