Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) stands as a rare and locally aggressive soft tissue tumor, characterized by intricated molecular alterations. The imperative to unravel the complexities of intratumor heterogeneity underscores effective clinical management. Herein, we harnessed single-cell RNA sequencing (scRNA-seq) to conduct a comprehensive analysis encompassing samples from primary sites, satellite foci, and lymph node metastases. Rigorous preprocessing of raw scRNA-seq data ensued, and employing t-distributed stochastic neighbor embedding (tSNE) analysis, we unveiled seven major cell populations and fifteen distinct subpopulations. Malignant cell subpopulations were delineated using infercnv for copy number variation calculations. Functional and metabolic variations of diverse malignant cell populations across samples were deciphered utilizing GSVA and the scMetabolism R packages. Additionally, the exploration of differentiation trajectories within diverse fibroblast subpopulations was orchestrated through pseudotime trajectory analyses employing CytoTRACE and Monocle2, and further bolstered by GO analyses to elucidate the functional disparities across distinct differentiation states. In parallel, we segmented the cellular components of the immune microenvironment and verified the presence of SPP1+ macrophage, which constituted the major constituent in lymph node metastases. Remarkably, the CellChat facilitated a comprehensive intercellular communication analysis. This study culminates in an all-encompassing single-cell transcriptome atlas, propounding novel insights into the multifaceted nature of intratumor heterogeneity and fundamental molecular mechanisms propelling metastatic DFSP.

Factors influencing cognitive function in patients with Huntington's disease from China: A cross-sectional clinical study.

BACKGROUND AND AIM: Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. Cognitive decline contributes to the loss of daily activity in manifest HD. We aimed to examine the cognition status in a Chinese HD cohort and explore factors influencing the diverse cognitive domains. METHODS: A total of 205 participants were recruited in the study with the assessment by neuropsychological batteries, including the mini-mental state examination (MMSE), Stroop test, symbol digit modalities test (SDMT), trail making test (TMT), verbal fluency test (VFT), and Hopkins verbal learning test-revised, as well as motor and psychiatric assessment. Pearson correlation and multiple linear regression models were applied to investigate the correlation. RESULTS: Only 41.46% of patients had normal global function first come to our center. There was a significantly difference in MMSE, Stroop test, SDMT, TMT, and VFT across each stage of HD patients (p < .05). Apathy of PBA-s was correlated to MMSE, animal VFT and Stroop-interference tests performance. Severity of motor symptoms, functional capacity, age, and age of motor symptom onset were correlated to all neuropsychological scores, whereas education attainment and diagnostic delay were correlated to most neuropsychological scores except TMT. Severity of motor symptoms, functional capacity, and education attainment showed independent predicting effect (p < .05) in diverse cognitive domains. CONCLUSION: Cognitive impairment was very common in Chinese HD patients at the first visit and worse in the patients in advanced phase. The severity of motor symptoms and functional capacity were correlated to the diverse cognitive domains.

Silencing of miRNA-148a by hypermethylation activates the integrin-mediated signaling pathway in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) play a pivotal role in carcinogenesis by suppressing oncogenes or tumor suppressor genes. Various studies have identified numerous miRNAs and their diverse targets; however, the consequences of dysregulated miRNAs in nasopharyngeal carcinoma (NPC) remain unclear. For this study, we found that miR-148a is downregulated through hypermethylation in NPC biopsies and NPC cell lines compared with adjacent normal and NP cells respectively. Promoter assays demonstrated that upstream stimulatory factor 1 (USF1) is a crucial transcription factor that activates miR-148a promoter activity. EMSA assays confirmed that purified USF1 binds better toward the unmethylated than the methylated CG-containing USF1 consensus probe. The ectopic expression of miR-148a inhibits cell migration in NPC cells through the suppression of integrin-mediated signaling by targeting VAV2, WASL and ROCK1. Biochemical and functional assays provided supporting evidence that these 3 genes are the downstream targets of miR-148a in NPC cells. Furthermore, immunohistochemical staining and Western blotting analysis revealed that the 3 oncogenic targets of miR-148a were overexpressed in NPC biopsies, suggesting that the inactivation of miR-148a caused by DNA methylation promotes NPC progression. Overall, our findings revealed that miR-148a can act as tumor suppressor miRNA and serve as a biomarker as well as a therapeutic target for NPC.