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Myocardial ischemia–reperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow is restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, is pivotal in myocardial I/R injury. Preventing cell death during the process of I/R is vital for improving ischemic cardiomyopathy. These multiple forms of cell death can occur simultaneously, interact with each other, and contribute to the complexity of myocardial I/R injury. In this review, we aim to provide a comprehensive summary of the key molecular mechanisms and regulatory patterns involved in these five types of cell death in myocardial I/R injury. We will also discuss the crosstalk and intricate interactions among these mechanisms, highlighting the interplay between different types of cell death. Furthermore, we will explore specific molecules or targets that participate in different cell death pathways and elucidate their mechanisms of action. It is important to note that manipulating the molecules or targets involved in distinct cell death processes may have a significant impact on reducing myocardial I/R injury. By enhancing researchers’ understanding of the mechanisms and interactions among different types of cell death in myocardial I/R injury, this review aims to pave the way for the development of novel interventions for cardio-protection in patients affected by myocardial I/R injury.

The coronavirus disease 19 (COVID-19) pandemic poses a serious global threat to human health and the economy. Based on accumulating evidence, its continuous progression involves not only pulmonary injury but also damage to the cardiovascular system due to intertwined pathophysiological risks. As a point of convergence in the pathophysiologic process between COVID-19 and heart failure (HF), cytokine storm induces the progression of COVID-19 in patients presenting pre-existing or new onset myocardial damage and even HF. Cytokine storm, as a trigger of the progression of HF in patients with COVID-19, has become a novel focus to explore therapies for target populations. In this review, we briefly introduce the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and illuminate the mechanism and links among COVID-19, cytokine storm, and HF. Furthermore, we discuss drugs and therapeutic targets for patients with COVID-19 and HF.

IntroductionAs populations age and climate variability intensifies, seasonal migration has emerged as a strategy among older adults to reduce exposure to climatic extremes and optimise living conditions. In China, millions of older adults migrate annually between cold northern and tropical southern regions, providing a natural setting to examine the health effects of seasonal migration. The Frigid-Tropical Migratory Population Health (ftMPH) cohort was established to assess the short- and long-term health effects of this migration and the underlying biological, behavioural and social pathways.Methods and analysisThe ftMPH cohort is a prospective, dynamic cohort jointly conducted in Heilongjiang (a cold region) and Hainan (a tropical region) in China, with a planned sample size of approximately 26 000 participants. Adults aged ≥60 years are recruited and classified into four subcohorts: cold-origin seasonal migrants, cold-region residents, tropical-origin seasonal migrants and tropical-region residents. Baseline assessments include questionnaires, clinical examinations, biospecimen collection and environmental exposure measurements. Each migration cycle is assessed at predefined time points spanning the departure and return phases. Migration exposure will be updated longitudinally at each follow-up interval.The primary outcome is the incidence of major cardiovascular disease events, including non-fatal myocardial infarction, coronary revascularisation, stroke and cardiovascular mortality. Secondary outcomes include non-cardiovascular mortality, chronic disease events, healthcare utilisation and ageing-related measures. Time-to-event analyses will be performed using Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) will be used to control for baseline confounding, with stabilised weights and covariate balance assessed using standardised mean differences. Longitudinal changes in repeated measures will be analysed using mixed-effects models.Ethics and disseminationEthical approval was obtained from the Ethics Review Committee of Harbin Medical University (approval No HMUIRB2024029PRE) and the Ethics Review Committee of Hainan Medical University (approval No HYMLL-2025-102). Findings will be disseminated through peer-reviewed publications, conference presentations and policy or technical reports.Trial registration numberThe ftMPH cohort is registered with the Chinese Clinical Trial Registry (ChiCTR2500102337; registered on 13 May 2025).

