Search Results (392)

Objectives: Neuroinflammation is recognized as a significant characteristic of Alzheimer’s disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation. Methods: In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism. Results: Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner. Conclusions: Maltol exhibits significant protective effects against Alzheimer’s disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer’s disease neuroinflammation using traditional Chinese medicine. Full article

A comprehensive multiregional characterization of the spectral response of cassava leaves across different ontogenetic stages was performed. For this, ultraviolet (UV), visible (VIS) and shortwave near-infrared (UV-VIS-NIR; 200–900 nm) regions were used to identify spectral signatures and indices for their potential use as biomarkers of leaf development and physiological status of plants under induced senescence conditions. Manihot esculenta Crantz (HMC-1 variety) was used as a model. Spectral signatures were obtained from leaves at two phenological stages (4 and 6 months after planting) using UV-VIS-NIR spectroscopy by the diffuse reflectance technique. Classical and experimental spectral indices were evaluated, and their discriminatory power through different ontogenies was assessed using ANOVA/Kruskal–Wallis and post hoc tests. Senescence effects were further examined by postharvest monitoring (1–20 days), with temporal, ontogenetic, and interaction effects validated using linear mixed models (LMMs), while multivariate structure and spectral convergence were explored via principal component analysis and hierarchical clustering (PCA-HCA). Functionally Enhanced Derivative Spectroscopy (FEDS), comparative analysis, and spectral correlation mapping allowed signal’s selective enhancement and the identification of phenolic compounds, photosynthetic pigments, and structural molecular components. Results showed high ontogenetic stability of UV-associated phenolic signals (~210–220 nm), whereas the VIS region (420–600 nm) clearly differentiated young leaves. The NIR region was stable across ontogeny but highly sensitive to temporal degradation, reflecting changes in water status and internal structure. UV-VIS-NIR indices effectively differentiated young leaves and changes by stress. It is concluded that multiregional characterization of the spectral response supported by FEDS allows the extraction of robust indices with strong potential as biomarkers of leaf maturation and senescence in cassava. Full article

This paper presents Resilient Edge-IVA (Intelligent Video Analytics), an integrated framework designed to ensure real-time inference stability and high-speed embedding-based similarity search in resource-constrained edge computing environments. Conventional systems often face Quality of Experience (QoE) degradation caused by computational overhead and hardware-level bottlenecks. To address these challenges, this study proposes a “Whole-cycle” methodology employing a perception-driven, three-tier adaptive control algorithm. This algorithm dynamically modulates encoding parameters, such as resolution and bitrate, by utilizing real-time inference latency and CPU utilization as feedback signals. Furthermore, the framework incorporates an event-density-based Data Diet mechanism. This mechanism selectively adjusts video quality based on object detection results, preserving high-fidelity imagery for critical events while significantly reducing data volume during static intervals. The backend implements a hybrid storage architecture combining the Milvus vector database for CLIP-based high-dimensional visual embeddings with a PostgreSQL relational database for structured metadata. These systems are linked via a deterministic hash key to ensure data atomicity and facilitate high-speed, multi-dimensional embedding-based retrieval. Experimental evaluations conducted on a Raspberry Pi 5 and Hailo-8 NPU demonstrate that the proposed framework maintains a frame drop rate below 0.3% even under extreme workloads, providing a 13-fold improvement in operational stability over static configurations. The results also confirm a 54.2% reduction in total storage occupancy and a Hash Mapping Consistency (HMC) score of 0.89. These findings validate the framework’s effectiveness in reconciling real-time processing stability with storage efficiency. Building upon this baseline, future research will extend the framework to multi-class environments, targeting applications such as Intelligent Transport Systems (ITS). Full article

