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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.

Edge localised modes (ELMs) in highly confined plasmas are notoriously difficult to regulate. Here, the authors analyse multiscale modes and interactions by combining experimental measurements from DIII-D and modeling, showing promising results in ELM control.

Synovial sarcoma (SyS) is a cancer driven by a fusion oncoprotein, SS18::SSX, but the mechanism underlying the oncoprotein-mediated tumorigenesis remains unclear. Here, the authors employ transgenic mouse models and multi-omics to show how SS18:SSX modifies the activity and recruitment of BAF-family chromatin remodeling complexes to drive SyS tumorigenesis.

Gas-phase actinium monofluoride (AcF) has been produced and spectroscopically studied at the CERN-ISOLDE radioactive ion beam facility; the results highlight the potential of ²²⁷AcF for exceptionally sensitive searches of CP violation.

Photonic time crystals (PTCs) have unveiled unusual band structures and phenomena due to temporal modulation of optical properties. Here, the authors address non-Hermitian features of PTCs within a purely Hermitian Hamiltonian description, bridging classical and quantum approaches.

Radical chain initiation strategies are fundamental to the synthesis of small molecule drugs and macromolecular materials. Here a general, thermally driven and scalable method for reductive initiation is reported, in which inexpensive azo initiators are reacted with formate salts to form a carbon dioxide radical anion.

Drug combination therapy is often required to overcome the limited benefits of monotherapy in cancer treatment. Here the authors present SynergyLMM, which harmonizes analyses of drug combination experiments in animal studies, helping researchers statistically test synergy and antagonism, design well-powered experiments, and enhancing eventual translation to more effective combination therapies.

Quantifying ecosystem dynamics is critical in the face of rapid environmental change. This study uses airborne eDNA to quantify changes in organism abundances across the tree of life and reveal a regional decline in biodiversity over three decades.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

Most active particles studied to date lack the ability to undergo controlled shape transformations and control over their propulsion in response to environmental stimuli. Here, the authors present a class of active particles made from stimuli-responsive materials that exhibit fully reversible shape-dependent propulsion.

Neri et al. develop elegant tools to understand how the sympathetic nervous system regulates intrascapular brown adipose tissue (iBAT) function. Using these tools, they find that sympathetic nerves targeting the iBAT parenchyma control local blood flow and heat production, while those innervating the iBAT vasculature regulate systemic glucose metabolism.

Numerous methods predict unmeasured gene expression in spatial transcriptomics data, but most focus on individual genes and yield variable results. Here, the authors present an approach that leverages cell type and spatial context for robust pathway expression prediction.

Several moons in the outer Solar System have oceans encased beneath an ice shell. If the ice shell thins, ocean pressure decreases. Modelling shows that on Mimas, Enceladus, and Miranda, the ocean can boil. On larger bodies, instead, compressional forces form tectonic features.

Age-related macular degeneration (AMD) is a common cause of vision loss with a large genetic risk in older individuals. Here, for a high-risk AMD subtype, the authors identify an association with a chromosome 10 risk region containing a long non-coding RNA.

Chiral γ-butenolides, which are widely prevalent in natural products and pharmaceuticals, necessitate synthetic methods that precisely control both stereochemistry and substituent diversity. Here, the authors report a Cu/PyBim-catalyzed asymmetric lactonization of 2,3-allenoic acids initiated by sulfonyl or phosphonyl radicals.

Programming microbial interactions can enhance biomanufacturing. Here, the authors develop a synthetic yeast toolbox that programs cell–cell adhesion and cross-feeding, enabling spatial patterning coupled with division of labor to boost production of the high-value antioxidant resveratrol.

Engineered Escherichia coli strains expressing a colibactin antitoxin, ClbS, on the surface prevent the genotoxic effects of colibactin released by genotoxin-producing bacteria in the mouse gut.

In this study, the authors show that integrating a host gene biomarker with a large language model (LLM) improved lower respiratory tract infections diagnosis in a cohort of critically ill patients. The LLM plus biomarker outperformed the diagnosis made by the initial medical team and each component alone.

The authors report the discovery of charge order with onset temperature of 800 K in the kagome superconductor YRu₃Si₂. In addition, they observe time-reversal symmetry breaking below 25 K, field-induced magnetism below 90 K and bulk multi-gap superconductivity below 3.4 K.

The universality of the energetic equivalence rule has long been debated. Here, the authors show that across 183 soil invertebrate food webs, size–density and energy use varied with trophic level, energy measure, and food web structure, showing that ecosystem energetics depend on context and trophic complexity.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

Rare loss-of-function mutations in SETD1A are associated with schizophrenia, but how SETD1A haploinsufficiency leads to disease phenotypes remains unknown. Here, authors show that SETD1A regulates genes at common schizophrenia risk loci regulating genomic stability and synaptic function.

