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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.

In this work, authors show that micro- and nanoplastics at environmentally relevant levels promote conjugative transfer of antibiotic resistance genes between bacteria by altering oxidative stress, membrane permeability and energy metabolism.

Nonsense mutations in OTOF cause hereditary deafness. RESTART v3 achieves efficient, precise readthrough at Otof c.1315 C > T (p.R439*) sites, reinstating arginine to yield full-length, functional otoferlin, markedly restoring hearing in mice and showing strong promise for clinical translation.

Intramolecular coupling of extended biphen[n]arenes is developed to yield cycloparaphenylenes (CPPs). The modular nature of biphen[n]arenes makes it possible to customize CPP structures, which permits tuning of their photophysical properties. The syntheses are short and excellent yields are achieved. Moreover, postsynthetic functionalization is possible.

Hydrogen oxidation in alkaline media is limited by slow reaction kinetics. Here, the authors develop a family of bimetallic catalysts by theoretical analysis and reveal that RuIr achieves superior activity and durability through synergistic adsorption of hydrogen and hydroxyl intermediates.

Reactive capture bypasses CO₂ regeneration, enabling efficient CO production but with low Faradaic efficiency. The authors report a Ni–N₃ molecular catalyst that resists amino acid adsorption and promotes efficient CO production in amino-acid systems.

ARMH2 is identified as a previously unknown cytosolic component of the sperm-specific CatSper channel, critical for its normal assembly and pH/calcium sensitivity. Loss of ARMH2 impairs sperm hyperactivation and causes severe subfertility.

Treatments to cure chronic hepatitis B (HBV) infection are currently lacking. Here, the authors identify an HBV targeting siRNA that exhibits potent and broad-spectrum antiviral activity in preclinical animal models and demonstrates a favorable safety profile and functional cure indicators, promising clinical translation potential.

Mutation detection in cfDNA is crucial for cancer diagnosis and monitoring. Here, the authors develop an Enzymatic Cleavage-directed Single Nucleotide Variant Sequencing by integrating Argonaute-mediated cleavage and stem-loop DNA-initiated PCR amplification for cfDNA mutation detection.

The reconstruction of rutile TiO2 (110) impacts its surface chemistry and catalytic properties. Here, the authors offer a detailed understanding of the asymmetric surface reconstruction of TiO2 (110)-(1×2) through a combination of STEM and DFT calculations.

This study introduces the Protein Importance Calculator (PIC), a deep learning model designed to predict human essential proteins (HEPs) crucial for survival and development. Unlike conventional methods, PIC offers a comprehensive assessment of HEPs across three levels: humans, cell lines and mice.

Electrocardiogram is crucial for cardiovascular disease prevention, diagnosis, and prognosis. Here, the authors present a motion-unrestricted dynamic electrocardiogram system utilizing skin-conformal, imperceptible electronics for long-term, comfortable, and accurate 12-lead monitoring.

Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.

Viscoplastic surface effects in polymeric elastomers drive the development of sealing platforms with high hermeticity and large stretchability to safeguard stretchable electronics from degradation.

Macropinocytosis enables cancer cells to absorb nutrients from their environment, supporting growth and therapy resistance. In this Review, Tang, Wang, Kroemer and Kang outline its regulatory mechanisms, implications for treatment strategies and potential as a target for enhancing therapeutic efficacy in oncology.

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.

Glioblastoma stem cells (GSCs) contribute to tumor recurrence and resistance to therapy. Here, the authors show that ICAM1 enhances GSC stemness and promotes immune evasion through the β-catenin/PD-L1 signaling pathway.

Crystal facets are known to be important in traditional heterogeneous catalysis, yet this effect has not been studied in plasmon-assisted catalysis. Here, the authors investigate the impact facets have on CO₂ reduction using plasmonic Au NPs.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

Genomic analyses of 2,191 global common wheat accessions and over 47,000 yellow rust (YR) response data points across several environments and pathogen races provide a genome-wide landscape of YR resistance genes and effective alleles.

Stereoisomers can exhibit distinct chemical behaviors despite identical formulas. Here, the authors reveal how geometric isomers of electrolyte additives tailor solvation and interphasial chemistry, enhancing Zn-ion kinetics and long-term stability in aqueous zinc metal batteries.

Searching non-charge-based devices is crucial for sustainable information processing. Here, the authors make a nonvolatile magnon field effect transistor at room temperature, enabling efficient magnon transport control via the gate voltage pulses.

Layered materials typically compress along the out-of-plane direction under pressure. Here, a pressure-induced insulator-to-metal transition is observed in the altermagnet La₂O₃Mn₂Se₂, accompanied by in-plane lattice collapse.

A new procedure for cataract removal that preserves lens epithelial progenitor cells in mammals, which require Pax6 and Bmi1 for their self-renewal, achieves lens regeneration in rabbits, macaques and in infants with cataracts.

The role of outer mitochondrial membrane proteins in Myocardial Ischemia-reperfusion Injury (MIRI) largely remains unknown. Here, the authors demonstrate that the outer mitochondrial membrane protein Myocardial Mitochondrial Antiviral Signaling (MAVS) protein promotes MIRI suggesting MAVS protein as potential therapeutic target.

Controllable synthesis of higher alcohols from CO hydrogenation remains a great challenge. Here the authors show that potassium-decorated edge-rich MoS₂ enables selective CO hydrogenation to higher alcohols by regulating the reaction kinetics of C-O cleavage, C-C coupling and desorption of alcohols.

Many studies have shown that progressive human kidney disease seriously affects the quality of life of patients and may lead to their death. Here, the authors show that targeting of NRP1 represents a promising strategy for the treatment of kidney injury and subsequent chronic kidney disease.

Mobility impairment reduces autonomy and social participation. Here, the authors discuss how wearable technologies are transforming assisted mobility towards more adaptive, intuitive, and user-centered solutions.

The catalytic performance of dilute Pd-in-Au alloys depends on the Pd ensemble size on the bimetallic nanoparticle surface. Here the authors reveal how Pd ensemble formation on Au nanoparticles depends on the deposition sequence and nanoparticle–support wetting interactions, consequently affecting reactivity.

Single atom catalysts offer a promising approach for CO₂ electroreduction to CO, but achieving high efficiency remains challenging. Here, the authors report lanthanide single atom catalysts with the transition ability from bridge to linear adsorption that exhibit efficient CO production.

A new AI generative model leverages the use of synthetic images to effectively augment existing datasets, boosting performance across multiple medical applications

Calmodulin (CaM) activates target proteins to regulate a variety of cellular processes. Here, the authors report that CaM–target binding is disturbed by a fungal effector PdCDIE1, leading to ROS-dependent plant cell death.

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.

In this work the authors present Token-Mol, a token-only 3D drug design model, which deploys the Gaussian cross-entropy (GCE) loss function for regression tasks. It exhibits superior performance in molecular conformation generation, property prediction, and pocket-based generation, thus opening up new avenues for drug design.

A strategy is introduced for promoting the folding in metallopeptide nanostructures, resulting in high mechanical rigidity. The mechanical properties are reflected in enhanced peptide-binding properties and heightened antimicrobial activities relative to their unfolded counterparts.