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关键词： extracellular vesicles   herpes simplex virus type 2   Lactobacillus rhamnosus GG   NOD2   type I interferons  

摘要： The immune evasion strategies and lifelong latency of herpes simplex virus type 2 (HSV-2) present significant challenges for effective treatment. Recent studies have demonstrated that the commensal microbiota plays an important role in regulating immunity against viral infections. We previously reported that Lactobacillus rhamnosus GG (LGG) activates the expression of type I interferons (IFN-I) to inhibit HSV-2 infection. However, the specific molecular mechanisms remain unclear. Bacterial extracellular vesicles (EVs) are small lipid bilayer-bound particles secreted by bacteria, which can serve as intercellular communication vehicles between the host and pathogens, functioning as immunomodulatory vectors defending against viral infections. In this study, we confirmed that LGG-EVs activate the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)-IFN-I signalling pathway, inducing the expression of interferon-stimulated genes (ISGs) to combat HSV-2 infection both in vivo and in vitro. Furthermore, we explored the specific components within LGG-EVs and identified the presence of muramyl dipeptide (MDP). We demonstrated that MDP-enriched LGG-EVs effectively inhibit HSV-2 infection via activation of the NOD2-IFN-I pathway. These findings suggest that LGG-EVs could serve as a novel therapeutic strategy for HSV-2 and provide a mechanistic foundation for future antiviral research.

关键词： 超敏反应   尘螨科   Th2细胞   免疫球蛋白E   白细胞介素-13   白细胞介素-33   皮炎,特应性   婴儿  

摘要： 目的 探究孕晚期室内尘螨水平对母婴血液中Th2相关因子水平的影响。方法 选择于我院孕检并于2023年7月—2024年6月足月顺产单胎的78例健康产妇及其婴儿作为研究对象,根据产妇是否为特异性体质将产妇及婴儿分为特异性组和非特异性组,采用酶联免疫吸附试验（ELISA）测定孕晚期产妇家中尘螨暴露水平,并据此将产妇及婴儿进一步分为低、中、高暴露亚组。收集各组产妇的性别、年龄、体质量指数及婴儿性别、出生体质量、喂养方式等一般资料,采集产妇产前即刻的外周静脉血和婴儿出生时的脐带血,检测血清中Th2相关因子（IL-33、IL-13、IgE）的水平并进行比较,随访产后早期（3个月内）婴儿特应性皮炎（AD）发生情况。结果 特异性组中,中、高暴露亚组产妇血清IL-33、IL-13、IgE及婴儿血清IL-33、IL-13水平均显著高于低暴露亚组（F=3.764～9.454,P<0.05）;非特异性组中,高暴露亚组婴儿血清IgE水平显著高于低暴露亚组（F=3.327,P<0.05）。此外,特异性组中、高暴露亚组产妇血清IL-13、IgE水平及婴儿血清IL-33、IgE水平显著高于非特异性组中、高暴露亚组（t=2.552～8.604,P<0.05）。婴儿早期AD发病与其出生时血清IL-33、IgE水平,以及产妇的特异性体质和产前血清IL-33、IL-13、IgE水平有关（χ2=11.522,t=2.805～4.490,P<0.05）。结论 母婴围生期血清Th2相关因子水平升高与孕晚期室内尘螨水平升高有关,该关联在具有特异性体质的产妇中尤其明显,且遗传与环境的交互作用会增加婴儿早期患AD的风险。

关键词： 3D hESC-derived exosomes   hsa_circ_0076798/miR-1184/DICER1 axis   liver fibrosis   macrophages   TNF/NF-kappa B signaling pathway  

摘要： Here, we employed human embryonic stem cell spheroid (3D hESCs)-derived exosomes to assess inflammatory responses of macrophages in liver fibrosis, and found that 3D hESC-exosomes promoted the transformation of macrophages from M1 to M2 phenotype in vitro. The transplantation of 3D hESC-exosomes exhibited a notable decrease of pro-inflammatory factors, and significant increase of anti-inflammatory factors, and led to a reduction of CD86+M1 macrophages and an increase of Arg-1+M2 macrophages in the livers of treated fibrotic mice, restricting the advancement of liver fibrosis. hsa_circ_0076798, derived from 3D hESC-exosomes, acts as a molecular sponge that sequesters miR-1184, thereby mitigating miR-1184-mediated repression of DICER1 expression within macrophages. Further investigation revealed that DICER1 ultimately mitigated macrophage inflammation by deactivating TNF/NF-kappa B signaling pathway. Therefore, our findings demonstrated that 3D hESC-exosomes alleviated inflammatory responses by suppressing TNF/NF-kappa B pathway through hsa_circ_0076798/miR-1184/DICER1 axis, and offers insights into the targeted treatment of liver fibrosis via exosome-based cell-free therapy.