Background: Progesterone (P4) is used as an antiseizure medication (ASM) to treat catamenial epilepsy, refractory to first-line drugs. P4 and other neurosteroids (NSs) are important regulators of multiple nervous system functions, including neuronal excitability and synaptic plasticity. In addition to their antiseizure properties, P4 and other NSs are also anti-inflammatory agents. Neuroinflammation is an important pathophysiological mechanism of epilepsy refractory to ASMs. Accordingly, we evaluated the ability of P4 to modulate neuroinflammation, using human microglia activated by lipopolysaccharide (LPS). Methods: Human microglia (HMC3) were stimulated for 3 h with LPS in the absence or presence of various concentrations of P4. Thereafter, levels of (i) toll-like receptor 4 (TLR4), (ii) the NLRP3 inflammasome, and (iii) pro-inflammatory cytokines were quantitated by real-time PCR and Western blot analyses. Phagocytic activity was also assessed using a phagocytosis assay employing fluorescent beads. Results: P4 treatment significantly reduced the microglial inflammatory state induced by LPS, which was mediated by upregulation of the TLR4- and NLRP3-axes. The protective effects of P4 were mediated by inhibition of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFκB) phosphorylation and reduced activation of Mitogen-Activated Protein Kinases (MAPK). The effects of P4 included a significant reduction in mRNA levels of the main pro-inflammatory cytokines and a reduction in phagocytic activity of HMC3. Conclusions: P4 is endowed with significant anti-inflammatory properties, which may be involved in the beneficial effects reported for drug-resistant catamenial epilepsy. Further research is required to clarify P4 post-receptor mechanisms of action and to explore the roles of other P4-derived NSs. Full article

This research investigates the effects of incorporating cyanobacterium Oscillatoria limnetica (OL) powder into aquafeeds on the growth rates, activity of digestive enzymes, antioxidant status, and innate immune responses of white-leg shrimp, Litopenaeus vannamei. The shrimps’ resistance against possible infection with Vibrio harveyi was also examined. For 12 weeks, shrimps (1.26 ± 0.088 g) were nourished on experimental diets with 0.0, 0.75, 1.5, 2.25, and 3.0 g OL/kg feed, represented as OL0, OL0.75, OL1.5, OL2.25, and OL3.0, respectively. At the end of the feeding trial, shrimps were challenged by V. harveyi, and their mortality was further observed for further ten days. The shrimps fed on OL-enriched diets, particularly OL3.0, showed significantly greater growth, digestive enzyme activities, and innate immunity performance than those fed on the control diet (OL0). Compared to the control group, enzymatic antioxidant parameters (CAT and SOD) were significantly (p < 0.05) higher; meanwhile, MDA levels showed marked declines in shrimps fed on OL-containing diets (particularly OL3.0). The relative mRNA expression of antioxidant-related genes (cMn-SOD, CAT, and GPx) and immune-related genes (HMC, Alpha2M, ProPO, and Pen3a) was upregulated in the OL-fed animals compared to the control group. The intestinal morphometry was markedly enhanced in the animals fed on OL-enriched diets, especially with respect to the OL3.0 diet. After the bacterial challenge assay against V. harveyi for ten days, shrimps fed on the control diet had 83.3% mortality; meanwhile, the mortality rate was lower in shrimp groups fed on OL diets, particularly OL3.0 (46.7%). This study demonstrates that L. vannamei benefits from dietary inclusion of O. limnetica (3.0 g/kg feed) through accelerating its growth due to better digestion of diets. Additionally, the OL meal acts as a functional ingredient that fortifies the shrimp against possible V. harveyi infection by enhancing their biological defense system. Full article

To investigate the role of the adenosine A2A receptor (A2AR) in methamphetamine (MA)-induced microglia-mediated neuroinflammation and to explore the potential signaling mechanism, postmortem human striatal tissue from MA users, a male C57BL/6 mouse model of MA exposure, and the human microglial cell line HMC3 were examined by Western blotting, immunofluorescence, and related assays. Across all three experimental systems, MA exposure significantly upregulated A2AR expression together with alterations in downstream PKA and PKC signaling. These signaling changes were accompanied by parallel upregulation of pro-inflammatory mediators (iNOS, IL-1β, and IL-18) and of anti-inflammatory and repair-associated factors (Arg-1 and IL-10), suggesting that MA did not trigger a simple unidirectional inflammatory program but instead induced multidimensional phenotypic remodeling of microglia that varied with exposure time and dose. Intervention with the selective A2AR antagonist SCH58261 showed that pharmacological inhibition of A2AR markedly attenuated MA-induced alterations in PKA/PKC signaling and suppressed the accompanying shifts in inflammatory mediator expression, thereby mitigating the neuroinflammatory response. These results suggest that A2AR is involved in the modulation of MA-induced microglial inflammatory responses and may contribute to the mixed inflammatory state characterized by simultaneous changes in pro-inflammatory and anti-inflammatory markers, possibly associated with PKA/PKC signaling. This study expands current understanding of the inflammatory basis of MA-related neurotoxicity and suggests A2AR as a potential target for therapeutic intervention in MA abuse. Full article

