Yumeng Jia

Early‐life nutrition may influence long‐term health, but its impact on organ‐specific biological aging is unclear. We investigated associations of birthweight and breastfeeding with multi‐organ aging and potential mediating pathways in adulthood. Using UK Biobank data, we examined associations of retrospectively reported birthweight ( n = 21,446) and breastfeeding history ( n = 29,713) with 19 proteomics‐derived aging indices, comprising 18 organ‐specific indices and one composite index. Multivariable linear regression assessed individual and joint associations, effect modification by sex and socioeconomic factors, and mediation by allostatic load (AL) and C‐reactive protein (CRP). Higher birthweight was inversely associated with aging across 11 organ systems (all FDR‐adjusted p < 0.05), with strongest associations in the intestine ( β = −0.069), esophagus ( β = −0.055), and stomach ( β = −0.053). Breastfeeding exposure was associated with slower aging of the intestine ( β = −0.047) and adrenal gland ( β = −0.030), but modestly faster thyroid aging ( β = 0.033). The combination of higher birthweight and breastfeeding was associated with favorable aging profiles, particularly in the intestine (β = −0.13), stomach (β = −0.09), and kidney (β = −0.08). Associations were stronger among females and socioeconomically advantaged or healthier‐behavior subgroups. AL mediated up to 35.3% of the birthweight–aging association, whereas CRP showed minimal mediation. Higher birthweight and breastfeeding, particularly in combination, produce the most favorable profiles of multi‐organ biological aging in adulthood, with AL partially mediating these effects. These findings provide novel evidence that prenatal and postnatal nutrition leave enduring, system‐wide imprints on adult aging trajectories.

Kashin-Beck disease (KBD) is a multifactorial endemic osteoarthropathy that has been associated with nutritional and environmental factors, including selenium deficiency and T-2 toxin exposure. However, whether combined selenium deficiency and T-2 toxin exposure affects hepatic xenobiotic metabolism has not been systematically investigated. Male C57BL/6 mice were fed a selenium-adequate or selenium-deficient diet for 4 weeks, followed by another 4 weeks with or without daily oral T-2 toxin (0.2 mg/kg). Plasma selenium and glutathione peroxidase (GPx) activity were measured. Hepatic histology, activities of major mouse cytochrome P450 (Cyp450) isoforms, and corresponding mRNA and protein expression were assessed. RNA sequencing was performed using liver samples from four biological replicates per group to identify differentially expressed genes (DEGs) and enriched pathways. Selenium deficiency was confirmed by significantly reduced plasma selenium levels and GPx activity. Histological examination revealed marked hepatic steatosis. Transmission electron microscopy further showed prominent ultrastructural alterations including endoplasmic reticulum dilation. The activities of five hepatic Cyp450 isoforms, Cyp1a2, Cyp2b10, Cyp2c29, Cyp2c50, and Cyp3a11, were significantly increased to 1.64–2.51 times the control levels, consistent with increased mRNA and protein expression. Combined selenium deficiency and T-2 toxin exposure was associated with increased hepatic Cyp450 enzyme activity and expression, identifying the liver as a responsive target of KBD-related exposures. These findings suggest the need to further evaluate hepatic xenobiotic metabolism in populations from KBD-endemic areas.

Background Comorbidity between schizophrenia (SCZ) and chronic diseases is well documented. However, it remains unknown whether unaffected individuals with elevated SCZ genetic liability also face increased risk, and what biological pathways may underlie these associations. Methods We analyzed 426,237 UK Biobank participants without SCZ to test associations between SCZ polygenic risk score (SCZ-PRS) and 24 chronic diseases using logistic regression. Multi-omics mediation analysis incorporated seven inflammatory markers, 1,463 plasma proteins, and 250 circulating metabolites to delineate intermediate pathways linking genetic liability to disease outcomes. Genetic colocalization analyses were further conducted to determine whether SCZ genetic liability and chronic diseases share common association signals at the locus level. Results Higher SCZ-PRS was associated with increased risk of asthma (OR=1.018, 95% CI 1.008–1.029), COPD (1.033, 1.017–1.050), liver disease (1.033, 1.015–1.051), peptic ulcer (1.032, 1.013–1.051), and fluid/electrolyte disorders (1.027, 1.014–1.040), while conferring reduced risk of diabetes (0.979, 0.968–0.991) and renal disease (0.978, 0.964–0.992). Multi-omics mediation revealed that these bidirectional associations were linked to immune cell activity (notably eosinophils, neutrophils, and monocytes), lipid and energy metabolism (lipoprotein composition, fatty-acid unsaturation, creatinine, lactate), and immune-regulatory proteins (e.g., HLA-E, CD1C, SPINT1). Shared genetic signals, notably at HLA and SLC39A8, reinforced these immune–metabolic pathways. Conclusions SCZ-PRS is associated with multiple chronic diseases among unaffected individuals, and these associations suggest shared biological pathways. These findings support a psycho-neuro-immune-metabolic interpretation of SCZ-related chronic physical comorbidity and a more integrated psychosomatic understanding of the shared biology linking psychiatric vulnerability with chronic physical disease.

