3D reconstruction of a gastrulating human embryo.

Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.

Moderation Effects of Streetscape Perceptions on the Associations Between Accessibility, Land Use Mix, and Bike-Sharing Use: Cross-Sectional Study.

Background: Cycling is known to be beneficial for human health. Studies have suggested significant associations of physical activity with macroscale built environments and streetscapes. However, whether good streetscapes can amplify the benefits of a favorable built environment on physical activity remains unknown. Objective: This study examines whether streetscape perceptions can modify the associations between accessibility, land use mix, and bike-sharing use. Methods: This cross-sectional study used data from 18,019,266 bike-sharing orders during weekends in Shanghai, China. A 500 × 500 m grid was selected as the analysis unit to allocate data. Bike-sharing use was defined as the number of bike-sharing origins. Street view images and a human-machine adversarial scoring framework were combined to evaluate lively, safety, and wealthy perceptions. Negative binomial regression was developed to examine the independent effects of the three perceptual factors in both the univariate model and fully adjusted model, controlling for population density, average building height, distance to nearest transit, number of bus stations, number of points of interest, distance to the nearest park, and distance to the central business district. The moderation effect was then investigated through the interaction term between streetscape perception and accessibility and land use mix, based on the fully adjusted model. We also tested whether the findings of streetscape moderation effects are robust when examinations are performed at different geographic scales, using a small-sample statistics approach and different operationalizations of land use mix and accessibility. Results: High levels of lively, safety, and wealthy perceptions were correlated with more bike-sharing activities. There were negative effects for the interactions between the land use Herfindahl-Hirschman index with the lively perception (ß=-0.63; P=.01) and safety perception (ß=-0.52; P=.001). The interaction between the lively perception and road intersection density was positively associated with the number of bike-sharing uses (ß=0.43; P=.08). Among these, the lively perception showed the greatest independent effect (ß=1.29; P<.001), followed by the safety perception (ß=1.22; P=.001) and wealthy perception (ß=0.72; P=.001). The findings were robust in the three sensitivity analyses. Conclusions: A safer and livelier streetscape can enhance the benefits of land use mix in promoting bike-sharing use, with a safer streetscape also intensifying the effect of accessibility. Interventions focused on streetscape perceptions can encourage cycling behavior and enhance the benefits of accessibility and land use mix. This study also contributes to the literature on potential moderators of built environment healthy behavior associations from the perspective of microscale environmental perceptions.

Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy.

The human placenta has a vital role in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA sequencing and single-nucleus ATAC sequencing analyses of human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their correspondence with human trophoblast stem cell (hTSC)-derived STB. Furthermore, we identified transcription factors associated with diverse STB nuclear lineages through their gene regulatory networks and experimentally confirmed their function in hTSC and trophoblast organoid-derived STBs. Together, our data provide insights into the heterogeneity of human STB and represent a valuable resource for interpreting associated pregnancy complications.

Regulation of Tumorigenesis in Hepatocellular Carcinoma via the AKT3 Pathway in Cell Lines.

BACKGROUND: The estimation of hepatocellular carcinoma (HCC) is tremendously inferior because of the formation of chemoresistance, integrated with essentially increased stemness belongings. At present, the relevance between miR-122 and cancer development was mostly undisclosed with single study reflecting its importance in glioblastoma. Material and Methods. The research here was focused to investigate the task of miR-122 to modulate tumorigenesis in hepatocellular carcinoma by aiming AKT3 in the management of hepatocellular carcinoma stemness and chemosensitivity. The method of QRT-PCR was performed to investigate the aspect of miR-122 and AKT3 in tissue sample and cell lines. The evaluation was done using gain- or loss-of-function in order to retrieve the function of miR-122 in the hepatocellular carcinoma cells, including cell multiplication and stemness effects. The properties of hepatocellular carcinoma were discovered by the development of sphere development, cell feasibility, and the emergence of colony. RNA immunoprecipitation (RIP), luciferase reporter, and the RNA pull down evaluation were conducted to investigate the communication between the miR-122 and AKT3. Therefore, a naked mouse xenograft specimen was set up for the in vivo analysis. RESULTS: Here, we determined the new role of AKT3 and unmediated target of miR-122. The reimposition of miR-122 appearance in the hepatocellular carcinoma cell lines reduces the levels of AKT3 and also hinders the relocation and expansion of cells by prompting apoptosis. These phenotypes are antitumor in nature and can be retrieved by the reorganization of the AKT3 expression which signals the crucial role of AKT3 in the miR-122 arbitrated HCC modification. The in vivo analysis demonstrated the reimposition of miR-122 entirely obstructing the xenograft expansion to manage tumorigenesis in hepatocellular carcinoma and a prospective remedial entrant for the liver cancer. CONCLUSION: In this study, it was observed that miR-122 encourages the stemness role of hepatocellular carcinoma and diminishes the chemosensitivity by cleaning the miR-122 in order to initiate the AKT3. The in vivo study reflected the restoration of miR-122 which completely hinders the xenograft growth to regulate the tumorigenesis in the HCC.