关键词： aging   canine personality   canine inflammation   cytokines  

摘要： As dogs live longer, they face an increased risk of functional age-related changes, including physiological and behavioral alterations. However, data on these age-related processes in domestic dogs remain limited. In this study, we assessed serum concentrations of cytokines (TNF-alpha, IL-6, IL-10), personality and cognition using validated scales (Dog Reinforcement Sensitivity Theory Personality Questionnaire (RSTQ-D), Dog Impulsivity Assessment Scale (DIAS), and Canine Cognitive Assessment Scale (CCAS)) in 44 healthy pet dogs from two non-overlapping age groups (1-4 years old and >= 11 years old). Generalized linear models revealed small but significant (p = 0.001) negative effects of age-by-cytokine interactions in predicting sensitivity to RST personality traits related to fear and anxiety in older dogs. Specifically, higher TNF-alpha and IL-10 levels predicted lower scores on the Fight/Flight/Freeze System (FFFS) and the Behavioral Inhibition System (BIS). These findings provide novel insights into previously unrecognized associations between the immune system and personality in healthy older dogs, possibly contributing to broader profiles of vulnerability or, conversely, resilience. Further research is needed to confirm these associations and clarify their functional meaning. Such knowledge could facilitate the early identification of complex aging-related phenotypes and inform individualized preventive strategies to support the health and well-being of aging companion dogs.

关键词： central nervous system inflammation   depression   electroacupuncture   inflammatory bowel disease   interleukin-4   microglia  

摘要： Aims: Depression is prevalent in inflammatory bowel disease (IBD) and linked to neuroinflammation. However, the underlying mechanisms remain unclear. Therefore, we investigated the efficacy of electroacupuncture in mice with IBD and depression. Methods: An IBD mouse model of depression was established using 2.0% dextran sodium sulfate (DSS). After electroacupuncture, general condition and behavior were evaluated. Colon morphology was observed using hematoxylin and eosin staining. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. Microglial activation was measured using immunofluorescence. Hippocampal protein expression was assessed using Western blotting and real-time fluorescence quantitative polymerase chain reaction. Results: DSS-induced model mice exhibited significant depression-like behaviors and colon pathology. Serum and colon IL-1 beta expression was elevated (p < 0.01), while IL-4, IL-10, and TGF-beta 1 expression was decreased (p < 0.01 or p < 0.05). Hippocampal microglial activation was evident, with increased IL-1 beta expression (p < 0.01) and reduced IL-4, IL-10, TGF-beta 1, JAK1, STAT6, and p-STAT6 expression (p < 0.01 or p < 0.05). Electroacupuncture resolved these changes;though its effects were significantly weakened after IL-4 and p-STAT6 inhibitor administration (p < 0.01 or p < 0.05). Transcriptomic sequencing of hippocampal tissue indicates that pro-inflammatory pathways such as TNF/NF-kappa B/mTOR are activated in the model group. Electroacupuncture can activate the IL-4-mediated JAK-STAT signaling pathway, inhibit the activation of pro-inflammatory signaling pathways, upregulate neuroprotective genes such as Slc2a3, Mef2d, and Jak1, and exert anti-inflammatory effects. Conclusion: IL-4-JAK1-STAT6 signaling may be an important pathway in mediating the efficacy of electroacupuncture in IBD with comorbid depression, particularly promoting microglial M2 polarization and improving neuroinflammation.

关键词： Ascites   Barcoding   CRISPR screening   Interferon   Lineage tracing   Metastasis   Omentum   Ovarian Cancer   Single cell analysis  

摘要： Metastasis is an emergent continuum, driven by evolving reciprocal adaptations between continuously disseminating tumor cells (DTCs) and the specialized metastatic niches of distant organs. The interplay between intrinsic and niche-driven mechanisms that enables DTCs to survive and home to distant organs remains incompletely understood. Here, using MetTag, a single-cell barcoding and transcriptome profiling approach with time-stamped batch identifiers (***), we mapped temporal, clonal dynamics of DTCs and the immune cell landscape across ovarian cancer metastatic niches. Deep sequencing of barcodes revealed preferred enrichment of early-disseminated clones across metastatic niches. Mechanistically, single-cell RNA sequencing (scRNA-seq) coupled with velocity analyses in ascites and metastasis-bearing omenta uncovered an emergent, distinct interferon-gamma (IFNγ) centric transcriptional trajectory, enriched among early seeding clones. Moreover, CRISPR/Cas9 screening of metastatic niche-specific signatures demonstrated that genes belonging to the ascites IFNγ signature, including , , are functionally important for peritoneal metastasis. Knockout of IFNγ receptor 1 () in tumor cells significantly reduced metastatic burden and extended survival, underscoring the importance of tumor cell intrinsic IFNγ signaling in ovarian cancer metastasis. Furthermore, we identified that the tumor intrinsic IFNγ response and ascites-derived tumor-associated macrophages (TAMs) protect cancer cells from anoikis-mediated death within the IFNγ-rich ascites environment. Our study resolves temporal dynamics of disseminating tumor cells and highlights an ascites-driven, IFNγ program as a necessary pro-metastatic adaptation in the ovarian metastasis cascade.

关键词： span id="cetext0002">Allogeneic Hematopoietic Cell TransplantationAcute Myeloid LeukemiaOutcomesMinimal Residual Disease  

关键词： coding change   exon 2   italic>HLA-A*25:95   NGS  

摘要： The novel HLA-A*25:95 allele differs from HLA-A*25:01:01:01 by one nucleotide substitution in exon 2.

关键词： HLA-A   HLA-B   HLA-C   NGS   novel allele  

摘要： Nine novel HLA alleles were detected during the HLA typing process.