Advanced Science最新文献

Obstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder characterized by chronic intermittent hypoxia (CIH), which has been increasingly recognized for its systemic effects on pediatric skeletal development. However, the mechanism by which CIH influences bone growth and homeostasis remains largely unexplored. In this study, it is demonstrated that CIH exposure in young murine models induces cellular senescence within the metaphysis of long bones, resulting in compromised bone formation and growth retardation. Through single cell sequencing and in situ immunostaining, it is identified that the senescent cells predominantly consist of osteoprogenitors. Mechanistically, CIH enhances the activity of hypoxia-inducible factor 1-alpha (HIF-1α) in osteoprogenitors and subsequently downregulates trimethylation of histone H3 at lysine 27 (H3k27me3) through the suppression of polycomb histone methyltransferase enhancer of zeste homolog 2 (EZH2), thereby facilitating the expression of senescence-associated genes. Employing both genetic and pharmacological strategies, it is demonstrated that the restoration of H3K27me3 levels via UTX inhibition (achieved through in vivo knockout or GSK-J4 treatment) effectively prevents CIH-induced senescence, promotes osteogenesis, and alleviates bone loss and growth retardation. These findings elucidate a novel epigenetic mechanism that underlies the skeletal impairments associated with CIH and underscore the therapeutic potential of targeting histone methylation to mitigate hypoxia-induced bone defects.

Tendinopathy represents a major musculoskeletal health problem, yet its pathogenesis remains poorly understood. Tendinopathy development is studied in humans with early (< 3 months of symptoms, n = 14) (ET) or chronic (> 3 months, n = 16) (CT) patellar tendinopathy and in healthy subjects (n = 15) (CTRL). Pain increases, and function declines with tendinopathy duration and correlated with tendon size (3T and 7T MRI). Tendon blood flow (Doppler ultrasonography) increases gradually in ET and CT, while peritendinous blood flow only rose in CT. Microscopy-based mapping (immunofluorescence microscopy and Cell DIVE) of vasculature shows marked changes in CT only, indicating flow increases in existing vessels early in tendinopathy, whereas angiogenesis is a late phenomenon. Cell DIVE indicates perivascular cell recruitment and potential lymphatic expansion in tendinopathy. Further, proteomics reveals that most matrix regulation occurs late in tendinopathy. Data from a previous study from the lab demonstrate faster treatment effect in tendinopathy with shorter symptom duration, supporting that early tissue changes may be more receptive to treatment. It is concluded that early tendinopathy is dominated by pain correlating with tendon swelling and hyperperfusion, whereas chronic tendinopathy is characterized by neovascularization and matrisome changes. These findings suggest that targeting early tissue changes can lead to superior treatment effects in tendinopathy.

Aspirin provides long-term health benefits but can cause gastrointestinal toxicity, and the role of gut microbiota in aspirin metabolism and enterotoxicity remains unclear. In this study, the contribution and mechanisms of microbiota-aspirin interactions in intestinal injury are investigated. In a mouse model, aspirin-induced enteropathy is found to be more severe in microbiota-replete than in microbiota-depleted mice, implicating a detrimental role of gut microbiota. Co-cultivation experiments revealed that gut microbes facilitated the biotransformation of aspirin into salicylic acid, a metabolite more harmful than aspirin itself in disrupting epithelial cell integrity and renewal, both in vitro and in vivo. Through metagenomic screening, selective bacterial interrogation, and functional validation, Lysinibacillus sphaericus is identified as the culprit bacterium, and its secreted carboxylesterase EstB as the key enzyme catalyzing aspirin hydrolysis to salicylic acid. Importantly, inhibition of microbial EstB with the dietary compound flavanomarein abrogated aspirin biotransformation and prevented intestinal injury. Together, these findings reveal L. sphaericus and EstB as central drivers of aspirin enterotoxicity, highlight the functional importance of gut microbiota in drug metabolism, and suggest microbiota- and metabolite-guided precision prevention strategies.

