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The cave automatic virtual environment (CAVE) can provide a large-scale immersive and interactive virtual reality (VR) learning environment, which is suitable for the navigation of visualized learning objects and communication among teachers and students. Its applications have gained attention in the field of architecture, engineering, and construction (AEC). This empirical study aimed to examine the effects of the CAVE-VR learning environment on enhancing students' perception of essential building elements compared with the traditional learning environment and explore the factors influencing students' technology acceptance of this teaching innovation. Initially, the study developed teaching materials related to essential building elements on the CAVE-VR system and implemented the teaching innovation in an undergraduate course, Introductory Construction Technology and Materials. A two-round comparison was adopted in this study to evaluate the effects of the innovative learning environment created by the CAVE-VR system and the traditional learning environment using slides projected on the whiteboard. Two in-class quizzes were designed to test students' comprehension of essential building elements; a questionnaire survey, which was devised based on the cognitive load theory and technology acceptance model, was utilized to evaluate students' attitudes toward the learning experience. According to the descriptive and statistical analysis of the quiz results and questionnaire survey responses, the findings of this empirical study are as follows: (1) for the first-round implementation, it was found that students learning through the proposed CAVE-VR environment attained an enhanced perception of the building elements compared with students learning through the slides; for the second-round implementation, it was detected that the perception of building elements of students learning through the CAVE-VR environment for a second time was significantly enhanced compared with students learning through the CAVE-VR environment for the first time; (2) based on the descriptive analysis of students' responses to the questionnaire survey, most students held a positive technology acceptance attitude toward the immersive CAVE-VR learning environment and experienced a moderate level of cognitive workload to complete their learning tasks, facing few difficulties in interactive operations; and (3) according to the statistical analysis of the feedback of students from different learning programs, Higher Diploma students experienced a significantly lower degree of time pressure, effort demand, and sense of accomplishment than Bachelor students in the CAVE-VR learning environment; at the same time, students from both learning programs considered that the perceived usefulness had a direct impact on their intention to use the CAVE-VR learning environment.

Gluten is a natural byproduct derived from wheat starch, possessing ideal biocompatibility. However, its poor mechanical properties and heterogeneous structure are not suitable for cell adhesion in biomedical applications. To resolve the issues, we prepare novel gluten (G)/sodium lauryl sulfate (SDS)/chitosan (CS) composite hydrogels by electrostatic and hydrophobic interactions. Specifically, gluten is modified by SDS to give it a negatively charged surface, and then it conjugates with positively charged chitosan to form the hydrogel. In addition, the composite formative process, surface morphology, secondary network structure, rheological property, thermal stability, and cytotoxicity are investigated. Moreover, this work demonstrates that the change can occur in surface hydrophobicity caused by the pH−eading influence of hydrogen bonds and polypeptide chains. Meanwhile, the reversible non−covalent bonding in the networks is beneficial to improving the stability of the hydrogels, which shows a prominent prospect in biomedical engineering. [ABSTRACT FROM AUTHOR]

There is a growing demand for the identification of alternative sources of collagen not derived from land-dwelling animals. The present study explored the use of pepsin- and acid-based extraction protocols to isolate collagen from the swim bladders of Megalonibea fusca. After extraction, these acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) samples respectively were subjected to spectral analyses and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) characterization, revealing both to be comprised of type I collagen with a triple-helical structure. The imino acid content of these ASC and PSC samples was 195 and 199 residues per 1000 residues, respectively. Scanning electron microscopy demonstrated that samples of freeze-dried collagen exhibited a compact lamellar structure, while transmission electron microscopy and atomic force microscopy confirmed the ability of these collagens to undergo self-assembly into fibers. ASC samples exhibited a larger fiber diameter than the PSC samples. The solubility of both ASC and PSC was highest under acidic pH conditions. Neither ASC nor PSC caused any cytotoxicity when tested in vitro, which met one of the requirements for the biological evaluation of medical devices. Thus, collagen isolated from the swim bladders of Megalonibea fusca holds great promise as a potential alternative to mammalian collagen. [ABSTRACT FROM AUTHOR]

The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene is present in human chromosome and is linked to the learning deficits of Down syndrome. The study shows that DYRK1A does not require any tyrosine phosphorylation for activity in vitro, as it has enough enzymatic activity in hand.

The mechanism of epigallocatechin-3-gallate (EGCG) inhibition of minibrain kinase/dual-specificity tyrosine phosphorylation regulated kinase 1A (MNB/DRYK1A) is investigated using a combination of genetic and biochemical approaches. In the testing system using MNB/DYRK1A-promoted Gli 1-dependent transcription as the readout, NIH3T3 cells expressing EGCG resistant MNB/DYRK1A mutant R21 are found to acquire EGCG resistance for a wide range of drug concentrations.

Mnb/Dyrk1A is shown to phosphorylate dynamin 1 and alter its interactions with several SH3 domain-containing endocytic accessory proteins. Three potential Mnb/Dyrk1A phosphorylation sites (S778, S795 and S857) are determined using a combination of deletion mutants and synthetic peptides.

Minibrain kinase/dual-specificity tyrosine phosphorylation regulated kinase IA (MNB/DYRKIA) is a proline/arginine-directed serine/threonine kinase implicated in the learning deficits of Down syndrome. Epigallocatechin-3-gallate (EGCG), the major tea polyphenolic compound, is a potent MNB/ DYRK1A inhibitor. In this study, we investigated the mechanism of EGCG inhibition of MNB/DYRKIA using a combination of genetic and biochemical approaches. In the testing system using MNB/DYRKIA-promoted Gli l-dependent transcription as the readout, NIH3T3 cells expressing EGCG resistant MNB/DYRKIA mutant R21 were found to acquire EGCG resistance for a wide range of drug concentrations. Mutant R21 harbors a single K465R substitution, which produces a 3-fold gain in the EGCG resistance in vitro. However, the gain in the EGCG resistance alone cannot fully interpret the effectiveness of mutant R21 in suppressing EGCG in cultured cells. Kinetic analysis suggests that EGCG functions as a noncompetitive inhibitor against ATP. Interestingly, the K465R mutation changes the mode of EGCG inhibition on MNB/DYRKIA so that it becomes a competitive inhibitor against ATP. This competitive mode of EGCG inhibition coupled with high intracellular ATP concentrations and an elevated EGCG resistance are likely to be the basis for the resistant property of mutant R21 in cultured cells. The K465R mutation apparently transforms the intramolecular interactions required for MNB/DYRKIA catalysis. This mutant would also be valuable for the elucidation of the mechanisms of MNB/DYRK 1 A-catalyzed reaction. [ABSTRACT FROM AUTHOR]

The Mnb/Dyrk1A gene is localized in human chromosome 21 and its aberrant expression is associated with the learning and memory deficits of Down syndrome. Mnb/Dyrk1A contains an Y319XY321 motif shared by all members of the Mnb/Dyrk1A protein kinase family. Tyrosine residues in the YXY motif are phosphorylated in Mnb/Dyrk1A prepared from Escherichia coli and from eukaryotic cells. It has been proposed that phosphorylation of the YXY motif is required for kinase activation, a mechanism similar to the activation of mitogen activated protein through phosphorylation of the TXY motif. In this study, the role of tyrosine phosphorylation in the activity of Mnb/Dyrk1A was investigated in detail. Wild-type Mnb/Dyrk1A with a reduced level of PY was prepared by treating Escherichia coli-produced Mnb/Dyrk1A with two different protein tyrosine phosphatases. The resulting PY-depleted Mnb/Dyrk1A could not regain PY during autophosphorylation but was as active as the untreated control. These findings were further supported by the observation that Mnb/Dyrk1A retained measurable enzymatic activity when both tyrosine residues in the YXY motif were replaced with either histidine or glutamine residues. Together, we conclude that tyrosine phosphorylation as well as tyrosine residues in the YXY motif are not directly involved in Mnb/Dyrk1A enzymatic activity. [ABSTRACT FROM AUTHOR]

Background and Aim: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants., Methods: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables., Results: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979)., Conclusions: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants., Trial Registration: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

Exosomes are a subtype of extracellular vesicles. They contain bioactive molecules, including nucleic acids, proteins and lipids. Among the currently described exosomes, a majority are potential candidates for the diagnosis and treatment of necrotizing enterocolitis (NEC). In this work, we reviewed existing literature reports on exosomes and explored their roles in NEC. Exosomes derived from intestinal epithelial cells (IECs) participates in the development of intestinal diseases, thus can potentially be utilized as biomarkers for NEC. Besides, exosomes of human milk have been demonstrated to protect IECs from oxidative stress, stimulate intestinal stem cells activity, improve the proliferation and migration of IECs, and lower the incidence and severity of experimental NEC. Further, exosomes produced by stem cells can reduce the severity of experimental NEC and protect the intestinal barrier function during NEC. Conclusively, exosomes have been shown to influence the pathogenesis of NEC and exert a protective effect on NEC. However, additional investigations would be urgently necessary to comprehensively elucidate the underlying mechanisms of exosomes in NEC., Competing Interests: None., (AJTR Copyright © 2020.)

