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Abstract Background Heavy metal exposure is an emerging environmental risk factor linked to cardiovascular disease (CVD) through its effects on vascular ageing. However, the relationship between heavy metal exposure and vascular age have not been fully elucidated. Methods This cross-sectional study analyzed data from 3,772 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016. We measured urinary concentrations of nine heavy metals and assessed their associations with vascular age, estimated pulse wave velocity (ePWV) and heart vascular age (HVA). Additionally, sex-stratified analyses, Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression were conducted to explore the effects of individual and mixed metal exposures. Results Exposure to metals such as cadmium (Cd) cesium (Cs), cobalt (Co), and lead (Pb) was significantly associated with increased vascular age, with odds ratios (OR) ranging from 1.05 to 3.48 in full adjusted models. Sex-stratified analyses indicated that individual metal including cobalt (Co) and cadmium (Cd) exposures had a more substantial impact on males. WQS analysis consistently showed combined heavy metals exposure had stronger associations with increased vascular age in men (OR for HVA = 3.89, 95% CI 2.91–5.28). Conclusions This study highlights a significant association between heavy metal exposure and increased vascular age. Stratified analyses illustrated men might be more susceptible to the combined effects of multiple heavy metal exposure. The findings underscore the importance of considering sex-specific responses and interventions measures in cardiovascular risk assessments and managements. Further research is needed to validate these findings and to develop more precise public health strategies targeting environmental risks. Graphical Abstract

Bone loss caused by ageing has become one of the leading health risk factors worldwide. Wheat germ (WG) is consists of high amounts of bioactive peptides, polyunsaturated fatty acids, and dietary fibre. Currently, WG has been proven to possess strong antioxidant and anti-inflammatory properties. We recently explored the beneficial effects and relevant mechanisms of a WG-rich diet (2.5% and 5% WG, m/m) on bone homeostasis in aged rats. Our results showed that 5% WG supplementation for 12 months effectively attenuated ageing-induced microstructural damage and differentiation activity changes in the femur. The 5% WG supplementation also significantly increased the levels of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) (P < 0.01), and superoxide dismutase (SOD) (P < 0.05), and decreased inflammatory cytokine levels (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) (P < 0.01). Furthermore, the WG-rich diet reshaped the composition of the gut microbiota, enhancing short-chain fatty acids (SCFAs)-producing microbes and reducing inflammation-related microbes. In addition, metabolomics analysis showed that 5% WG supplementation improved plasma metabolites related to bone metabolism. Conclusively, our study purports long-term WG-rich diet may preserve bone homeostasis by regulating gut microbiota and plasma metabolites in aged rats.

Objective To examine recent patterns regarding oral anticoagulant (OAC) use among patients hospitalised with atrial fibrillation (AF) and quantify the impact of insurance coverage for non-vitamin K oral anticoagulants (NOACs) on quality of care and care inequality regarding OAC use among hospitalised patients with AF.Design Interrupted time series analysis.Setting Hospitals in China.Participants A total of 36 393 patients hospitalised with non-valvular AF were involved between 2015 and 2019 across China.Primary and secondary outcome measures Outcome was the impact of insurance coverage for NOACs on quality of care regarding OAC prescription using interrupted time series analysis with segmented regression models.Results OAC prescription rate during hospitalisation was 52.1% (31.3% for warfarin and 20.8% for NOACs) in patients with high-risk AF and 66.3% (29.8% for warfarin and 36.5% for NOACs) in low-risk patients. Insurance coverage for NOACs was associated with an immediate 10.9% (95% CI 7.6% to 14.3%) increase in NOAC prescription and a 0.33% (95% CI 0.08% to 0.58%) increase in the slope of the secular trend of NOAC prescription among all the patients. Disparities in NOAC prescription among hospitals decreased from 18.9 before the insurance coverage for NOACs to 3.4 after that. Similar results were found in patients with high risk of stroke.Conclusion A large gap exists between clinical practice and guideline recommendations regarding OAC prescription among patients hospitalised with AF in China. Insurance coverage may be an effective healthcare strategy to improve quality of care and reduce care disparities regarding OAC prescription among patients with AF.Trial registration number NCT02309398.

