This study investigates how musical prediction mechanisms – specifically uncertainty and surprise – shape emotions and bodily sensations across the lifespan. To examine this, we conducted online experiments with 784 participants aged 10 to 88, using eight chord progressions derived from computational predictive models to assess emotional responses and bodily sensation maps. The results showed that overall bodily sensation intensity peaked in the 20s to 30s and then declined with age, while the relative proportion of head-centered sensations increased significantly across the lifespan. In contrast, subjective valence ratings remained stable across the lifespan, whereas arousal levels increased with age and showed a strong correlation with predictable musical structures. These findings suggest an age-related shift toward top-down cognitive prediction alongside preserved emotional appraisal, while supporting the relationship between top-down processing shaped by accumulated experience and the predictability of music, as indicated by previous research. By accounting for the unique physical and emotional characteristics of each age group, this study may support the development of prediction- and music-based interventions aimed at understanding generation-specific emotional and interoceptive responses to music.
Early neurological improvement (ENI) at 24 h after endovascular treatment (EVT) is a surrogate marker for predicting functional improvement of acute ischemic stroke (AIS) patients; however, using delayed neurological improvement (DNI) at seven days post-EVT remains understudied. We investigated differences between ENI and DNI in predicting functional outcome of AIS patients undergoing EVT.
Objective:Sepsis elicits neuroinflammation in the medullary visceral zone (MVZ), which disrupts the cholinergic anti-inflammatory pathway (CAP). However, the underlying mechanisms and translational therapeutic potential remain poorly defined. Methods:Adult male Sprague-Dawley rats received either intracerebroventricular lipopolysaccharide (LPS; 25 μg/25 μL) to induce MVZ neuroinflammation model rats, or intraperitoneal LPS (6 mg/kg) to establish polymicrobial sepsis model rats. Anti-inflammation groups were involved with minocycline sucrose solution (120 mg/L) which was administered by drinking for 4 days prior to LPS challenge. CAP transection groups were undergone right cervical vagotomy 7 days before anti-inflammation interventions. Murine sepsis score (MSS), mortality rates, heart rate variability (HRV), cytokine levels in blood and medulla, systemic immunity level, and the expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA-1), CD22, tumor necrosis factor-α (TNF-α), Munc13-1, Synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the MVZ were measured and analyzed. Results:Both sepsis and MVZ neuroinflammation model rats showed significantly increased mortality and MSS scores, depressed HRV parameters, and upregulated expressions of GFAP, IBA-1, CD22, and TNF-α, with downregulated expressions of Munc13-1, SYN, and PSD-95 in the MVZ. Synaptic structural damage including reduced synaptic vesicles, decreased RT1.D expression on lymphocytes, increased percentages of Th17 and Treg lymphocytes, and increased serum levels of TNF-α, IL-10, and INF-γ were observed. Anti-inflammatory intervention reversed these changes in both model rats, whereas CAP transection partially abolished the anti-inflammatory benefits, confirming CAP dependence. Conclusions:Sepsis-induced MVZ neuroinflammation dismantles synaptic integrity and CAP modulation, which intensifies peripheral cytokine storm. Early central anti-inflammation repairs MVZ synaptic plasticity and reinstates vagal immunomodulation, which may provide a translational strategy to limit septic escalation.
Neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are discussed as representative examples of conditions in which oxidative stress and proteostasis imbalance contribute to progressive neuronal dysfunction. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, is widely recognized as a key contributor to ND pathogenesis. Excessive ROS disrupt cellular homeostasis and promotes protein misfolding and aggregation, thereby compromising the proteostasis network. In response to this stress, molecular chaperones, including members of heat shock protein (Hsp) family, play a crucial protective role by maintaining protein folding integrity and preventing toxic aggregation. Furthermore, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) serve as carriers of bioactive molecules, including antioxidants and molecular chaperones, offering a unique mechanism to restore cellular homeostasis. This review explores the interplay between oxidative stress and molecular chaperones in the pathogenesis of NDs and highlights the emerging therapeutic potential of MSC-EVs as modulators of oxidative and proteostatic imbalance.
Objectives:Alzheimer's disease (AD) involves cognitive impairment, neuronal degeneration, oxidative imbalance, and abnormal MAPK signaling. This study investigated the protective effects of Ershiwuwei Shanhu Pills (ESP) on cognition, oxidative stress, neuronal apoptosis, and MAPK pathway regulation in APP/PS1 mice. Methods:Sixty mice were used, including 50 APP/PS1 transgenic mice randomly assigned to five groups: untreated AD model, donepezil (0.5 mg/kg), and low- (100 mg/kg), medium- (200 mg/kg), or high-dose (400 mg/kg) ESP. Ten wild-type C57BL/6J mice served as normal controls. All treatments were administered orally for 60 days. Cognitive performance was assessed by the Morris water maze. Hippocampal pathology and apoptosis were evaluated by histology and TUNEL staining, while oxidative stress markers, AD-related proteins, and MAPK phosphorylation were measured via ELISA and Western blot. Results:ESP treatment improved learning and memory performance, reduced hippocampal neuronal damage, and decreased neuronal apoptosis. Antioxidant enzyme activities (SOD, CAT, GSH, GSH-PX) increased, whereas MDA and GSSG levels decreased. Circulating Aβ1-40, Aβ1-42, TAU181, and γ-secretase levels were reduced. ESP also downregulated phosphorylation of JNK, ERK, and p38. The medium-dose group showed therapeutic effects comparable to donepezil. Conclusions:ESP exerts neuroprotective effects in APP/PS1 mice by alleviating oxidative stress, inhibiting neuronal apoptosis, and modulating MAPK signaling. These findings suggest ESP as a promising multi-target therapeutic strategy for AD.