Each year, cardiac diseases may cause a high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) that contained ultra-conserved elements (UCEs) may play important roles on cardiomyocytes differentiation. Further investigations underlying mechanisms of lncRNA-UC regulating embryonic heart development are necessary. In this study, we investigated the effects of lnc-uc.245 on proliferation, migration, apoptosis, and cardiomyocyte-like differentiation in P19 cells with DMSO stimulation, and hypothesized that lnc-uc.245 would influence cardiomyocytes differentiation via FOG2. Lentiviral vectors of pGPU6/GFP/Neo-uc.245 and pGPU6/GFP/Neo-shRNA-uc.245 were respectively transfected into P19 cells to overexpress or silence uc.245. MTT assay, Annexin V-FITC/PI double-staining, scratch test and transwell assay were performed and the results showed that uc.245 overexpression could significantly suppress P19 cell proliferation, migration, cardiomyocyte-like differentiation but promote cell apoptosis. Contrarily, sh-uc.245 treatment caused the opposite changes. Uc.245 overexpression obviously downregulated the expression of cardiomyogenic-specific molecular markers (cTnI, ANP, α-MHC, Nkx2.5, GATA4, MEF2C) but remarkably upregulated the expression of FOG2. Subsequently, we transfected the recombinant vectors loaded FOG2 or shRRNA-FOG2 into P19 cells to further address the functional significance of FOG2 in uc.245-regulated cardiomyocyte-like differentiation. Interestingly, we found that overexpressing of FOG2 promoted cell proliferation, migration, and inhibited apoptosis both in uc.245 overexpressed and silenced P19 cells, especially in uc.245 silenced cell line. In addition, sh-FOG2 promoted cardiomyocyte-like differentiation and upregulated the expression of cardiomyogenic-specific markers at the gene and protein levels both in uc.245 overexpressed and silenced P19 cells. Similarly, this upregulation effect of sh-FOG2 was more obvious after uc.245 silencing. These findings suggest that FOG2 is a key mediator during uc.245-regulated differentiation of P19 cells into cardiomyocytes. It is expected that lnc-uc.245/FOG2 will become a promising therapeutic target for cardiac diseases., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: To explore and validate the differential expression of circRNAs in the myocardium of congenital ventricular septal defect (VSD) and to explore a new avenue of research regarding the pathological mechanisms of VSD. Methods: We detected circRNAs expression profiles in heart tissues taken from six aborted fetuses with VSD and normal group using circRNA microarray. Some differentially expressed circRNAs were studied by bioinformatics analysis. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. Results: This study found abundant circRNAs in the myocardium taken from individuals in the normal group and the VSD group. After that, totally 6234 differentially expressed circRNAs between the normal group and the VSD group were confirmed (Fold change ≥ 2.0; p < 0.05 ). Then, this research carried out bioinformatics analysis and predicted the potential biological functions of circRNAs. Finally, the over-expression of hsa&#95;circRNA&#95;002086 and under-expression of hsa&#95;circRNA&#95;007878, hsa&#95;circRNA&#95;100709, hsa&#95;circRNA&#95;101965, hsa&#95;circRNA&#95;402565 were further validated by qRT-PCR. Conclusions: There is a significant difference in expression of the circRNA in cardiac tissue from VSD group compared to the normal group. Combined with the microarray results and previous researches, circRNAs may contribute to the occurrence of VSD by acting as miRNA sponges or by binding proteins, these possible roles for circRNAs in VSD require elucidation in additional studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Hyperbilirubinemia occurs in most healthy term and late-preterm infants, and must be monitored to identify those who might develop severe hyperbilirubinemia. Total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) nomograms have been developed and validated to identify neonatal hyperbilirubinemia. This study aimed to review previously published studies and compare the TcB nomograms with the TSB nomogram, and to determine if the former has the same predictive value for significant hyperbilirubinemia as TSB nomogram does., Methods: A predefined search strategy and inclusion criteria were set up. We selected studies assessing the predictive ability of TSB/TcB nomograms to identify significant hyperbilirubinemia in healthy term and late-preterm infants. Two independent reviewers assessed the quality and extracted the data from the included studies. Meta-Disc 1.4 analysis software was used to calculate the pooled sensitivity, specificity, and positive likelihood ratio of TcB/TSB nomograms. A pooled summary of the receiver operating characteristic of the TcB/TSB nomograms was created., Results: After screening 187 publications from electronic database searches and reference lists of eligible articles, we included 14 studies in the systematic review and meta-analysis. Eleven studies were of medium methodological quality. The remaining three studies were of low methodological quality. Seven studies evaluated the TcB nomograms, and seven studies assessed TSB nomograms. There were no differences between the predictive abilities of the TSB and TcB nomograms (the pooled area under curve was 0.819 vs. 0.817)., Conclusions: This study showed that TcB nomograms had the same predictive value as TSB nomograms, both of which could be used to identify subsequent significant hyperbilirubinemia. But this result should be interpreted cautiously because some methodological limitations of these included studies were identified in this review.