Wound infections are prevalent and can result in prolonged healing times. In this study, we referred to the "trap-capture-kill" antibacterial strategy to create a wound dressing (DS/PDA@GO-L) by coupling graphene oxide (GO) with lysine and coating it onto the decellularized mushroom stem (DS) using polydopamine (PDA). The mechanism of action of the bacteria-killing process involves lysine chemotaxis and the siphoning effect of DS aerogel, with the process of killing the bacteria being initiated via near-infrared photothermal treatment. In vitro studies demonstrated that DS/PDA@GO-L exhibited excellent blood and cell compatibility, while in vivo experiments revealed its remarkable efficacy in combating bacterial infections. Specifically, the combination of DS/PDA@GO-L with photothermal therapy led to the elimination of over 95 % of S. aureus, E. coli, and Pseudomonas aeruginosa. Furthermore, the aerogel, when used in conjunction with photothermal therapy, significantly reduced bacterial infection at the wound site and accelerated wound healing. During the wound's proliferative phase, it notably enhanced vascularization and extracellular matrix deposition. Furthermore, immunohistochemical staining revealed that bacterial clearance led to a reduction in pro-inflammatory responses and a decrease in the expression of pro-inflammatory cytokines, thereby restoring the wound's inflammatory environment to a pro-regenerative state. Taken together, the developed DS/PDA@GO-L holds great potential in the field of infected skin wound healing.
© 2025 The Authors.

Vascular cells express various G-protein-coupled receptors (GPCRs) with yet unknown function, among them orphan receptor GPR153. GPR153 was upregulated in smooth muscle cells (SMCs) in response to injury, and knockdown of GPR153 resulted in reduced proliferation and mildly altered differentiation in human SMCs. Mice with tamoxifen-inducible, SMC-specific GPR153 deficiency were partially protected against ligation-induced neointima formation, and their SMCs were characterized by reduced proliferation and dedifferentiation. Mechanistically, we show that GPR153 negatively regulates cellular cAMP levels, and thus the absence of GPR153 leads to an increase in CREB phosphorylation, reduced YAP/TAZ levels, and diminished NF-κB activation. Interestingly, a similar role of GPR153 was observed in endothelial cells (ECs), where loss of GPR153 resulted in reduced inflammatory gene expression and protected mice with EC-specific GPR153 deficiency in models of neuroinflammation and stroke. Taken together, orphan receptor GPR153 facilitates pro-inflammatory and pro-proliferative gene expression in ECs and SMCs by controlling cellular cAMP levels, thereby contributing to inflammation and vascular remodeling.
© 2025. The Author(s).

Current therapies ultimately fail to eradicate metastatic renal cell carcinoma (RCC). Validated biomarkers and a better understanding of the mechanisms causing therapy resistance are still needed. Here we demonstrate that interleukin-34 (IL34) is associated with poor prognosis, metastasis, and therapy resistance in RCC. In mice, single-nucleus RNA sequencing and phenotyping reveal that the IL34-enriched tumor microenvironment displays immunosuppression and nonfunctional vasculature, two key features of therapy resistance. Mechanistically, IL34 increases migration of monocyte-derived tumor-associated macrophages (MD-TAMs) in primary tumors and lung metastases through colony-stimulating factor 1 receptor (CSF1R). Blockade of CSF1R by the Food and Drug Administration-approved drug pexidartinib contrasts MD-TAMs accumulation observed in the IL34-enriched microenvironment and improves response to sunitinib or anti-PD1 treatment to reduce metastatic growth. Altogether, our data highlight the role of the IL34-CSF1R axis in regulating the tumor immune-vascular crosstalk in RCC and indicate pexidartinib as a therapeutic alternative in combination with current therapies.
© 2025 The Author(s).

In homeostasis, counterbalanced morphogen signalling gradients along the vertical axis of the intestinal mucosa regulate the fate and function of epithelial and stromal cell compartments. Here, we use a disease-positioned mouse and human tissue to explore the consequences of pathological BMP signalling dysregulation on epithelial-mesenchymal interaction. Aberrant pan-epithelial expression of the secreted BMP antagonist Grem1 results in ectopic crypt formation, with lineage tracing demonstrating the presence of Lgr5(-) stem/progenitor cells. Isolated epithelial cell Grem1 expression has no effect on individual cell fate, indicating an intercompartmental impact of mucosal-wide BMP antagonism. Treatment with an anti-Grem1 antibody abrogates the polyposis phenotype, and triangulation of specific pathway inhibitors defines a pathological sequence of events, with Wnt-ligand-dependent ectopic stem cell niches forming through stromal remodelling following BMP disruption. These data support an emerging co-evolutionary model of intestinal cell compartmentalisation based on bidirectional regulation of epithelial-mesenchymal cell fate and function.
© 2025. The Author(s).

Futile recanalization affects more than half of acute ischemic stroke (AIS) patients. Neutrophil extracellular traps (NETs) are a major factor of microvascular hypoperfusion after stroke. Deoxyribonuclease I (DNase) targeting NETs exhibited a neuroprotective effect in young mice with AIS. This study explored a novel direct intra-arterial administration of DNase therapy and its effect in aged mice with AIS.
AIS was induced in aged C57BL/6 mice followed by reperfusion and immediate, intra-arterial DNase administration via the internal carotid artery. Cerebral blood flow (CBF), neurological function, cerebral infarct volume, and NET markers were examined.
Direct intra-arterial DNase therapy significantly increased CBF, reduced neurological deficit scores, increased the latency to fall in the wire hang test, reduced cerebral infarct volume, and decreased neutrophil and NET count in both the parenchyma and micro vessels in aged mice with AIS compared with age-matched vehicle controls.
Our data is the first to demonstrate that successful, direct intra-arterial DNase therapy provides more efficient cerebral reperfusion and better outcomes after recanalization during the treatment of large vessel occlusion in aged mice. This study provides evidence for the potential clinical application of catheter-delivered intra-arterial DNase therapy post-recanalization.
© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.