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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.

Native crystallographic defects are often introduced during synthesis of battery materials, but has been overlooked. Here, using in situ synchrotron X-ray probes and electron microscopy, the authors have revealed their adverse effect during battery operation.

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.

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.

Precise editing of DNA methylation has emerged as a promising tool in disease biology but most applications are limited to in vitro systems. Here, we develop two transgenic mouse lines harboring an inducible dCas9-DNMT3A or dCas9-TET1 editor to enable tissue-specific DNA methylation editing in vivo.

This study leverages plasma proteomics from over 50,000 individuals to build organ-specific aging models and uncover underlying genetic mechanisms. It also investigates causal links between organ aging, diseases, and lifestyle, providing insights for promoting healthy longevity.

This study demonstrates how CO₂ directs defect control during the synthesis of Mn-rich sodium layered oxides, improving the stability and performance of earth-abundant positive electrode materials in non-aqueous sodium-based rechargeable batteries.

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.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Multi-ancestry genome-wide association meta-analyses of polycystic ovary syndrome in women of East Asian and European ancestries identify 94 independent susceptibility regions, including 73 novel loci.

Prostate cancers (PCa) are characterized by an immunosuppressive tumor microenvironment. Here the authors identify a subset of iron-loaded cancer-associated fibroblasts secreting myeloid cell-associated proteins and driving immunosuppression in PCa.

Immune interactions are complex, dynamic and difficult to capture using static imaging modalities on in vitro or ex vivo tissue cultures. In this Review, the authors discuss techniques for in vivo imaging of the immune system including one-photon near-infrared II fluorescence and two-photon and multiphoton microscopy for longitudinal tracking of immune cells, as well as a translational path that integrates near-infrared II, positron-emission tomography or MRI and artificial intelligence-enabled analysis towards quantitative, clinically compatible, multimodal immuno-imaging.

The study of isotopes away from the beta stability valley is crucial for the understanding of nuclear structure, especially for neutron-deficient heavy nuclei. Here, the authors report the observation of the alpha-decay isotope 210-protactinium (Pa), extending the alpha-decay systematics of underexplored regions of the nuclides chart.

Zhu and colleagues identify GREMLIN1 as an FGFR1 ligand that promotes plasticity and castration resistance in prostate cancer through regulation of MAPK signaling, and show that anti-GREMLIN1 antibody therapy synergizes with androgen deprivation.

Safe lithium-ion batteries require stable electrolytes with high chemical resistance and high thermal tolerance. Chen et al. find a solid lithium-salt electrolyte that is able to give rise to a prolonged battery life and a delayed decomposition of battery cathodes.

Zhu and colleagues show that a subpopulation of spleen-derived fibroblasts secrete Gremlin 1, which suppresses chronic myeloid leukemia progression by inducing leukemia stem cell apoptosis through the BMP signaling pathway.

Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype with limited effective therapeutic options. Here, the authors identify the RNA-binding protein ELAVL3 as a driver of differentiation into NEPC via a positive feedback loop with MYCN and demonstrate the use of the repurposed drug pyrvinium pamoate to target this axis using preclinical models of NEPC.

Crystallization of noble metal atoms usually leads to the thermodynamically stable face-centred cubic phase. Sunet al. show that internal strain in silver nanoparticles leads to lattice distortion and a stable body-centred tetragonal phase.

The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus.

The synthesis of atom-thin amorphous films remains challenging as their thermodynamically favourable grains are neither two dimensional nor layered. Here a droplet-driven nanoribbon-to-film growth strategy is reported to achieve amorphous metal chalcogenides at the single-layer limit.

An integration of 3D chromatin structure and gene expression at single-cell resolution has not yet been demonstrated. Here, authors develop a multi-omic data integration algorithm applied to a breast cancer model, identifying topologically conserved domains and integrated subpopulations.

The authors identify feeblin, an inhibitory compound of the proinflammatory TLR7/8/9-IRF5 pathway with therapeutic potential, which acts by binding SLC15A4 via an allosteric mechanism mediating degradation of its signaling partner TASL.

A combination of adenovirus-vectored and subunit protein intranasal vaccine enhances immune response against SARS-CoV-2 variants in animal models and humans.

The red fluorescent protein mScarlet3-H is bright, photostable and very robust to high temperature, chaotropic conditions and oxidative environments. mScarlet3-H works well in correlative light and electron microscopy, tissue clearing and time-lapse super-resolution microscopy.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

This study aims to address a critical knowledge gap concerning the unique microstructure in 3D-printed metals by quantitatively characterizing the phase and dislocation density during the printing process using operando synchrotron X-ray diffraction.

A scanning tunnelling microscopy study of monolayer FeSe on strontium titanate reveals that this intriguing system has a plain s-wave pairing symmetry.

The efficacy of cancer immunotherapy relies on the sufficient functional immune cells recruited. Here this group designs an abemaciclib-loaded supramolecular peptide hydrogel achieving sustained release after intratumoral injection to effectively induce cancer cell death and increase IL-2 secretion, thereby exerting immunotherapy for triple-negative breast cancer.

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

The conventional approach with applying self-assembled monolayer suffers from limited interface coverage and weaker dipole interactions. Here, authors employ ferroelectric molecule to construct a dipole layer, achieving certified efficiency of 25.36% for inverted perovskite solar cells.

CDK5 is known to drive glioblastoma tumorigenicity but the downstream molecular mechanism is unknown. Here, the authors show that CDK5 activates STAT3 signalling via the nuclear import of TRIM59, which leads to the degradation of the tumour suppressor macroH2A1.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Oxygen redox instability at high voltages hinders the application of high-energy battery cathodes. Here the authors report that elimination of domain boundaries in single-crystal cathodes improves the redox stability and consequently the electrochemical performance in extended high-voltage cycling.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The formation of organelles was a pivotal point in eukaryotic evolution. Here they show that Archaea possess Arf-like GTPases that can perform key organelle-producing mechanisms when expressed in a eukaryotic cell, laying the foundation for the evolution of endomembrane organelles.

Energy stress activates AMPK leading to metabolic plasticity and therapy resistance in cancer. Here, the authors show that AMPK activation decreases Prospero-related homeobox 1 (PROX1) levels impairing branched amino acid metabolism and tumourigenesis in liver and lung cancer models.

The shuttling effect in Li–S batteries can be drastically suppressed by using a single-atom Co catalyst and polar ZnS nanoparticles embedded in a macroporous conductive matrix as a cathode. Using this strategy, Li–S pouch cells show stable cycling and high energy performances.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Relating the degree of network crosslinking as a descriptor to the desalination performance of crosslinked polymer membranes remains challenging. Here, the authors introduce a parameter based on distinct amide bonds per unit mass of polyamide, to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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 LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

RNA polymerase II (Pol II) transcription factories play a central role in gene expression and 3D chromatin organization. Here, the authors demonstrate that RUVBL2 directly regulates Pol II clustering at active gene promoters.