Biofilm-associated infections pose a significant clinical challenge due to the high resistance of bacteria within biofilms to conventional antibiotics. Extracellular DNA (eDNA) is a key structural component that facilitates bacterial adhesion and biofilm development. Metal complexes that target eDNA represent a promising strategy to disrupt biofilm integrity and eliminate biofilm-protected bacteria. In this study, four cyclometalated iridium complexes (Ir1-4) were rationally designed and synthesized, which selectively targeted Gram-positive bacteria through interactions with lipoteichoic acids (LTA) in their cell walls. Among them, Ir2, with chlorine atoms in the meta position, demonstrated superior antimicrobial activity. Ir2 efficiently killed bacteria by damaging the bacterial membrane and degrading genomic DNA. Additionally, Ir2 penetrated biofilms and disrupted them by degrading eDNA, thereby facilitating the eradication of resident bacteria. Metabolomics analysis revealed that Ir2 induced bacterial metabolic dysregulation, including inhibition of amino acid synthesis, obstruction of ABC transport, and elevation of DNA damage. In vivo experiments confirmed that topical application of Ir2 significantly suppressed Staphylococcus aureus (S. aureus) biofilm-infected wounds in murine models, promoting wound healing. This work provides a promising platform for developing antimicrobials focused on the targeting of eDNA to eliminate biofilm-associated infections.

Hemolysis is associated with the release of damage-associated molecular patterns, including free heme and extracellular DNA (ecDNA). Using several mouse models of bleeding anemia and hemolysis, we demonstrate a significant increase in plasma ecDNA, independent of neutrophil extracellular trap formation. This ecDNA forms G-quadruplex (G4) structures, which we detected in both mice and patients with systemic lupus erythematosus. Catalytic complexes (DNAzymes) formed by G4 ecDNA and heme drive oxidative stress, tissue injury, and inflammation. In anemic mice lacking deoxyribonuclease 1L3 (DNase1l3-/-), we found elevated polynucleosomal ecDNA in the plasma, reduced expression of the heme-degrading enzyme heme oxygenase-1 in macrophages, but also increased plasma creatinine, renal iron accumulation, and complement C3 deposition along elevated apoptosis and DNA damage. ecDNA isolated from these mice also triggered toll-like receptor 9-dependent inflammatory responses in vitro and in vivo. In summary, these findings suggest that concurrent release of heme and ecDNA during hemolysis promotes inflammation and tissue damage, contributing to lupus pathogenesis.

Extracellular DNA in bronchoalveolar lavage fluid as a candidate biomarker of disease severity in autoimmune pulmonary alveolar proteinosis.

Priming with humic acid nanoparticles reduces copper cytogenotoxicity in hydroponic culture of wheat seedlings.

Deciphering the regulatory role of the pfs gene on biofilm formation in Lactobacillus plantarum R: Insights from transcriptome and metabolome.

Supernatants from DNase-deficient Prevotella intermedia strains enhance oral squamous cell carcinoma cell migration and invasion by activating inflammatory and epithelial-mesenchymal transition pathways.

Novel mechanism of Guizhi Jia Huangqi decoction disrupting HBV lifecycle via cAMP/PKC/PKB axis beyond NTCP blockade.

Biofilm-associated infections remain a major barrier to wound healing, implant integration, and chronic infection management. Rare-earth oxides (REOs) have emerged as promising antibiofilm materials, though their mechanisms, limitations, and translational potential are still being defined. Cerium oxide (CeO2) serves as the benchmark due to its redox adaptability, oxygen-vacancy-driven catalytic activity, and host compatibility. In contrast, non-ceria REOs show antibiofilm effects under more restricted conditions, often requiring surface functionalization, composite architectures, or hybrid organic–inorganic interfaces—such as polyphenol coatings or hydroxyapatite-based composites—to achieve comparable activity. Across systems, biofilm control arises not from bactericidal potency but from matrix-level mechanisms including extracellular polymeric substance (EPS) destabilization, extracellular DNA (eDNA) sequestration, redox modulation, and quorum-sensing interference. Preclinical and near-clinical evidence, particularly in chronic wound models, supports the translational relevance of these mechanisms, though the evidence base remains preliminary. This review synthesizes mechanistic data across cerium-, samarium-, lanthanum-, and strontium-based systems to establish a unified framework for REO-mediated biofilm disruption. REOs are positioned as biofilm-modulating platforms that complement antibiotics, enhance healing, and improve outcomes. Design rules emphasize controlled redox activity, targeted coordination chemistry, functional surface engineering, and host-compatible performance, alongside regulatory and manufacturing guidance for future development.

