Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we first reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited pronounced scoliosis during later stages of development, effectively recapitulating the IS phenotype. We observed that the epha4a mutants displayed defects in left-right coordination during locomotion, which arose from disorganized neural activation in these mutants. Our subsequent experiments indicated that the disruption of the central pattern generator (CPG) network, characterized by abnormal axon guidance of spinal cord interneurons, contributed to the disorganization observed in the mutants. Moreover, when knocked down efnb3b, the ligand for Epha4a, we observed similar CPG defects and disrupted left-right locomotion. These findings suggested that ephrin B3-Epha4 signaling is vital for the proper functioning of CPGs, and defects in this pathway could lead to scoliosis in zebrafish. Furthermore, we identified two cases of IS in NGEF, a downstream molecule in the EPHA4 pathway. Collectively, our data provide compelling evidence that neural patterning impairments and disruptions in CPGs may underlie the pathogenesis of IS.

Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes ( ITPR2 , TBX6 , TPO , H6PD , and SEC24B ). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Background: Oral squamous cell carcinoma (OSCC) has been the sixth most common cancer worldwide. Emerging studies showed long non-coding RNAs to play a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of OSCC remained to be further explored. Objective: The present study aimed to identify differentially expressed lncRNAs and mRNAs in OSCC. Methods: GSE30784 was analyzed to identify differentially expressed lncRNAs and mRNAs in OSCC. Protein-protein interaction network and co-expression network analyses were performed to reveal the potential roles of OSCC related mRNAs and lncRNAs. Results: In the present study, we identified 21 up-regulated lncRNAs and 54 down-regulated lncRNAs in OSCC progression. Next, we constructed a lncRNA related co-expression network in OSCC, which included 692 mRNAs and 2193 edges. Bioinformatics analysis showed that lncRNAs were widely co-expressed with regulating type I interferon signaling pathway, extracellular matrix organization, collagen catabolic process, immune response, ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling pathway. A key network, including lncRNA C5orf66-AS1, C21orf15, LOC100506098, PCBP1-AS1, LOC284825, OR7E14P, HCG22, and FLG-AS1, was found to be involved in the regulation of immune response to tumor cell, Golgi calcium ion transport, negative regulation of vitamin D receptor signaling pathway, and glycerol- 3-phosphate catabolic process. Moreover, we found higher expressions of CYP4F29P, PCBP1- AS1, HCG22, and C5orf66-AS1, which were associated with shorter overall survival time in OSCC samples. Conclusions: Our analysis can provide novel insights to explore the potential mechanisms underlying OSCC progression.

Unplanned exposure to radiation can cause side effects on high-risk individuals; meanwhile, radiotherapies can also cause injury on normal cells and tissues surrounding the tumor. Besides the direct radiation damage, most of the ionizing radiation- (IR-) induced injuries were caused by generation of reactive oxygen species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and multilineage differentiation capabilities, are a critical population of cells to participate in the regeneration of IR-damaged tissues. Therefore, it is imperative to search effective radioprotectors for hMSCs. This study was to demonstrate whether natural source ginger oleoresin would mitigate IR-induced injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin was also investigated. The results showed that ginger oleoresin could induce the translocation of Nrf2 to cell nucleus and activate the expression of cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger oleoresin has a potential role of being an effective antioxidant and radioprotective agent.

The modernization of traditional Chinese medicine (TCM) is a foundation of TCM to go abroad and get international recognition. It is the only way to revitalize the TCM industry. But in the process of it, we are facing various challenges: heavy metal contamination, low content of active ingredients, less innovation, the contradiction between resource utilization and protection, and so on. How to apply new technology and new theory of life science to solve these problems becomes an urgent matter. In recent years, the studies found that endophytic fungi played an irreplaceable positive role in the growth and development of herbal medicine, and had great impact on the quality of traditional Chinese medicine. Therefore this paper introduces the effect of endophytic fungi on genuine traditional Chinese medicines, cultivation of TCM, development and protection of TCM, et al, and explores its applicative prospect, providing new idea and new power for promoting the development of modernization of TCM.

In contrast to cardiomyocytes, autophagy in cardiac microvascular endothelial cells (CMECs) during ischemia/reperfusion (I/R) injury has not been fully investigated. Tongxinluo (TXL), which is a traditional Chinese medicine formulation consists of extractions or powders from Radix ginseng, Buthus