Background: Long-read, single-CpG-resolution sequencing is redefining the information-to-depth ratio in epigenomics. While conventional methylome analysis often requires high coverage, we propose a scalable pipeline designed to extract high-density regulatory logic from shallow sequencing data. Methods: By utilizing the progenitor-like HepaRG cell line as a model for liver plasticity, we validated this framework across two divergent developmental trajectories: hepatic maturation and sphere-induced retrodifferentiation. Our technical approach combines CpG-centric enrichment and regional methylation aggregation to reconstruct regulatory landscapes from sparse data. Using long-read Nanopore sequencing, we mapped the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Results: Our pipeline revealed that these trajectories are not inverse processes but engage distinct epigenetic strategies. Hepatic maturation is characterized by the accumulation of 5hmC that partially targets repressive heterochromatin (H3K9me3, H4K20me3) and pioneer factors such as FOXA2. In contrast, retrodifferentiation increases 5mC, potentially silencing adult regulators such as HNF1A via Polycomb-associated networks. In addition, aggregation-based analysis can distinguish widespread focal perturbations from a restricted subset of transcription factors that translate epigenetic changes into regional accessibility. Conclusions: This study provides a scalable computational framework for investigating cellular fate transitions, proving that high-value epigenetic insights are attainable even at reduced sequencing depths. Full article

Ether phospholipids from marine organisms represent an understudied class of bioactive lipids with unique structural features. In this study, we isolated, for the first time, an ether phosphatidylserine (ePS) species from the soft coral Sclerophytum heterospiculatum and assessed its biological activity on human microglial clone 3 (HMC-3) cells. The isolated ePS contained an ether bond at the sn-1 position and very-long-chain polyunsaturated fatty acids (PUFA) (24:5) at the sn-2 position. Using an MTS assay, we demonstrated that ePS was non-cytotoxic at all tested concentrations (0.39–100 μg/mL) and even increased microglial proliferation at 50–100 μg/mL. In microglial cells activated by lipopolysaccharide (LPS-activated), ePS significantly reduced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). A lipidomic analysis by HPLC–MS/MS revealed that ePS modulated the membrane lipid composition of microglial cells, increasing the content of polyunsaturated phosphatidylserines (PS 36:3, PS 40:5) and decreasing the levels of phosphatidylinositols (PI 18:1/20:4; PI 18:0/20:4, 18:1/20:3). Furthermore, a fatty acid analysis showed that ePS prevented LPS-induced accumulation of saturated fatty acids and preserved PUFA levels in HMC-3 cells. These findings suggest that marine-derived ePS can be considered as promising agents with antioxidant and anti-inflammatory properties. Full article

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by poor survival. Despite a high tumor mutation burden, biomarker discovery in SCLC remains challenging due to rapid tumor plasticity and limited tissue availability, highlighting the promise of liquid biopsy-based approaches. Epigenetic dysregulation of DNA 5-hydroxymethylcytosine (5hmC) has emerged as a cancer hallmark. However, its role in SCLC remains largely unexplored. Here, we characterized the cell-free DNA (cfDNA) 5hmC landscape in SCLC and evaluated its potential applications. We profiled the cell-free hydroxymethylomes of 107 pre-treatment SCLC patients and 53 matched controls using the 5hmC selective chemical labeling (5hmC-Seal) assay. SCLC displayed higher global 5hmC levels and distinct enrichment at neurodevelopmental and synaptic pathways, consistent with the neuroendocrine identity of SCLC. Concordance between plasma and matched circulating tumor cell patient-derived xenograft (CDX) demonstrated that cfDNA 5hmC reflects tumor epigenetic states and correlates with transcriptomic-derived molecular subtypes. Elevated SCLC-specific 5hmC levels and extensive stage (ES) disease were associated with inferior survival, with ES disease showing enrichment of pathways linked to cellular plasticity and neurodevelopment. Together, these findings indicate that cfDNA 5hmC profiling has potential as a biologically informative and clinically relevant biomarker in SCLC, with possible applications in tumor subtyping and risk stratification. Full article

This study investigated the effects of feeding High-Moisture Corn (HMC) on meat production performance, mutton quality, muscle metabolism, and gut microbiota in Kazakh rams. Thirty-two 6-month-old Kazakh rams were divided into a control group (CT) and an experimental group (GS). Both groups received a basal diet consisting of 30% whole-plant corn silage, 30% cotton residue, and a concentrate mixture. In the CT group, the concentrate contained 24% ordinary crushed corn (on a dry matter basis). In the GS group, half of the ordinary crushed corn was replaced with HMC, resulting in a concentrate containing 12% ordinary crushed corn and 12% HMC. After a 120-day feeding period, backfat thickness was significantly higher in the GS group (p < 0.05); For meat quality, muscle shear force was significantly lower (p < 0.01) and intramuscular fat content was significantly higher (p < 0.01) in the GS group; Amino acid analysis showed that aspartic acid content was significantly lower (p < 0.01), arginine and glutamine contents were significantly lower (p < 0.05), and glycine content was significantly higher (p < 0.05) in the GS group; Fatty acid analysis revealed that the contents of methyl undecanoate, methyl myristate, methyl palmitate, methyl heptadecanoate, methyl alpha-linolenate, and all-cis-4,7,10,13,16-docosapentaenoic acid were significantly higher in the GS group (p < 0.01), while the contents of ten other fatty acids, including methyl caprate, methyl laurate, and methyl tridecanoate, were significantly higher (p < 0.05); A total of 668 metabolites were detected by muscle metabolomics, and 20 of them were identified as significantly differential metabolites, with the GS group showing 15 upregulated and 5 downregulated, mainly enriched in four pathways: valine, leucine and isoleucine biosynthesis; taurine and hypotaurine metabolism; pantothenate and CoA biosynthesis; and the citrate cycle (TCA cycle); Gut microbiota analysis showed no significant difference in alpha diversity, but beta diversity was significantly separated between the two groups (p < 0.01); Correlation analysis revealed that Firmicutes_A was significantly negatively correlated with most fatty acids, while Proteobacteria was significantly positively correlated with multiple fatty acids (p < 0.05). In conclusion, The GS group had significantly increased backfat thickness, reduced muscle shear force, increased intramuscular fat content, and significantly enriched beneficial fatty acids in Kazakh rams, thereby improving meat quality. Full article

Cervical cancer (CC) is an alarming global health problem, with predominantly higher incidence, lethal progression, and mortality among women of African ancestry (AA) than women of European ancestry (EA). Although persistent high-risk human papillomavirus (HPV) integration and infection are the key etiological factors, currently available evidence implicates epigenetic reprogramming as a prime contributor to ancestry-associated differences in CC pathogenesis. To address these disparities, we performed genome-wide DNA methylation profiling of HPV-positive cervical intraepithelial neoplasia (CIN) lesions from AA (n = 15) and EA (n = 15) women. Differential methylation analysis identified a distinct epigenomic landscape in AA-CIN lesions, with widespread hypermethylation and hypomethylation at promoter-associated and regulatory CpG sites. Pathway enrichment analyses highlighted dysregulation of ECM-receptor interaction, focal adhesion, PI3K-Akt, MAPK, Ras, Rap1, and RUNX-dependent transcriptional networks. Comparative analysis across CIN grades (CIN1–CIN3) revealed progressive epigenetic reprogramming affecting cell cycles, cytoskeletal dynamics, signaling, and metabolic pathways. Among hypermethylated tumor suppressor genes, SH3GL2 and ARHGAP25 showed significantly higher methylation in AA lesions, accompanied by concomitant loss of their protein expression. MBD1, a methylation-binding regulator, was upregulated in AA-CIN lesions, coinciding with global loss of 5-hydroxymethylcytosine (5hmC), suggesting enhanced transcriptional repression. In contrast, EA lesions retained protein expression and 5hmC levels. Collectively, these findings indicate that early, ancestry-specific epigenetic modifications target tumor suppressor pathways and converge on oncogenic signaling, cytoskeletal remodeling, and cell–cell adhesion. Our study provides mechanistic insight into CC health disparities, identifying SH3GL2 and ARHGAP25 hypermethylation as potential biomarkers, and highlighting epigenetic regulation as a contributor to disparate CC progression in AA women. Full article