: Atherosclerosis plaque rupture (PR) is the pathological basis and chief culprit of most acute cardiovascular events and death. Given the complex and important role of macrophage apoptosis and autophagy in affecting plaque stability, an important unanswered question include is whether, and how, immunity-related GTPase family M protein (IRGM) and its mouse orthologue IRGM1 affect macrophage survival and atherosclerotic plaque stability. To investigate whether serum IRGM of ST-segment elevation myocardial infarction (STEMI) patients is related to plaque morphology, we divided 85 STEMI patients into those with and without plaque rupture (PR and non-PR, respectively) based on OCT image analysis, and quantified the patients' serum IRGM levels. Next, we engineered deficient mice ( ) and chimera mice with deficiency in the bone marrow on an background, which were then fed a high-fat diet for 16 weeks. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. In addition, immunofluorescence, immunohistochemical staining and western blot were used to detect the apoptosis of macrophages in the plaques. , THP-1 and RAW264.7 cells were stimulated with ox-LDL to mimic the environment, and IRGM/IRGM1 expression were modified by specific siRNA (knockdown) or plasmid (knocked-in). The effect of on autophagy and apoptosis of macrophages induced by ox-LDL was then evaluated. In addition, we introduced inhibitors of the JNK/p38/ERK signaling pathway to verify the specific mechanism by which regulates RAW264.7 cell apoptosis. The serum IRGM levels of PR patients is significantly higher than that of non-PR patients and healthy volunteers, which may be an effective predictor of PR. On a high-fat diet, -deficient mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis is inhibited in the plaques of -deficient mice. , deficiency rapidly inhibits ox-LDL-induced macrophage autophagy while inhibiting ox-LDL-induced macrophage apoptosis in late stages. Additionally, deficiency suppresses reactive oxygen species (ROS) production in macrophages, while removal of ROS effectively inhibits macrophage apoptosis induced by IRGM overexpression. We further show that can affect macrophage apoptosis by regulating JNK/p38/ERK phosphorylation in the MAPK signaling pathway. Serum IRGM may be related to the process of PR in STEMI patients, and deficiency increases plaque stability. In addition, deficiency suppresses macrophage apoptosis by inhibiting ROS generation and MAPK signaling transduction. Cumulatively, these results suggest that targeting may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.

Background Preventing cardiovascular disease (CVD) in adults with hypertension is essential, but it remains uncertain whether optimizing modifiable factors can eliminate the excess CVD risk associated with new-onset hypertension. Methods In this prospective cohort study, 29,597 adults with new-onset hypertension and no prior CVD (from 2006–2016 surveys) were each matched by age and sex to a normotensive control. Eight modifiable factors were assessed using the American Heart Association’s Life’s Essential 8 algorithm. We followed participants for incident CVD until December 2020, estimating 10-year and lifetime (age 25–95) CVD risks using the Fine-Gray competing risks model. Results Over a median follow-up of 9.81 years, adults with new-onset hypertension had higher 10-year (8.97% vs. 6.31%) and lifetime CVD risks (45.55% vs. 34.98%) compared to normotensive controls. After adjusting for age, sex, and other unmodifiable factors, each additional favorable factor was associated with a stepwise reduction in CVD risk ( P -trend < 0.05). Hypertensive participants with four or more favorable factors had a 17% lower 10-year CVD risk (HR 0.83; 95% CI 0.72–0.97) and a similar lifetime CVD risk (HR 0.90; 95% CI 0.78–1.05) compared to normotensive controls. Notably, the protective effect was weaker among those with early-onset (before age 45) hypertension than those with later-onset (age ≥ 60) hypertension ( P -interaction < 0.05). Conclusions In adults with new-onset hypertension, maintaining four or more modifiable factors at favorable levels was associated with a CVD risk comparable to that of normotensive individuals. However, young hypertensive adults may require more aggressive interventions to mitigate CVD risk.

Background Although numerous reports suggest sex-related differences in atherosclerosis, limited data describing gender-associated differences in plaque morphology and composition are currently available. The aim of the present study was to compare coronary nonculprit plaque characteristics in women and men with coronary artery disease (CAD) by optical coherence tomography (OCT). Methods This was a retrospective study. A total of 187 nonculprit plaques were identified in 103 patients with CAD who underwent OCT imaging of all 3 coronary arteries. These patients included 77 (74.8%) men and 26 (25.2%) women. Results Female patients were significantly older than males (mean age, 70.8 ± 7.3 vs 60.8 ± 9.8 years; P  < 0.001) and less likely to be current smokers ( P  = 0.007). OCT analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and the incidence of thin-cap fibroatheroma (TCFA). Nonculprit plaques in men exhibited greater lipid-core length and LI compared with those of women (9.4 ± 4.5 vs. 7.3 ± 4.3 mm, P  = 0.024; 1615.1 ± 893.8 vs. 1237.8 ± 859.8, P  = 0.035, respectively). In the univariate linear regression model, sex and current smoker were all associated with a larger LI, whereas only use of statin was independent risk factor for a larger LI in multivariate analysis. Conclusions Coronary nonculprit plaques in male patients with CAD contain larger lipid cores than those of female patients.

