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CD4 ⁺ Tregs Regulate Heart Growth and Regeneration Through MRG15/TIP60-Mediated Epigenomic Remodeling in Proliferating Cardiomyocytes

BACKGROUND: Cardiovascular disease remains a leading cause of mortality globally, with the adult mammalian heart exhibiting limited regenerative capacity. The chromatin regulatory network plays a crucial role in the dynamic changes in gene expression that orchestrate the regenerative response in the neonatal heart. This study aims to identify key chromatin regulators in neonatal cardiomyocytes and to elucidate their roles in heart regeneration. METHODS: We generated genetic knockout mouse models by crossing Mrg15 fl/fl and Tip60 fl/fl mice with various Cre-driver lines such as Isl1-Cre and Myh6-MerCreMer to evaluate the function of MRG15 (MORF-related gene 15)/TIP60 in cardiac progenitor cells and cardiomyocytes during heart development and regeneration. The epigenetic regulation of cardiomyocyte proliferation by MRG15/TIP60 was investigated through a variety of methods, including histological, cellular, genomic, transcriptomic, computational, and pharmacological approaches. In addition, we assessed the regulation of transient MRG15 induction in the regenerating neonatal heart by CD4 + regulatory T cells through both adoptive transfer and monoclonal antibody–based depletion in mice. RESULTS: MRG15, but not its cofactor TIP60, was transiently expressed in neonatal cardiomyocytes, with its expression downregulated as the regenerative potential of the heart declined. We generated knockout mice targeting Mrg15 in cardiac progenitor cells and cardiomyocytes, revealing that MRG15 is critical for neonatal heart regeneration and plays a key role in regulating cardiomyocyte proliferation. Mechanistically, MRG15 forms an activator complex with TIP60, p300, and RNA polymerase II, facilitating histone acetylation at the Ccnd1 enhancer region. Furthermore, regulatory T cells were shown to induce MRG15 expression, promoting cardiomyocyte proliferation through paracrine signaling. Notably, adeno-associated virus 9–mediated overexpression of Mrg15 rescued the impaired heart regeneration after Treg depletion in vivo. Furthermore, recapitulating MRG15 expression into the juvenile heart promoted regeneration by enhancing cardiomyocyte proliferation. CONCLUSIONS: This study elucidates the critical role of regulatory T cells in regulating the transient expression of MRG15 in regenerating cardiomyocytes and its subsequent control of cardiomyocyte proliferation and heart regeneration through TIP60-mediated chromatin modification. Our findings highlight the important interplay between the cardiac and the immune system during neonatal development, particularly through the MRG15/TIP60 axis regulated by regulatory T cells. This cross-talk suggests promising therapeutic strategies for enhancing cardiac repair by targeting these pathways.

Identification of overoxidizing and non-overoxidizing NAD-dependent methanol dehydrogenases and implications for synthetic methylotrophy

Nasopharyngeal airway oxygenation enhances safe apnea time in patients at moderately high altitude: a randomized clinical trial

Improving on-field decision making using video-based training – A pilot study with young volleyball players

Decision making is a crucial skill in several sports, which researchers and practitioners have for a long time sought to improve. Recent studies have focused on the potential of video-based training, but most examined adult athletes and did not typically measure transfer to on-field performance. Therefore, we investigated the effect of a 4-week video-based training on youth volleyball players’ on-field decision making. Twenty female volleyball players between 13 and 15 years old were initially assigned to either an experimental or control group, of whom 16 (eight per group) completed the entire study. Decision making skill was assessed on a video-based task, as well as an on-field task. The results of our pilot study demonstrated that only the experimental group significantly improved their decision making skills on both the video-based assessment and on-field test (motor decision) between baseline and retention. This pilot study indicates that video-based training can be an effective way to improve young players’ on-field decision making skills, although improvements in motor execution may require intermittent physical practice.

Letter by Sun and Ren Regarding Article, “METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis”

Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex

Mysterious illnesses have supernatural and ritualistic cures: Evidence from 3,655 century-old Irish folk cures

Why and when do people draw upon religious and supernatural solutions to problems? Cognitive scientists and anthropologists have proposed a range of answers, stressing religion and ritual’s capacity to alleviate anxiety, create a sense of order, or explain otherwise inexplicable events. Here, we leverage a unique dataset of 3,655 folk cures for 35 diseases, collected in 1937/8 from a mostly rural Irish sample born roughly between 1850 and 1925. Since the diseases vary in theory-relevant ways and the cures vary in the degree to which they include religious and supernatural elements, this dataset facilitates a unique test of these predictions in a premodern western population. In preregistered tests, we find that diseases judged by two doctors to have causes and mechanisms that would be unclear to the patients were more likely to have supernatural/religious treatments. Contra common predictions, severe and disabling diseases did not have more supernatural/religious cures and anxiety-provoking diseases did not have more ritualistic cures.

