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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.

Although river protection is core to social and environmental well-being, the extent to which river conservation policies are effective is difficult to assess. This study reveals that, under all relevant protection mechanisms in the contiguous USA, only 12% of rivers are adequately protected.

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.

Oncolytic viruses, including Zika virus, have been proposed as therapeutic option for glioblastoma (GBM) treatment, however, efficacy in patients remains suboptimal. Here, the authors show that expanding peripheral T cells with long-acting IL7 prior to intratumoral oncolytic treatment improves survival in GBM preclinical models.

Here the authors identify the fungal effector Hap1 as a key driver of maize leaf tumor growth. Hap1 rewires plant metabolism and the cell cycle via SnRK1 signaling, promoting starch accumulation and cell enlargement.

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.

Little work has been done to describe and address the variability inherent in the agroinfiltration and genetic engineering of Nicotiana benthamiana. Here, the authors identify and quantify the sources of virtually all variation and develop recommendations for minimizing variation.

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.

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.

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.

Here, the authors show that myoferlin is a crucial host factor that helps move viral genetic cargo to the cell surface, boosting influenza, RSV and Sendai virus spread, highlighting a common weak spot for future antivirals.

Nicotinamide adenine dinucleotide (NAD) biosynthetic enzymes have been reported to be oncogenic. Here, the authors show that NAPRT, a key enzyme in the deamidated NAD biosynthesis pathway, functions as a suppressor of colon inflammation and tumorigenesis by maintaining DNA repair capability.

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.

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Conventional slurry electrodes limit high-energy lithium batteries. This work shows that dry-processed electrodes with molecularly coupled carbon–binder networks enable high mass and active material loading, supporting stable high-voltage operation and enhancing battery energy density.

Over the past 40 years, 42% of tropical and subtropical ecosystems have experienced an increase in plant reliance on past precipitation, consistent with greening during the late growing season in drylands and drying during the wet-to-dry period in non-drylands.

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.

Many vascular‑disease risk loci lack defined causal genes. Here, the authors integrate functional genomics and CRISPR screens to identify genes influencing smooth muscle cell behaviour, validating roles for FES, BCAR1, CARF and SMARCA4, with Fes loss promoting atherosclerosis and hypertension.

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

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

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.

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.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

Biochemical and structural studies show that the bacterial dGTPase CloA is activated by virally produced dTTP and inhibited by 5′-triphosphothymidyl-3′5′-thymidine produced by its regulatory partner CloB, and thereby balances antiviral defence and immune-mediated toxicity.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

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.

Using two newly developed immunoassays tested in three clinical cohorts, this study highlights CSF DOPA decarboxylase as a promising biomarker for differentiating dementia with Lewy bodies and Parkinson’s disease from Alzheimer’s disease and controls.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

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.

This study identifies KAT7 as a key factor converting zinc deficiency into reduced H3K14ac. This signal drives both physiological zinc homeostasis and, upon prolonged deficiency, pathophysiological liver fat accumulation.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

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.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

Synthetic materials are known for their outstanding durability and water stability, however, in contrast with biological structures they are not biodegradable. Here, the authors produce a biological material that gains strength in contact with water and becomes waterproof.

The electronic behaviour of complex oxides such as LaNiO₃ depends on many intrinsic and extrinsic factors, making it challenging to identify microscopic mechanisms. Here the authors demonstrate the influence of oxygen vacancies on the thickness-dependent metal-insulator transition of LaNiO₃ films.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Aperiodic composite crystals were discovered that emulate 2D moiré materials, demonstrating a potentially scalable approach for producing moiré materials for next-generation electronics and a generalizable approach for realizing theoretical predictions of higher-dimensional quantum phenomena.

Chen et al. developed a self-powered smart magnetoelastic stent for real-time hemodynamic monitoring and stenosis detection.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

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.