The flexible tower structure of offshore floating wind turbines is a crucial load-bearing component connecting the floating platform and wind turbine unit, and its structural dynamic response exhibits significant nonlinear characteristics and multiscale coupling effects under complex marine environmental loads. To accurately reveal the dynamic behavior of floating wind turbine towers, this study focuses on the flexible tower of a semi-submersible floating wind turbine. A nonlinear dynamic theoretical model based on Cosserat rod theory is established and discretized using the finite element method. The dynamic response characteristics of the tower under the concentrated loads from turbine blades are analyzed in depth. Furthermore, by comparing results from the theoretical model with independently developed numerical simulation programs, the accuracy and reliability of the theoretical model are validated. Additionally, the influence of element mesh density on the simulation accuracy and reliability of tower vibration modes, as well as the sensitivity of the dynamic response of the upper structure under various wind speeds, are systematically investigated. The findings of this study can provide reliable theoretical foundations and technical support for the optimal design and safe operation of offshore floating wind turbine flexible towers.

By shaping T cell immunity, tolerogenic dendritic cells (tDCs) play critical roles in the induction of immune tolerance after transplantation. However, the role of long noncoding RNAs (lncRNAs) in the function and immune tolerance of dendritic cells (DCs) is largely unknown. Here, we found that the lncRNA MALAT1 is upregulated in the infiltrating cells of tolerized mice with cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch in DCs toward a tolerant phenotype. Mechanistically, ectopic MALAT1 promoted dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression by functioning as an miR155 sponge, which is essential for the tolerogenic maintenance of DCs and the DC-SIGN-positive subset with more potent tolerogenic ability. The adoptive transfer of MALAT1-overexpressing DCs promoted cardiac allograft survival and protected from the development of experimental autoimmune myocarditis, accompanied with increasing antigen-specific regulatory T cells. Therefore, overexpressed MALAT1 induces tDCs and immune tolerance in heart transplantation and autoimmune disease by the miRNA-155/DC-SIGH/IL10 axis. This study highlights that the lncRNA MALAT1 is a novel tolerance regulator in immunity that has important implications in settings in which tDCs are preferred.

Abdominal aortic aneurysm (AAA) and the attendant catastrophic event of rupture remain a leading cause of death. Germline mutation of RRAS2 cause Noonan Syndrome, yet little is known about its function in AAA pathogenesis. Integrated analysis of RNA-seq data revealed RRAS2 a potential regulator of AAA. Its mRNA and protein levels reduced in abdominal aorta of AAA patients and AAA mice. Mice with SMCs-specific knockout of Rras2 were more vulnerable to Ang II and porcine pancreatic elastase-induced AAA, while overexpression of Rras2 in SMCs inhibited AAA progression. Maternally expressed gene 3 (MEG3) prevented RRAS2 mRNA degradation through binding with ELAV-like protein 1 (ELAVL1/HuR). Mechanistically, loss of R-Ras2 reduces phosphorylation, nuclear translocation, and transcriptional activity of general transcription factor 2I (GTF2-I/TFII-I) to reduce contractile-related genes expression in a MET tyrosine kinase-dependent manner. Here, we show an essential role of R-Ras2 in preserving VSMCs homeostasis and provide potential therapeutic targets for AAA. This work reveals critical role of R-Ras2 in abdominal aortic aneurysm (AAA) progression. R-Ras2 maintains VSMCs function via c-MET-TFII-I axis, with MEG3 stabilizing its mRNA stability. Findings identify R-Ras2 a potential AAA therapeutic target.

Percutaneous coronary intervention, which is safe, effective, and timely, has become an important treatment for coronary artery diseases and has been widely used in clinical practice. However, there are still some problems that urgently need to be solved. Permanent vessel caging through metallic implants not only prevents the process of positive vessel remodeling and the restoration of vascular physiology but also makes the future revascularization of target vessels more difficult. Bioresorbable scaffolds (BRSs) have been developed as a potential solution to avoid the above adverse reactions caused by permanent metallic devices. BRSs provide temporary support to the vessel wall in the short term and then gradually degrade over time to restore the natural state of coronary arteries. Nonetheless, long-term follow-up of large-scale trials has drawn considerable attention to the safety of BRSs, and the significantly increased risk of late scaffold thrombosis (ScT) limits its clinical application. In this review, we summarize the current status and clinical experiences of BRSs to understand the application prospects and limitations of these devices. In addition, we focus on ScT after implantation, as it is currently the primary drawback of BRS. We also analyze the causes of ScT and discuss improvements required to overcome this serious drawback and to move the field forward.