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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

关键词： 辅酶Q10   法舒地尔   不稳定型心绞痛   IL-6   sST2   BNP  

摘要： 探究对不稳定型心绞痛患者采用辅酶Q10联合法舒地尔治疗在改善患者生理指标方面的作用。方法 在本院近两年接收的冠心病患者中选取100例不稳定型心绞痛患者,随机分为观察组(n=50)和对照组(n=50)。对比两组心功能指标、炎症因子水平、sST2及BNP以及治疗效果。结果 观察组患者心功能、sST2、BNP改善程度更好,炎症因子水平更低,整体治疗效果更为显著,p<0.05。结论 对不稳定型心绞痛患者使用辅酶Q10联合法舒地尔治疗,可降低炎症因子水平,降低sST2和BNP指标,改善心功能,有效提升治疗效果,有利于患者心血管健康。

关键词： Biological sciences   Biochemistry methods   Immunology   Proteomics  

摘要： Recent studies suggest that CD4+ T cells can exert potent anti-tumor effects and improve immunotherapy efficacy by aiding CD8+ T cells. However, characterizing the mechanism of CD4+ T cells' anti-tumor activity has been challenging due to inaccurate major histocompatibility complex class II (MHC-II) peptide prediction algorithms and the lack of high-quality reagents for immune monitoring. To address this, we developed MHC2-substitution of CLIP and analytical LCMS evaluation (MHC2-SCALE), a streamlined approach combining affinity optimized class II-associated invariant chain peptide (CLIP) exchange technology, high throughput 2D-LCMS analysis, and rapid generation of peptide-bound MHC-II monomers for subsequent multimer assembly. We validated MHC-II peptide candidates predicted by the immune epitope database (IEDB) algorithm, as well as uncovered many true and immunogenic MHC-II binders that were not predicted by IEDB. Thus, MHC2-SCALE expands the opportunities for discovering, tracking, and phenotyping antigen-specific CD4+ T cells in preclinical and clinical settings, thereby improving therapies for cancer, autoimmunity, or infectious diseases.

关键词： welding and metal fumes   zinc (Zn)   copper (Cu)   metal (nano)particle exposure   nanotoxicology   oxidative stress   inflammatory response   cytokines (IL-6   IL-8   MIP-1 beta/CCL4   TNF-alpha)   early-stage marker   occupational health  

摘要： Zinc (Zn)- and copper (Cu)-containing welding fumes elevate inflammatory markers (CRP, TNF-alpha, IL-6, IL-8) in healthy individuals and welders. Zn- and Cu-containing nanoparticles are toxic to human macrophages. Therefore, ZnO exposure limits are under discussion. In this study, the effects of Zn/Cu-containing welding fume suspensions on A549 alveolar epithelial cells (exposure concentrations: 0.01/0.1/1/10/100 mu g/mL) and THP-1 macrophages (additionally 0.001 mu g/mL) were investigated over a period of 48 h. Effects on apoptosis, cytotoxicity, genotoxicity, superoxide dismutase (SOD) activity, and cytokine levels (IL-6, IL-8, MIP-1 beta/CCL4, TNF-alpha) were evaluated. Welding fume exposure increased SOD activity, and it increased Annexin-V binding and cytotoxicity effects starting at 10 mu g/mL in A549 cells and particularly in THP-1 macrophages. A549 cells showed increased IL-6 at 10 and 100 mu g/mL, and significant IL-8 release occurred at 10 mu g/mL for A549 and 0.1 mu g/mL for macrophages. Exposed macrophages released TNF-alpha at 1 mu g/mL after 24 and 48 h and MIP-1 beta/CCL4 at 0.01 mu g/mL after 6 h and at 0.001 mu g/mL after 48 h. No genotoxic effects were detected. MIP-1 beta/CCL4 is a sensitive new biomarker for human macrophages exposed to Zn/Cu-containing welding fumes. The findings suggest that Zn/Cu particles affect lung cells already at doses below current occupational thresholds.

关键词： 根治性放疗   比卡鲁胺   前列腺癌   血清前列腺特异抗原   骨转移  

摘要： 根治性放疗联合比卡鲁胺对前列腺癌患者血清前列腺特异抗原水平及骨转移发生率的影响。方法 2021年60例前列腺癌患者随机单盲分组,对照组根治性放疗,观察组根治性放疗联合比卡鲁胺治疗,对比效果。结果 治疗后观察组PSA、F-PSA、血清睾酮水平下降更多(P<0.05),治疗1年、3年后最大尿流率、EPIC评分高于对照组(P<0.05),并发症发生率和治疗1年、3年后的骨转移发生率均低于对照组(P<0.05)。结论 根治性放疗联合比卡鲁胺用于前列腺癌患者治疗中有效,可以降低其特异性的肿瘤相关指标,包括PSA、F-PSA等,减少放疗生活质量的不良影响,改善最大尿流率,还能降低骨转移风险,并发症发生率比单一放疗更低。

关键词： Periodontitis   DNA methylation   Immune cells   Neutrophils   Gene expression   Methyltransferases   Inflammatory diseases   Protein-protein interactions  

摘要： Background Periodontitis is a typical oral disease. Polymorphonuclear neutrophils (PMNs) are crucial immune cells in periodontal tissues, relating to infection, inflammation, and innate immunity. We herein aimed to explore important periodontitis PMN related genes. Methods Periodontitis and control samples were downloaded from Gene Expression Omnibus database, including GSE173082 (methylation data, n=72), GSE10334 (n=127), GSE43525 (n=23), GSE16134 (n=134). Differential expression analysis and differential methylation analysis was employed to find candidate genes. Receiver operating characteristic analysis was performed to evaluate the diagnostic value of the hub gene. The functional pathways were determined by gene set enrichment analysis. Using CIBERSORT software, the immune cell infiltration landscape of periodontitis tissue was explored. The mRNA and protein levels of target gene in clinical tissue samples were determined employing RT-qPCR and western blotting. All statistical analyses were conducted in R software. Results After integrating DNA methylation with transcriptome profiles, GRASP, HLA-DMB, HLA-DMA, CAB39, NCOA2 and TLE4 were identified as candidate genes in periodontitis PMNs. HLA-DMB showed the highest correlation with core DNA methyltransferase DNMT3B (p < 0.05). Between high and low HLA-DMB expression samples, multiple immune related pathways were enriched, and differential immune cell infiltration was observed (p < 0.05). HLA-DMB exhibited significantly higher expressions in both public database and clinical tissue samples (p < 0.05). HLA-DMB was a diagnostic marker for periodontitis (GSE43525 AUC=0.777 and GSE16134 AUC=0.783). Conclusions Significantly higher HLA-DMB expression was noticed in PMNs of periodontitis, which probably contributed to the development of periodontitis. HLA-DMB is a promising diagnostic marker for periodontitis.