Juan Xia

The spatiotemporal distribution of gaseous mediators is critical for maintaining physiological functions. Biofilms both contain gas-producing bacteria and possess complex architectures that reshape gaseous mediator distribution. However, whether biofilm pathogenicity is linked to such gaseous regulation remains unclear. In this study, we reveal that extracellular DNA (eDNA) within the biofilm matrix contributes to the local retention and enrichment of H₂S. This enrichment stabilizes eDNA, strengthens biofilm barriers, impedes gas clearance, promotes bacterial persistence, and induces macrophage immunosuppression, creating a reciprocally protective defensive loop. To dismantle this defense, we engineered a stepwise-responsive biohybrid system in which probiotic-derived engineered minicells actively target hypoxic biofilm regions, while H₂S-triggered nanoparticle degradation enables deeper matrix penetration and concurrent H₂S scavenging. The retained minicells then catalyze in situ glucose oxidation to generate H₂O₂, which, together with Fe²⁺-mediated Fenton-like reactions, degrades eDNA and collapses the biofilm. This strategy eradicates persistent bacteria, reverses immunosuppression, and provides a therapeutic strategy to reduce recurrence and optimize refractory infection treatments.

Mechanical overload‑related cytokines contribute to temporomandibular joint osteoarthritis (TMJOA) pathogenesis. This study investigated the role of

Depression is a recognized risk factor for cancer progression, but the underlying metabolic mediators remain unclear. Here, we identify circulating C16-ceramide depletion as a key mechanism linking depression to oral squamous cell carcinoma (OSCC) progression. Mendelian randomization analysis first established a genetic causal link between depression and increased head and neck cancer risk. In mice, chronic stress, mimicking depression, accelerated orthotopic tongue tumor growth and concurrently reduced circulating levels of C16-ceramide. Exogenous restoration of C16-ceramide reversed this tumor-promoting effect. Mechanistically, C16-ceramide was taken up by OSCC cells via the scavenger receptor SCARB1, accumulated in mitochondria, and induced opening of the mitochondrial permeability transition pore (mPTP), thereby triggering mitochondrial apoptosis. Inhibition of mPTP opening abolished the anti-tumor effects of C16-ceramide. Clinically, a gene signature reflecting this C16-ceramide–mPTP–apoptosis axis was associated with favorable survival in OSCC patients. Our study reveals a novel metabolic pathway whereby depression promotes oral carcinogenesis by depleting a circulating tumor-suppressive lipid, highlighting the therapeutic potential of targeting the C16-ceramide-mPTP-apoptosis pathway.

Selective gene expression is pivotal in orchestrating human development. Specifically, trithorax group (TrxG) and polycomb group (PcG) components play crucial roles in transcriptional activation and repression of state-specific stem cell expression programs, yet the mechanisms underlying their selective genomic binding remain poorly understood. In this study, we report that the polycomb repressive complex 1 (PRC1) subunit RYBP co-localizes with TrxG component WDR5 and selectively enriches PcG component RING1B in condensates in murine embryonic stem cells (ESCs). RYBP deficiency impairs the genomic binding of WDR5 and RING1B. Further, STAT3 excludes RING1B binding at RYBP-associated transcriptionally active loci. Additionally, RYBP depletion attenuates WDR5-dependent activation of DNA repair gene expression and facilitates the transition of ESCs to 2-cell-like cells. Finally, RYBP depletion disrupts RING1B deposition at lineage-specific genes, promoting ESC differentiation towards mesendoderm fate. These findings uncover RYBP as a regulator of selective genomic binding of TrxG and PcG components, providing insights into their roles in cell fate determination during development.

