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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.

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.

Single strontium atoms are trapped in optical tweezer arrays generated via holographic metasurfaces, overcoming a critical barrier to realizing scalable neutral-atom quantum technologies.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

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.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Kumazawa, Xu, Wang and colleagues identify nuclear egress as the mechanism by which cytoplasmic chromatin fragments relocate from the nucleus to the cytoplasm in senescence. They link inflammation to metabolism by showing this egress is regulated by AMPK and metformin.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

An atomic stencilling method based on the co-adsorption of iodide and 2-naphthalenethiol on gold is described, yielding more than 20 different types of nanoparticle with masked and painted regions and patchy particle morphologies not reported previously.

The authors find low-energy magnetic excitations and a flat band near the Fermi level in kagome metal superconductor CsCr3Sb5 by angle-resolved photoemission and resonant inelastic X-ray scattering. They suggest that the flat band plays a role in the emergence of charge/magnetic order at low temperatures.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Here, the authors demonstrate a multi-momentum transformation metasurface. The orbital angular momentum meta-transformer reconstructs different vortex beams into on-axis distinct patterns, and the linear momentum meta-transformer converts red, green and blue beams to vivid color images.

Electroreduction of CO₂ into C2 hydrocarbons and liquid fuels is a promising but challenging energy conversion technology, with copper exhibiting fair selectivity for these products. Here, the authors report that N-doped graphene quantum dots can also catalyze the electrochemical reduction of CO₂into multi-carbon hydrocarbons and oxygenates.

Single layers of group-VI transition metal dichalcogenides have emerged as direct bandgap semiconductors in the two-dimensional limit. The authors show that monolayer molybdenum diselenide is an ideal system enabling electrostatic tunability of charging effects in neutral and charged electron-hole pairs, so-called excitons.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

Experimental demonstration of quantum speedup that scales with the system size is the goal of near-term quantum computing. Here, the authors demonstrate such scaling advantage for a D-Wave quantum annealer over analogous classical algorithms in simulations of frustrated quantum magnets.

In situ methods for water quality monitoring is crucial for global water use and management, though many conventional sensors have slow response time and are non-recyclable. Here, the authors report a recyclable amphiphobic dielectric material for fast monitoring of water pollutants.

The authors use time-resolved scanning near-field optical microscopy to probe the ultrafast excitonic processes and their impact on waveguide operation in transition metal dichalcogenide crystals. They observe significant modulation of the complex index by monitoring waveguide modes on the fs time scale, and identify both coherent and incoherent manipulations of WSe₂ excitonic resonances.

Amino acid changes in the envelope and non-structural 2A protein attenuate the virulent yellow fever virus (YFV) and enhance host antiviral responses upon infection in vivo. These traits explain the potency of the YFV vaccine.

Eye2Gene’s next-generation phenotyping of multimodal images increases diagnostic yield for inherited retinal diseases by improving screening, phenotype-driven variant prioritization and automatic similarity matching in phenotypic space to drive gene discovery.

Silver nanoparticles with thin palladium shells are active and selective catalysts for the production of hydrogen from formic acid at room temperature.

Oby, Degenhart, Grigsby and colleagues used a brain–computer interface to challenge monkeys to override their natural time courses of neural activity. They found the time courses to be highly robust, suggestive of network-level computational mechanisms.

Smargon et al. show that small nuclear RNAs can improve the cellular safety and efficacy of endogenous protein-mediated RNA base editing, enhancing nuclear RNA editing and the rescue of premature termination codon disease.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Broadly neutralizing antibodies (bNAbs) are promising as potential therapies targeting HIV-1 but their overall antiviral activity remains to be fully elucidated. Here the authors evaluate the ability of a panel of bNAbs to trigger antibody-dependent cellular cytotoxicity and identify the most effective antibody combinations.

A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Electrophysiological, structural and biochemical studies on the bestrophin-2 anion channel reveal asymmetric permeability to glutamate and show that it forms a cooperative machinery in complex with glutamine synthetase for glutamate release.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Transcription factors (TFs) represent an emerging class of therapeutic targets in oncology. Here, the authors develop Epiregulon, a computational method that constructs gene regulatory networks from ChIP-seq, ATAC-seq and RNA-seq data for accurate prediction of TF activity at the single-cell level, thereby facilitating the discovery of therapeutics targeting TFs.

A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.

Brown adipose tissue (BAT) burns, rather than stores, energy and has thus been explored as a way to combat obesity. Aaron Cypess and his colleagues isolate neck fat from adult humans and show that BAT exists in this region, define its anatomical localization in the neck relative to white adipose tissue and demonstrate that it is functional.

Bestrophin anion channels are critical for the health of eyes. Here, authors identify multiple bestrophin activators including glutamate and γ-aminobutyric acid.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

An inverse design strategy is reported for the organization of nanoscale matter using DNA-programmable bonds and the fabrication of hierarchically ordered 3D assemblies.

During chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy through WSTF interaction with ATG8 in the nucleus, leading to WSTF nuclear export and its subsequent degradation.

Tomonaga-Luttinger liquid behavior has been observed within 1D defects in transition metal dichalcogenides. Here, using complementary experiments and engineered defects, the authors demonstrate the importance of graphene as a substrate and its role in the formation of this quasiparticle excitation in 2D WS₂.

Bestrophin-1 (Best1) is an anion channel genetically linked to eye diseases. Here, the authors identify GAD65 and GAD67 as Best1 activators with distinctive functional influences and characterize Best1 as a γ-Aminobutyric acid (GABA) type A receptor.

Detection of quantum oscillations in thermal transport could shed light on the origin of thermal Hall effect in correlated materials but it is challenging. Here the authors report quantum oscillations in the thermal Hall effect in the kagome metal CsV₃Sb₅ indicating strong violation of the Wiedemann–Franz law.

Deconvolution methods infer levels of immune infiltration from bulk expression of tumour samples. Here, authors assess 6 published and 22 community-contributed methods via a DREAM Challenge using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells.