Background Cardiorespiratory fitness (CRF) is a key metric for risk stratification and clinical decision-making in cardiovascular disease (CVD). CRF assessment in Chinese patients with CVD currently relies on reference standards derived from other patients, which may lead to prognostic risk misclassification. Objectives This study aimed to establish CRF reference standards for Chinese patients and assess their utility in stratifying major adverse cardiovascular event (MACE). Methods We conducted a multicenter retrospective study including 56,495 patients with CVD from 20 hospitals across China from 2018 to 2024. Sex- and age-specific CRF reference values and percentiles were derived using 10-year age groups and compared with those of healthy Chinese adults. Prognostic performance was evaluated in a validation cohort of 6,317 patients (median follow-up: 24 months [IQR: 12-36]) using Kaplan-Meier and Cox regression analyses. Results The established CRF reference standards demonstrated significant differences across sex, age, and CVD subtype (P < 0.001). Compared with age- and sex-matched healthy adults, patients with CVD had lower peak oxygen uptake, with relative CRF levels of 73.3% to 78.7% in men and 75.4% to 84.0% in women. Compared with the high-CRF group, the adjusted MACE risk was higher in the middle-CRF (HR: 1.46; 95% CI: 1.16-1.83; P < 0.001) and low-CRF groups (HR: 2.29; 95% CI: 1.81-2.90; P < 0.001). Kaplan-Meier analysis revealed significantly lower event-free survival with decreasing CRF (log-rank P < 0.001). Conclusions This study establishes the first CRF reference standards specific to Chinese patients with CVD and demonstrates their prognostic utility for MACE risk stratification. These findings provide a data-driven framework for functional risk assessment, secondary prevention, and individualized rehabilitation strategies in clinical practice.

Widespread environmental exposure to tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a commonly used organophosphate esters, has raised significant concerns due to its structural similarity to organophosphate pesticides with known immunotoxicity. However, the immunotoxic and underlying mechanisms remain insufficiently understood. In this study, we used mRNA sequencing (mRNA-seq) to investigate the mechanisms underlying TDCPP-induced immunotoxicity following long-term low-dose exposure in THP-1 macrophages. Our findings revealed that TDCPP induces ROS generation, antioxidant depletion, iron accumulation, and lipid peroxidation lead to ferroptosis, as evidenced by lipid peroxidation and mitochondrial morphological changes observed via electron microscopy. Furthermore, TDCPP exposure led to a collapse of the cellular antioxidant defense system. The accumulation of Fe²⁺ and H₂O₂ triggered the Fenton reaction, resulting in oxidative stress and immune disorder. At the individual level, intravenous administration of TDCPP in BALB/C mice increased serum MDA levels and decreased GSH content, significantly affecting Fe²⁺ homeostasis in lymphocytes, confirming the systemic effects of TDCPP exposure. This study is the first to demonstrate TDCPP activates ferroptosis in macrophages through mitochondrial iron imbalance and oxidative stress, resulting in lipid peroxidation in mouse blood and iron imbalance in lymphocytes, providing a theoretical basis for potential health risks in humans. There is an urgent need for further regulatory action and the development of safer alternatives.

Pathological cardiac hypertrophy is a major contributor to heart failure and is often accompanied by ferroptosis and mitochondrial dysfunction. However, the upstream transcriptional mechanisms governing these processes remain poorly defined. We performed integrative bioinformatics analysis using transverse aortic constriction (TAC)-induced hypertrophic heart datasets to identify mitochondria-related differentially expressed genes (MitoDEGs), followed by transcription factor prediction and experimental validation in both in vivo and in vitro models. Adeno-associated virus-mediated overexpression and knockdown strategies were used to assess the regulatory effects of Irx3 and its downstream target Etfa. We identified Etfa as a hub MitoDEG directly regulated by the transcription factor Irx3, which was significantly upregulated in hypertrophic hearts. Mechanistically, Irx3 directly bound to the Etfa promoter and restored Etfa expression in hypertrophic cardiomyocytes. Through integrated transcriptomic analysis, an angiotensin II-induced cardiomyocyte hypertrophy model, and a TAC mouse model, we demonstrate that the Irx3-Etfa axis attenuates hypertrophic remodeling by suppressing ferroptosis. In vitro, overexpression of Irx3 or Etfa alleviates cardiomyocyte hypertrophy and ferroptotic injury, whereas Etfa knockdown abolishes the protective effects of Irx3. In vivo, Irx3 overexpression improves cardiac function, reduces ferroptosis, and limits structural remodeling in TAC mice. These findings reveal a novel transcriptional pathway connecting mitochondrial metabolism to ferroptosis regulation and suggest the Irx3-Etfa axis as a promising therapeutic target for pathological cardiac hypertrophy.