Biofilm-infected diabetic ulcer represents a formidable clinical challenge due to the limited penetration and poor efficacy of conventional antimicrobials. Although photothermal therapy offers a non-invasive alternative, its efficacy is severely constrained by the inadequate infiltration of photothermal agents into deep biofilm regions. To address this barrier, we engineered a dissolvable microneedle patch incorporating ceria-decorated oxidized mesoporous carbon nanospheres (MN/OMCN@CeO2). This design leverages the intrinsic DNA-hydrolyzing activity of the CeO2 nanozyme to selectively degrade extracellular DNA (eDNA), a key structural component of the biofilm matrix. Enzymatic disruption of eDNA loosens the biofilm structure, thereby facilitating the deep penetration of the OMCN@CeO2 nanocomposite. Upon near-infrared light irradiation, the infiltrated nanocomposite generates localized hyperthermia, efficiently ablating deeply seated bacteria while simultaneously enhancing the catalytic activity of CeO2. In vitro assays demonstrated superior biofilm penetration and disruption by the MN/OMCN@CeO2 patch, along with robust bactericidal activity against Staphylococcus aureus and Escherichia coli. Further, in a murine model of diabetic ulcer biofilm infection, patch application significantly accelerated wound healing through effective bacterial clearance, attenuation of inflammatory responses, and promotion of tissue repair. Collectively, this DNA-hydrolyzing nanozyme-potentiated photothermal platform offers a promising therapeutic strategy for refractory, biofilm-associated diabetic ulcers.

Streptococcus mutans (SM) is one of the key pathogenic bacteria in the occurrence and development of dental caries. Its complex virulence regulation network has become an important target in current ecological caries prevention research. This study explored how dltD attenuates SM cariogenicity using standard strain SMUA159, high-cariogenic clinical strain SM593, and their dltD deletion/complemented strains. In this study, the clinical serotype C SM593 clinical strain isolated from caries-active patients (DMFT6), the SM593 dltD deletion strain (SM593-dltD), and SM593-dltD complementary strain (SM593-dltD-c) were selected as the experimental strains. Rat caries model was constructed to detect the cariogenicity. Colony forming counting units (CFU) counting was used to detect the colonization ability in vivo. The adhesion ability and surface hydrophobicity of each strain were examined by tube attachment assay and microbial adhesion to hydrocarbons method. Biofilm of each strain was constructed in vitro., CFU counting and MTT staining were used to analyze the SM biofilm formation. Laser confocal scanning microscope were used to observe the biofilm morphology, live/dead staining distribution. Anthrone-sulfuric acid assay, laser confocal scanning microscope, SYTOX probe assay and BCA protein kit assay were used to detect the extracellular polysaccharide content, extracellular polysaccharide distribution, eDNA content and extracellular protein content of the biofilm. Acid production was examined by detecting the pH of the biofilm supernatant. Potassium iodide assay and lactate dehydrogenase detection kit assay were used to examine intracellular polysaccharides and lactate dehydrogenase activity. CFU counting was used to detect the adaptive acid tolerance ability. Laurdan fluorescent probe was used to examine the cell membranes fluidity under the acidic condition. The expression of genes related to biofilm formation and acid tolerance was detected by RTqPCR. In vivo, dltD deletion significantly reduced fissure and proximal caries severity (P<0.05), with strain-specific colonization differences. In vitro, dltD deletion strains showed decreased biofilm viable cells (P<0.05), metabolic activity (P<0.01), and water-insoluble polysaccharides (P<0.01), associated with downregulated gtfB and gtfC expression (P<0.05), increased autolysis, and extracellular DNA (P<0.01). Acidogenicity and acid tolerance were impaired, associated with downregulated dexA, fabM, and atpD expression (P<0.05). These findings confirmed that dltD deletion attenuates SM cariogenicity by disrupting biofilm EPS and acid metabolism, supporting dltD as a potential target for caries prevention.

