We aimed to examine the mediating role of accelerated aging in the association between diet quality and CVD incidence and mortality. Data were obtained from the UK Biobank cohort. Diet quality was evaluated using four established indices: the Healthy Eating Index-2020, the Alternative Healthy Eating Index, the Dietary Approaches to Stop Hypertension index, and the Mediterranean Diet Score. Accelerated aging was assessed by the Phenotypic Age Acceleration and Biological Age Acceleration. Outcomes included incident CVD and CVD mortality. Multivariable linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. Subgroup analyses were conducted according to sex, age, and CVD subtypes. This analysis comprised 52,718 UK Biobank participants who were followed for a mean of 12 years. Accelerated aging significantly mediated the associations between diet quality and both incident CVD and CVD mortality across the four indices. The proportion mediated ranged from 21.81 to 40.84% for incident CVD and from 16.67 to 35.87% for CVD mortality. Our study indicates that accelerated biological aging may serve as a potential intermediate pathway linking diet quality to CVD. These findings suggest that aging-related physiological dysregulation may be a potential target for future dietary intervention research. Incorporating population stratification by sex, age, and disease subtype is essential to develop more precise and effective dietary guidelines to improve cardiovascular health.

Post-stroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and substantially limits functional recovery. Brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase-β (Trkβ) signalling plays an important role in synaptic plasticity and cognitive function; however, the contribution of individual NTRK2/Trkβ isoforms to PSCI remains poorly understood. This study investigated (a) isoform-specific NTRK2 mRNA expression, (b) genetic association of the isoform-specific variant rs6559833 with post-stroke cognitive outcomes and (c) DNA methylation patterns potentially regulating NTRK2 expression using blood as primary biosource. Isoform-specific expression was analysed in 50 subjects, rs6559833 was genotyped in 280 ischemic stroke patients, and DNA methylation was assessed in 10 samples using whole-genome bisulfite sequencing. The TRKβ-FL expression was significantly reduced in stroke patients compared with healthy controls, whereas TRKβ-SHC expression was higher in PSCN individuals than in PSCI patients. The latter showed positive correlation with MEK2 expression and memory performance. The 'TT' genotype of the rs6559833 variant showed marginal associations with post-stroke memory status and overall BMSE scores (p = 0.0442 and 0.0488, respectively). Furthermore, hypermethylation was observed within the NTRK2 gene body and in genes encoding its splicing regulators, whereas no evident difference in promoter methylation was observed. Collectively, these findings suggest that Trkβ-SHC expression may be associated with preserved cognitive function after stroke and indicate a potential relationship between isoform-specific NTRK2 expression, genetic regulation and cognitive outcomes in PSCI.

Breast cancer treatment remains limited by therapeutic resistance, recurrence, and incomplete responses to immunotherapy, largely because tumor cells continuously adapt to the dynamic tumor microenvironment (TME). Mitochondria are central regulators of energy metabolism, redox balance, cell death, inflammatory signaling, and immune modulation. Stressors within the breast cancer TME, including hypoxia, nutrient deprivation, acidosis, matrix stiffening, oxidative stress, and treatment pressure, can remodel mitochondrial metabolism and dynamics, thereby promoting tumor survival, invasion, immune evasion, and therapy resistance. Conversely, stressed mitochondria reshape the TME through metabolic byproducts, reactive oxygen species, mitochondrial DNA release, inflammatory mediators, and stromal or vascular remodeling signals. This reciprocal mitochondria-TME crosstalk forms a self-reinforcing pathological loop that supports breast cancer progression. Biomaterial-based mitochondria-targeted nanomedicine offers a strategy to intervene in this loop by integrating multilevel delivery, microenvironment-responsive release, mitochondrial targeting, metabolic regulation, and immune activation. This review summarizes how the breast cancer TME remodels mitochondrial function, how mitochondrial stress reciprocally reshapes the TME, and how biomaterial-based therapeutic platforms can be designed to target this axis. We further discuss translational challenges, including tumor specificity, intratumoral penetration, long-term biosafety, subtype-specific intervention, and clinically relevant combination strategies.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-associated systems have emerged as powerful tools for next-generation molecular diagnostics, particularly for nucleic acid detection. However, ultrasensitive protein detection is equally critical across diverse applications in biology and medicine, especially for diagnosing and prognosing diseases such as cancer, traumatic brain injury (TBI), Alzheimer's disease, and cardiovascular diseases. Despite recent efforts to adapt CRISPR/Cas systems for protein detection, these methods have typically achieved sensitivity in the femtomolar to picomolar range, underscoring the need for enhanced detection capabilities. Here, we developed CRISPR-AMPED, a CRISPR/Cas-based immunoassay enhanced by magnetic proximity extension and detection. This approach combines proximity extension assay (PEA) with magnetic beads to convert protein targets into DNA barcodes while enabling effective washing to reduce background noise. The resulting DNA barcodes are detected through recombinase polymerase amplification (RPA) coupled with CRISPR/Cas12a, eliminating thermocycling and providing simultaneous target and signal amplification. CRISPR-AMPED achieves attomolar-level sensitivity, surpassing ELISA by over three orders of magnitude and outperforming existing immunoassays and CRISPR/Cas-based protein detection systems. As an initial demonstration of clinical utility, we applied CRISPR-AMPED to detect the inflammatory biomarker interleukin-8 (IL-8) in serum samples from patients with TBI and healthy controls. Further integration with a smartphone-based detection device demonstrates its potential for portable testing, while the digital format extends the dynamic range and enhances quantitation precision. Together, these results establish CRISPR-AMPED as a sensitive protein detection approach using IL-8 as an initial model target and provide a framework for future adaptation to additional protein biomarkers.

