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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.

Species synchrony is considered a major mechanism of biodiversity–ecosystem stability relationships. Here, by combining theory, modelling and empirical work, the authors show that with time series length species synchrony decreases and its relationship with diversity switches from positive to negative.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

This work introduces DeepTernary, a deep learning method for rapid and accurate prediction of PROTAC and molecular glue-induced ternary complex structures, achieving state-of-the-art results by learning from a curated dataset, TernaryDB.

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.

Ethnic disparities in severe outcomes of COVID-19 were observed from early in the pandemic. Here, the authors investigate whether differences in mortality and cardiovascular disease outcomes persisted until 2.5 years after the start of the pandemic using electronic health record data from England and Wales.

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.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

In this work, authors study a molecular signature in STING protein that is critical for distinguishing activation from inhibition and demonstrates therapeutic potential in correcting STING-related mutations in autoimmune conditions like STING-Associated Vasculopathy with onset in Infancy (SAVI).

Ojer et al. use data from the American National Election Studies to map US voters in a two-dimensional ideological space. Democrats and Republicans have grown more polarized over the past 30 years, while partisan sorting has declined since 2010.

Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Neural circuit mechanisms underlying feeding behavior regulation are not fully understood. Here authors provide quantitative mapping of the brain-wide input and output configuration of tuberal nucleus somatostatin neurons, a key player of feeding regulation, in mouse brain for a deeper understanding of the feeding regulation network.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

Genome-wide sequencing of 180 ancient individuals shows a continuous gradient of ancestry in Early-to-Mid-Holocene hunter-gatherers from the Baltic to the Transbaikal region and distinct contemporaneous groups in Northeast Siberia, and provides insights into the origins of modern Uralic and Yeniseian speakers.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Long-acting injectable drugs for viral suppression of HIV are not yet available in African settings. Here, the authors present a mathematical modelling and cost effectiveness study of a long-acting drug combination in adults living with HIV in East, Central, Southern and West Africa.

Currently, the biological and clinical implications of copy number alteration (CNA) size heterogeneity and co-occurrence are incompletely understood. Here, the authors use 691 meningiomas and 29 cancer types from The Cancer Genome Atlas to develop size-dependent CNA and CNA co-occurrence models to optimize individualized pan-cancer risk stratification.

Diffusion models excel at molecular generation. Here, authors present SiMGen, a complementary local similarity-based approach. SiMGen offers more control over the generation process and can guide existing models to generate specific fragments.

Natural and sexual selection can be in opposition favouring different trait sizes, but disentangling these processes empirically is difficult. Here Okada et al. show that predation on males shifts the balance of selection in experimentally evolving beetle populations, disfavoring a sexually-selected male trait but increasing female fitness.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

Álvarez-Cubela et al. show that a BMP-7-like peptide induces β-cell regeneration and lowers hyperglycemia in diabetic mice, and reveal the transition of ductal cells into insulin-expressing cells. These results have potential therapeutic implications

Control of chiral light is essential in numerous fields from biosensing to quantum optics. Here, authors demonstrate a universal method to tune chiral response with metasurfaces using the interplay of resonator and lattice symmetries, enabling flexible design platform for advanced applications.

A modelling study suggests that Mars had a desert-like climate with intermittent liquid-water oases regulated by a negative feedback among solar luminosity, liquid water and carbonate formation.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Sustainable lighting requires balancing the preservation of biodiversity with the needs of urban residents. This study offers a valuable tool and meaningful insights to assist urban planners in achieving this equilibrium.

A short-lived carbon release preceded the PETM. Here the global nature of this is confirmed, effects on the surface ocean carbon cycle are resolved, and a thermogenic CO₂ source is inferred.

Understanding past warming events is essential to project the consequences of anthropogenic carbon emissions. Here, carbon and hydrological cycle changes of the Carnian Pluvial Episode are revealed, offering insights into Earth System functioning.

Phytochrome photoreceptors are master regulators of plant development. This paper describes 3D structures of soybean phytochrome A in both Pr (inactive) and Pfr (signalling) states, revealing changes that might transmit the light signal to the cell.

In this cross-sectional study, the authors used structural MRI to compare subcortical volumes, cortical thickness and surface area between early-onset anorexia nervosa, avoidant/restrictive food intake disorder and typically developing young individuals.

CMOS-based circuits can be integrated with silicon-based spin qubits and can be controlled at milli-kelvin temperatures, which can potentially help scale up these systems.

A dysprosium amide–alkene complex shows soft magnetic hysteresis loops up to 100 kelvin, arising from the high charge density of the amide ligands and the structural role of the pendant alkene.

Natural variation in the courtship song of Drosophila is mapped to the intronic insertion of a retroelement at the slowpoke locus, which encodes an ion channel.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbone generation for rapid and custom design of macrocyclic peptide binders.

DNA hybridisation thermodynamics parameters underlie rational design of oligonucleotides for diagnostics and nanotechnology. Here, the authors present an accurate method to measure the free energy of a given DNA structure at specific temperature and buffer conditions.

Methylation and mass cytometry investigations demonstrate the consequences of smoke exposure in humans at the single-cell level.

This study employs a citizen science approach to identify and classify over 230,000 light sources in German city centers, suburbs and villages. The results underscore the pivotal role of citizen science in expanding knowledge of artificial light emissions and bolstering policymaking efforts to mitigate urban light pollution.

Observational constraints, along with a better understanding of climate model behaviour, suggest that the projected weakening of the Atlantic meridional overturning circulation in the twenty-first century will be less severe than previously anticipated.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

A genomic study of 125 individuals from the Carpathian Basin (4800–3900 BCE) reveals different kinship systems in nearby Copper Age communities, and highlights both genetic continuity and contrasting patterns of social organization.

A unique Arp2/3 complex in malaria parasites enables DNA segregation during the rapid formation of male gametes by safeguarding the attachment of chromosomes to the mitotic spindle.

Brogan et al. uncover a signalling pathway in which levels of the nucleotide second messenger c-di-AMP increase in response to defects in cell wall synthesis. This regulatory pathway decreases turgor pressure and protects the cell from lysis.