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This study introduces a genomic typing system for Moraxella catarrhalis, revealing two major lineages with distinct evolution, variability, and virulence traits.

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.

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

Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

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.

Natural variation in hecw-1 encoding an E3 ubiquitin ligase influences the avoidance of pathogenic bacteria by Caenorhabditis elegans and forms a molecular basis for behavioural variation.

Here, the authors use a mouse model of multiple sclerosis to show that CD38⁺Foxp3⁺ T_reg cells persist in postinflammatory CNS tissues and are needed for maintaining immune homeostasis. These localized stress-tolerant T_reg cells have developed mechanisms to exploit the limited availability of IL-2 in this tissue.

DEAD-box helicase 6 (DDX6), the regulator of P-body assembly, is essential for the survival of acute myeloid leukemia (AML) cells. Here the authors report that DDX6 undergoes phase separation to preserve mRNA subsets in P-bodies, promoting branched-chain amino acid metabolism and chemoresistance in AML.

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.

Here they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

Grain chalkiness is an undesirable trait that severely compromises rice quality. Here, the authors report the cloning of an E3 ubiquitin ligase encoding gene Chalk9 and reveal its crucial role in regulating grain chalkiness through mediating the ubiquitination-dependent degradation of OsEBP89.

Tumor pericytes are located surrounding blood vessels, and can regulate tumor vascular structure. Here, the authors discover that a subpopulation of NKX2-3 high tumor pericytes modulates vasodilation and hemodynamics to promote metastasis.

Using a mouse model with a macrophage-specific DNA repair defect, Niotis, Arvanitaki et al. identify DNA damage-induced autophagy in macrophages as a link from aging to autoimmunity.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

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.

The genetic basis underlying resistance to Sclerotinia stem rot (SSR) in oilseed rape remains elusive. Here, the authors identify BnaA07.MKK9 as a pivotal regulator of SSR resistance in oilseed rape by GWAS, providing new insights into plant defense mechanisms against necrotrophic pathogens.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Li, Cui, Yang, Lu, Jiang, Zhang and colleagues identify a lactate transport mechanism from tumour-associated macrophages that regulates DNA repair and immune cell infiltration, which could be targeted to enhance immunotherapy efficacy in glioblastoma models.

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.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

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.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

Neo et al. map blood emergence from three hemogenic endothelial (HE) populations biased toward distinct blood fates. HE primed for stem progenitors shows elevated chromatin and RNA splicing gene expression and greater isoform diversity.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

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.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

This study presents LoopID, which profiles proteins at targeted interacting enhancer–promoter (E-P) pairs, identifying the histone demethylase JMJD2 as a regulator of E-P interactions through biomolecular condensate formation independent of its catalytic activity.

Veiga-Fernandes and colleagues show that neuroepithelial interactions differentially control type 1 and type 2 enteric immunity via VIP–VIPR1 signaling.

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.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Reactive carbanions are typically formed by deprotonating relatively acidic C–H bonds. Here, the authors demonstrate that combining sodium tris(pyrazolyl)borate with mesityllithium in the presence of a donor ligand generates a reactive organometallic mixture that deprotonates benzylic C–H bonds, enabling the isolation of cationic sodium benzyl species.

Signalosomes amplify cellular responses, but how they avoid uncontrolled activation is unclear. The authors use quantitative super-resolution imaging and mathematical modeling to reveal optimal RIP3:RIP1 ratios that ensure precise cell death signaling.

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.

How α-synuclein interacts with the neuronal cell surface to contribute to disease pathology is not fully understood. Here, the authors conducted a comprehensive search for neuronal membrane proteins mediating α-synuclein aggregate uptake, and identified mGluR4 and NPDC1 as essential for Parkinson’s disease related neurodegeneration triggered by extracellular α-synuclein fibrils.

Decadal-scale observations reveal that plant diversity stabilizes ecosystem productivity over time. Phylogenetic diversity is the key driver of long-term stability, whereas plant height shapes short-term productivity dynamics.

Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, authors provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human myelodysplastic syndrome.

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.