This study aimed to investigate the effects of feeding high-moisture corn (HMC) on weight performance, serum immune and antioxidant indices, rumen fermentation, microbial community, and metabolomics in Kazakh rams. A total of 32 healthy Kazakh rams were randomly divided into a control group (CT, diet with only ordinary crushed corn) and an experimental group (GS, diet with 50% ordinary crushed corn + 50% HMC), following a 7-day adaptation period and a 120-day trial period. Results showed that the F/G was significantly lower in the GS group than in the CT group (p < 0.05). FBW, net weight gain and ADG increased by 4.58%, 8.69%, and 8.70%, respectively, while ADFI decreased by 7.04% (p > 0.05). Regarding serum immune indices, IgA in the GS group was significantly higher at 40 d (p < 0.01), and IgM was significantly higher at 40, 80, and 120 d (p < 0.05). For antioxidant indices, the SOD activity in the GS group was significantly higher than that in the CT group at 120 d (p < 0.01). The CAT activity in the GS group was significantly higher at 40, 80, and 120 d (p < 0.01). Among rumen fermentation parameters, the concentration of butyric acid in the GS group was significantly lower than in the CT group (p < 0.01). Microbial diversity analysis indicated no significant differences in Alpha- and Beta-diversity of rumen microorganisms between the two groups. However, the relative abundance of Firmicutes_A at the phylum level was significantly higher in the GS group (p < 0.05), and the abundance of Cryptobacteroides was significantly higher than in the CT group (p < 0.01). Rumen metabolomic analysis identified a total of 1357 differential metabolites, among which 1130 showed significant differences, with 459 upregulated and 671 downregulated. These were mainly enriched in pathways such as Glutathione metabolism, Beta-alanine metabolism, Sphingolipid metabolism, and lysine degradation. In conclusion, feeding HMC can improve feed conversion efficiency and weight performance in Kazakh rams, regulate the structure of dominant rumen microorganisms, and enhance immune and antioxidant capacities. Full article

Heterogeneous multi-core systems (HMCSs) typically face a dilemma: heuristics (e.g., Linux CFS) are fast but blind to global constraints, while meta-heuristics (e.g., GAs) are globally optimal but too slow for real-time OS interaction. To bridge this gap without relying on “black-box” neural networks, we introduce the Tissue P System-Inspired Task Allocator (TPSTA). By mapping HMCS and parallel task scheduling to Tissue P System models and vectorized linear algebra problems, TPSTA achieves a computational complexity of $\mathrm{O}\left(\mathrm{M}/\mathrm{W}\right)$, effectively compressing the decision space. Our rigorous evaluation across four dimensions reveals a system strictly bound by physical constraints rather than algorithmic heuristics. (1) Under sufficient resource provisioning (four chips), TPSTA achieves a 0.00% Deadline Miss Ratio (DMR). Crucially, stress tests on constrained hardware (two chips) show graceful degradation to a 12.88% DMR, matching the optimal theoretical bound of EDF, whereas standard heuristics collapse to failure rates > 68%. On a massive 4096-core cluster, TPSTA outperforms the Linux GTS scalar baseline by 14.4×, maintaining low latency where traditional algorithms fail (>8 s). (3) Adaptability: The system demonstrates adaptive routing in handling hardware heterogeneity; without explicit rule-coding, it autonomously prioritizes data locality during NUMA transfers and migrates compute-bound tasks during thermal throttling events. (4) Physical Limits: Finally, our roofline analysis confirms that while the algorithmic speedup is theoretically linear, practical performance saturates at ~375× due to the Memory Wall, validating the isomorphism between synaptic bandwidth and hardware memory channels. Full article

