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This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

This study reports on an AI-powered autonomous experimentation platform that overcomes data scarcity in electronic materials discovery by using an AI advisor for real-time progress monitoring, data analysis and interactive human–AI collaboration. Applied to mixed ion–electron conducting polymers, it rapidly optimized performance in 64 experimental trials, revealing morphology–property relationships and an unreported polymer polymorph.

ENTRAP-seq systematically links protein sequence to transcriptional output in a native plant context.

A multiscale photoproximity labeling proteomics workflow captures dynamic neighborhoods of extracellular and intracellular epidermal growth factor (EGF) receptor interactomes during early, middle and late signaling upon activation by EGF.

To efficiently unlock the cooling power of sweat for human body remains a great challenge for next-generation textiles. Here the authors report an integrated cooling (i-Cool) textile showing high evaporation ability and sweat evaporation cooling efficiency for personal perspiration management.

DNA affinity purification and sequencing (DAP-seq) allows genome-scale studies of transcription factor (TF)-binding sites with high reproducibility. Here, Lax et al. use this technique to characterize 58 TFs encoded by genes regulated by adenine methylation, and provide insights into the regulatory mechanisms of gene expression in an opportunistic pathogenic fungus.

A family of host-derived bile acid–methylcysteamine conjugates functions as FXR antagonists, forming part of a microbiota-dependent metabolic network that regulates FXR-dependent physiology.

Gradients of cell recognition molecules wire a sensorimotor interface in Drosophila.

Microbial decomposition of plant litter initially increases the molecular diversity of dissolved organic matter, but prolonged microbial recycling diminishes this diversity, highlighting how microbial metabolism influences soil carbon turnover.

Human and mouse astrocytes express the protocadherin PcdhγC3, which promotes self-recognition of individual astrocytes, thereby contributing to normal astrocyte and brain development.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Transcription Factor 4 (TCF4) has been associated with autism and schizophrenia. Here, the authors demonstrate aberrant proliferation and differentiation in neural cells and organoids carrying mutations in TCF4.

PKU patients have elevated phenylalanine levels which can result in neurological impairment. Here the authors utilize biosensor-based ultra-high-throughput screening to optimize PAL activity in a synthetic biotic platform for improved in vivo performance.

Non-syndromic orofacial cleft is a relatively common congenital anomaly. Many non-coding genetic variants are associated with this disorder but only a subset is functional. Here the authors use reporter assays and stem cells to reveal members of this subset.

Malonyl-CoA (M-CoA) is essential for polyketide biosynthesis, but its limited availability constrains production. Here the authors engineer and evolve an orthogonal M-CoA pathway in Escherichia coli to improve M-CoA metabolism, increasing M-CoA levels and polyketide yields.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Hematopoietic cell transplantation (HCT) may be a promising therapy for treatment-refractory multiple sclerosis (MS). Mader et al. Describe beneficial effects of autologous HCT in a mouse model of MS and identify a myeloid transcriptional signature associated with neuroprotection.

Durable anti-tumour responses can be triggered by maximizing the cooperative phagocytic potency of macrophages through the disruption of the CD47–SIRPα macrophage checkpoint and by delivering a tumour-opsonizing monoclonal antibody.

Strong genetic evidence points to a significant role for heterozygous mutations to general chromatin remodeling factors, such as CHD8, in autism. Gompers et al. combine genomic, neuroanatomical and behavioral approaches to present an initial integrative picture of transcriptional mechanisms and widespread impacts of Chd8 haploinsufficiency across brain development in mice.

Aging is the most important risk factor for breast cancer in women without genetic mutations. Shalabi and colleagues now show that histologically normal mammary epithelial cells genetically predisposed to cancer exhibit features of accelerated aging, such as the loss of cell lineage markers, differentiation defects and transcriptome-wide enrichment of expression of genes related to aging and inflammation.

DNA-programmed assembly of cells (DPAC) allows the reconstitution of organoid-like structures with controlled size, shape, cell-type composition and spatial heterogeneity.

Rebecca Fitzgerald and colleagues report the whole-genome sequences of 129 esophageal adenocarcinomas, showing frequent copy number alterations and prevalent mutations in receptor tyrosine kinases concomitant with mitogenic activation. They further characterize mutation signatures and find three distinct molecular subtypes with potential for application to clinical diagnosis and treatment.

