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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Here the authors report that brown adipocyte-derived vaspin reduces heat-producing activity in brown fat by blocking adrenergic signals, helping to regulate energy expenditure and maintain metabolic balance.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

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

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution. Here, the authors demonstrate that physiologic aging induced involution and thermogenic dysfunction result from pyroptotic signalling activation.

Methane emission from a very cool brown dwarf, perhaps arising from an aurora, has been detected in James Webb Space Telescope observations.

A cortical premotor network in HVC, once initiated, can sustain and regulate the sequential production of zebra finch song syllables without major extrinsic inputs.

Untargeted metabolomics demonstrate that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched, and inosine is identified as a metabolite released during apoptosis regulating thermogenic fat and counteracting obesity.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this work, researchers build a scalable photonic Chern insulator by twisting a fibre during fabrication, breaking an effective time-reversal symmetry and inducing a pseudo-magnetic field. The team reveals a ‘Goldilocks’ regime that guarantees topological protection against fabrication-induced disorder of any symmetry class in the fibre cross-section.

The study shows how ship traffic in the Baltic Sea modifies seafloor morphology and disrupts water layers, thereby increasing the mixing of oxygen, nutrients and greenhouse gases, suggesting broad impacts on Baltic marine ecosystems.

Uncertainties in the absorptive properties of black and brown carbon particles limit our understanding of their warming potential. Following an extensive field campaign, Liuet al. report that the magnitude of warming is dependent on particle coatings, which vary due to source and photochemical aging.

Mitochondrial function is essential for energy metabolism in brown adipocytes. Here, the authors show that LCN2 plays a critical role as a phosphatidic acid binding protein in phospholipid acyl chain remodeling and mitochondrial bioenergetics, influencing signaling pathway activation.

Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.

Moiré field-effect transistors based on graphene/hexagonal boron nitride heterostructures are promising for their high room-temperature carrier mobilities and magnetotransport properties. Here, high-temperature molecular beam epitaxy growth of graphene/hBN gives rise to a moiré-fringed hexagonal superlattice with Hofstadter butterfly electronic band structure and quantum magneto-oscillations above room temperature.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

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.

PhenoMol integrates graph theory and biological knowledge to reduce multi-omic dimensionality, predict phenotypes, and reveal causal patterns. It outperforms conventional models that lack biological constraints and is openly available for health, performance, and disease research.

This study presents a clinical-grade autonomous pipeline combining high-resolution whole-slide tomography, edge computing and artificial intelligence, achieving high accuracy in cervical cytology and enabling scalable and objective diagnostics.

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

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.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

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.

Dermatoscopy is a common method to aid in diagnosis of melanoma, however, its utility in predicting metastasis is not fully known. Here, the authors leverage a cohort of 30 dermatologists to develop models to predict prognosis from dermatoscopic images.

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.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

As presented at the ESMO Congress 2025: In patients with locally advanced or metastatic solid tumours, including mesothelioma, treatment with a first-in-class inhibitor of the Hippo−YAP−TEAD pathway was safe and led to encouraging clinical response rates in patients with mesothelioma.

Spectroscopic detection and characterization of an irradiated substellar donor planet in an accreting white-dwarf binary system reveals a donor mass of 0.055 ± 0.008 solar masses, an average spectral type of L1 ± 1 and an average irradiation-induced temperature difference between the dayside and nightside of 57 kelvin.

Spatial transcriptomics (ST) technologies link tissue morphology with gene expression, but remain expensive to use; furthermore, models that predict ST data from histopathology images possess considerable limitations. Here, the authors develop STimage, a deep learning probabilistic framework for ST prediction from histopathology images while prioritising robustness and interpretability.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The early events preceding the development of morphological abnormalities represent a key gap in the understanding of cancer. Here, the authors employ an oncogenic tagging strategy to define the contributions of HIF1A and HIF2A to the cell-type specific early events in VHL-associated oncogenesis and support therapeutic targeting of HIF2A early in VHL-associated cancers.

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.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.