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ASPP1 promotes apoptosis of cardiomyocytes by increasing the trafficking of p53 to the nucleus. Here the authors show that, in fibroblasts, ASPP1 promotes the ubiquitination and degradation of p53, decreasing myofibroblast activity and improving cardiac fibrosis and function after myocardial infarction.

Fibroblast-to-myofibroblast differentiation is crucial for wound healing and regeneration. Davis et al. describe a new regulatory mechanism underlying myofibroblast differentiation via the RNA-binding protein MBNL1, which promotes the maturation of certain mRNA transcripts that are integral nodes in fibroblast differentiation.

Myocardial substrate metabolism in cardiac hypertrophy or heart failure shifts from fatty acid oxidation to a greater reliance on glycolysis. Here, the authors show that KLF7 can simultaneously regulate key enzymes in glycolysis and fatty acid oxidation to mitigate metabolic imbalance during cardiac hypertrophy.

Expression and activation of Heat shock factor 1 (HSF1) in cancer associated fibroblasts have been associated with protumorigenic functions. Here the authors show that, in a model of colitis-induced colorectal cancer, HSF1 is activated in stromal fibroblasts in the early stages of inflammation, leading to extracellular matrix remodelling that sustains tumor initiation and progression.

Zhang et al. report that the lncRNA H19 stabilizes dystrophin by competing with the ubiquitin E3 ligase TRIM63 for association with dystrophin, thereby alleviating muscular dystrophies.

Irreversible damage of the lung epithelium in idiopathic pulmonary fibrosis patients causes high mortality worldwide, with no lung repair approaches available currently. Here, the authors show that cloned human airway basal progenitor cells could repair the fibrotic lung through re-epithelialization of the damaged alveolar area.

Beneficial and detrimental effects have been ascribed to the different Thrombospondin (Thbs) proteins in the adult mammalian heart. Here, the authors show that Thbs1-mediated activation of PERK-eIF2α-ATF4-induced autophagy regulates adult cardiomyocyte size in the stressed heart.

Hu et al. describe how histone H1.0 regulates myofibroblast activation, linking force generation to nuclear organization and gene transcription.

The prediction of chronic toxicity is a major challenge in nanotoxicity studies. Here, the authors present an in silico framework for predicting ENM-induced lung fibrosis, displaying 85% accuracy in experimental validation and leading to identification of key events at nano-bio interfaces that allows mechanism interpretation of ENM-induced lung fibrosis.

The overexpression of β-catenin and the transcription factor Gata4 in skin fibroblasts induces these cells to secrete reparative exosomes, as shown in mice models of myocardial infarction and Duchenne muscular dystrophy.

Two approaches using an adenine base editor and a Cas9 nuclease prevented the development of hypertrophic cardiomyopathy in mice carrying a pathogenic mutation on the Myh6 gene, highlighting the potential of single-dose genetic therapies for the treatment of cardiac disease.

Loss of let-7, a key microRNA, causes lung alveolar stem cells to grow abnormally and dieprematurely, leading to scarring and lung damage. Here the study links let-7 loss to cancer-like signals and epigenomic gene changes, revealing new treatment paths for lung fibrosis.

Pianca and Sacchi et al. unveil an important role for glucocorticoids and their receptor (GR) in cardiomyocyte cytoarchitectural/metabolic maturation, cell cycle exit and loss of regenerative ability, and they propose GR antagonization as a strategy for heart regeneration.

Immune cells contribute to adverse remodeling following myocardial infarction. Here the authors show in mice and pigs that CD8⁺ lymphocytes release Granzyme B in the infarcted heart leading to cardiomyocyte death, enhanced inflammation and deterioration of cardiac function.

Here the authors show that the biological fate of rare earth nanoparticles can be genetically controlled by SMPD1 in cells, offering insights for the prevention or treatment of rare earth associated hazard effects, such as inflammation and pneumoconiosis.

Hydrogels are essential for stem cell-based tissue regeneration but struggle with hard tissue repair. The authors report a shell-hardened macroporous hydrogel with spatiotemporally programmed mechanics to enhance stem cell-driven bone regeneration.

Self-assembled multidomain supramolecular peptide hydrogels that engage in dynamic covalent bonding with small-molecule drugs and biologics are shown to offer sustained release, extend the activity, and maintain safe and potent drug levels in vivo.