Patescibacteriota, also known as Candidate Phyla Radiation (CPR), is a diverse clade of ultra-small bacteria with an epibiotic lifestyle. Despite their ubiquity across diverse ecosystems and ecological importance in microbial networks, the global distribution of Patescibacteriota and functional interactions with their host organisms remain largely unknown. Here, by leveraging comprehensive Patescibacteriota genomic resources and global multi-habitat metagenomic datasets, it is demonstrated that ribosomal protein S3 (rpS3) as a reliable phylogenetic marker, enabling accurate recovery of Patescibacteriota diversity from short-read metagenomes. Using this framework, extensive taxonomic diversity and pronounced community heterogeneity are uncovered across eight ecosystems. Through network analysis and genome-wide functional screening, habitat-specific co-occurrence patterns are also revealed between Patescibacteriota and host-associated bacteria, especially potential functional synergies mediated by metabolic pathway cascades. Notably, Patescibacteriota-encoded NirK may assist sulfate-reducing bacteria in resisting nitrite stress, while NorB can mitigate nitric oxide toxicity for complete ammonia-oxidizing bacteria. Taken together, this study highlights the underappreciated diversity of Patescibacteriota and elucidates its important role in supporting host metabolism through complementary biochemical functions, offering new insights into its ecological significance and evolutionary adaptations in the global ecosystem.

Auditory Circuits

The cover illustrates the Research Article by Boris Gourévitch and co-workers (DOI: 10.1002/advs.202508777) on the neural code of the auditory system. Sound waves, as a physical phenomenon, converge toward the ear before being transduced into a neural code–an internal language in which information is carried by the activity of neural circuits across the brain. This code can be thought of as sequences of “0”s and “1”s, reflecting the firing or silence of neurons. Surrounding the head in the background are spectrograms of complex sounds, showing how acoustic energy unfolds over time and frequency. Image credit: Typhaine Dupont

Prevention of Biofilm Formation by Metal-Organic Framework Surfaces

The cover image demonstrates a mechano-bactericidal (MB) surface based on metal–organic frameworks (MOFs). The sharp nano features could physically rupture bacterial envelopes and lead to bacterial lethality. In the Research Article by Zhejian Cao, Lars Öhrström, Ivan Mijakovic, and co-workers (DOI: 10.1002/advs.202505976), MB surfaces are designed using an epitaxial MOF-on-MOF strategy. Two methods of MOF surface assembly are applied, i.e., in situ growth and ex situ dropcasting. Distinct mechano-bactericidal actions are discussed, including stretching, impaling, and mechanical injury.

Integrating Popular Human Genomics Tools for Cancer Drug Target Screening

Differential expressed gene (DEG) analysis and Mendelian randomization (MR) are two widely-used human genomics tools to identify associations between genes and diseases, but have not been integrated together to strengthen causal inference in population-based studies. In their Research Article (DOI: 10.1002/advs.202507451), Jie Zheng, Qian Yang, Haoyu Liu, and co-workers propose a new concept “MR-DEG pleitropy exclusion”, which uses DEG evidence to filter out the putative causal effects of genes on diseases. By applying the concept to immune-cell RNA-seq data among cancer patients and healthy controls, 33 genes are prioritized as potential drug targets for cancers.

Iron Single-Atom Catalyzed N-Alkylation of Amines

This cover illustrates the solvent-free N-alkylation of amines with alcohols over an N-doped graphene-supported iron single-atom catalyst. The artwork highlights the catalytic Fe–N₄ interface where efficient hydride transfer takes place. The catalyst delivers outstanding catalytic efficiency along with record turnover number (1032.7) and turnover frequency (413.1 h⁻¹) for the N-alkylation reaction, outperforming all previously reported systems. More details can be found in the Research Article by Radek Zboril, Yifeng Wang, Manoj B. Gawande, and co-workers (DOI: 10.1002/advs.202507915).

Ingestible Bioprinter

The cover art describes a first-of-a-kind ingestible bioprinter, a pill-sized, tetherless device that navigates the gastrointestinal tract via magnetic guidance and patterns therapeutic bioink directly over damaged tissue using near-infrared activation. By uniting the worlds of ingestibles and bioprinting, Sanjay Manoharan and Vivek Subramanian realize the vision of a pill that prints, opening paths to future ingestibles that do not merely deliver molecules, but actively construct tissue in the very spaces where disease took hold. More details can be found in the Research Article (DOI: 10.1002/advs.202512411).