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Here, the authors develop Q4ddPCR, a high-throughput assay to quantify genetically intact HIV reservoirs by targeting four regions, and demonstrate that it reduces assay dropout to 5%, tracks reservoir decay, and closely correlates with viral outgrowth.

Introgression shapes eukaryotic genomes, yet its prevalence in nature remains unclear. Sequencing 216 Neotropical S. cerevisiae genomes reveals that recurrent introgression is widespread and a major driver of lineage evolution within a structured population.

Most patients with B-cell leukemia respond to chimeric antigen receptor T cell (CAR T) therapy, yet many relapse due to loss of CAR T function. Here, the authors show that the metabolism of CAR T from short- and long-term responders is different, which may explain why CAR T lose functionality.

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.

Here, the authors investigate the association between sleep characteristics, such as sleep quality, daytime sleepiness, social jet lag and chronotype, and the gut microbiome composition in a Dutch cohort of 6941 participants.

A distinctive population with high hunter-gatherer ancestry persisted 3,000 years later than in most European regions, contributing to later Lower Rhine–Meuse Bell Beaker users.

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 study shows that vaccination with two doses of recombinant zoster vaccine is associated with a 51% reduction in the risk of dementia in adults aged ≥65 years. Reduction in risk is comparable across subgroups and remains statistically significant after accounting for healthy vaccinee bias.

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.

The combination of within-species variation in pathogen load, the shape of the relationship between pathogen load and infectiousness, and vector feeding preferences shape transmission of multi-host vector-borne pathogens. Here, the authors use experimental and wild bird infection data to characterize the role of 17 host bird species in avian malaria transmission in Hawaii.

Birds are iconic and valued users of urban parks. An assessment of 935 parks across 186 US cities shows that a range of park features across multiple parks are needed to broadly support avian diversity and that the regional and seasonal effects of tree canopy cover are especially important.

The acetyl-CoA pathway is the most ancient CO₂ fixation pathway in nature. Here, the authors show that metals selectively reduce CO₂ to the intermediates and end-products of the acetyl-CoA pathway, which is consistent with a prebiotic origin of this pathway.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

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.

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.

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

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

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.

Transportation infrastructure threatens forests, but past studies have been regional or focused on single metrics like forest cover. This global analysis finds road-adjacent forests lose cover, height, and productivity and become more fragmented.

Aqueous two-phase systems have potential as biomimetic materials, but often lack stability and are prone to collapse. Here, the authors use interfacial assembly of chitin nanofibres and cellulose nanocrystals to prepare a biobased system with permeability and switchable motility.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.

Self-DNA has been implicated in the activation of cGAS/STING/IFN-I responses in autoimmunity and inflammatory diseases. Here the authors show that macrophage uses a process termed ‘nucleocytosis’ to extract nuclear DNA from lysosome-impaired, dying target cells, thereby activating downstream cGAS-STING signaling and IFN-I production.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

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.

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.

This study uses brain recordings, self-reports, and facial analysis to decode acute pain in epilepsy patients. Machine learning reveals stable neural markers in mesolimbic, striatal, and cortical regions, plus facial cues, enabling reliable pain detection in naturalistic settings.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

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.

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.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Nitrogen isotope tree-ring chronologies show that rising atmospheric CO₂ has reduced nitrogen availability in boreal forests in Sweden, suggesting that elevated atmospheric CO₂ is causing oligotrophication in boreal forests.

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.

In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

How cellular metabolism influences tissue-resident macrophage survival is currently unknown. The authors here demonstrate that SerpinB2 regulates mitochondrial function to promote tissue-resident macrophage survival.

This study reports a post-assembly, reversible crosslinking strategy that enhances lipid nanoparticle (LNP)-mediated mRNA delivery while preserving efficient intracellular release. The resulting crosslinked LNPs enable improved endosomal escape, sustained in vivo expression and robust immune and antitumor responses across multiple clinically relevant LNP platforms.

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.

Population-based studies from Sweden with replication in Norway identify associations between host genetic variants and gut microbial composition and implicate short-chain fatty acid chemosensors as modulators of gut microbial richness.

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.