Search

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.

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.

This study reports highly selective Li⁺Mg²⁺ separation via concentration gradient-driven transport using negatively charged membranes with high charge content. The separation mechanism involves selective partitioning of Li⁺ ions into the membrane and uphill transport of Mg²⁺ ions. Bench-scale diffusion dialysis experiments with model brine solutions demonstrate effective monovalent/divalent ion separation.

Electrochemical CO reduction to multi-carbon products offers a carbon-negative approach to produce chemicals, but the intricate reaction pathways lead to a broad spectrum of products. Now it has been shown that alkali cations alter the mechanistic pathways that govern the reaction selectivity involved in the formation of hydrocarbons versus oxygenates.

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

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

During the Last Glacial Maximum, the deep Northwest Atlantic was only about 2 °C colder than today, suggesting sustained production of relatively warm North Atlantic Deep Water during the Last Glacial Maximum.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

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.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

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.

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.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Soil microbial populations bloom and then die-off in ecosystems with seasonal snowpack. This study showed that distinct taxa utilize different N sources for growth or energy during the microbial bloom and alter the fate of N after snowmelt.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

Fractional Chern insulators have been observed in moiré MoTe₂ at zero magnetic field, but the expected zero longitudinal resistance has not been demonstrated. Now it is shown that improving device quality allows this effect to appear.

Lithium has an essential role in the brain and is deficient early in Alzheimer’s disease, which can be recapitulated in mice and treated with a novel lithium salt that restores the physiological level.

Garnet-type LLZO electrolytes are considered among the most promising solid-state electrolytes for all-solid-state batteries; however, numerous challenges need to be addressed before they are integrated into a cell. By precipitating amorphous zirconium oxide onto grain boundaries, increased ionic conductivity is observed and dendrite growth is suppressed.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

Lithium-ion batteries rely on lithium diffusion within particles, traditionally assumed to follow concentration gradients. Here, authors use X-ray microscopy to track lithium movement in single particles, discovering that lithium can move against concentration gradients due to strain effects.

Liu, Liu, Wu and Yao et al. developed a peptide inhibitor that selectively blocks the Ada-two-A-containing histone complex by targeting the YEATS2 YEATS domain and suppresses tumor growth in non-small cell lung cancer.

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.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Tools to identify who will develop Crohn’s disease in the future are limited. Here, the authors develop and validate a proteomics-based model that predicts disease onset up to 16 years before clinical diagnosis.

Seasonal variation in K isotopes of rivers that drain the Chinese Loess Plateau indicates that riverine K isotopes can trace changes in silicate weathering intensity over time, offering a tool to track Earth’s climate–rock interactions.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Li-metal batteries often utilize liquid electrolytes that yield a solid–electrolyte interphase on electrodes; however, the role of anions in interphase formation remains unclear. Now it has been shown that anion-decomposition products provide varying contributions to interphase formation and that high-performance electrolytes balance effective interfacial passivation with minimized degradation.

A forward genetic screen in Caenorhabditis elegans reveals that decreased levels of the ferredoxin FDX2 suppress the loss of frataxin in worms and in mice by relief of FDX2 inhibition of frataxin-stimulated NFS1 activity.

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.

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.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

Volcano plots are useful catalyst design tools for acidic oxygen reduction reaction, but have proved less successful for alkaline oxygen reduction reaction. Here, a modified volcano plot for this environment is developed and used to design PdH_x@Pt nanosheets with high oxygen reduction reaction performance.

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.

This work identifies ERECTA–EPFL genes as major regulators of maize meristem activity and the development of maize shoots and ears. The findings highlight genetic targets that influence kernel row number and plant architecture to increase maize yield.

Human genetic variation influences instability of DNA repeats that commonly expand as we age.

The authors conduct a national inventory on individual tree carbon stocks in Rwanda using aerial imagery and deep learning. Most mapped trees are located in farmlands; new methods allow partitioning to any landscape categories, effective planning and optimization of carbon sequestration and the economic benefits of trees.

Proton-exchange membrane water electrolysers rely on iridium to catalyse their anodic reaction, and while ruthenium is a less costly alternative due to its similar activity, it is not as stable. Now, a hierarchical machine-learning catalyst discovery workflow, termed mixed acceleration, is put forward to predict catalyst synthesis, activity and stability, and identify promising RuO_x-based water oxidation catalysts.

A COVID vaccine developer, an Arctic voyager and a prime minister are some of the people behind the year’s big research stories.

Materials with variable and reversible thermal conductivities are important in technologies, and yet such materials are rare. Here, Cho et al. report in situmeasurements of thermal conductivity of lithium cobalt oxide, and show how to reversibly modulate thermal conductivities over a considerable range.

Analysis of shallow-water marine carbonate samples from 101 stratigraphic units allows construction of a record of lithium isotopes from the past 3 billion years, tracking the evolution of the global carbon and silicon cycles.

Here, the authors show that two residues in FDX1 control both protein lipoylation and copper-induced cell death, suggesting these roles are interconnected. They also identify DLD as an upstream regulator that strengthens FDX1’s link to the lipoylation pathway.