The quantitative associations of prenatal exposure to fine particulate matter (PM2.5) and its components with neonatal blood amino acid (AA) and acylcarnitine (AC) profiles, as well as the critical exposure windows, remain largely unknown. Using data from a birth cohort in Shanghai, we aimed to explore these associations in 4802 mother-infant pairs, with metabolite levels measured by liquid chromatography-tandem mass spectrometry. All neonatal metabolite levels were log-transformed and standardized. We found that per interquartile range increase in prenatal PM2.5 exposure was significantly associated with 18 neonatal metabolites. Specifically, levels of aspartic acid (β: 0.395), glycine (β: 0.364) and medium-chain ACs (C6DC (β: 0.374), C10 (β: 0.409), C12 (β: 0.378)) were increased, while levels of arginine (β: -0.465), citrulline (β: -0.355) and short-chain ACs (C2 (β: -0.376), C3 (β: -0.349), C4 (β: -0.554)) were decreased. Pathway analysis revealed four exploratory metabolic pathway signals linked to prenatal PM2.5 exposure: the urea cycle, oxidation of branched-chain fatty acids, arginine and proline metabolism, and aspartate metabolism. Organic matter, approximated as residual organic matter (estimated), was the major contributor among PM2.5 components. Mid-gestation exposure showed the strongest associations with AA metabolism and the urea cycle pathways, whereas late-gestation exposure was more strongly linked to oxidation of branched-chain fatty acids. Mediation analyses suggested that, for the associations of PM2.5 and its components with glutamine and short-chain ACs, there were possible and small mediation effects by thyroid-stimulating hormone, but results were not statistically robust. Overall, prenatal exposure to PM2.5 was significantly associated with alterations in neonatal AAs and ACs, with residual organic matter (estimated) being the most important component of PM2.5.

Chronic diseases, with a focus here on non-cancerous conditions including cardiovascular, metabolic, neurological, and musculoskeletal disorders, as well as other relevant disorders, share pathological characteristics, such as persistent oxidative stress, reduced metabolic flexibility, and progressive tissue degeneration. Ferroptosis, an iron-dependent cell death triggered by lipid peroxidation, is now recognized as a critical factor in these pathological processes. Natural polyphenols, derived from plant sources, exhibit antioxidant and anti-inflammatory properties and demonstrate potential in regulating ferroptosis-related signaling pathways. This review systematically explores the molecular crosstalk between ferroptosis and polyphenols across major chronic diseases, highlighting their therapeutic and translational potential. Specifically, it elucidates the regulatory role of polyphenols in iron homeostasis, the inhibition of lipid peroxidation, and the restoration of redox balance, thus uncovering novel opportunities for dietary or pharmacological interventions targeting ferroptosis. Elucidating this interaction underscores the therapeutic potential of natural polyphenols as an innovative strategy for the prevention and treatment of chronic diseases.

Bioenergetics has emerged as a critical lens for understanding health promotion and disease pathogenesis, thus offering potential biomarkers for various energy-related diseases and crafting innovative interventional strategies. This article comprehensively covers the significant role of bioenergetic processes in health, focusing on the systemic implications of cellular energy dynamics, such as adenosine triphosphate production, mitochondrial efficacy, redox balance, and metabolic adaptability. Through highlighting the complexity of these processes, this article underscores the collective impact on health, suggesting that deeper insight into bioenergetic flux can inform both diagnostic and therapeutic advancements. Moreover, this article explores how diets can modulate energy balance and bioenergetic flow, offering innovative approaches for health promotion through precision nutrition and food-based therapeutic strategies.

The integration of artificial intelligence (AI) in precision exercise nutrition is reshaping how athletes optimize their dietary intake for performance, recovery, and overall well-being. This article discusses the intersection of AI technologies in formulating precision nutrition strategies tailored to distinct physiological and metabolic requirements of athletes. AI-based mechanisms, such as real-time diet monitoring, continuous glucose monitoring, and nutrient optimization systems, offer unique insights into the impact of AI on advancing precision nutrition applications through the involvement in analyzing complex datasets, merging genetic, metabolic and environmental factors, thereby contributing precise dietary recommendations that adjust to evolving necessities of an athlete. However, the obstacles presented by AI in this domain, including ethical considerations, data confidentiality, and the necessity for uniformity across diverse populations are also confronted. By using AI, athletes can attain greater precision in their nutrition plans, ultimately enhancing exercise performance and promoting fatigue or injury recovery in ways that traditional methods cannot rival. This article further culminates with an address on future trends, emphasizing the role of AI in boosting precision nutrition engagement for athletes, even common exercise enthusiasts.

