Generation of the induced pluripotent stem cell line SFMUi001-A from a patient with usher syndrome type 2 caused by biallelic variants in the USH2A gene.

Biallelic variants in the USH2A gene cause Usher syndrome type 2 (USH2), in which patients' symptoms are progressive night blindness, reduced visual field, decreased central vision and sensorineural hearing impairment. There is currently no effective drug for USH2. In this study, we isolated peripheral blood mononuclear cells from a patient with USH2. The pluripotency of induced cells was verified by the presence of cell surface markers, the expression of pluripotent genes, and the formation of teratomas. The generation of this induced pluripotent stem cell line provides an effective way to study USH2, such as disease modeling and drug screening. Usher syndrome type 2 (USH2) is a genetic disease mainly caused by biallelic variants in the USH2A gene. Patients usually present with progressive night blindness, reduced visual field, and then reduced central vision. Patients with USH2 also have sensorineural hearing impairment. There is currently no effective treatment for USH2, and the pathogenesis is still unclear. Therefore, it is of great significance to study the pathogenic mechanism of USH2A gene variants for the study of therapeutic targets. In this study, we obtained induced pluripotent stem cell (iPSC) line containing USH2A gene variants. We isolated mononuclear cells from the peripheral blood of patient and established iPSCs by reprogramming with nonintegrating vectors. We then confirmed the pluripotency of our generated iPSCs through the detection of multiple cell surface markers, the expression of pluripotency-related genes, and the ability to form teratomas with three germ layer structures in vivo. The generation of this cell line will facilitate research on USH2 disease and will play a role that cannot be underestimated in future organoid generation, drug screening, and research on drug targets as well as mechanisms.

Precise theoretical model for quantum-dot color conversion.

Quantum-dot color conversion (QDCC) is a promising technique for next-generation full-color displays, such as QD converted organic light-emitting diodes and micro light-emitting diodes. Although present QDCC research has made some progress on the experimental aspect, the optical model and corresponding mathematical expression that can lay an indispensable foundation for QDCC have not been reported yet. In this paper, we present a theoretical model for precisely describing the complete optical behavior of QDCC, including optical transmission, scattering, absorption, and conversion process. A key parameter of QDCC, called dosage factor (DoF), is defined to quantitatively express the total consumption of QDs that can be calculated as the product of film thickness and QD concentration. Theoretical relations are established between DoF and three key performance indicators of QDCC, namely the light conversion efficiency (LCE), blue light transmittance (BLT), and optical density (OD). The maximum LCE value can be predicted based on this theoretical model, as well as the relationship between the slope of the OD curve and the molar absorption coefficient of blue light. This theoretical model is verified by both simulation and experiment. Results show that the simulation and experimental data highly match the theoretical model, and the goodness of fit reaches higher than 96% for LCE, BLT, and OD. Based on this, the optimal interval of DoF is recommended that provides key guiding significance to the QDCC related experiment.

Portable and multiplexed lateral flow immunoassay reader based on SERS for highly sensitive point-of-care testing.

A portable surface-enhanced Raman scattering (SERS)-based lateral flow immunoassay (LFIA) reader with multiplexed detection was developed using an integrated LFIA reaction column. The proposed LFIA reader was designed to simultaneously detect multiple samples or samples with multiple biomarkers. With the integrated LFIA reaction column, we achieved the specific detection of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA) with a detection limit of 0.01 ng/mL, which was three orders of magnitude lower than that of the visual signal. We also investigated the uniformity of channels based on an eight-channel integrated LFIA reaction column. The relative standard deviation values of the SERS intensity of the eight-channel for measuring the AFP, CEA, and PSA antigens at 1323 cm-1 were 13%, 4.8%, and 5%, respectively. We detected 45 clinical serum samples of the three antigens using the proposed portable SERS-based LFIA reader to further confirm its applicability to clinical samples. The SERS signals of the positive sera were higher than those of the negative sera and their thrice standard deviation. This result indicated the practicality of the developed integrated reaction column and the proposed portable and multiplexed Raman reader. This work provides a new high-sensitivity, multiplexed, and automated SERS-based LFIA detector for use in the point-of-care setting.

Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D.

Dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) is localized in the Down syndrome critical region of chromosome 21. As a candidate gene responsible for learning defects associated with Down syndrome and Alzheimer's disease (AD), DYRK1A has been implied to play pivotal roles in cell proliferation and brain development. MEF2D, a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors, was proved to be in control of neuronal cell differentiation and development. Here we demonstrated that MEF2D could upregulate DYRK1A gene expression through specific activation of DYRK1A isoform 5 gene transcription. A MEF2D responsive element from -268 to -254 bp on promoter region of DYRK1A isoform 5 was identified and confirmed by luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). The coordinated expression of DYRK1A and MEF2D in mouse brain development indicated a possibility of the cross-interaction of these two genes during neurodevelopment. The DYRK1A kinase activity was also affected by MEF2D's transcriptional regulation of DYRK1A. Therefore, the molecular regulation of DYRK1A by MEF2D further supported their involvement in neurodevelopment.

[Study on cytotoxicity tests of medical devices based on IC50].

To discuss IC50 application in cytotoxicity tests of medical devices, we firstly investigated the vibrating condition and endpoint of MTT method specified in ISO 10993-5: 2009. Furthermore, we demonstrated the application of IC50 in the result evaluation of MTT method. The experimental results show that usage of IC50 in quantitative evaluation of MTT method is feasible.

REST regulates DYRK1A transcription in a negative feedback loop.

DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) has been shown to be involved in learning and memory impairments in Alzheimer disease and Down syndrome. As a homolog of Drosophila minibrain gene, DYRK1A also plays important roles in neurodevelopment; however, the function and regulatory mechanism of DYRK1A in neurodevelopment remain elusive. REST (RE1 silencing transcription factor) plays vital roles in neuronal differentiation. Here, we found that REST can activate DYRK1A transcription via a neuron-restrictive silencer element at bp -833 to -815 of human DYRK1A promoter. The coordinated expression of DYRK1A and REST in mouse brain further supports the cross-interaction of DYRK1A and REST during neurodevelopment. Moreover, we showed that DYRK1A dosage imbalance reduced REST protein stability and transcriptional activity through facilitating ubiquitination and subsequent degradation of REST protein. Therefore, the regulation of DYRK1A by REST in a negative feedback loop suggests that DYRK1A and REST are closely related in neurodevelopment.