Scalable iPSC-based platform to produce tissue-specific Extracellular Vesicles

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The Antiviral Effector IFITM3 Disrupts Intracellular Cholesterol Homeostasis to Block Viral Entry

SummaryVesicle-membrane-protein-associated protein A (VAPA) and oxysterol-binding protein (OSBP) regulate intracellular cholesterol homeostasis, which is required for many virus infections. During entry, viruses or virus-containing vesicles can fuse with endosomal membranes to mediate the cytosolic release of virions, and alterations in endosomal cholesterol can inhibit this invasion step. We show that the antiviral effector protein interferon-inducible transmembrane protein 3 (IFITM3) interacts with VAPA and prevents its association with OSBP, thereby disrupting intracellular cholesterol homeostasis and inhibiting viral entry. By altering VAPA-OSBP function, IFITM3 induces a marked accumulation of cholesterol in multivesicular bodies and late endosomes, which inhibits the fusion of intraluminal virion-containing vesicles with endosomal membranes and thereby blocks virus release into the cytosol. Consequently, ectopic expression or depletion of the VAPA gene profoundly affects IFITM3-mediated inhibition of viral entry. Thus, IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry, further underscoring the importance of cholesterol in virus infection

Development of a classification model for Cynanchum wilfordii and Cynanchum auriculatum using convolutional neural network and local interpretable model-agnostic explanation technology

Cynanchum wilfordii is a perennial tuberous root in the Asclepiadaceae family that has long been used medicinally. Although C. wilfordii is distinct in origin and content from Cynancum auriculatum, a genus of the same species, it is difficult for the public to recognize because the ripe fruit and root are remarkably similar. In this study, images were collected to categorize C. wilfordii and C. auriculatum, which were then processed and input into a deep-learning classification model to corroborate the results. By obtaining 200 photographs of each of the two cross sections of each medicinal material, approximately 800 images were employed, and approximately 3200 images were used to construct a deep-learning classification model via image augmentation. For the classification, the structures of Inception-ResNet and VGGnet-19 among convolutional neural network (CNN) models were used, with Inception-ResNet outperforming VGGnet-19 in terms of performance and learning speed. The validation set confirmed a strong classification performance of approximately 0.862. Furthermore, explanatory properties were added to the deep-learning model using local interpretable model-agnostic explanation (LIME), and the suitability of the LIME domain was assessed using cross-validation in both situations. Thus, artificial intelligence may be used as an auxiliary metric in the sensory evaluation of medicinal materials in future, owing to its explanatory ability

Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics

We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label-free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free.1

Induction of IL-10-producing CD4(+)CD25(+ )T cells in animal model of collagen-induced arthritis by oral administration of type II collagen

Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4(+)CD25(+ )T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG(1 )and decreased serum IgG(2a )as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-β from mononuclear lymphocytes was increased in the tolerized animals, and CD4(+ )T cells isolated from tolerized mice did not respond with induction of IFN-γ when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4(+)CD25(+ )subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4(+)CD25(+ )T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect