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Pressure overload in the heart, such as from aortic stenosis, triggers early molecular changes before visible damage occurs. Here, the authors show that combining proteomics, transcriptomics, and genetic data reveals key drivers of heart failure, highlighting potential targets for treatment.

In a randomized trial of patients with a previous myocardial infarction and with residual inflammation, a monoclonal antibody targeting the LOX-1 receptor, thought to contribute to atherosclerotic plaque progression and inflammation, reduced soluble LOX-1 and interleukin-6 levels but did not lead to a substantial reduction in coronary plaque volume.

Mellor et al. report that deficiency of GABARAPL1, an ATG8-specific linking protein, impairs diastolic function in diabetic mice. This effect can be reversed by gene delivery of the gene encoding GABARAPL1 in diabetic mice and a human organoid model of type 2 diabetes.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

Arrhythmia-induced cardiomyopathy (AIC) refers to heart failure caused or exacerbated by arrhythmias, which resolves completely after restoration of sinus rhythm. In this Review, Fabritz and colleagues focus on atrial fibrillation as the cause of AIC, describing its pathophysiology, epidemiology and clinical presentation, and the various approaches to the diagnostic–therapeutic strategy of rhythm restoration.

Semantic segmentation of cardiac chambers in ultrasound is critical, but laborious and error-prone. Here the authors develop a manual-label free, clinically valid, and scalable method for segmentation from cardiac ultrasound.

Kacira et al. develop an apical 4-chamber-long-axis (A4CLAX) echocardiographic imaging approach for mice. They demonstrate that the A4CLAX method provides clinically comparable and comprehensive evaluation of cardiac function in murine models, with the sensitivity to detect subtle changes in cardiac performance during disease progression.

The retreat of the Fennoscandian Ice Sheet during the last deglaciation led to the infiltration of seawater into a submarine groundwater system on the Norwegian continental shelf, according to an analysis of groundwater geochemistry on the Norwegian shelf.

Understanding the molecular events controlling melanoma progression are necessary to find improved therapeutics. Here, the authors report oncogenic SOX2-GLI1 transcriptional complex to drive melanoma invasion through the induction of the sialyltransferase ST3GAL1, and report ST3GAL1-AXL axis as driver of melanoma metastasis.

The sedimentary DNA signal obtained from Black Sea sedimentary archives revealed the past dynamics of microorganisms able to transform mercury into the neurotoxin methylmercury. Water column anoxia during the mid-Holocene Climate Optimum appeared to be the main driver of potential methylmercury production in the Black Sea.

Key neurons in the orbitofrontal cortex form memories for best action strategies when mice seek rewards. Here, the authors show that these neurons have more mature dendritic spines than neighboring cells, this maturation requiring concurrent plasticity in the amygdala.

In a randomized phase 2 clinical trial, the angiotensin receptor blocker valsartan improved cardiac structure and function in patients with early-stage hypertrophic cardiomyopathy, a condition for which there are no effective therapies for modifying disease progression.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

In this work, authors develop obex inhibitors that target a distinct binding pocket in the ATPase domain of Topoisomerase II. They demonstrate how Topobexin, a Topoisomerase IIβ - selective catalytic inhibitor, blocks conformational changes and protects against anthracycline cardiotoxicity.

Loescher, Freundt et al. investigated the contribution of each cytoskeletal filament to passive myocardial stiffness by using a mouse model that allows for specific cleavage of titin; they show that titin is a major cytoskeletal filament controlling myocardial elastic forces, whereas viscous forces are controlled by titin, the microtubules and actin.

MAP1B is bound and regulated by fragile X protein FMRP. Here, the authors show that elevated levels of MAP1B reduce the morphological and physiological maturation of human neurons and impair social behavior in mice.

Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective effects in Alzheimer’s disease.

The authors identify two coexisting incommensurate charge density waves whose interplay leads to joint commensuration and a long-period moiré structure.

Intraventricularly delivered monovalent and trivalent CAR T cells exhibit greater therapeutic efficacy as compared with intravenously delivered CAR T cells in medulloblastoma xenograft mouse models and show potency in ependymoma xenograft mouse models.

