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In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light.

Most rod-shaped bacteria elongate using a protein complex, the elongasome, that inserts new cell wall material into the cell sidewall. Here, Middlemiss et al. track the movement of individual elongasomes around the circumference of Bacillus subtilis cells, providing evidence for a molecular motor tug-of-war competition between oppositely oriented cell-wall synthesis complexes.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

The Southern Atlantic-Southwest Indian ridges hold mid-ocean ridge basalts with a residual subduction-related geochemical signature, whose origin is unsolved. The study suggests a link to a subduction-modified mantle transported inland >2280 km by a large-scale flat slab event.

Accelerating global warming is driving profound Arctic environmental change. The authors show that the structure and evolution of new stream networks are influenced by the evolving character of geometric ground patterns related to the response of permafrost to recent climate change.

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but establish good ligandability of ATG8 isoforms through fragment screening and docking.

In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked long-lived persistence of neoantigen-specific CD8⁺ T cell clones, which correlated with prolonged recurrence-free survival at a 3.2-year follow-up.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

Kao et al. provide insight into the metabolic requirements of IL-17A-producing γδ T cells, offering an actionable target to treat psoriasis by inhibiting fatty acid synthesis.

In quantum optical technologies, identical emitters of indistinguishable single photons are difficult to realize due to the inherent dissimilarity of each emitting device. Here, Rogers et al.demonstrate a solid-state uniform single-photon source, which does not require external tuning of optical properties.

In this Resource, the authors present FedProt, a tool that enables privacy-preserving, federated differential protein abundance analysis across multiple institutions. Its results match the results of centralized analysis, enabling secure, collaborative proteomics without sensitive data sharing.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Understanding how biosilica forms is crucial to our knowledge of this important biomaterial. Now, the role of collagen as structuring agent for the metre-long spicules of a primitive glass sponge has been revealed and found to have an unusual peptide motif.

Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.

A new Cretaceous arachnid fossil encased in Burmese amber sheds light on the evolution of spiders, as it preserves both primitive and derived features, suggestive of a basal Araneae position.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

A lack of models has hindered the study of Ebola virus (EBOV) persistence and sequelae, which are now shown to occur in rhesus monkeys. Progressive EBOV spread into eyes, brain and testes with CD68⁺ cells as the cryptic EBOV reservoir.

Mutations in mexZ, encoding a negative regulator of efflux pump genes, are frequently acquired by Pseudomonas aeruginosa during early lung infection, but do not confer high antibiotic resistance as measured in lab tests. Here, Laborda et al. show that mexZ mutations affect quorum sensing pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within tissues.

IL-27 promotes tumour control by preventing dysfunction and enhancing cytotoxicity of tumour-specific CD8⁺ T cells.

This work compares the preclinical lung biodistribution and efficacy profile of inhaled anti-CCN2 (cellular communication network factor 2) Anticalin® protein PRS-220 for the treatment for idiopathic pulmonary fibrosis (IPF) compared to systemic delivery of a CCN2 inhibitor.

Species-specific gamete recognition is needed to maintain species boundaries. Here, Müller et al. show that ARTUMES regulates pollen tube recognition between different Arabidopsisspecies, representing the first gene known to exclusively influence inter- but not intraspecific gamete interaction in plants.

A technique that combines retrograde axon tracing with single-cell transcriptomics is used to characterize neurons innervating pancreatic ductal adenocarcinoma and healthy pancreas, providing insight into the role of neural connections in cancer progression.

Müller-Tidow and colleagues demonstrate that hotspot DNMT3A mutations found in clonal hematopoiesis and acute myeloid leukemia render cancer cells sensitive to the DNMT1 inhibitor azacitidine through focal DNA demethylation, viral mimicry and interferon activation.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

There is considerable interest in generating broadband frequency combs at terahertz frequencies. Here, Tammaro et al.achieve this using coherent synchrotron radiation where the electron bunches emit quasi-synchronous terahertz pulses with high power, broad frequency, zero frequency offset, and high density.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

New treatments for cocaine use disorder (CocUD) require an understanding of the underlying neurobiology. Here, the authors show opposing effects of ZEB1 in CocUD and highlight disrupted synaptic signaling and phosphodiesterase inhibitors as potential therapeutic targets.

Polar ordering in materials enables fascinating properties; however, achieving beyond binary responses remains a challenge. Here, the authors demonstrate control on the polar-to antipolar transition and multiple polarization states in BiFeO₃ thin films.

Archaeopteryx had a mix of traits seen in non-flying dinosaurs and flying birds, leading to debate on whether it had powered flight. Here, Voeten et al. compare wing bone architecture from Archaeopteryx and both flying and non-flying archosaurs, supporting that Archaeopteryx had powered flight but with a different stroke than that of modern birds.

Mellman and colleagues present a multiomic single-cell analysis of the effects of combined anti-TIGIT and anti-PD-1 blockade on T cell populations trafficking from the draining lymph node to the blood and tumor.