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T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

Chandrakanthan et al. identify Mesp1-derived PDGFRA⁺ stromal cells as aortic endothelial precursors that regulate long-term haematopoietic-stem-cell generation during development, thus providing a new potential tool to generate engraftable haematopoietic stem cells.

Malignant cardiac tumors have a dismal prognosis left untreated but pose a therapeutic challenge to oncologists and cardiac surgeons. Extensive resection can be required and the positions of the tumors create technical difficulties. Primary malignant tumors can also represent aggressive disease. The clinical manifestations and therapeutic options are discussed in this Review.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The motions of subducted slabs are expected to drive mantle flow around slab edges, however, evidence of deep mantle flow has so far remained elusive. Here, the authors present a Full Waveform Inversion 3-D anisotropy model which allows them to infer deep subduction-induced mantle flows underneath the Mid-Americas and the Caribbean.

Here, the authors describe a clinical protocol for ‘back-to-base’ combined hypothermic and normothermic machine perfusion of human livers.

In a short-term study in which hearts from gene-edited pigs were transplanted into two recently deceased human recipients, the hearts were able to function for the duration of the study without signs of rejection and without evidence of pig virus transmission, encouraging further clinical study of cardiac xenotransplantation.

Tweaking immune characteristics of donors and recipients could allow for successful cross-species organ transplantation. Here, the authors show that an anti-CD40 antibody therapy of baboons that received heart transplants from genetically modified pigs is key to their long-term survival.

Hunter et al. use RNA labelling to investigate RNA transfer between organs in mice. They show that RNA potentially moves en masse from liver to kidney and that this movement is augmented in acute liver injury, although the physiological relevance of the phenomenon is not yet known.

ACSS2 catalyzes the conversion of acetate to acetyl-CoA. Here, authors show that ACSS2 regulates iron metabolism and ferroptosis in alcoholic liver disease by modulating the histone acetylation of HAMP1/2.

Recently, a Luttinger liquid state was reported in a moiré superlattice of bilayer tungsten ditelluride at small twist angles and temperatures of a few kelvins. Here, the authors extend this result to millikelvin temperatures, supporting the existence of the 2D anisotropic Luttinger liquid as a stable ground state.

A materials platform using tantalum as a base layer and silicon as the substrate to construct superconducting qubits enables device performance improvements such as millisecond lifetimes and coherence times, as well as high time-averaged quality factors.

The strange metal state, characterized by a linear-in-temperature resistivity, is often seen in the normal state of high-temperature superconductors. Here, the authors report the breakdown of both the strange metal and superconducting states at a pressure-induced quantum critical point in an iron-pnictide superconductor.

MTH1 hydrolyzes oxidized nucleotides to prevent their mis-incorporation into DNA under oxidative stress. Here, the authors show that MTH1 is expressed in platelets and its deficiency increases mitochondrial DNA oxidative damage, impairs platelet function and hemostasis.

The gut microbiota can influence immune-cell function by the production of short-chain fatty acids. Mackay and colleagues show that diets enriched for acetate and butyrate protect non-obese diabetic mice from insulitis and diabetes progression.

Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.

This Review provides a comprehensive overview of epidemiology and molecular determinants of relapsed rhabdoid and other non-nephroblastoma childhood and adolescent kidney tumours, which are usually rare and challenging to cure. The most updated results in this field are discussed to highlight how understanding tumour biology can be used to inform therapeutic strategies in these patient populations.

This work presents SCIGEN, a machine learning framework integrating geometric constraints into material generation. The framework enables the discovery of stable quantum material candidates, and the authors synthesize two predicted magnetic materials.

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.

Treatment strategy of solid tumors requires continuous development. Here the authors develop a Macrophage Drug Conjugate (MDC) platform by loading ferritin-drug complexes to macrophages. MDC transfers the ferritin to cancer cells via ‘TRAnsfer of Iron binding protein’ (TRAIN) process and reduces tumor volume in various mouse tumor models.

Organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), are not offered for transplantation due to a high risk of transmission. Here, Galasso et al. develop a method for treatment of HCV-infected human donor lungs that is safe and prevents HCV transmission in the pig model.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

GDF-15 is a cytokine regulating food intake and a potential therapeutic target for treating obesity. Here, the authors show that macrophage infiltration in adipose tissue increases GDF-15 during obesity and type 2 diabetes, and hepatocyte stress further increases its levels when developing MASH.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

Using kidneys from a genetically engineered porcine donor transplanted into a cynomolgus monkey model, the design, creation and long-term function of kidney grafts supporting life are explored.

The nuclear factor kappa B subunit c-Rel acts as a master regulator of metabolism and signalling in epithelial cells and macrophages that drives inflammation and fibrogenesis in various models of fibrosis.

Decellularized whole porcine livers revascularized with human endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days.