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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.

Bright electron bunches power particle physics and photon science. Here, reproducible bunches were generated in a plasma with simultaneous high charge per unit energy and low emittance, advancing a scheme to produce ultra-bright bunches in future.

People living with HIV (PLWH) have an increased risk for aging-related comorbidities. Here, the authors develop a proteomics-based immune aging framework for PLWH and demonstrate that immune aging is accelerated in HIV infection, is closely linked to total viral reservoir burden, and is modulated by antiretroviral therapy.

Protected areas (PAs) are central to China’s forest conservation strategy, yet their carbon storage effectiveness under different governance and management contexts remains uncertain. Here, authors show that stronger protection enables substantially greater forest carbon gains in China’s PAs, both now and in the future.

This case report presents a multi-omics case analysis of intravenous phage-antibiotic co-therapy in a patient with cystic fibrosis during an acute-on-chronic pulmonary exacerbation caused by multidrug-resistant Pseudomonas aeruginosa.

Superoscillations enable waves to oscillate faster beyond classical limits. Here, the authors demonstrate simultaneous spatial and temporal superoscillations in structured light pulses, achieving extreme both subwavelength and ultrafast focusing in space-time.

Kv7.4 channels regulate auditory function. Here, authors use electrophysiological, optical and computational methods to investigate the structural changes that drive Kv7.4-channel opening, and how these are impaired by a deafness-causing mutation

Here, the authors propose the Antarctic Ecosystem Value Index, an Earth systems model-based measure of marine ecological value. The index identifies potential present and future high-value locations, which often fall within coastal polynyas.

Species compete intensely with their own kind, and this self-limitation shapes how species coexist within communities. This study shows that in large competitive ecological communities, coexistence is almost always stable.

CRISPR/Cas9 screens have identified genetic contributions to many phenotypes. However, studying combinations of genes or regulatory elements remains challenging. Here, the authors use CRISPR/Cas12a to overcome those challenges and enable new approaches to study combinatorial genetic mechanisms.

Excess nitrogen fertilization in maize production harms the environment and society, yet farmers face yield risks when reducing inputs. Using field trials across the US Corn Belt, this study suggests that nitrogen rates can be reduced by 12–16% with minimal yield risk, reducing emissions and leaching.

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.

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.

Most GWAS have focused on common variants or rare protein coding variants. Here, the authors interrogate the contribution of rare non-coding variants for anthropometric traits, identifying new genes associated with increased BMI and height.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

Neural mechanisms underlying active avoidance are not fully understood. Here authors show that avoidance actions are positively reinforced by learned safety signals. With training, control shifts from goal-directed to habitual behavior via distinct dorsal striatal circuits, like reward-based learning.

Weakly coordinating anions are commonly used to stabilize high-valent, electrophilic transition-metal complexes, owing to their low nucleophilicity and minimal coordinating ability. Here, the authors report a cobalt platform that generates a directional, protic cavity for ion pairing.

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.

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.

Histological analysis of the human pancreas provides insight into initiation and progression of type 1 diabetes (T1D). Here the authors utilize pancreatic tissue sections across different disease stages and apply whole slide imaging and digital pathology to identify endocrine cell composition, immune cell burden and spatial islet relationships in health and over the course of T1D.

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.

The burden of dengue disease in infants has increased in Brazil over the last 25 years. Here, the authors analyse spatiotemporal heterogeneity in disease incidence to characterise the contribution of changing maternal immunity to infant dengue risk.

The existence of multi-centennial natural variability in the North Atlantic is demonstrated over the last millennia by compiling proxy data. This variability mode will potentially amplify northern Europe warming by up to 30% over 2000-2035.

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.

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.

Mangrove ecosystems are facing severe climate threats. However, this study shows that strategically expanding protected areas to include the most climate-resilient sites can safeguard biodiversity and ecosystem services for the future, and this can be achieved with only a modest increase in protected area.

LC retention time prediction of peptides and their modifications is useful but is hindered by variations in experimental parameters. Here, the authors show how fine-tuning a deep learning model on a wide variety of experimental setups and modified peptides substantially improves predictions.

This study shows that strain-stabilized interfacial polarization in metallic RuO₂/TiO₂ heterostructures modulates the work function by over 1 eV and the metallicity, establishing a new route to control the electronic properties of functional metals.

Neuromorphic photonic systems can incur significant energy for moving and converting data between digital and analog domains. This work shows that integrating analog memory into these processors can save 26 × power over conventional digital-to-analog architectures while keeping  > 90% inference accuracy.

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.

Water-based fabrication is of potential use for a range of applications, but can be challenging. Here, the authors report the use of silk fibroin as an absorbate for the preparation of high density nanoparticle layers by water-based processing.

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.

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.

Cholera remains a significant public health burden in sub-Saharan Africa, but the mechanisms of continental and regional spread remain undefined. Here, the authors investigate recent patterns of spread using Vibrio cholerae genomic surveillance data collected by a consortium of seven African Union member states from 2019-2024.

The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer’s disease. Here, Brutman et al. identify a deletion common in people of African ancestry that reduces the relative risk conferred by the APOE-ε4/ε4 genotype.

In the context of ongoing A(H5N1) outbreak events, in this study, the authors use a ferret transmission model to show that genotype B3.13 viruses are shed into the air at higher levels than other A(H5N1) strains, highlighting the need for continued surveillance and aerobiological analyses.

A rate-limiting step to oncology clinical trial enrollment is prescreening. Here, the authors conduct a randomised trial using retrospective electronic health records to compare the accuracy and efficiency of prescreening by trained research staff alone vs. a human + artificial intelligence (AI) model in lung and colorectal cancer cohorts, showing that AI language models can approximate and augment human-driven prescreening in accuracy without changes in efficiency.

Using cloud observations from 44 US cities and large-eddy simulations, this study shows that taller buildings strengthen urban-breeze updrafts, while denser buildings suppress vertical turbulence, together reshaping moisture transport and cloud formation in urban environments.

Repeated rapid structural MRI scans substantially improve the precision of individual differences in brain change. This allowed for individualized insight into subtle differences in the detected rates of brain aging and neurodegeneration to be detected.

Many thermophiles that are abundant in geothermal systems have never been cultivated and are poorly understood. Here, Lai et al. describe the cultivation of one such organism, a deeply branching member of the archaeal phylum Thermoproteota, and provide evidence that it has evolved to specialize in branched-chain amino acid metabolism.

Radical protein footprinting reveals protein structure and interactions, but has not – to the best of the authors knowledge - been applied in whole blood. Here, authors demonstrate in-blood footprinting in mice, uncovering diabetes-associated protein conformational changes that were validated by orthogonal assays.

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.

Long-term follow-up of participants in the ADVENT trial, which compared pulsed field to conventional thermal ablation in patients with paroxysmal atrial ablation, shows preserved effectiveness of pulsed field ablation over the course of four years.

Symbiotic bacteria can have exceedingly small genomes. This study finds that ancient bacterial symbionts of planthoppers have repeatedly evolved the smallest known genomes, losing most biosynthetic functions, revealing how extreme genome reduction shapes life at the edge of cellular complexity.

Talin has been believed to be indispensable for integrin activation. Here, the authors show that the curvature-sensing protein FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions formed at curved membranes.

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.

Black-hole masses are estimated from broad emission-line widths and luminosity. Here, the authors show that over decades the luminosity varies while line widths remain constant biasing mass estimates, but using narrow-line luminosity corrects this.

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.