What mechanisms enable brains to maintain behaviors after neuron loss? Based on behavioral, neuronal and modeling data, Wang et al. find that unsupervised cellular and systems-level restorative mechanisms can ensure behavioral resilience.

In this Review, the authors explore the state of artificial intelligence (AI) applications in echocardiography, discussing the integration of AI throughout the echocardiographic workflow and highlighting the clinical implementation, challenges and future directions of AI-supported echocardiography.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

Takotsubo disease, a stress induced cardiomyopathy mimicking acute coronary syndrome, increases the risk of heart failure and cardiac death. The authors show here that heart function and structure keep on deteriorating continuously after a single acute stress, this snowball effect being triggered by abnormalities incardiac metabolism.

Pampols-Perez et al. identify the mechanosensitive ion channel PIEZO2 as a novel marker for embryonic coronary artery endothelial cells and as a critical regulator of coronary vascular remodeling. They show that in a distinct subset of coronary endothelial cells, PIEZO2 translates mechanically activated ionic currents into biological signals guiding coronary artery morphogenesis.

A violation of Lorentz symmetry would represent a fundamental departure from the physics of the standard model. Searching for anomalous neutrino oscillations, the IceCube collaboration reports no violation, and puts stringent bounds on its existence.

Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.

Lei et al. show that cold preservation of heart transplants triggers mineralocorticoid receptor clustering in cardiomyocyte nuclei, and blocking this improves heart transplant function.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

The aging myopathy is characterized by diastolic dysfunction of unknown aetiology. Rota et al. show that increased late Na⁺ current (I_NaL) underlies diastolic dysfunction in the aged heart, and that inhibiting I_NaLimproves diastolic indices and corrects the kinetics of cardiomyocyte contraction and relaxation in aged mice.

Annexin-A1 shields against hypertension-induced cardiovascular damage, with heightened effects in females. Estrogen-driven upregulation of annexin-A1 unveils a novel, sex-specific protective axis, offering innovative targets for tailored cardiovascular therapies.

A customizable soft robotic aortic sleeve can recapitulate the haemodynamics and biomechanics of aortic stenosis, as shown in a porcine model of the disease.

This study aims at enhancing hematopoietic stem cell (HSC) gene therapy potential to treat neurodegenerative diseases via innovative approaches. Findings demonstrate the therapeutic benefits of intracerebral transplantation of TREM2-engineered HSCs in an Alzheimer’s disease mouse model.

T-UCRs encode long non-coding RNAs implicated in human carcinogenesis, but the underlying mechanisms are poorly understood. Here, the authors identify uc.339 as an oncogene in lung cancer that is upregulated through the loss of TP53 and promotes Cyclin E activation by entrapping regulatory miRNAs.

Arrayed and pooled high-throughput screening is crucial for drug discovery and CRISPR functional genomics. Here, the authors present dFLASH; a dual FLuorescent transcription factor Activity Sensor for Histone-integrated live-cell reporting for high performance screening applications across numerous pathways and screening contexts.

High-voltage amorphous oxide semiconductor thin-film transistors can be integrated on top of a silicon integrated circuit containing 100-nm-node fin field-effect transistors using an in-air solution process.

Maatz, Lindberg et al. identify molecular alterations and immune response changes in endomyocardial biopsies from patients with myocarditis after COVID-19 infection, after anti-COVID-19 vaccination or from non-COVID-related causes.

Kadyrov et al. reveal that the hypoxia sensing through HIF1A is an important regulator of monocyte-derived macrophage differentiation, which determines the extent of inflammation and cardiac remodeling after injury.

Human myocardial proteomic and metabolomic analyses reveal ventricle-specific metabolic remodelling from normal hearts to heart failure, showing differential regulation in glucose and lipid metabolism, with a left ventricular pathological bias.

A single-center, observational cohort study assessing the mitochondrial bioenergetics of left ventricular tissue from patients undergoing coronary artery bypass grafting surgery suggests that viable myocardium has global alterations in bioenergetics and transcriptome without large regional differences between areas with or without inducible ischemia.

Lai et al. present the machine learning model MAARS to predict arrhythmic sudden cardiac death from multimodal imaging and clinical data in patients with hypertrophic cardiomyopathy.