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Hepatitis C virus remains a health burden due to the lack of an effective vaccine, hindered by difficulties in replicating the native E1E2 antigen structure. Here, the authors engineer a stabilized E1E2 heterodimer using cryo-EM-guided modifications, enhancing immunogenicity and paving the way for future HCV vaccine development.

In this study, the authors describe how light shapes a long-term threat avoidance behavior via a visual circuit linking the eye with the limbic system in mice.

Brief ultrasound to human frontal eye fields, but not motor cortex, rapidly biases eye movement contralaterally in a perceptual choice task. The size of this effect scales with individual baseline FEF inhibitory tone.

The transformations for aragonite precursors in coral are not fully understood but have implications in bio, biogenic and geological mineralization. Here, the authors use high-resolution mapping and observe exponential decay from the edge of four precursors to coral aragonite skeleton in Stylophora pistillata.

Spectroscopic observations of the ultra-hot Jupiter WASP-189b reveal both volatile (H₂O, CO, OH) and refractory (Fe, Mg, Si) gas in its atmosphere. Here, the authors show that the abundance ratio of refractory species reflects that of the host star.

DNA recognition and cleavage control in type II topoisomerases are poorly understood processes. Here, the authors determine cleaved and uncleaved structures of supercoiled DNA-bound topoisomerase VI that reveal how the enzyme activates its cleavage state and prefers to act at deformable substrates.

ASXL1 is often mutated in myeloid cancers. Here, the authors describe the molecular and structural mechanism by which ASXL1 associates with the transcriptional coactivator BRD4, helping to explain their high correlation in cancers.

Most patients with B-cell leukemia respond to chimeric antigen receptor T cell (CAR T) therapy, yet many relapse due to loss of CAR T function. Here, the authors show that the metabolism of CAR T from short- and long-term responders is different, which may explain why CAR T lose functionality.

Here the authors identify nicotine-derived inhibitors of the SARS-CoV−2 main protease that outperform Paxlovid in cells and mice, remain effective against resistant variants, and show broad activity against multiple human coronaviruses.

PAN2-PAN3 complexes trim poly(A) tails of mRNAs. Here, the authors show that PAN2 associates with translation initiation factors and that germline-specific deletion of Pan2 in mice causes male infertility and compromises stability of key components of the translational machinery.

Supersolid phases are quantum-entangled states of matter exhibiting the dual characteristics of superfluidity and solidity. Here, the authors map the phase diagram of K₂Co(SeO₃)₂. and identify signatures of two supersolid phases separated by a 1/3 magnetization plateau.

Dynamos can generate magnetic fields, which are present across various scales in space plasmas. Here, the authors show evidence for a turbulent dynamo in the terrestrial magnetosheath, indicating that Earth’s magnetosheath may be used as a natural laboratory for testing dynamo theories and simulations.

Large biospecimen banks are limited by a lack of fast, flexible, database-like retrieval. Here, authors encode metadata as DNA barcodes on silica-encapsulated samples and demonstrate numerical range, categorical, and Boolean queries, enabling rapid, precise recall from pooled DNA/RNA archives.

2D covalent organic frameworks usually possess a polycrystalline nature as well as lower porosity and surface area than 3D counterparts, limiting their gas storage application. Here, the authors report the formation of single-crystal 2D covalent organic frameworks isomers with atom-resolution structures for methane storage.

Exhaustion is a functional state that hampers anti-cancer and antiviral CD8 T cell activity, and is preceded by a stem-like state, maintained by the transcription factor TCF1. Here authors develop mouse models that allow a precise understanding of the developmental trajectory between the stem-cell-like and exhausted states of CD8 T cells and find that while constitutive overexpression of TCF1 expands the stem-like T cell pool, TCF1 expression specifically in already exhausted cells is unable to promote dedifferentiation.

De novo Calcineurin (CN) variants cause DEE91, with E282K being the most common. E282K alters CN’s acidic substrate binding pocket to basic, thus shifting substrate preference and dephosphorylation signaling, subsequently impacting neurodevelopment.

Long-term patterns of physical activity and the importance of consistent adherence to the recommended level remain poorly understood. Here, the authors show that maintaining physical activity over the long term offers added benefits beyond activity volume alone for chronic disease prevention.

Continuously trapped atoms provide advantage for atom interferometry, yet current schemes are limited by dephasing. Here, the authors develop a Floquet-engineered atom interferometry platform for quantum force sensing purposes, unveiling regimes where the interferometric phase is insensitive to noise.

High spatial resolution is essential for resolving cellular and subcellular organization in tissues. Here, authors present Seq-Scope-X, which integrates tissue expansion with Seq-Scope to achieve an order-of-magnitude improvement in resolution of spatial transcriptomics and proteomics.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

The study shows that incorporating information on pre-existing moisture conditions into the atmospheric river scale improves early-warning identification of flood-generating events.

