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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.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Results from integrative population-based investigations indicate co-occurring types of clonal hematopoiesis are highly enriched and markedly increase blood cancer risk, highlighting new opportunities for early detection and targeted surveillance of high-risk individuals.

How GPCRs choose between different G proteins remains unclear. Here, authors show that the prototypical Gi-coupled melatonin receptor MT₁ also couples to G_s, resolve the MT₁-G_s structure, and identify ICL3 as a key determinant of this coupling.

Selecting appropriate treatment for breast cancer is guided by molecular subtypes and clinical characteristics. Here, the authors show that their AI-based approach, which integrates digital pathology images and clinical data, demonstrates robust accuracy in predicting the risk of cancer recurrence across major molecular breast cancer subtypes, including triple negative breast cancer.

H3K27-altered diffuse midline gliomas are a highly aggressive form of paediatric brain cancer. Here, the authors present molecular profiling of 68 patients, and show the efficacy of precision-guided therapy based on this profiling.

Metabolic liver disease is strongly linked to cardiovascular risk, but mechanisms connecting hepatic and cardiac pathology remain unclear. Here the authors show that PWK/PhJ mice develop diet-induced MASH with fibrosis and cardiac dysfunction, establishing this strain as a valuable model to dissect MASLD–CVD cross talk.

Migration of microbial communities is poorly understood. Here, the authors use a meso-tube assay to show that hundreds of microbial species co-migrate over metre scales via chemotaxis, which restructures communities, enriches motility traits and facilitates dispersal of viruses and non-motile ‘hitchhikers’.

Satellite radar altimetry is used to map the wave-affected Antarctic marginal ice zone-the outer icepack where waves penetrate the ice- providing a decade-long climatology of its extent and knowledge on its drivers.

School closures and reopenings were widely used as a control policy during the COVID-19 pandemic. Here, the authors use counterfactual models to explore impacts of elementary and secondary school closure policies implemented during different phases of the pandemic in the Netherlands.

Signal peptides are highly variable, yet the signal peptidase complex processes them with remarkable specificity. Here, authors combine cryo-EM, molecular dynamics simulations and modeling to reveal a unified binding mechanism.

Various types of the agr quorum-sensing system, defined by distinct autoinducing peptides, regulate virulence in Staphylococcus aureus. Here, Bär et al. use microfluidics and single-cell imaging to show that agr types differ in signal-peptide sensitivity and activation heterogeneity, and that cross-inhibition between types produces distinct interaction behaviours.

Targeted therapy (with BRAK and MEK inhibitors) and immune checkpoint blockade have improved survival for patients with advanced BRAF-mutant cutaneous melanoma, however, the optimal scheduling for these treatments remain to be further refined in poor prognosis groups. Here the authors present the results of a feasibility trial to determine the role of circulating tumour DNA in guiding a switch between targeted therapy and immune therapy in patients with advanced melanoma.

Global uncertainty demands technological sovereignty. The authors define ‘strategic advanced materials’ as those that achieve high-performance using local inputs, showing Europe can replace risky imports with resilient, home-grown alternatives.

Here they show that blood flow and early endothelial stress responses interact to drive abnormal angiogenic remodeling and inflammation, revealing how vascular disease susceptibility can arise during development.

This study reveals that the divergent Plasmodium NEK4 kinase acts as a central regulator of early post-zygotic meiosis. It couples crucial cytoskeletal reorganisation, such as MTOC duplication and nuclear migration, with chromosomal dynamics to drive meiotic entry and parasite development.

Interferometric scattering microscopy combined with photoluminescence imaging enables the fast, high-throughput screening of size and quantum yield for thousands of perovskite nanocubes at the single-particle level across their entire life cycle.

Relativistic jets launched from stellar-mass black holes (BHs) in our galaxy have been observed in less relativistic regime than those seen in the extra-galactic supermassive BHs named active galactic nucleus (AGN). Here, the authors show two relativistic jets from galactic BH X-ray binary 4U 1543−47, which are comparable to those seen in AGN.

Spin chains enable quantum simulation of scattering-related phenomena of interest for highenergy- and condensed-matter-physics, yet current approaches are limited to low dimensional cases. Here, the authors address this gap by studying magnon scattering in 2D quantum Ising models via tree tensor networks. This unveils new resonances and induced false vacuum decay dynamics.

Here, in a large-scale study of over 900 companion dogs, the authors examine how the gut microbiome varies as dogs age, identifying consistent microbial shifts associated with age, as well as associations with diet, behavior, and health.

The ability to observe and control proteins in living cells is essential for biological research and drug development. Here, the authors engineer the self-labelling protein tag BromoCatch, enabling selective covalent labelling of fused proteins with biotin, clickable, fluorogenic, and degrader probes for protein manipulation and multiplex cell imaging.

Antibody discovery often requires major experimental effort. Here, authors report a virtual screen using AlphaFold-Multimer that identified nanobody binders to MRGPRX2, a therapeutic target for itch, demonstrating fully in silico antibody discovery.

KMT2A-rearranged and NPM1-mutant acute leukemias treated with menin inhibitors frequently acquire resistance due to MEN1 mutations. Here, the authors use CRISPR base-editor screens to predict shared and drug-specific MEN1 resistance mutations across five clinical menin inhibitors.

During mitosis, chromosomes undergo a dramatic metamorphosis. Here, the authors show that Condensin I, but not Condensin II, is important for establishing chromosome stiffness and elasticity, as well as for maintenance of centromeric cohesion.

