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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.

N-terminal acetylation shapes protein fate during protein biosynthesis at the ribosome. Here the authors show that the NatA enzyme forms dynamic multi-factor complexes at the ribosome, acting as an interaction hub that coordinates cotranslational protein maturation.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Authors study links between amyloid secondary nucleation and growth defects, demonstrating these sites on Aβ40/Aβ42 fibrils are rare compared to the number of protein molecules. Re-analysis of published data suggests that defects may also drive secondary nucleation generally.

The limited tunability of threshold voltage is a major obstacle for applying two-dimensional transistors in post-silicon electronics. Here, the authors show that bimetallic thiophosphates, such as LiInP₂S₆, enable programmable threshold voltages in both n-type and p-type 2D transistors, leading to low-power, high-speed complementary logic inverters.

Autopsy brain studies can be distorted because time and temperature alter gene expression. Here, the authors show that neurons, then oligodendrocytes, sequentially activate artifact genes, and provide a tool to measure these effects in RNA sequencing data.

Finding solutions to the Boolean satisfiability problem (SAT) in computer science can be costly due to its computational complexity. Im and Böhm et al. propose a SAT solver accelerator architecture using in-memory computing hardware to achieve a  ~ 10 × speedup and a  ~ 1000 × gain in energy efficiency.

By generating whole genomes of 150 participants representing 12 Khoe-San click-speaking groups, the authors, reveal over 1.3 million unknown DNA variants, distinct San and here described Damara genetic trajectories, while achieving century-long global predominance.

Using diffusion MRI data from over 10,000 youth, the authors develop 30 tract-specific brain age models and show that developmental deviations in association and limbic tracts are linked to concurrent and future cognition and psychiatric risks.

By combining optimal transport with machine learning, this study infers trade frictions in global food markets, highlighting how conflict, trade disputes, and shifts in political-economic relations are associated with changes in agricultural supply.

The pivotal role of Al in the spatiotemporal alignment of hole transfer and surface catalytic water oxidation in SrTiO₃:Al enables highly efficient photocatalytic overall water splitting.

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.

This study shows that in anxiety, circulating LPA16:0 produced by platelets inhibits adult hippocampal neurogenesis, resulting in increased susceptibility to stress and depression. These results support LPA16:0 as a potential therapeutic target for mood disorders.

Alternative splicing generates diverse protein isoforms, yet the functions of most exons remain unknown. Here, the authors introduce scCHyMErA-Seq, a scalable single-cell CRISPR exon-deletion platform that maps exon-specific transcriptional functions shaping gene expression and cell-cycle states.

Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.

Estimating respiratory infection rates in the community is challenging as testing is usually limited to people with more severe infections. Here, the authors develop a statistical method to estimate infection rates using data from a community survey that performed lateral flow testing in England and Scotland in 2023-24.

Battery electrode binders are hard to image but strongly affect battery performance. Here, authors use silver and bromine staining to reveal common cellulose- and rubber-based binders in graphite and Si negative electrodes and identify processing that reduces electrode resistance.

R2SP belongs to the R2TPlike quaternary chaperone family and consists of RUVBL1/RUVBL2 AAA+ ATPases, SPAG1 and PIH1D2. Here, authors combined biochemistry, NMR, structural MS and cryo-EM to investigate its 3D organization, mode of assembly and ATPase activity.

This study reports a maturation-dependent requirement for transferrin receptor -mediated iron uptake in pancreatic β-cells, whereby iron deficiency disrupts metabolic integrity and survival in developing cells but not in mature β-cells. The results show iron is a cue for β-cell maturation.

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.

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.

Reducing the assumptions required for certification of genuinely quantum behaviour is important both for quantum foundations and technologies. Here, the authors propose a theory-independent framework for quantum process tomography, and test it on a superconducting qubit, witnessing decoherence, loss of contextuality and non-Markovian evolution.

Here the authors present a compendium of avirulence genotypes for epidemiologically significant strains of wheat stem rust based on nuclear phased genome assemblies and functional assays to inform resistance gene deployment and pathogen surveillance.

This study presents a process that upcycles mixed end-of-life vehicle scrap into aluminium alloys surpassing current automotive alloy performance. It operates without sorting or downcycling for circular, low-emission aluminium recovery.

The authors in this work present a study with multiplexed gene editing that is used to assess all possible mutations at a native drug binding site. The approach yields data that predicts spontaneous resistance, that aligns with in silico predictions, and that promises to facilitate drug discovery.

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.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

After two years of mass azithromycin distribution to preschool age children in rural Niger, in this study, authors present evidence that selection of antibiotic resistance genes was not spread from treated villages to nearby untreated villages.

Decoding motor intents from peripheral nerves remains challenging. The authors record intraneural sciatic activity in transfemoral amputees and use a spiking neural network to decode phantom leg movements. These findings support bidirectional, neurally-controlled prosthetic systems.

Succinate metabolism is reported to be involved in acute myeloid leukemia (AML) tumorigenesis. Here, the authors demonstrate that succinate receptor 1 (Sucnr1) restricts hematopoiesis via regulation of S100A9, counterbalancing the Sucnr1-independent tumorigenic effect of succinate in AML.

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.

GDF15 has been associated with cancer-associated cachexia. Here, the authors show that STK11/LKB1 loss-of-function mutations in non-small cell lung cancer result in an exaggerated integrated stress response culminating in the tumor cell secretion of the cytokine GDF15 promoting cachexia.

Transesterification reactions are essential in organic chemistry, however, performing these reactions in aqueous media is challenging due to the competing hydrolysis reaction. Here, the authors report a mutant of alcohol oxidase from Phanerochaete chrysosporium (PcAOx-VPN) that exhibits no hydrolytic activity, enabling transesterification reactions in water.

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.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

Exposure to inflammation drives hematopoietic stem cells (HSC) aging, limiting their self-renewal capacity and differentiation. Here, the authors explore the mechanistic link between inflammation and HSC aging. Using mouse models, they identify the innate immune RNA sensor MDA5 as a key mediator of HSC aging and show that MDA5 loss ameliorates the aging phenotype by improving proteostasis in aged HSCs.

Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

Oat consumption, particularly a short-term, high-dose oat diet, improves metabolic health in individuals with metabolic syndrome by increasing microbially produced phenolic metabolites, leading to lower blood cholesterol levels.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

Although antiretroviral therapies (ART) have expanded the life expectancy of patients with HIV, they are not curative due to the presence of latently infected cells. Here, the authors present IMC-M113V, a bispecific soluble TCR targeting the HIV peptide Gag_77-85 complexed to HLA-A*02:01 as an approach for targeting HIV reservoirs and test safety, tolerability and pharmacodynamics in a first-in-human clinical trial on 12 HLA-A*02:01-positive male individuals on ART.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

He and colleagues develop a METTL3-based RNA base-editing screening strategy to identify functional N⁶-methyladenosine (m⁶A) sites that are important for prostate cancer cells and validate the role of a top m⁶A target, CHD9, in this context.

Here, the authors found that human NAT16 acetylates histidine in vitro and in vivo. Biochemical and structural characterisation uncovered a double-GNAT fold with distinct active site architecture that is conserved across species.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.