In this study, endoplasmic reticulum (ER) stress inducer tunicamycin (TM) and inhibitor 4-phenylbutyric acid (4-PBA) were used to treat postmortem chicken breast muscle to investigate changes in tenderness and effects on apoptosis and autophagy during 5 days ageing. TM-induced ER stress reduced shear force, enhanced myofibril fragmentation index (MFI), disrupted myofibril structure, increased desmin degradation, and activated μ-calpain and caspase-12. In addition, TM-induced ER stress increased the expression of Bax, Bim, and cytochrome c, and decreased the expression of Bcl-xL. Furthermore, TM-induced ER stress improved the conversion of LC3I to LC3II, raised the expression of Beclin-1, and decreased the expression of p62, PI3K, and mTOR. The opposite results were observed after 4-PBA treatment. These results suggested that ER stress could improve chicken tenderness, promote apoptosis and autophagy during chicken postmortem ageing.

Abstract Bioactive food ingredients contribute to the promotion and maintenance of human health and wellbeing. However, these functional ingredients often exhibit low biopotency after food processing or gastrointestinal transit. Well‐designed oral delivery systems can increase the ability of bioactive food ingredients to resist harsh environments inside and outside the human body, as well as allow for controlled or triggered release of bioactives to specific sites in the gastrointestinal tract or other tissues and organs. This review presents the characteristics of common bioactive food ingredients and then highlights the barriers to their biopotency. It also discusses various oral delivery strategies and carrier types that can be used to overcome these biopotency barriers, with a focus on recent advances in the field. Additionally, the advantages and disadvantages of different delivery strategies are highlighted. Finally, the current challenges facing the development of food‐grade oral delivery systems are addressed, and areas where future research can lead to new advances and industrial applications of these systems are proposed.

Abstract Inhibitors of α‐amylase have been developed to regulate postprandial blood glucose fluctuation. The enzyme inhibition arises from direct or indirect inhibitor‐enzyme interactions, depending on inhibitor structures. However, an ignored factor, substrate, may also influence or even decide the enzyme inhibition. In this work, it is innovatively found that the difference in substrate enzymolysis modes, i.e., structural composition and concentration of α‐1,4‐glucosidic bonds, triggers the diversity in inhibitor‐enzyme aggregating behaviors and α‐amylase inhibition. For competitive inhibition, there exists an equilibrium between α‐amylase‐substrate catalytic affinity and inhibitor‐α‐amylase binding affinity; therefore, a higher enzymolysis affinity and concentration of α‐1,4‐glucosidic structures interferes the balance, unfavoring inhibitor‐enzyme aggregate formation and thus weakening α‐amylase inhibition. For uncompetitive inhibition, the presence of macromolecular starch is necessary instead of micromolecular GalG2CNP, which not only binds with active site but with an assistant flexible loop (involving Gly304‐Gly309) near the site. Hence, the refined enzyme structure due to the molecular flexibility more likely favors the inhibitor binding with the non‐active loop, forming an inhibitor‐enzyme‐starch ternary aggregate. Conclusively, this study provides a novel insight into the evaluation of α‐amylase inhibition regarding the participating role of substrate in inhibitor‐enzyme aggregating interactions, emphasizing the selection of appropriate substrates in the development and screening of α‐amylase inhibitors.

Paroxysmal atrial fibrillation is a common arrhythmia, and its development process and prediction of the degree of atrial fibrosis are of great significance for treatment and management. Optical imaging technology provides a new means for non-invasive observation of atrial electrical activity. The aim of this study is to investigate the predictive effect of sinus node recovery time on the degree of atrial fibrosis in patients with paroxysmal atrial fibrillation, and to provide a basis for the application of optical imaging technology in the study of atrial fibrosis. The study collected clinical and optical imaging data from a group of patients with paroxysmal atrial fibrillation, and used statistical analysis methods to investigate the relationship between sinus node recovery time and the degree of atrial fibrosis. The research results indicate that there is a significant correlation between the recovery time of the sinus node and the degree of atrial fibrosis, that is, there is a positive correlation between the prolonged recovery time of the sinus node and the aggravation of atrial fibrosis. SNRT can serve as an effective indicator for evaluating atrial matrix and can be applied to predict recurrence after catheter ablation of paroxysmal atrial fibrillation. Shortening SNRT through catheter ablation can become an important predictor of effective catheter ablation.