This chapter comprehensively summarizes the pivotal role of exercise in fostering optimal bone health during adolescence, a critical period for skeletal development and the attainment of peak bone mass (PBM). It delves into the fundamental aspects of bone biology, including its dynamic nature, physiological functions, and continuous regeneration processes. The discussion highlights how adolescence, often referred to as the "bone bank" period, is crucial for establishing long-term skeletal health, with approximately 40% of PBM gained during the 4-year period surrounding peak height velocity (PHV). Meanwhile, this chapter also explores the multifaceted factors influencing adolescent bone growth, categorizing them into modifiable (physical activity, nutrition, hormonal regulation, lifestyle) and non-modifiable (genetics, ethnicity) elements. A significant focus is placed on the mechanical loading induced by weight-bearing exercises, such as running, jumping, and resistance training, and their profound impact on stimulating osteoblast activity, enhancing bone density, and improving architectural integrity. Conversely, the detrimental effects of sedentary habits and non-osteogenic sports are also addressed. Furthermore, the physiological mechanisms underpinning bone development-modeling, remodeling, and ossification-are elucidated, detailing the coordinated actions of osteoblasts, osteocytes, and osteoclasts. The interplay of these processes in shaping bone size, density, and strength in response to mechanical forces and hormonal fluctuations during puberty is thoroughly discussed. This chapter further incorporates findings from key studies, including the Canadian Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) and the Bone Mineral Density in Childhood Study (BMDCS), to illustrate patterns of bone mineral accrual and identify periods of increased fracture risk in adolescents. Ultimately, this chapter underscores the imperative of targeted exercise interventions during adolescence as a non-pharmacological strategy to maximize PBM, mitigate the risk of osteoporosis and fractures in later life, and promote enduring skeletal well-being.

Background Alzheimer’s disease (AD) presents a significant challenge to global healthcare systems, with an exacerbation by an aging population. Although the plethora of hypotheses are proposed to elucidate the underlying mechanisms of AD, from amyloid-beta (Aβ) accumulation and Tau protein aggregation to neuroinflammation, a comprehensive understanding of its pathogenesis remains elusive. Recent research has highlighted the critical role of calcium (Ca2+) signaling pathway in the progression of AD, indicating a complex interplay between Ca2+ dysregulation and various pathological processes. Aim of Review This review aims to consolidate the current understanding of the role of Ca2+ signaling dysregulation in AD, thus emphasizing its central role amidst various pathological hypotheses. We aim to evaluate the potential of the Ca2+ signaling hypothesis to unify existing theories of AD pathogenesis and explore its implications for developing innovative therapeutic strategies through targeting Ca2+ dysregulation. Key Scientific Concepts of Review The review focuses on three principal concepts. First, the indispensable role of Ca2+ homeostasis in neuronal function and its disruption in AD. Second, the interaction between Ca2+ signaling dysfunction and established AD hypotheses posited that Ca2+ dysregulation is a unifying pathway. Third, the dual role of Ca2+ in neurodegeneration and neuroprotection, highlighting the nuanced effects of Ca2+ levels on AD pathology.

Multimorbidity, therapeutic complexity, and polypharmacy, which greatly increases the risk of drug-drug interactions (DDIs) and adverse medical outcomes, have become important and growing challenges in clinical practice. Statins are frequently prescribed to manage post-transplant dyslipidemia and reduce overall cardiovascular risk in solid organ transplant recipients. This study aimed to determine whether rosuvastatin has significant DDIs with tacrolimus (the first-line immunosuppressant) and to evaluate the risk of hepatotoxicity associated with concomitant therapy. We first studied whether a rat model could be established to assess the magnitude of rosuvastatin-tacrolimus DDI. The liver function index and histopathological examination were performed to investigate the characteristics of hepatotoxicity in the presence and absence of DDI. The clinical DDI potential between rosuvastatin and tacrolimus was also explored. Single-dose intravenous administration of tacrolimus did not significantly affect the area under the plasma concentration–time curve (AUC0-∞), clearance (CL), and volume of distribution at steady-state (Vss) of rosuvastatin in rats, despite a 96.7