DNA methylation heterogeneity and dynamics hinder distinguishing early pathological changes from normal variation. Here, the authors identify stable sites whose disruption is linked to blood cancers, aging, and cardiovascular risk.

Gestational exposure of mice to the obesogen tributyltin alters 3-D chromatin interactions in primordial germ cells leading to stable reduction of hepatic Ide expression and predisposing male descendants to insulin dysregulation and obesity.

Here researchers reveal a microexon in the Ank3 gene encoding Ankyrin G allows cortical interneurons to fine-tune calcium signaling and firing, revealing the contribution of alternative splicing to the functional diversity among different types of neurons.

Here, the authors propose the Antarctic Ecosystem Value Index, an Earth systems model-based measure of marine ecological value. The index identifies potential present and future high-value locations, which often fall within coastal polynyas.

Most studies assessing food self-sufficiency look at calories and neglect nutrient gaps. Comparing food demand and potential food production under land and water constraints, this study quantifies 9 key nutrient gaps for each of African’s 54 countries.

Neuropathic pain is commonly treated with opioids due to limited alternatives. Here, authors determine cryo-EM structures of the neuronal glycine transporter GlyT2 and develop a reversible inhibitor that provides analgesia in vivo without side effects.

Using recent TMTH-sulfoximine (THS)-based biorthogonal chemistry in live cells, Smits et al. identify micro- and nanodomains in cell-cell and cell-matrix contacts of heterogenous glycocalyx density in invading melanoma cells.

In this study, the authors develop a stoichiometric-thermodynamic model linking seismic decarbonation to Mw 5.9–6.5 earthquakes. They demonstrate that seismic CO₂ pressurization can sustain dynamic slip and enhance the destructive potential of earthquakes.

Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

Precise and efficient CRISPR genome editing requires specialized delivery systems. Here, the authors develop Coomassie lipidoids that deliver purified adenine base editors into retinal tissues, making it possible to achieve robust genome editing with a defined, non-viral nanomedicine.

Mass spectrometry (MS)-based proteomics is increasingly central to systems biology. Here, the authors present a high-throughput, multi-organ workflow that profiles 11,472 proteins in 507 mouse samples, enabling rapid, system-level evaluation of drug efficacy and toxicity.

The existence of multi-centennial natural variability in the North Atlantic is demonstrated over the last millennia by compiling proxy data. This variability mode will potentially amplify northern Europe warming by up to 30% over 2000-2035.

Extracellular electron transfer (EET) in bacteria requires the spatiotemporal coordination of many proteins. Here, authors show that the inner-membrane protein CymA reorganizes spatially into condensates and drives the colocalization of partner proteins to enable EET in Shewanella.

In this study, the authors designed potent Enterovirus D68 capsid inhibitors that block viral binding and show that the lead compounds reduce virus levels, prevent paralysis and improve survival in EV-D68-challenged mice, even when treatment starts days after infection.

The SONAR trial showed that the endothelin receptor antagonist atrasentan improves kidney outcomes in patients with type 2 diabetes and chronic kidney disease, though individual responses varied. Here the authors report exploratory analyses of the SONAR trial that identify urinary clusterin as a potential predictor of kidney disease progression and response atrasentan in type 2 diabetes.

Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.

Here, the authors show that myoferlin is a crucial host factor that helps move viral genetic cargo to the cell surface, boosting influenza, RSV and Sendai virus spread, highlighting a common weak spot for future antivirals.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

Attention fluctuates over time and across contexts—how is this reflected in the brain? Fitting a dynamical systems model to fMRI data, Song and colleagues show that the geometry of neural dynamics along the attractor landscape reflects changes in attention.

Authors find a twin-spin state in antiferromagnets, quantifies its magnetic octupole spin–orbit torque, and shows that it enables exceptionally long-distance spin transport beyond conventional spin currents.

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.

This study quantifies the environmental impact associated with photovoltaics manufacturing and demonstrates significant CO₂ emissions savings, depending on solar cell technology and the composition of the electricity mix in the region of manufacture.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Kohl et al. combine high-resolution Ribo-seq and cryo electron microscopy to show that the bacterium Staphylococcus aureus uses extended Shine-Dalgarno motifs to initiate translation, which can make start-site decoding incompatible with phylogenetically distant ribosomes.

Repurposing existing drugs to target new disease-associated genes is a promising strategy, but identifying these targets can be challenging. Here, the authors develop GenT, an approach that uses GWAS data to identify disease-associated druggable genes.

Femtosecond X-ray solution scattering reveals how solvent environments direct the outcome of ultrafast roaming reactions in bromoform, determining whether transient hot isomers undergo rapid solvolysis or rearrange into long-lived isomeric products.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.