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DNA in many bacteriophages contains unusual chemical modifications. Here, the authors discover that carboxymethylcytosine is a natural DNA base and reveal its role as an intermediate enabling further DNA hypermodification.

Multi-modal integration of spatial transcriptomes and metabolomes via haCCA reveals metabolic heterogeneity and NETs-mediated Scd1 upregulation driving fatty acid metabolism in intrahepatic cholangiocarcinoma.

Using magnetic tweezers and atomistic simulations, the authors investigated RNA dynamics and uncovered how cations and, more surprisingly, anions, drastically distorts and softens RNA.

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.

A model, trained to generate synthetic, patient-specific angiography images, reduced radiation exposure to patients and clinicians by two-thirds in a multicenter randomized controlled trial involving 1,068 patients.

Peritoneal metastasis remains a major clinical challenge due to the lack of effective therapeutic options. In this study, the authors present intraperitoneal programming of tailored chimeric antigen receptor macrophages (CAR-Ms) as a strategy against peritoneal metastasis.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

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.

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 basis of the drought tolerance of upland rice is unclear. Here, the authors report the cloning of a COBRA-like protein encoding gene DROT1 and reveal that it is repressed by ERF3 and activated by ERF71 to help control the balance between growth and drought tolerance in upland rice.

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.

Low temperature is a major factor limiting productivity in rice. Here the authors show that theCTB4a gene confers cold tolerance to japonicavarieties adapted to cold habitats at the booting stage of development, and propose that CTB4a acts via an interaction with the beta subunit of ATP synthase.

Psychological stress-mediated dysregulation of catecholamine signalling rewires the hepatic kynurenine pathway, which in turn impairs liver CD8⁺ T cell function and promotes liver cancer progression.

Qifa Zhang and colleagues report the map-based cloning of the quantitative trait locus GS5, which regulates grain size and yield in rice. GS5 encodes a putative serine carboxypeptidase and increased expression is associated with larger grain.

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.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

This study presents LoopID, which profiles proteins at targeted interacting enhancer–promoter (E-P) pairs, identifying the histone demethylase JMJD2 as a regulator of E-P interactions through biomolecular condensate formation independent of its catalytic activity.

IBI318 is a recombinant bispecific IgG1 antibody that targets PD-1 and PD-L1. Here the authors report the results of a phase II trial of IBI318 combined with the receptor tyrosine kinase inhibitor lenvatinib in patients with advanced non-small cell lung cancer with acquired resistance to first-line immune checkpoint inhibitors.

Reducing the embodied carbon emissions of building material stock is essential for mitigation. Using a high-resolution multiyear dataset in China, researchers show the historically massive contributions of these emissions during past decades of rapid urbanization and the potential risks for future climate goals.

Large language models are starting to be used in safety-critical tasks such as controlling robots. Zhou et al. present LabSafety Bench, a benchmark evaluating the ability of large language models to identify hazards and assess laboratory risks.

The mechanical reliability and scalability of flexible perovskite solar cells remain challenging. Mingzhu He et al. design β-cyclodextrin derivatives to reinforce grain boundaries, enhancing both the efficiency and stability of cells and modules.

Insights from surface science studies on model catalysts very often do not translate to practical catalytic systems due to the so-called pressure and materials gaps. Now, a combination of in situ microscopy, spectroscopy and computational modelling is used to bridge the knowledge from surface science and powder catalysts for FeO–Pt during CO oxidation.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

A large, multicenter, double-blind RCT in 150 children and adolescents found that external trigeminal nerve stimulation, although safe and well tolerated, did not produce significant short-term or long-term clinical benefits for ADHD compared to sham treatment.

The authors generate transcriptomic profiles and construct 3D genome maps for nine giant panda tissues, revealing tissue-specific 3D genome reorganization linked to gene expression and function.

Direct observation of the Migdal effect in neutron–nucleus collisions is reported, which resolves a long-standing gap in experimental validation.

T-cell engager (TCE)-based immunotherapy requires further development in solid tumors due to limited T cell penetration, immunosuppressive tumor microenvironment and toxicity. The authors here develop a glypican-3 targeting mRNA TCE (MTS105) which manifests superior T cell activation and tumor regression hepatocellular carcinoma mice model comparing to conventional TCE, and safety with cynomolgus monkey studies.

Man-made ammonia emissions have harmful effects on human health and ecosystems, yet global mitigation strategies remain underexploited. A study now finds that emissions could be halved cost-effectively by 2050 through targeted and prioritized measures, with benefits far outweighing costs.

Forest management primarily drives the carbon sink enhancement in China from 2001 to 2021, achieving carbon gains at a rate over 4 times higher than afforestation, according to an integrated framework combining remote sensing-driven and climate-driven process models.

Chen et al. report the design and characterization of a systemically injectable oncolytic virus with tumor-targeting and low-immunogenic properties, engineered to induce tumor cell pyroptosis under local mild hyperthermia.

PAK4 promotes Mdm2-mediated NLRP1 ubiquitination and degradation by phosphorylating Mdm2 at Ser186, thereby suppressing GEM-induced pyroptosis via the NLRP1/caspase-9/caspase-3/GSDME axis in pancreatic cancer cells

Cutaneous tuberculosis is an infectious disease associated with extracellular matrix remodeling and granuloma-driven fibrosis. Here, the authors present an in vitro model of this disease using skin organoids infected with Mycobacterium tuberculosis, and describe infection-induced alterations in specific pathways and cell populations.

Noise-induced hearing loss is commonly attributed to direct damage to sensory hair cells. Here, the authors reveal that non-sensory supporting cells play a critical role in the damage through Gasdermin D-mediated exacerbation of hair cell oxidative stress.

Due to the complexity of controlling factors and the diversity of reaction components, accurately delineating the bond formation mechanisms for copper-catalyzed radical transformations poses a challenge. Here, the authors reveal the linear free energy relationships for the C–C bond formation of Cu-catalyzed radical transformations.

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.