Inflammasomes are pivotal for the initiation and control of host inflammatory responses. This is particularly important in the respiratory system due to its direct exposure to noxious environmental and infectious stimuli, which can cause local inflammation, tissue damage and impaired function. Inflammasomes are activated by a variety of processes that result in a loss of cellular homeostasis, leading to the oligomerisation of specific innate immune sensors. Inflammasome complex formation then results in a form of programmed cell death known as pyroptosis and release of cleaved active pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, and the subsequent inflammatory cascade. While acute inflammasome activation can be protective in controlling infection, chronic inflammasome activation is detrimental and can lead to irreversible changes in the lung micro-environment such as chronic inflammation, emphysema, lung fibrosis and impaired gas exchange and lung function. In this review, we describe the role of inflammasomes in the pathogenesis of acute and chronic respiratory diseases, highlight currently available preclinical and clinically available therapies that regulate or inhibit inflammasome activation, and outline the use of multi-omics to identify novel inflammasome biomarkers and therapeutics.

A previously healthy woman in her early 30s developed rash, fever and arthralgia 3 weeks after SARS-CoV-2 infection, rapidly progressing to multiorgan failure. Laboratory studies revealed severe thrombocytopenia (23×10⁹/L), microangiopathic haemolytic anaemia, acute kidney injury and ferritin >100 000 ng/mL. Kidney biopsy demonstrated thrombotic microangiopathy with negative antinuclear antibody, supporting atypical haemolytic uraemic syndrome (aHUS). Concurrently, low haptoglobin, elevated lactate dehydrogenase (2500 U/L), interleukin-2 receptor (18 644), triglycerides (425 mg/dL) and splenomegaly supported haemophagocytic lymphohistiocytosis (HLH). Despite plasmapheresis, corticosteroids, etoposide, eculizumab and continuous renal replacement therapy, she died 7 weeks after SARS-CoV-2 infection. Autopsy confirmed aHUS with extensive thrombotic microangiopathy and HLH with bone marrow haemophagocytosis. This case underscores the importance of recognising concurrent aHUS and HLH after COVID-19, as complement-mediated injury and hyperinflammation may produce catastrophic outcomes.

Multiple prospective cohort studies, including the multi-ethnic study of atherosclerosis (MESA), have documented elevations in cardiovascular risk factors after the Great Recession (GR) of 2008, despite other studies that report mortality declines after the GR. It is possible that the deleterious effects of the GR on cardiovascular risk profiles are short-lived and reversed. We examine whether risk factor elevations seen in MESA in the 2010-2011 wave persist into the 2016-2018 wave of data collection.

Individual fixed effects (IFE) analysis of prospective cohort data from MESA, with rate of change in the risk factor (from wave 2 to later waves) as the dependent variable, effectively controlling for individual-specific linear trends in ageing and all time-invariant characteristics. Models included controls for time-varying characteristics.

Communities centred around Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles, California; New York City, New York; and St. Paul, Minnesota.

All MESA participants who participated in at least two pre-GR waves and both post-GR waves; n=3101 (47% men, 25% African American, 21% Hispanic, 13% Asian).

Primary: Systolic blood pressure (SBP), pulse pressure (PP), fasting blood glucose, serum C-reactive protein (CRP). Secondary: Serum low density lipoprotein cholesterol (LDL-C) and Body Mass Index (BMI) RESULTS: Mean SBP and PP in 2016-2018 were greater by 8.6 (95% CI 5.9 to 11.4) and 8.0 (95% CI 6.0 to 9.9) mm Hg, respectively, than predicted by individual-specific pre-GR linear ageing trends, and fasting blood glucose was 6.3% higher (95% CI 4.6 to 8.1). In comparison, corresponding increases in 2010-2011 were 2.5 and 3.0 mm Hg and 3.3%. CRP increased by 29.7% (95% CI 21.8 to 38.2) in 2010-2011 and 45.1% (95% CI 28.3 to 64.2) in 2016-2018. Mean BMI did not change in 2010-2011 but decreased by 0.5 kg/m² (95% CI -0.7 to -0.2) in 2016-2018. LDL-C decreased by 4.4 (95% CI -6.5 to -2.2) and 5.2 (95% CI -9.5 to -0.9) mg/dL in the two post-GR waves.

Post-GR increases in blood pressure, blood glucose and CRP in the USA not only persisted for 8-10 years after the GR but also grew in magnitude. In contrast, mean BMI and mean LDL-C reduced post-GR. Further studies are needed to uncover mechanisms (behavioural or otherwise) underlying the BMI and LDL-C reductions seen here, and the mortality consequences of these risk factor changes.

The growing prevalence of chronic diseases and population ageing have increased the need for end-of-life care, particularly in home settings. Death literacy, encompassing knowledge, skills, attitudes and emotional preparedness related to death and dying, is recognised as an important component of quality end-of-life care. However, little is known about caregivers' perceptions of death literacy in the Iranian context.

To explore the perceptions of professional and family caregivers regarding death literacy in home-based end-of-life care.