Mitochondrial dysfunction of mesenchymal stem cells (MSCs) has been implicated in impaired osteogenesis, resulting in bone loss following radiation therapy. However, the underlying mechanisms remain to be fully elucidated. This study reveals the critical role of Fis1 in regulating mitochondrial dynamics and MSC osteogenesis in radiation-induced bone injury. Specifically, radiation activates Fis1 expression, which induces excessive mitochondrial fission, leading to mitochondrial fragmentation, along with reduced capacities for oxidative phosphorylation, ATP synthesis, and antioxidant defense, that collectively impairs MSC osteogenesis and results in bone loss in radiation-induced bone injury. This process involves increased calcium (Ca ²⁺ ) influx that stimulates calcineurin (CaN) to promote nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) dephosphorylation and nuclear translocation, which in turn, activates the transcriptional expression of Fis1. Consistent with the pivotal role of Fis1 in regulating mitochondrial fission and MSC osteogenesis, inhibition of Fis1 remarkably reduced mitochondrial fragmentation, enhanced MSC osteogenesis and reduced bone loss, highlighting the therapeutic potential of targeting Fis1 in radiation-induced bone injury. Our study provides new insights into the mechanisms and therapeutic strategies for radiation-induced bone injury.

Background: Periodontitis is a highly prevalent chronic inflammatory disease characterized by the progressive destruction of periodontal tissues, which can lead to tooth loss and affect systemic health. This pathological process is driven by both epithelial barrier disruption and a self-perpetuating cycle of dysregulated inflammatory immune responses. Although neurotransmitters, including acetylcholine, are abundant in saliva and gingival crevicular fluid, their role as key mediators of immune homeostasis in the pathogenesis of periodontitis remains poorly understood. Methods: Utilizing single-cell RNA sequencing (scRNA-seq) data (205,334 cells, 40 human gingival samples) and gingival spatial transcriptomics data (46,230–25 μm ² spots), we revealed that the gingival epithelium exhibits the most significant functional reprogramming of neural signaling pathways in the periodontitis state. Through experiments in vivo and in vitro , we validated the functional role of acetylcholine in periodontitis. Results: Our findings reveal that cholinergic signals change with the progression of periodontitis and that gingival epithelial cells possess an extensive distribution of non-α7-type nicotinic receptors. The acetylcholine-degrading enzyme, acetylcholinesterase (AChE), is primarily expressed by myeloid immune cells that extensively infiltrate the epithelium, and its expression is significantly upregulated following periodontal treatment. In human oral keratinocytes (HOKs), acetylcholine played a dual role: it promoted epithelial barrier repair by reversing Porphyromonas gingivalis ( P. gingivalis )-induced tight junction disruption, yet it also exacerbated inflammation by upregulating key chemokines and inflammasome components. In vivo , mouse models of periodontitis showed that topical application of acetylcholine aggravated periodontal tissue damage. Conclusion: In conclusion, our results reveal a complex, multifaceted role for acetylcholine in periodontal pathogenesis, highlighting its ability to both protect the epithelial barrier and drive inflammatory tissue destruction. These findings establish a new “neuro-epithelial-immune axis” in the pathogenesis of periodontal disease and reveal potential targets for therapeutic intervention.

An interactive bidirectional relationship between periodontitis and diabetes poses great challenges for the treatment of diabetic periodontitis in clinical practice. The hyperglycemic inflammatory periodontal microenvironment is characterized by oxidative damage, chronic invasive infection, excessive inflammation, unbalanced immunomodulation, progressive neuropathy, diabetic vasculopathy, and uncoupled bone resorption and formation responses. The neuromodulation strategy holds great potential to mediate and coordinate temporally the complex microenvironment for diabetic periodontal regeneration. Herein, natural grape seed polyphenols (GSPs) were used to modify the surface of exosomes derived from Schwann cells (SC Exo) through polyphenolic polymerization and noncovalent interactions. The GSP-coated SC Exo (GSP@SC Exo) system demonstrated antibacterial and antioxidative properties. Furthermore, these GSP@SC Exo nanoparticles could induce axonal growth of dorsal root ganglia explants, production of anti-inflammatory factors, M2 polarization of macrophages, tube formation of human umbilical vein endothelial cells, and human periodontal ligament stem cell osteogenic differentiation in vitro. Additionally, diabetic periodontal destruction was reversed through nerve regeneration, anti-inflammatory effect, immunomodulation, neovascularization, and alveolar bone formation in vivo. Therefore, this study provided a facile and effective neural engineering strategy for guiding the treatment of diabetic periodontitis in clinical applications.