Background: Recent studies have identified solute carrier family 19 member 1 (SLC19A1) as a second messenger transporter that regulates massive immune-related signaling cascades, but current studies provide limited information. This study aims to evaluate its role and the potential mechanisms across various cancers. Methods: We analyzed multi-omics data from a pan-cancer cohort to evaluate SLC19A1 expression and its association with multiple features, including prognosis, tumor stemness, genome instability, and immune infiltration. Immunofluorescence staining was performed to validate SLC19A1 expression in tumor tissues and its relationship M2 macrophages. In addition, we used web tools such as ROCplotter to evaluate the association between SLC19A1 and response to chemotherapy and immunotherapy. Results: SLC19A1 was found to be overexpressed in multiple cancer types compared to normal tissues, correlating with poor prognosis. High SLC19A1 levels were associated with increased genomic instability and immune suppression. In addition, SLC19A1 was negatively correlated with CD8+ T-cell infiltration and positively correlated with M2 macrophage infiltration. The association of SLC19A1 with M2 macrophages was confirmed in multiple immunofluorescence staining. Finally, SLC19A1 was associated with the response to chemotherapy and immunotherapy in a variety of tumors. Conclusions: Our findings position SLC19A1 as a novel unfavorable prognostic marker in cancer, closely linked to immune suppression and genomic instability. This study highlights the need for further exploration of SLC19A1 as a therapeutic target and its implications in cancer treatment strategies.

Lower grade gliomas (LGGs) exhibit invasiveness and heterogeneity as distinguishing features. The outcome of patients with LGG differs greatly. Recently, more and more studies have suggested that infiltrating inflammation cells and inflammation-related genes (IRGs) play an essential role in tumorigenesis, prognosis, and treatment responses. Nevertheless, the role of IRGs in LGG remains unclear. In The Cancer Genome Atlas (TCGA) cohort, we conducted a thorough examination of the predictive significance of IRGs and identified 245 IRGs that correlated with the clinical prognosis of individuals diagnosed with LGG. Based on unsupervised cluster analysis, we identified two inflammation-associated molecular clusters, which presented different tumor immune microenvironments, tumorigenesis scores, and tumor stemness indices. Furthermore, a prognostic risk model including ten prognostic IRGs (ADRB2, CD274, CXCL12, IL12B, NFE2L2, PRF1, SFTPC, TBX21, TNFRSF11B, and TTR) was constructed. The survival analysis indicated that the IRGs risk model independently predicted the prognosis of patients with LGG, which was validated in an independent LGG cohort. Moreover, the risk model significantly correlated with the infiltrative level of immune cells, tumor mutation burden, expression of HLA and immune checkpoint genes, tumorigenesis scores, and tumor stemness indices in LGG. Additionally, we found that our risk model could predict the chemotherapy response of some drugs in patients with LGG. This study may enhance the advancement of personalized therapy and improve outcomes of LGG.

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease that causes disability and diminishes quality of life. The pathogenesis of OA remains poorly understood, creating an urgent need for biomarkers to aid research, diagnosis, and treatment. Methods: This study integrated transcriptome data from the GEO database with bioinformatics analyses to identify biomarkers associated with OA. The bioinformatics methods utilized include the Limma package, WGCNA, PPI network analysis, and machine learning algorithms. Genetic variants were used as instrumental variables to evaluate the potential causal impact of circulating white blood cell (WBC) counts on OA. Data sources encompassed the largest genome-wide analysis for OA and a comprehensive GWAS summary for circulating WBC counts. Four mendelian randomization (MR) methods were employed to investigate the genetic association, with a primary focus on findings from the inverse variance-weighted (IVW) method. Results: Total of 233 OA-related genes were identified, showing significant enrichment in pathways associated with WBC function. Key biomarkers, including CD4, CSF1R, and TYROBP, were upregulated in OA samples and exhibited strong diagnostic potential. MR analysis findings provided evidence of a genetic association between elevated neutrophil counts and a reduced risk of OA across sites (IVW: OR = 0.97, 95% CI 0.93–1.00, p = 0.047). Additionally, higher circulating WBC counts, particularly neutrophil counts, were associated with a suggestive decrease in hip OA (WBC IVW: OR = 0.94, 95% CI 0.89–0.99, p = 0.015; neutrophil IVW: OR = 0.93, 95% CI 0.88–0.99, p = 0.017). Conversely, reverse MR analysis found no evidence to support a genetic effect of OA on circulating WBC counts. Conclusion: Our findings suggest that elevated neutrophil counts may offer protective effects against OA, underscoring the interplay between the immune functions and OA pathogenesis. CD4, CSF1R, and TYROBP emerge as promising OA biomarkers, meriting further validation in prospective studies.

Background: Observational studies have demonstrated the correlation between various inflammatory proteins and osteoarthritis (OA). However, the causal relationship and directionality between them are still unclear. This study aims to analyze the potential causal relationship between circulating inflammatory proteins and OA using Mendelian randomization (MR) analysis. Methods: This study used bidirectional two-sample MR analysis, employing the inverse variance-weighted as the primary MR method. The GWAS summary data for OA were derived from The Musculoskeletal Knowledge Portal, while the GWAS summary data for 91 circulating inflammatory proteins were obtained from a recently published study. Furthermore, this study used two transcriptomic cohorts from the GEO database to explore differentially expressed inflammation-related genes (IRGs) in OA and identify key inflammatory markers. Results: This study provides suggestive evidence. The forward two-sample MR analysis found that the levels of urokinase-type plasminogen activator, adenosine deaminase, C-C motif chemokine 19, interleukin-10 receptor subunit alpha and latency-associated peptide transforming growth factor beta 1 have causal effects on lower risk of OA, and the levels of fractalkine, C-X-C motif chemokine 1, hepatocyte growth factor and interleukin-8 have causal effects on higher risk of OA. Reverse two-sample MR analysis showed that hip OA has causal effects on the increased levels of caspase 8, protein S100A12, interleukin-10 receptor subunit alpha, interleukin-7 and monocyte chemoattractant protein 2 and a causal effect on the decreased level of fms-related tyrosine kinase 3 ligand. Knee OA has a causal effect on the increased level of monocyte chemoattractant protein-3 and decreased level of interleukin-1-alpha respectively. Furthermore, we identified six key OA-related IRGs through comprehensive transcriptomic analysis, which could serve as potential diagnostic biomarkers for OA. Conclusion: This study supports the causal relationship between OA and specific circulating inflammatory proteins and develops potential OA-related inflammatory biomarkers.

We demonstrate the construction of the optical system in the atomic clock-beyond atomic fountain based on ⁸⁷Rb atom. The optical system includes a high-stability laser system and an optical lattice. The high-stability laser system with the new scheme of frequency locking and shift is introduced in detail, which is an important laser source for laser cooling. The optimized frequency and intensity stability are achieved to 4 × 10^–14τ−1/2 (τ is the averaging time) and 4 × 10^–5τ−1/2, respectively, which are highly stable. On the basis of the conventional atomic fountain clock, the optical lattice is specially investigated along the direction of gravity and its characteristics are studied systematically. For the optimized and novel exploration, we predict the achievable stability of 3.6×10−14τ−1/2 and it has the potential to be improved to 3.6×10−15τ−1/2. The realizability of the construction due to the stabilized laser and optical lattice makes the beyond fountain promising candidate for the next-generation high performance microwave atomic clock.