Background Acute myocardial infarction (AMI) is a leading cause of cardiac mortality, necessitating accurate risk prediction models; however, current risk assessment models may not reflect the changes in risk factors in current medical practice. This study aimed to develop and validate a machine learning-based risk prediction model for 1-year post-discharge cardiac mortality among patients with AMI who survived hospitalization, utilizing a multidimensional dataset that integrates environmental determinants and angiographic findings. Methods Data were sourced from a multicenter prospective cohort study (NCT03297164) along with the supplementary AMI cohort from the coordinating medical center, covering the period from January 2017 to July 2022. Patients from the coordinating center constituted the discovery cohort (n = 11,752), while patients from the participating centers served as the external validation cohort (n = 2,593). Random forest, XGBoost, logistic regression, CatBoost, decision tree, and LightGBM algorithms were applied, and the feature selection was performed using SelectFromModel.The model with the strongest overall performance in the internal testing cohort underwent external validation. Results The random forest model was selected, achieving areas under the curve (AUCs) of 0.86 (95% CI: 0.82–0.89) and 0.81 (95% CI: 0.75–0.86) in the internal testing and external validation cohorts, respectively. Frequently selected predictors included age, body mass index, temperature, PM2.5 concentration, Gensini score, weighted diffuse lesion value, and ejection fraction. Random forest outperformed the global registry of acute coronary events (GRACE) score in both cohorts, with AUCs of 0.80 (95% CI: 0.75–0.84) and 0.77 (95% CI: 0.71–0.83), respectively. Compared with the GRACE-based stratification, the risk stratification based on the random forest algorithm also resulted in greater discrimination in both cohorts (AUC: 0.83 vs. 0.64; 0.77 vs. 0.68). Conclusion This study presents a discharge-oriented model for 1-year post-discharge cardiac mortality risk stratification in AMI survivors. Developed and validated using multidimensional data, the model demonstrates superior predictive performance compared with the GRACE score.

Asthma remains the most prevalent chronic respiratory condition affecting pediatric populations, with no curative therapy currently available. Dendritic cells (DCs) are pivotal in initiating Th2 polarization during asthmatic responses, though molecular mechanisms governing DC activation remain incompletely elucidated. As a constituent of the membrane palmitoylated protein family, membrane-associated guanylate kinase (MAGUK) p55 subfamily member 7 (MPP7) has potential therapeutic implications for respiratory disorders, yet its specific involvement in asthma pathogenesis requires further investigation. This study aimed to elucidate MPP7’s protective effects against allergic airway inflammation by analyzing its impact on Th2 immune responses and DC functionality. Clinical data revealed notably reduced MPP7 levels in asthmatic patients’ peripheral blood samples. Experimental models using house-dust-mite (HDM)-exposed mice demonstrated that MPP7 deficiency intensified airway inflammatory responses, with pathological manifestations including amplified leukocyte infiltration, heightened Th2 cytokine production, and elevated serum levels of HDM-specific IgE. Notably, MPP7 caused a marked reduction in pulmonary CD11b+CD103− DCs populations while inhibiting DC activation via interference with NF-κB pathway signaling. These results collectively suggest that MPP7 exerts its anti-inflammatory effects through dual mechanisms involving both cellular subset modulation and intracellular signaling pathway inhibition in DCs, positioning it as a promising candidate for managing allergic respiratory disorders and associated immune-mediated conditions.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women. Accumulating evidence indicates that gut dysbiosis and metabolic disturbances are associated with the pathogenesis of PCOS. However, the mechanisms by which metabolic alterations influence gut homeostasis and contribute to PCOS progression remain poorly understood. Here, we show that N-acetylneuraminic acid (Neu5Ac) exacerbates dehydroepiandrosterone (DHEA)-induced PCOS phenotypes in female mice in a gut microbiota-dependent manner. Specifically, Neu5Ac promotes the expansion of the gut Ligilactobacillus salivarius (L. sa) with bile salt hydrolase (BSH) activity. Administration of L. sa to DHEA-treated mice worsens PCOS symptoms by reducing levels of the conjugated bile acid tauroursodeoxycholic acid (TUDCA) via BSH activity. Reduced TUDCA enhances intestinal farnesoid X receptor (FXR) activation, leading to suppression of IL-22 production. Mechanistically, IL-22 attenuates DHEA-induced ovarian ferroptosis by activating the STAT3 signaling pathway. These findings reveal that sialic acid-mediated bile acid-FXR-IL-22 signaling contributes to PCOS pathogenesis, highlighting a potential therapeutic strategy for PCOS intervention.

Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that the data shown for the p-AMPKα blots with the RT-qPCR analysis in Fig. 2B on p. 203 are strikingly similar to the ATG7 blots shown in Fig. 4A on p. 205. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, although up to this time, no response from the authors has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 39: 199-207, 2017; DOI: 10.3892/ijmm.2016.2824].

BACKGROUND:This study aims to employ a prospective cohort design to quantitatively assess the association between exposure levels of common ambient air pollutants and the risk of cardiovascular disease (CVD) in patients across stages 0-3 of Cardiovascular-kidney-metabolic (CKM) syndrome. By doing so, it addresses a critical knowledge gap in environmental exposure research within this specific clinical context. METHODS:We analyzed baseline differences between CVD cases/controls using descriptive statistics, parametric/nonparametric tests, and Pearson correlations for air pollutants (PM₁, PM2.5, PM₁₀, NO₂, O₃). Cox regression (Models 1-3, adjusting for sociodemographic/behavioral factors) and RCS assessed pollutant-CVD associations. WQS/qgcomp models evaluated mixture effects via weighted indices and directional weighting. Sensitivity analyses used BKMR, WQS-CVD exposure-response curves, and 2-year lag to address reverse causality. RESULTS:In single-pollutant analyses, per-interquartile range (IQR) increases in PM₁, PM₂.₅, PM₁₀, and NO₂ were associated with 30% (HR = 1.30, 95% CI 1.17-1.45), 35% (HR = 1.35, 95% CI 1.21-1.51), 52% (HR = 1.52, 95% CI 1.35-1.70), and 30% (HR = 1.30, 95% CI 1.17-1.45) elevations in CVD risk, respectively. No significant association was found for O₃. In mixture analyses, all three quantile g-computation (qgcomp) models linked combined pollutant exposure to significantly higher CVD risk (Model 1: HR = 1.10, 95% CI 1.04-1.17; Model 2: HR = 1.11, 95% CI 1.04-1.18; Model 3: HR = 1.12, 95% CI 1.05-1.19). PM₁₀ emerged as the dominant driver of the mixture effect. CONCLUSION:Higher exposure levels to ambient air pollutants are associated with an increased risk of cardiovascular disease in patients with Stage 0-3 CKM syndrome.

Heart failure after acute myocardial infarction (post-MI HF) has become a major global health problem. Accurate risk prediction is essential for optimising management and preventing post-MI HF. However, existing models rely mainly on resting-state clinical examinations and inadequately reflect the complex pathophysiology of post-MI HF. We aimed to develop and validate a multimodal machine learning (ML) model incorporating cardiopulmonary exercise testing (CPET) data to predict post-MI HF risk and to quantify CPET’s incremental value.This study included 3172 acute myocardial infarction (AMI) patients who underwent CPET at three hospitals from 2018 to 2023. The primary outcome was post-MI HF within 1 year. Thirteen ML algorithms were used to select clinical and CPET variables and to construct multimodal prediction models. The incremental predictive value of CPET was evaluated by the area under the curve (AUC), integrated discrimination improvement index (IDI), and net reclassification improvement index (NRI).After screening, 2221 patients were included, of whom 221 (10.0

