Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals.

Despite of the substantial potential of human-derived retinal organoids, the degeneration of retinal ganglion cells (RGCs) during maturation limits their utility in assessing the functionality of later-born retinal cell subtypes. Additionally, conventional analyses primarily rely on fluorescent emissions, which limits the detection of actual cell functionality while risking damage to the 3D cytoarchitecture of organoids. Here, an electrophysiological analysis is presented to monitor RGC development in early to mid-stage retinal organoids, and compare distinct features with fully-mature mouse retina. This approach utilizes high-resolution 3D printing of liquid-metal microelectrodes, enabling precise targeting of specific inner retinal layers within organoids. The adaptable distribution and softness of these microelectrodes facilitate the spatiotemporal recording of inner retinal signals. This study not only demonstrates the functional properties of RGCs in retinal organoid development but also provides insights into their synaptic connectivity, reminiscent of fetal native retinas. Further comparison with fully-mature mouse retina in vivo verifies the organoid features, highlighting the potential of early-stage retinal organoids in biomedical research.

Tick Diversity and Pathogen Transmission in Daejeon, Korea: Implications from Companion Animals and Walking Trails.

With the ongoing global warming-induced climate change, there has been a surge in vector-borne diseases, particularly tick-borne diseases (TBDs). As the population of companion animals grows, there is growing concern from a One Health perspective about the potential for these animals to spread TBDs. In this study, ticks were collected from companion animals and the surrounding environment in Daejeon Metropolitan City, Korea, using flagging and dragging, and CO2 trap methods. These ticks were then subjected to conventional (nested) PCR for severe fever with thrombocytopenia syndrome virus (SFTSV), Anaplasma spp., Ehrlichia spp., and Borrelia spp. We identified a total of 29,176 ticks, consisting of three genera and four species: H. longicornis, H. flava, I. nipponensis, and A. testudinarium. Notably, H. longicornis was the predominant species. The presence of A. testudinarium suggested that the species traditionally found in southern regions are migrating northward, likely as a result of climate change. Our PCR results confirmed the presence of all four pathogens in both companion animals and the surrounding environment, underscoring the potential for the indirect transmission of tick-borne pathogens to humans through companion animals. These findings emphasize the importance of the ongoing surveillance of companion animals in the management and control of TBDs.

Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells.

Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells. ISO caused the deacetylation of α-tubulin and stimulated cell migration in an HDAC6-dependent manner. HDAC6 expression was increased by treatment with selective activators of cAMP-dependent protein kinase (PKA) or exchange protein activated by cAMP (Epac). ISO activated Rap1 via Epac, and constitutively active Rap1A increased the HDAC6 level; however, the knockdown of Rap1A decreased the 8-(4-cholorophenylthio)-2'-O-methyl-cAMP-induced increase in HDAC6 expression. Both PKA and Rap1A decreased c-Raf activation to inhibit extracellular signal-regulated kinase (ERK) signaling. Inhibition of ERK caused an increase in HDAC6 expression, and constitutively active MEK1 decreased the ISO-induced HDAC6 expression. We concluded that ISO increases HDAC6 expression via a PKA/Epac/ERK-dependent pathway that stimulates the migration of lung cancer cells. This study suggests that stress signals can stimulate the migration of cancer cells by inducing HDAC6 expression in lung cancer cells.