An electrophysiological and proteomics roadmap for human induced glutamatergic neurons: fine-tuning of culture conditions for pathophysiological studies.

Cognitive impairment is characterized by deficits in learning, memory, attention, and executive function and is commonly observed in older adults []. It has been associated with several metabolic abnormalities, including oxidative stress [], mitochondrial dysfunction [], impaired energy metabolism [], dysregulated amino acid metabolism, and altered lipid metabolism [,]. These metabolic changes can lead to neuronal dysfunction, synaptic damage, and cognitive decline []. Therefore, understanding these metabolic changes may help identify potential targets for preventing or alleviating cognitive impairment. Although cognitive impairment primarily affects the central nervous system, direct analysis of brain tissue is not feasible in most experimental and clinical settings []. Peripheral blood has emerged as a practical and minimally invasive biospecimen for investigating systemic metabolic alterations associated with cognitive impairment []. Blood metabolomics provides a valuable approach for identifying metabolic signatures, investigating metabolic alterations, and evaluating therapeutic responses []. Among the available analytical platforms, untargeted H-NMR metabolomics enables comprehensive profiling of circulating metabolites and simultaneous assessment of multiple metabolic pathways, including oxidative stress, amino acid, lipid, and energy metabolism []. Sonn., a tropical fruit valued for its high nutritional quality, is rich in bioactive phytochemicals, including polyphenols, flavonoids, phenolic acids, anthocyanins, and proanthocyanidins [,]. These compounds exhibit a broad spectrum of biological activities, including antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloidogenic, and acetylcholinesterase inhibitory effects [,]. To enhance these health benefits, postharvest thermal processing is applied to produce black lychee as a value-added functional food. The resulting browning reactions alter its phytochemical composition, significantly boosting total phenolic content and antioxidant capacity compared with fresh lychee [,]. This enriched phytochemical profile may contribute to the biological activities of black lychee, particularly its antioxidant and neuroprotective properties.