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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.

Personal names vary across cultures. Here, the authors show how historical name systems share a common information structure, reflecting pressure for efficient communication, as well as laws changing these systems and introducing systematic bias.

Here, the authors conduct a GWAS for eGFR, then a three-stage regional meta-analysis using GWAS summary data from the Eastern, Western, and Southern African geographical regions. Followed by fine mapping, colocalization, functional annotation, pathway analysis, and phenome-wide association studies showing weaker APOL1 effects in Africa.

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.

Electroreduction of CO is an emerging route to produce multicarbon molecules, but achieving this efficiently in solid-state devices is challenging. Here the authors develop a cation-functionalized layer using polyacrylate in a solid-state electrolyser that produces ethylene stably and efficiently from syngas.

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

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue.

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.

Systemic flavivirus dissemination in mosquitoes following initial infection requires protein–protein interactions within extracellular vesicles, which enable infectious particles to be transported through haemolymph and confer species specificity.

Displacement reshapes how we experience cities. Through my eyes, Tehran surfaces in fragments within Boston — its streets, trees and voices woven through memory. Each city holds its own rhythm: one of order and precision, and the other of memory and longing. Together, they trace the delicate threads of belonging, loss and resilience.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

The meningeal compartment communicates with the brain to modulate homeostatic functions. Here, the authors demonstrate that natural killer (NK) cells and innate lymphoid cells (ILC) 1 shape synaptic neuronal transmission and affect mouse behavior.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Nanoparticles sensing glycosaminoglycan loss in osteoarthritis enable disease-severity-responsive delivery of ghrelin messenger RNA to cartilage lesions, reducing cartilage damage, bone thickening and pain in animal models.

The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

Plasmodium falciparum proteins were engineered to create a nanoparticle vaccine platform capable of displaying multiple antigens at 48 sites. Displaying a designed malaria circumsporozoite protein immunogen on this platform achieves full sterile protection in mice.

A streamlined blood test using mass spectrometry improves measurement of amyloid-β for early Alzheimer’s disease diagnosis, requiring less sample volume and reagents while maintaining high accuracy, sensitivity and strong agreement with brain imaging.

A soft robotic probe enables continuous in utero monitoring of fetal physiological parameters, including heart rate, blood oxygen saturation, temperature and electrocardiogram data, during open or fetoscopic surgery to provide real-time information on fetal condition and distress.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

A label-free, DNA-based proximity ligation assay that uses ligatable staple pairs enables the longitudinal quantification of DNA origami structural stability dynamics in vivo, with single-helix resolution for both wireframe and lattice designs.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

A modular nanobody-based approach assembles combination vaccines by stably attaching diverse antigens to hepatitis E virus-like particles, preserving native immunogenicity and inducing broad protection against respiratory pathogens.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Calcium imaging of mouse hippocampal neurons while mice learn a reward-based task over several weeks provides insight into the evolution of the hippocampal reward representation during extended periods of experience.

Here, the authors combine bioinformatic, mass spectrometric, and sequencing-based mapping tools to identify previously undescribed phosphorothioate epigenetic systems widespread in the human gut microbiome.

Multi-omics profiling of diverse cancer cachexia models uncovers a multi-tissue metabolite-coordinated response associated with disease progression and links multi-tissue one-carbon metabolism to wasting.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

The enteric nervous system regulates gut function but is difficult to study due to sparse neuron distribution and gut motion. Here, the authors showcase a bioelectronic implant for electrophysiological monitoring of the enteric neural activity in freely-behaving animals.

Gastrointestinal motility disorders affect over 20% of the population, yet current therapies provide limited relief. Here, the authors show that in a swine model a closed-loop GI neuroprosthesis restores peristalsis and enhances metabolic responses via targeted electrical and chemical stimulation

Buchwald et al. conducted a year-long prospective, open-enrollment cohort study in southern Malawi and examined the demographic, temporal, and spatial clustering of transmission-relevant (gametocyte containing) Plasmodium falciparum infections. They found that school-age children are the primary driver of ongoing Plasmodium falciparum transmission.