This qualitative study used conventional content analysis based on Graneheim and Lundman's approach. Data were collected through semistructured interviews with 12 professional and family caregivers involved in end-of-life care for patients with advanced chronic diseases in Tehran, Iran. Participants were recruited using purposive and snowball sampling. Interviews were transcribed verbatim and analysed until data saturation was reached.

Four core dimensions of death literacy emerged: (1) situational knowledge of dying, (2) experiential learning trajectory, (3) emotional reconciliation with death and (4) dignity-centred ethical practice. Two additional contextual domains (5) caregiver burden and relational challenges and (6) structural and organisational barriers described the relational and structural conditions in which death literacy was developed and enacted. Death literacy was described as a dynamic and culturally embedded process shaped by caregiving experiences, emotional engagement, informal learning, spirituality and interactions with families and the healthcare system.

Death literacy develops through lived experience, emotional reflection and cultural influences rather than formal education alone, while relational and structural conditions shape how these capacities are developed and enacted in practice. Educational, psychological and organisational support may strengthen caregiver preparedness and improve end-of-life care.

The implantation of cardiac implantable electronic devices (CIEDs) has become an important treatment for various types of arrhythmias and severe heart failure, effectively improving patient prognosis and increasing survival rates. However, patients after CIED implantation need to go through a process of coexisting with and adapting to the internal electronic device. This may result in limitations in daily activities, discomfort and lifestyle changes, which can easily lead to negative emotions and psychosocial maladjustment in the patients, seriously affecting their physical and mental rehabilitation and prognosis. This study aims to explore the trajectory of psychosocial adaptation and its influencing factors among patients after CIED implantation and to gain an in-depth understanding of their process of physical and psychological adjustment. Drawing on the research findings and existing literature, this study will develop an intervention programme to improve psychosocial adaptation among patients after CIED implantation, thereby providing a theoretical and practical basis for future clinical interventions in this population.

This study focuses on patients who have undergone CIED implantation. A mixed-methods approach will be adopted, combining a cross-sectional survey, a prospective longitudinal quantitative design and a qualitative design. (1) Quantitative study: The Basic Information Questionnaire, Chinese version of Self-report Psychosocial Adjustment to Illness Scale, Chinese version of Medical Coping Modes Questionnaire, Chinese version of Acceptance of Illness Scale, Chinese version of Multidimensional Scale of Perceived Social Support, Self-efficacy for Managing Chronic Disease and Health Literacy Management Scale will be administered to patients after CIED implantation to explore the latent categories, associated factors and longitudinal trajectories of psychosocial adaptation. Statistical analysis will be conducted using Statistical analysis was performed using IBM SPSS Statistics version 26 (SPSS 26) and Mplus software. (2) Qualitative study: Based on descriptive phenomenology, semi-structured interviews will be conducted with patients after CIED implantation to gain an in-depth understanding of their life experiences of psychosocial adaptation, as well as their process of physical and psychological adjustment. The data will be analysed using the Colaizzi 7-step method of phenomenological analysis, supported by NVivo software for data organisation and coding. (3) Development of the intervention programme: Based on the literature review and theoretical framework, and integrating findings from both the quantitative and qualitative phases, an intervention programme for improving the psychosocial adaptation among patients after CIED implantation will be initially developed. The Delphi method will be used to evaluate and revise the initially developed intervention programme. A pilot test will subsequently be conducted to further refine the programme.

This research plan has been approved by the Ethics Committee of the First People's Hospital of Foshan (Approval Number: LSY-2025-019). Data collection is authorised by the Ethics Committee of the First People's Hospital of Foshan. The results of this study will be published in relevant peer-reviewed journals.

ChiCTR2600124496.

Alternative splicing is a fundamental post-transcriptional mechanism that contributes to cardiovascular development, homeostasis, and disease. Serine/arginine-rich splicing factors (SRSFs), a conserved family of 12 RNA-binding proteins, regulate splice-site selection and other RNA-processing events through their RNA-recognition motifs and arginine/serine-rich domains. Growing evidence implicates SRSF dysregulation in congenital heart disease, cardiac hypertrophy and heart failure, ischemic injury, vascular remodeling, inflammatory myocardial injury, and cardiovascular aging. In this review, we summarize the structural characteristics, cardiovascular expression patterns, and physiological functions of SRSFs, and discuss their context-dependent roles across cardiovascular diseases. We further examine regulatory mechanisms involving phosphorylation, target-specific RNA processing, interactions with other cardiac splicing regulators, and non-coding RNAs. Finally, we evaluate emerging small-molecule and gene- or RNA-based strategies targeting SRSFs and highlight major barriers to translation, including target specificity, delivery, causal validation, and safety. These advances provide a framework for defining disease-relevant SRSF networks and prioritizing mechanistically supported therapeutic targets in cardiovascular disease.