Thermal behavior in compact-type cryogenic needle valve with integrated heat sinks

Abstract A cryogenic needle valve is used to precisely control the flow rate of working fluids such as liquid hydrogen and liquefied natural gas, making it essential to design the valve with consideration of the cryogenic environment. To prevent freezing of the packing materials, which directly affects leakage, extended bonnet-type valves are commonly used. In these designs, the bonnet length is increased to position the packing farther from the flow path. However, due to spatial constraints, extended bonnet structures are often unsuitable for installation in confined spaces. To address this limitation, a compact-type valve was developed by significantly shortening the bonnet length and incorporating a heat sink capable of providing the required heat transfer performance within the reduced length. In this study, a cryogenic environment test using liquid nitrogen, along with heat transfer analysis, was conducted on the compact-type cryogenic needle valve to evaluate the thermal behavior of its components. A parametric study and size optimization were performed by treating the heat sink’s outer diameter and thickness as shape design variables, with the goal of minimizing its size while maintaining the necessary heat transfer performance in the shortened bonnet. As a result of the optimization, the heat sink volume was reduced by approximately 54% compared to the initial design. A cryogenic leakage test was subsequently conducted on a prototype equipped with the optimized heat sink, in accordance with BS6364, confirming that no leakage occurred.

Correction: Identifying key physiological and clinical factors for traumatic brain injury patient management using network analysis and machine learning

Pragmatic Approaches to the Evaluation and Monitoring of Artificial Intelligence in Health Care: A Science Advisory From the American Heart Association

The rapid development and integration of artificial intelligence (AI), including predictive, generative, and emerging agentic tools, into cardiovascular and stroke care is outpacing traditional evaluation frameworks and the generation of robust clinical evidence. This science advisory addresses the urgent need for pragmatic, risk-proportionate approaches to the evaluation and monitoring of health care AI. AI implementation practices often rely on real-world or anecdotal evidence, with considerable variability in local validation, bias assessment, and postdeployment monitoring. Several evaluation frameworks exist, but they can be difficult to operationalize, especially outside of well-resourced health systems. We propose and discuss evaluation across 3 phases: predeployment, implementation, and postdeployment. We also provide 4 pragmatic guiding principles for health systems that are beginning to set up AI governance processes, including strategic alignment, ethical evaluation, usefulness and effectiveness evaluation, and financial performance, to inform health system selection, validation, deployment, and actionable monitoring of AI tools. The American Heart Association’s extensive hospital and volunteer network and commitment to evidence-based practice position it as a trusted leader in advancing responsible AI governance. By grounding evaluation and monitoring in these principles, this science advisory aims to ensure that AI adoption in health care is safe, effective, equitable, and sustainable, ultimately improving patient outcomes and supporting high-quality AI-enabled care.

Ferroelectricity in graphene nanoribbon devices enabled by collective water molecule dynamics

Abstract Water is omnipresent in nanoscale systems, yet its collective dynamics and impact on emerging electronics remain poorly understood. Here, we investigate the role of water molecule dynamics in the ferroelectric response of graphene nanoribbon devices. Our findings demonstrate that the collective dynamics of water molecules stabilize the ferroelectric effect. We find that a minimum bi-layer thickness is required for the temperature stability of the ferroelectric effect. In contrast, mono-layer ribbons show a 70% shrinkage of the hysteresis window between 120 and 400 K. Using a combination of electrical transport measurements and molecular dynamics simulations, we conclude that water molecules bridging between graphene nanoribbon layers stabilize the formation of water clusters via intermolecular Coulomb interactions, driving a robust ferroelectric behavior and remnant polarization observed at the device level. This work lays the foundations for exploiting water dynamics in next-generation ferroelectric heterostructures, with direct implications for neuromorphic computing and memory devices.

