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关键词： 犬细小病毒2c型   病原分离   原核表达   单克隆抗体  

摘要： 本研究从病死北极狼体内分离并鉴定犬细小病毒（CPV），将该株病毒暂时命名为CPV-JL-23。并制备该毒株的中和活性单克隆抗体。本研究以病死北极狼的临床症状、分子检测和病原分离结果为依据，分离鉴定对北极狼为高致病性的CPV病毒，通过序列分析进行亚型鉴定；以病毒基因组DNA为模板，利用PCR扩增VP2基因，通过原核系统表达VP2蛋白，以纯化后的蛋白为抗原对BALB/c小鼠进行免疫；取免疫后的脾细胞与SP2/0进行细胞融合。以VP2蛋白或病毒悬液为包被抗原，利用间接ELISA、Western-blot和IFA检测方法筛选CPV单抗，并在细胞水平进行中和活性分析。经鉴定，本研究分离到CPV-2c型病毒1株，筛选到15株识别CPV的单克隆抗体；其中4B1和5F1两株单克隆抗体具有中和活性。

关键词： Cellular immune response   Genetic diseases   Genetics   Immunology  

关键词： Cell biology   Immunology   Immunotherapy   Therapeutics   Urology  

摘要： Tumor cells often employ many ways to restrain type I IFN signaling to evade immune surveillance. However, whether cellular amino acid metabolism regulates this process remains unclear, and its effects on antitumor immunity are relatively unexplored. Here, we found that asparagine inhibited IFN-I signaling and promoted immune escape in bladder cancer. Depletion of asparagine synthetase (ASNS) strongly limited in vivo tumor growth in a CD8⁺ T cell–dependent manner and boosted immunotherapy efficacy. Moreover, clinically approved L-asparaginase (ASNase),synergized with anti–PD-1 therapy in suppressing tumor growth. Mechanistically, asparagine can directly bind to RIG-I and facilitate CBL-mediated RIG-I degradation, thereby suppressing IFN signaling and antitumor immune responses. Clinically, tumors with higher ASNS expression show decreased responsiveness to immune checkpoint inhibitor therapy. Together, our findings uncover asparagine as a natural metabolite to modulate RIG-I–mediated IFN-I signaling, providing the basis for developing the combinatorial use of ASNase and anti–PD-1 for bladder cancer. © 2025, Wei et al.

关键词： IDO1   immunohistochemistry   TMA   metabolic reprogramming  

摘要： Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and malignant disease with a limited number of biomarkers and insufficient targeted therapies. The current therapeutic landscape is challenged by low response rates, underscoring the need for new therapeutic targets. The success of immunotherapy in HNSCC has highlighted the importance of the immune microenvironment, and since metabolic reprogramming, especially altered tryptophan metabolism, is an important aspect in immune evasion, the interplay of the two enzymes IDO1 and IL4I1 was investigated in HNSCC to assess their immunosuppressive roles and potential as prognostic biomarkers. The immunohistochemical expression of IDO1 and IL4I1 was evaluated by an experienced head and neck pathologist in a tissue microarray (TMA) of 402 patients with HNSCC. Clinical and pathological data were retrieved, and the overall survival of the patients was calculated. In this study, IDO1 and IL4I1 were expressed by HNSCC tumor cells in the TMA of 402 patients. The overall survival analysis of the clinical data of the patients revealed that high IL4I1 expression was significantly associated with worse OS (p = 0.0073), while IDO1 expression did not reach statistical significance (p = 0.087). The combination of both markers led to a clinically significant stratification of patients. Especially p16-negative OPSCC with a high IL4I1 expression demonstrated poor survival. Immunologic differences between IDO1 and IL4I1 were detected in a TMA of 403 patients, with IDO1 and IL4I1 being expressed by HNSCC. A low IL4I1 expression in HNSCC led to a significantly better OS in this study, while IDO1 expression did not have a significant effect. Additional studies are necessary to investigate the complex interplay in the metabolic reprogramming of tumor cells.

