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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 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.

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.

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.

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.

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.

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.

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.

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.

Studies in zebra finches show that dopamine has a key role as a reinforcement signal in the trial-and-error process of learning that underlies complex natural behaviours.

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.

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.

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.

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 lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

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.

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.

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.

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.

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.

A measurement strategy is described that is able to read out the parity of minimal two-site Kitaev chains in real time, by coupling two Majoranas and resolving their quantum capacitance.

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.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

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.

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

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.

This study utilized a longitudinal cohort of adolescents to identify distinct brain signatures linked to ADHD symptom trajectories, revealing that specific cortical and subcortical changes correlate with symptom persistence, remission and emergence, enhancing predictive capabilities for ADHD outcomes.

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.

The authors realize two- and three-site Kitaev chains in semiconducting quantum dots coupled via superconductors and tune them to the sweet spot where zero-energy Majorana modes appear at the chain ends. To assess Majorana localization, they couple the system to an additional quantum dot.

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.

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.

The authors demonstrate that targeted protein degradation of the dengue virus capsid suppresses infection through capsid-dependent pathways rather than classical inhibition, revealing a new antiviral strategy effective against resistant viral variants.

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.

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.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

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

Peroxidases have long been considered to use ferryl heme intermediates (Fe(IV) = O) to catalyze oxidative chemistries. Here, Williams et al. find that ferric-oxyl (Fe^III–O^•–) excited states exist along the catalytic reaction coordinate of a peroxidase.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

Butenolides are important features of many bioactive compounds but known butenolide biosynthetic pathways are complex and challenging to harness. In this study, the authors report that avenolide, a 4-alkylbutenolide that regulates avermectin production in Streptomyces avermitilis, is assembled from a fatty acyl thioester by a multifunctional flavoenzyme and an iterative cytochrome P450.

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.

This paper presents an active pixel power control (APPC) to minimize crosstalk in all-optical neural interrogation. Tested in vivo, APPC suppresses optogenetic artifacts while preserving Ca2+ imaging quality, enabling precise neural circuit analysis.

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.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

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.

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.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

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.