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The ability to observe and control proteins in living cells is essential for biological research and drug development. Here, the authors engineer the self-labelling protein tag BromoCatch, enabling selective covalent labelling of fused proteins with biotin, clickable, fluorogenic, and degrader probes for protein manipulation and multiplex cell imaging.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

This study describes a novel mechanism of calcium control of metabolism found in the mitochondrial intermembrane space that is entirely independent of matrix Ca²⁺ uptake.

Atmospheric short-wave absorption due to wildfire smoke is caused predominantly by dark brown carbon particles, according to observations from smoke plumes in the United States.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Improvements in the Articulate Medical Intelligence Explorer, a large language model designed for diagnostic dialogue, enable the model to request, interpret and reason about multimodal medical data.

Methane emission from a very cool brown dwarf, perhaps arising from an aurora, has been detected in James Webb Space Telescope observations.

mRNA vaccine efficacy is enhanced by silencing cell-type-specific expression.

Human CEACAM6, which is widely expressed in the lung, is identified as a receptor used by the spike proteins of Cardioderma cor (heart-nosed bat) alphacoronaviruses to enter cells.

In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

An ‘intracrine’ signaling mechanism is proposed whereby a G-protein-coupled receptor (free fatty acid receptor 4) senses locally released fatty acids on intracellular membranes associated with lipid droplets to efficiently regulate lipolysis in adipocytes.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

Cyclin-dependent protein kinase 16 (CDK16) regulates various processes, including autophagy, spermatogenesis and cancer. Here, the authors show that 14-3-3 protein binding modulates the conformation of a key moiety of the CDK binding surface of cyclin Y, thereby enabling CDK16 activation.

In this individual participant data meta-analysis, and across 321,345 smartphone-ratings of affective well-being and nearly 1 million hours of physical activity measurement, Rehder et al. clarify the nature and extent of activity–well-being relations and document their relevance in humans’ everyday life.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Single-atom alloys can exhibit unique catalytic properties. Here, using reactivity measurements, atomic-scale imaging, simulation and spectroscopic analysis, it is shown that 1 atom% addition of Pt to Cu nanoparticles substantially decreases deactivation in single-atom alloys via sintering. A general predictive model of catalyst stabilization is developed.

Symmetry breaking is key to tissue formation. Now it is shown that symmetry breaking of epithelial spheroids is controlled by an interplay of collective migration with curvature and matrix remodelling.

Elevated eripheral serotonin reduces brown adipose tissue thermogenesis and promotes obesity and metabolic dysfunction.

Despite extensive structural studies elucidating how antigens are anchored to antigen-presenting molecules and presented to T cells, little is known about the display mechanism of the lipid-antigen-presenting molecule CD1c. Here, by combining structural immunology, lipidomics, and biophysical analysis, the authors reveal that the CD1c binding cleft accommodates two different lipids, one of them with a bulky headgroup positioned sideways for display to T cells, rather than upwards, different from the conventional upright antigen-presentation mode

Glucocorticoid receptor activation is a key driver of resistance of triple-negative breast cancer to both CD8⁺ T cells and natural killer cells during initial metastatic seeding.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Group II intron splicing in plant chloroplasts likely requires Maturase K, a relative of bacterial maturases. Here, the authors demonstrate that, unlike its bacterial ancestors, Maturase K acts within a heteromultimeric splicing complex.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Super spreading events are considered important contributors to the spread of COVID−19, but the extent to which superspreading varies by transmission setting is unclear. Here, the authors demonstrate heterogeneity in superspreading and the generation interval between COVID−19 cases in different settings using data from Hong Kong.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

How to choose a workplace that is welcoming and safe, and where your career will thrive.

Cowan and colleagues have developed a method to efficiently differentiate human pluripotent stem cells into functional white or brown adipocytes, through the transient expression of PPARG2 alone or in combination with CEBP and PRDM16. The programmed cells are able to give rise to ectopic fat pads with white or brown adipose tissue characteristics.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

A hand stencil painted on a cave wall on a small island off the coast of Sulawesi more than 67,800 years ago suggests a very early occupation of Wallacea.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

The isolation of catenated nitrogen compounds is difficult, in part because these chains can readily lose nitrogen, creating a strong thermodynamic push towards decomposition. Now, a series of molecules containing radical anions of four-atom nitrogen chains have been synthesized and studied under ambient conditions; the chain can cleave into N1 and N3 fragments, and can act as a source of nitrene radical anion.

Starburst galaxies are seen to host galaxy-scale winds, which are super-fast and could be powered entirely by the thermal pressure of gas heated by supernovae.

The early events preceding the development of morphological abnormalities represent a key gap in the understanding of cancer. Here, the authors employ an oncogenic tagging strategy to define the contributions of HIF1A and HIF2A to the cell-type specific early events in VHL-associated oncogenesis and support therapeutic targeting of HIF2A early in VHL-associated cancers.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

An atomic single electron transistor, which utilizes a single atomic defect in a van der Waals material as an ultrasensitive, high-resolution potential sensor, is used to image the electrostatic potential within a moiré unit cell.

Homogeneous catalytic hydroboration represents a valuable strategy for the synthesis of alcohols but reports which employ iron-based catalysts are somewhat limited. Here, the authors report an iron metalloborane complex as an efficient pre-catalyst for hydroboration of ketones, cyclic esters and CO₂ with mild conditions.

Early Pleistocene artefacts at Calio suggest that Sulawesi was populated by hominins at around the same time as Flores, if not earlier.