Hyperthermia (HT) has broad potential for disease treatment and health maintenance. Previous studies have shown that far-infrared rays (FIRs) at 8–10 μm can potentially reduce inflammation, oxidative stress, and gut microbiota imbalance. However, the effects of FIR HT on energy metabolism require further investigation. To investigate the effects of graphene-FIR HT therapy on diet-induced obesity and their regulatory mechanisms in energy metabolism disorders. After 8 weeks of hyperthermia, mice fed standard chow or a high-fat diet (HFD) underwent body composition analysis. Energy expenditure was measured using metabolic cages. The protein changes in adipose tissue were detected by molecular technology. Graphene-FIR therapy effectively mitigated body fat accumulation, improved dyslipidemia, and impaired liver function while enhancing insulin sensitivity. Furthermore, graphene-FIR therapy increased V_O2, V_CO2, and EE levels in HFD mice to exhibit enhanced metabolic activity. The therapy activated the AMPK/PGC-1α/SIRT1 pathway in adipose tissue, increasing the expression of uncoupling protein 1 (UCP1) and glucose transporter protein four (GLUT4), activating the thermogenic program in adipose tissue, and improving energy metabolism disorder in HFD mice. In short, graphene-FIR therapy represents a comprehensive approach to improving the metabolic health of HFD mice.

Background/Objectives: Baichuan Baile (BCBL), a novel functional dietary formula, has been shown to exert antidepressant-like effects through modulation of the 5-HT system in our prior studies. Given the close neurobiological connections between depression and insomnia, along with its pharmacodynamic profile guided by TCM theory and nutritional assessments, BCBL is likely to possess beneficial effects against insomnia. However, this hypothesis and its underlying mechanisms require further validation. Methods: The chemical constituents of BCBL were analyzed by UPLC-Q-TOF-MS, and network pharmacology was applied to predict potential sleep-relevant targets and pathways. Subsequently, BCBL was evaluated for sedative-hypnotic effects using pentobarbital-induced hypnosis, locomotor activity, and polysomnography (EEG/EMG). Its therapeutic efficacy was further assessed in insomnia models induced by environmental stress, serotonin depletion, and rotarod-based sleep deprivation. The rotarod-induced chronic model was selected for mechanistic studies due to its sustained insomnia-like phenotype. Finally, key network-predicted targets were validated in this model through histopathology, Western blotting, and ELISA. Results: Pharmacological evaluation confirmed that BCBL significantly promoted sleep at both behavioral and EEG levels, confirming its sedative-hypnotic properties. BCBL mitigated environmental stress-triggered impairments in NREM sleep continuity and duration, and exerted protective effects against body weight loss and sleep disturbances in a serotonin depletion-induced insomnia model. In the rotarod sleep deprivation model, BCBL treatment increased spontaneous alternation rates and recognition indices, ameliorated hippocampal pathological alterations, and reduced hippocampal levels of HIF-1α, TNF-α, and IL-1β. Furthermore, BCBL elevated the p-GSK3β/GSK3β ratio and enhanced SIRT₁ expression in the hypothalamus. It also modulated the activity of key sleep–wake neurotransmitters/neuromodulators (serotonin, dopamine, adenosine, and glutamate) and key circadian rhythm regulators (BMAL₁, PER₂, and CLOCK) in this region. Conclusions: BCBL exhibits significant therapeutic efficacy against insomnia, indicating its potential as a dietary supplement for managing insomnia. Its mechanisms appear to involve anti-inflammatory effects, rebalancing of neurotransmitters/neuromodulators, and stabilization of circadian rhythm gene expression.

Pathological fatigue has emerged as a significant contributor to cardiac dysfunction. Unfortunately, suitable animal models to study cardiac dysfunction caused by fatigue are lacking, and the underlying mechanisms remain unclear. This study aimed to establish a pathological fatigue model induced by 5‐week combined stress and explore the mechanisms of cardiac dysfunction triggered by fatigue. Five‐week combined stress induced fatigue‐like phenotypes, which included reluctance to move, reduced exercise endurance, and muscle strength. Moreover, the 5‐week combined stress resulted in a significant reduction in both EF and FS, along with a marked upregulation of several myocardial injury biomarkers, thereby confirming the presence of abnormal cardiac function. Targeted metabolomics analysis indicated that 80% of the differential metabolites were downregulated, suggesting a hypometabolic profile in the heart. Interestingly, among the downregulated fatty acid metabolites, we identified two bacterial metabolites, namely acetate and butyrate. More importantly, we observed an inverse correlation between the levels of acetate and butyrate and the concentrations of certain cardiac injury markers. We then observed disturbances in gut bacteria, and group differences at the genus level revealed that all six differential bacteria, which ranked in the top 10 in terms of relative abundance, may directly or indirectly influence the production of acetic acid and butyric acid. Among them, the abundance of Akkermansia bacteria was positively correlated with reduced acetic acid levels. In summary, the present study provides a novel animal model of pathological fatigue‐induced cardiac dysfunction and suggests that hypometabolic features and gut microbiota dysbiosis may be an important mechanism.

Acute lung injury (ALI) pathogenesis is intricately linked to microvascular permeability. Soluble guanylate cyclase (sGC) is prominently expressed in the vascular system, playing a central role in vascular function. In contrast, its expression and function diminish notably during the progression of ALI, indicating sGC’s potential significance as a pivotal modulator in the pathological processes of ALI. Nonetheless, the precise localization of sGC within lung tissue and its distinct mechanism in maintaining vascular homeostasis remain unclear. Furthermore, there is a necessity for a pharmacological agent capable of consistently activating sGC for the treatment of ALI. A novel sGC stimulator, sGC003, was engineered through structural modification of Riociguat. In a mouse model of ALI, sGC003 exhibited superior sGC activation and more potent anti-inflammatory effects relative to Riociguat. It also exhibited superior efficacy in improving respiratory function and reducing pulmonary edema. Through single-cell RNA sequencing and immunofluorescence co-localization analysis, we confirmed predominant expression of soluble guanylate cyclase in pericytes. The sGC stimulators were found to modulate the LPS-induced pericyte transcriptome reprogramming via the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway. Differential gene expression analysis categorized pericytes into nine distinct subgroups, which were sequentially activated during vascular development, inflammation, and myofibrosis. Pseudotime analysis revealed that sGC003 more effectively suppressed the myofibroblast differentiation of pericytes compared to Riociguat. In conclusion, sGC003 mitigates ALI-induced pulmonary inflammation by modulating pericyte differentiation, particularly in preserving microvascular integrity outstanding performance. Its exceptional efficacy suggests that it could potentially serve as a safer and more efficient option as a novel sGC stimulant in the future.