关键词： Epoxy resin   MXene   PBA   Fire safety   Ionic Liquid   Mechanical property  

摘要： Epoxy resins (EP) are renowned for their chemical stability, ease of processing, and cost-effectiveness, which has led to their extensive utilisation. However, their flammability and associated fire risks impose significant limitations on their broader application. Developing effective flame retardants to enhance the fire safety of EP remains a pressing need. In this study, a flame-retardant nanohybrid MXene@PBA@IL (MPL) with excellent fire safety properties for EP was developed by modifying MXene with a trimetallic Prussian blue analogue (PBA) incorporated with Ionic Liquid (IL). MPL demonstrated good compatibility with EP and effectively enhanced its flame retardancy, smoke suppression, durability, and mechanical properties at very low addition levels. Specifically, the EP-2 %MPL sample, containing 2 wt% MPL, achieved a UL-94 V-0 rating and a high limiting oxygen index of 30.8 %. Moreover, compared to pure EP, the peak heat release rate (pHRR), total heat release (THR), peak smoke production rate (pSPR) and total smoke production (TSP) of EP-2 %MPL were reduced by 39.18 %, 23.16 %, 44.09 %, and 50.22 %, respectively. The synergistic carbonization effect of MXene, PBA, and IL played a key role in enhancing the flame retardancy of EP-2 %MPL. Additionally, the flexural strength, impact strength, and water contact angle of EP-2 %MPL increased by 21.82 %, 39.18 %, and 61.76 %, respectively, compared to pure EP. This study offers a promising strategy for the development of multifunctional polymeric nanocomposites based on MXene derivatives.

关键词： 肠致病性大肠杆菌   脂多糖   O-抗原   血清型   结构鉴定  

摘要： O-抗原是细菌脂多糖最外层的组成部分， 其结构的复杂性与多样性对细菌的免疫逃逸、致病性及宿主相互作用具有重要影响。本研究开展了肠源性大肠杆菌EPEC080菌株脂多糖O-抗原的提取纯化。通过分子量测定、单糖组分分析、红外光谱分析以及核磁共振谱分析完成了该细菌脂多糖O-抗原化学结构的解析。该O-抗原的平均分子量为14.3 kDa， 由五糖重复单元→4)-[α-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-[β-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-α-L-Rhap-(1→构成， 其化学结构与已知的大肠杆菌各血清型O-抗原结构均不同， 表明EPEC080菌株是一种新的大肠杆菌血清型。本研究结果可为肠致病性大肠杆菌的致病机制探索， 以及相关疾病的预防和治疗方法研发提供基础。

关键词： AGT/AGTR1a/IL-1 beta axis   extracellular matrix metabolism   osteoarthritis   renin-angiotensin system   SEMA6D  

摘要： The tissue-localized renin-angiotensin system (tRAS) plays a pivotal role in the crosstalk between cardiovascular factors and osteoarthritis (OA). Semaphorin 6D (SEMA6D), a cardiovascular neuroeffector, may contribute to chondrocyte homeostasis;however, its cartilage-specific functions remain unclear. Chondrocytes with altered SEMA6D expression were established via gene transfection. RNA sequencing was performed to identify SEMA6D-related genes and pathways, with preliminary validation in human OA samples. Furthermore, biochemical methods were employed to investigate the role of the AGT/AGTR1a/IL-1 beta axis in mediating SEMA6D-associated extracellular matrix metabolism (ECM). An AAV5-based lentiviral vector was used to generate OA rat models overexpressing SEMA6D, followed by radiological and histological analyses. SEMA6D overexpression significantly enhanced ECM homeostasis, marked by increased Aggrecan, COL2A1 and decreased COL10A1, MMP13, and Runx2 expression. These SEMA6D-induced genes were enriched in the tRAS pathway, with AGT, AGTR1a, and IL-1 beta identified as critical targets. Furthermore, the AGT/AGTR1a/IL-1 beta axis activated ECM degradation in chondrocytes, while SEMA6D overexpression effectively suppressed this signaling. In the OA rat model, elevated SEMA6D expression significantly reduced cartilage degradation. SEMA6D confers chondroprotective effects in OA by modulating the tRAS pathway, likely through inhibition of the AGT/AGTR1a/IL-1 beta axis, thereby regulating ECM metabolism and chondrocyte hypertrophy. These findings enhance our understanding of cardiovascular influences on cartilage health and reveal tissue-specific regulatory mechanisms in OA.

