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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.

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.

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.

Cyclisation of R27 plasmid TrhA pilin occurs via a Gly1–Asp69 bond. Here, authors show Gly1/Lys and Asp69/Lys substitutions impose positive pilus charge, abolishing conjugation into wild-type recipients, rescued in phosphatidylethanolamine-deficient recipients, highlighting phospholipid importance in both donors and recipients.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

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.

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.

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.

Long COVID is associated with challenges in energy management, with limited interventions available. In this study, a just-in-time app-based energy management intervention for long COVID did not reduce postexertional malaise compared to usual care, though both groups improved over time, showing the approach was safe but not effective.

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.

Here, the authors report that the protein language model ESM-2 is broadly useful for variant effect prediction, including unobserved changes, and can be applied to understand novel viral pathogens with the potential to be applied to any protein sequence, pathogen or otherwise.

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.

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.

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.

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.

Researchers show that twisting SnS₂ nanosheets and anchoring single Ni atoms strengthens spin-orbit coupling, reshaping CO₂ photoreduction to favor ethane by generating and coupling methyl radicals from CO₂ and water.

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.

Plant diversity plays a key role in regulating ecosystem processes, yet its influence on global soil carbon release remains unclear. This study suggests that higher plant species richness is associated with greater soil respiration in low- to mid-productivity forests but has little effect in highly productive systems.

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.

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.

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.

Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

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.

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.

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.

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.

Neurotrophic factor Nerve Growth Factor (NGF) is involved in bladder physiopathology. Here the authors report that mast-cell derived NGF sustains the pro-tumoral functions of ILC2s in bladder cancer (BC), showing that selective targeting of the NGF receptor TrkA improves survival and response to immune checkpoint blockade in BC models.

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.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

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.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

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.

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.

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.

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 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.

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.

Sporulation in diderm Firmicutes requires the remodeling of an inner membrane into a functional outer membrane. Uncharacterized to date, this process involves the complete replacement of all proteins and lipids within a membrane. Here, the authors present a model in which the self-insertion of BamA triggers the inner-to-outer membrane remodeling.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

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.

Fast excitatory neurotransmission is mediated by AMPA receptors. Here, the authors discover that the GluA4 AMPA receptor subunit has distinct structural properties and conformational plasticity that tune its activation to glutamate.

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.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Loss of KRIT1 or CCM2 drives harmful KLF4 overexpression in brain vessels. Here, authors show a single KRIT1 must recruit two CCM2 proteins via dual PTB-NPxF interactions to suppress KLF4, revealing a previously unknown PTB clustering mechanism.

Nuclear protein homeostasis relies on proteasome import into the nucleus. Here the authors identify how assembled human proteasomes are transported across the nuclear pore complex and reveal a mechanism enabling the large complex to bypass pore size limitations.

Conventional slurry electrodes limit high-energy lithium batteries. This work shows that dry-processed electrodes with molecularly coupled carbon–binder networks enable high mass and active material loading, supporting stable high-voltage operation and enhancing battery energy density.

Cryo-electron microscopy structures of nucleotide excision repair complexes reveal the roles of the constituent proteins XPA, XPB, XPC, XPD, XPF, XPG and RPA in DNA bubble formation and excision of the lesion strand.