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关键词： Renal cell carcinoma   JUN/AP-1   IL-17 pathway   Gut microbial metabolites   Icaritin   Molecular docking  

摘要： The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites against RCC. GMM were selected from the gutMgene database and analyzed for common targets using DisGeNET, Gene Card, and OMIM. Downstream analysis included gene ontology, KEGG pathway enrichment, metabolite-target-pathway-disease network construction, and protein-protein interaction analysis. Further, key metabolites were evaluated for drug-likeness, ADMET properties, and molecular docking, followed by molecular dynamics simulations (MDS) to assess complex stability. The JUN/AP-1 gene emerged as the prime target, exhibiting the highest binding affinity with Icaritin (- 5.9 kcal/mol), followed by Quercetin and Luteolin. MDS confirmed the stable binding of Icaritin to the active site throughout the simulation. These GMM may influence anticancer activity through distinct regulatory pathways involving the JUN/AP-1 gene, either by inhibiting or modulating its function. These insights establish a basis for further in vitro and in vivo investigations, supporting the development of microbiome-based therapeutic *** abstractThe graphical abstract illustrates a computational network pharmacology and computer-aided analysis approach to investigating gut microbiota-derived metabolites in renal cell carcinoma (RCC). It highlights core target genes, gene ontology, KEGG pathways, and network analyses. The right section depicts gut microbiota, specifically Bacterium sp. MRG-PMF-1 produces Icaritin, which inhibits the JUN gene, potentially suppressing RCC progression. Molecular docking and molecular dynamics simulations confirm stable binding interactions, supporting

关键词： 吴茱萸碱(EVO)   免疫抑制剂   细胞周期   细胞因子   流式细胞术  

摘要： 目的 探究吴茱萸碱（EVO）对活化T细胞增殖的抑制特性。方法 采用密度梯度离心法从健康供体中提取外周血单个核细胞（PBMC），采用免疫磁珠法纯化T细胞，抗人CD3/CD28抗体活化T细胞。以不同浓度的EVO（0.37、1.11、3.33、10）μmol/L作用于T细胞。流式细胞术测定T细胞增殖率、凋亡率、存活率、CD25表达水平以及细胞周期分布。ELISA分析细胞因子白细胞介素2（IL-2）、IL-17A、IL-4和IL-10的表达水平。结果 EVO（1.11、3.33、10）μmol/L能有效抑制活化T细胞增殖，其半数抑制浓度IC50为（1.5±0.3）μmol/L。EVO不诱导活化T细胞凋亡，且不影响静息T细胞的存活率。EVO不影响活化T细胞CD25的表达及IL-2的分泌。EVO阻滞T细胞周期于G2/M期，使G2/M期细胞增加，且具有浓度-效应关系。EVO不影响活化T细胞分泌IL-4、IL-10，但显著抑制IL-17A的分泌。结论 EVO对T细胞的活化过程无显著影响 ， 但可通过阻滞细胞周期于G2/M期 ， 从而抑制T细胞的增殖 ， 并显著抑制促炎因子IL-17A的分泌。提示EVO有望作为先导物 ， 促进低毒高效性免疫抑制剂的研发 ， 并有助于阐释传统中药吴茱萸在抗炎及免疫调节中的作用机制。

关键词： 恒温扩增-实时荧光法   呼吸道多病原检测   抗原法  

摘要： 呼吸道多病原检测中分别使用抗原法和恒温扩增-实时荧光法,对比两种检测方法应用效果。方法 观察患者选择我院诊断的呼吸道多病原检测120例,观察开始于2024年9月,观察结束于2025年1月,并且根据患者采取的检测方法不同分成荧光法组与抗原法组,方法均以传统的核酸定量荧光法(qPCR)为金标准,荧光法组使用恒温扩增-实时荧光法检测,抗原法组使用抗原法检测,对比两组应用效果。结果 (1)荧光法组和抗原法组操作时间、操作满意度情况:荧光法组操作时间高于抗原法组操作时间,荧光法组操作满意度高于抗原法组操作满意度,(t=3.785,p=0.032)。(2)荧光法组和抗原法组检测阳性率情况:荧光法组检测阳性率高于抗原法组检测阳性率,(x2=14.904,p=0.008)。(3)荧光法组和抗原法组诊断效能情况:荧光法组特异性高于抗原法组特异性;荧光法组灵敏度高于抗原法组灵敏度,荧光法组准确率高于抗原法组准确率,(x2=13.271,p=0.009)。结论 呼吸道多病原检测中使用恒温扩增-实时荧光法检测效果优良,可推广。

摘要： Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. Interleukin-22 (IL-22) has emerged as a promising therapeutic target due to its hepatoprotective properties mediated through the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the upregulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits and limitations.

