The global rise in obesity is closely associated with the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndromes, posing significant health challenges. This study explored the ameliorative effects of Ophiocordyceps sinensis mycelia (TCM-NA01 formula: 1.4 mg adenosine and 55.2 mg polysaccharide/capsule) on hepatosteatosis development in a high-fat diet (HFD)-fed mice. TCM-NA01 supplementation significantly reduced (p < 0.05) body weight, adipose tissue, serum triglyceride (TG)/cholesterol (TC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), liver TG/TC levels in HFD-fed mice. Increased (p < 0.05) fecal-lipid and bile-acid outputs were observed. Apparent reductions in lipid-droplet and steatosis scores (p < 0.05) in the HFD-fed mice supplemented with TCM-NA01. Furthermore, TCM-NA01 modulated lipid metabolism by decreasing fatty acid synthesis and promoting fatty acid β-oxidation. TCM-NA01 also enhanced liver antioxidant capacity and decreased proinflammatory cytokines (p < 0.05). These findings underscore the potential of O. sinensis mycelia as a nutraceutical agent for alleviating hepatosteatosis, liver oxidative stress, and chronic inflammation, offering a promising strategy for the management of obesity and NAFLD.

Mitochondrial protein import through the outer and inner membranes is key to mitochondrial biogenesis. Recent studies have explored how cells respond when import is impaired by a variety of different insults. Here, we developed a mammalian import blocking system using dihydrofolate reductase fused to the N terminus of the inner membrane protein MIC60. While stabilization of the dihydrofolate reductase domain by methotrexate inhibited endogenous mitochondrial protein import, it neither activated the transcription factor ATF4, nor was affected by ATAD1 expression or by VCP/p97 inhibition. On the other hand, notably, plugging the channel of translocase of the outer membrane) induced YME1L1, an ATP-dependent protease, to eliminate translocase of the inner membrane (TIM23) channel components TIMM17A and TIMM23. The data suggest that unoccupied TIM23 complexes expose a C-terminal degron on TIMM17A to YME1L1 for degradation. Import plugging caused a cell growth defect and loss of YME1L1 exacerbated the growth inhibition, showing the protective effect of YME1L1 activity. YME1L1 seems to play a crucial role in mitochondrial quality control to counteract precursor stalling in the translocase of the outer membrane complex and unoccupied TIM23 channels.

Background: Mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD), are characterized by significant psychological and behavioral fluctuations, with mobility patterns serving as potential markers of emotional states. Objective: Leveraging GPS data as an objective measure, this study explores the diagnostic and monitoring capabilities of Fourier transform, a frequency-domain analysis method, in mood disorders. Methods: A total of 62 participants (BP: 20; MDD: 27; healthy controls: 15) contributed 5,177 person-days of data over observation periods ranging from 5 days to 6 months. Key GPS indicators—location variance (LV), transition time (TT), and entropy (EN)—were identified as reflective of mood fluctuations and diagnostic differences between BP and MDD. Results: Fourier transform analysis revealed that the maximum power spectra of LV and EN differed significantly between BP and MDD groups, with BP patients exhibiting greater periodicity and intensity in mobility patterns. Notably, BP participants demonstrated consistent periodic waves (e.g., 1-day, 4-day, and 9-day cycles), while such patterns were absent in MDD. Daily GPS data showed stronger correlations with ecological momentary assessment (EMA)-reported mood states compared to weekly or monthly aggregations, emphasizing the importance of day-to-day monitoring. Depressive states were associated with reduced LV and TT on weekdays, and lower EN on weekends, indicating that mobility features vary with social and temporal contexts. Conclusions: This study underscores the potential of GPS-derived mobility data, analyzed through Fourier transform, as a non-invasive and real-time diagnostic and monitoring tool for mood disorders. The findings suggest that the intensity of mobility patterns, rather than their frequency, may better differentiate BP from MDD. Integrating GPS data with EMA could enhance the precision of clinical assessments, provide early warnings for mood episodes, and support personalized interventions, ultimately improving mental health outcomes. This approach represents a promising step toward digital phenotyping and advanced mental health monitoring strategies.

No abstract available.

Pei-Lin Lee serves as Clinical Associate Professor, School of Medicine, National Taiwan University; Consultant, Center of Sleep Disorder, National Taiwan University Hospital. Her current academic positions at international sleep societies include American Academy of Sleep Medicine Fellow and Co-Chair International Assembly; Asian Society of Sleep Medicine, Sleep Medicine Education Task Force committee member. Her current research focuses on the era of new technology and big data in sleep medicine; and intervention on sleep and metabolism in sleep disordered breathing.