Dawei Cui

Chromodomain Y-like protein (CDYL), a member of the CDY-related gene family, plays a pivotal role in nervous diseases, reproductive systems and tumors by chromatin remodeling and disrupting normal transcriptional regulation. However, the expression and biological functions of CDYL in rheumatoid arthritis (RA) remain unclear. This study aims to investigated the role of CDYL in the pathogenesis of RA. A cohort of 43 RA patients and 36 healthy subjects were included in the study. The transcript levels of CDYL, interleukin-17 A (IL-17 A) and IL-22 were detected by quantitative real-time PCR. Flow cytometry and Western blot were used to analyze the relationship between CDYL and Th17 cells. The GSE100191 dataset from the GEO database was downloaded to conduct a comprehensive bioinformatics analysis of the potential functions of CDYL. The interaction of CDYL and EZH2 and the effects of the EZH2 antagonist on Th17 cells were measured by Western blot. The CDYL was highly expressed in the PBMCs derived from RA patients, exhibiting positive correlations with DAS28 score (r = 0.36, p < 0.0177) and serum anti-cyclic citrullinated peptide antibody titers (r = 0.4255, p = 0.004). Moreover, the transcript levels of CDYL were positively correlated with elevated IL-17 A levels (r = 0.5140, p < 0.001) and IL-22 (r = 0.4540, p = 0.002) levels in RA patients and the RA dataset. CDYL expression is markedly upregulated in Th17 cells, while the proportion of Th17 cells is increased in RA patients. Mechanistically, CDYL knockdown significantly inhibited Th17 differentiation in vitro, which suggests that CDYL is associated with and functionally contributes to the differentiation of Th17 cells. Our findings indicate that CDYL expression is associated with and promotes the differentiation of Th17 cells in RA patients and may be involved in the process of RA.

Purpose: CD36 deficiency predisposes to fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractoriness (PTR), yet its genetic architecture remains incompletely understood. In particular, the contribution of large structural variants has been difficult to assess using conventional genotyping approaches. This study aimed to reconstruct full-length CD36 haplotypes using long-read sequencing and to systematically characterize its genetic architecture. Methods: We developed a long-read sequencing approach to reconstruct full-length (~ 77 kb) CD36 haplotypes from four overlapping amplicons. Samples from 43 CD36-deficient individuals (14 type I, 29 type II) were analyzed. Structural variants were validated via PacBio whole-genome sequencing, platelet CD36 expression was quantified by flow cytometry, and a gap-PCR assay screened 600 blood donors for large deletions. Results: Full-length CD36 haplotypes were reconstructed for the first time using overlapping amplicons. Candidate pathogenic variants were identified in all 28 haplotypes from type I deficiency samples, including a novel structural variant (c.1-15966_c.120 + 3887 delinsCCAATGCTAAGGTTGA, 19,971 bp deletion-insertion) spanning intron 1–3 that eliminates exons 2/3 and the canonical translation initiation site. Among 58 haplotypes from type II cases, potentially pathogenic variants were identified in only 26/58 (44.8%) (including one haplotype carrying the novel structural variant), while 32/58 (55.2%) lacked detectable variations. Gap-PCR screening revealed a 0.50% carrier frequency for this structural variant in blood donors. All heterozygous carriers showed normal platelet CD36 expression, indicating absence of haploinsufficiency. Conclusions: This study establishes a robust PolySeq nanopore sequencing-based framework for full-length CD36 haplotype reconstruction and identifies a large structural deletion as a major, previously underrecognized candidate genetic mechanism underlying type I CD36 deficiency. Our findings suggest that many unresolved cases of type I deficiency may be attributable to cryptic structural variants missed by conventional methods, highlighting the necessity of long-read sequencing for accurate molecular diagnosis.

The pathogenesis of autoimmune diseases remains unclear, which is associated with T helper (Th) cell subsets such as Th1, Th2, Treg and Tfh cells. Recent studies have indicated the involvement of N⁶-methyladenosine (m⁶A) modification in the pathogenesis of autoimmune diseases, and m⁶A also affects the differentiation, and function of Th cells. However, few reports focused on the relationship between m⁶A modification in Th cell subsets and autoimmune diseases. This review summarizes the latest research progress on m⁶A modification in common autoimmune diseases, specifically highlighting how various m⁶A-modifying enzymes influence the differentiation and function of Th cells and disease progression. Elucidating the relationship between m⁶A modification and Th cells in autoimmune diseases may provide a new perspective for disease prevention and targeted therapy. Finally, this review also elaborates on the impact of m⁶A on the clinical diagnosis and treatment of autoimmune diseases, as well as the challenges that need to be addressed.

As one distinct origin of hematological malignancies, diffuse large B-cell lymphoma (DLBCL) has caused a major public health problem. However, the molecular mechanisms that underlie this association have not been clearly elucidated. To improve this situation, it is urgent to explore disease-specific diagnostic biomarkers and mechanisms. Three microarray datasets (GSE25638, GSE12195 and GSE12453) were downloaded from the Gene Expression Omnibus (GEO) database. The key genes in DLBCL patients were screened by differentially expression gene (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis and protein-protein interaction (PPI) network construction were employed to reveal DLBCL-related pathogenic molecules and underlying mechanisms. Candidate biomarkers were screened using random forest (RF) analysis. A diagnostic nomogram and Kaplan-Meier (KM) survival analysis were constructed to predict the risk of patients. Single-sample gene set enrichment analysis (ssGSEA) was used for exploring immune cell infiltration in lymphoma. The validation of the hub genes expressions was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) tests. A total of 95 key genes were acquired from three datasets of DLBCL patients by DEG analysis and WGCNA. DEGs were significantly enriched in pathways associated with inflammatory response, biological process involved in interspecies interaction between organisms, C-X-C chemokine receptor binding as well as chemokine activity. This was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, four hub genes (CXCL9, CCL18, C1QA and CTSC) were significantly screened from the three datasets using RF algorithms. They were closely correlated with the overall survival of DLBCL patients. The dysregulated infiltration of immune cells, including natural killer (NK) cells and T cells, were positively linked to the expression levels of the four hub genes. The receiver operating characteristic (ROC) results were promising via the construction of a nomogram model. Additionally, the increased expression of the four key genes was further verified in DLBCL patients. Four crucial hub genes (CXCL9, CCL18, C1QA and CTSC) that could predict the risk of DLBCL were systematically identified. In particular, CXCL9 may be the most important potential biomarker for the progression of DLBCL patients.

Non-small-cell lung cancer (NSCLC) is the predominant subtype of lung cancer. Despite the demonstrated effectiveness of established treatments such as radiotherapy, chemotherapy, and immunotherapy, the prognosis for patients with advanced NSCLC remains poor. Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), play a crucial role in the tumor microenvironment (TME) of NSCLC. This review explores the classification and biological functions of DCs, highlighting the specific molecular pathways and external factors that influence their maturation and function in NSCLC, which is novel in this review. Moreover, we discuss the potential therapeutic applications of DCs in the management of NSCLC, presenting novel possibilities for future treatments.