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This study demonstrates a role of cholesterol metabolism-related gene, Lrp3, in cartilage degeneration and osteoarthritis pathogenesis. LRP3 positively regulates cartilage extracellular matrix metabolism by targeting syndecan-4 via Ras signalling, implicating the cholesterol-LRP3-SDC4 axis in osteoarthritic cartilage degeneration.

The design and assembly of interlocked supramolecular cages is of interest due to their exquisite topological configuration and excellent performance in a variety of applications. Here, the authors synthesize interlocked cages from half-sandwich rhodium building blocks and prepare membranes for applications in photothermal seawater desalination.

An Ohmic contact interface engineering strategy was proposed by loading copper nano islands on indium hydroxide nanocubes, which could trigger and stabilize the polarized Cu0 -Cuδ+ active sites. Such catalyst enabled effective ammonia electrosynthesis with nitrate under ambient conditions

Nonalcoholic steatohepatitis (NASH) is a heterogeneous disease with complicated pathogenesis. Here the authors identify that the E3 ligase TRIM26 confers protection against NASH development via suppression of CCAAT/enhancer binding protein delta (C/EBPδ).

A genome-wide association study of cardiac magnetic resonance-derived left ventricular mass index including 43,000 UK Biobank participants reveals 12 associations (11 novel), implicating genes involved in cardiac contractility and cardiomyopathy.

Existing datasets of nitrogen (N) balance in agriculture are often discrepant. Comparing 13 of them regarding five metrics (fertilizer application, manure application, biological N fixation, atmospheric deposition, and N harvested as crop products) over 1961–2015 reveals why. Recommendations for improving N quantification and an N budget benchmark dataset are also proposed.

Costa-Verdera et. al describe a mechanism by which AAV vector genomes activate P53-mediated signalling in CNS cells involving downstream STING activation and pro-inflammatory responses. Inhibition of either P53 or STING prevented target-cell apoptosis and inflammatory signalling.

Sayers et al. reveal that heart regeneration during the neonatal period in mice extends to conduction system restoration after insult, highlighting the difference between this process and pathological remodeling in the adult heart.

Alterations in myocardial mitochondrial metabolism following myocardial infarction (MI) lead to structural and functional abnormalities of the heart. Here, the author shows that inhibiting the palmitoylation of CD36 alleviates lipid metabolism disorders and mitochondrial dysfunction in cardiomyocytes post-MI.

Shao, Li, Liu et al. identify the GAS6–ATF3 axis as a central regulator of survival and proliferation of protective resident MerTK⁺ cardiac macrophages and show that GAS6 administration improves cardiac repair after ischemic–reperfusion injury in mice in an ATF3-dependent manner.

Heat barriers pose significant challenges to hypersonic flight. Here, authors demonstrate a direct liquid cooling system using a structured thermal armor that elevates the Leidenfrost point, effectively managing temperatures up to 3000 °C.

In this study, Hsu et al. show that inhibition of CDK7/12/13 attenuates maladaptive transcriptional activation in cultured cardiomyocytes and a mouse model of heart failure, suggesting that targeting the transcription machinery might be a therapeutic approach to treat heart failure with reduced ejection fraction.

Qi et al. show that bile acids produced by the gut microbiota can suppress platelet activation and reduce atherothrombosis, protecting atherosclerotic mice from myocardial ischemia/reperfusion injury.

Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.

Wilms tumours are the most common malignant kidney tumour type in children, and their low mutational burden has impeded the development of targeted therapies. Here, the authors perform a proteogenomic characterisation of Wilms tumours, revealing molecular subtypes with different clinical features and identifying EHMT2 as a potential prognostic marker and therapeutic target.

The heart relies on fatty acid oxidation as its main energy source. Here they show that impaired fatty acid metabolism disrupts mitophagy in the heart and that enhancing mitophagy via USP30 inhibition can restore heart function in models of fatty acid oxidation deficiency.

The mechanisms linking neuropsychiatric and metabolic disorders remain unclear. The authors show a pancreas–hippocampus feedback loop whereby metabolic and circadian factors drive behavioral fluctuations, with potential relevance for bipolar disorder.

Genome-wide association and multitrait analyses for dilated cardiomyopathy (DCM) using 9,365 cases and 946,368 controls provide insights into the mechanisms underlying DCM and myocardial resilience

Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spectrometry. Now a method has been developed to profile protein arginylation ex vivo and is tested on different samples, revealing 235 unique arginylation sites in the human proteomes.

Here the authors combine an experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes to provide a comprehensive map of Atrial Fibrillation risk variants and genes.

Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

HACE1 is an E3 ubiquitin ligase known to regulate various cell biological processes. Here, Zhang et al.identify HACE1 as a protective factor in the heart, demonstrating that HACE1 inhibits the development of heart failure in response to haemodynamic stress by regulating protein degradation pathways.

Li₅FeO₄ is a high-capacity prelithiation agent but suffers from poor air stability. Here, authors apply a carbon coating strategy to significantly improve its resistance to moisture, enabling over 92% capacity retention after 72 h exposure to ambient air.

Nanog regulates embryonic stem cell (ESC) pluripotency but what controls Nanog protein stability is unclear. Here, the authors show that in mouse ESCs, Nanog protein is ubiquitinated and stabilized by the deubiquitinase USP21, which in turn is regulated by extrinsic signals, STAT3 and ERK.

This study evaluates nitrogen surplus reduction scenarios across Europe using century-long sub-national data and a multidimensional clustering algorithm. The findings show that a 20% fertilizer reduction alone is insufficient to meet Farm to Fork targets and that region-specific strategies, combined with advances in technology and management practices, are essential.

Lysosomes are best known for their roles in inflammatory responses via autophagy. Here, Xing et al., find that lysosomes regulate macrophage inflammatory responses by finely controlling interleukin-1β production, altering lysosomal Fe2+ release through the TRPML1 channel.