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This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

This Commission aims to resolve the current dialysis policy challenges in Thailand and generate lessons for the global kidney community by drawing on empirical evidence, systems thinking and multidisciplinary expertise to generate policy goals and recommendations.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Metals shortage threatens climate goals by affecting adoption of key technologies for the energy transition. Optimizing technology mixes is now shown to limit the supply-constrained energy transition metals to only copper, lithium, and vanadium, though economy-wide resource sobriety remains urgent.

Exposure to inflammation drives hematopoietic stem cells (HSC) aging, limiting their self-renewal capacity and differentiation. Here, the authors explore the mechanistic link between inflammation and HSC aging. Using mouse models, they identify the innate immune RNA sensor MDA5 as a key mediator of HSC aging and show that MDA5 loss ameliorates the aging phenotype by improving proteostasis in aged HSCs.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site of central nervous system immune entry and barrier regulation.

Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

GPSeq is a genome-wide method for probing the radial organization of the genome in cells or nuclei by progressive in situ digestion of chromatin with a restriction enzyme diffusing inward from the periphery followed by high-throughput sequencing.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Natural rubber is a widely used biopolymer and further improving its resistance to crack growth will extend its service life. Here the authors show a strategy to amplify the resistance to crack growth in natural rubber by forming a tanglemer.

Chlorine electrosynthesis from seawater is limited by poor selectivity and stability under industrial-scale conditions. Here atomic-step-enriched ultrafine high-entropy alloy nanowires enable highly efficient chlorine evolution at 10 kA m⁻² for over 5,500 h through dynamic Pt–O active sites, reducing electricity consumption and feedstock costs for next-generation chlor-alkali processes.

Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

JWST imaged three of the gas giants orbiting the star HR 8799 to study their atmospheres. The uniform enrichment of heavy elements, including sulfur, indicates that they formed like Jupiter and Saturn by accreting a lot of icy and rocky solids.

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.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Alternative splicing generates diverse protein isoforms, yet the functions of most exons remain unknown. Here, the authors introduce scCHyMErA-Seq, a scalable single-cell CRISPR exon-deletion platform that maps exon-specific transcriptional functions shaping gene expression and cell-cycle states.

The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Noradrenergic circuits support and balance aggressive behavioural states in predatory nematodes, distinguish predatory from non-predatory nematode species and are associated with the evolution of complex behavioural traits.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

The authors find that distinct radial glia subtypes generate and support midbrain dopaminergic neurons, revealing specialized function and lineage relationships among the diverse cell types that shape dopamine neuron development.

In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

MASH is driven by the secreted GPNMB ectodomain, which binds hepatocyte RYK to activate ERK1/2 and promote lipid uptake and lipogenic programs; blocking the GPNMB–RYK axis prevented and treated MASH in preclinical models.

Cryo-electron microscopy structures of three large ornate natural bacterial RNA molecules reveal their quaternary structures and intra- and intermolecular interactions that stabilize them.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

Boosting mitochondrial metabolism in neurons in central memory circuits by enhancing Ca²⁺ retention in the mitochondrial matrix is shown to improve long-term memory formation in flies and mice.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Without key cell cycle control genes, SAR11 cells experience aneuploidy and growth inhibition when exposed to changes in nutrients, carbon sources or temperature stress, a vulnerability that may represent an evolutionary trade-off for adaptation to oligotrophic environments.

Thermogenetics enables spatiotemporal control of protein activity using temperature. Now, engineering of a compact, insertable thermoresponsive protein module diversifies the classes of proteins amenable to allosteric thermoregulation.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

To enable a sensed RNA to activate diverse RNA effectors, the authors engineer a programmable dual-site ribozyme that, upon RNA trigger binding, self-cleaves to release an embedded RNA. It enables trigger-dependent release of diverse ncRNAs and controls CRISPR-Cas9 editing in zebrafish and human cells.

Frequency converters for wireless internet of things applications typically require separate circuits for different functions, causing energy and performance inefficiencies. Using an epitaxially grown VO2 memristor array, Liu et al. present a frequency converter with in-situ frequency synthesis and mix functionality.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Here they show that the adhesion GPCR Gpr126/Adgrg6 regulates trabeculation during heart development. Its N-terminal fragment is required for maintaining cell adhesion and compact wall integrity while its C-terminal fragment is essential to provide trabecular identity.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

Solid-state batteries promise high energy and safety but face challenges in ion transport and scalability. Here, authors develop entropy-driven zwitterionic dry polymer electrolytes enabling scalable, high-energy all-solid-state batteries operating efficiently under practical conditions.

Chang et al. found that nuclear reactive electrophile stress suppresses translation through HNEylation at C436 of NCBP1, triggering alternative splicing of S6K1, a key regulator of translation.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.