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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.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

Lactate fuels cancer growth by activating ERK signaling through GCN5-mediated lactylation of ERK, which disrupts ERK–MEK interactions. Development of a cell-penetrating peptide blocking lactylation slows KRAS-mutant tumor development.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

The joint analysis of datasets from NOvA and T2K, the two currently operating long-baseline neutrino oscillation experiments, provides new constraints related to neutrino masses and fundamental symmetries.

Administrative-driven hierarchical management (ADHM) encourages general practitioners to act as voluntary gatekeepers in China’s non-mandatory medical system. Here the authors show that ADHM lowers cardiovascular events, mortality, and healthcare costs in atrial fibrillation patients compared with usual care.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

MuSCs are vital for muscle renewal with unclear regulatory mechanisms. Here, the authors show that cytosolic TBC1D1 inhibits nuclear entry of the AS160-STAT3 complex and regulates MuSC proliferation. Deficiency of TBC1D1 improves muscle regeneration.

Allenes are versatile substrates in synthetic chemistry. Now an iron catalyst enables unusual regioselectivity by mediating an electrophilicity reversal of allenes for stereoselective alkenylzincation reactions affording 1,4-diene zinc products.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

To emulate nature biological processing, highly-integrated ultra-sensitive artificial neuromorphic system is highly desirable. Here, the authors report flexible sensor array of 1024 pixels using combination of carbon nanotubes and perovskite QDs as active matetials, achieving highly responsive device for reinforcement learning.

Viruses such as EBV use various mechanisms to avoid antiviral responses. Here the authors propose that the EBV protein BRRF2 is secreted via extracellular vesicles from NPC cells, disrupts the cGAS-STING pathway, reduces cGAS-DNA phase separation and the subsequent antiviral response.

Si anodes could be an alternative to Li anodes in the application of solid-state batteries, but they suffer from issues such as severe volume expansion and sluggish kinetics. Here the researchers develop a Li–Si alloy anode that is stabilized by hard carbon, which leads to exceptional high-performance solid-state batteries.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

The role of KLF10 in exercise-mediated anti-obesity effects is not clear. Here, the authors show that exercise-induced adipose KLF10 interacts with FOXO1 and recruits KDM4A to transactivate lipolytic genes, which defends against obesity in male mice.

Lab strains of Bacillus subtilis have lost a plasmid that encodes phosphatase RapP, which targets the Spo0A sporulation pathway and thus regulates sporulation and growth. Here, Zu et al. show that RapP enhances growth by preventing expression of the Spo0A-mediated adaptive response during exponential phase, resulting in reallocation of cellular resources towards biosynthetic pathways without compromising long-term fitness during stationary phase.

The formyl peptide receptor 2 (FPR2) is involved in the pathogenesis of Alzheimer’s disease. Structures of FPR2 bound to Aβ₄₂, humanin, or formyl peptides offer insight into Aβ₄₂ neurotoxicity, humanin neuroprotection, and FPR ligand selectivity

Single-cell datasets continue to grow in size and complexity, calling for computational tools to process and analyse data. Yang et al. present a contrastive learning framework to learn cell representations from single-cell multiomics datasets.

Structures of human cholecystokinin receptors in complex with various ligands or G-proteins reveal how different ligand types are recognized and the basis of peptide selectivity in this receptor family, and suggest a stepwise activation mechanism.

Integrating the Pancharatnam–Berry phase with integrated resonant nanoantennas in a metalens design produces an achromatic device capable of full-colour imaging in the visible range in transmission mode.

An ideal thermoelectric material has a large Seebeck coefficient, and a high electrical but low thermal conductivity; however, optimizing all three is difficult. Zhao et al. discover three types of coexisting multi-localization transport behaviours in filled skutterudite materials that aid this optimization.

So-called two-dimensional superconductivity has been reported in several material systems but just how thin a system can be and maintain a superconducting state has been difficult to determine. Da Jiang and colleagues demonstrate that Bi2Sr2CaCu2O8+xcontinues to be superconducting even when it is just half a unit cell thick.

Here, the authors suggest a role of the lysine acetyltransferase KAT7 in inhibiting procentriole formation and colorectal tumorigenesis via competitive antagonism of its crotonylation against acetylation.

Pentacyclic triterpenoids (PTs) functionalized at the D/E rings possess a wide spectrum of biological activities but are poorly accessible. Here, the authors report a site-selective C-H hydroxylation at the D/E rings of PTs by exploiting transient pyridine-imino directing groups and disclose the synthesis of related natural products.

R9AP is a key receptor for entry of Epstein–Barr virus into human epithelial and B cells, and interacts directly with the viral glycoprotein gH/gL complex to mediate virus–host membrane fusion.

Despite the significant regulatory effects of protein post-translational modifications (PTMs) on liquid-liquid phase separation, specific data resources and predictors are lacking. Here, the authors report a manually curated database of PTM regulation (PTMPhaSe) and develop a graph neural network-based deep learning model (PhosLLPS) to predict functional phosphorylation sites regulating liquid-liquid phase separation, demonstrating their application to proteome-scale predictions.

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.

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.

Radiosensitising agents can enhance radiotherapy and improve outcomes. Here, the authors report on the design of bioinspired Radiosensitising and biocatalytic nanoparticles to increase radiation tiggered cell death and immunogenic response to combat both primary and metastatic tumours.

Training foundation models often requires a costly budget and excessive computational resources. In this study, a low-cost instruction learning framework is proposed that could enable the rapid adoption of visual-language pathology applications.

Long non-coding mRNAs play important roles in muscle development and regeneration. Here the authors identify a long non-coding mRNA that promotes myogenesis by sequestering miR-125b, leading to increased expression of insulin-like growth factor 2.

Hereditary deafness lacks effective biological treatments. Here, the authors develop a base editing therapy that corrects a common MPZL2 deafness gene mutation in a humanized mouse model and restores hearing, highlighting base editing as a potential treatment for hereditary deafness.

Currently, there are no treatments or vaccines against Epstein-Barr virus (EBV) infection. Here, Zhu et al. isolate gH/gL-specific antibodies from infected donors and identify 1D8, that substantially reduces infection levels in both, B- and epithelial cells, and reduces tumor burdens in EBV-challanged humanized mice due to interferance with the gH/gL-mediated membrane fusion and binding.

A suite of bridged rhodamine dyes (BriDyes) offers excellent brightness, solubility, photostability, and tunable cell permeability along with resistance to photoblueing, making them exceptional all-purpose dyes for fluorescence biomaging.

Shrub encroachment into grasslands affects species biodiversity and ecosystem functioning, but its impact on herbaceous diseases and the role of climatic factors remain unclear. This study finds that shrubs reduce pathogen load in colder regions but may increase it in warmer regions, with temperature being the primary driver of these variations.

Spacia is a multiple-instance learning model for cell–cell communication (CCC) interference in single-cell resolution spatially resolved transcriptomics data. Spacia can map complex CCCs by modeling cell proximity and CCC-driven gene perturbation.

Cryo-electron microscopy structures of a short prokaryotic Argonaute (pAgo) and the associated TIR-APAZ proteins bound by guide RNA and target DNA shed light on the mechanisms of assembly and activation of pAgo systems.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Employing appropriate catalysts in room-temperature sodium-sulfur batteries can significantly enhance performance. Here, authors utilize natural language processing techniques in conjunction with a binary descriptor to screen preferrable single-atom catalysts to achieve high specific capacity.

The role of Cdo1 in exercise-mediated metabolic health and NAFLD is not clear. Here, the authors show that hepatic Cdo1 tethers Camkk2 to AMPK by interacting with both of them, thereby activating AMPK signaling to blunt hepatosteatosis and to promote exercise-mediated alleviation of NAFLD in mice.

Platelet-activating factor (PAF) and PAF-like phospholipids were identified as propagators of ferroptosis, whereas PAFAH2 suppressed synchronized ferroptosis and, thus, prevented tubular cell death in acute kidney injury.

Metallic altermagnets are promising for applications due to the spin-polarized electric current that originates from their spin-split band structure. Now d-wave altermagnetism with antisymmetric spin polarization has been demonstrated in KV₂Se₂O.