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McGavern and colleagues identified a CD8⁺ T cell population that expresses GZMK in ʽtau-richʼ brains, where it may play a protective role against neurodegeneration.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Obesity leads to pathological expansion of white adipose tissue driving vascular dysfunction. Here, the authors utilize single-cell RNA sequencing to elucidate endothelial heterogeneity and demarcate key differences in obesity-associated vascular alterations in subcutaneous and visceral white adipose tissue.

Bacterial genes required for plant colonization are highly host- and organ-specific. An efflux pump detoxifies specific Arabidopsis glucosinolates to protect commensal bacteria from plant chemical defenses during colonization.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Fas ligand (FasL) regulates immunotherapeutic cancer-cell death. Here, the authors show a human-specific amino-acid substitution which renders human FasL more susceptible for plasmin cleavage and is relevant for the efficacy of T-cell-based immunotherapies.

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

In the primary report of a phase 1b trial, adeno-associated virus gene therapy with fordadistrogene movaparvovec in patients with Duchenne muscular dystrophy was well tolerated in an ambulatory cohort, and mini-dystrophin expression was increased in the high-dose cohort.

Anti-NMDA receptor encephalitis is a severe brain disorder caused by autoantibodies that trigger NMDA receptor loss. Here, the authors show that ART5803, a monovalent antibody, blocks this process and restores function in cell and primate models.

Single-cell transcriptomes from the fetal–maternal interface of six species of mammals reveal a conserved gene expression signature of invasive trophoblast, stepwise evolution of decidual stromal cell types and co-evolutionary patterns in cell–cell signalling.

Whether neurocomputational mechanisms that speed up human learning in changing environments also exist in other species remains unclear. Here, the authors show that both rats and humans sequentially test different abstract hypotheses to infer rules.

The development of microelectronics requires precursors that can deposit conductive features, however Al is normally deposited using pyrophoric AlH₃ etherates/aminates. Here, the authors use ligands to impart stability and report an aluminium complex that can undergo conversion to Al(0) at 100 °C.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

Hu et al. discovered that the truncated form of human epidermal growth factor receptor 2 (HER2), called p95HER2, drives tumor progression and resistance to the antibody–drug conjugate trastuzumab deruxtecan in HER2⁺ breast cancer. Blocking p95HER2 restores antitumor immunity.

Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

A study reports the development of a method to trace intercellular transfer of mitochondria, and demonstrates that cancer cells that receive mitochondria from neurons have enhanced metastatic capabilities.

Mesocosm experiments revealed that both phytoplankton community composition and cellular acclimation influence marine particulate C:N:P ratios, with community shifts more sensitive to nitrogen supply and acclimation to the nutrient N:P supply ratio

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

Lipoprotein uptake dependent on sulfated glycosaminoglycans linked to cell-surface proteoglycans is a key determinant of ferroptosis sensitivity in cancer.

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

Progerin, a truncated version of lamin A, causes Hutchinson–Gilford progeria syndrome characterized by premature aging and cardiovascular complications. Here the authors show that the most common progeria-causing mutation, LMNA c.1824C>T, is a somatic mutation in arteries from patients with chronic kidney disease, and that clonal propagation of the mutation in the vascular wall results in vascular aging phenotypes in mice.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

Thompson et al. report clinical outcomes and immunological correlates of a phase 1 trial of a peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma.

Using reactivity-based metabolomics, methylglyoxal and its main metabolite lactoylglutathione were found to react rapidly with cysteines to generate l-lactoylated and d-lactoylated thioesters, suggesting additional pathways to enable protein lactoylation.

Mice flexibly shift attention between specific whiskers on a rapid timescale based on recent stimulus reward history in a detection task. Attention is correlated with a somatotopically precise enhancement of neural coding in somatosensory cortex.

Clean cooking fuels can be unaffordable. A year-long randomized control trial in Tanzania finds that a lockbox intervention along with behavioural nudging to encourage savings modestly increased liquefied petroleum gas use but did not lead to exclusive adoption, and that gendered financial constraints explain these results.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

Total cell cycle duration is a key hallmark of cancer initiation, and determines whether defects in apoptosis, senescence, immune surveillance, angiogenesis, DNA repair, polarity and proliferation lead to cancer development.

Relapsed and/or refractory acute myeloid leukemia (AML) postallogeneic hematopoietic cell transplantation has limited treatment options. Here the authors report the clinical results and immune correlates of a phase I/II trial of adoptively transferred virus-specific donor CD8 + T cells engineered to express a WT1-specific T cell receptor in patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation.

Foetal haematopoiesis takes place in the liver before the bone marrow is seeded. Here the authors used imaging analysis and mouse genetics to look at nascent bone marrow formation and show that yolk-sac-derived myeloid cells promote haematopoiesis by promoting specification of a VCAM1⁺ sinusoidal colonisation niche.

Remyelination can restore neural function. Here, the authors characterize the drivers and limits of endogenous remyelination and explore a therapy that rescued remyelination deficits and accelerated neuronal functional recovery, although complete remyelination was not required.

TGFβ superfamily proteins can affect cellular differentiation, thermogenesis, and fibrosis in mammalian adipose tissue. Here the authors described a role for the TGFβ superfamily protein GDF3 in the regulation of lipolysis, glucose tolerance and glycemic variability in mice.

Myostatin and activin A are the two primary negative regulators of muscle mass. Blocking these circulating ligands during GLP-1 therapy induces improved body composition through preservation of lean mass and enhanced fat mass loss in obese primates.

ADP-heptose binds to ALPK1, triggering transcriptional reprogramming and NF-κB activation, endowing pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation.

During visual learning, neural plasticity is driven by unsupervised learning in mice.

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.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

While BH3-mimetics can be effective for treatment of haematological malignancies, their efficacy in solid tumours is limited. Here, using a range of patient-derived prostate cancer models, the authors demonstrate that increased replication stress induced by RB1 loss confers sensitivity to BH3 mimetics targeting BCL-XL.

Pituitary gonadotrophs secrete LH and FSH, regulating gonadal function. Here authors show that in the mouse pituitary most gonadotrophs originate from postnatal stem cells, while a minor population of cells born in the embryo persist.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Myeloid cells contribute to the etiology of multiple sclerosis (MS), but the dynamics of myelopoiesis during disease progression is still unclear. Here the authors show, in both mouse models and clinical data, that myelopoiesis is differentially regulated via M-CSF modulation in different organs at distinct stages of MS, with diet and lifestyle being potential modifiers.

A wireless device for measuring bioimpedance during breastfeeding allows accurate quantification of the volume of expressed milk in 12 new mothers in a neonatal intensive care unit and in home settings.