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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.

Micromitophagy is found to occur in plant male germline cells, mediated by ATG5–HSP90.2 signalling, and is evolutionarily conserved in angiosperms. This mechanism underpins paternal mitochondrial elimination and supports the zygote-to-embryo transition.

Two-dimensional poly(arylene vinylene) frameworks are promising polymer semiconductors, yet obtaining highly crystalline materials is a major challenge. Now a series of 11 highly crystalline or single-crystalline 2D poly(arylene vinylene)s have been prepared—from 2D imine-linked covalent organic frameworks through a Mannich-elimination strategy—with diverse lattices, enhanced conjugation and specific surface areas up to 2,000 m² g⁻¹.

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.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

The Casimir effect is based on quantum electrodynamical effects between two electrically neutral objects in close proximity. Here Zou et al. observe the Casimir effect between two silicon components on a single micromechanical chip, allowing for an on-chip exploitation of the Casimir force.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

Composites of carbon nanotubes and superconductors provide technologically important new, or improved, functionalities. Here, with a chemical solution approach, well-aligned carbon nanotube forests embedded in a superconducting NbC matrix are shown to effectively enhance the superconducting properties of NbC.

The molecular basis for the enrollment of X family DNA polymerases in non-homologous end joining (NHEJ) is unclear. Here the authors elucidate the structure of Pol λ within the DNA-PK long-range complex and Pol μ in association with Ku70/80 and characterize the interaction between the BRCT domains of Pol λ and μ with Ku70/80.

The authors report on a method for precise control of stoichiometry and surface termination during thin-film growth of a wide range of perovskite ABO₃ phases that exploits dynamic B-site layer inversion seen in the in situ electron diffraction.

Previous ophthalmic foundation models have struggled to generalize effectively to diverse and rare fundus diseases, restricting their clinical applicability. Here, the authors introduce a vision-language foundation model that demonstrates superior performance in diagnosing both common and rare fundus conditions.

The stabilization of perovskites in both solution and solid phases is critical to the fabrication of solution-processed perovskite solar cells. Here, 4-(trifluoromethyl)phenylhydrazine is introduced to enhance storage stability, achieving consistent high efficiency of 26.0% in stable devices.

Stable and robust topological edge modes are observed at finite temperatures in an array of 100 programmable superconducting qubits because of emergent symmetries present in the prethermal regime of this system.

Phosphorus addition alone reduces phosphorus-acquiring enzyme activities by 14%, while phosphorus combined with nitrogen addition boosts nitrogen-acquiring enzyme activities by 21%, according to a meta-analysis based on 155 field studies across various ecosystems.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

Co-occurring mutations in the tumor suppressor LKB1 are frequent in KRAS-mutant lung cancers. Here, the authors show that LKB1 regulates JNK-dependent stress signaling apoptotic dependencies of KRAS-mutant tumors, making LKB1-deficient cells vulnerable to MCL-1 inhibition.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

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.

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.

¹⁴C can be absorbed by trees as a result of the interaction of cosmic rays produced by high-energy phenomena with the Earth’s atmosphere. Here, the authors observe a rapid increase of ¹⁴C in an ancient buried tree from BC 3372 to BC 3371, and suggest that it could originate from a large solar proton event.

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.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

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.

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.

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.

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.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

Reaching a quantum advantage in metrology usually requires hard-to-prepare two-mode entangled states such as NOON states. Here, instead, the authors demonstrate single-mode phase estimation using Fock states superpositions in a superconducting qubit-oscillator system.

Crystalline dispersoids are commonly used to strengthen metals by obstructing dislocation movement, but this often comes at the cost of ductility. Here, the authors demonstrate that amorphous nanoparticles, introduced via additive manufacturing, enhance both the tensile strength and fatigue resistance of metallic materials.

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-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

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.

Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.

Using spin-5/2 nuclei of ¹⁷³Yb atoms trapped in an optical lattice, a Schrödinger-cat state persists for a coherence time of 1.4 × 10³ s. In measuring external magnetic fields, the cat state exhibits a sensitivity approaching the Heisenberg limit.

Porous materials with very different pore sizes and structures are commonly used for various applications. But although bicontinuous pore networks — with two interwoven yet unconnected channels — have been reported, tricontinuous structures have so far only been predicted theoretically. Now, researchers have prepared a mesoporous silica with three identical, interpenetrating channels.

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.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

A high-confinement plasma that is potentially useful for controlled fusion has now been sustained for over 30 s. The Experimental Advanced Superconducting Tokamak in Hefei, China, achieved this record pulse length by first confining the plasma using lithium-treated vessel walls, and then maintaining it with a so-called lower hybrid current drive.

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.

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