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Background: Improving childcare quality is an important goal in South Korea as many infants attend childcare centers. The quality of teacher-child interactions is a common and crucial predictor of childcare quality. Thus, it is imperative to identify the relative contributions of the variables associated with improving the interaction quality of childcare providers. Objective: This study explored predictors of interaction quality among childcare providers. This study hypothesized that multiple variables in each domain impact the interaction quality of childcare providers. These variables include childcare providers' background, psychological well-being, classroom characteristics, and work environment. Methods: Survey data were collected from 803 childcare providers who were responsible for classes comprising children aged 0 to 2 years. A factor analysis of the dependent variable, correlation, and hierarchical regression were performed in this study. Results: Among the predictors of each domain that influence interaction quality, the "happiness" of childcare providers included in the psychological well-being domain emerged as the strongest variable. Subsequently, the variables "belief," "expectation," "value," "distress and loneliness," "teacher-director relationship," and "children's age" in the professional work environment domain followed. Conclusion: Future studies and interventions should explore diverse ways to mitigate the negative emotions experienced by childcare providers. Furthermore, ongoing professional development should be emphasized as a cost-effective way to improve interaction quality.

Background: Despite the recent emphasis on technology and engineering in early childhood education, the importance of teaching relevant concepts in early education has been underappreciated in South Korea. This study examined the feasibility and efficacy of a science, technology, engineering, art, and mathematics (STEAM) program integrated into the national curriculum in a Korean early childhood education setting. Children aged 5-6 years (231 girls and 219 boys; treatment group: 334 children; control group: 116 children) were tested on computational thinking, vocabulary, numeracy, self-regulation, and social behavior before and after receiving STEAM curriculum that included robotics activities or an equivalent curriculum. Results: Findings revealed that among the outcome measures, young children in the treatment group exhibited significant increases in computational thinking and expressive vocabulary. Moreover, gender demonstrated a significant interaction effect with the increase in computational thinking as measured by an assessment developed for a specific robotic material as well as in self-regulation and social behavior. Conclusions: This study provides empirical and comprehensive evidence regarding the effectiveness of an integrated STEAM program with developmentally appropriate robotic kits for young children.

Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-[beta] signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic [CD8.sup.+] T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-LI therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80., Introduction Despite the widespread utilization of immunotherapy, the poor clinical response by immune-suppressive tumors is an emerging challenge in use of current immune checkpoint inhibitors. Triple negative breast cancers (TNBCs) [...]

Class B G protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because their large orthosteric peptide-binding pocket embedded deep within the transmembrane domain limits the identification and development of nonpeptide small molecule ligands. Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination of molecular dynamics simulations and elastic network model-based methods, we demonstrate that PTHR druggability can be effectively addressed. Here we found a key mechanical site that modulates the collective dynamics of the receptor and used this ensemble of PTHR conformers to identify selective small molecules with strong negative allosteric and biased properties for PTHR signaling in cell and PTH actions in vivo. This study provides a computational pipeline to detect precise druggable sites and identify allosteric modulators of PTHR signaling that could be extended to GPCRs to expedite discoveries of small molecules as novel therapeutic candidates.

The parathyroid hormone (PTH) type 1 receptor (PTHR) is a class B G protein–coupled receptor (GPCR) that regulates mineral ion, vitamin D, and bone homeostasis. Activation of the PTHR by PTH induces both transient cell surface and sustained endosomal cAMP production. To address whether the spatial (location) or temporal (duration) dimension of PTHR-induced cAMP encodes distinct biological outcomes, we engineered a biased PTHR ligand (PTH7d) that elicits cAMP production at the plasma membrane but not at endosomes. PTH7d stabilized a unique active PTHR conformation that mediated sustained cAMP signaling at the plasma membrane due to impaired β-arrestin coupling to the receptor. Experiments in cells and mice revealed that sustained cAMP production by cell surface PTHR failed to mimic the pharmacological effects of sustained endosomal cAMP production on the abundance of the rate-limiting hydroxylase catalyzing the formation of active vitamin D, as well as increases in circulating active vitamin D and Ca2+ and in bone formation in mice. Thus, similar amounts of cAMP generated by PTHR for similar lengths of time in different cellular locations, plasma membrane and endosomes, mediate distinct physiological responses. These results unveil subcellular signaling location as a means to achieve specificity in PTHR-mediated biological outcomes and raise the prospect of rational drug design based upon spatiotemporal manipulation of GPCR signaling.

