ABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in early childhood and can persist to adulthood. It can affect many aspects of a patient's daily life, so it is necessary to explore the mechanism and pathological alterations. For this purpose, we applied induced pluripotent stem cell (iPSC)-derived telencephalon organoids to recapitulate the alterations occurring in the early cerebral cortex of ADHD patients. We found that telencephalon organoids of ADHD showed less growth of layer structures than control-derived organoids. On day 35 of differentiation, the thinner cortex layer structures of ADHD-derived organoids contained more neurons than those of control-derived organoids. Furthermore, ADHD-derived organoids showed a decrease in cell proliferation during development from day 35 to 56. On day 56 of differentiation, there was a significant difference in the proportion of symmetric and asymmetric cell division between the ADHD and control groups. In addition, we observed increased cell apoptosis in ADHD during early development. These results show alterations in the characteristics of neural stem cells and the formation of layer structures, which might indicate key roles in the pathogenesis of ADHD. Our organoids exhibit the cortical developmental alterations observed in neuroimaging studies, providing an experimental foundation for understanding the pathological mechanisms of ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Neural Stem Cells , Humans , Child, Preschool , Attention Deficit Disorder with Hyperactivity/pathology , Telencephalon/pathology , Cerebral Cortex/pathology , OrganoidsABSTRACT
Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common rheumatic diseases in the world. Although there are standard methods for the diagnosis of both RA and OA, the differentials in some cases are poor. With deepening research, the role of autophagy in maintaining cell homeostasis and thus enabling cells adapt to external environments has become increasingly prominent. Both RA and OA, two diseases with inherent differences in pathogenesis, gradually show differences in autophagy levels. Our study therefore aims to further understand differences in pathogenesis of RA and OA through in-depth studies of autophagy in RA and OA. We also define appropriate autophagy-related markers as recognition indicators. Differences in autophagy levels between RA and OA were found based on analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment (ssGSEA). These differences were mainly caused by 134 differentially expressed genes (DEGs). In two autophagy-related genes, CXCR4 and SERPINA1, there existed significant statistical difference between RA and OA. An autophagy related index (ARI) was thus successfully constructed based on CXCR4 and SERPINA by binary logistic regression of the generalized linear regression (GLR) algorithm. Pearson analysis indicated that the expression of CXCR4, SERPINA1, and ARI were closely correlated with autophagy scores and immune infiltration. Moreover, ARI showed high disease identification through receiver operating characteristic (ROC) analysis (AUCtesting cohort = 0.956, AUCtraining cohort = 0.867). These results were then verified in GSE12021 independent cohort. In conclusion, ARI associated with autophagy and immune infiltration was successfully constructed for accurately identifying OA and RA. The index, thus, has great potential in clinical applications.
ABSTRACT
In a free space optical communication system based on vortex beams, the effects of spread and crosstalk caused by atmospheric turbulence should not be ignored. The orbital angular momentum (OAM) spectrum of the signal based on elliptic Gaussian beam (EGB) after propagation through non-Kolmogorov turbulent atmosphere are deduced, and a theoretical model of the spiral spectrum of EGB propagating through turbulent atmosphere is obtained. Numerically calculated OAM modes detection and crosstalk probability under different ellipticity parameters. The results show that the ellipticity parameter has a significant impact on the OAM spectral distribution of EGB and the transmission characteristics after turbulent atmosphere. The selection of appropriate ellipticity parameter can correspondingly reduce the degradation and crosstalk caused by turbulent atmosphere. We also compared a Laguerre-Gaussian beam (LGB) with EGB and pointed out the advantages and limitations of these two kinds of beams. The research results may be useful in the field of short distance optical communication and OAM-based multiplex communication.
ABSTRACT
MicroRNAs (miRNAs) play a critical role in various biological processes through regulation of gene expression post-transcriptionally. Although miRNAs are involved in cell proliferation and differentiation in mammals, few reports regarding the effects of host miRNAs on macrophage activation and differentiation are available in birds. Here, we reported that gga-miR-200b-3p acts as a positive regulator, enhancing macrophage activation and differentiation using an avian model. We found that ectopic expression of gga-miR-200b-3p in HD11 cells enhances the amount of MHC-II-positive cells and promotes the expression of pro-inflammatory cytokines and that gga-miR-200b-3p directly targets monocyte to macrophage differentiation-associated (MMD). The inhibition of MMD by gga-miR-200b-3p enhances the activation and differentiation of HD11 cells and increases the expression of pro-inflammatory cytokines. Collectively, these findings highlight a crucial role of gga-miR-200b-3p in macrophage activation and differentiation in birds.