Acute myocarditis (AM) in children and adolescents remains a diagnostic and therapeutic challenge because of its heterogeneous presentation, overlap with dilated cardiomyopathy, and potential for fulminant deterioration, with approximately 5.9% risk of early mortality. We performed a narrative review integrating contemporary guidelines, consensus documents, and weighted analyses from systematically selected large pediatric cohorts to summarize current evidence on epidemiology, diagnosis, risk stratification, and treatment. Pediatric AM shows a male predominance and a bimodal age distribution. Early recognition is often difficult because initial manifestations may be non-specific and the differential diagnosis varies across age groups. Younger children more often present with dilated phenotypes and prominent gastrointestinal symptoms, frequently reflecting low cardiac output and systemic congestion, whereas adolescents may present with an uncomplicated phenotype characterized by chest pain and regional wall motion abnormalities. Severe disease remains a relevant burden, with fulminant myocarditis accounting for approximately one quarter of cases and carrying markedly higher mortality. Initial evaluation should therefore focus on early risk stratification, integrating clinical severity, biomarkers, electrocardiogram, echocardiography, and etiological testing. This approach may help identify high-risk viral phenotypes associated with enteroviruses or parvovirus B19, while also recognizing systemic inflammatory syndromes such as multisystem inflammatory syndrome in children, which may mimic AM but usually responds to timely immunomodulatory treatment. We propose a practical risk-based strategy that classifies patients into low-, intermediate-, and high-risk groups to guide monitoring, referral, cardiac magnetic resonance, endomyocardial biopsy, and therapy. High-risk patients require early referral to tertiary centers with pediatric intensive care, cardiac surgery, and temporary mechanical circulatory support availability. Treatment should be individualized according to risk, ranging from supportive care to mechanical circulatory support, transplant evaluation, and selected immunomodulation. Prospective registries and randomized trials are needed to validate risk-based pathways and define evidence-based therapies.

The relationship between systolic blood pressure variability (SBP-V) and clinical outcomes in patients with atrial fibrillation (AF) remains unclear.

Using the Korean National Health Insurance database, we included patients with prevalent AF who received health checkups in 2013-2014, with at least three checkups in total (n = 235,091). SBP-V was defined as the standard deviation of SBP. The outcomes, including stroke, major bleeding, and all-cause death, were assessed during follow-up.

During the follow-up period (median, 4.9 years; interquartile range, 4.3-5.3), 5,339 strokes (0.5/100 person-years [PYs]), 3,432 major bleeding incidents (0.3/100 PYs), and 16,755 all-cause mortality (1.5/100 PYs) occurred. Compared to patients with SBP 120 to < 130 mmHg at the index health checkup, those with SBP ≥ 130 mmHg had a significantly higher risks of stroke and major bleeding. All-cause mortality was elevated at both high (≥ 150 mmHg) and low (< 120 mmHg) SBP levels. Compared to the lowest SBP-V group, the highest SBP-V group had significantly higher risks of stroke (adjusted hazard ratio [aHR], 1.211; 95% confidence interval [CI], 1.125-1.304), major bleeding (aHR, 1.125; 95% CI, 1.025-1.234), and all-cause death (aHR, 1.189; 95% CI, 1.141-1.239). No significant interactions were observed between oral anticoagulation use and SBP-V for any of the clinical outcomes.

SBP and SBP-V were independently associated with higher risks of stroke, major bleeding, and all-cause death in patients with AF. These findings highlight the importance of not only achieving target blood pressure levels but also minimizing SBP variability through optimal hypertension management to improve outcomes in this population.

Disrupted axonal transport and astrocyte dysfunction are implicated in amyotrophic lateral sclerosis (ALS). Here we show these processes are linked-human-induced pluripotent stem-cell-derived astrocytes carrying the C9ORF72 mutation disrupt mitochondrial axonal transport and mitochondrial function in cocultured motor neurons (MNs). Conversely, isogenic gene-corrected astrocytes or boosting astrocytic mitochondrial bioenergetics rescue axonal mitochondrial transport deficits in C9ORF72 MNs. Our results delineate a non-cell-autonomous role for astrocytes in regulating mitochondrial transport along axons in ALS models.

High fructose consumption, particularly from sugar-sweetened beverages, contributes to cardiometabolic disease. Here we study the metabolic effects of 6-week pharmacological inhibition with PF-06835919 of ketohexokinase, the enzyme that catalyses the first committed step of fructose metabolism, in a randomized placebo-controlled crossover trial in 15 participants with metabolic dysfunction-associated steatotic liver disease. The primary outcome was hepatic insulin sensitivity, measured by insulin-stimulated suppression of endogenous glucose production. Secondary outcomes included fat distribution, peripheral and adipose tissue insulin sensitivity, and fat oxidation. While PF-06835919 treatment did not affect body weight, it improved hepatic insulin sensitivity and reduced intrahepatic lipid and saturated fatty acid content. Besides these beneficial hepatic effects, PF-06835919 also improved insulin-stimulated glucose disposal, adipose tissue insulin sensitivity, adipose tissue distribution and nocturnal fat oxidation. These changes are accompanied by changes in very low-density lipoprotein particle size distribution and circulating hepatokines. These results show that inhibition of fructose metabolism has beneficial metabolic effects that extend beyond the organs that metabolize fructose. ClinicalTrials.gov identifier: NCT05463575 .