PATJ and MPDZ are required for trophectoderm lineage specification in early mouse embryos.

In brief: During the morula to blastocyst transformation, polarity establishment in outer cells is a prerequisite for trophectoderm lineage specification. This study reveals the roles of polarity proteins PATJ and MPDZ in trophectoderm lineage fate decision. Abstract: In mouse preimplantation embryos, cell polarity plays a crucial role in the first lineage specification. PATJ and its homolog MPDZ are the main members of CRB-PALS1-PATJ (CRUMBS-Protein associated with Lin7 1-Pals-associated tight junction protein) apical polarity complex. They act as adaptor proteins connecting CRB-PALS1 and tight junction proteins, making them essential for cell polarization and stabilization of apical junctions. However, their roles in regulating trophectoderm differentiation and blastocyst development remain unclear. In this study, PATJ and/or MPDZ were downregulated by the microinjection of specific RNA interference constructs into zygotes. Downregulation of PATJ alone did not severely affect early embryonic development and trophectoderm lineage differentiation although it slowed down the blastocyst formation. Depletion of PATJ and MPDZ did not affect compaction and morula development but impaired blastocyst formation. Furthermore, the expression of trophectoderm-specific transcription factors and trophoblast differentiation was compromised in the absence of PATJ/MPDZ. These abnormalities might result from the breakdown of apical domain in the outer cells of the embryo. The loss of PATJ/MPDZ caused the breakdown of CRB and PAR polarity complexes as well as deficiencies in tight junctions and actin filaments. These defects led to ectopic activation of Hippo signaling in the outer cells of developing embryos, ultimately suppressing Cdx2 expression and trophectoderm differentiation. Altogether, PATJ and MPDZ are essential for trophectoderm lineage differentiation and normal blastocyst morphogenesis via the regulation of the establishment of apical domain, formation of tight junctions, phosphorylation and localization of YAP, and expression of trophectoderm-specific transcription factors.

A Wearable Diagnostic Assessment System vs. SNAP-IV for the auxiliary diagnosis of ADHD: a diagnostic test.

OBJECTIVE: We design a diagnostic test to evaluate the effectiveness and accuracy of A non-intrusive Wearable Diagnostic Assessment System versus SNAP-IV for auxiliary diagnosis of children with ADHD. METHODS: This study included 55 children aged 6-16 years who were clinically diagnosed with ADHD by DSM-5, and 55 healthy children (typically developing). Each subject completes 10 tasks on the WeDA system (Wearable Diagnostic Assessment System) and Parents of each subject complete the SNAP-IV scale. We will calculate the validity indexes, including sensitivity, specificity, Youden's index, likelihood ratio, and other indexes including predictive value, diagnostic odds ratio, diagnostic accuracy and area under the curve [AUC] to assess the effectiveness of the WeDA system as well as the SNAP-IV. RESULTS: The sensitivity (94.55% vs. 76.36%) and the specificity (98.18% vs. 80.36%) of the WeDA system were significantly higher than the SNAP-IV. The AUC of the WeDA system (0.964) was higher than the SNAP-IV (0.907). There is non-statistically significant difference between groups (p = 0.068), and both of them have high diagnostic accuracy. In addition, the diagnostic efficacy of the WeDA system was higher than that of SNAP-IV in terms of the Youden index, diagnostic accuracy, likelihood ratio, diagnostic odds ratio and predictive value. CONCLUSION: The advantages of the WeDA system in terms of diagnostic objectivity, scientific design and ease of operation make it a promising system for widespread use in clinical practice.

FedEYE: A scalable and flexible end-to-end federated learning platform for ophthalmology.

Data-driven machine learning, as a promising approach, possesses the capability to build high-quality, exact, and robust models from ophthalmic medical data. Ophthalmic medical data, however, presently exist across disparate data silos with privacy limitations, making centralized training challenging. While ophthalmologists may not specialize in machine learning and artificial intelligence (AI), considerable impediments arise in the associated realm of research. To address these issues, we design and develop FedEYE, a scalable and flexible end-to-end ophthalmic federated learning platform. During FedEYE design, we adhere to four fundamental design principles, ensuring that ophthalmologists can effortlessly create independent and federated AI research tasks. Benefiting from the design principles and architecture of FedEYE, it encloses numerous key features, including rich and customizable capabilities, separation of concerns, scalability, and flexible deployment. We also validated the applicability of FedEYE by employing several prevalent neural networks on ophthalmic disease image classification tasks.

Asymmetric distribution of CRUMBS polarity complex proteins from compacted 8-cell to blastocyst stage during mouse preimplantation development.

During mouse preimplantation development, blastomeres are equipotent until polarity establishment at compacted 8-cell stage. The intrinsic nature of polarity is the asymmetric distribution of polarity proteins between inside and outside blastomeres along the direction of apical-basal axis. This study investigated the early developmental temporal and spatial expression of the main CRUMBS polarity complex proteins in the mouse preimplantation embryo. We observed that Crb3, Pals1, Patj and Mpdz are transcribed in the mouse preimplantation embryo. However, the asymmetric distribution of these polarity proteins is not established until the compacted 8-cell stage. From compaction and thereafter, CRB3 and PALS1 are progressively enriched in the apical membrane, while PATJ and MPDZ are discretely localized at both tight junctions and the apical membrane adjacent to tight junctions. These temporal and spatial distribution patterns suggest that CRUMBS polarity complex might be involved in the cell polarity establishment in the early mouse embryo and reinforce the viewpoint that developmentally spatial asymmetries are first set up at the compaction stage. The present study provides a foundation for further investigation on the functions of CRUMBS polarity complex in trophectoderm specification and blastocyst morphogenesis.