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Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

Lipid nanoparticles (LNPs) are a versatile class of clinically approved drug delivery vehicles, particularly for nucleic acid cargoes, but they often suffer from instability issues. Here, the authors report that the room temperature stability of small interfering RNA LNPs formulated with unsaturated ionizable lipids can be improved by inclusion of mildly acidic, antioxidant-containing buffers.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

This study introduces a label-free imaging and machine learning platform that predicts hematopoietic stem cell function based on their dynamic behaviors, offering new insights into stem cell diversity and potential clinical applications.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

Cross-linkable co-SAMs improve hole-selective SAM stability, preventing defects and thermal degredation in perovskite solar cells, enabling 26.92% efficiency with high heat durability, and guiding the design of more efficient and durable solar cells.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

Previous ophthalmic foundation models have struggled to generalize effectively to diverse and rare fundus diseases, restricting their clinical applicability. Here, the authors introduce a vision-language foundation model that demonstrates superior performance in diagnosing both common and rare fundus conditions.

Resources are finite for living organisms; therefore, compromises are required when partitioning resources to different tasks. Here, the authors use the Pareto concept to show how a trade-off is achieved in terms of the performance and metabolic efficiency in a panel of 97 Arabidopsis thalianaaccessions.

Complexes of the transcription factor Ume6 bridge morphogenesis, adherence and hypoxic genes that determine biofilm architecture in the human fungal pathogen Candida albicans.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

Expression of the transporter SID-1 in Caenorhabditis elegans neurons renders the cells sensitive to systemic RNAi and permits previously unidentified neuronal phenotypes to be uncovered. This expression also reduces RNAi in nonneuronal cell types, allowing examination of neuronal functions of lethal genes.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

The human coronary artery disease gene TCF21 promotes the transformation of smooth muscle cells within atherosclerotic plaques into a newly identified population of fibroblast-like cells that contribute to plaque stability.

The discovery of 2023 KQ₁₄, a Sedna-like object with a perihelion of 66 au, fills a gap in the known population. Its orbit does not align with other Sedna-like objects, shedding light on the diversity and dynamical history of the outer Solar System.

Performing a CRISPR–Cas9 screen in aged mice, Sun and colleagues identify clusterin as a driver of myeloid-biased hematopoietic stem cell differentiation in aging, through regulation of mitochondrial function via a Mnf2-OXPHOS-p38-Cebpb regulatory axis.

Hematopoietic stem cells (HSCs) differentiate into multiple lineages, with such capacity impacted by aging. Here the authors identify Kit^lo HSCs as a functionally distinct population that exhibits distinct lymphoid-primed chromatin landscapes, which drive enhanced lymphoid reconstitution capacity, and is altered in aged hosts.

High-pressure minerals in meteorites reflect the conditions prevailing when they were excavated and launched from their parent bodies. Tissint—a recent Martian meteorite—contains an unusual number of large high-pressure minerals, suggesting excavation from an impact of larger magnitude than for previous Martian samples.

This study shows that UTX (KDM6A) suppresses myeloid leukemogenesis through noncatalytic functions. UTX loss leads to alterations in H3K27ac, H3K4me1 and chromatin accessibility, and in gene-regulatory programs mediated by ETS and GATA transcription factors.

The authors analyze rare coding variants in 1990 individuals with congenital kidney anomalies, finding diagnostic variants in 14.1% of cases. They identify two new causal genes, ARID3A and NR6A1, along with 38 candidate genes, providing evidence for shared genetics with other developmental disorders.

Finite momentum superconducting pairing refers to a class of unconventional superconducting states where Cooper pairs acquire a non-zero momentum. Here the authors report a new superconducting state in bulk 4Hb-TaS₂, where magnetic fields induce finite momentum pairing via magnetoelectric coupling.

The authors uncover a mechano-metabolic adaptation where confinement induces rapid mitochondrial relocalization to the nuclear periphery, generating localized nuclear ATP surges that support chromatin remodeling, DNA repair, and cell cycle progression.

In this Review, Nicholas Chew and colleagues use epidemiological data on the cardiovascular–liver–metabolic disease syndemic to illustrate current and future projections on the burden of these diseases and their risk factors, and propose a unified framework for integrating and implementing effective multisystem interventions to tackle key components of this syndemic.

Akincilar, Fidan et al. report a conserved role for telomerase reverse transcriptase in regulating inflammation via the cGAS–STING nucleic acid-sensing pathway in myeloid cells, independent of its telomerase activity.

An adaptive supramolecular system is designed which exhibits complex droplet growth and phase behaviours, driven by the interplay between environmental factors (light input) and intrinsic chemical activity. This process is powered by light-induced bond scission of strained cyclic disulfides in monomers and the formation of diverse oligomers with linear disulfide linkages.

MicroRNAs are small RNAs involved in regulation of cognate mRNAs, but predicting their exact targets has been difficult. Using a cross-linking immunoprecipitation technique, a comprehensive examination of endogenous mRNA target sites associated with the C. elegans Argonaute family member ALG-1 is now presented.

Classical type 1 dendritic cells (cDC1s) are essential for activation of antiviral and anticancer T cell responses. Murphy and colleagues describe a genetic circuit that involves the transcription factors Nfil3, Id2 and Zeb2. This circuit imposes a molecular switch that allows cDC1 specification and development.

Transcriptomic and proteomic analyses of cells and matrix along the fibrotic trajectory in mouse lung identified PI16 as an anti-fibrotic factor with potential for therapeutic application in humans.

LaccID, an engineered laccase, enables hydrogen-peroxide-free proximity labeling and electron microscopy (EM) in mammalian cells. Notably, LaccID is selectively active at the cell surface, enabling the mapping of the dynamic T cell–tumor surfaceome and its use as a genetically encodable EM tag, expanding the toolkit for cell-based imaging and proteomics.

Nellie is a comprehensive automated pipeline for studying the structure and intracellular dynamics of diverse organelles that offers accurate segmentation, tracking and feature extraction on both 2D and 3D data.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

This study establishes how aperiodic activity, a ubiquitous signal linked to neural noise, develops in localized brain regions and illuminates the development of prefrontal control during adolescence in the development of attention and memory.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration.