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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.

A series of spontaneously blinking dyes in the far-red range facilitate single-molecule localization microscopy. These dyes vary in their blinking properties and can be matched to the applications and microscopy modalities as needed.

The cellular mechanisms to initiate allergic responses involve various immune cells in the lungs. Here the authors identify a Ly6G⁺Nur77⁺ macrophage population involved in initiation of HDM-driven Th2 responses that detect Derp1 allergen through PAR2 and modulate migration of conventional DC to draining lymph nodes via cysteinyl leukotriene production.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

High spatiotemporal precision tracking using 3D MINFLUX shows that nuclear import and export occur in overlapping regions of the central pore, providing insight into transport across the nuclear pore complex.

Here the authors design tripeptides that form dynamic soluble dispersions and undergo phase separation upon drying to assemble into porous particles. This evaporation-driven emulsification can be harnessed to encapsulate and stabilize biomolecules.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Here, the authors introduce the Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT), which allows researchers to study the information encoded in the physical proximity of individual transcripts by detecting persistent subcellular patterns.

Microexons play a crucial role in neural development and are evolutionarily conserved. Comparing microexons across bilaterians, the authors find a new protein domain responsible for the evolution of neural specificity of microexons.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Premalignant stromal cells from women with germline BRCA1 mutations exhibit increased expression of secreted factors regulating epithelial homeostasis in a paracrine fashion. These secreted factors, such as MMP3, promote premalignant epithelial changes including elevated proliferation and altered differentiation of a subpopulation of luminal progenitor cells.

Wesley et al. describe the developmental trajectories of human foetal liver cell types at single-cell resolution and generate bipotential hepatoblast organoids, which can serve as a new platform to investigate human liver development.

Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.

Delineating the specific role of Polycomb Repressive Complex 2 (PRC2) in various cancer systems is desirable as inhibitors for EZH2 inhibitors are approved for some cancers. Here the authors show haplo- and full-insufficiency of EZH2 drive divergent phenotypes in lung cancer. 3D tumoroids recapitulate transcriptional profiles, including FOXP2 derepression, and drug responses of in vivo tumors.

Genome-wide analysis in individuals of African ancestry identifies a nonsense variant in CD36 associated with increased risk of dilated cardiomyopathy (DCM), partly accounting for the higher incidence of DCM in African-ancestry populations.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Drought is a major factor limiting crop productivity. Here, via eQTL analysis and comparative genomics, the authors show compensatory evolution between trans-regulatory loci and transcription factor binding sites that shape the drought response networks in the model C4 grass Panicum hallii.

A catalogue of human long non-coding RNA genes and their expression profiles across samples from major human primary cell types, tissues and cell lines.

Common bean is an evolutionary model for studying adaptive diversity in legumes. Here, the authors present the common bean pangenome based on five high-quality genomes and whole-genome reads of 339 wild and domesticated genotypes, and reveal adaptive gene loss during expansion and domestication.

Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer’s disease reveals how this complex and chronic disease evolves over many decades.

The role of alternative splicing in pancreatic cancer (PDAC) development remains to be explored. Here, RBFOX2 is shown to regulate exon splicing events in transcripts encoding proteins involved in cytoskeletal remodelling programs and its downregulation promotes PDAC progression and liver metastasis.

The design and construction of a stereo-defined DNA-encoded chemical library, featuring the four different 4-amino-proline stereoisomers as a central scaffold, has now enabled the discovery of potent ligands to proteins of pharmaceutical interest. Parallel screening with closely related isoforms (anti-targets) facilitated the isolation of hits with high selectivity ratios.

The future challenges and potential opportunities of robotics and autonomous systems in urban ecosystems, and how they may impact biodiversity, are explored and prioritized via a global horizon scan of 170 experts.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Dishevelled (DVL) is the key component of Wnt signaling pathway that acts as a signaling hub. Here, authors study the conformational dynamics of DVL3 in vivo using their engineered FlAsH-based FRET biosensors and describe how Wnt activation opens DVL and facilitates Frizzled recruitment.

In mice, persistent activation of mitochondrial cannabinoid receptors in astroglia impairs cellular glucose metabolism and lactate production, leading to an increase in redox stress in neurons and altered behavioural responses.

How the epigenomic landscape linked to transcription regulates human embryonic development is unclear. Here, the authors analyse the dynamics of H3K27Ac, H3K4me3 and H3K27me3 during the period when organs first assemble as a platform for understanding noncoding developmental disorders.

Survival outcomes in Burkitt lymphoma differ between adult and paediatric patients. Here, the authors show differences in mutational frequencies between age groups, and a transition between mutational profiles which occurs between 25 and 40 years.

The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features.

Ragonnet-Cronin et al scanned SARS-CoV-2 genomes from >12,000 treated patients, identifying nine treatment-emergent mutations that increased in frequency after treatment with antibodies. In the laboratory, synthetic viruses harbouring those mutations escaped the antibodies, suggesting the mutations are driven by immune evasion.

To date, no therapeutic agents against enterovirus 71, the causative agent of hand, foot and mouth disease, exist. Here, using Cryo-EM Huang et al. characterize two plasmablast-derived plateau-binding neutralizing antibodies conferring effective protection against lethal EV71 challenge in vivo.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

This work introduces a passive method for capturing CO₂ directly in the solid form using a carbonate crystallizer. This system harnesses wind-driven evaporation to enable rapid CO₂ capture and carbonate crystallization. This method provides a simplified and scalable alternative to conventional air contactors, which require substantial capital investments.

Dynamic supramolecular systems can be designed to adapt phases in a pre-programmable way. Here the transient nature of a gel system is exploited, in combination with the application of mechanical stimuli, to obtain soft materials with aligned fibres in a controllable way.

A post eradication polio vaccine should be safe and easy to produce. Here, the authors characterize a recombinant virus-like particle polio vaccine with stabilized capsid proteins and show comparable immunogenicity to the current inactivated polio vaccine.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Kabir et al. show that aged bone marrow induces smooth muscle cell (SMC) polyclonality in atherosclerosis. Decreased TET2 levels in aged myeloid cells lead to silenced integrin β₃, resulting in increased TNFα signaling and the expansion of multiple SMC progenitors.

Lysosomal storage diseases like mucopolysaccharidosis type I (MPS I) cause pathology before birth and result in early morbidity and mortality. Here, the authors show that in utero base editing mediates multi-organ phenotypic and survival benefits in a mouse model recapitulating a common human MPSI mutation.

Lipid membrane fusion is an essential function in many biological processes but little is known about membrane fusion in prokaryotes. The authors here study how haloarchaeal pleomorphic viruses (HRPVs) infect archaeal hosts. The structure-function analysis of the spike proteins shed light on prokaryotic membrane fusion.

It remains unclear why some paediatric tumours appear to have such a low mutation burden. Here, the authors shed light on this paradox by analysing Wilms tumours using high resolution and high depth sequencing approaches, finding that - due to an unusual clonal architecture - standard methods significantly underestimate the mutation burden at the cellular level.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

The genetic basis of collective behaviour is complex. Single-cell transcriptomics of honeybee brains and gene regulatory network analysis showed differences in brain gene regulation and gene regulatory network plasticity between aggressive soldiers and non-aggressive foragers.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.