Surface-enhanced Raman scattering (SERS) has emerged as a valuable technique for molecular identification. Due to the characteristics of high sensitivity, excellent signal specificity, and photobleaching resistance, SERS has been widely used in the fields of environmental monitoring, food safety, and disease diagnosis. By attaching the organic molecules to the surface of plasmonic nanoparticles, the obtained SERS tags show high-performance multiplexing capability for biosensing. The past decade has witnessed the progress of SERS tags for liquid biopsy, bioimaging, and theranostics applications. This review focuses on the advances of SERS tags in biomedical fields. We first introduce the building blocks of SERS tags, followed by the summarization of recent progress in SERS tags employed for detecting biomarkers, such as DNA, miRNA, and protein in biological fluids, as well as imaging from in vitro cell, bacteria, tissue to in vivo tumors. Further, we illustrate the appealing applications of SERS tags for delineating tumor margins and cancer diagnosis. In the end, perspectives of SERS tags projecting into the possible obstacles are deliberately proposed in future clinical translation.

Background: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral serum markers commonly utilized as cost-effective indicators of inflammation. However, their efficacy as predictors of clinical disease activity in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), remains uncertain. To address this ambiguity, we conducted a meta-analysis to evaluate the clinical significance of NLR, PLR, and LMR in patients with IBD.Methods: A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane databases, with the last search date being October 2024. Baseline values of NLR, PLR, and LMR during active and remission phases, as well as moderate and severe conditions, were analyzed as primary endpoints in patients with IBD compared to healthy populations, using risk ratios (WMD) and corresponding 95% confidence interval (CI) estimates.Results: Twenty-three cohort studies involving 3550 IBD patients and 1010 healthy people were finally included in this meta-analysis. The results of the meta-analysis showed that peripheral serum NLR and PLR were significantly higher in IBD patients than in the healthy population NLR [WMD=1.57,95%CI(1.14,2.01),P<0.001], PLR [WMD=60.66,95%CI(51.68,69.64),P<0.001]; NLR in active versus remission stage of IBD, PLR, LMR had significant differences NLR [WMD=1.50,95%CI(1.23,1.78),P<0.001], PLR [WMD=69.02,95%CI(39.66,98.39,P<0.001], LMR [WMD=-1.14,95%CI(-1.43,-0.86,P<0.001]; IBD active period and remission period NLR, PLR and LMR had significant differences. 0.001]; there were significant differences in NLR and PLR between moderate and severe IBD NLR [WMD=-1.41,95%CI(-2.13,-0.69),P<0.001], PLR [WMD=-112.03,95%CI(-143.87,-80.19),P<0.001]; the diagnostic accuracy of markers in predicting the clinical activity of IBD was relatively good. The diagnostic accuracy of markers in predicting IBD clinical activity was more favorable AUC [ES=0.72,95%CI(0.69,0.75),P<0.001].Conclusion: In patients with IBD, elevated NLR and PLR are associated with increased disease activity and severity in UC and CD. Conversely, an elevated LMR is linked to reduced disease activity in IBD. Based on diagnostic accuracy results, inflammatory markers NLR and PLR serve as effective biomarkers for assessing IBD activity, thereby providing valuable insights for treatment decisions in IBD patients. However, LMR may not be a reliable independent marker due to conflicting or non-significant results. We anticipate that further high-quality prospective studies will validate our findings in the future.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024608118.

