Social determinants of health (SDoH) significantly influence female reproductive health. However, existing research has predominantly focused on examining the impact of SDoH on individual reproductive health indicators, lacking comprehensive assessments of their cumulative effects on overall reproductive health and systematic evaluations of multidimensional SDoH exposures. Investigating the influence of SDoH on reproductive health under conditions of cross-national comparability holds critical public health significance for advancing health equity goals. To explore the association between multidimensional SDoH scores and the composite reproductive health index (RRS) and to identify potential causal mechanisms. Additionally, to assess whether the impact of SDoH on reproductive health varies based on individual behavioral characteristics and/or metabolic health status. This cross-sectional study analyzed data from the UK Biobank (UKB, n=12,512) and the US National Health and Nutrition Examination Survey (NHANES, n=2,834). Weighted and unweighted SDoH scores were constructed based on the five core domains outlined in Healthy People 2030. The reproductive risk score (RRS) was derived from 17 (UKB) and 12 (NHANES) reproductive health variables, respectively. Multivariable linear regression models were employed to assess the association between SDoH and RRS, supplemented by subgroup and interaction analyses. Additionally, two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) summary statistics to evaluate potential causal relationships between educational attainment and 13 RRS-related variables. Higher SDoH scores (indicating greater disadvantage) were linearly associated with increased RRS in both cohorts (UKB: Unweighted SDoH score: β=0.048, 95% CI=0.037, 0.059, P<0.001; Weighted SDoH score: β=0.100, 95% CI=0.084, 0.117, P<0.001. Unweighted SDoH score: β=0.118, 95% CI=0.065, 0.171, P<0.001; Weighted SDoH score: β=0.129, 95% CI=0.078, 0.180, P<0.001). Compared with the favorable SDoH group, the unfavorable SDoH group exhibited significantly higher RRS in the UKB population (Unweighted: β=0.237, 95% CI=0.172, 0.302, P<0.001; Weighted: β=0.309, 95% CI=0.243, 0.375, P<0.001). In the NHANES population, both the medium SDoH group (Unweighted: β=0.409, 95% CI=0.095, 0.723, P=0.011; Weighted: β=0.378, 95% CI=0.082, 0.674, P=0.013) and the unfavorable SDoH group (Unweighted: β=0.432, 95% CI=0.118, 0.747, P=0.008; Weighted: β=0.613, 95% CI=0.278, 0.947, P<0.001) demonstrated significantly elevated RRS. Subgroup analyses revealed effect modification by age, BMI, diabetes status, smoking, and physical activity. Mendelian randomization (MR) analysis identified significant causal associations between educational attainment and six RRS-related variables, an inverse association with one variable, and no significant associations with six variables. This study provides the first systematic evidence of a positive dose-response relationship between SDoH scores and female reproductive risk. The findings highlight complex, multi-pathway mechanisms through which SDoH influences reproductive health, modulated by behavioral and metabolic factors. These results underscore the importance of targeted socioeconomic interventions-including improved educational opportunities, economic support, and social environment enhancements-to mitigate disparities in women's reproductive health outcomes.

Organoids are moving from self-organized three-dimensional (3D) cultures toward engineered living systems with translational intent. Yet most platforms still rely on static, poorly defined matrices and limited control over architecture, maturation, and batch reproducibility. Clinical translation exposes scale dependent constraints AIM OF REVIEW: This review reframes organoid translation as an engineering continuum that links controllable variables across three stages: in vitro microenvironment engineering, engineering enabled in vitro translational workflows, and in vivo clinical translation. We summarize how engineered microenvironments provide quantitative control over stiffness, geometry, and transport to improve reproducibility during organoid construction. We then discuss engineering enabled workflows that introduce dynamic conditioning and functional benchmarking to bridge in vitro performance with translational requirements. For in vivo application, we highlight vascularization and immune compatibility as a coupled bottleneck and define functional integration as measurable system level contribution rather than structural persistence alone. Together, these strategies outline a scale aware and clinically aligned engineering framework for organoid translation.

The honeys produced by Apis mellifera ligustica Spinola (A. mellifera) and Apis cerana cerana Fabricius (A. cerana) are the two predominant varieties in terms of global yield, each recognized for its distinct functional properties. Our previous studies identified the characteristic markers distinguishing A. cerana honey and A. mellifera honey. However, the mechanistic links between species-specific metabolism and functional properties remain unclear, presenting a formidable challenge. This study aimed to elucidate how bee species-specific metabolism shapes honey bioactivity. We used topological and enrichment analyses to map the characteristic markers onto metabolic pathways. Also, we quantified the in vitro antioxidant capacity of both honeys and their respective markers via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. We further evaluated the anti-inflammatory efficiency of these honeys in lipopolysaccharide-stimulated Caco-2 cells by measuring cytokine expression and cellular responses. Tryptophan metabolism primarily contributed to the formation of honey in both A. cerana and A. mellifera. A. cerana preferentially metabolized tryptophan via the indoleacetic acid pathway, yielding higher concentrations of methyl indole-3-acetate (MIA), whereas A. mellifera favored the kynurenine pathway, producing elevated levels of kynurenic acid (KYNA). Both compounds enhanced intestinal barrier integrity through their antioxidant and anti-inflammatory activities, despite differing in their specific mechanisms and efficacy. MIA exhibited superior anti-inflammatory and antioxidant properties compared with KYNA, which directly correlated with the enhanced bioactivity of A. cerana honey. KYNA primarily strengthened barrier function by upregulating the expression of tight junction proteins Zonula occludens protein-1(ZO-1), claudin-1, and occludin, whereas MIA demonstrated greater efficacy in suppressing the expression of inflammatory proteins. Correlation analyses confirmed MIA and KYNA as the key drivers of the intestinal barrier-protective activities of honey. The complementary mode of action-KYNA providing structural reinforcement and MIA offering anti-inflammatory modulation-highlights the synergistic bioactivity underlying the protective properties of honey. These findings provide a mechanistic understanding of how bee species-specific tryptophan metabolism in A. cerana and A. mellifera drives the bioactivity divergence in honey, with MIA and KYNA linked to differential antioxidant and intestinal anti-inflammatory activities.