Mitigating Cell Lysis in PET Hydrolase Production: Nuclease Supplementation and Growth-Decoupled Co-cultivation Enable Scalable Enzymatic PET Recycling.

Sepsis-associated acute kidney injury (SAKI) remains a life-threatening condition with limited therapeutic options, primarily driven by rampant oxidative stress, inflammatory dysregulation. Importantly, aberrant formation of neutrophil extracellular traps (NETs) and sustained innate immune activation further exacerbate renal injury, highlighting the need for strategies that precisely modulate these intertwined pathological mechanisms. Here, we present neutrophil-mimetic nanoscavengers (MD@NM) that comprise a catalytic core of DNase-1-loaded Mn3O4 nanozymes enveloped by a neutrophil membrane engineered to actively target and simultaneously disrupt multiple pathological circuits in SAKI. The neutrophil membrane confers chemokine-receptor (e.g., CXCR2) mediated homing to injured kidneys, while the Mn3O4 nanozymes catalytically scavenge ROS and the loaded DNase-1 enzymatically degrades NETs-derived extracellular DNA, thereby suppressing the cGAS-STING pathway and skewing macrophage polarization toward an M2 reparative phenotype. In a murine model of LPS-induced SAKI, MD@NM treatment facilitated robust renal targeting, attenuated neutrophilic infiltration, resolved cytokine storm, and ameliorated structural kidney damage. Collectively, this biomimetic platform represents a novel strategy for precision immunomodulation and multi-mechanistic therapy against SAKI by integrating antioxidative, NETs-scavenging, and anti-inflammatory functions into a single nanotherapeutic agent.

Regulated cell death in COPD: Modulators, crosstalk mechanisms, and therapeutic opportunities.

Neutrophil extracellular traps are released from activated neutrophils and are involved in the pathogenesis of atherosclerotic lesions, atherothrombosis, and myocardial injury. We investigated the prognostic value of circulating neutrophil extracellular trap biomarkers in patients with suspected acute coronary syndrome (ACS). A total of 1482 patients admitted with suspected non-ST-segment elevation ACS were included and followed for a median of 4.2 years. The primary end point was a composite of death from any cause, incident myocardial infarction and hospitalization for heart failure. Secondary end points were all-cause mortality, cardiovascular death, incident myocardial infarction, hospitalization for heart failure, and new-onset atrial fibrillation. Admission blood samples were analyzed for the neutrophil extracellular trap biomarkers double-stranded DNA (dsDNA), CitH3 (citrullinated histone H3), and myeloperoxidase-DNA. A doubling of dsDNA concentration was associated with a hazard ratio (HR) of 3.11 (95% CI, 1.61-5.98, P<0.001) for the primary end point after adjusting for traditional risk factors, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. DsDNA served as a prognostic marker both in patients with (adjusted HR, 5.33 [95% CI, 1.67-17.06], P=0.005) and without ACS (adjusted HR, 2.86 [95% CI, 1.30-6.28], P=0.009). In contrast, CitH3 and myeloperoxidase-DNA showed no significant prognostic value. In patients with suspected ACS, dsDNA emerged as a long-term prognostic marker for a composite outcome of death, incident myocardial infarction, or heart failure hospitalization, independent of conventional risk factors. DsDNA can independently from established risk factors identify high-risk patients with and without ACS who may benefit from risk reduction.

