Jun Wu

Background: Childhood health adversity and socioeconomic disadvantage may shape late-life health, but evidence for incident disability and multimorbidity remains limited. Cross-cohort inference is complicated by non-equivalent measures of childhood experiences and differences in timing. We estimated cohort-specific prospective associations in the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE). Methods: ELSA childhood-health/material-adversity indicators and health were assessed at wave 3. SHARE material/cultural disadvantage was assessed at wave 3 or wave 7, with health landmarks at waves 4 and 8; the two inception samples were analyzed separately. Outcomes were the first observed onset of difficulty in at least one of six activities of daily living (ADL-6) and the first observed onset of at least two of seven disease groups (MM-7). Complementary log–log person–period models incorporated interval duration, repeated observations, available survey-design information and baseline weights, and stabilized inverse-probability-of-censoring weights; death was a competing event. Highest exposure categories were compared with zero, without assuming measurement equivalence. Results: Combined survey/attrition-weighted models included 4,290/3,424 ELSA participants, 13,863/9,064 SHARE wave-3 participants, and 23,026/12,560 SHARE wave-7 participants for ADL-6/MM-7, respectively. In the mortality-ascertained ELSA wave 4–6 window, highest-versus-zero hazard ratios (HRs) were 1.43 (95% confidence interval [CI] 1.09–1.87) for ADL-6 and 1.35 (1.02–1.80) for MM-7. After excluding ADL-6 onset observed at wave 4, the lagged ELSA HR was 1.03 (0.70–1.52) through wave 6. Over waves 4–9, HRs were 1.47 (1.19–1.82) and 1.24 (0.98–1.57). SHARE wave-3 HRs were 1.36 (1.08–1.71) and 1.34 (1.09–1.64); wave-7 HRs were 1.60 (1.06–2.43) and 0.93 (0.68–1.27). Standardized competing-risk estimates showed a higher risk of ADL-6 in the primary ELSA analysis and both SHARE inception-sample analyses. MM-7 risk differences were positive in ELSA and SHARE wave 3, whereas the SHARE wave-7 contrast was imprecise and compatible with no association. Conclusion: The highest cohort-specific exposure category versus zero was associated with incident ADL disability in the primary ELSA and SHARE landmark analyses, but the ELSA association appeared strongest in the earliest interval and was not clearly sustained later. Associations with multimorbidity varied by observation window and SHARE inception sample. The findings neither establish measurement equivalence nor explain the observed cross-cohort heterogeneity.

Cardiac fibrosis is a critical pathological feature that drives pressure overload (PO)-induced heart failure (HF). This process involves a complex intercellular crosstalk between cardiac fibroblasts (CFs) and cardiomyocytes. Cardiomyocyte hypertrophy is a compensatory response to PO and undergoes metabolic reprogramming; however, the specific metabolite(s) transmitting the pro-fibrotic signals from hypertrophic cardiomyocytes to CFs remain largely unknown. In this study, we demonstrated that hypertrophic cardiomyocytes secreted elevated level of isoleucine metabolite ketoisoleucine (Ket), which activated CFs to exacerbate PO-induced cardiac fibrosis and dysfunction. Mechanistically, Ket docked with the membrane transporter MCT1, subsequently activating Smad2/3 signaling to upregulate EGR3 expression and its nuclear accumulation, where EGR3 directly bound to the promoter regions of Acta2 and Col3a1 , driving their transcription and promoting CF activation. Remarkably, inhibition of Ket secretion from hypertrophic cardiomyocytes attenuated their pro-fibrotic effects on CF activation, establishing this pathway as a key driver of PO-induced cardiac remodeling. We identify Ket as a metabolic mediator linking cardiomyocyte hypertrophy to cardiac fibrosis in PO conditions. Targeting the Ket-dependent cardiomyocyte-to-fibroblast signaling axis offers potential therapeutic targets for managing PO-induced HF by limiting pathological cardiac fibrosis.

Background: International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) scoring is a standard bedside framework for infection-associated coagulopathy but does not capture anticoagulant-pathway markers. The study examined whether admission antithrombin III (AT-III) activity provided risk-enrichment information for septic shock among adults admitted with infection below the ISTH 2001 overt-DIC threshold. Methods: The study retrospectively analyzed 1,286 adults admitted with infection. AT-III activity was evaluated in the ISTH-complete and below-threshold subsets and compared with ISTH 2001 and 2025 SSC overt-DIC scores. Retrospective temporal adjudication compared first valid AT-III report availability with operational septic-shock onset. In a clinically indicated lactate-measured subset, the study assessed whether AT-III added discrimination beyond age, sex, and lactate. Firth-penalized regression evaluated the conditional association of AT-III with septic shock beyond age, sex, and raw ISTH components. Results: Among 1,027 ISTH-complete patients, 974 (94.8%) were below the ISTH 2001 overt-DIC threshold, including 44 of 60 septic-shock cases. In this subgroup, 43 of 44 shock cases had AT-III activity n = 518), AT-III increased AUC beyond age, sex, and lactate from 0.740 to 0.821; this increment persisted in the incident-shock analysis (0.680–0.792). In the primary Firth model, lower AT-III activity remained conditionally associated with shock (OR 3.10 per 1-SD decrease); the apparent and bootstrap-corrected AUCs were 0.900 and 0.888. Conclusion: Admission AT-III activity was associated with septic shock within the large ISTH below-threshold infection subgroup and provided high-sensitivity, low-positive-predictive-value enrichment information. Retrospectively reconstructed temporal ordering demonstrated a report-release-to-operational-onset interval in incident cases but does not establish prospective prediction, prospective workflow performance, or clinical benefit. AT-III should not be used as a standalone trigger for escalation decisions. Prospective, time-stamped validation is required.

Accurate medical image segmentation with low model complexity remains difficult because lesions are often small in scale and boundary cues are easily corrupted by noise. Although recent segmentation methods have achieved strong performance, many of them rely on increasingly complex architectures with high computational costs, limiting their applicability in resource‐constrained settings. To alleviate this issue, we propose PLNet, a lightweight hybrid segmentation framework for medical image analysis. The network improves representation learning by integrating fine‐grained local‐structure perception with long‐range contextual modelling, thereby enhancing the representation of complex medical images. In addition, a feature selection mechanism is employed to emphasise informative feature responses and suppress redundant activations while preserving discriminative representations. Extensive experiments on multiple datasets demonstrate that PLNet achieves competitive IoU and Dice scores with relatively low model complexity. Overall, these results highlight the potential of PLNet as an effective lightweight framework that balances segmentation performance and computational complexity.

Ischemic heart disease (IHD) remains a leading cause of death globally. Most of previous predictive models rely on conventional factors or inaccessible bio

Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, and its activity has been linked to the risk of atherosclerosis (AS). CETP inhibitors, such as obicetrapib, represent a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides a comprehensive overview of the structure of CETP, the mechanisms of lipid transfer and the progress of immunotherapy in the last decade, which provides possible ideas for future development of novel drugs and optimization of immunization strategies.