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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.

This Commission aims to resolve the current dialysis policy challenges in Thailand and generate lessons for the global kidney community by drawing on empirical evidence, systems thinking and multidisciplinary expertise to generate policy goals and recommendations.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

Understanding interfaces at sub-nanometer scales is vital for complex chemical reactions. Here, the authors advance Pattern-enhanced Resonant Soft X-ray Scattering, enabling efficient operando probing of chemical and structural dynamics at solid-liquid interfaces.

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.

This study shows that mithramycin suppresses the EWS::FLI1 transcription factor in Ewing sarcoma using a hybrid CUT, Tag & GRO assay, revealing mechanism, need for continuous dosing, and supporting clinical use of next-gen analog AIT-102.

Using large-scale genetics and Genomic SEM/E-SEM, the study shows broad shared genetic risk between many physical illnesses and internalizing, neurodevelopmental, and substance-use disorders, revealing a transdiagnostic illness factor and cross-cutting disease pathways.

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.

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.

Protein citrullination is linked to autoimmunity and inflammation but is challenging to detect globally. Here, the authors report a high-throughput chemical proteomics workflow and demonstrate its utility by quantifying the dynamic citrullinome in human neutrophils.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

The mediobasal hypothalamus plays a central role in integrating nutritional and sex-related signals to regulate energy homeostasis. Here, through snRNA-seq of the mediobasal hypothalamus in female and male mice across nutritional states, authors show that Agrp neurons are nutrition-sensitive, DA neurons exhibit transcriptional differences in a sex-dependent manner, and KNDy neurons are responsive to both sex and nutrition.

Traditional scientific methods struggled to identify causes of seagrass losses in Canada (Eeyou Istchee). Here the authors combine Indigenous and scientific knowledge and find that eelgrass losses were caused by local hydroelectric development compounded by extreme climate events.

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.

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.

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.

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.

Recent work has revealed quantum coherent phase slips and current quantization in superconductors, phenomena dual to Cooper pair tunneling and voltage quantization. By combining the two effects, the authors demonstrate a Bloch transistor, a device that delivers quantized current and features a unique phase-locking mechanism.

Non-additive effect and trait-trait interactions are often overlooked in current genomic prediction approaches. Here, the authors extend quadratic phenotypic selection index to the genomic domain to enable phenotype-free, rapid-cycle multi-trait selection while capturing genome-wide nonlinear relationships.

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.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been associated with adverse effects affecting both the cardiovascular and gastrointestinal systems. Here the authors show that NSAIDs lower plasma tryptophan concentrations in humans and mice and that replacement of tryptophan in mice treated with naproxen leads to decreased adverse effects.

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.

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.

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.

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.

MASH is driven by the secreted GPNMB ectodomain, which binds hepatocyte RYK to activate ERK1/2 and promote lipid uptake and lipogenic programs; blocking the GPNMB–RYK axis prevented and treated MASH in preclinical models.

Expression of agouti signalling protein in neurons in the medial preoptic area is increased by group housing and negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Wnt signaling is activated in more than half of gastric cancers through a ligand-dependent manner. Here the authors show with mouse models that tumor-derived Wnt ligands activate liver stromal fibroblasts to facilitate hyaluronan accumulation in the microenvironment, promoting gastric cancer liver metastasis.

FBH1 is a DNA helicase and ubiquitin ligase that reverses stalled replication forks and limits RAD51 association with chromatin. Here, the authors describe the biochemical requirements for DNA unwinding and fork reversal activities and a cryo-EM structure of the SCF^FBH1 complex bound to a DNA fork.

Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

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.

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.

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.

Soft electrostatic actuators are crucial for advancing robotic systems that require adaptability and safety in unstructured environments. This study introduces ultralight soft electrostatic actuators utilizing solid-liquid-gas architectures, achieving significant improvements in power-to-weight ratio and actuation speed, exemplified by a 60% increase in jump height in a jumping robot compared to traditional designs.

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.

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.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

Chlorine electrosynthesis from seawater is limited by poor selectivity and stability under industrial-scale conditions. Here atomic-step-enriched ultrafine high-entropy alloy nanowires enable highly efficient chlorine evolution at 10 kA m⁻² for over 5,500 h through dynamic Pt–O active sites, reducing electricity consumption and feedstock costs for next-generation chlor-alkali processes.

A 3D soft electronic mesh allows high-resolution electrical recording and stimulation across the full surface of neural organoids, enabling long-term studies, drug testing and optogenetic control without compromising their viability owing to its porous design.

Natural rubber is a widely used biopolymer and further improving its resistance to crack growth will extend its service life. Here the authors show a strategy to amplify the resistance to crack growth in natural rubber by forming a tanglemer.