DNA polymerase beta (Polβ) is a 39 kDa, single polypeptide enzyme that possesses both gap tailoring and nucleotidyl transferase activity and is the key polymerase involved in base excision repair (BER) and the final steps of active gene demethylation. We demonstrated that residues in the mouse Polβ protein, L301 and V303, are critical for Polβ’s interaction with the BER scaffolding protein X-ray repair cross-complementing 1 (XRCC1), and mutation of these residues impairs Polβ’s ability to bind to XRCC1, negatively impacting BER complex assembly. We developed Polβ^{L301R-V303R/L301R-V303R} knock-in mice to explore how defects with this essential protein complex impact genome stability in the mouse. We found these mice to be viable and fertile yet exhibited a modest reduction in body weight. Here, we examined the protein and mRNA levels in tissues from wild-type (WT), heterozygous (HET), and homozygous (HOM) Polβ^{L301R-V303R/L301R-V303R} mice and the derived fibroblast cell lines. We show that HOM mice have significantly diminished Polβ protein levels, as compared to WT mice, in several tissues, yet Polβ mRNA levels were not significantly different, suggesting the decreased levels of Polβ protein could not be attributed to lower gene expression. Upon examination of Polβ stability in mouse ear fibroblasts derived from WT and HOM mice, results are consistent with human cell studies that the Polβ^L301R-V303R protein is unstable and undergoes proteasome-mediated degradation. Finally, we evaluated WT, and HOM, liver and brain genomic DNA samples for 5-methylcytosine/5-hydroxymethylcytosine (5mC/5hmC) levels by nanopore sequencing to investigate the impact of suppressed Polβ protein levels on active gene demethylation. As expected, we found tissue-specific trends in methylation, when comparing the brain and liver. However, we were unable to discern substantial differences in methylation levels between WT and HOM mice, suggesting that in the absence of external stressors, low Polβ levels do not impact methylation patterns. Full article

The cause of chronic neurological effects associated with Lyme disease (LD) remains unclear. We propose that bacterial extracellular vesicles (BEVs) released by Borrelia burgdorferi, the causative agent of LD, exacerbate spirochete-induced damage and serve as a persistent source of antigenic stimulation. We showed that, over a 10-day period, in vitro cultures of B. burgdorferi B31 produced 38,000 BEVs per spirochete with a distinctive double-membrane structure and median diameter of 143.3 nm. BEVs contained known immunogenic and immunomodulatory molecules such as peptidoglycan, p66, flagellar filament protein (FlaB), basic membrane proteins A/B/D, BdrV, GroEL, CRASP-1, ErpA8, glycerophosphodiester phosphodiesterase, p37, OMS28, p13, OspA/B/C, VlsE, and outer membrane glycolipids (e.g., cholesteryl 6-O acyl beta D galactopyranoside). Chromosome-encoded 16S ribosomal RNA and cp32 plasmid-encoded OspE and terminase genes were also detected in the BEVs. Of the 45 Borrelia proteins identified in the urine of a C3H/HeJ murine model of Lyme disease, 14 were associated with BEVs. In human urine samples, 31 of 289 spirochete proteins detected in patients with either acute Lyme disease or persistent borreliosis post-treatment symptoms, including p66 and FlaB, were also BEV-associated. BEV treatment of HMC3 human microglial cells reduced phagocytic activity and triggered aberrant activation of inflammatory and immunometabolic pathways, including upregulation of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and Toll-like receptor 2 (TLR2) gene expression. BEVs also induced NRF2 nuclear translocation. In conclusion, these findings support that BEVs can amplify spirochete-induced damage and act as antigenic debris, driving dampened phagocytic activity and dysregulated inflammation, with implications for diagnostics and therapeutics targeting vesicle-mediated pathology. Full article