Background: Endothelial dysfunction is a complication of diabetes mellitus (DM), characterized by impaired endothelial function in both microvessels and macrovessels, closely linked to atherosclerosis (AS). Endothelial dysfunction, characterized by impaired endothelial cell (EC) function, is a pivotal factor in AS and DM. Circular RNAs (circRNAs) are endogenous non-coding RNAs that can act as competing endogenous RNAs (ceRNAs) and regulate gene expression. However, the role of circRNAs in ECs dysfunction and AS under high glucose (HG) condition remains elusive. Methods: We performed high-throughput sequencing to identify differentially expressed (DE) circRNAs in human umbilical vein endothelial cells (HUVEC) exposed to HG, one risk factors of endothelial dysfunction and AS. We then validated eight candidate circRNAs by qRT-PCR and functional analysis, directing our attention to hsa_circ_0122319. Moreover, microarray analysis identified the differential expression profiles of miRNAs and mRNAs regulated by hsa_circ_0122319. Subsequently, the construction of the ceRNAs network employed bioinformatic analysis and Cytoscape software. Furthermore, the role of the PI3K-Akt signaling pathway in regulating ceRNAs was evaluated. Results: We detected 917 DE circRNAs in HG treated HUVEC. The parental genes of these circRNAs were enriched in cell cycle, cellular senescence and endocytosis related pathways. The differential expression of hsa_circ_0122319 was confirmed to be most obvious at the cellular level and in clinical samples by qPCR experiments. After overexpression of hsa_circ_0122319, 49 DE miRNAs and 459 DE mRNAs were identified using microarray analysis. Subsequently, a ceRNAs network was constructed, comprising hsa_circ_0122319, 8 miRNAs, and 41 mRNAs. Conclusion: In summary, our study delves into the role of circRNAs in endothelial dysfunction associated with DM and AS. Through high-throughput sequencing and validation, we identified hsa_circ_0122319 as a pivotal regulator of ECs function under HG conditions. It also showed that hsa_circ_0123319 has the potential to serve as a biomarker for DM and its vascular complications, and provides new evidence for future exploration of the intricate molecular mechanisms of endothelial dysfunction in the progression of DM and AS.

Quercetin compounds have antioxidant, anti-inflammatory and anticancer pharmacological functions. Long-term exposure to acrylamide (AA) can cause liver injury and endanger human health. However, whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear. Here, we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro. In vivo studies found that quercetin-like compounds protect against AA-induced liver injury by reducing oxidative stress levels, activating the Akt/mTOR signaling pathway to attenuate autophagy, and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis. In vitro studies found that quercetin compounds protected HepG2 cells from AA by attenuating the activation of AA-induced autophagy, lowering reactive oxygen species (ROS) levels by exerting antioxidant effects and thus attenuating oxidative stress, increasing mitochondrial membrane potential (MMP), and improving apoptosis-related proteins, thus attenuating AA-induced apoptosis. Furthermore, the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity, with quercetin showing the best protective capacity due to its strongest antioxidant activity. In conclusion, quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress, autophagy and apoptosis, and their protective capacity correlates with antioxidant activity.

The process of energy decarbonization in island power systems is accelerated due to the swift integration of inverter-based renewable energy resources (IBRs). The unique features of such systems, including rapid frequency changes resulting from potential generation outages or imbalances due to the unpredictability of renewable power, pose a significant challenge in maintaining the frequency nadir without external support. This paper presents a unit commitment (UC) model with data-driven frequency nadir constraints, including either frequency nadir or minimum inertia requirements, helping to limit frequency deviations after significant generator outages. The constraints are formulated using a linear regression model that takes advantage of real-world, year-long generation scheduling and dynamic simulation data. The efficacy of the proposed UC model is verified through a year-long simulation in an actual island power system using historical weather data. The alternative minimum inertia constraint, derived from actual system operation assumptions, is also evaluated. Findings demonstrate that the proposed frequency nadir constraint notably improves the system’s frequency nadir under high photovoltaic (PV) penetration levels, albeit with a slight increase in generation costs, when compared to the alternative minimum inertia constraint.

