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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.

C-prenylated flavonoids possess notable pharmaceutical potential, but their production is hindered by the challenging selective prenylation of their unstable polyphenolic cores. Here, the authors present a directed evolution strategy to reshape the active pocket of the prenyltransferase AtaPT, uncovering an aromatic cage that governs both regioselectivity and donor specificity, and achieve efficient and scalable synthesis of 27 C-prenylated flavonoids.

The study of highly active electrodes in organic electrosynthesis remains an under-investigated component of the subfield. This work introduces a bottom-up route to prepare chitin-derived composite carbon aerogel electrodes (CCAEs), which can be directly used as electrodes in organic electrosynthesis systems.

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.

Here, the authors develop Q4ddPCR, a high-throughput assay to quantify genetically intact HIV reservoirs by targeting four regions, and demonstrate that it reduces assay dropout to 5%, tracks reservoir decay, and closely correlates with viral outgrowth.

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.

Coronaviruses use suboptimal codons yet efficiently translate proteins. Here, the authors show that SARS-CoV-2 and HCoV-OC43 infections reprogram four host tRNA modifications, linking stress-induced tRNA remodelling to enhanced viral translation.

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.

The authors show that aging of metastable protein condensates can lead to amyloid formation and impair biochemical activity. Certain small molecule metabolites can selectively impede this transition, preserving condensate function.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

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.

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.

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.

Pertussis notifications reduced during the COVID-19 pandemic in the Netherlands but increased in 2023 to the highest levels since vaccination introduction. Here, the authors use longitudinal serological data from a nationwide cohort study to investigate waning immunity and infection incidence.

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.

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.

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

Here the authors report a kilowatt-scale, alkali-cation-free CO₂ electrolysis system using high-diffusion-flux gas diffusion electrodes, achieving over 1000 h of stability for efficient CO or C₂H₂ production at industrially relevant current densities.

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.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

The majority of microbial metabolites remain cryptic or minimally expressed under laboratory conditions. Here authors show that high-energy pulsed electron beams (HEPE) can be used to induce extensive structural variation, activating secondary metabolite biosynthesis.

Interfacial charge transfer limits fast-charging sodium-ion batteries. Here, authors demonstrate a P2-type positive electrode that utilizes potential-dependent anion-specific adsorption to accelerate charge transfer, enabling high-rate capability and stable cycling in Ah-scale pouch cells.

LARP6 is an EMT-associated RNA-binding protein with diverse RNA targets. Here, the authors show that the N-terminal disordered region of LARP6 promotes RNA-binding selectivity by modulating the adjacent La-module and forming auxiliary contacts with RNA.

Tiny protein crystals often evade X-ray methods. Here, authors solved the seed protein crambin at 0.85 Å by ab initio MicroED from 58 self-formed nanocrystals on standard 200 kV hardware, resolving hydrogen atoms using anisotropy-aware merging.

CRISPR-Cas12a catalyses RNA-guided DNA cleavage. Here, authors present structure-function studies of a high-fidelity Cas12a variant that reveal how helical transition of a conserved “bridge helix” facilitates R-loop propagation and DNA cleavage.

Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

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.

Vocal fold cancer tumours lose some of their malignant traits when mechanically stimulated by physiological stretch or vibrations, mimicking the opening and closing of vocal folds and phonation.

ATPγS, a slowly-hydrolysed ATP analogue, causes kinesin to take extra backsteps under load. Here, the authors examine single-molecule mechanics and propose a state in which forward steps and coupled ATP hydrolysis are turned off, but unsteered steps are allowed.

Human and swine H3N2 influenza A viruses were shown to use MHC class II as a sialic acid–independent, host-specific entry receptor, potentially expanding viral cell tropism. Furthermore, affinity for swine MHCII was higher in viruses adapted to pigs, suggesting a role in host range.

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.

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

Chronic inflammation and impaired immune tolerance are hallmarks of inflammatory bowel disease. Here, the authors report on Treg and platelet fused exosomes for targeted delivery of attached MMP cleavable IL-23 antibodies for immune modulation to prevent IBD progression.

Independently folding domains can be seen as the functional and evolutionary structural units of proteins. Here, the authors assess effects of >7000 mutations in a model PDZ domain, to quantify how two small extensions to a protein domain reshape its energetic and allosteric landscape.