Polymicrobial biofilms of Staphylococcus aureus and Pseudomonas aeruginosa pose serious clinical challenges due to their persistence, metabolic adaptability, and antibiotic tolerance. The present study investigated the ability of these two bacteria to co-exist and form mixed-species biofilms and evaluated the antibiofilm potential of piperine, a plant-derived alkaloid from Piper nigrum. Co-existence of S. aureus and P. aeruginosa was confirmed by enumeration of colony-forming units, growth kinetics, cross-streaking, metabolic fingerprinting, Gini coefficient analysis, and antibiotic susceptibility. Sub-minimum inhibitory concentrations of piperine significantly inhibited mixed-species biofilm formation, as demonstrated by biochemical, microbiological and microscopic analysis. Piperine treatment led to noticeable reductions in biofilm biomass, exopolysaccharide content, total protein content, metabolic activity and extracellular DNA. Mechanistic investigations revealed that piperine impaired biofilm-forming determinants by reducing cellular co-aggregation and cell surface hydrophobicity, inducing intracellular reactive oxygen species (ROS) accumulation, and increasing membrane permeability. Significantly, piperine effectively disrupted pre-established mixed-species biofilms, and its antibiofilm efficacy was further validated in a catheter model, highlighting its relevance against device-associated infections. Collectively, these findings demonstrate that piperine inhibits and disintegrates S. aureus-P. aeruginosa biofilms through diverse mechanisms, positioning it as a promising phytochemical for managing biofilm-associated infections.

Quorum sensing inhibition: A novel mechanism for ferrate-mediated removal of antibiotic resistance genes in swine wastewater.

Von Willebrand factor (VWF) is a large multimeric glycoprotein critical for hemostasis, mediating platelet adhesion to injured vessels and stabilizing circulating factor VIII. However, accumulating evidence reveals a complex, context-dependent role for VWF in inflammation and innate immunity that extends well beyond coagulation. VWF acts not only as a biomarker of endothelial activation but also as an active participant in immune responses. VWF directly interacts with major immune cell types-including macrophages, polymorphonuclear leukocytes (neutrophils), and dendritic cells-through both its endothelial-anchored and plasma forms. VWF facilitates leukocyte recruitment and transmigration across the vessel wall, while its interactions also promote macrophage and neutrophil activation as well as NET formation. VWF's immunomodulatory functions are further highlighted by its binding to extracellular DNA, smooth muscle cells, complement components (C1q and C3), and bacterial pathogens under flow conditions. Furthermore, VWF indirectly influences inflammation via its crucial role in Weibel-Palade body formation, a process that co-packages vital inflammatory mediators like P-selectin and angiopoietin-2. Markedly elevated VWF levels are consistently observed across acute and chronic inflammatory conditions such as sepsis, COVID-19, and autoimmune disorders, confirming its relevance as both a diagnostic marker and a therapeutic target. A comprehensive understanding of VWF's diverse functions in vascular inflammation is crucial for developing targeted therapeutics-including nanobodies, ADAMTS13 variants, and VWF interaction inhibitors-capable of modulating pathological thrombo-inflammation while preserving physiological hemostasis.

Targeting age-related cell-free DNA for prevention, early diagnosis and treatment of rheumatoid arthritis.

Dermatophytoma is a type of onychomycosis with distinctive clinical features. Clinically, it typically appears as a linear spike, triangular, or round white- or yellow-colored mass on the nail plate. Dermatophytes are thought to adhere to the nail surface and secrete extracellular polysaccharides (EPS), proteins, DNA, and other components, forming a biofilm matrix. EPS typically encases this microbial aggregation and is synthesized by the microbial constituents of the biofilm. Herein, we review dermatophytoma and the relationship between nail infection and biofilm. We also discuss green nails with dermatophytoma and infection models of biofilm formation.

Ovarian cancer is one of the leading causes of gynecologic cancer-related mortality in women. However, a significant proportion of ovarian cancer cases are only detected at an advanced stage (III or IV) and are complicated to treat because of metastasis to the peritoneum. This challenge is compounded by vague symptoms and insufficient screening methods for early ovarian cancer detection. A promising solution is liquid biopsy, where the presence of biomarkers (proteins, lipids, and nucleic acids) associated with cancer is identified in the blood circulation. This approach facilitates the real-time monitoring of cancer progression and treatment effects in a non-invasive manner. This contrasts with traditional tumor biopsy, where only a small portion of the tumor is sampled, serial sampling of the tumor is impractical, or sometimes, tumor biopsy is not feasible. This review discusses the cell-free and extracellular vesicle components in blood, highlighting their DNA as a target in liquid biopsies for cancer diagnostics, with a specific emphasis on ovarian cancer. It also underscores the need for further research into the biological underpinnings and functional roles of these DNA fragments to integrate them into multi-omics approaches for detailed insights into tumor biology and treatment resistance in ovarian cancer.