Exercise injuries present a significant challenge in medicine and public health, impacting exercise performance, career longevity, and overall quality of life. While OMICS technologies such as genomics, transcriptomics, proteomics, and metabolomics offer unprecedented insights into individual susceptibility, recovery, and performance optimization, their full potential is realized through the integration of artificial intelligence (AI). This article explores the transformative role of OMICS biomarkers in understanding the molecular underpinnings of exercise injuries. Crucially, it emphasizes how AI and advanced data analytics are essential for processing and interpreting the vast, complex datasets generated by multi-OMICS strategies. By leveraging machine learning algorithms, AI can identify subtle patterns and predictive biomarkers, thereby significantly enhancing the accuracy of injury risk assessment, enabling personalized intervention strategies, and facilitating real-time monitoring of exercise, health and recovery. This integration moves beyond traditional biological insights, paving the way for truly predictive and preventive precision exercise medicine. Furthermore, this article addresses the ethical, legal, and logistical challenges associated with the application of OMICS and AI technologies, emphasizing the need for robust regulatory frameworks and equitable access to these advancements. The synergistic combination of OMICS and AI stands as a cornerstone of future precision exercise medicine, promising a safer, more effective, and highly personalized exercise experience.

Obesity cardiomyopathy (OCM) represents a rapidly growing health concern globally, characterized by metabolic, structural, and functional abnormalities of the heart. Current research has demonstrated that inflammation plays a pivotal role in obesity-induced cardiomyopathy, and that regular exercise can ameliorate lipid disturbances and inflammatory abnormalities effectively. However, the underlying mechanisms are not fully elucidated. We investigated the effects of an 8-week aerobic exercise intervention on myocardial structure, function, and inflammation in HFD-induced obese mice. The results revealed that aerobic exercise alleviated myocardium pyroptosis and inflammation by down-regulating the PI3K/AKT signaling pathway. Furthermore, the inhibition of the PI3K pathway by LY294002, coupled with exercise, attenuated and suppressed HFD-induced myocardial impairments, inflammation, and pyroptosis, with a synergistic effect. Based on these findings, we concluded that eight weeks of aerobic exercise synergizes with the inhibition of PI3K through inflammatory and pyroptosis mechanisms to improve obesity-associated myocardial remodeling and dysfunction. Therefore, long-term regular aerobic exercise represents a potential strategy in the treatment of OCM.

Nutrigenomics is an emerging research field to investigate the interactions between food components and genes and elucidate their impacts on health and diseases. Exercise, another critical factor influencing human health, is intricately linked with nutrition and genetics, and is influenced by a combination of genetic background, lifestyle choice, and environmental factors. The high-throughput sequencing technologies and advanced bioinformatic tools have offered researchers to delve deeper into how individual genetic expression responses to exercise and how dietary interventions can enhance exercise performance and recovery through the gene expression changes and modifications. Among these mechanisms, gene expression emerges as the primary focus, highlighting its role in linking nutrients and exercise to metabolic pathways, muscle synthesis, and inflammation. While epigenetic modifications are briefly considered, the emphasis remains on how direct and indirect influences on gene expression drive physiological adaptations. Herein, the article reviews recent advancements in nutrigenomics within the context of exercise science, exploring gene-regulating mechanisms affected by specific nutrients and dietary patterns on exercise capacity, muscle synthesis, and damage repair. It also outlines the potential applications of personalized nutrition plans in athletic training and general fitness. In addition, this article addresses current challenges and potential issues in the practical implementation of nutrigenomics in exercise-induced health promotion. Future studies should emphasize interdisciplinary collaboration to unravel the intricate gene-nutrition-exercise interaction networks, thereby providing a solid theoretical foundation and technological support for the advancement of precision exercise nutrition.