关键词： MC-LR   Apoptosis   TNF-R1   RIPK1   HEK293  

摘要： In recent years, the outbreak of cyanobacterial blooms has become increasingly frequent. Microcystin-LR (MC-LR), a metabolite of cyanobacteria, poses a significant threat to the ecosystem and human health. Several studies have demonstrated that MC-LR might induce renal cell apoptosis, as a consequence of tissue damage. However, the molecular mechanisms underlying MC-LR-initiated renal injury remain to be determined. This investigation aimed to determine the role of apoptosis in MC-LR-induced kidney damage and its potential underlying mechanisms using the human embryonic kidney (HEK293) cell line. The results of TUNEL and immunofluorescence assays indicated that MC-LR induced increased apoptosis in HEK293 cells. Compared to control, the mRNA expression levels of RIPK1, caspase-8, and TNF-alpha were elevated following incubation with MC-LR, while the mRNA expression level of Bcl-2/Bax was decreased. The protein levels of RIPK1, TNF-R1, and caspase-8 were elevated in the MC-LR-treated HEK293 cells. Data demonstrated that MC-LR induced renal cell apoptosis through activation of the TNF-R1/RIPK1 pathway, providing new insights into understanding the toxic mechanisms attributed to MC-LR.

关键词： 机器人   无地图导航   POMDP   LSTM   模仿学习   深度强化学习   未知动态环境   Sim2Real  

摘要： 针对轮式机器人导航方法对高精地图的依赖以及在动态复杂场景中的适应性问题，文中提出了一种基于IL-TD3(Imitation Learning Enhanced Twin Delayed Deep Deterministic Policy Gradient)的无地图导航方法。将导航任务建模为POMDP(Partially Observable Markov Decision Process)，并结合LSTM(Long Short-Term Memory)处理历史信息，以改进环境状态建模。机器人通过模仿学习迅速获得了有限的无地图导航能力，不断探索和训练TD3深度强化学习网络从而提高导航技能。仿真实验结果表明，IL-TD3在未知动态环境中的导航轨迹稳定、连续、安全，具有较好的导航性能。Sim2Real(Simulation to Reality)测试结果表明，未经调整的IL-TD3模型在现实世界的导航任务中表现较好，证明了所提模型的鲁棒性和泛化能力。

关键词： bioinformatics   differentially expressed genes   IL-10   IL-18   immunoregulation   pneumonia   sepsis  

摘要： Pneumonia and sepsis are severe diseases with high mortality and recurrence rates globally, especially fatal among immunocompromised patients. The dual regulatory effects of the cytokines Interleukin-10 (IL-10) and interleukin-18 (IL-18) in inflammatory responses have been observed across various diseases. However, their specific mechanisms in pneumonia and sepsis remain unclear. This study aims to explore the expression characteristics and functions of IL-10 and IL-18 in these diseases using bioinformatics approaches. The pneumonia and sepsis dataset GSE218494 was downloaded from the gene expression omnibus database. Differentially expressed genes were identified using the R package "limma," and functional enrichment analyses were performed using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Additionally, weighted gene co-expression network analysis was conducted to identify key module genes, and the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software were used to construct a protein-protein interaction network to identify core genes. Further analysis of miRNA targets associated with these core genes was performed to elucidate their potential molecular mechanisms in the diseases. The analysis revealed that IL-10 and IL-18 were downregulated in patients with pneumonia and sepsis, closely associated with poor prognosis. Functional enrichment analysis showed that these genes are primarily involved in biological processes related to inflammation and immune regulation, including the cell cycle, TGF-beta signaling pathway, and Jak-STAT signaling pathway. Protein-protein interaction network analysis identified IL-10 and IL-18 as potential key regulatory genes in pneumonia and sepsis. miRNA prediction indicated that several miRNAs are closely associated with the regulation of these genes' expression. IL-10 and IL-18 play critical immunoregulatory roles in the development and progression of pneumonia