Cardiac hypertrophy is a major pathological response to cardiovascular stress and a critical contributor to heart failure (HF). Gentiopicroside (GPS), a naturally occurring iridoid glycoside derived from Gentiana scabra, exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties. However, its role and molecular mechanisms in cardiac hypertrophy and HF remain unclear. A pressure overload-induced cardiac remodeling model was established in C57BL/6 mice by transverse aortic constriction (TAC), followed by GPS treatment with or without the EGFR tyrosine kinase inhibitor Canertinib. Cardiac function and remodeling were evaluated by echocardiography, hemodynamic analysis, and histological staining. In vitro, neonatal rat ventricular myocytes (NRVMs) and cardiac fibroblasts (NRCFs) were used to investigate the cellular effects of GPS. EGFR knockdown, conditioned medium transfer, cellular thermal shift assay (CETSA), and lysosomal/proteasomal inhibition experiments were performed to elucidate the mechanism underlying GPS-mediated EGFR regulation. GPS markedly alleviated TAC-induced cardiac hypertrophy and fibrosis in vivo and suppressed Ang II-induced cardiomyocyte hypertrophy. GPS also reduced cardiomyocyte apoptosis and oxidative stress. Mechanistically, GPS acted as an EGFR degrader rather than a conventional kinase inhibitor, reducing total EGFR abundance without inhibiting the kinase activity of remaining receptors, thereby attenuating excessive AKT/ERK1/2 signaling. CETSA and molecular docking indicated direct GPS-EGFR interaction. GPS-induced EGFR reduction was mediated primarily through lysosomal degradation, as demonstrated by chloroquine rescue experiments, whereas proteasome inhibition had limited effects. Co-administration of Canertinib with GPS conferred no additional benefit. EGFR depletion abolished the protective effect of GPS in cardiomyocytes, indicating a cardiomyocyte-autonomous mechanism. This study identifies GPS as a regulator of EGFR stability during pathological cardiac remodeling. By promoting lysosome-dependent EGFR degradation and suppressing excessive AKT/ERK1/2 signaling, GPS attenuates cardiac hypertrophy and remodeling while preserving basal EGFR function, highlighting its potential therapeutic value for HF.

Increasing life expectancy has led to a growing prevalence of age-related disorders, including dementia, cardiovascular disease, frailty, osteoporosis, sarcopenia, and cancer. Heme oxygenase-1 (HO-1), a stress-inducible enzyme that degrades heme into carbon monoxide (CO), biliverdin which is then reduced to bilirubin by the biliverdin reductase enzyme, and iron, has emerged as a key regulator of several hallmarks of aging, including oxidative stress, inflammation, autophagy, mitochondrial dysfunction, and cellular senescence. This review evaluates age-associated changes in HO-1 expression across major organs and examines the roles of HO-1 and its metabolites in age-related diseases, with particular emphasis on dementia and cardiovascular disorders. Current evidence suggests that the biological effects of HO-1 depend not only on expression level but also on temporal regulation, tissue specificity, and the balance between protective and deleterious downstream pathways. Future research should focus on defining physiological and therapeutic ranges of HO-1 activity in different tissues, sexes, and stages of aging, while clarifying the distinct contributions of CO, bilirubin, and iron metabolism. Such studies may enable precision-medicine approaches that harness HO-1 modulation to promote healthy aging and prevent age-related diseases.

