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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.

Comparative analyses of rice centromeres from 70 high-quality genomes of the Oryza AA group provide insights into rice centromere evolution and genetic factors that shape these genomic regions.

Metal–support interfaces play a crucial role in dictating the catalytic behavior of heterogeneous systems. Here, the authors reveal a unique looping metal–support interaction in NiFe–Fe₃O₄ catalysts, where spatially separated yet coupled redox cycles boost hydrogen oxidation, providing new insights for the design of efficient heterogeneous catalysts.

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.

A low-noise, fast avalanche photodetector that operates in the 1,550 nm telecommunications band provides high sensitivity for data communications applications.

Here the authors analyze data from COVAIL trial participants receiving an mRNA second COVID-19 vaccine boost and show that, while neutralizing antibody titer is correlated with Omicron COVID-19 risk, the correlation is weak in naïve individuals compared to previously infected ones.

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Yeast surface display technology enables real-time monitoring and effective screening of libraries of millions of disulfide-cyclised peptides against diverse protein targets. Selected ligands are characterised rapidly and quantitatively without the need for chemical synthesis and purification.

A cryo-electron microscopy study of the gasdermin D pore reveals a model of pore assembly and a charge-based mechanism for the preferential release of mature cytokines.

A protein foundation model represents protein sequence, structure and function.

Covalent inhibitors that selectively target bacterial enzymes are potential antibiotic drug candidates. Here, the authors apply high-throughput screening to identify selective covalent inhibitors that target serine hydrolases in Staphylococcus aureus

Covalent inhibitors with high selectivity are rapidly identified by phage display.

Gene modules are widespread and important for studying cancer. Here, authors propose an explainable deep learning-based framework, CGMega, which incorporates multi-omics information from the three-dimensional genome, epigenome, and protein-protein interactions to dissect cancer gene modules.

Vascular smooth muscle cells (VSMCs) are known for their fate plasticity in atherosclerosis plaque progression. Here, Zhai et al. show that extracellular traps generated from CD68 ⁺ VSMCs adversely contribute to plaque progression and highlight their unexpected role in plaque stability by regulating the direction of VSMC trans-differentiation.

Dysfunction of enteropeptidase (EP) can result in pancreatitis, a life-threatening disease. Yang et al. report a series of EP structures representing the EP catalytic cycle and propose a mechanistic model of enzyme function.

Kagome materials host 2D planes which give rise to kagome physics, but these are typically embedded in the bulk. Huang et al. demonstrate a strategy for generating surface kagome electronic states by vertical p-d electronic hybridization between surface atoms and the buried Co kagome network in Co₃Sn₂S₂.

Structures of complexes containing GajA and GajB proteins of the prokaryotic Gabija anti-phage defence system reveal the mechanism of its activation after DNA cleavage upon ATP depletion.

Disulfiram is an FDA-approved drug for treating alcoholism. Wu and colleagues show that disulfiram can be repurposed to efficiently inhibit pyroptosis by specifically blocking gasdermin-mediated pore formation.

High-resolution cryo-electron microscopy structures of the membrane-pore-forming domain of the mouse gasdermin GSDMA3 show that it forms pores with 26-, 27- or 28-fold symmetry and indicate that it may also form a parallel, soluble, pre-pore ring structure.

In the CNS, glutamatergic neurons directly control functional hyperemia via synaptic-like transmission onto arteriolar smooth muscle cells. Inhibiting this process reduces brain atrophy following cerebral ischemia.

Tumor associated macrophages (TAMs) contribute to the immunosuppressive tumor microenvironment, including hepatocellular carcinoma (HCC). Here the authors show that macrophage-derived microparticles modified with a M2-like macrophage targeting peptide and loaded with the TLR7/8 agonist resiquimod reprogram TAMs from immunosuppressive to inflammatory, promoting anti-tumor immune responses in preclinical HCC models.

Phase separated p62 body plays pivotal roles in autophagy. Here, the authors describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation.

Epithelial cells can use an immune-like mechanism to extrude neighboring precancerous cells; however, the recognition and control mechanisms of this process are unclear. Maruyama and colleagues demonstrate that LILRB3 on normal epithelial cells recognizes elevated MHC class I on transformed cells and triggers the extrusion process.

Continuous industrialization and human activities have led to severe water quality deterioration. Here, a structure-function integrated system is developed by Douglas fir wood inspired metamaterial catalysts with robust and high throughput water purification performances.

How β-AR signaling coordinates epigenetic and transcriptional pathways is unknown. Here the authors show that cold-induced β-AR signaling negatively regulates MYPT1-PP1β phosphatase activity to orchestrate both pathways for beige adipogenesis.

The gasdermin E protein is shown to act as a tumour suppressor: it is cleaved by caspase 3 and granzyme B and leads to pyroptosis of cancer cells, provoking an immune response to the tumour.

A scalable approach is provided for preparing and verifying intermediate-scale genuine entanglement on a 66-qubit superconducting quantum processor.

Achieving shape assembly behaviour in robot swarms with adaptability and efficiency is challenging. Here, Sun et. al. propose a strategy based on an adapted mean-shift algorithm, thus realizing complex shape assembly tasks such as shape regeneration, cargo transportation, and environment exploration.

Direct seawater electrolysis is promising for sustainable hydrogen production but suffers severe side reactions and corrosion. Here, the authors report a corrosion-resistant electrocatalyst with in situ-formed chloride-ion-repelling cation layer for efficient and long-lasting seawater oxidation.

Solid-state sodium metal batteries require solid electrolytes with high ionic conductivity and optimal electrode compatibility. Here, the authors introduce the Na₅SmSi₄O₁₂ solid electrolyte with a crystalline-to-amorphous transformation, achieving 4000 cycles lifetime without capacity decline.

Layer-stacking domain walls in van der Waals heterostructures form a broadly tunable Luttinger liquid system, including both isolated and coupled arrays.

TMEPro profiles the glycosylated secreted and plasma membrane proteome of 100 human pancreatic tissue samples, defines cell type origins and identifies potential paracrine cross-talk mediated through tyrosine phosphorylation.

Ferroelectric phase stability is a pivotal challenge for fluorite-structure ferroelectrics. Using electron microscopy, a ferroelastically protected reversible polar-to-non-polar phase transition in ZrO₂ is observed and the critical strain state to break the reversibility is measured.

Understanding the tumour microenvironment is essential for the efficacy of immunotherapies. Here the authors describe the immune landscape in esophageal squamous cell carcinoma and suggest several immunosuppressive mechanisms, which upon targeting may restore anti-tumour immune response.

Stable electrodes which operate at large current density are essential for industrial water electrolysis. Here, a highly active Chevrel phase electrode is reported to achieve 2500 mA/cm⁻² current density for 300 hours at small overpotentials.

Water electrolysis is a promising hydrogen production technique but is restricted from large-scale application due to poor performance and high cost. Here, the authors report a mechanically stable monolith electrocatalyst that achieves superior hydrogen evolution at large current densities.

RXFP3 and RXFP4 regulate pleiotropic processes. Chen et al. report the cryo-EM structures of the RXFP3–Gi (bound to relaxin-3 or compound 4) and the relaxin-3–RXFP4–Gi complexes, revealing the mechanism of ligand recognition and subtype selectivity.

Analysis of mitochondrial replacement therapy shows, even with efficient mutant mitochondrial DNA replacement and maintenance in embryonic stem cells, a gradual loss of donor mitochondrial DNA in some lines owing to a polymorphism in the D-loop, potentially causing preferential replication of specific mitochondrial DNA haplotypes.