Current guidelines diverge on the optimal door-to-balloon time (DTBT) for acute ST-segment elevation myocardial infarction (STEMI), and whether a ≤60 min target benefits all patients equally remains unclear.

This study aimed to investigate whether the association between DTBT ≤60 min and short- and long-term prognosis in STEMI patients varies by Global Registry of Acute Coronary Events (GRACE) risk score.

Retrospective cohort study.

Single high-volume tertiary cardiology centre in China.

This study initially included 5516 STEMI patients undergoing primary percutaneous coronary intervention (PPCI) treatment. 4513 were included after applying inclusion criteria (age >18 years, presentation within 12 hours of symptom onset, complete medical records) and exclusion criteria (symptom duration ≥12 hours, failure to receive PPCI, incomplete outcome data).

Not applicable (observational study).

The primary outcomes were in-hospital, 1-year and 3-year all-cause mortality. Secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACCE) at 1 and 3 years post-discharge.

Among 4513 STEMI patients, 2433 (54.0%) were high-risk (HR-STEMI) and 2080 (46.0%) low-risk (LR-STEMI). DTBT ≤60 min was achieved in 45.7% of HR-STEMI and 52.0% of LR-STEMI patients. For HR-STEMI patients, DTBT >60 min was associated with significantly higher risks of in-hospital mortality (OR=2.381, 95% CI 1.160 to 4.883, p=0.018), 1-year mortality (HR=1.715, 95% CI 1.194 to 2.464, p=0.003), 1-year MACCE (HR=1.212, 95% CI 1.001 to 1.467, p=0.049), 3-year mortality (HR=1.689, 95% CI 1.267 to 2.253, p<0.001), and 3-year MACCE (HR=1.230, 95% CI 1.042 to 1.453, p=0.014). Among LR-STEMI patients, no significant differences were observed between DTBT groups.

DTBT ≤60 min was significantly associated with better short- and long-term outcomes, particularly in patients with GRACE >140. Sensitivity analysis suggested that the benefit may also extend to patients with GRACE scores between 120 and 140.

Not applicable (observational study).

Autophagy is a fundamental cellular process essential for maintaining homeostasis, particularly in the context of aging and age-related diseases. Increasing evidence highlights biological sex as a critical modulator of autophagy, influencing its basal activity, regulatory pathways, and responsiveness to stress. Distinct autophagic profiles in males and females (across tissues, species and developmental stages) may underlie sex-specific vulnerabilities and divergent disease trajectories. These differences are evident in conditions such as neurodegeneration, cardiovascular disease, cancer, sarcopenia or chronic inflammation, all of which are commonly associated with aging. Indeed, aging is a major risk factor for the onset and progression of these pathologies. Importantly, sex-dependent variations in autophagy might also impact the efficacy and safety of therapeutic interventions, challenging the validity of uniform treatment strategies. Despite growing recognition of these disparities, significant knowledge gaps remain. This review summarizes current understanding of sex-related differences in autophagy, focusing on genetic and hormonal influences across the lifespan. The evidence supports the need for future research to systematically incorporate sex as a biological variable in experimental design and data analysis, utilize dynamic assessments of autophagy flux and investigate the interplay among genetic, hormonal, epigenetic, and post-translational regulatory mechanisms. Developing preclinical models that reflect human diversity-including genetic heterogeneity and relevant hormonal states-is imperative. Embracing the complexity of sex-dependent autophagy regulation is essential for translating mechanistic insights into effective, personalized interventions that improve health outcomes for both women and men.

Although enteric-coated aspirin is widely used instead of chewable formulations in patients with atherosclerotic cardiovascular diseases (ASCVD), its effects on cardiovascular and gastrointestinal outcomes remain uncertain. Separately, air pollution is a driver of cardiovascular risk, yet individual-level interventions have not been tested in outcomes trials.