The functional role of airway basal cells has not been comprehensively studied in idiopathic pulmonary fibrosis (IPF). Here, the authors show that airway basal cells of IPF patients display a distinct phenotype, are profibrotic if transplanted to mice and that fibrosis can be ameliorated by Src iinhibitors.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Yu et al. show that Piezo1 is the stretch-activated mechanosensor that provides the calcium source to activate TRPM4 and the downstream CaMKII-HDAC4-MEF2 pathway, a key mediator in the cardiomyocytes’ hypertrophic response in pressure overload models.

Senolytic compounds have the ability to eliminate senescent cells from tissues and have been shown to be beneficial in various animal models of age-related diseases. Here the authors show that cardiac glycosides commonly used for heart diseases have senolytic properties in humanized mouse models of tumorigenesis and lung fibrosis.

Tau-mediated neurodegeneration is driven by disease-activated microglia and suppressed by their pharmacological blockade. The authors identified drug dose- and sex-dependent residual microglial phenotypes, neuronal excitotoxicity, and animal survival.

During chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy through WSTF interaction with ATG8 in the nucleus, leading to WSTF nuclear export and its subsequent degradation.

Liver fibrosis is a disease that lacks effective treatments. This study reveals that ATF4 drives fibrosis by activating hepatic stellate cells and that pharmacological inhibition of ATF4 reduces liver fibrosis, offering an opportunity for new therapies.

A dilute water–polymer mixture exhibits a percolation-induced gel–gel phase separation, resulting in a two gel co-continuous substrate, which is used for adipose tissue development.

A truncating variant of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), a lipid droplet -associated protein, associates with lower risk of chronic liver disease. Here the authors identify a phosphorylation site in 17β-HSD13 which promotes lipolysis, and report that a knock-in mouse with a 17β-HSD13 mutant defective for phosphorylation is more susceptible to nonalcoholic steatohepatitis.

Thrombospondin 4 has been shown to protect the heart and the skeletal muscle by enhancing matrix secretion and membrane stability thanks to its intracellular function. Here the authors show that thrombospondin 3 exacerbates injury-induced cardiomyopathy and promotes destabilization of the cardiomyocyte membrane by impairing integrin trafficking to the sarcolemma.

Blockade of lymphotoxin β-receptor (LTβR) signalling restores WNT signalling and epithelial repair in a model of chronic obstructive pulmonary disease.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

McHugh et al. identify COPI trafficking as a vulnerability of senescent cells. N-myristoyltransferase inhibitors phenocopy COPI inhibition and are potent senolytics.

Acquiring subcellular-level three-dimensional (3D) tissue structures efficiently without damaging the tissue remains challenging in histopathology. Here, the authors integrate holotomography with deep learning to generate 3D virtual H&E staining images from label-free thick cancer tissues, and apply this approach to colon and gastric cancer samples.

Persistent diabetic complications despite controlled blood glucose levels, known as hyperglycemic memory, remain a poorly understood phenomenon in diabetic kidney disease. Here the authors identify senescence-associated gene p21 as a regulator of hyperglycemic memory, the suppression of which improves hyperglycemic memory and renal function.

The intercalated disc (ICD) is a membrane structure of the cardiac muscle involved in normal heart function. Here the authors report that knockdown of the ICD-bound transmembrane protein 65 results in impaired ICD structure, abnormal cardiac electrophysiology and cardiomyopathy in mice.

Mouse fibroblasts can be simultaneously directly reprogrammed into cardiomyocytes, endothelial cells and smooth muscle cells to form cardiac tissue structures that improve cardiac function on implantation into infarcted mouse hearts.

Ye et al. characterize the cardioprotective effect of SIRT2 in primates and reveal an important role for the SIRT2–STAT3–CDKN2B regulatory axis in primate cardiac aging, improving understanding of the epigenetic mechanism governing cardiac aging.

A functional interfacial material has been developed for soft integration of bioelectronic devices with biological tissues. This has been applied in battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy as well as wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays.

Renal tubular epithelial cells (TECs) can initiate an adaptive or maladaptive response after injuries of different severity. Here, the authors elucidate a chromatin-mediated mechanism underlying the responses of TECs to varying kidney injuries.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

It is unclear if neuromelanin plays a role in Parkinson’s disease pathogenesis since common laboratory animals lack this pigment. Authors show here that overexpression of human tyrosinase in the substantia nigra of rats resulted in an age-dependent production of human-like neuromelanin within nigral dopaminergic neurons and is associated with a Parkinson’s disease phenotype when allowed to accumulate above a specific threshold.

Grockowiak et al. explore bone marrow niche heterogeneity in myeloproliferative neoplasms, polycytemia vera and essential thrombocytemia and find JAK2-mutated hematopoietic stem cells occupying distinct niches affecting cell growth and therapy response.