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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.

Most studies assessing food self-sufficiency look at calories and neglect nutrient gaps. Comparing food demand and potential food production under land and water constraints, this study quantifies 9 key nutrient gaps for each of African’s 54 countries.

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.

Spiking neural networks are generally used for sequential information and event data processing but still lack high performance. Through algorithm and hardware co-design, Zhang et al. report a State Space Model based approach to implement on compute-in memory hardware, enabling asynchronous and real-time processing capability with high energy efficiency for event sequences.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Applications of optical laser-based techniques are limited by the long wavelengths of the lasers. Now, observations of phonons and thermal transport at nanometre length scales are reported with an all-hard X-ray transient-grating spectroscopy technique.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

Zinc is an essential micronutrient for plants, however its excess causes cellular damage. Here, the authors report that natural variation of Trichome Birefringence (TBR) gene confers zinc toxicity tolerance through modulating root cell wall pectin methylesterification in Arabidopsis.

This study demonstrates a low-energy photon device based on the kagome metal RbV₃Sb₅. It demonstrates that Fermi surface reconstruction, driven by a phase transition, leads to the emergence of van Hove singularities near the Fermi level.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Ferroelectric ordering of moiré excitons and collective photon emission emerge in WSe₂/WS₂ heterobilayers near the Mott state driven by strong dipolar interactions and a transition to symmetry-broken ferroelectric phases.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

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.

There is a lack of effective therapies for patients with non-V600E BRAF mutant cancer. Here, the authors report limited response in a phase II trial investigating the combination of binimetinib (MEK inhibitor) and encorafenib (BRAF inhibitor) for the treatment of non-V600E BRAF mutant cancer and subsequently investigate resistance mechanisms and combination therapeutic strategies in patient-derived models.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Butyrophilin 2A2 is a member of the B7 costimulatory family that is expressed on antigen presenting cells and is linked to the regulation of T cells. Here the authors implicate butyrophilin 2A2 in enhancement of CD45 phosphatase activity within the immunological synapse during T cell activation, leading to expansion of regulatory T cells and reduction of proinflammatory Th17 CD4 T cells.

Recent work has revealed that dendritic cells (DCs) are more heterogeneous than previously thought, yet the functional roles of these newly described DC subsets remain unclear. Here, Li et al. find that in mice, TSLP from keratinocytes activates transitional DC-derived DC2 to promote GATA3⁺ regulatory T cells and mediate immunosuppression during inflammation and cancer.

Root-knot nematodes locate host plants by sensing microbial volatiles shaped by plant defence metabolites, revealing a surprising ecological link between plant chemistry, soil microbes and parasite behaviour in the rhizosphere.

Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.

MsbA mediates the transport of lipopolysaccharide across the inner membrane. Here, the authors show specific MsbA-lipid interactions can tune the selectivity for binding ATP over ADP and present five structures of MsbA with one bound to lipid.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

The role of protein UFMylation in cancer remains to be understood. Here, the authors show that UFM1-specific ligase 1 and AKT positively regulate each other through UFMylation and phosphorylation, facilitating lipid synthesis and breast tumor growth.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

Magnetic heliknotons are hopfions embedded in helical spin backgrounds. Current-induced nucleation and Hall-effect-free motion of isolated magnetic heliknotons is demonstrated in the chiral magnet FeGe.

In this longitudinal cohort study, Wang et al. examine how depression and recall of adverse childhood experiences interact over time among Chinese university students.

The study introduces radio interferometric multiplexed spectroscopy (RIMS), a method designed to efficiently monitor the radio emissions of massive samples of stars. Applying it to LOFAR data, the authors identify stellar bursts, offering clues to possible star–planet magnetic interactions.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

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

The nuclear clock transition of ^229mTh in ²²⁹Th:CaF₂ crystals is characterized as a function of doping concentration, temperature and time, demonstrating high reproducibility and identifying ideal operating characteristics of these crystals as nuclear clocks.

Short-circuiting during fast charging through lithium dendrite intrusion into electrolytes is a major challenge in solid-state batteries. Here, using thermally annealed 3-nm-thick Ag coatings, lithium penetration into brittle electrolyte Li_6.6La₃Zr_1.6Ta_0.4O₁₂ is inhibited at local current densities of 250 mA cm⁻² due to an increase in surface fracture toughness.

Engineering of bacterial outer membrane vesicles to express anti-PD-L1 antibody and plasmids encoding the CAR target antigen boosts CAR-T therapeutic efficacy in solid tumours.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Fluorescence microscopy during CryoFIB milling produces an interferogram that can be used to direct lamella production to labeled structures with accuracy beyond the axial diffraction limit. The approach relies only on real-time feedback from the structure, requiring no image registration.

Dredging and dumping in the North Sea strongly disturb sediment and carbon fluxes, affecting coastal Blue Carbon systems. Global estimates show these activities rival natural fluxes and should be included in sediment and carbon budgets.

The authors develop textile electronic substrates with tailored stiffness and interfacial affinities by selective and controllable laser-matter interaction, addressing the mechanical mismatch between hybrid electronics and elastic textiles.

The Zhang-Rice singlet is known for the superconductivity of high-temperature superconductors cuprate but is rarely studied for an electrochemical catalyst. Here, the authors use operando spectroscopic tools and observe Cu active site evolves into high-valent CuO₄ geometry with Cu³⁺ active species, so-called Zhang-Rice singlet state, during oxygen evolution reaction.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

The magnitude of the increase in global river flow between 1980 and 2014 is 13.6% lower than Earth system models estimate and is expected to be 9.3% lower in the future, according to an analysis of emerging constraints on the components of the water cycle.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

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.

Jahn-Teller distortions alter molecular structures, but are usually only probed on the basis of electronic signatures. Here, the authors demonstrate that tip-enhanced Raman imaging in real space can map the associated vibrational changes in a single molecule.

An electrochemical cobalt-catalysed reductive coupling reaction between alkynes and cyclobutenes enables diastereodivergent cyclobutane synthesis. By modulating the steric and electronic properties of the proton source, the trans/cis diastereoselectivity is altered. Mechanistic studies indicate a Co(II)–hydride pathway, with selectivity arising from interactions between the cyclobutyl cobalt intermediate and the proton source.