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The complexity of the evolved metabolic networks of flavonoids complicates pathway elucidation and design. Here, the authors identify enzymes that modify isoflavan scaffolds from the genome and transcriptome data of Glycyrrhiza glabra, and reconstruct de novo glabridin biosynthesis in yeast.

Structural variants are an underexplored source of genetic diversity. Here, the authors use phased pangenome graphs to improve detection of these variants in dairy cattle and link these variants to traits of economic importance.

The longevity of leaves determines the overall duration of photosynthesis for plants. This study suggests that climate change drives leaf longevity convergence toward intermediate ranges, which, by altering leaf traits and enhancing photosynthetic capacity, strengthens ecosystem stability and is closely linked to vegetation diversity.

This study shows that excessive atmospheric nitrogen deposition can enhance methane production and emissions by impacting microbial phosphorus acquisition due to the change of N/P ratios in oxygenated surface oceans.

Here they show that NONO collaborates with HOXA1 to modulate gene expression during early cardiomyocyte differentiation. This interaction facilitates activation of the Wnt signaling pathway, establishing the NONO-HOXA1-Wnt axis as a key mechanism in cardiac development.

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.

Here, the authors combine bioinformatic, mass spectrometric, and sequencing-based mapping tools to identify previously undescribed phosphorothioate epigenetic systems widespread in the human gut microbiome.

The authors consider the changing sensitivity of the leaf-onset date to temperature (S_T) for boreal deciduous broadleaf forests. S_T increased between 1982–1996 and 1998–2012—potentially linked to enhanced chilling accumulation—but this increase is underestimated in phenology models.

The Huayuan biota exhibits extraordinary biodiversity, illuminating the impact of the Phanerozoic mass extinction around 513 million years ago and offering critical insights into the transformation of global ecosystems in the early Cambrian.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The authors develop a low carbon cement-based material which exhibits hierarchical structure with low density (0.75 g cm⁻³), high specific compressive strength (344 (kN m⁻²)/(kg m⁻³)) and fracture toughness (4865 kJ m⁻³).

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

Silicon anodes promise much higher battery capacity but are limited by poor storage life. This work identifies key ageing mechanisms and suggests ways to improve long-term stability.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

An extreme barocaloric effect in NH₄SCN aqueous solutions is enabled by pressure-induced dissolution and precipitation, but without using a separate heat-transfer liquid.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

A generative AI approach is developed for predicting materials synthesis recipes—a complex challenge in materials science. Using this approach, the authors experimentally synthesized a material using AI-generated synthesis recipes.

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 CD11b-positive regulatory B cells and low expression of CD40 in melanoma cells have been associated with resistance to agonist CD40 (aCD40) and immune checkpoint blockade (ICB). Here the authors show that the addition of RAS/MEK/PI3K inhibitors to aCD40 abrogates these effects and reverses ICB resistance in preclinical melanoma models.

Liu, Liu, Wu and Yao et al. developed a peptide inhibitor that selectively blocks the Ada-two-A-containing histone complex by targeting the YEATS2 YEATS domain and suppresses tumor growth in non-small cell lung cancer.

The nature of the defects in amorphous materials, analogous to vacancies and dislocations in crystals, remains a matter of debate. Scalliet et al. show that localized and extended defects coexist in a wide range of conditions, yet are associated with distinct energy scales in a prototypical glass model.

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

Native crystallographic defects are often introduced during synthesis of battery materials, but has been overlooked. Here, using in situ synchrotron X-ray probes and electron microscopy, the authors have revealed their adverse effect during battery operation.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

An in situ multistep edge-contact process is developed for MoS₂ transistors, achieving quasi-non-volatile capacitorless two-transistor dynamic random-access memory with 5-bit accuracy and nanosecond write speeds.

Structural, genetic, functional and biochemical analyses of the complex flagellar motor of Campylobacter jejuni reveal structural adaptations with an ancient origin also found more widely across bacterial species, including elements exapted from the type IV pilus machinery.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Down syndrome (DS) increases gene dosage that disrupts neurodevelopment and cognition. Using human-derived isogenic neurons, this study reveals altered network activity, synaptic dysfunction, and ion channel defects underlying DS neural impairment.

Self-supervised reconstruction structured illumination microscopy (SSR-SIM) is a reconstruction approach for SIM that improves image reconstruction by including light modulation priors and information on reconstruction artifacts, while simultaneously eliminating the need for ground-truth images. The improvements allow long-term imaging of sensitive cellular processes.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

De novo domestication was performed on the brassica Thlaspi arvense (pennycress) by identifying and stacking CRISPR-induced mutations to create a new intermediate oilseed crop that can be grown in the off-season, with seed compositions similar to canola (low erucic acid and reduced glucosinolate).

This work identifies ERECTA–EPFL genes as major regulators of maize meristem activity and the development of maize shoots and ears. The findings highlight genetic targets that influence kernel row number and plant architecture to increase maize yield.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Negative refraction—light bending opposite to conventional refraction—and a hyperlens effect is observed in an excitonic system in the two-dimensional magnet CrSBr. The effect is mediated by the magnetic order of the material.

In a cluster-randomized trial including 84 schools in China, schools that received the Life Gatekeeper Training Program for suicide prevention saw significantly reduced suicide stigma and improved willingness of teachers to intervene, compared to schools without the training.

An outstanding question about the iron-based superconductors has been whether or not their magnetic characteristics are dominated by itinerant or localized magnetic moments. Absolute measurements and calculations of the magnetic response of undoped and Ni-doped BaFe₂As₂ indicate the latter.

A membrane system operating without electricity and inspired by natural fractal transport patterns achieves exceptional nanofiltration performance, offering a simple and reliable source of potable water for decentralized communities.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

Optical heterostructures have potential in integrated photonics and optoelectronics but are challenging to prepare in single-component systems. Here, the authors report an intrinsic optical heterostructure in an organic nanosheet, with enhanced fluorescence in an inner zone.

The perceived toxicity of organometallic reagents has limited their use in living systems. Now it has been shown that balancing flexible chelation with biocompatible ligands without precluding chemical reactivity enables organonickel-mediated S-arylation inside cells. This reaction enables deep chemical surveys of reactive proteins and covalent tracking of intracellular viral and bacterial pathogens.