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Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. Here authors show that stressed dopaminergic neurons actively induce a state of transmissive dormancy and appear to prioritize viability over functionality.

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.

New insights into the actions of the hormone glucagon are provided by a recent study in rodents, which shows that glucagon can suppress hepatic glucose production by acting through the mediobasal hypothalamic region of the brain. This central regulatory mechanism is impaired in rats fed a high-fat diet, suggesting that hypothalamic glucagon resistance may be relevant to the hyperglycemia observed in obesity, diabetes or both (pages 766–772).

Exercise promotes recovery after stroke, but the underlying mechanisms are unclear. Here, the authors show that regulatory T cells enable exercise-induced repair by reducing neuronal hyperexcitability via interleukin-10, linking immunity to functional regeneration.

Large language models can describe and classify changing objects in astronomical images with high accuracy. This enables searches for visual features using text and introduces a new way to interact with sky survey data.

Here, the authors demonstrate increased global lactylation levels and in the joints of rheumatoid arthritis patients. NFATc2 is identified as a key target gene regulated by histone H3 lysine 9 lactylation that exacerbates disease progression by enhancing the cartilage invasive function of fibroblast-like synoviocytes.

Mitochondrial dysfunction contributes to septic cardiomyopathy and poor outcomes. Here, the authors identify a cardiomyocyte-enriched non-coding RNA that preserves mitochondrial function and reduces mortality in septic mice by preventing citrate synthase acetylation.

The intestinal brush border consists of an array of densely packed microvilli that regulate absorption of nutrients. In this Review, the authors provide an overview of the many components that form the highly organized brush border domain and discuss pathological causes and consequences of a loss of brush border integrity.

Type 2 diabetes predisposes individuals to multiple comorbidities, but causal mechanisms are unclear. Here, the authors use Mendelian randomisation to show that distinct genetic pathways underlie diabetes-related risks, with ancestry-specific differences.

In this Review, Lemon and colleagues describe the interactions of the RNA genome of hepatitis C virus with various host proteins and microRNAs. They discuss how these interactions affect viral RNA synthesis and decay, and how they influence the long-term persistence of the virus.

KCTD10 interacts with the DNA replication machinery and the RNA polymerase complex, inducing ubiquitination and removal of the transcription machinery in the event of co-directional transcription–replication conflicts.

Bacterial deaminase toxins are weapons used in interbacterial antagonism and valuable tools in genome engineering. Here, the authors show how a single-stranded DNA-specific deaminase toxin, SsdA, deaminates cytosines in a sequence context-independent fashion and its utility in base editing.

E. coli sequence type 131 is a significant cause of community-onset infection. Here, the authors perform a prospective household-based cohort study in Singapore including samples from humans, companion animals, the environment, and food, to characterise transmission and carriage dynamics.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Here authors report that mutations in the neurodevelopmental risk gene ZMYND11 disrupt human cortical neuron development by altering chromatin regulation and RNA splicing.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

Dietary cysteine enhances intestinal stem cell-mediated intestinal repair following injury by promoting CD8 T cell-regenerative immune responses.

Li, He, Liu and colleagues characterize the dynamic bivalent chromatin landscape during mouse peri-implantation development. They find that factor ZBTB17 works with KDM6A/B to resolve transiently maintained bivalent domains and prime gene activation.

In vitro transcribed circular RNAs (ivcRNAs) offer a stable and efficient platform for protein replacement therapy. Here, the authors show that localized ivcRNA delivery restores MSI2 and SOX5 expression in chondrocytes, mitigating osteoarthritis progression in mice.

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.

Spiking neural networks promise fast and energy-efficient information processing. The ‘time-to-first-spike’ coding scheme, where the time elapsed before a neuron’s first spike is utilized as the main variable, is a particularly efficient approach and Göltz and Kriener et al. demonstrate that error backpropagation, an essential ingredient for learning in neural networks, can be implemented in this scheme.

Oxaloacetate is sensed by MDH1, which primes innate immune antiviral defence against influenza virus infection, thus resulting in the activation of ETS2 to promote TBK1-centred type I interferon signalling.

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.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

To date, experimental induction of hair cell regeneration in mammals leads to immature and poorly differentiated hair cells. Here the authors show that the transcription factor prdm1a plays a crucial role in specifying sensory hair cell types with loss of prdm1a in zebrafish leading to misspecification of hair cells in the sensory lateral line system into ear hair cells.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Selecting the appropriate Cas12a among the many orthologs for a given target sequence remains difficult. Here, Peng Chen et al. evaluate the activity and specificity of Cas12a variants and facilitate the selection of guide RNA and appropriate Cas12a candidates for gene editing.

Genetic background, plasma metabolome and dietary data from 4,215 women and 1,490 men reveal 57 metabolites whose associations with dementia risk vary by APOE4 genotype and other risk variants.

Li and colleagues report that a septo-enteric polysynaptic circuit that is activated by chronic stress links the brain to the tumor microenvironment to promote colorectal cancer growth.

Immune check point therapies have not been successful for prostate cancers, but the underlying mechanisms are unclear. Here the authors show that a transcription factor, YY1, may promote the SUMOylation and stability of HIF-1α to suppress anti-tumor immunity, while targeting YY1 helps improve tumor control, in mouse prostate cancer models.

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.

In urethral damage, exogenous implants designed for urethral repair are hindered by the open and harsh urethral microenvironments and the isotropic compression and swelling properties of the material. Here, Yang et al. develop a tri-layer hydrogel with anti-fouling and low-swelling properties for scarless urethral repair.

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.