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Unlike that in plants, fungi, and marine animals, bacteria are vastly underrepresented in the production of terpenoids. Here, the authors report a systematic screening of terpene synthases from bacteria and identify three new skeletons that are not found in other organisms.

Mutations in mtDNA contribute to mitochondrial disease and aging only if they rise in abundance. Here, the authors show that deleterious mutations reach high abundance by hitchhiking on genomes that have a replicative advantage.

In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.

High ambient temperatures are associated with reduced sleep duration and quality, and increased obstructive sleep apnoea (OSA). Here the authors quantify the effect of 24 h ambient temperature on nightly OSA severity and report projected in losses of healthy life years and workplace productivity due to OSA in scenarios of projected temperatures ≥1.8° C above pre-industrial levels by 2100.

Systemic lipid homeostasis requires hepatic autophagy to recycle intracellular fat. Here, the authors identify peripheral mechanisms regulating energy homeostasis, showing that MC3R is a regulator of hepatic autophagy, hepatic fat accumulation, and fat partitioning, controlling systemic adiposity.

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.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

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 limited infiltration and migration of T cells in the brain can hinder the success of immune checkpoint blockade in glioblastoma (GBM). Here the authors show that an adeno-associated virus-based gene therapy for the intratumor delivery of CXCL9 promotes T cell infiltration and enhances response to anti-PD1 in GBM preclinical models.

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.

Comparison of non-invasive [¹¹C]metomidate PET-CT with adrenal vein sampling for predicting biochemical remission of primary aldosteronism showed non-superiority, suggesting that the non-invasive method is suitable for the diagnosis of unilateral primary aldosteronism.

Congestion is the main reason for hospitalization in patients with acute decompensated heart failure and is an important target for therapy. In this Review, Boorsma and colleagues distinguish between intravascular congestion and tissue congestion, and hypothesize that specifically treating these two different forms of congestion could improve patient outcomes.

Xenotransplantation is an imminent clinical reality but concerns remain around the logistics of procurement and the experimental immunosuppression regimens required to achieve long-term xenograft survival. Here the authors show more than 6 month survival of genetically modified porcine kidneys in baboons after regulatory compliant organ procurements, clinically relevant organ preservation times and FDA-approved immunosuppressive reagents.

Bouvain et al. develop fluorine-loaded nanotracers engineered with binding peptides targeting the neutrophil-specific receptor CD177 for specific and non-invasive mapping of murine and human neutrophil dynamics by whole-body MRI.

In this cross-species translational study, the authors look at the longitudinal consequences of stress during adolescent development on HPA function and postpartum behaviors in mice and in humans and suggest that glucocorticoid receptor antagonists may serve as a potential treatment for postpartum depression.

The binding of the leukocyte integrin Mac1 to the platelet receptor GPIbα is important for the physiological response to tissue injury. Here the authors show that this interaction also regulates thrombosis, without influencing bleeding time, which may provide clues for the development of new anti-thrombotic drugs.

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.

Heterogeneity in leiomyosarcomas (LMS) makes treatment of the disease challenging. Here the authors analyze LMS heterogeneity and molecular LMS subtypes using genomics and transcriptomics, finding origins in distinct lineages and associations with survival, in addition to the early emergence of metastatic clones.

Sestan et al. find a conserved mechanism during systemic viral infection in which γδ T cells produce IFNγ to increase pancreatic insulin secretion, lowering blood glucose and then enhancing type I interferon-mediated protection against viral infection.

Originally intended for life-saving salvage therapy, the use of temporary mechanical circulatory support (MCS) devices has become increasingly widespread. In this Review, Salter and colleagues discuss the functionality, indications, management and complications associated with temporary MCS in specific clinical scenarios.

Here, in a longitudinal case study, Weigang et al. demonstrate that evolution of SARS-CoV-2 within a persistently infected immunosuppressed patient can result in the emergence of novel variants with reduced sensitivity to antibody neutralization.

A supramolecular drug design yields anticoagulants that are rapidly reversible.

Detailed analyses of the serotonin receptor 5-HT_1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

Porcine kidney xenotransplantation is accelerating towards clinical testing. Here the authors present preclinical results examining xenograft growth and participation in renal endocrine pathways that can be used to inform clinical study design.

O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

Venomous animals typically disrupt nervous, locomotor, and cardiovascular systems to incapacitate prey, but certain fish-hunting cone snails evolved toxins that specifically target glucose homeostasis. Here, the authors show the combinatorial nature of weaponized insulin and somatostatin mimetics, exemplifying the use of combinatorial chemical mimicry for prey capture.

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.

These authors describe a molecular pathway by which endothelial cells sustain liver regeneration after surgical resection. Activation of vascular endothelial growth factor-A receptor-2 in a defined subpopulation of liver endothelial cells leads to the upregulation of the endothelial-specific transcription factor Id1, which in turn induces Wnt2 and hepatocyte growth factor, which are secreted from the endothelial cells and trigger hepatocyte proliferation.

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.

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.

Zhu et al. designed and manufactured a mitral annuloplasty ring based on human high-resolution cardiac magnetic resonance imaging exams, demonstrating axis-specific flexibility and rigidity. This ring demonstrates excellent ex vivo hemodynamics and biomechanics while allowing mitral annulus dynamic changes in a survival in vivo large animal model.

TREM-1 is a receptor that amplifies acute pro-inflammatory responses in infection. Here the authors show that TREM-1 plays an important role in atherosclerosis, a chronic and non-infectious disease, by critically skewing myelopoiesis towards preferential monocyte differentiation and by contributing to CD36-driven cellular lipid accumulation.