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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.

Immunoglobulin M (IgM) is the Ig isotype that serves as the first line of host defence during infection. Here, the authors image the full-length IgM pentamer by cryo-EM, revealing the structure and hinge motion of the antigen binding domains.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

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.

Single-cell transcriptomic analyses delineate the differentiation of human iPSCs into ectodermal ocular lineages, highlighting defined developmental trajectories and the sequential formation and maturation of distinct ocular cell types in vitro.

Plant functional diversity is highly dynamic over time, driven by seasonal cycles and wet–dry periods and varying across biomes, based on an analysis of over 4,000 hyperspectral satellite scenes at the global scale.

This study shows that photosynthesis in the Arctic Ocean can occur at lower light levels than previously thought. This finding is based on unique measurements made on microalgae underneath sea ice in the high Arctic at the end of the polar night.

Insights into Late-Pleistocene Northern Hemisphere storm track variability are hampered by a lack of well-dated proxy records. Here, the authors present a precisely dated record of meteoric precipitation between 30 and 14.7 ka, and show that obliquity may have played a vital role in Alpine glacier advance.

Although synchrotron facilities routinely operate in a multi-bunch regime for maximum average brilliance, studies relying on time-of-flight schemes require single-bunch operation. Here, Holldack et al.isolate and apply single bunch X-ray pulses from multibunch radiation using pulse picking by resonant excitation.

Toxoplasma gondii virulence in wild-derived mice is restricted by Immunity-Related GTPases (IRG). Here, the authors show specific binding of the IRG tandem protein Irgb2-b1 with the virulence effector ROP5, and provide insights into how different ROP5 isoforms and IRG alleles shape virulence among T. gondii strains.

Dysregulated autophagy and mitochondrial function are two well-described hallmarks of aging. Here, the authors describe an unexpected age-associated upregulation of mitophagy in response to neuroinflammation triggered by leaked mtDNA.

While hydrogen offers a potential carbon neutral fuel, its production from water using earth-abundant, heterogeneous materials has proven challenging to understand. Here, authors present a series of molecular electrocatalysts based on molybdenum, sulphur, and oxygen for aqueous hydrogen evolution.

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.

Here, the authors present mtDNA and chronological data for sediments from excavations in the South Chamber of Denisova Cave, from which they construct a timeline of hominin and faunal occupation that fills stratigraphic gaps in other parts of the cave.

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.

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.

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.

CHIMERYS is a spectrum-centric and data acquisition method-agnostic algorithm for the analysis of MS2 spectra. It is capable of deconvoluting any MS2 spectrum, regardless of whether it was acquired by DDA, DIA or PRM, thus unifying the analysis of bottom-up proteomics data.

The conduction electron and magnon interactions are essential for the understanding and development of spintronics and superconductivity. Here the authors show a deep binding energy kink in spin-resolved photoemission spectra which is understood as a signature the many-body spin flip excitation in Fe single crystal thin film.

Bacillus anthracis causes the infectious disease anthrax. Here, the authors synthesized deoxy glycosides that are effective against B. anthracis and related bacteria and found that these amphiphilic compounds kill bacteria via an unusual mechanism of action.

Retinal pigment epithelium (RPE) plays an important role in diabetic retinopathy (DR) progression. Here, the authors show AKT1 and AKT2 are reciprocally regulated in the RPE of DR donor tissue and diabetic mice, reducing Akt2 in RPE causing a compensatory increase in Akt1 and attenuating DR.

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.

Conodonts, early vertebrates, are thought to have evolved complex tooth tissue as an adaptation for feeding. Here, the authors use Electron Backscatter Diffraction to show increasing dental crystallographic order through conodont evolution, in parallel with dietary adaptations.

In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.

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.

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.

Advances in electron microscopy are enabling ever smaller features to be probed, with the measurement of atomic electric fields standing as a major challenge. Towards that aim, Müller et al.present a simplified theoretical approach for enhancing the resolution in differential phase contrast microscopy.

Tropical forests and savannah are more resilient to climate disturbances when they have been exposed to higher rainfall variability in the long-term past, finds an analysis of Brazilian rainfall and tree-cover observations.

Quantum light sources operating at telecom wavelength are a long-sought goal for quantum technologies. Here, the authors show electrically injected emission of single photons and entangled photon pairs from indium phosphide based quantum dots, operating up to a temperature of 93 K.

Polymers are known to spontaneously produce micro- and nanoplastics but the mechanisms by which environmentally-triggered Å-level random bond breaking events lead to the formation of these relatively large fragments are unclear. Here, the authors show that chain scission accumulates in the amorphous phase of a semicrystalline morphology which leads to mechanical failure and the concurrent release of nanoplastics even under quiescent conditions.

Premature truncations of ASXL1, a subunit of a deubiquitinase complex, are frequent in myeloid leukemia. Here, the authors show that expression of truncated ASXL1 in a haematopoietic precursor cell line enhances the deubiquitinase activity and leads to differentiation to the mast cell lineage.

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, but its spike protein doesn’t efficiently bind human ACE2. Here, the authors show that exchange of spike residue 403 between RaTG13 and SARS-CoV-2 spike proteins affects binding to human ACE2 and entry of pseudotyped viruses.

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.

Mycoplanecins show promising activity against tuberculosis. Here, the authors identify and study mycoplanecins’ biosynthesis, antibacterial effects, and binding mechanism to DnaN, suggesting potential for fighting multidrug-resistant tuberculosis.

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.

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.

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.

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.

This analysis shows that demand-side policies can reduce emissions by 51–85% in buildings and 37–91% in transport by 2050, with electrification having the greatest impact. Adopting a mix of strategies offers benefits for the overall energy system.

Our ability to identify associations between behaviour and brain imaging is important for uncovering markers of cognition and disease. Here, the authors illustrate the importance of the reliability of behavioural measurements to accurately investigate brain-behaviour associations using machine learning.

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.

Here, the authors demonstrate Phospho-seq, a single-cell multiomics method capable of quantifying chromatin accessibility alongside intracellular proteins, including post-translationally modified proteins. Then, they apply Phospho-seq to organoid models of neurodevelopment.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.