Background:Zika virus (ZIKV) infection can result in severe neurological complications, yet no approved antiviral treatments are currently available. Ginseng, a medicinal herb extensively utilized in Asian traditional medicine, has demonstrated efficacy against various diseases, which has sparked interest in exploring its potential antiviral properties for the treatment of ZIKV. Methods:We evaluated the antiviral effects of ginsenoside Rb2 (G-Rb2) in human neuronal cell lines (SK-N-SH and CCF-STTG) and in a lethal ZIKV-infected mouse model. The antiviral efficacy was assessed using bioluminescence imaging with a NanoLuc luciferase reporter ZIKV. In vitro assays were conducted to determine the direct impact of G-Rb2 on ZIKV, while surface plasmon resonance (SPR) was employed to analyze its interaction with ZIKV envelope proteins and viral particles. Results:G-Rb2 (200 μM) significantly inhibited ZIKV infection in vitro and protected mice from ZIKV-induced mortality. Bioluminescence imaging validated its antiviral efficacy. In vitro studies demonstrated that incubation with G-Rb2 reduced viral infectivity, and SPR analysis confirmed direct binding between G-Rb2 and ZIKV components. Conclusion:G-Rb2 effectively inhibits ZIKV infection both in vitro and in vivo, presumably through direct interaction with viral particles. Given the accessibility of ginseng and its established processing methods, G-Rb2 emerges as a promising candidate for the treatment of ZIKV in humans. Further research is warranted to elucidate its mechanisms of action and evaluate its clinical potential.

Chronic diseases, broadly defined as long-duration conditions that require sustained medical care and/or limit activities of daily living, are a major problem that threatens human health and imposes large social and economic burdens. Physical activity has many beneficial effects for human health and is among the most cost-effective ways to prevent and treat chronic diseases. Animal exercise intervention studies are widely used and provide valuable scientific evidence about the cellular and molecular mechanisms underlying the effects of exercise training in a variety of chronic disease models. This consensus statement will provide expert opinions and recommendations for the appropriate design and application of animal exercise intervention studies and models in fundamental investigations of prevention and treatment of chronic diseases, especially focusing on cardiovascular and cerebrovascular diseases (coronary artery disease and stroke), metabolic diseases (obesity and type 2 diabetes mellitus), chronic respiratory diseases (chronic obstructive pulmonary disease), and neurological diseases (Alzheimer’s disease). This statement highlights various exercise models (as determined by frequency, intensity, time, and type of exercise intervention) utilized for each disease. Additionally, it includes a list of functional, structural, biochemical, and disease-specific evaluation metrics of exercise effects, followed by outlined recommendations for the exercise study design and evaluations for the mentioned chronic diseases. This consensus aimed to offer practical recommendations for better design and conduct of fundamental research in animal exercise intervention studies to improve our understanding of the effects of exercise on chronic diseases, and to further develop physical exercise or exercise-mimetic interventions for disease prevention and treatment.

Changes to the extracellular matrix support acute wound healing following myocardial infarction. Fibroblasts regulate the composition of the extracellular matrix, in part, by secreting hyaluronan. Details surrounding the regulation, source, and impact of hyaluronan production after MI are largely unknown. We recently showed that activated fibroblasts produce hyaluronan via Has2; however, the extent to which this function impacts acute ventricular remodeling following myocardial infarction (MI) has not been tested. Hence, the goal of the present study was to elucidate the impact of fibroblast-borne Has2 expression in acute ventricular remodeling. Adult, male and female mice were subjected to non-reperfused myocardial infarction and followed for 1 week and subjected to echocardiography and hearts were harvested for pathology and biochemical analyses. Mice were deficient in fibroblast-derived Has2 (Has2-/-) or were littermate controls that were sufficient in fibroblast Has2. At 1-week post-MI, Has2-/- male mice had exacerbated heart failure reflected by lower cardiac output due to lower stroke volume, when compared to littermate males. The genotype effect was not evident in female mice. To assess potential mechanisms, we examined hearts for fibrosis, cardiomyocyte cross-sectional area, and capillary density; there were no significant differences in any of these endpoints. Deletion of Has2 also did not impact collagen organization, which could have indicated changes in ventricular stiffness. Fibroblast-derived Has2 supports cardiac function early after MI. The mechanism responsible for this and why it is not evident in female mice is unclear.