Here, the authors characterize the epigenetic landscape of the human fungal pathogen Rhizopus microsporus with a focus on symmetric DNA N6-methyladenine, revealing its regulatory role in gene expression and its essentiality for viability.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

Angelman syndrome (AS) is a neurogenetic disorder. Here, the authors found that PIEZO2 activity is reduced in sensory neurons from a mouse model of AS and used a linoleic acid-enriched diet to enhance PIEZO2 function and ameliorate AS-associated gait deficits.

Here, Lax et al characterise the role and distribution of an epigenetic mark, adenine methylation (6mA), in the genomes of early diverging fungi and find the enzymes that write symmetric and asymmetric 6mA in their DNA.

Smale and colleagues explore evolutionary divergence in the NF-κB family. They show that intrinsic DNA-binding affinity rather than specificity led to neofunctionalization in mammals within this transcription factor family, supporting immunoregulatory rewiring in mammalian species.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with novel topologies is of both fundamental and practical interest but the construction of highly crystalline 3D COF remains challenging. Here, the authors report highly crystalline 3D COFs with pto and mhq-z topologies by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains.

The autonomic nervous systems densely innervate the pancreas, but its contribution to pancreatic ductal adenocarcinoma (PDAC) progression is not fully understood. Here, the authors characterize the pattern of sympathetic innervation by 3D imaging in a murine model of PDAC and show that sympathectomy aggravates cancer progression.

Lateral intraparietal cortex (LIP) has been implicated in both attention and oculomotor control, but whether these functions are spatially overlapping remains unknown. Here the authors co-injected muscimol, to temporarily inactivate areas of LIP, and manganese, to enable MRI imaging of the inactivation site. They found that dorsal LIP is primarily an oculomotor planning area, whereas ventral LIP shows dissociable circuits for both attentional and oculomotor processes.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Dendritic cells experience cell shape changes while migrating within the complex physical environment of tissues. Sensing of these shape changes modifies their migratory properties and imprints these cells with immunoregulatory properties.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Glycomic profiling of mucosal surfaces identified O-mucin glycoconjugate motifs that regulate Candida albicans virulence. Synthetic analogs based on these glycans suppress fungal filamentation, offering potential for antifungal development.

Prenylated indole alkaloids contain spirooxindole rings with a 3R or 3S carbon stereocenter, which determines their bioactivities, but the biocatalytic mechanism controlling the 3R- or 3S-spirooxindole formation was unclear. Here, the authors report the biochemical and structural characterization of the oxygenase/semipinacolase CtdE that catalyses the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A.

Agrobacterium-mediated transformation of plants and fungi is enhanced by plasmid copy number variants.

Few genetic studies have focused on BaTwa populations in southern Africa. Here, the authors have examined the genetic ancestry of 80 individuals from two isolated BaTwa communities in Zambia, finding evidence of hunter gatherer and Western African ancestry.

The authors find low-energy magnetic excitations and a flat band near the Fermi level in kagome metal superconductor CsCr3Sb5 by angle-resolved photoemission and resonant inelastic X-ray scattering. They suggest that the flat band plays a role in the emergence of charge/magnetic order at low temperatures.

The precise mechanism by which gut microbiota influence the immunotherapy response of tumors in anatomically distant locations remains debated. In this study, using organoids and animal models, Zhang and colleagues show that Bifidobacterium-derived extracellular vesicles synergize the anti-tumor effect of anti-PD-1 via modulation of key cytokines, immune response and oncogenic pathways, and increase in tumor-infiltrating CD8 + T cells.

Rajshekar et al. show that a hierarchy of affinities layers pericentromeric heterochromatin around nucleoli, with the RNA helicase Pitchoune (DDX18) acting as a key dual-affinity linker in Drosophila melanogaster.

Metagenomics and Hi-C proximity-ligation sequencing show that viruses in dense microbial communities can interact with multiple, distantly related microbial hosts.

Animal gut microbiomes are fairly stable over time despite large daily fluctuations in diet and introductions of environmental bacteria. Here the authors report that fruit flies maintain the stability of their microbiome in part through a physical niche in the esophagus.

Many microorganisms are auxotrophic, that is, unable to synthesize the compounds they require for growth. Here, Ramoneda et al. predict amino acid biosynthetic capabilities of over 26,000 bacterial genomes using a metabolic pathway model validated with empirical data, and identify ecological contexts in which auxotrophy can be a successful strategy.