Background:Peak heart rate (HR peak) and first ventilatory threshold heart rate (HR VT1) guide exercise prescription formulation, but existing formulas lack accuracy in coronary heart disease (CHD) patients due to unaccounted pathophysiological differences. This study aimed to construct prediction equation for HR peak and HR VT1 in CHD patients. Methods:This was a multicenter retrospective study that included 14,465 cases of cardiopulmonary exercise test (CPET) data from CHD patients in 20 hospitals in China. Seventy percent of the cohort was divided into a development group (n = 10,125), and the remaining 30% served as a validation group (n = 4340). Stepwise multiple backward regression established HR peak and HR VT1 equations, with accuracy compared to traditional formulas. Results:Age, weight, resting heart rate (HR rest), CHD diagnostic category, and β-blockers were included in the equation. The mean absolute percentage error (MAPE) of China-CPET-HR peak is 9.04%, with an adjusted coefficient of determination (R 2) of 0.399. For the China-CPET-HR VT1 formula, the MAPE is 7.32% and the adjusted R 2 is 0.509. The %HR peaks of the FOX, TANAKA, KETEYIAN, and China-CPET-HR peak formulas are 82 ± 11%, 79 ± 11%, 105 ± 13%, and 100 ± 11%, respectively. Conclusion:Based on CPET data from CHD patients, we developed prediction equations for HR peak and HR VT1. The prediction accuracy of these equations is significantly higher than others, which helps to formulate accurate individualized exercise prescriptions and rehabilitation training guidance for CHD patients.

Abstract Background Chronic psychological stress drives neuroimmune crosstalk and accelerates atherosclerosis progression. Physical exercise confers broad health benefits and is associated with reduced inflammation. However, the exercise‐mediated factors and mechanisms that mitigate stress‐induced vascular inflammation remain unclear. Methods Chronic restraint stress (CRS) and voluntary exercise models were established to investigate the role of exercise in neuroimmune crosstalk. RNA sequencing identified kinesin family member 4 (Kif4) as a key gene associated with the attenuation of stress‐induced inflammatory responses in peripheral blood monocytes following exercise. Combined co‐immunoprecipitation–mass spectrometry and membrane proteomics identified T cell‐interacting activating receptors on myeloid cell 1 (TARM1) as the Kif4 cargo. The function of TARM1 was validated using an immobilized TARM1‐Fc fusion protein. Brain‐derived neurotrophic factor (BDNF), a key effector during exercise and stress, regulated the Kif4–TARM1 axis using recombinant BDNF (rBDNF) and the TrkB inhibitor ANA‐12. Finally, exercise‐mediated effects and mechanisms were examined in atherosclerotic CRS‐exposed mouse models and in patients with coronary artery disease (CAD) experiencing high psychological stress. Results Physical exercise alleviated stress‐induced neuroimmune crosstalk, reduced the proinflammatory CD11b+Ly6Chigh monocyte phenotype, and suppressed M1 macrophage polarization. Kif4 knockdown mitigated proinflammatory responses in peripheral blood monocytes and BMDMs in the CRS model mice. Mechanistically, kinesin Kif4 facilitates microtubule‐dependent transport of TARM1 to the plasma membrane, thereby promoting macrophage inflammatory responses and enhancing monocyte‒endothelial cell adhesion. Conversely, neurogenic BDNF, regulated by exercise and stress, activated the TrkB receptor in monocytes/macrophages and inhibited the p‐STAT3/Kif4/TARM1 signalling pathway. Furthermore, in both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress‐induced inflammation via the BDNF–Kif4–TARM1 axis. Conclusions Physical exercise alleviates stress‐induced neuroimmune crosstalk through the BDNF–Kif4–TARM1 axis, revealing a novel neuroimmune‐mediated brain–heart axis that supports exercise‐based therapeutic strategies for psychogenic CAD. Key Points Chronic psychological stress drives systemic inflammation through neuroimmune mechanisms, thereby accelerating the progression of coronary artery disease (CAD). Physical exercise alleviates stress‐induced neuroimmune crosstalk, partly by suppressing proinflammatory responses in monocytes/macrophages. This study provides novel insights into exercise‐regulated neuroimmune mechanisms involving the monocyte BDNF–Kif4–TARM1 axis. In both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress‐induced inflammation via the BDNF–Kif4–TARM1 axis.

