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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.

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 evolution of cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, the authors employ multi-omics and multi-scale analyses to explore the genetic evolution of keratinocytes to cSCC, finding key pathogenic mutations that break the resistance to ultraviolet radiation as well as spatial heterogeneity patterns.

This work presents a degradable ionizable lipid, AMG1541, for mRNA vaccines that significantly enhances potency and enables similar protective immunity at doses 100-fold lower than current standards, while also reducing toxicity and improving clearance in vivo.

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.

Defective insulin secretion is observed early in the development of diabetes. Here the authors report that β cell-specific deficiency of the insulin prohormone convertase 1/3 (PC1/3) leads not only to hyperglycemia, but also to hyperphagic obesity in mice.

Here the authors report results from a randomized clinical trial testing a combination of ChAOx1/MVA.HTI vaccines and the TLR7 agonist vesatolimod in men living with HIV-1. While the treatment showed a good safety profile and induction of HTI-focused T-cell responses, viral rebound was similar in treatment arm and placebo arm.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.

Increasing rates of multidrug-resistant bacterial infections has renewed interest in the therapeutic use of phages. Here the authors report an individual with cutaneous M. chelonae infection, and the improvement of disease upon treatment with a bacteriophage in combination with antimicrobial therapy.

Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

How do low-mass binaries age? Astronomers have constrained a tight, circular orbit of a close-in companion around a dying giant star, raising new questions about how tidal forces shape binary orbits in the final phases of stellar evolution.

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.

Mathematical representations of overflow metabolism, mixotrophy, exoenzymes and reactive oxygen species detoxification recapitulate dynamics in co-cultures of Prochlorococcus and eight heterotrophic bacteria.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.

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

Previously undescribed hierarchical arrangements in haematopoietic stem cells and their niches that mediate both regenerative potential and immune privilege are identified.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Epithelial organoids are grown without Matrigel using a single-chain antibody.

Here, the authors use detailed temporal nutrition intake data captured through real-time food logging via a smartphone app and gut microbiota profiles from ~1,000 participants of a digital cohort on personalized nutrition to associate dietary regularity and quality with gut microbiome diversity.

This study reveals an important chondrocytic progenitor population for maintenance of adult articular cartilage marked by Gremlin 1. Loss of these progenitors causes osteoarthritis and suggests methods to sustain them may be effective future targets for management of osteoarthritis.

Topoisomerases resolve topological DNA stress via double-strand breaks and are established targets of cancer chemotherapies. Here, the authors link genomic binding of TOP2B with localized mutational processes in cancer genomes that include prominent driver genes and translocation hotspots.

Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.

Yabut and Drucker discuss clinical and preclinical evidence about the potential roles of GLP-1 medicines on cancer incidence, development and therapy and speculate about their mechanism on cancer cells and the tumor microenvironment.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Base editing to treat diseases is progressing but tissue delivery and progenitor cells correction are challenging. Here, the authors show sustained effects and propagation of mutation-corrected progenitors by transient adenine base editor expression, improving the skin phenotype of HGPS mice.

Researchers induced ploidy reduction in human oocytes generated by somatic cell nuclear transfer, enabling fertilization and embryo development with integrated somatic and sperm chromosomes, highlighting a proof-of-concept for in vitro gametogenesis.

Aging is associated with increased atherosclerosis risk and a changing immune landscape. In this study, the authors examined T cell changes in atherosclerotic plaques in mice with age and report an accumulation of clonally expanded effector and memory CD8⁺ T cells, including Gzmk⁺CD8⁺ T cells, which have cytotoxic transcriptomic signatures.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Mouse lineage tracing in regenerating bone marrow after myeloablation shows a dynamic dedifferentiation of mature adipocytes into bone marrow stromal cells. Lipolysis disruption obstructs adipocyte dedifferentiation and hematopoietic stem cell regeneration.

High-resolution satellites reveal major uncertainties in methane emissions from global waste sites, highlighting the need to reconcile observed and reported data, with actionable insights to improve estimates and guide targeted mitigation efforts.

Ramachandran et al. identify a previously unappreciated function for transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength, and provide mechanistic insight into the molecular underpinnings of this function.

Happloinsufficiency of Myc delays onset of cancers in mice. Here, the authors generated a mouse model of reversible cMyc hypomorphism and show that metronomic reduction of c-Myc in adult mice confers protection against cancers without side effects and that the bottleneck in early cancer evolution is dependent upon Myc.

Using various mouse models, human plaque data and isolated B cells combined with state-of-the-art imaging and transcriptomic analysis, the authors show that the G-protein-coupled orphan receptor GPR55 regulates B cell activation and plasma cell differentiation during hypercholesterolemia, which crucially affects atherosclerosis.

Reduced sulfate aerosols due to ship fuel regulation may increase shortwave radiation on the Great Barrier Reef, exacerbating the impact of marine heatwaves on coral bleaching, according to model analysis of ship emission impacts on aerosols, clouds and solar radiation.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Magmas beneath the Main Ethiopian Rift ascend through the crust on timescales of only weeks to months, indicating that, during continental rifting, a magmatic plumbing system can be well established before the lithosphere has thinned.

Broad-spectrum vaccines have been proposed as a tool for rapid response to emerging infectious disease threats and are in pre-clinical development. Here, the authors use mathematical modelling to assess the potential impacts of broadly protective sarbecovirus vaccines for a hypothetical “SARS-X” outbreak.

The authors describe stem cell-derived bone marrow organoids that accurately model the structural and functional properties of the human bone marrow niche.

An analysis of 52 million births in 26 countries shows small reductions in preterm birth during the first to third months of lockdown. Further research is needed to examine causal pathways.

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.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

The human pelvis exhibits distinct spatiotemporal ossification patterns and an ilium cartilage growth plate that is shifted perpendicularly compared with those of other mammals and non-human primates—two key adaptations that underlie bipedalism.

Cibisatamab is a T-cell bispecific antibody targeting the carcinoembryonic antigen (CEA) on tumor cells and CD3 epsilon chain on T cells. Here the authors report the results of two clinical trials of cibisatamab as monotherapy (NCT02324257) and in combination with atezolizumab (anti-PD-L1; NCT02650713) in patients with CEA-positive solid tumors.

This study uncovers a U-shaped trajectory in gray matter volume during pregnancy and postpartum, linked to hormonal changes. Brain recovery postpartum correlates with maternal attachment, highlighting the interplay between neuroplasticity, hormones, and maternal well-being.