Structure-specific endonucleases play an important role in several DNA repair pathways. Here the authors present structures of the endonuclease XPF-ERCC1 in complex with SLX4, SLX4IP, and DNA. Combined with functional analysis, these results provide insight into the mechanisms of XPF-ERCC1 recruitment and activation during DNA repair.

Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Most plastic waste is landfilled, and polyolefin recycling needs external H₂. This work couples decalin dehydrogenation with polyethylene hydrocracking, using in situ H₂ to yield liquid fuels efficiently, improving both economic and environmental sustainability.

This study shows that optimally sized nanocarriers reach Duchenne muscular dystrophy muscle primarily through transcytosis, where they can deliver tamoxifen to improve muscle health and strength in mice.

Degraders of SMARCA2/4 have so far relied on bivalent designs. Here, a targeted discovery campaign identified the first monovalent degraders, revealing a highly potent, selective compound that recruits FBXO22 through a covalent mechanism.

Methods used to date a network of marine sediment cores reveal that rapid retreat of the Ross Ice Shelf was contemporaneous with the lowering of nearby outlet glaciers, implicating warm ocean waters as a driver of Antarctic deglaciation.

Plant mitoribosomes are crucial for mitochondrial protein synthesis. Here, authors use cryo-EM to determine high-resolution structures of cauliflower mitoribosomes, and combined with sequencing and mass spectrometry, identified 19 rRNA base modifications.

ABC toxins are bacterial insecticides with biotechnological potential. Here, Low et al. have deciphered soluble and membrane-inserted structures of YenTc that highlight structural and mechanistic diversity in the ABC toxin family and provide insights into their evolution.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

Phototoxicity can distort live-cell microscopy results, yet tools to measure it are limited. Here, the authors present PhotoFiTT, a machine learning–based framework that quantifies light-induced stress on cells, helping researchers optimise imaging protocols while protecting sample health.

Repetitive DNA sequences shape genome evolution and instability. Here, the authors analyze repeat length distributions across over 300 mammals and show that long repeats arise and persist through a dynamic balance of mutation processes, without requiring natural selection.

This work introduces Cyclone, an acyclovir-controlled cassette that enables regulation of both transgene and endogenous gene expression with minimal background activity.

A dual-cofactor artificial metalloenzyme is developed, incorporating a biotinylated nickel complex and a Strep-tagged peptide catalyst in adjacent streptavidin-binding sites. This synergistic artificial metalloenzyme achieves enantiodivergent Michael addition reactions with tunable stereochemistry and high turnover numbers across diverse ketone and enal substrates.

PPARγ regulates glucose and lipid metabolism, yet safer PPARγ-targeted insulin sensitizers are needed to treat metabolic disorders. Here, Kuang-Ting et al. elucidate structure–function relationships of non-covalent inverse agonists that enhance receptor binding and improve insulin sensitivity, providing a framework for next-generation drug design.

Two groups of ammonia-oxidizing archaea drive marine nitrification. Stuehrenberg et al. reveal that their distribution reflects substrate use, with one relying on urea and the other on ammonia to maintain nitrification in open-ocean waters.

In patients with hormone receptor positive, human epidermal growth factor receptor 2-negative (HR+/HER-) breast cancer, endocrine therapy is standard of care but resistance often occurs. Here, the authors report a phase I trial investigating the ER degrader, AC699, in patients with locally advanced or metastatic ER+/HER2- breast cancer.

Chimeric antigen receptor T (CAR-T) cell therapy uses engineered donor T cells to recognize and eliminate cancer cells through cognate antigen-dependent activation. Here authors develop an alternative to bead-based or cancer-cell-induced CAR-T cell activation by presenting the antigen on the surface of engineered yeast cells, which allows precise regulation of antigen density.

Estrogen receptor α is a primary driver of ER+ breast cancer and reproductive development. Here, the structure of the apo state is reported, providing a revised model for ligand-dependent and -independent regulation of receptor function.

Single-molecule tracking reveals nanoscale domains within fused-in-sarcoma condensates. These nanodomains migrate to the condensate surface during ageing, seeding amyotrophic lateral sclerosis-linked fibrils, a process accelerated by small-molecule drugs.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

In Li-mediated electrochemical N₂ reduction to ammonia, selectivity and activity are governed by the solid electrolyte interphase (SEI). This study reveals how the applied potential shapes the SEI properties and composition, thereby influencing reaction performance.

Li et al. conducted a nationwide, three-generation study in the Netherlands (n = 15 million) to investigate familial associations between ADHD, autism and cardiometabolic conditions using population-based registers.

The authors show that babies conceived during the COVID-19 pandemic have a different parental socioeconomic composition than expected had the pandemic not occurred.

89ZED88082A is a zirconium-89-labeled one-armed anti-CD8α antibody for the non-invasive whole-body visualization of CD8 + T-cells by positron emission tomography (PET). Here the authors report the results of a phase 2 study of 89ZED88082A for whole-body CD8 + T-cell PET imaging in patients with large B-cell lymphoma before and during CD19-directed CAR T-cell therapy.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.