Background: Elevated levels of SPP1 ⁺ tumor-associated macrophages (TAMs) are associated with reduced CD8 ⁺ T cell infiltration and poorer prognosis in cancer patients, but direct evidence demonstrating a causal role for SPP1 ⁺ TAMs in excluding CD8 ⁺ T cells is still missing. The precise mechanisms by which SPP1-activated signaling pathways and macrophage-derived factors regulate CD8 ⁺ T cell trafficking remain poorly understood. Methods: We established multiple tumor mouse models to study the function of macrophage SPP1 in the tumor environment, especially its role in the relationship between macrophages and CD8 T cells. We combined the single-cell (sc) RNA sequencing data of clinical tumor samples and tumor tissues from Spp1 ^{fl/fl-Lyz2-Cre} mice to identify the differences in SPP1-related genes and found that SPP1 could regulate the expression of CXCL9 and CXCL10 in macrophages. Through Western blotting, immunofluorescence staining, and flow cytometry analyses, we elucidated the mechanistic basis by which macrophage-specific SPP1 deficiency suppressed tumorigenesis. Results: This study demonstrated that macrophage-derived SPP1 played a crucial role in suppressing CD8 T cell infiltration, promoting tumor progression, and diminishing the effectiveness of immune checkpoint inhibitor (ICI) therapy. Sc-RNA sequencing analysis revealed a marked increase in CD8 T cell populations within tumor tissues of Spp1 ^{fl/fl-Lyz2-Cre} mice. Furthermore, a negative correlation was observed between CD8 T cells and SPP1 macrophages in human colorectal cancer specimens. Genetic deletion of SPP1 in macrophages markedly enhanced tumor growth suppression in a manner dependent on CD8 T cell-mediated immunity. Mechanistically, SPP1 deficiency in macrophages led to elevated mitochondrial reactive oxygen species (ROS) production, resulting in the accumulation of cytosolic double-stranded DNA (dsDNA) fragments. This accumulated dsDNA activated the cGAS-STING pathway, leading to subsequent STAT1 phosphorylation. The enhanced STAT1 activity upregulated the expression of chemokines CXCL9 and CXCL10, thereby facilitating CD8 T cell recruitment into the tumor microenvironment. Conclusions: Deletion of SPP1 in TAMs upregulates CXCL9/10 production by activating the ROS-DNA fragment/cGAS-STING/STAT1 pathway, thereby enhancing CD8 T cell infiltration, inhibiting tumor progression, and improving ICI treatment outcomes in tumors.

The objective of the present study was to screen the key genes of ribavirin in hepatocellular carcinoma (HCC) and provide novel therapeutic targets for HCC treatment. The mRNA expression datasets of GSE23031 and GSE74656, as well as the microRNA (miRNA) expression dataset of GSE22058 were downloaded from the Gene Expressed Omnibus database. In the GSE23031 dataset, there were three HCC cell lines treated with PBS and three HCC cell lines treated with ribavirin. In the GSE74656 dataset, five HCC tissues and five carcinoma adjacent tissues were selected. In the GSE22058 dataset, 96 HCC tissues and 96 carcinoma adjacent tissues were selected. The differentially expressed genes (DEGs) and differentially expressed miRNAs were identified via the limma package of R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed with the Database for Annotation, Visualization and Integrated Discovery. The target mRNAs of DEMs were obtained with TargetScan. A total of 559 DEGs (designated DEG‑Ribavirin) were identified in HCC cells treated with ribavirin compared with PBS and 632 DEGs (designated DEG‑Tumor) were identified in HCC tissues compared with carcinoma adjacent tissues. A total of 220 differentially expressed miRNAs were identified in HCC tissues compared with carcinoma adjacent tissues. In addition, 121 GO terms and three KEGG pathways of DEG‑Ribavirin were obtained, and 383 GO terms and 25 KEGG pathways of DEG‑Tumor were obtained. A total of five key miRNA‑mRNA regulated pairs were identified, namely miR‑183→CCNB1, miR‑96→DEPDC1, miR‑96→NTN4, miR‑183→NTN4 and miR‑145→NTN4. The present study indicated that certain miRNAs (including miR‑96, miR‑145 and miR‑183) and mRNAs (including NAT2, FBXO5, CCNB1, DEPDC1 and NTN4) may be associated with the effects of ribavirin on HCC. Furthermore, they may provide novel therapeutic targets for HCC treatment.