PTCHD1-AS, which encodes a long non-coding RNA, is associated with the aetiology of autism spectrum disorder in humans through striatal molecular and circuit-level dysregulation.

The authors present a geothermal cement design that confines metastability during phase evolution from curing to service, enabling structurally stable materials under prolonged supercritical water exposure.

In this study, the authors analyse 17,565 Plasmodium falciparum genomes from 39 countries to show global patterns of parasite population structure, drug-resistance spread and positive selection, providing improved resolution for genomic surveillance of malaria parasite adaptation worldwide.

Covalent labelling is a promising modality relying on electrophilic warheads that form covalent bonds with their targets. Here, authors present the oxygen-to-sulfur exchange strategy that transforms traditional carboxamides to thioamides, yielding several electrophilic warheads, including chlorothioacetamides and fluorothioacetamides, with enhanced cysteine reactivity, while retaining aqueous stability and selectivity.

Allogeneic haematopoietic cell transplantation is a potential therapeutic strategy for patients with mature T-/NK-cell lymphoma. Here the authors present the results of a phase II clinical trial of allogeneic haematopoietic cell transplantation for mature T or NK-cell lymphoma and suggest induction of graft versus tumor immunity is linked to remission even in the context of refractory disease.

Ribonuclease P (RNase P) is an essential metallonuclease found in all three domains of life. Here, the authors present cryoEM structures of Geobacillus stearothermophilus RNase P aporibozyme (apoE) in various states of the catalytic cycle.

Aluri et al. show that TGF-β1 disrupts red blood cell production by rewiring chromatin, simultaneously blocking cell growth and forcing premature maturation. Inhibiting this pathway restores normal erythropoiesis, revealing a potential therapeutic strategy.

Cuffless hemodynamic monitoring via wearables holds great potential to detect, monitor, and treat patients with cardiovascular disease. Here, the authors establish the mechanistic link between fluid and electrical quantities and develop an algorithm to measure cuffless blood pressure and velocity with a smartwatch.

Visualizing protein-protein interactions in live bacteria remains technically challenging. Here, Meiresonne et al. develop and use a FLIM-FRET assay to study, with spatial resolution, the interactions between proteins involved in cell division and peptidoglycan synthesis in Staphylococcus aureus.

The study shows that global gross primary productivity is more limited by air dryness than by soil moisture. This influence strengthens with temperatures and more severe, prolonged droughts, suggesting rising air dryness may accelerate declines in land carbon storage.

A deep-tissue light source made from mechanoluminescent transducers stimulated by focused ultrasound enables wide imaging of live animal vasculature, and modulation of neuronal activity and behaviour.

This study reconstructs Earth’s temperature over the past 539 million years by integrating rock chemistry and climate models, showing that global temperatures remained within ~10–30 °C, challenging ideas of anomalously high early Paleozoic climates.

Autophagic activity has a protective role in Alzheimer’s disease in mice. Here the authors investigate the role of autophagy-initiating protein ULK1 and report that its overexpression stimulates autophagic flux, reduces amyloid and tau pathology and delays cognitive decline.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

A drawing-like task designed to study compositional generalization identifies a specific neural population in the ventral premotor cortex in primates that encodes action symbols.

Cell migration depends on controlled adhesion turnover, but its regulation remains unclear. Here the authors show that AAK1 promotes focal adhesion disassembly via PDLIM5 and Talin1 phosphorylation, enabling efficient cell migration.

Natural silk, mechanically strong and biodegradable, offers great potential for sustainable functional materials. Here the authors present a simple thermomechanical method for fabricating high-performance structural and optically active materials directly from silk fibres.

l-2-Hydroxyglutarate is identified as a legitimate physiological signalling metabolite, and control of its levels is essential for postnatal growth and survival and correct renal development and function.

This study reports a paralog-selective p300 degrader with potent anti-cancer activity in hematological malignancies, demonstrating a strategy to selectively target transcriptional coactivators through protein degradation.

The authors show that non-cognitive skills, including motivation and attitudes towards learning, mediate associations between education-related genetic disposition and academic achievement across compulsory education.

MOSAIC is a versatile multimodal microscope that allows seamless transition between various light-sheet, two-photon, label-free and super-resolution modalities. It is demonstrated in various systems ranging from cell culture to mice.

The study showed in a placebo-controlled crossover design that 4-week treatment with β2-adrenergic agonist clenbuterol enhances insulin-stimulated glucose uptake in skeletal muscle but not brown adipose tissue in individuals with obesity.

The success of KRAS G12C mutation specific inhibitors in patients with KRAS-driven tumours is limited by the emergence of acquired resistance. Here, the authors characterise olomorasib, a next-generation covalent KRAS G12C-mutant inhibitor, demonstrating efficacy in the presence of clinically relevant resistance mutations in preclinical KRAS-driven cancer models.

The genetically encoded voltage indicators JEDI3sub and JEDI3hyp enhance monitoring of subthreshold neuronal activity in the awake mouse brain using a variety of two-photon microscopy techniques.

The real space magnetic texture of kagome materials is often complex and temperature dependent. Here, the authors demonstrate spectroscopic access to a single magnetic domain in kagome metal DyMn₆Sn₆ and provide insights into the orbital magnetization.

High-resolution analyses of blood-derived whole-genome sequence data from UK Biobank detect new mosaic chromosomal alterations and identify rare protein-coding variants associated with clonal expansions of copy-neutral loss-of-heterozygosity mutations.