Regulation of eukaryotic-like cell cycle progression in archaea is coming into focus

The protective effects of dapagliflozin on cisplatin-induced ovarian toxicity via NRF2-HO-1 pathway and TNF-α/Cas3 signaling

Nurse–physician collaboration, autonomy, and decision-making ability among intensive care unit nurses in Tehran, Iran: A cross-sectional study

Background Clinical decision-making by intensive care unit nurses is vital for ensuring patient safety. It is hypothesized that professional autonomy and interprofessional collaboration are determinants that influence the quality of decision-making; however, empirical evidence supporting this hypothesis within Iranian intensive care unit settings remains limited. Objective To examine the correlations between perceived autonomy, nurse–physician collaboration, and clinical decision-making ability among intensive care unit nurses. Methods This study employed a cross-sectional design, with 400 intensive care unit nurses from two university hospitals in Tehran completing validated Persian versions of the P-AITCS-II, the Dempster/DPBS, and the Lauri & Salanterä instruments to measure interprofessional collaboration, professional autonomy, and clinical decision-making, respectively. We followed STROBE reporting recommendations. Descriptive statistics characterized the sample and scale scores. Bivariate associations were assessed using correlation and group-comparison tests, and multiple linear regression was employed to estimate the independent associations of autonomy and collaboration with decision-making after adjusting for relevant covariates. Ethical approval and informed consent were obtained. Results The study sample comprised 400 participants, with a mean age of 33.19 years (SD = 5.67). In bivariate analyses, higher perceived autonomy and greater interprofessional collaboration were positively associated with better clinical decision-making (p < 0.05). In multivariable linear regression models that included covariates, perceived autonomy and interprofessional collaboration remained independent predictors of decision-making ability (p < 0.05). The entire model explained approximately 14.2% of the variance in decision-making, suggesting that additional determinants may influence nurses’ decision-making processes. The total mean score of the participants was classified at an intuitive–analytic decision-making level, indicating a combined reliance on experience-based intuition and structured analytic processes. Conclusions Among the intensive care unit nurses within this sample, higher perceived professional autonomy and enhanced interprofessional collaboration were independently correlated with improved self-reported clinical decision-making capabilities. Given the cross-sectional nature of the study, causality cannot be established. Longitudinal research employing objective performance metrics is necessary to examine causal relationships and to guide organizational strategies that foster both autonomy and collaborative practice.

State of the Art: Evaluation and Medical Management of Nonobstructive Coronary Artery Disease in Patients With Chest Pain: A Scientific Statement From the American Heart Association

Risk stratification of patients with chest pain has traditionally focused on identifying obstructive coronary artery disease (CAD). Using this traditional approach, many symptomatic individuals are found to have nonobstructive CAD. The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance chest pain guideline widened the scope of cardiac computed coronary angiography, resulting in increased identification of patients with nonobstructive CAD. In addition, recent advances in artificial intelligence solutions, hardware, and software have allowed identification of microvascular disease and introduced new risk categories within nonobstructive CAD with a risk continuum between primary and secondary prevention. There is thus a growing need for care teams to remain current on the diagnosis, risk stratification, and management of patients with nonobstructive CAD. Whereas only a subset of patients with chest pain are found to have true angina despite nonobstructive CAD, underlying nonobstructive CAD warrants attention. Medical management of nonobstructive CAD plays an essential role in plaque stabilization and regression to decrease the risk of acute coronary syndromes. New pharmacologic therapies and noninvasive plaque evaluation raise the potential for plaque-driven medical interventions. However, data in patients with chest pain who are found to have nonobstructive CAD are limited, and, in clinical practice, multiple factors lead to missed opportunities for precision therapies, with proven disparities in care. We review the current evidence on risk stratification for nonobstructive CAD and discuss its implications and medical management options.

Periodic asymmetric field enhances electrofusion of nanoscale lipid systems

Lineage tracing of both quiescent G0 and active Hoxb5+ LT-HSCs that actively contribute to homeostatic mouse hematopoiesis