Background While associations between exposure to air pollution and the prevalence of acute ischaemic stroke (AIS) have been investigated, only a few studies have reported the relationship between air pollution and stroke severity. This study aimed to assess the impact of air pollution on AIS severity based on hourly monitoring data and a stroke-specific registry from 2017 to 2021 in Shanghai.Methods Hourly concentrations of particulate matter (PM2.5 and PM10), O3, SO2, CO and NO2 were monitored from 2017 to 2021. A conditional logistic regression model and a Quasi-Poisson model, both coupled with a distributed lag non-linear model and a time-stratified case-crossover design, were used to evaluate a cohort of 106 623 AIS events documented within the Shanghai Stroke Service registry correspondingly. Counterfactual analyses were applied to reveal the potential reducible fractions (PRFs) of air pollution on baseline National Institute of Health Stroke Scale (NIHSS).Results Conditional logistic regression model suggested that PM2.5 (excessive risk (ER) 2.31% (95% CI 1.32% to 3.32%), p<0.001), PM10 (ER 2.60% (95% CI 1.97% to 3.23%), p<0.001) and SO2 (ER 4.53% (95% CI 3.37% to 5.70%), p<0.001) have the most significant effects on increased baseline NIHSS score, which remained robust in the two-pollutant model. Counterfactual analysis based on a conditional logistic regression model revealed PRFs (PM2.5 1.77% (95% CI 0.86% to 2.68%), p<0.001; PM10 1.01% (95% CI 0.28% to 1.73%), p<0.001 and SO2 4.04% (95% CI 3.04% to 5.03%), p<0.001). Quasi-Poisson analysis showed similar results.Conclusions Short-term exposure to ambient air pollution, particularly PM2.5, PM10 and SO2, was shown to increase AIS severity. This finding underscored the need for targeted emission controls and stroke prevention strategies.

Oxygen uptake at anaerobic threshold (VO2AT) is an important indicator for guiding cardiovascular disease (CVD) rehabilitation training and evaluating cardiac function, which varies according to race and specific disease conditions. However, there is no well-established nonexercise prediction equation for VO2AT. This study aims to develop a nonexercise predictive equation for VO2AT that is applicable to Chinese patients with CVD. A cohort was established with 22,336 cases of cardiopulmonary exercise testing data from CVD patients across 20 hospitals in China. Approximately 70

BACKGROUND:Aspirin-exacerbated respiratory disease (AERD) is a refractory type 2 inflammatory disorder affecting the unified airway. Conventional treatments offer limited efficacy with high recurrence. Biologics are approved for chronic rhinosinusitis with nasal polyps or asthma, but AERD-specific randomized controlled trials remain critically scarce, and quantitative synthesis of biologic efficacy specifically in AERD subgroups is limited. OBJECTIVE:To evaluate the efficacy of biologics on selected upper- and lower-airway outcomes in AERD subgroups. METHODS:We searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials of biologics in AERD. Upper- airway outcomes included the Nasal Polyp Score, Nasal Congestion Score, 22-item Sino-Nasal Outcome Test, and University of Pennsylvania Smell Identification Test. Lower airway outcomes included the 5-item Asthma Control Questionnaire and FEV1. RESULTS:Eleven studies (15 randomized controlled trials, 818 patients with AERD) were included. Biologics significantly improved upper-airway outcomes when compared with placebo: Nasal Polyp Score (mean difference [MD], -1.33 [95% CI, -2.07 to -0.59]), Nasal Congestion Score (MD, -0.84 [95% CI, -1.15 to -0.53]), 22-item Sino-Nasal Outcome Test (MD, -19.16 [95% CI, -25.62 to -12.69]), and University of Pennsylvania Smell Identification Test (MD, 8.00 [95% CI, 1.33 to 14.66]). Lower-airway outcomes were also significantly improved: 5-item Asthma Control Questionnaire (MD, -0.90 [95% CI, -1.32 to -0.48]) and FEV1 (MD, 0.29 L [95% CI, 0.21 to 0.37]). All improvements exceeded the respective minimal clinically important difference thresholds. CONCLUSIONS:In AERD subgroups, biologics produced statistically significant and clinically meaningful improvements across all evaluated upper- and lower-airway outcomes, with pooled effect sizes exceeding respective minimal clinically important difference thresholds.

BACKGROUND AND AIMS:Several protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in statin-intolerant patients, but none have been verified in Chinese patients. This study aimed to evaluate the efficacy and safety of ongericimab, a novel PCSK9 monoclonal antibody, in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia. METHODS:This was a randomized, multicenter, double-blind, placebo-controlled phase 3 study designed to enroll 120 statin-intolerant adult patients. Eligible patients were randomly assigned in a 2:1 ratio to receive ongericimab 150 mg or placebo subcutaneously every 2 weeks for 12 weeks in the double-blind treatment period, followed by 40 weeks of ongericimab treatment during the open-label period. The primary endpoint was a percentage change in LDL-C from baseline to week 12. The key secondary endpoints included percentage change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC), and lipoprotein(a) [Lp(a)]. RESULTS:From February 6, 2023, to September 23, 2024, a total of 139 patients were enrolled. The least-squares (LS) mean difference between ongericimab and placebo groups in LDL-C from baseline to week 12 was -66.2 % (95 % CI: 74.2 %, -58.2 %; p < 0.0001), with reductions sustained up to week 52. Ongericimab also significantly reduced levels of non-HDL-C, ApoB, TC, and Lp(a). The overall incidence of treatment-emergent adverse events was comparable between the ongericimab and placebo groups. CONCLUSION:Ongericimab significantly reduced LDL-C as well as other atherogenic lipid levels and was well tolerated in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia. CLINICAL TRIAL REGISTRATION:http://www. CLINICALTRIALS:gov; Unique Identifier: NCT05621070.

