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Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

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.

Carbapenemase blaIMP genes between 1996-2023 were analysed across 4,556 genomes, revealing variant-specific epidemiologies and endemicities. Horizontal gene transfer enabled broad inter-species transmission, along with expansion of successful clones.

Fungal parasites infect key nitrogen-fixing cyanobacteria during Baltic Sea blooms, drawing on carbon and nitrogen reserves. Here, authors find up to a fifth of newly fixed nitrogen is diverted to fungi in the cyanobacterium Dolichospermum, altering the fate of new nitrogen and trophic transfer.

Ramaglia and colleagues show that aberrant formation of B cell-rich lymphoid structures in the brain meninges is associated with high CXCL13:BAFF ratios. Inhibiting the kinase BTK reduces the lymphotoxin signaling needed to sustain such structures, lowers CXCL13:BAFF ratios and reduces cortical tissue injury.

In this work authors demonstrate how photocontrolled tag-targeted degradation enables precise, spatiotemporal control of protein expression in tumor cells and CAR T cells, offering an esapproach for regulating engineered proteins with light.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

Breast cancer has been associated with long term negative personal and household level economical impact in survivors. Here the authors find that while financial losses exist across the population, they are mitigated by robust social safety nets however, certain subgroups including students and individuals with poor baseline health, experience a disproportionate economic burden that persists long after diagnosis.

In ancestral SARS-CoV-2 infection, NK cell interferon-stimulated gene (ISG)-driven activation correlated with poor antibody breadth. In vitro, NK cell ISG expression boosts cytotoxicity toward T_FH-like cells, suggesting a mechanism for impaired antibody responses.

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).

Translation initiation and elongation factors can be targets for cancer treatment. Here, the authors show that inhibiting translation elongation through eIF5A impairs mitochondrial function, slowing the proliferation of tumour cells.

The study reports a metal-organic framework (MOF) - covalent organic framework (COF) nanocomposite with dual amine sites that captures CO₂ efficiently and remains stable under humid, harsh conditions, offering a promising path for next-generation carbon capture.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

It remains uncertain whether genetic variants and day–night cycles affect the efficacy of drugs in acute disease settings. Here, the authors show that metoprolol reduces risk only in patients who carry two Arg389 alleles of the beta-1 adrenoceptor, and specifically when myocardial infarction occurs at the beginning of the light cycle.

Metagenomes from prairie soils in Kansas, USA, show how historical exposure to water stress impacts soil microorganisms and subsequently drought responses in plants.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Risk stratification in non-small cell lung cancer (NSCLC) remains challenging. By combining multiplex immunofluorescence, H&E histology, and AI, the study identifies spatial “cell-niche” patterns that enhance survival prediction beyond UICC8 staging. These patterns reclassify many stage I patients as high risk, revealing potentially undertreated cases and establishing spatial tumor microenvironment features as clinically actionable biomarkers.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

This Review outlines the fundamental role of chimeric antigen receptor (CAR) T cell therapy for children, adolescents and young adults (CAYAs) with relapsed and/or refractory B cell acute lymphoblastic leukaemia, emphasizing the crucial need to further exploit CAR T cells and other immunotherapies to improve survival with broadened access across disease states. Opportunities and challenges for expanding CAR T cell therapy to other haematological and non-haematological malignancies in CAYAs are also discussed.

Rad51/RecA filament formation is key to homologous recombination. Here the authors combine structural studies with analyses in yeast to show that an 85-residue segment of Rad52 acts as a chaperone that binds Rad51 monomers promoting nucleation on ssDNA and counteracting the Srs2 translocase.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Saturation mutagenesis screening examines 11,520 point mutations in the kinase domains of FGFR1, FGFR2, FGFR3 and FGFR4, identifying their activating and resistance properties to the FGFR inhibitors pemigatinib and futibatinib.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

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

This work uses gene expression and single cell analyses to group extrapulmonary tuberculosis patients into three immune types, revealing immune pathways driving pathogenesis and markers that could improve diagnosis and guide tailored treatments.

The authors develop a microwave interferometer method to measure how electric and acoustic waves mix inside piezoelectric materials. Using this approach, they detect and quantified electric-acoustic heterodyning in lead zirconium titanate, showing the mixed signal scales linearly with both input powers.

Analyzing 12,000 metaphors of AI from a year-long U.S. survey, this study introduces a scalable framework for quantitatively analyzing implicit perceptions from open-ended language and shows that Americans increasingly view AI as warm and human-like.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Nguyen et al. show that the splenic environment provides sequential signals via lymphotoxin and retinoic acid that guide cDC2A development and retention.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Viral proteins can achieve high multifunctionality, but mechanisms are poorly understood. This study shows structural flexibility of rabies virus P protein enables RNA binding and phase separation to expand functions by infiltrating host condensates.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

The genetic basis of sex differences in Alzheimer’s disease (AD) is not well characterized. Here, authors report 2,320 sex-specific gene associations with 3 AD endophenotypes using bulk RNAseq data from 3 brain regions in ROS/MAP.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

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.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

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.