The Coated Or Chewable Aspirin in Patients with Established AThErosclerotic Disease and a Hybrid Strategy to Mitigate the Adverse Effects of AIR Pollution (COATED-AIR) is a randomized trial with a 2x2 factorial design planned to address these knowledge gaps. Patients with ASCVD receiving low-dose aspirin are considered for inclusion. Major exclusion criteria consist of being within 72 hours of acute/unstable ASCVD or revascularization, triple antithrombotic therapy, active/recent bleeding, life expectancy <1 year, or other barriers or unwillingness for enrollment. Eligible consenting patients are randomized, in a double-blind fashion, to enteric coated vs chewable aspirin 81mg daily, and (via factorial randomization) to a hybrid strategy to mitigate the adverse effects of air pollution vs usual care. The hybrid strategy includes 1. an educational flashcard, 2. real-time air quality alerts via cellular text messages, and recommendations to 2a. limit outdoor activity or 2b. to use a KN-95 facemask when outdoors, and 2c. to increase citrus fruit intake on days with elevated pollution levels. The primary efficacy outcome for the aspirin randomization is a composite of fatal/nonfatal ischemic stroke, thrombotic/thromboembolic myocardial infarction, and acute limb ischemia. For the AIR randomization, other forms of cardiovascular death are additionally included in the primary composite outcome. The median planned duration of follow-up is 2 years. Enrollment was completed on 01/28/2026. Clinical follow-up and blinded event adjudications are ongoing.

COATED-AIR will determine whether aspirin coating affects its safety or effectiveness, and whether individual-level strategies can mitigate cardiovascular risks from air pollution in patients with ASCVD.

The Visceral Adiposity Index (VAI) is proposed as a surrogate marker of visceral adipose dysfunction. We evaluated its association with metabolic syndrome (MetS) and its components in a large Iranian population.

This cross-sectional study included 10,520 participants from the PERSIAN Guilan Cohort Study. VAI was calculated using sex-specific equations. MetS was defined according to Adult Treatment Panel III criteria. Multivariable logistic regression assessed associations between VAI and MetS, while ROC analysis evaluated the discriminatory ability of VAI for identifying MetS.

MetS was present in 40.7% of participants (24.5% of men, 54.7% of women). VAI was significantly higher in individuals with MetS than in those without [3.31 (IQR 2.40-4.69) vs. 1.64 (1.14-2.32); p < 0.01]. In the fully adjusted model, each one-unit increase in VAI was associated with higher odds of MetS in the overall population (OR = 2.41; 95% CI: 2.31-2.51), with a stronger association in women than in men (OR = 3.20 vs. 1.92; p for interaction < 0.001). VAI showed good discriminatory ability for identifying MetS in the total population (AUC = 0.84; 95% CI: 0.83-0.84), men (AUC = 0.83; 95% CI: 0.81-0.84), and women (AUC = 0.84; 95% CI: 0.83-0.85). Optimal VAI cut-off values were 2.42 in the overall population, 2.08 in men and 2.69 among women. VAI was most strongly associated with triglycerides and HDL-C, while significant associations were also observed with elevated fasting plasma glucose (FPG) and blood pressure (BP).

VAI was strongly associated with the presence of MetS in this large Iranian population and demonstrated good discriminatory ability. Although part of this association may reflect shared components between VAI and the MetS definition, its significant associations with elevated FPG and BP suggest a broader relationship with cardiometabolic risk. Prospective studies and external validation are warranted before clinical application.

Congenital heart disease (CHD) has a high burden of disease in terms of morbidity and mortality in children under 5 years. Maternal obesity (MO) could be a significant risk for developing CHD.

To analyze the associated risk of CHD in newborns according to MO.

Retrospective analytical and transversal design of newborns studied by echocardiography, with a 1:1 relationship between newborns with vs. without CHD. Maternal age, maternal body mass index (BMI), gestational age at birth, and birth weight were collected. Bivariate and multivariate analyses using binary logistic regression were conducted to calculate odds ratios (OR) and evaluate the association between maternal nutritional status and CHD in the newborn, adjusting for maternal age.

We analyzed 800 newborns from 785 pregnancies (15 twin pregnancies). The prenatal mother's BMI was 24.38 kg/m2, and 26.7% were obese. Bivariate analysis showed significant differences in sex (female 41% vs. 54%), gestational age (37 vs. 36 weeks), and MO (7% vs. 19.9%). Regression analysis showed that maternal BMI (beta 0.156, IC 95% Exp beta 1.118-1.222, p = 0.0001), obesity (OR 5.23, IC 95% 3.26-8.39, p = 0.0001), and female sex (OR 1.38, IC 95% 0.977-1.966, p = 0.067) have an associated risk of cardiopathy.