T-2 toxin, a potent mycotoxin produced by Fusarium species, is recognized for its neurotoxic, hepatotoxic, and reproductive toxic effects. However, its impact on chondrocyte differentiation and cartilage development is not well understood. This study combines transcriptomic and metabolomic analyses to investigate the impact of T-2 toxin on ATDC5 cells during differentiation at days 3, 7, 14, and 21, following 48 h of exposure. Additionally, real-time quantitative PCR (RT-qPCR) was used to evaluate the expression levels of key chondrocyte differentiation-related genes (e.g., Fn1, Sox9, Runx2, Acan, Col1a1, Col2a1, and Col10a1) under T-2 toxin exposure alone or in combination with recombinant Mouse BMP2, BMP4, or both. Our results show that T-2 toxin disrupts several genes and signaling pathways crucial for chondrogenesis, including the BMP signaling pathway, extracellular matrix organization, and arachidonic acid metabolism. Significant temporal alterations in Bmp2, Bmp4, and other key genes were observed, disrupting chondrocyte differentiation. Notably, these changes were mitigated by BMP2 and BMP4 co-treatment, highlighting their protective effects. These findings provide insights into the molecular mechanisms underlying T-2 toxin-induced disruptions in chondrocyte differentiation and support the potential use of BMP signaling pathways as the therapeutic strategies to counteract the detrimental effect of T-2 toxin exposure.

Purpose This study aims to explore the interaction of Selenium (Se) deficiency and HT-2 toxin on cartilage homeostasis and the effect of Notch signaling pathway in this process. Methods Male C57BL/6 mice were randomly assigned to different dietary groups and subjected to either a Se-deficiency diet or a control diet for 4 weeks, followed by exposure to varying doses of HT-2 toxin for 4 weeks. Primary mouse chondrocytes were extracted and treated with DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a γ-secretase inhibitor for the Notch signaling pathway, before combined intervention. Histological evaluation and transmission electron microscopy (TEM) were applied to assess cartilage damage, while immunohistochemical (IHC) analysis and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect extracellular matrix (ECM) metabolism and Notch signaling. Results HT-2 toxin, alone or in combination with Se deficiency, led to significant cartilage injury characterized by chondrocyte necrosis and ultrastructural abnormalities. IHC revealed increased expression of Adamts5 and decreased expression of Col2a1 and Acan in cartilage following exposure to HT-2 toxin, indicative of ECM degradation, which could be aggravated under Se deficiency. Additionally, activation of the Notch signaling pathway was observed in response to HT-2 toxin and Se deficiency, with upregulation of Notch pathway-related components. In vitro experiments further confirmed the role of the Notch pathway in ECM metabolism regulation, with partial protection against ECM depletion caused by HT-2 toxin and Se deficiency observed upon inhibition of the Notch pathway using DAPT. Conclusion This study demonstrate that Se deficiency exacerbates HT-2 toxin-induced cartilage degradation via Notch signaling activation, highlighting the interplay of environmental mycotoxins and nutritional deficits in KBD etiology and identify Notch signaling as a therapeutic target to mitigate disease progression.

The aim of this study was to provide a comprehensive understanding of similarities and differences in mRNAs, lncRNAs, and circRNAs within cartilage for Kashin–Beck disease (KBD) compared to osteoarthritis (OA). We conducted a comparison of the expression profiles of mRNAs, lncRNAs, and circRNAs via whole-transcriptome sequencing in eight KBD and ten OA individuals. To facilitate functional annotation-enriched analysis for differentially expressed (DE) genes, DE lncRNAs, and DE circRNAs, we employed bioinformatic analysis utilizing Gene Ontology (GO) and KEGG. Additionally, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), we validated the expression levels of four cartilage-related genes in chondrocytes. We identified a total of 43 DE mRNAs, 1451 DE lncRNAs, and 305 DE circRNAs in KBD cartilage tissue compared to OA (q value < 0.05; |log₂FC| > 1). We also performed competing endogenous RNA network analysis, which identified a total of 65 lncRNA-mRNA interactions and 4714 miRNA-circRNA interactions. In particular, we observed that circRNA12218 had binding sites for three miRNAs targeting ACAN, while circRNA12487 had binding sites for seven miRNAs targeting COL2A1. Our results add a novel set of genes and non-coding RNAs that could potentially serve as candidate diagnostic biomarkers or therapeutic targets for KBD patients.