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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.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

ROSE-3D is a single-molecule localization microscopy approach that achieves high isotropic resolution via interferometric localization. The approach is capable of whole-cell and multicolor imaging.

Identifying genetic variants using long-read RNA sequencing (lrRNA-seq) is useful but hampered by high error rates and biological complexities. Here, the authors developed Clair3-RNA, a deep-learning tool that improves variant calling accuracy in lrRNA-seq data and accurately identifies RNA editing sites.

Here, Xian et al. use phosphoproteomics to identify that the Shigella effector OspG interacts with a regulator of Cullin-RING ubiquitin ligases to promote the ubiquitination of septins and consequent inhibition of septin cage formation.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

A telomere-to-telomere gap-free pig genome assembly (T2T-pig1.0) for a Wuzhishan boar highlights Y chromosome structure and genomic regions potentially associated with body stature.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

Genetic muscle diseases are difficult to treat due to challenges in delivering gene editors to muscles throughout the body. Here, authors engineer muscle-specific virus-like particles that fuse with skeletal muscle cells to deliver CRISPR tools and restore dystrophin in a DMD model.

Conditional knockout of LARP4 in naive CD4⁺ T cells leads to attenuated quiescence exit and clonal expansion.

The accurate detection of somatic variants in cancer without matched normal controls remains challenging, particularly for long-read sequencing data. Here, the authors develop ClairS-TO, a deep learning method for long-read tumour-only somatic variant calling that outperforms similar algorithms and can also work with short-read sequencing data.

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction, but several studies have suggested a role of FSH and its receptor in extragonadal tissue. Here, the authors show that FSH orchestrates glucose-stimulated insulin secretion (GSIS) via its receptor on pancreatic β-cells, with pre-menopausal FSH levels dose-dependently promoting GSIS and postmenopausal FSH levels inhibiting this effect.

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.

In a multicenter randomized phase 3 trial, stapokibart, a humanized monoclonal antibody that targets IL-4R alpha, significantly improved daily nasal and ocular symptom scores during the pollen phase in patients with moderate-to-severe seasonal allergic rhinitis.

DrugGPT outperforms existing LLMs to answer questions related to drug interactions and recommendations.

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.

Researchers use organic ligands to reclaim energy lost during the relaxation of secondary X-rays generated by the interaction of high-energy particles with scintillators. Enhanced radioluminescence within lanthanide metal complexes and capture of dark triplet excitons with near-unity extraction efficiency are achieved.

In a phase 1/2 trial in patients with advanced non-small-cell lung cancer (NSCLC), followed by a phase 2 trial in an EGFR-mutant selected population, treatment with the TROP2-targeting antibody–drug conjugate sacituzumab tirumotecan led to encouraging clinical response rates, especially in patients with EGFR-mutant NSCLC, which was supported by mechanistic data.

The authors identify long-lasting transcriptional programmes in neurons and glia that are associated with the storage of a remote memory.

Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

Two impact-melt fragments in Chang’e-6 lunar soils reveal that the Apollo basin was formed at ~4.16 Ga, implying a non-cataclysmic late heavy bombardment on the Moon between 3.8 and 4.0 Ga.

Chromatin topology can impact gene regulation. Here, Wu et al. show that evolutionary changes in chromatin structure, particularly CTCF loops, can drive distinct transcriptional landscapes and isoform diversity contributing to human-specific traits.

The authors describe a new mechanism of AD pathogenesis in which the histone methylase G9a regulates translation of hippocampal proteins associated with AD pathology. Targeting this mechanism with a brain-penetrant inhibitor of G9a helped rescue brain pathology in AD mouse models.

Photocatalytic disinfection is a known pollution-free water treatment strategy. However, its efficiency is limited due to the spin-forbidden feature of O₂, which hinders photocatalytic ·O₂⁻ formation and limits its disinfection efficiency. Here the authors produce a strained Mo_4/3B_2-xT_z MBene that can increase ·O₂⁻ photocatalytic production, which results in high levels of photocatalytic disinfection.

Controlling the coherence of chaotic waveforms holds the promise to explore novel light‐matter interactions. Here, the authors demonstrate a fourth‐order‐dispersion driven laser that delivers the coherence‐controlled chaotic soliton bunch.

Interleukin-18 (IL18) has a pivotal role in interferon signalling and T cell development, but increasingly recognized as an adipokine that regulates energy metabolism in fat tissue. Authors here dissect the function of IL18 signalling in the adipose compartment by targeted genomic deletion of its two receptors individually and in combination in brown and white adipose tissues.

Transcription elongation is an essential step for gene expression control but remains unclear during spermatogenesis. Here, the authors report that NKAPL, a testis-specific protein distantly related to RNA splicing factors, is a crucial regulator of transcription pause-release.

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.

A versatile nano-adaptor is used to construct multi-specific nano-antibodies for treatment of tumours in mice.

In a large-scale, international, multicenter, phase 1/1b trial, treatment of patients with advanced solid tumors with the B7H3-targeting antibody–drug conjugate YL201 was safe and showed preliminary clinical efficacy.

Proof-of-principle photonic quantum simulations of molecular vibronic spectra have been realised, but scalability to more complex systems is hindered by the difficulties in generating squeezed coherent states with multiple modes. Here, the authors demonstrate an alternative approach relying on vacuum-squeezed state.

An effector protein called LnaB from Legionella pneumophila catalyses a unique type of AMPylation, and LnaB and its homologues represent a distinct family of AMPylases with specific structural features.

Minimizing toxicity of herpes simplex virus 1 (HSV) based tools for anterograde tracing is important for functional studies. Here the authors generate an anterograde monosynaptic tracer system based on HSV amplicon, which shows fast tracing, bright labeling, low toxicity, input-defined postsynaptic neurons’ anterograde monosynaptic tracing feature, and has potential for functional mapping.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

Spatial and single-cell transcriptomic analyses of the mouse basolateral amygdala reveal transcriptomic signatures, spatial resolution and interactions of cells that constitute the memory engram, including crucial neuron–astrocyte interactions.