MO is a significant risk factor for CHD in Mexico. It is urgent to take public health measures to control MO, and all newborns of mothers affected by MO must have a screening for congenital heart disease.

Cardiac extracellular volume (ECV) is a quantitative imaging biomarker of myocardial interstitial expansion and diffuse fibrosis, with cardiac magnetic resonance regarded as the reference standard method for assessment. Interest in computed tomography (CT)-derived cardiac ECV is increasing owing to its wide availability and potential integration into routine cardiac CT examinations. This systematic review was conducted within the framework of the European Network for the Assessment of Imaging in Medicine (EuroAIM).

This PRISMA-compliant systematic review searched PubMed, Embase, and Scopus, with the last search performed in December 2025. Extracted data included study design, target pathology, CT technology, acquisition approach, timing of delayed imaging, hematocrit estimation, region-of-interest methodology, type of comparator, and reporting and definition of ECV cutoff values. Study quality was evaluated using the Newcastle-Ottawa scale.

Of 304 unique records, 113 studies were included, with a marked increase in publications over the last 3 years (30 studies in 2025). Studies covered a broad range of clinical settings, including aortic stenosis, amyloidosis, heart failure, cardiomyopathies, myocarditis, and cardio-oncology. Sixty-seven studies were retrospective, and forty-six were prospective. ECV was assessed using single-energy CT (n = 65), dual-energy CT (n = 34), and photon-counting CT (n = 14, 10 of them in 2025). Cutoff values were reported in only 38 studies. The Newcastle-Ottawa Scale score was 6.33 ± 1.42 (mean ± standard deviation).

Cardiac ECV is rapidly expanding, with photon-counting CT emerging as a promising platform. Nevertheless, substantial methodological heterogeneity and inconsistent cutoff reporting persist, highlighting the need for standardized protocols and harmonized reporting.

PROSPERO CRD420251147762.

Question What evidence is available in the literature about photon-counting CT-derived myocardial ECV quantification? Findings CT-derived myocardial ECV enables noninvasive assessment of diffuse myocardial fibrosis across multiple cardiovascular diseases. Relevance statement The rapidly expanding evidence and the emergence of photon-counting CT highlight its potential integration into routine cardiac CT imaging. Evidence spans multiple cardiac and systemic disease categories; heterogeneous methods limit cross-study comparability; standardized reporting is needed for clinical translation.

The therapeutic efficacy of ischemic stroke (IS) treatment is severely limited by insufficient accumulation of therapeutic agents within ischemic lesions and persistent secondary injury after ischemia-reperfusion. Herein, we report a cRGD-functionalized exosome-based nanoplatform that enhances ischemic lesion-associated accumulation and antioxidative neuroprotection for the treatment of IS. Neural stem cell-derived exosomes were functionalized with cyclic RGD peptides (cRGD) and subsequently loaded with Mn₃O₄ nanoparticles to construct a hybrid nanosystem (cRGD-Exo@Mn₃O₄). The engineered exosomes preserve intrinsic brain tropism, while cRGD modification promotes preferential accumulation in ischemic regions, potentially through interaction with α_vβ₃ integrin that is upregulated in ischemic lesions. The incorporated Mn₃O₄ nanoparticles confer robust reactive oxygen species (ROS) scavenging capability, thereby mitigating oxidative stress in ischemic microenvironments. In vitro and in vivo studies demonstrate that cRGD-Exo@Mn₃O₄ exhibits enhanced accumulation in ischemic regions compared with non-modified counterparts. The nanosystem effectively attenuates oxidative stress and neuroinflammation, leading to reduced infarct volume, alleviation of cerebral edema, and improved neurological function in MCAO/R mice. Mechanistically, transcriptomic analysis suggests that the therapeutic effects are associated with modulation of inflammation-and cell death-related pathways, including suppression of the RIPK1/RIPK3/MLKL signaling cascade. Collectively, this study presents a rationally designed exosome-based nanoplatform integrating ischemic lesion-associated accumulation with ROS-scavenging capability.

