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BackgroundHypercholesterolemia, a critical contributor to cardiovascular disease, is not fully understood in terms of its relationship with serum metabolites and their role in disease pathogenesis.MethodsThis study leveraged GWAS data to explore the relationship between serum metabolites and hypercholesterolemia, pinpointing significant metabolites via Mendelian Randomization (MR) and KEGG pathway enrichment analysis. Data on metabolites were sourced from a European population, with analysis focusing on individuals diagnosed with hypercholesterolemia.ResultsOut of 486 metabolites analyzed, ten showed significant associations with hypercholesterolemia, categorized into those enhancing risk and those with protective effects. Specifically, 2-methoxyacetaminophen sulfate and 1-oleoylglycerol (1-monoolein) were identified as risk-enhancing, with odds ratios (OR) of 1.545 (95% CI: 1.230–1.939; P_FDR = 3E−04) and 1.462 (95% CI: 1.036–2.063; P_FDR = 0.037), respectively. On the protective side, 3-(cystein-S-yl)acetaminophen, hydroquinone sulfate, and 2-hydroxyacetaminophen sulfate demonstrated ORs of 0.793 (95% CI: 0.735–0.856; P_FDR = 6.18E−09), 0.641 (95% CI: 0.423–0.971; P_FDR = 0.042), and 0.607 (95% CI: 0.541–0.681; P_FDR = 5.39E−17), respectively. In addition, KEGG pathway enrichment analysis further revealed eight critical pathways, comprising “biosynthesis of valine, leucine, and isoleucine”, “phenylalanine metabolism”, and “pyruvate metabolism”, emphasizing their significant role in the pathogenesis of hypercholesterolemia.ConclusionThis study underscores the potential causal links between particular serum metabolites and hypercholesterolemia, offering innovative viewpoints on the metabolic basis of the disease. The identified metabolites and pathways offer promising targets for therapeutic intervention and warrant further investigation.

Rhythmic neural activities are critical to the efficiency of regulatory procedures in brain functions. However, brain functions usually decline in aging as accompanied by frequency shift and temporal dedifferentiation of neural activities. Considering the strong oscillations and long-lasting after-effects induced by rhythmic brain stimulations, we suggest that non-invasive rhythmic brain stimulation technique may help restore the natural frequencies of neural activities in aging to that in younger and healthy brains. Although with tremendous work to do, this technique offers great opportunities for the restoration of normal brain functions in aging, or even in those suffering from neurodegenerative diseases and neuropsychiatric disorders.

BackgroundThe vigilance fluctuation and decrement of sustained attention have large detrimental consequences to most tasks in daily life, especially among the elderly. Non-invasive brain stimulations (e.g., transcranial direct current stimulation, tDCS) have been widely applied to improve sustained attention, however, with mixed results.ObjectiveAn infraslow frequency oscillatory tDCS approach was designed to improve sustained attention.MethodsThe infraslow frequency oscillatory tDCS (O-tDCS) over the left dorsolateral prefrontal cortex at 0.05 Hz was designed and compared with conventional tDCS (C-tDCS) to test whether this new protocol improves sustained attention more effectively. The sustained attention was evaluated by reaction time and accuracy.ResultsCompared with the C-tDCS and sham, the O-tDCS significantly enhanced sustained attention by increasing response accuracy, reducing response time, and its variability. These effects were predicted by the evoked oscillation of response time at the stimulation frequency.ConclusionSimilar to previous studies, the modulation effect of C-tDCS on sustained attention is weak and unstable. In contrast, the O-tDCS effectively and systematically enhances sustained attention by optimizing vigilance fluctuation. The modulation effect of O-tDCS is probably driven by neural oscillations at the infraslow frequency range.