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In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

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.

Aging is a key risk factor for chronic diseases of the elderly. Here the authors perform large-scale miRNA profiling of blood from individuals of a range of ages and show that common diseases alter the physiological age-related blood microRNA profile.

Lalioti, Romero-Mulero et al. combine metabolomics, lipidomics and transcriptomics of haematopoietic stem and progenitor cells during differentiation, ageing and leukaemia, finding a role for choline and showing that supplementation enhances stemness.

Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Rare-earth permanent magnets are engineered with a complex microstructure of composition and phase, grains and grain boundaries, and it is this complex structure which leads to the magnetic performance. Here, Giron and coauthors, through thorough microstructural analysis, demonstrate that the grain microstructure, not grain boundaries, are primarily responsible for optimal magnetic properties.

The role of CXCR2 in epithelial and endothelial cells on lung infection remains unclear. The authors here use conditional CXCR2 knockout mice to manifest that epithelial and vascular CXCR2 mediates transcytosis of CXCL1, leading to neutrophil infiltration and controlled lung inflammation.

Repeated stress triggers habituation, an important stress coping response. Here, authors chart the dynamic gene expression changes that underlie stress habituation in the mouse brain and reveal two distinct molecular mechanisms behind this process.

3D printing can be used to manufacture composite materials, but to modify material properties multiple feedstocks are required. Here the authors modify printing temperature or light intensity to modify the material properties and achieve property differentiation from a single feedstock.

The performance of flexible all-perovskite tandem solar cells remains limited by interfacial losses in narrow-bandgap subcells. Here, authors incorporate Triton X-100 to disrupt the vertical phase segregation in PEDOT:PSS films, achieving maximum cell and mini-module efficiencies of 25.4% and 19.7%.

Non-antibiotic drugs from a wide range of therapeutic classes can alter the ability of gut commensals to resist invasion by enteropathogens, a previously underappreciated side effect of such drugs.

Realizing strong magnon-phonon coupling (i.e., magnon-polaron formation) is challenging and typically involves a material or cavity that confines the magnon to a small volume. Here, by combining a YIG film with a ZnO acoustic resonator, Künstle and coauthors achieve magnetic field tuneable magnon-polarons in a virtually infinite magnetic film, and succeed in observing Rabi-like oscillations in the time domain.

SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1’s role in muscle homeostasis, offering insights for new therapeutic strategies.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

Obesity is associated with changes in levels of many blood-based factors, such as cytokines and adipokines. This Review explores the utility of such factors as biomarkers for quantifying and predicting obesity-associated disease risk, including the identification of causal relationships.

Complexes of the transcription factor Ume6 bridge morphogenesis, adherence and hypoxic genes that determine biofilm architecture in the human fungal pathogen Candida albicans.

Dopaminergic medication and deep brain stimulation exert a shared therapeutic modulation of cortex-subthalamic nucleus network activity in Parkinson’s disease, through a suppression of high beta synchrony mediated by the hyperdirect pathway.

Gómez-Sánchez et al. show that generation of phagophore–endoplasmic reticulum exit sites (ERES) membrane contact sites, mediated by Atg2 and the TRAPPIII complex, triggers Ypt1 activation, which is a signal to initiate phagophore elongation.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

CLPP-deficiency-driven mitochondrial dysfunction in brown adipose tissue leads to the accumulation of d-2-hydroxyglutarate, in turn promoting lipid-droplet enlargement by altering gene expression and epigenetically regulating nuclear stiffness.

Fluorescent proteins are widely used in molecular biology to visualize protein expression and localization. Here, Krizet al. describe an efficient and flexible modular plasmid-based eukaryotic expression cloning strategy for the homogeneous expression of several fluorescent proteins in one cell.

Climate change effects on animals are typically measured as decreases or increases in performance, compared to controls. Because both directions can have cascading effects at the ecosystem level, this study conducts a meta-analysis testing for deviations in biological responses using absolute rather than relative changes, showing that impacts on marine animals might have been largely underestimated.

Here, the authors show that the oral microbe Streptococcus mutans, elevated in the gut microbiome of Parkinson’s patients, produces imidazole propionate via UrdA that in mice reaches the brain and triggers Parkinson’s-like pathology, suggesting a causal gut–brain axis disease link.

How ocean acidification will impact coastal biogenic habitats is unclear. This study predicts that indirect effects on habitat-forming organisms, combined with direct effects on biodiversity, will cause changes in structural complexity and extent of these habitats.

In addition to reducing protein adsorption, modifying polymer nanocarriers with poly(ethylene glycol) or poly(ethyl ethylene phosphate) can alter the type and amount of plasma proteins that do get adsorbed, offering new insights on how the stealth effect is defined.

Sedimented hydrothermal systems can be a significant source of hydrogen in addition to ultramafic rock-hosted systems, according to analysis of chemical data from hydrothermal vent fluids at the Jøtul hydrothermal field.

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.

Here, the authors show that task-focused brain activity builds on background activity during rest, supporting the Active Cortex Model—the idea that the brain is surprisingly always active, and tasks boost specific resting processes.

How the brain controls pain perception remains elusive. Here, authors show that layers 5 and 6 of the somatosensory cortex suppress or enhance nociception through cell-type-specific cortical and corticothalamic interactions.

Light detection and ranging (lidar) is an active remote sensing technology that produces foundational geospatial datasets across natural systems. This Primer introduces core lidar technological components, concepts and applications for assessment of vegetation, topography, bathymetry and glaciology. Current methods, outlooks and considerations for acquiring and processing lidar data are introduced.

The authors develop an EM-based method to directly visualize R-loops. Applying this method to transcription-replication conflicts in human and bacterial cells, they show that DNA:RNA hybrids accumulate primarily behind replication forks, and are linked to fork slowing and fork reversal.

Oligomerisation of transcription factors regulates their translocation into the nucleus, DNA binding affinity and sequence specificity. Here, Hinde et al. present a microscopy analysis, pair correlation of molecular brightness, that tracks the molecular mobility of different oligomeric species in the same cell.

In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanisms of SPNS2’s transport and inhibition.

Using computer simulations, this study quantifies the potential effect of ocean acidification on marine biogenic sulphur emissions and the resulting feedback mechanisms on future climate. It emphasizes that a reduction of anthropogenic carbon dioxide emissions is not only necessary to limit the negative effects of ocean acidification on marine life, but also to avoid amplified climate warming due to changes in biogenic sulphur production.

This molecular-level study provides a comprehensive assessment of groundwater quality in three German research sites. Hydroclimatic variability is causing fundamental changes in groundwater ecosystems, with implications for global water resources.

Adenovirus produces two early proteins, E1B55K and E4orf6, that become components of the host cell ubiquitin ligase complex comprising elongin-B and C, cullin-5 and RBX1. The authors identified new protein substrates that are ubiquitinated by the E1B55K–E4orf6 complex and find that hnRNP-C and RALY play an inhibitory role on late viral RNA transcripts and that this is counteracted by ubiquitination due to a reduction on the capacity of these proteins to interact with viral RNA.

Therapeutic antibodies are crucial in treating severe diseases. Here, the authors introduce scifAI, an open-source explainable AI framework for analyzing imaging flow cytometry data, enabling rapid screening of therapeutic antibody candidates.

How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.