The optimal dietary lipid requirement and underlying lipid metabolic mechanisms remain elusive in greasyback shrimp (Metapenaeus ensis), presenting significant obstacles to the advancement of their culture development. Five isonitrogenous diets (38.39% crude protein) containing lipid levels of 2.25%, 4.72%, 7.50%, 10.18%, and 12.71% were formulated to evaluate the effects of dietary lipid levels on growth, lipid metabolism, fatty acid composition and antioxidant capacity of juvenile greasyback shrimp. The results indicated that shrimps fed a diet with 7.50% lipid exhibited significantly higher percent weight gain (161.36%) and specific growth rate (1.72%/d) than those fed other diets (P < 0.05). As the dietary fat content increased, the lipid levels of the whole shrimp, muscle, hepatopancreas, and serum exhibited similar elevations. Concurrently, H&E staining clearly revealed the occurrence of hepatocyte swelling and hepatocyte vacuolization in the 10.18% and 12.71% groups, and hepatic lipid accumulation was further observed in these groups by Oil red O staining. In addition, with the increase in dietary fat levels, saturated fatty acids (SFA) decreased and polyunsaturated fatty acids (PUFA) increased in both hepatopancreas and muscle. The expression of genes involved in lipogenesis (fas, acc and dgat) was initially up-regulated and subsequently down-regulated with increasing dietary lipid levels, whereas the expression trends of lipolysis genes (hsl, atgl) remained similar. The mRNA levels of genes associated with long-chain PUFA biosynthesis (elovl5, lxrβ, srebp1) and fatty acid oxidation (cpt1, acox1) in the hepatopancreas of shrimp fed a diet with 7.50% lipid were significantly elevated compared to those in other dietary groups (P < 0.05). With the increase in dietary fat levels, the expression of fatty acid transport genes fatp4 and fabp1 was up-regulated. Antioxidant enzyme activities in the hepatopancreas initially increased with dietary lipid levels, peaking in shrimp fed the 7.50% lipid diet, but subsequently declined. In conclusion, optimal dietary fat levels enhance growth performance, while high lipid levels impede growth, decrease antioxidant enzyme activities, and regulate lipid deposition in greasyback shrimp by modulating lipid metabolic pathways.

Objectives: Hypertension, a key contributor to mortality, is impacted by biological aging. We investigated the relationship between novel biological aging metrics - Phenotypic Age (PA) and Phenotypic Age Acceleration (PAA) - and mortality in individuals with hypertension, exploring the mediating effects of arterial stiffness (estimated Pulse Wave Velocity, ePWV), and Heart/Vascular Age (HVA). Methods: Using data from 62,160 National Health and Nutrition Examination Survey (NHANES) participants (1999–2010), we selected 4,228 individuals with hypertension and computed PA, PAA, HVA, and ePWV. Weighted, multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating PA, PAA to mortality, and mediation roles of ePWV, PAA, HVA were evaluated. Mendelian randomization (MR) analysis was employed to investigate causality between genetically inferred PAA and hypertension. Results: Over a 12-year median follow-up, PA and PAA were tied to increased mortality risks in individuals with hypertension. All-cause mortality hazard ratios per 10-year PA and PAA increments were 1.96 (95% CI, 1.81–2.11) and 1.67 (95% CI, 1.52–1.85), respectively. Cardiovascular mortality HRs were 2.32 (95% CI, 1.97–2.73) and 1.93 (95% CI, 1.65–2.26) for PA and PAA, respectively. ePWV, PAA, and HVA mediated 42%, 30.3%, and 6.9% of PA’s impact on mortality, respectively. Mendelian randomization highlighted a causal link between PAA genetics and hypertension (OR = 1.002; 95% CI, 1.000–1.003). Conclusion: PA and PAA, enhancing cardiovascular risk scores by integrating diverse biomarkers, offer vital insights for aging and mortality evaluation in individuals with hypertension, suggesting avenues for intensified aging mitigation and cardiovascular issue prevention. Validations in varied populations and explorations of underlying mechanisms are warranted.