Pyroptosis is a caspase-dependent, inflammatory programmed form of cell death that is evolutionarily conserved among eukaryotic cells. Increasing evidence indicates that pyroptosis plays significant pathological roles in various human diseases and inflammatory conditions. Infertility, particularly female infertility, and ovarian dysfunction are closely associated with inflammation, with recent findings pinpointing a role for pyroptosis in the pathogenesis of these pathologies. Accordingly, this narrative review aims to provide an updated overview of recent discoveries elucidating the role of pyroptosis in ovarian infertility and related diseases, the underlying molecular mechanisms and signaling pathways involved, and emerging therapeutic compounds with the potential to inhibit pyroptosis and alleviate ovarian infertility and diseases. In addition, we highlight key research gaps and propose future directions that warrant further investigation.

Myocardial infarction causes persistent mitochondrial and metabolic dysfunction that drives adverse cardiac remodeling. Here we develop NAD⁺-genipin nanomedicine for metabolic balance (NGB), a physiologically adaptive nanomedicine with staged intracellular release. In a mouse myocardial infarction model, NGB preferentially accumulates in ischemic myocardium, rapidly replenishes nicotinamide adenine dinucleotide (NAD⁺) and subsequently provides mitochondria-associated sustained NAD⁺-genipin exposure. This phase-linked delivery limits early mitochondrial stress, apoptosis and inflammation and later restores coordination between oxidative phosphorylation, glycolysis and fatty-acid utilization. Mechanistically, NGB supports sirtuin-1-associated oxidative metabolism and suppresses sustained upregulation of the mitochondrial uncoupling protein 2 (UCP2). In hypoxic cardiomyocytes, UCP2 knockdown plus NAD⁺ supplementation partially reproduces the NGB metabolic phenotype, whereas UCP2 overexpression and sirtuin 1 inhibition reverse distinct components of NGB-mediated respiratory and glycolytic recovery. NGB thereby reduces fibrosis and ventricular remodeling and preserves cardiac function, supporting temporally coordinated metabolic intervention after myocardial infarction.

Moyamoya (MM) is a progressive arteriopathy of the internal carotid artery and its branches that can lead to stroke and can be treated with surgical revascularization. The enzyme Nit2/ω-amidase (NIT2) is involved in glutaminase II and methionine salvage pathways. Recent studies have shown correlations between these metabolic pathways and MM arteriopathy, specifically increases in L-methionine, NO metabolites, and homocysteine. Here, we present data demonstrating that elevated levels of NIT2 correlate with the presence of MM, suggesting that it may have potential utility as a non-invasive biomarker for this condition.

Urine (n = 58) and blood plasma (n = 29) samples were collected from MM patients (aged 0-19) who were undergoing surgical revascularization and compared to samples collected from age- and sex-matched healthy controls (n = 23). The samples were then analyzed using Olink Explore 3072 proteomic proximity extension assays (PEA) to determine expression levels across ~ 3000 validated protein assays, revealing NIT2 as significantly elevated in MM patients compared to controls. We then conducted a secondary analysis of NIT2 using enzyme-linked immunosorbent assay (ELISA) for independent validation. Results were further analyzed for salient radiographic and clinical features, including Suzuki grade, bilateral vs. unilateral disease, radiographic stroke, and transient ischemic attack (TIA).

ANOVA analysis of the MM urine and plasma samples showed a statistically significant increase in Nit2/ω-amidase (NIT2) compared to the control samples, with MM patients exhibiting 1.6-2.3-fold increases in plasma expression (p = 0.04) and 4-11-fold increases in urinary expression (p ≤ 0.001). Higher levels of NIT2 in the urine were associated with moyamoya, bilateral disease, higher grade, stroke, and TIA.

NIT2 levels are significantly elevated in MM patients compared to matched controls, and higher levels correlate with measures of more severe disease. These novel data, coupled with the association of this molecule with metabolic pathways impacted by MM, support further investigation into NIT2 as a putative biomarker for MM.