Studying the lineage commitment and differentiation potential of long-term hematopoietic stem cells (LT-HSCs) is important to understand the dynamics of hematopoiesis. A central question concerns which hematopoietic stem and progenitor cell populations are responsible for sustaining steady-state hematopoiesis in vivo without conditioning. Noninvasive HSC fate-mapping strategies to address this question require specific labeling of LT-HSCs only. In this study, we selectively labeled a subset of Hoxb5+ LT-HSCs—excluding short-term HSCs (ST-HSCs) and multipotent progenitors (MPPs)—to track the progeny of these cells. Hoxb5+ LT-HSCs comprise ~1 in 100,000 bone marrow cells. MPPs were not labeled until several months post-induction, indicating their derivation from LT-HSCs. At no time were MPPs labeled and LT-HSCs not, consistent with the origin and maintenance of MPPs from LT-HSCs. Hoxb5+ LT-HSCs are the principal contributors to steady-state in situ hematopoiesis, but only a fraction of LT-HSCs were labeled by the Cre/LoxP conversion to a lineage-tracing color. We tested whether quiescent HSCs could have incised the DNA at loxp sites, but did not finish the rearrangement. Analysis of phosphorylated H2AX (γ-H2AX) revealed that quiescent LT-HSCs retain Cre/LoxP-induced DNA incisions, which are repaired upon cell cycle entry, leading to the appearance of newly labeled LT-HSCs at later time points, mainly of the myeloid-biased HSC. Moreover, most LT-HSCs exhibit marked expansion in response to hematopoietic stress. With the age-related shift of blood formation from balanced to myeloid biased, the myeloid-biased HSCs expand preferentially after 6 mo of tracking.

Genetic diversity of native Cucumis melo L. accessions from Iran and Iraq revealed by SCoT and ISSR markers

Correction: Overcoming barriers to NHS adoption of innovative IPC products: A qualitative study of SMEs in the Liverpool city region

Prognostic Value of Exercise Right Ventricular–Pulmonary Arterial Coupling in Primary Mitral Regurgitation

BACKGROUND: Managing clinically significant primary mitral regurgitation is challenging. Right ventricular–pulmonary arterial coupling, assessed with tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) ratio, reflects right ventricular adaptability to afterload. This international multicenter cohort study aimed to evaluate the prognostic value of rest TAPSE/sPAP and exercise TAPSE (exTAPSE)/sPAP in primary mitral regurgitation. METHODS: Between January of 2019 and December of 2023, 211 patients assigned to a derivation cohort (64±12 years of age, 40% women) and 146 patients assigned to a validation cohort (66±13 years of age, 39% women), all of whom had moderate or severe primary mitral regurgitation, no or discordant symptoms, and no left ventricular systolic dysfunction or atrial fibrillation, underwent semisupine cycle–ergometry cardiopulmonary exercise testing combined with exercise echocardiography. TAPSE/sPAP was measured at rest and at intermediate (defined as the first ventilatory threshold) and peak exercise. The primary end point was a composite of cardiovascular death, unplanned cardiovascular hospitalizations, and new atrial fibrillation. RESULTS: In the derivation cohort, 48 patients reached the composite outcome (median follow-up, 24 months [interquartile range, 12–51]). Intermediate and peak exTAPSE/sPAP were strongly correlated ( r =0.84; P <0.001), with intermediate exTAPSE/sPAP offering superior feasibility (98% versus 92%) with comparable prognostic accuracy to peak exTAPSE/sPAP (area under the receiver operating characteristic curve, 0.794 [0.730–0.849] versus 0.765 [0.698–0.823]) and therefore was used as the exercise TAPSE/sPAP measure. Patients with a reduced rest TAPSE/sPAP (cutoff 0.8 mm/mm Hg) and intermediate exTAPSE/sPAP (cutoff 0.6 mm/mm Hg) had a lower event-free survival (log-rank P <0.0001). Intermediate exTAPSE/sPAP and percent-predicted peak VO 2 were independently associated with the primary end point (hazard ratio, 0.64 [0.51–0.80] per 0.1 mm/mm Hg increase [ P <0.001] and hazard ratio, 2.03 [1.05–3.93] if <80% [ P =0.04], respectively) and had incremental prognostic value beyond age, left atrial volume index, mitral regurgitation severity, rest TAPSE/sPAP, and mitral valve intervention (time-dependent covariable). Similar results were found when rest and intermediate exTAPSE/sPAP were included in the multivariable model as categorical measures. Validation in an independent cohort confirmed the consistent and robust performance of both multivariable models, irrespective of whether TAPSE/sPAP was modeled as a continuous or categorical variable. CONCLUSIONS: Exercise right ventricular–pulmonary arterial coupling, particularly intermediate exTAPSE/sPAP, is a robust and feasible measure independently associated with adverse outcomes, and provides prognostic information beyond resting variables and cardiorespiratory fitness, potentially refining risk stratification and guiding management in patients with primary mitral regurgitation.