Background:This study aimed to investigate the role and mechanism of long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) in macrophage ferroptosis during atherosclerosis (AS). Methods:The clinical characteristics and disease severity were assessed in 84 patients with coronary heart disease (CHD). The role of NEAT1 in high-fat diet-induced AS and the impact of exercise were examined in APOE-/- and NEAT1-/- mice. Human monocyte THP-1 cells were utilized to explore cellular mechanisms underlying AS. Quantitative real-time PCR, immunofluorescence staining, and Western blot analysis were employed to analyze gene expression. Transmission electron microscopy and fluorescence in situ hybridization were used to examine cellular and tissue-level changes. Bioinformatics analyses were conducted to explore protein interactions and functional networks. Results:NEAT1 expression and iron levels were correlated with disease severity in CHD patients. In THP-1 cells, oxidized low-density lipoprotein (ox-LDL) induced NEAT1 expression, ferroptosis marker ACSL4, reactive oxygen species (ROS), and mitochondrial abnormalities. Knockdown of NEAT1 reversed these effects. NEAT1 overexpression increased pSTAT3, ACSL4, and ROS production, reversed by STAT3 inhibitor. NEAT1 physically interacted with STAT3 via FBXW11. Knockdown of NEAT1 promoted pSTAT3 ubiquitination, reduced ACSL4 expression, and reversed ox-LDL effects. NEAT1 deletion attenuated macrophage ferroptosis and AS in APOE-/- mice. Exercise reduced NEAT1 and ferroptosis indicators in mice and CHD patients. Conclusions:NEAT1 plays a crucial role in macrophage ferroptosis during AS. Targeting NEAT1 or exercising may provide therapeutic interventions against AS.

Cardiac remodelling, a pathological process induced by various cardiovascular diseases, remains a significant challenge in clinical practice. Here, we investigate the potential of Danuglipron (PF-06882961, PF), a novel oral glucagon-like peptide-1 (GLP-1) receptor agonist, in alleviating pressure overload (PO)-induced cardiac hypertrophy and fibrosis. Using both in vivo and in vitro models, we demonstrate that PF treatment (1 mg/kg/day, orally for 8 weeks) significantly attenuates aortic banding-induced cardiac dysfunction and pathological remodelling in mice. Mechanistically, we show that PF mitigates apoptotic responses and enhances autophagy by promoting AMPK phosphorylation and increasing HSP70 expression. Notably, the cardioprotective effects of PF are abolished in AMPKα2 knockout mice, with no observable increase in HSP70 levels. Our findings reveal a previously unrecognised role of PF in cardiac protection, mediated through the AMPKα-HSP70 signalling pathway, and suggest its potential as a therapeutic strategy for PO-induced cardiac remodelling.

Objectives:To quantify the tracheal, bronchial, and lung cancer burden attributable to particulate matter pollution in selected countries, and thereby provide evidence for context - specific public health interventions. Methods:Based on Global Burden of Disease (GBD) 2021 data,we appliedJoinPoint to analyze the temporal trends from 1990-2021 in the burden of PM2.5 - attributable tracheal, bronchial, and lung (TBL) cancer in China, the US, Japan, and South Korea. And we explored the age, period, cohort effects and predicted future trends using the age-period-cohort mode and Bayesian analysis. Results:Globally, the age-standardized mortality rate (ASMR) for TBL cancers due to PM2.5 exposure showed a declining trend with an average annual percentage change (AAPC) of-1.2811 from1990 to 2021, projections suggest continued decreases in ASMR in selected countries over the next 29 years, but a global increase is expected. Conclusion:Studies have demonstrated a global decline in the mortality burden attributed to bronchogenic carcinoma linked to PM2.5. Nevertheless, future projections indicate that the global burden of air pollution-related TBL cancer will rise, effective public health strategies are urgent to develop.