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.

Design of a dynamic dual-foveated imaging system.

A new kind of dynamic dual-foveated imaging system in the infrared band is designed and optimized in this paper. Dual-foveated imaging refers to the variation in spatial resolution at the two selected fields across the image. Such variable resolution imaging system is suitable for a variety of applications including monitoring, recognition, and remote operation of unmanned aerial vehicle. In this system, a transmissive spatial light modulator (SLM) is used as an active optical element which is located near the image plane instead of pupil plane creatively in order to divide the two selected fields.

Construction of Au quantum dots/nitrogen-defect-enriched graphite carbon nitride heterostructure via photo-deposition towards enhanced nitric oxide photooxidation.

The challenge of mitigating pollution stemming from industrial exhaust emissions is a pressing issue in both academia and industry. This study presents the successful synthesis of nitrogen-defect-enriched graphite carbon nitride (g-C3N4) using a two-step calcination technique. Furthermore, a g-C3N4-Au heterostructure was fabricated through the photo-deposited Au quantum dots (QDs). When subjected to visible light irradiation, this heterostructure exhibited robust nitric oxide (NO) photooxidation activity and stability. With its fluffy, porous structure and large surface area, the nitrogen-defect-enriched g-C3N4 provides more active sites for photooxidation processes. The ability of g-C3N4 to absorb visible light is enhanced by the local surface plasmon resonance (LSPR) effect of Au QDs. Additionally, the lifetime of photogenerated charge carriers is extended by the presence of N defects and Au, which effectively prevent photogenerated electron-hole pairs from recombining during the photooxidation process. Moreover, the oxidation pathway of NO was analyzed through In-situ Fourier transform infrared (FT-IR) spectroscopy and Density Functional Theory (DFT) calculation. Computational findings revealed that the introduction of Au QDs decreases the activation energy of the oxidation reaction, thereby facilitating its occurrence while diminishing the formation of intermediate products. As a result, NO is predominantly converted to nitrate (NO3-). This work unveils a novel approach to constructing semiconductor-cocatalyst heterostructures and elucidates their role in NO photooxidation.

Exploration of the immune-related signature and immune infiltration analysis for breast ductal and lobular carcinoma.

BACKGROUND: In this study, we aimed to explore the tumour associated immune signature of breast cancer (BC) and conduct integrative analyses with immune infiltrates in BC. METHODS: We downloaded the transcriptome profiling and clinical data of BC from The Cancer Genome Atlas (TCGA) database. The list of immune-related signatures was from the Innate database. The limma package was utilized to conduct the normalization, and we screened the differential immune signatures in BC. A univariate Cox regression model and the LASSO method were used to find the hub prognostic immune genes. The TAIG risk model was calculated based on the multivariate Cox regression results, and a receiver operating characteristic (ROC) curve was generated to assess the predictive power of TAIG. Moreover, we also conducted a correlation analysis between TAIG and the clinical characteristics. Additionally, we utilized the METABRIC cohort as the validation data set. The TIMER database is a comprehensive resource for performing systematic analyses of immune infiltrates across various malignancies. We evaluated the associations of immune signatures with several immune cells based on TIMER. Furthermore, we used the CIBERSORT algorithm to determine the fractions of immune cells in each sample and compared the differential distributions of immune infiltrates between two TAIG groups using the Wilcoxon rank-sum test. RESULTS: A total of 1,178 samples were obtained from the TCGA-BRCA database, but only 1,045 breast tumour samples were matched with complete transcriptome expression data. Meanwhile, we collected a total of 1,094 BC patients from the METABRIC cohort. We found a list of 1,399 differential immune signatures associated with survival, and functional analysis revealed that these genes participated in cytokine-cytokine receptor interactions, Th1 and Th2 cell differentiation and the JAK-STAT signalling pathway. The TAIG risk model was established from the multivariate Cox analysis, and we observed that high TAIG levels correlated with poor survival outcomes based on Kaplan-Meier analysis. The Kruskal-Wallis test suggested that high TAIG levels correlated with high AJCC-TNM stages and advanced pathological stages (P<0.01). We validated the well robustness of TAIG in METABRIC cohort and 5-year AUC reached up to 0.829. Moreover, we further uncovered the associations of hub immune signatures with immune cells and calculated the immune cell fractions in specific tumour samples based on gene signature expression. Last, we used the Wilcoxon rank-sum test to compare the differential immune density in the two groups and found that several immune cells had a significantly lower infiltrating density in the high TAIG groups, including CD8+ T cells (P=0.031), memory resting CD4+ T cells (P=0.026), M0 macrophages (P=0.023), and M2 macrophages (P=0.048). CONCLUSIONS: In summary, we explored the immune signature of BC and constructed a TAIG risk model to predict prognosis. Moreover, we integrated the identified immune signature with tumour-infiltrating immune cells and found adverse associations between the TAIG levels and immune cell infiltrating density.