This study analyzes changes in distance travelled by Illinois youth ages 5-17 between 2016 and 2024 for mental health hospitalizations at Illinois hospitals.

We obtained records for admissions with a mental health principal diagnosis in each year. Patient and hospital zip codes were used to estimate distance. We present bivariate and multivariable analyses of change in distance between years by patient and hospital characteristics.

There were 22,516 youth mental health admissions in 2016 to 101 hospitals and 18,316 in 2024 to only 56 hospitals. Hospitalizations of youth who travelled ≥50 miles increased from 15.7% in 2016 to 21.9% in 2024 (p<0.001). Youth who were younger, non-Hispanic White, covered by Medicaid and those from 'downstate' Illinois counties had the longest travel distances. Travel distance ≥50 miles for youth hospitalized for depression increased from 15.4% in 2016 to 23.8% in 2024. As compared to 2016, the adjusted odds of youth having to travel more than 50 or 100 miles in 2024 were 1.76 (95% CI=1.36-2.28) and 2.05 (95%CI=1.30-3.24) respectively.

By 2024, more than one in five children traveled ≥50 miles and one in ten traveled ≥100 miles to access mental health hospital care. The odds of travel ≥100 miles more than doubled between 2016 and 2024. The increase in travel distance appears to be related to a large reduction in admissions to community hospitals with a small number of 2016 admissions, with a corresponding trend towards hospitalizations at a small number of specialty behavioral health hospitals.

Objective: To explore college student-athletes' preferences and perceived needs for online mental health interventions. Participants: 772 collegiate athletes based in the United States. Methods: Mixed-methods, comprising a cross-sectional survey and focus groups. The survey assessed athletes' current and lifetime mental health diagnoses, mental health literacy, help-seeking intentions, and program preferences, with a focus on gender differences. Focus groups provided insights into participants' experiences and expectations for interventions Results: Athletes expressed a strong preference for mental health programs that emphasize practical skills, are self-paced, and digital-first interventions with interactive components. Intentions were highest for seeking help from peers and family members. Stigma and confidentiality concerns emerged as major barriers to engagement. Men reported lower interest in almost all mental health topics, and higher intentions to not seek help from anybody for mental health problems. Conclusion: These findings highlight the need for athlete-centered, gender-sensitive mental health programs that are accessible and engaging.

Brain-computer interface (BCI) systems combined with motor imagery (MI) have emerged as promising tools in neurorehabilitation. Real-time neurofeedback may further enhance motor recovery by promoting use-dependent neuroplasticity; however, evidence in chronic stroke remains limited, particularly from controlled pilot studies.

This case series explored the feasibility and preliminary effects of EEG-based BCI neurofeedback combined with MI and physiotherapy on upper-limb motor function and brain activation patterns in individuals with chronic stroke.

In a double-blind, controlled protocol, seven individuals with chronic stroke were allocated to either an experimental group receiving MI with real-time EEG-based BCI neurofeedback or a control group receiving MI with sham feedback. All participants completed a standardized four-week physiotherapy program. Motor outcomes were assessed with the Action Research Arm Test, Fugl-Meyer Assessment, Motor Assessment Scale, and grip strength, with functional changes interpreted against minimal clinically important difference (MCID) thresholds. Neuroplastic changes were explored using EEG-derived symmetry measures and task-related functional MRI.

Participants receiving real neurofeedback exhibited consistent improvements exceeding MCID thresholds in at least one functional outcome, most notably grip strength. This group also demonstrated more symmetrical EEG activity and more consistent sensorimotor and cerebellar activation patterns on fMRI. In contrast, responses in the sham group were more variable and appeared influenced by a single high responder.

These findings support the feasibility of integrating EEG-based BCI neurofeedback with MI and physiotherapy in chronic stroke rehabilitation. The observed functional gains and associated neurophysiological changes suggest a preliminary, exploratory role for this intervention in promoting upper-limb recovery in this small sample.