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Granzyme B is an important factor in cytotoxic T lymphocytes anti-tumour immunity. Here, the authors report on a Pd-FTn granzyme B-mimicking nanozyme with a binuclear catalytic centre, delivered by functionalised nanovesicles to selectively trigger caspase-dependent apoptosis for a T cell-inspired cancer therapy.

Astrocyte-to-neuron (AtN) conversion is limited by intrinsic barriers, hindering its efficiency. Here, the authors show that Olig2 acts as an inducible barrier to in vivo Ngn2-mediated AtN conversion, reducing reprogramming efficiency.

Van der Waals materials of the MB₂T₄ family (M = transition metal or rare-earth metal, B = Bi or Sb, T = Te, Se, or S) have attracted interest for their magnetic and topological properties, but their direct synthesis into 2D form remains challenging. Here the authors report a flux-assisted, phase-controlled growth strategy to directly grow six magnetic 2D MB₂T₄ crystals.

While neoadjuvant immunotherapy and chemoradiotherapy can improve rectal cancer patient outcomes, there is a need to better identify those who will respond well. Here, the authors present a single-arm phase II trial reporting the efficacy and safety of neoadjuvant chemoradiotherapy and sintilimab (anti-PD-1) in patients with locally advanced rectal cancer with proficient mismatch repair and intermediate/high Immunoscores.

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.

Amplification and optimal noise filtering in hyperpolarized noble-gas spins of observations from distributed intercity quantum sensors monitoring for unexpected transient rotations of polarized spins set parameter range constraints in the search for axion dark matter.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

While cyclo[16]carbon has been produced on the surface and is well characterized, C₁₆ isomers with other structures have been predicted only by theory. Here, the authors report the synthesis and structural characterization of a graphene-shaped C₁₆ flake on a bilayer NaCl surface grown on Au(111).

An annotation-free vision–language model based on contrastive learning performs pathology localization and clinical diagnosis on a wide variety of medical image datasets.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

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.

Altermagnets combine spin-split electronic bands with zero net magnetization, making them ideal for integration into spin-based information processing devices. Here Guo, Chen, Zeng, and coauthors demonstrate a magnetic memory making use of the altermagnetic spin splitting torque in a three terminal MRAM device.

This work demonstrates superadiabatic topological pumping on photonic chips, achieving a 20-fold device miniaturization and high-efficiency operation across a 650–920 nm bandwidth, paving the way for ultracompact integrated photonic transports.

RNA modifications are crucial regulators of gene expression but have been hard to detect accurately. Here, the authors introduce DeepRM, which uses a massive high-quality training dataset to detect and quantify m6A with near-perfect accuracy, producing a comprehensive human m6A atlas.

One area of interest in the field of molecular magnetism is the development of high-spin molecules. Here, the authors report a cyanide-bridged nanocage consisting of 18 high-spin iron(III) ions ferromagnetically coupled through 24 low-spin iron(II) ions, with a ground state spin of S=45.

The persistence of myofibroblasts after wound healing is ultimately responsible for scarring. Here, the authors show that fibromodulin enhances interleukin 1β ternary complex formation, promoting myofibroblast apoptosis and providing a potential strategy to mitigate scarring.

Crystal growth is visualized inside non-transparent liquid metals, while preserving their original state, using X-ray micro-computed tomography to reveal how liquid metal solvent composition and cooling conditions influence crystal formation.

Starch is a major component of wheat grains. Here the authors show that the PIL1 transcription factor positively regulates grain starch synthesis and identify elite alleles that could be used to enhance wheat yield and starch content.

Designing complete mRNA sequences for new vaccines and therapies is a complex challenge. Here, the authors develop mRNABERT, a foundational AI model that designs entire mRNA sequences and demonstrates superior performance across comprehensive benchmarks.

Fluorine-containing binders in battery dry electrode processing raise environmental concerns regarding restrictions on per- and polyfluoroalkyl substances. Here, authors show that a fluorine-free binder, Parafilm, can be an alternative to enable primer-free high-loading electrodes with stable cycling for sustainable lithium-ion batteries.

The synthesis of functionalized γ-lactams is challenging due to instability of the products and difficulties in controlling diastereoselectivity. Here, the authors report on the design and synthesis of a naphthyl-based pyrene-containing covalent organic framework and utilize it as a heterogeneous photocatalyst for synthesis of γ-lactams.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Here the authors propose an evaporation-driven approach to print various nanomaterials on porous substrates, allowing for high-throughput roll-to-roll and spatially programmable fabrication of functional nanomaterial films.

Surface melt is an important component of ice sheet dynamics, but for many remote regions the melt rates are mainly known from models. Here the authors present satellite observations of melt rates for Greenland and Antarctica, showing that East Antarctica has become a melting hotspot.

