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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.

Lymphangioleiomyomatosis (LAM) is a rare disease in women where TSC2 deficient mTOR signalling aberrant LAM cells and fibroblasts form nodules causing lung cysts and respiratory failure. Here the authors examine how mTOR dependent IL-6 causes senescence in alveolar type 2 cells which may result in impaired lung repair.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

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.

Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Metronomic photodynamic therapy is a long-term, low-dose treatment strategy limited by the need of continuous photosensitizer administration. Here this group reports combining the self-bioluminescent bacteria with a neutral red photosensitizer in alginate microcapsules as a self-driven metronomic photodynamic therapeutic system with preclinical anti-cancer effects.

Infant KMT2A-rearranged acute lymphoblastic leukemia is associated with poor overall survival rates. Here, the authors use WGS and WES of 36 relapsed KMT2A-rearranged ALL and AML patients and find alterations in drug response genes in ALL, which may correspond with relapse time. Longitudinal analyses of >250 samples could track residual leukemia cells, clonal drug responses, and the upcoming relapse.

In vivo gene editing hinges on identifying an ideal delivery vehicle from numerous candidates. Here, authors establish the GFP-on mouse model capable of translating successful adenine base editing to a fluorescent readout thus enabling the rapid evaluation of genome editing delivery vehicles.

Reframing of arousal as a latent dynamical system can reconstruct multidimensional measurements of large-scale spatiotemporal brain dynamics on the timescale of seconds in mice.

The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.

The slit diaphragm is a key component of the glomerular filter. This study reveals that the slit diaphragm of Drosophila nephrocytes exhibits a fishnet architecture, offering insights into the molecular basis of renal filtration.

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 UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids in peroxisomes is described and a previously unrecognized role for peroxisomes in adipose tissue thermogenesis is identified.

The authors estimate genomic vulnerability for closely related species of rainbowfish. They find that narrow endemic species that have hybridized with a warm-adapted generalist show reduced vulnerability to climate change and that hybridization may facilitate evolutionary rescue for such species.

Lee et al. show that the circadian clock protein REV-ERBα controls brain NAD⁺ levels by regulating the NAD⁺-consuming enzyme CD38. Global or astrocytic REV-ERBα deletion or pharmacologic REV-ERB inhibition protects against tau pathology in mice.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

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.

Viral vector integration can affect the safety of gene and cell therapies. Here, authors introduce MELISSA, a regression-based statistical tool that quantifies integration site risks and clone growth effects, aiding the safety evaluation of therapies in both research and clinical settings.

Bennu comprises components of intra- and extra-Solar System origins. The parent bodies of Bennu, Ryugu and CI chondrites likely formed from a shared but heterogeneous reservoir in the outer parts of the solar protoplanetary disk.

Non-invasive optical imaging tools for early detection of anti-tumor immune responses are essential for precision cancer immunotherapy. Here, the authors report a rare-earth-based NIR-II fluorescence ratiometric nanoprobe (DCGA) for in vivo real-time, precise, and non-invasive visualization of granzyme B activity for early prediction of immunotherapy efficacy.

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.

Glucocorticoid (GC) induced osteoporosis (GIOP) remains a significant clinical problem. Here, the authors find that GCs disrupt skeletal stem cell–endothelial crosstalk via Basigin that can be targeted as a potential therapy for GIOP.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition. This study presents a drug-free treatment strategy for IBD that targets bacterial adhesion, utilizing mannan oligosaccharide-loaded porous microgels to selectively capture adherent-invasive E. coli and competitively inhibit bacterial colonization on the gut epithelium.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Sandhoff disease (SD) is a lysosomal storage disorder caused by deficiency in the β subunit of the β-hexosaminidase enzyme. Here, the authors show via bone marrow-based microglial replacement in a SD mouse model that myeloid-derived β-hexosaminidase is necessary for maintaining neuronal health.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

Border and colleagues present FUSION, an open-source, web-based platform designed to integrate spatial omics with histological context. FUSION enables intuitive, interactive exploration of cellular and tissue-level features across diverse organs and assay types.

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.

UTe₂ is a proposed intrinsic topological superconductor, but its quasiparticle surface band has not yet been visualized. Now this is achieved using quasiparticle interference imaging, revealing the symmetry of the superconducting order parameter.

Proteomic analysis of paired cerebrospinal fluid and plasma samples from 2,171 individuals drawn from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium, reveals age-related changes in the ratios of proteins in the cerebrospinal fluid and plasma that are associated with cognitive function, enhancing understanding of blood–brain barrier dynamics in aging.

Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spectrometry. Now a method has been developed to profile protein arginylation ex vivo and is tested on different samples, revealing 235 unique arginylation sites in the human proteomes.

Lowering the levels of coagulation factor XII may prevent thrombosis without increasing the risk of bleeding. Here, Haj et al. use a large human dataset to show that this is the case for people carrying mutations that lower the levels of factor XII.

The ability to encode and recall information about food is critical for survival. We reveal that ventral hippocampus projections to the lateral hypothalamus encode meal-related memories, and that disruption of this circuit promotes excessive eating.

A geological, petrographic and geochemical survey of distinctive mudstone and conglomerate outcrops of the Bright Angel formation on Mars reveals textures, chemical and mineral characteristics, and organic signatures that warrant consideration as potential biosignatures.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Pathological B-cell receptor (BCR) signaling is a key driver of mantle cell lymphoma tumorigenesis. Here, the authors discover that CEACAM1, an immunoglobulin-like transmembrane protein, is essential for a subset of mantle cell lymphoma through activation of the BCR.

The detection of the auroral footprint of Jupiter’s moon Callisto is challenging, but a shift in Jupiter’s bright main auroral oval could provide an opportunity for potential detections. Here, the authors show observation of the ultraviolet footprint of Callisto using Juno spacecraft data, benefiting from such opportunity.

Biomolecular phase separation arises from collective molecular interactions and is emerging as a key theme for biological function. Here the authors propose a broadly applicable method to quantify these interactions based on compositional and energetic parameters.