Oral squamous cell carcinoma (OSCC) is the most invasive oral malignancy in adults and is associated with a poor prognosis. Accurate prognostic models are urgently needed, however, knowledge of the probable mechanisms behind OSCC tumorigenesis and prognosis remain limited. The clinical importance of the interplay between the immune system and tumor microenvironment has become increasingly evident. This study explored immune-related alterations at the multi-omics level to extract accurate prognostic markers linked to the immune response and presents a more accurate landscape of the immune genomic map during OSCC. The Cancer Genome Atlas (TCGA) OSCC cohort (n = 329) was used to detect the immune infiltration pattern of OSCC and categorize patients into two immunity groups using single-sample gene set enrichment analysis (ssGSEA) and hierarchical clustering analysis. Multiple strategies, including lasso regression (LASSO), Cox proportional hazards regression, and principal component analysis (PCA) were used to screen clinically significant signatures and identify an incorporated prognosis model with robust discriminative power on the survival status of both the training and testing set. We identified two OSCC subtypes based on immunological characteristics: Immunity-high and immunity low, and verified that the categorization was accurate and repeatable. Immunity_ high cluster with a higher immunological and stromal score. 1047 differential genes (DEGs) integrate with immune genes to obtain 319 immue-related DEGs. A robust model with five signatures for OSCC patient prognosis was established. The GEO cohort (n = 97) were used to validate the risk model’s predictive value. The low-risk group had a better overall survival (OS) than the high-risk group. Significant prognostic potential for OSCC patients was found using ROC analysis and immune checkpoint gene expression was lower in the low-risk group. We also investigated at the therapeutic sensitivity of a number of frequently used chemotherapeutic drugs in patients with various risk factors. The underlying biological behavior of the OSCC cell line was preliminarily validated. This study characterizes a reliable marker of OSCC disease progression and provides a new potential target for immunotherapy against this disease.

PFOA is a legacy Per- and Polyfluorinated Substances (PFAS), a group of chemicals widely used in various industrial applications and consumer products. Although there has been a voluntary phase out of PFOA since 2005, it is still widely detected in various water supplies. A growing body of evidence suggests an association between PFOA exposure, particularly during developmental stages, with increased risks of neurodegenerative diseases (NDs). The neurotoxic mechanism of developmental PFOA exposure, however, remains poorly understood. Utilizing human induced-pluripotent stem cell (hiPSC)-derived cortical neurons, we investigated the effect of PFOA exposure prior to differentiation and assessed changes in neuronal characteristics, transcriptome, and neurodegeneration markers mimicking a Developmental Origin of Health and Disease (DoHAD) paradigm. Exposure to PFOA before neuron differentiation resulted in persistent alterations in nuclear morphology, neuronal network, and calcium activity. RNA sequencing analysis further revealed transcriptomic changes aligning with Alzheimer's Disease (AD) after PFOA exposure. These observations were further corroborated by alterations in tau phosphorylation markers, the presence of fibrillar tau, an increase in liquid droplets, and a decrease in RNA translational efficiency characterized using a battery of biochemical assays. Taken together, our results revealed persistent deficits of key neuronal characteristics induced by pre-differentiation PFOA exposure, suggesting impairments in several AD-related pathways that can together contribute to the elevation of AD risk after pre-differentiation PFOA exposure.

Circulating tumor cells (CTCs) that survive in the blood are playing an important role in the metastasis process of tumor. In addition, they have become a tool for tumor diagnosis, prognosis and recurrence monitoring. CTCs can exist in the blood as individual cells or as clumps of aggregated cells. In recent years, more and more studies have shown that clustered CTCs have stronger metastasis ability compared to single CTCs. With the deepening of studies, scholars have found that cancer cells can combine not only with each other, but also with non-tumor cells present in the blood, such as neutrophils, platelets, etc. At the same time, it was confirmed that non-tumor cells bound to CTCs maintain the survival and proliferation of cancer cells through a variety of ways, thus promoting the occurrence and development of tumor. In this review, we collected information on tumorigenesis induced by CTC clusters to make a summary and a discussion about them. Although CTC clusters have recently been considered as a key role in the transition process, many characteristics of them remain to be deeply explored. A detailed understanding of their vulnerability can prospectively pave the way for new inhibitors for metastasis.

Purpose: Choroidal neovascularization (CNV) is one of the major clinical characteristics of neovascular age-related macular degeneration (AMD). Small non-coding RNAs, such as microRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play key roles in diverse biological functions. The purpose of the study was to investigate the roles and possible functions of the miRNAs and tsRNAs in CNV. Methods: The mouse model of laser-induced CNV was conducted by laser photocoagulation. The expression profiles of miRNAs and tsRNAs were accessed by small RNA sequencing (RNA-Seq) in RPE-choroid-sclera complexes of mice in CNV group and control group. Selected altered miRNAs and tsRNAs were validated by qRT-PCR. Target genes were predicted by informatics analysis and intersected with the previous microarray study of altered mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to reveal the biological functions and signaling pathways with which these target genes are most enriched. Results: The results revealed that 79 miRNAs and 72 tsRNAs in total were significantly altered in the RPE-choroid-sclera complexes of CNV mice. GO analysis revealed that the altered target genes of the selected miRNAs most enriched in immune response, integral component of membrane and peptide binding, while the altered target genes of tsRNAs most enriched in regulation of immune system process, extracellular region and core promoter binding. Moreover, KEGG pathway analysis demonstrated that altered target genes of miRNAs and tsRNAs most enriched in hematopoietic cell lineage and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, respectively. Conclusions: Our study identified differential expressions of miRNAs and tsRNAs in CNV model, and these altered miRNAs and tsRNAs might be novel potential targets in treating CNVs in patients with neovascular AMD.