Wastewater surveillance can be used to track infectious diseases. A six-plex digital PCR assay is shown to provide information on four respiratory diseases at the same time, with data that have a high level of agreement with reported case numbers.

This study presents ECloudGen, which uses latent diffusion to generate electron clouds from protein pockets and decodes them into molecules. The adopted two-stage training expands the chemical space accessible to generative drug design.

To fully realize LLMs’ potential value in clinical applications, effective methods to enhance their quality and credibility are required. Here, the authors present LINS, a framework to enhance medical LLM responses by integrating up-to-date evidence and supporting clinical tasks, and validate it through new physician-curated datasets and large-scale user trials.

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.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Behçet’s disease (BD) is characterized by polymorphonuclear neutrophils (PMN) and macrophage activation, but their interaction remains elusive. The authors here find PMN exosomes from BD patients are attenuated in suppressing proinflammatory macrophages when cocultured in vitro with the mechanism of decreased miR-122-5p/IRF5/TLR4 signaling and IFN-β autocrine pathway.

Monolayer amorphous carbon (a-C) has attracted attention due to its structural and electronic properties, but its synthesis has so far required the use of metal substrates. Here, the authors report the Te-assisted growth of large-scale 2D a-C patterns on various insulating substrates, confirming their insulating properties in quantum tunnelling devices.

Liquid films are essential in semiconductor lithography but microscopic behaviors of photoresist within these films remain unclear. This study uses cryo-electron tomography to reconstruct photoresist structures, achieving 99% defect reduction.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a drug target for inflammatory bowel disease (IBD), impacting immune cell movement, but current treatments carry immunosuppression risks. Here, the authors show that a Gi-biased S1PR1 agonist, SAR247799, protects the endothelial barrier in IBD models without affecting immune cell egress, offering a potential new treatment strategy.

High-power, tunable accelerator-based terahertz radiation is demonstrated. By electron-beam manipulation through laser heater beating, tunable capability from 7.8 to 30.8 THz, narrow spectral bandwidths (ranging from 7.7% to 14.7%) and pulse energies up to 385 μJ are obtained.

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.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

ATG8-family proteins are critical components of the autophagic machinery. Here, the authors demonstrate that noncanonical ATG8 conjugation to the vacuolar membrane enhances its invagination, mitigating vacuolar damage caused by ionophores and alkaline stress.

Multi-ancestry fine-mapping of breast cancer susceptibility regions identifies candidate causal variants and prioritizes likely effector genes supported by functional genomic evidence.

Loss of active DNA demethylation increases DNA methylation at numerous loci in plant vegetative tissues; however, resulting developmental phenotypes have not been observed. Yamamuro et al. show that mutation of the 5-methylcytosine DNA glycosylase ROS1 results in overproduction of stomatal lineage cells in Arabidopsis.

Spin-crossover complexes and single-chain magnets exhibit magnetic bistability and may be used in information storage applications. Here, the authors present a one-dimensional spin-crossover complex wherein the single-chain magnet behaviour is actuated by light-induced excited spin-state trapping.

Here, using samples from 146 mother-infant pairs and multi-omics, the authors characterize the dynamics of the gut microbiome, metabolome, and antibiotic resistance gene profiles during the first year of life in association with prenatal exposure to trace elements.

This study shows that tensile strain continuously tunes lone-pair expression in BiCuSeO, increases lattice disorder and phonon scattering, and lowers thermal conductivity, offering an effective approach to control heat transport in materials.

In a randomized phase 3 trial, neoadjuvant anti-PD-1 plus either paclitaxel and cisplatin or nab-paclitaxel and cisplatin elicited a significantly superior pathological complete response rate versus neoadjuvant paclitaxel and cisplatin alone in patients with resectable locally advanced esophageal squamous cell carcinoma.

The synthesis of high value heterocycles from cheap starting materials remains challenging. Here, the authors develop a new strategy to realize practical and modular synthesis of N-H indoles and analogs from toluene and nitrile derivatives using naturally abundant copper salt as catalyst.

The spin-orbit torque (SOT) induced magnetic switching makes metal/magnetic insulators bilayers preferred in the energy efficient spintronic applications. Here the authors show SOT switching in W/TmIG bilayers and reveal the dimension crossover of SOT as a function of TmIG thickness.

A 27 kDa photosensitizer protein (PSP) has now been developed and used to design a miniature photocatalytic CO₂-reducing enzyme. Visible light drives the PSP efficiently to the long-lived triplet excited state (PSP*), and then to a super-reducing radical (PSP^•), which is strong enough to reduce many CO₂-reducing catalysts. The 3D structure of PSP^• at 1.8 Å resolution was determined by X-ray crystallography.