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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.

This study finds that cell segmentation errors affect numerous downstream applications of spatial transcriptomics data and provides a method to correct these errors by factorizing molecular neighborhoods.

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

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

The longevity of leaves determines the overall duration of photosynthesis for plants. This study suggests that climate change drives leaf longevity convergence toward intermediate ranges, which, by altering leaf traits and enhancing photosynthetic capacity, strengthens ecosystem stability and is closely linked to vegetation diversity.

Applications of optical laser-based techniques are limited by the long wavelengths of the lasers. Now, observations of phonons and thermal transport at nanometre length scales are reported with an all-hard X-ray transient-grating spectroscopy technique.

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.

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.

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.

In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Oat consumption, particularly a short-term, high-dose oat diet, improves metabolic health in individuals with metabolic syndrome by increasing microbially produced phenolic metabolites, leading to lower blood cholesterol levels.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Strain can lead to emergent quantum states. Here, the authors identify a strain induced topological crystalline insulator phase in bilayer SnTe on bulk 2H-NbSe₂.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Genome-wide analyses identify 13 loci associated with susceptibility to infection with SARS-CoV-2 Omicron variants, including variation in ST6GAL1, previously associated with influenza susceptibility, and other genes involved in glycosylation processes.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

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.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Genetic and isotopic analyses of samples from the northeast Atlantic reveal that suspended prokaryotic dark carbon fixation substantially fuels carbon inputs below the sunlit ocean, while particle-attached communities make an overlooked contribution to carbon demand.

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.

The formation of glycylglycine, a simple peptide molecule, is possible under non-aqueous interstellar conditions, according to laboratory experiments. Thus, complex organics with biological relevance may predate planetary accretion.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

T-cell therapies have huge potential but face technical limitations. Here, the authors report on a dextran-based nanoparticle platform that efficiently expands T cells, enhances CAR T-cell potency, persistence, and anti-tumour efficacy, using simpler and faster methods than current techniques.

AvrPm4 is a chimeric powdery mildew effector that is recognized by the wheat kinase fusion resistance protein Pm4. The pathogen can evade Pm4 recognition by expressing the suppressor SvrPm4, an RNase-like effector with multiple roles.

The Greenland shark, the longest-living vertebrate, inhabits the dim, frigid depths of the Arctic Ocean. Despite its extreme lifespan, this study finds that its vision remains intact and well-adapted for life in dim light, revealing remarkable preservation of sensory function across centuries.

Longitudinal cerebrospinal fluid proteomics in multiple sclerosis uncovers dynamic antiviral immune activity, sex-based differences in damage and repair, and evolving myeloid-stromal cell interactions that correlate with disability development.

Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Pastoralism spread through cultural diffusion into the Green Sahara, where an isolated, distinct North African ancestry persisted.

Mitochondrial dysfunction in dopaminergic neurons is a pathological hallmark of Parkinson’s disease. Here, the authors find a conserved mechanism by which a single transcription factor controls mitochondrial health in dopaminergic neurons during the aging process.

The authors conduct a national inventory on individual tree carbon stocks in Rwanda using aerial imagery and deep learning. Most mapped trees are located in farmlands; new methods allow partitioning to any landscape categories, effective planning and optimization of carbon sequestration and the economic benefits of trees.

Addressing how the nitrogen-induced changes in plant diversity differ from those in soil organisms is critical. This global meta-analysis suggests that nitrogen enrichment has stronger negative effects on plant diversity but modest to negligible effects on soil bacterial and fungal diversity.

Here the authors show that transient cell cycle arrest reprograms CD8⁺ T cells into a highly energized state, increasing proliferation and antitumor activity and boosting efficacy of immunotherapies in cancer models.

Geminin regulates DNA replication by binding CDT1 and preventing MCM helicase loading. Using a reconstituted system and structural modelling, the authors find geminin inhibits via steric clash with MCM, not by blocking the CDT1–MCM interface. Combined with CDK activity, it fully halts licensing.

Comparative genomics and high-resolution mass spectrometry reveal the biosynthetic gene clusters, and vast chemical diversity of natural products that they encode, in Photorhabdus and Xenorhabdus, bacteria that interact with hosts as symbionts and entomopathogens.

Uncertainty-aware machine learning models predict human toxicity for more than 100,000 chemicals, highlighting potency and uncertainty hotspots to guide safer use and to focus efforts to improve prediction confidence.

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.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

The alveolate alga Chromera velia is a close relative of parasitic apicomplexans that possesses an unusual Photosystem I. Here, the authors present the cryo-EM structure of this complex, revealing several novel subunits, including a bound superoxide-dismutase heterodimer.

A hierarchical cross-entropy loss is presented, which incorporates ontology structure into training and improves the out-of-distribution performance of large-scale single-cell annotation models without additional computational cost.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

This study advances methods for benchmarking macromolecular complex predictions by introducing a scalable open-source framework used in recent community assessments to compare structures, interfaces and ligand interactions against experimental data.