The human placenta sustains pregnancy through intricate trophoblast lineage dynamics that are critical for fetal development and pregnancy success. While studies on protein-coding genes (PCGs) have advanced our understanding of placental biology, the regulatory roles of noncoding RNAs, particularly long noncoding RNAs (lncRNAs), in trophoblast lineage specification and function remain poorly understood. Here, we profile single-cell lncRNA dynamics across human placental development, revealing distinct cell-type- and gestational stage-specific expression profiles. Integrated analysis revealed that lncRNAs modulate histone modification levels at the regulatory regions of target genes via cis-action, thereby regulating the expression of key genes essential for trophoblast differentiation. Functional studies by using in vivo and in vitro models fully identify ECEL1P2–ALPP, SEMA3B–AS1–SEMA3B, and MYCNUT/MYCNOS–MYCN as pivotal regulatory axes driving cytotrophoblast self-renewal, syncytiotrophoblast fusion, and epithelial–mesenchymal transition, respectively, which are essential for trophoblast identity and function. Notably, dysregulation of lncRNA–PCG pairs in pathological pregnancies underscores the clinical relevance of these noncoding networks. Together, our findings uncover an unappreciated layer of lineage-specific noncoding regulation, providing mechanistic insight and potential biomarkers for placental development and associated disorders.
Areca nut is classified as a Group 1 carcinogen by the International Agency for Research on Cancer. It is a widely consumed psychoactive substance with profound cultural roots in regions including Hunan, Hainan, and Taiwan of China. Its key bioactive components include alkaloids (e.g. arecoline and arecaidine) and areca nut-specific nitrosamines, that induce DNA damage, reactive oxygen species bursts, and chronic inflammation in oral tissues. Coupled with mechanical trauma from chewing, these insults drive the malignant progression of oral submucous fibrosis to oral cavity carcinomas. This review systematically outlines the pathological progression from normal oral mucosa to invasive oral cavity carcinomas, highlighting two core mediators of oral submucous fibrosis carcinogenesis: immune microenvironment reprogramming and oncogenic signaling activation. Furthermore, this review elaborates the molecular mechanisms of areca nut-induced oral cancer, providing a theoretical foundation for biomarker discovery and the development of novel therapeutic strategies. It also provides actionable guidance for reducing the incidence of areca nut-related oral cavity carcinomas and improving patient prognosis.
Eosinophilic esophagitis (EoE) is a chronic immune disease requiring repeated endoscopies for diagnosis and monitoring in children. Saliva represents a promising non-invasive biofluid, and volatile organic compounds (VOCs) may indicate disease presence and activity. This study aimed to examine the VOCs profile in saliva samples from children with EoE and to compare it with other gastrointestinal (GI) conditions and healthy controls. Thirty-five samples from children with EoE (including 13 active and 22 non-active cases), 19 from children with other GI conditions, and 46 from healthy controls were analyzed. Gas chromatography–ion mobility spectrometry (GC–IMS) identified 63 distinct VOC signal areas. The abundance of 16 of them was found significantly different (P < 0.01) in EoE vs. controls, EoE vs. other GI conditions, and active vs. non-active EoE. Among them, cis-3-hexen-1-ol and 2-phenylethanol show a ubiquitous capability to discriminate EoE against different populations. Linear discriminant analysis (LDA) of the panel of 16 VOCs achieved 83.3% accuracy in classifying EoE vs. healthy controls, 81.2% accuracy in distinguishing EoE from GI controls, and 80.0% accuracy in classifying active vs. non-active EoE. Salivary VOC profiling enables accurate discrimination of pediatric EoE from controls and stratification by disease activity. This non-invasive approach holds promise as a diagnostic and monitoring tool in clinical practice, especially in children.