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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.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Instabilities in chiral plasmas can amplify electromagnetic waves, raising the question of whether chiral solids behave similarly. Now a magneto-chiral instability is demonstrated in tellurium, observed as growing terahertz emission after photoexcitation.

The authors estimate genomic vulnerability for closely related species of rainbowfish. They find that narrow endemic species that have hybridized with a warm-adapted generalist show reduced vulnerability to climate change and that hybridization may facilitate evolutionary rescue for such species.

The intestinal microbiome is shaped by genetics and environment. Here, the authors show in rats that host genetic effects, including indirect social effects, influence microbiome composition, identify replicated loci, and reveal mechanisms contributing to microbiome heritability.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Little is known on how mitonuclear interactions influence genomic divergence among hybrid and parental lineages. A study of hybridizing wood warbler species complex finds a nuclear gene block with mitochondrial functions coevolves with mitochondrial genome, driven by climate-associated divergent selection underlying hybrid-parental population divergence.

Using a multiproxy dietary analysis combining stable isotopes, tooth microwear and dental calculus of the extinct South American proboscidean Notiomastodon platensis, the authors confirm that it consumed fruits and may have acted as a seed disperser. They assess evidence that its extinction has had cascading consequences for the plants whose seeds it used to disperse.

Data provided by Amazonian peoples are used to estimate the value of wild animals as a source of food, including its spatial distribution and nutritional value, providing information that will be key for improved management of forest ecosystems in the region.

Mejía-Ramírez, Iáñez Picazo, Walter et al. explore how nuclear biomechanical changes limit the regenerative capacity of aged hematopoietic stem cells and show that targeting RhoA rejuvenates aged hematopoietic stem cells by reducing nuclear envelope tension and remodeling nuclear architecture.

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.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

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.

This Perspective proposes the Population Neuroscience-Dementia Syndemics Framework and model to develop knowledge of how multiple factors may interact to perpetuate inequities in dementia, especially for women in low- and middle-income countries.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Selective paraffin capture to afford high-purity olefins directly is critical but still challenging. Herein, the authors discover a distinctive ultramicroporous material featuring closely packed and linearly-extended isophthalic acid units and thus serving as a paraffin nano-trap for the efficient production of ultra-high purity olefins from paraffins.

Stroke affects the brain in complex, highly individual ways. Here, the authors show that applying generative and causal AI methods to routinely collected brain scans may enable more closely personalized treatment recommendations.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Large-scale geographic heterogeneity in extinction and recovery across the Cretaceous–Paleogene boundary, as indicated by preserved insect-damage of fossil leaves in Patagonia and the Western Interior of North America.

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).

Recycled aggregate concrete could be used in place of natural aggregate concrete, reducing the need to mine aggregate and the generation of concrete waste. This Review describes the production, use and challenges associated with using this recycled material.

There are many open questions about biogeochemical function in peatlands. Here, the authors investigate the nitrogen cycle of tropical peatlands, finding that a surprisingly high fraction of nitrous oxide production is abiotic and that denitrification is a coupled abiotic-biotic process.

A new approach to determine nitrogen fixation rates in the world's oceans is used; it involves interpreting nutrient distributions in the context of an ocean circulation model.

Conversion of achiral starting materials into enantiopure products without additional chiral additives is a challenging task. Here, the authors show a reaction where the precipitation of chiral product induces autocatalysis, ultimately leading to an enantiopure compound.

Mammals host a diversity of parasites including lice. Using cophylogenetics and phylogenetic comparative methods, the authors show that the main lineages of placental mammal lice had a single common ancestor and find that all parasitic lice had an avian ancestral host.

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.

The spatial and temporal control of material properties at a distance have been so far achieved with light, heat, or sound. Here, the authors control chemical reactions and further polymerization of composites with an electric field via inverse piezo-effect resulting in multi-stiffness gels.

The study reveals that TGF-β–driven epithelial-mesenchymal transition disrupts bile duct development in biliary atresia. Inhibiting this pathway restores epithelial structure and reduces disease features, highlighting a potential therapeutic target.

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.

In this paper, the authors describe the energy state-dependent regulation of the PVN^GLP-1R to DVC circuit, resulting in altered food intake and metabolic health, mediated by GLP-1 receptor signalling.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

Single, self-amplifying RNA molecules condensed by an oppositely charged polyelectrolyte self-assemble into compact globular nanoparticles that can be used as vaccines to generate potent immunological responses at low doses.

Redox signalling is emerging as an important regulator of metabolism and physiology, which is dysregulated in ageing and disease. Here, the authors show that redox regulation of a key redox sensitive cysteine in Atg4a induces autophagy in vivo and extends lifespan in female Drosophila.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Mineralization is common in biological materials for selective strengthening, but similar toughening in polymer composites is challenging. Here, the authors report a mechanically-mediated reaction for formation of mineralized microrods within a synthetic material.

Analysis of isotope data from the Azores Islands provides evidence for deep recycling of material that had undergone fractionation near the Earth's surface. It is though that this component is from melt- and fluid-depleted lithospheric mantle and is 2.5 billion years old, whereas other Azores basalts have been estimated to contain from ∼3 billion-year-old melt-enriched basalt.

DNA circulating in the plasma of cancer patients carries features of the primary tumour, however such DNA is found in low levels in brain cancer patients. Here, the authors show that circulating tumour DNA can be detected in the cerebral spinal fluid of cancer patients and that this better recapitulates the primary tumour compared to DNA from the plasma.