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Respiratory virus genomic surveillance output is unevenly distributed globally. Here, the authors show that addressing this imbalance could substantially reduce the time to first detection of novel (variant) viruses, enhancing surveillance effectiveness and efficiency.

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.

Dendritic cells (DCs) are required to establish thymic central tolerance. Here Srinivasan et al. use single-cell transcriptomics to define thymic conventional dendritic cell (cDC) subsets and find that CD8⁺ single-positive thymocytes modulate the thymus environment to regulate plasmacytoid DC and cDC2 homeostasis and interferon signatures in DCs, while CD4⁺ single-positive thymocytes regulate cDC1 activation via cognate and CD40L–CD40 interactions.

In colorectal cancer, therapeutic resistance is driven by MAPK-dependent epithelial cell plasticity.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Nucleoside triphosphates (NTPs) are important building blocks that underpin emerging enzymatic approaches to RNA therapeutics manufacturing. Here, authors develop a biocatalytic strategy to convert nucleosides into NTPs containing clinically relevant modifications, using simple phosphate donors.

LEVA is a label-free immobilization method for studying surface-bound extracellular vesicles.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Recognition of tumour antigen induces dendritic cell activation and migration to the lymph node. Here, the authors use photoconvertible mice to demonstrate that some activated dendritic cells are retained in tumours and gradually lose function, but their ability to support local anti-tumour responses can be augmented by anti-PD-L1 blockade.

Borgs are large extrachromosomal elements of anaerobic methane-oxidizing archaea. Here, via in silico protein structure prediction of ~10,000 Borg proteins, the authors reveal that Borgs share numerous features with giant eukaryotic viruses, suggesting that Borgs have a viral-like lifestyle and evolutionary convergence of large extrachromosomal elements across the Domains of Life.

High-resolution imaging and biochemical approaches provide insights into the structural and functional changes in the host cell nucleolus upon canine parvovirus infection.

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.

Many cancers metastasize to the lungs, yet immune cells rarely succeed in eliminating them. Here we show that although NK cells that patrol the lung vasculature are highly differentiated and cytotoxic to circulating tumor cells, these fail to access extravasated lesions, while NK cells that infiltrate the tumor parenchyma are less differentiated, exhibit poor cytotoxicity functionally restrained by TGF-β, allowing metastatic tumors to persist.

Global shark and ray populations have declined sharply, driven by expanding fisheries and inequitable gaps in catch, trade and distribution data. This Review assesses global status, highlights drivers of decline, and outlines the regulatory, market-based and conservation actions needed to reduce mortality and reverse shark and ray biodiversity loss.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

Satellite altimetry reveals intensifying global river water level variability (2016–2024) through increased seasonality, reduced seasonal fluctuations, and escalating hydrological extremes, signaling dual stress from concurrent droughts and floods.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Catalytic solvent regeneration is of interest to reduce energy consumption in CO2 separation, however, the development of engineered nanocatalysts remains a challenge. Here, a new avenue is presented for the next generation of advanced metal-organic frameworks (MOFs) in energy-efficient CO2 capture.

Zonal positioning in the liver determines whether the CTNNB1 oncogene can induce liver cancer.

Here the authors identify adenophages, a previously unknown macrophage population present in exocrine glands in mice and humans. These cells are dependent on ILC2-derived GM-CSF and support glandular homeostasis.

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.

Combining high-resolution mapping of foliar and herbivore faecal sodium concentrations across Africa, the authors show that plant-derived sodium availability constrains megaherbivore densities at a continental scale.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

Santos et al found that the ubiquitin ligase adaptor Fbxo42 is a critical regulator of terminal Unfolded Protein Response signaling through its control of Ataxin-2 granules containing Xbp1 mRNA.

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.

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.

Though understood to exist in large numbers, intermediate-mass black holes are difficult to identify. This Perspective makes a case for the use of time-domain variability studies to increase the known intermediate-mass black hole population.

Investigation of the reaction process at the single-bond interface is key to understanding the catalytic reaction mechanism. Here, the authors develop a STM-BJ method to monitor the catalytic process from the perspective of single-bond energy.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Active fluids exhibit properties reminiscent of equilibrium systems when their degrees of freedom are statistically decoupled. A theory for the fluctuating hydrodynamics of these fluids offers a probe of their anomalous transport coefficients.

How Meckel-Gruber syndrome protein TMEM67 functions in ciliogenesis and Wnt signaling simultaneously is unknown. Here the authors show that TMEM67 is proteolytically cleaved by the matrix metalloproteinase ADAMTS9 generating two functional isoforms.

Crystal structures of cyanobacterial protochlorophyllide oxidoreductases reveal the basis of the photocatalytic activities of this enzyme, through the role of its active site in enabling the light-driven reduction of protochlorophyllide.

Molecular glues are monovalent compounds that can recruit a protein of interest to an E3 ligase so the protein of interest can be targeted for degradation. Here, Hughes et al. identify a molecule that selectively and potently degrades BRD9.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Tumour endothelial cell macropinocytosis is the dominant mechanism for nanoparticle entry into the tumour. Enhanced nanoparticle tumour accumulation may be due to upregulated macropinocytosis membrane ruffling compared with most healthy tissues.

PRPF8 is a hotspot for mutations causing retinitis pigmentosa-type 13. Here the authors generated PRPF8 patient-specific retinal cells, demonstrating an important role for this splicing factor in spliceosome kinetics and 5’ splice site selection.

The crystallographically forbidden fivefold symmetry in icosahedra remains a long-standing mystery. Here, the authors resolve the three-dimensional atomic structure of Janus-like icosahedral nanoparticles with atomic resolution by electron tomography.

Terrestrially derived dissolved organic carbon is pervasive in the Arctic Ocean, especially within the Transpolar Drift current, and changing inputs could impact future marine carbon cycling, according to a dissolved organic carbon inventory.

As presented at the American Heart Association Conference 2025, patients with chest pain and without obstructive coronary artery disease benefit from treatment informed by cardiovascular magnetic resonance.

Phenomic and genomic approaches are required to evaluate the progress of breeding strategies. Here, the authors analyse 65 years of genetic progress in maize, showing that breeders have selected traits with stable effects on yield whereas not for adaptive traits key for climate change adaptation.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.