关键词： Biomarkers   Diagnostic tests   Periodontal disease   Saliva  

摘要： PURPOSE:The identification of specific target molecules and their appropriate cut-off values is crucial for the successful development of diagnostics. Salivary biomarkers, such as interleukin-1β (IL-1β) and matrix metalloproteinase-8 (MMP-8), have been investigated for their potential in diagnosing periodontal disease. This study aimed to evaluate the efficacy of IL-1β and MMP-8 as diagnostic tools and to establish their cut-off values for distinguishing active types of periodontal disease from healthy conditions. METHODS:We conducted a prospective cohort study involving 47 participants, who were divided into 2 groups: the control group consisted of 24 individuals with healthy or mild periodontal conditions (stages I-II of periodontal disease), and the periodontal group comprised 23 individuals with moderate to severe periodontal disease (stages III-IV). Saliva samples were collected from all participants, followed by an oral examination, periodontal charting, and radiographic assessments. The salivary concentrations of IL-1β and MMP-8 were quantified using enzyme-linked immunosorbent assays. RESULTS:Significant differences in salivary levels of IL-1β and MMP-8 were observed between the control group and those with periodontal disease. However, after adjusting for age and sex, these differences were not statistically significant for IL-1β. In contrast, the differences remained significant for MMP-8 in participants classified as having an active type of periodontal disease, specifically those in the periodontal group with more than 10% bleeding on probing. By setting a cut-off value of 200 ng/mL for salivary MMP-8, the sensitivity and specificity for diagnosing active periodontal disease were determined to be 70% and 86.5%, respectively. CONCLUSIONS:Our findings indicate that salivary MMP-8, using a cut-off value of 200 ng/mL, serves as a reliable biomarker for identifying active periodontal disease. This biomarker holds potential for further development into a diag

摘要： A tumor cell subpopulation of tumor-initiating cells (TIC) or "cancer stem cells" is associated with therapeutic resistance, as well as both local and distant recurrences. Signal transducer and activator of transcription (STAT) activity is elevated in TICs in claudin-low models of human triple-negative breast cancer, which enables enrichment of TICs using a STAT-responsive reporter. Lineage tracing of TICs as they undergo cell state changes could enable a better understanding of the molecular phenotypes of TIC and uncover strategies to selectively target TICs. In this study, we developed a STAT-responsive lineage-tracing system and used it in conjunction with the original reporter to enrich for cells with enhanced mammosphere-forming potential. This approach was able to detect TICs in some, but not all, basal-like triple-negative breast cancer xenograft models, indicating that STAT signaling has both TIC-related and TIC-independent functions. Single-cell RNA sequencing (RNA-seq) of reporter-tagged xenografts and clinical samples identified a common IFN/STAT1-associated transcriptional state in TICs that was previously linked to inflammation and macrophage differentiation. Surprisingly, most of the identified genes were not present in previously published TIC signatures derived using bulk RNA-seq. Finally, bone marrow stromal cell antigen-2 was identified as a cell surface marker of this state that functionally regulated TIC frequency. These results suggest that TICs may exploit the IFN/STAT1 signaling axis to promote their activity and that targeting this pathway may help eliminate ***: Coupling single-cell transcriptomics with tumor-initiating cell enrichment identified IFN response gene expression not previously reported in bulk RNA-sequencing-derived signatures and proposed IFN/STAT1 signaling as a candidate therapeutic target in breast cancer.