Introduction Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. Methods This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. Results Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). Conclusions Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.
Delayed endothelialization and persistent inflammation remain key challenges for long-term vascular healing after stent implantation. Here, we develop a temporally coordinated immunoregenerative coating (C15-NOGC) that couples sustained nitric oxide (NO) generation with C15-associated immunomodulation. The coating is fabricated via in situ re-crosslinking of Cu-DOTA-modified polyamine within a polydopamine coating, followed by bioorthogonal immobilization of the pro-resolving peptide chemerin-15 (C15), yielding a mechanically robust interface with stable peptide presentation and physiological-level NO release. Functionally, immobilized C15 promotes a pro-resolving macrophage phenotype associated with increased ChemR23 expression, enhances phagocytic activity, and reduces pro-inflammatory responses. Concurrently, continuous NO generation provides antithrombotic activity, promotes endothelial regeneration, and modulates smooth muscle cell phenotype and vascular remodeling. Following stent implantation in ApoE−/− rats, C15-NOGC significantly enhances early re-endothelialization, is associated with a reduced neointimal area, and shows favorable local vascular remodeling responses compared with bare metal and drug-eluting stents. PCR-array and proteomic analyses further reveal complementary molecular signatures associated with inflammatory regulation, vascular remodeling, and reparative processes, providing molecular context for the observed vascular responses. Together, these findings support a temporally coordinated strategy that integrates C15-associated immunomodulation with endothelial-mimetic NO generation for pro-healing vascular stent design.
Atherosclerosis (AS) is a progressive disease of the arterial wall characterized by metabolic dysregulation, inflammatory activation, and genetic susceptibility. Given the complex interactions across molecular layers, this review aims to summarize the key applications of multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, single-cell omics, spatial omics, plasma proteomics, and radiomics, in elucidating AS pathogenesis and clinical relevance. Recent multi-omics studies have enabled the construction of functional networks linking genetic variation, epigenetic regulation, gene expression, protein function, and metabolic imbalance, thereby providing complementary insights into AS mechanisms. These approaches have advanced the understanding of distinct pathological phenotypes, such as calcified versus non-calcified plaques and stable versus unstable lesions. Emerging evidence also highlights the clinical relevance of underexplored areas, including molecular subtyping, and plasma biomarker prediction. Furthermore, the integration of artificial intelligence (AI) has enhanced multi-omics data mining, particularly in radiomics-based phenotypic profiling and multidimensional risk modeling. This review synthesizes current advances in multi-omics strategies for AS research and discusses the sources and application status of human samples in representative studies, emphasizing differences in acquisition methods, utilization rates, and omics preferences across vascular beds. Collectively, these integrative approaches support systems biology frameworks and hold promise for informing precision strategies for early detection, risk stratification, and targeted intervention in AS.
Abstract Depression is a prevalent and debilitating psychiatric disorder that is frequently accompanied by chronic conditions such as cancer, cardiovascular diseases, and neurological disorders. Despite the availability of various pharmacological treatments, their limited efficacy and frequent side effects have prompted growing interest in natural compounds with antidepressant potential. Panax ginseng, a traditional herbal medicine widely used in East Asia, contains diverse bioactive components, among which ginsenosides are recognized as the principal active constituents. Ginsenosides, primarily classified into dammarane-type and oleanane-type saponins, exhibit antidepressant-like effects through multiple interconnected biological mechanisms. These include modulation of monoaminergic neurotransmission, regulation of the hypothalamic–pituitary–adrenal (HPA) axis, promotion of neurogenesis and synaptic plasticity, mitigation of neuroinflammation and oxidative stress, and restoration of gut microbiota homeostasis. Recent investigations also highlight enhanced bioavailability and therapeutic promises of rare ginsenosides, such as ginsenosides Rg3, Rk1 and Rg5, with fewer sugar moieties, suggesting unique advantages for clinical application. This review consolidates current evidence on the pharmacological activities, molecular targets, and therapeutic potential of ginsenosides in the management of depression. By integrating findings from experimental and limited clinical studies, it aims to provide a rational scientific framework to inform future investigation and development of ginsenoside-based strategies for depression, while emphasizing the need for further rigorous clinical validation.
Comorbidity and mutual transformation between psychiatric disorders (including autism spectrum disorder, attention-deficit/hyperactivity disorder, bipolar disorder, post-traumatic stress disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and anxiety disorders) and sleep disorders are common, with circadian rhythm disruption considered a potential biological basis, and neurodevelopmental abnormalities seemingly playing a key role. However, the extent to which shared genetic determinants contribute to these associations remains unclear. Extensive genetic correlations and overlaps were observed between sleep-related phenotypes and psychiatric disorders, with Mendelian randomization analysis further suggesting vertical pleiotropy in 21 of these pairs. Pleiotropic analysis identified 71,733 pleiotropic single nucleotide variants, 718 pleiotropic loci, and 226 co-located loci, with 1,225 candidate pleiotropic genes enriched in phenotypes related to neurodevelopment and brain tissues. A total of 187 candidate pleiotropic genes were screened through Polygenic Priority Score or summary data-based Mendelian Randomization. Pathway enrichment analysis further highlighted biological pathways primarily involving neurodevelopment, synaptic structure, and rhythmic behaviors. Additionally, key hub genes such as HNRNPK, GNL3 and YWHAE exhibited peak expression during early prenatal stages, followed by a decline or plateau throughout life. This study reveals a broad spectrum of pleiotropic genes shared between psychiatric disorders and sleep-related phenotypes, highlighting neurodevelopment as a key mechanism underlying their comorbidity. These findings provide new insights into potential therapeutic targets for these conditions.