The purpose of this study is to examine the perceptions of elementary school teachers and the conditions within which they teach. This study is expected to contribute to the preparation for the new technology demands of our rapidly changing society and the recent changes made to the 2015 Revised National Curriculum aimed at Fostering Creative-Convergence Human Resources in Korea. It is primarily expected to contribute to the application of the Science, Technology, Engineering, Arts and Mathematics (STEAM) education and Math-Focused STEAM education. For this purpose, we surveyed 273 teachers of 24 public schools in Seoul and Gyunggido area. The results showed that teachers recognized 'convergence' in STEAM education either as an 'integrated approach' in which specific subjects or topics are taught together or as a 'convergent approach' to teach together and further to a new one. In addition, positive responses were shown towards Math-Focused STEAM education in terms of its effectiveness on the education and needs of the students. The most significant problem in terms of the school environment was the lack of preparation time provided, materials, and educational resources. This study is expected to support the increased application of Math-Focused STEAM education in the field, and thus to expand the knowledge embodied in the subject of mathematics.

Purpose: To quantitatively investigate the microstructural properties of the optic nerve (ON) in vivo using diffusion magnetic resonance imaging (dMRI) tractography in an elderly population and to determine the differences between the ON diffusion properties stratified by basic demographics. Methods: We measured fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of the intraorbital ON in cognitively normal controls selected from the Alzheimer's Disease Neuroimaging Initiative 3 database (n =104; mean age = 73. 8 ± 8.1 years) using dMRI probabilistic tractography and evaluated the correlation between diffusion parameters and demographic factors. Diffusion parameters were measured in 20 equidistant nodes along the tract, and the data from proximal 70% (14 nodes) of the intraorbital ON were averaged. Results: The mean FA of the intraorbital ON was 0.392 ± 0.063, and the mean MD was 1.163 ± 0.165 μm2/s. The mean RD was 0.882 ± 0.152 μm2/s, and the mean AD was 1.693 ± 0.183 μm2/s. The multiple linear regression model showed a negative correlation between FA and age. FA in females was significantly higher than males, whereas RD in female was significantly lower. Conclusions: We measured the diffusion properties of the intraorbital ON using dMRI tractography in an elderly cognitively normal population. The diffusion properties detected by dMRI tractography may substantially reflect the microstructure of the ON.

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.

This study aims to validate a Korean version of the Brief Version of the Child Abuse Potential Inventory (BCAP-K) for use with childcare providers in South Korea. By employing a stratified sampling method, 808 childcare providers in charge of infants' classes were selected for participation. Participants completed a questionnaire that included socio-demographic characteristics, the BCAP-K, frequency of child abuse behaviors, and the Caregiver Interaction Scale. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to identify what the structure of the BCAP-K should be. Construct validity and internal reliability were also examined. Research Findings: The study's results revealed that the five-factor model ("Distress and loneliness," "Family conflict," "Happiness," "Rigidity," and "Feelings of Persecution") was the best model for child abuse potential. All BCAP-K subscales were positively related to the frequency of neglect behaviors and negatively associated with childcare providers' interaction quality. When controlling for the demographic variables, "Rigidity" was the strongest factor in predicting both child abuse behaviors and child-caregiver interaction. The internal reliability of the BCAP-K was good. Practice or Policy: The BCAP-K may therefore be an effective and time-efficient tool to screen for child abuse risk among South Korean childcare providers.