Ferroptosis is a programmed cell death, and its mechanism involves multiple metabolic pathways, such as iron and lipid metabolism, and redox homeostasis. Exerkines are important mediators that optimize cellular homeostasis and maintain physiological health during exercise stimulation. This article comprehensively examines the mechanisms and regulatory networks for governing ferroptosis and summarizes the impact of exercise and exerkines on ferroptosis under varying load intensities and disease contexts. Notably, despite its significant efficacy and minimal side effects, the therapeutic and prognostic potential of exercise in ferroptosis-related diseases remains largely unexplored. This article, by summarizing recent progresses in the regulation of exerkines-mediated ferroptosis, could further uncover the preventive or alleviative mechanisms of some diseases upon exercise interventions, which will be beneficial to design exercise interventional strategies for alleviating disease progression through the regulation of ferroptosis.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe mitochondrial dysfunction, associated with the production of mitochondrial reactive oxygen species (mROS). The substantial generation of mROS in the MASH liver, resulting from lipid surplus and electron transport chain (ETC) overload, impairs mitochondrial structure and functionality, thereby contributing to the development of severe hepatic steatosis and inflammation. Regular exercise represents an effective strategy for the treatment of MASH. Understanding the effects of exercise on oxidative stress and mitochondrial function is essential for effective treatment of MASH. This article reviews the pathological alterations in mitochondrial β-oxidation, ETC efficiency and mROS production within MASH liver. Additionally, it discusses how exercise influences the redox state and mitochondrial quality control mechanisms-such as biogenesis, mitophagy, fusion, and fission-within the MASH liver. The article emphasizes the importance of in-depth studies on exercise-induced MASH mitigation through the enhancement of mitochondrial redox balance, quality control, and function. Exploring the relationship between exercise and hepatic mitochondria could provide valuable insights into identifying potential therapeutic targets for MASH.

As an indoleamine with a long evolutionary history, melatonin's physiological functions have evolved from its initial role in regulating skin pigmentation in fish and amphibians to encompass a broad spectrum of critical physiological regulatory functions. In mammals, melatonin primarily serves to regulate the circadian rhythm system, which is essential for maintaining the sleep-wake cycle. Abnormal melatonin secretion has been strongly associated with the development of sleep disorders, which are recognized as significant risk factors for various chronic diseases. This article aims to comprehensively examine the diverse physiological functions of melatonin beyond its role in regulating circadian rhythms and the sleep-wake cycle, while analyzing its mechanisms of action in modulating oxidative stress, anti-inflammatory responses, and mitochondrial function. Furthermore, this article evaluates the multifaceted effects of melatonin on energy metabolism, bone metabolism, nervous system regulation, and cardiovascular health at pharmacological doses, highlighting its importance in managing sleep disorders. By synthesizing current research findings, this article provides an objective assessment of the scientific foundation for melatonin's role in enhancing sleep quality and promoting overall health, while emphasizing the need to distinguish between its physiological and pharmacological effects.

It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function. The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic. However, there remains an urgent need to elucidate its specific mechanisms. This study aimed to explore the impact of a high-fat diet (HFD) on liver health and cognitive function, and to further uncover the regulatory effect of aerobic exercise by liver-specific activating transcription factor 3 (Atf3) knockout (ATF3cKO) mice in a “liver-brain” axis mode. The 5-week-old C57BL/6 and ATF3cKO mice were fed with HFD for 32 weeks, and sequentially subjected to aerobic exercise intervention at the 20th week for another 12 consecutive weeks. Meanwhile, C57BL/6 mice were provided with a normal diet as the control group. The functional parameters of liver and brain of all mice were assessed. Cognitive capacity of all mice was assessed by the Morris water maze (MWM). Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammasomes was detected by immunohistochemistry (IHC). Additionally, the activation of nuclear factor-κB (NF-κB) and phosphoinositide 3-kinase (PI3K) signal pathways was analyzed by Western blotting. In this study, HFD impaired hepatic and brain functions, while aerobic exercise and liver-specific Atf3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms, thereby attenuating cerebral inflammation and preserving neurological integrity, as well as mitigating HFD-induced cognitive decline.

Objective This study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. Methods Using naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. Results Behavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota alpha-diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e. g., L-homocitrulline), antioxidant defense (e. g., L-carnosine), neuroprotection (e. g., lithocholic acid), and DNA repair (e. g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. Conclusion This study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammationinhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the "microbiota-metabolite-brain" axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiotametabolite modulation for combating neurodegenerative diseases.