Examining impacts of information system success and perceived stress on students' self-regulated learning mediated by intrinsic motivation in online learning environments: second-order structural equation modelling analyses.

The unanticipated switch from face-to-face learning to online education caused by the Covid-19 pandemic has led to a lack of familiarization preparation for students, potentially hampering their learning processes in several ways. The success of online learning is primarily based on the quality of the information systems, self-regulated learning, and intrinsic learning motivation. The severe stress amid epidemic lockdowns might trigger negative impacts on students' learning motivation and self-regulated learning. Nevertheless, studies examining the relationship between information system success, self-regulated learning, perceived stress, and intrinsic learning motivation in the context of developing countries are still scarce. The current research aims to address this gap in the literature. Participants were 303 university students. The results of second-order structural equation modelling revealed the positive direct and indirect relationships between information system success, intrinsic learning motivation, and online self-regulated learning. Besides, despite the insignificant relationships between perceived stress, intrinsic learning motivation, and online self-regulated learning, most participants in this study were found to have moderate to high stress levels. Hence, the potential adverse effect of stress on students' learning process should not be ignored. The results provide implications for educators and researchers studying online learning environments and educational psychology.

Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish.

Nrf2 plays critical roles in animals' defense against electrophiles and oxidative stress by orchestrating the induction of cytoprotective genes. We previously isolated the zebrafish mutant it768, which displays up-regulated expression of Nrf2 target genes in an uninduced state. In this paper, we determine that the gene responsible for it768 was the zebrafish homolog of phosphomannomutase 2 (Pmm2), which is a key enzyme in the initial steps of N-glycosylation, and its mutation in humans leads to PMM2-CDG (congenital disorders of glycosylation), the most frequent type of CDG. The pmm2it768 larvae exhibited mild defects in N-glycosylation, indicating that the pmm2it768 mutation is a hypomorph, as in human PMM2-CDG patients. A gene expression analysis showed that pmm2it768 larvae display up-regulation of endoplasmic reticulum (ER) stress, suggesting that the activation of Nrf2 was induced by the ER stress. Indeed, the treatment with the ER stress-inducing compounds up-regulated the gstp1 expression in an Nrf2-dependent manner. Furthermore, the up-regulation of gstp1 by the pmm2 inactivation was diminished by knocking down or out double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK), one of the main ER stress sensors, suggesting that Nrf2 was activated in response to the ER stress via the PERK pathway. ER stress-induced activation of Nrf2 was reported previously, but the results have been controversial. Our present study clearly demonstrated that ER stress can indeed activate Nrf2 and this regulation is evolutionarily conserved among vertebrates. Moreover, ER stress induced in pmm2it768 mutants was ameliorated by the treatment of the Nrf2-activator sulforaphane, indicating that Nrf2 plays significant roles in the reduction of ER stress.

Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish.

Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a(fh318). After treatment with 1mM sodium arsenite, the survival of nrf2a(fh318) larvae was significantly shorter than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity.

Genotoxicity of chemical compounds identification and assessment by yeast cells transformed with GFP reporter constructs regulated by the PLM2 or DIN7 promoter.

Yeast cells transformed with high-copy number plasmids comprising a green fluorescent protein (GFP)-encoding gene optimized for yeast under the control of the new DIN7 or PLM2 and the established RNR2 and RAD54 promoters were used to assess the genotoxic potential of chemical compounds. The activity of potential DNA-damaging agents was investigated by genotoxicity assays and by OxoPlate assay in the presence of various test compounds. The fluorescence signal generated by GFP in response to DNA damage was related to the different concentrations of analytes and the analyte-dependent GFP synthesis. The use of distinct DNA damage-inducible promoters presents alternative genotoxicity testing strategies by selective induction of promoters in response to DNA damage. The new DIN7 and PLM2 systems show higher sensitivity than the RNR2 and RAD54 systems in detecting 4-nitroquinoline-N-oxide and actinomycin D. Both DIN7 and PLM2 systems are able to detect camptothecin while RNR2 and RAD54 systems are not. Automated laboratory systems with assay performance on 384-well microplates provide for cost-effective high-throughput screening of DNA-damaging agents, reducing compound consumption to about 53% as compared with existing eukaryotic genotoxicity bioassays.

Exploring the Phytochemical Diversity and Antioxidant Potential of the Vietnamese Smilax glabra Roxb: Insights from UPLC-QTOF-MS/MS and Zebrafish Model Studies.

Research on natural products is growing due to their potential health benefits and medicinal properties. Despite regional variations in phytochemical composition and bioactivity, Smilax glabra Roxb (SGB) has attracted the interest of researchers. Scientists are particularly interested in the Vietnamese SGB variant, which is influenced by biological and environmental factors. Despite geographical differences in phytochemical makeup and bioactivities, SGB remains a fascinating subject in traditional herbal medicine. Using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), the phytochemicals in Vietnamese SGB extracts were investigated. This study revealed a wide range of phytochemical compounds, including flavonoids, terpenoids, glycosides, alkaloids, organic acids, phenolics, and steroids. Furthermore, utilizing zebrafish as a model organism, we discovered that these extracts have the surprising ability to greatly improve the survival rate of zebrafish larvae exposed to oxidative stress caused by arsenite (NaAsO2) and hydrogen peroxide (H2O2). Notably, our discoveries suggest the occurrence of new antioxidative pathways in addition to the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, expanding the understanding of the antioxidant properties and potential therapeutic uses of these plants. To summarize, our research findings shed light on the phytochemical composition of Vietnamese SGB, revealing its potential as a natural antioxidant and encouraging further exploration of its underlying mechanisms for future innovative antioxidant therapies.

Genetic hyperactivation of Nrf2 causes larval lethality in Keap1a and Keap1b-double-knockout zebrafish.

The Keap1-Nrf2 pathway is an evolutionarily conserved mechanism that protects cells from oxidative stress and electrophiles. Keap1 is a repressor of Nrf2 in normal cellular conditions but also a stress sensor for Nrf2 activation. Interestingly, fish and amphibians have two Keap1s (Keap1a and Keap1b), of which Keap1b is the ortholog of mammalian Keap1. Keap1a, on the other hand, is a gene found only in fish and amphibians, having been lost during the evolution to amniotes. We have previously shown that keap1b-knockout zebrafish have increased Nrf2 activity and reduced response to certain Nrf2-activating compounds but that they grow normally to adulthood. This may be because the remaining keap1a suppresses the hyperactivation of Nrf2, which is responsible for the post-natal lethality of Keap1-knockout mice. In this study, we analyzed keap1a;keap1b-double-knockout zebrafish to test this hypothesis. We found that keap1a;keap1b-double-knockout zebrafish, like Keap1-knockout mice, showed eating defects and were lethal within a week of hatching. Genetic introduction of the Nrf2 mutation rescued both the eating defects and the larval lethality, indicating that Nrf2 hyperactivation is the cause. However, unlike Keap1-knockout mice, keap1a;keap1b-double-knockout zebrafish showed no physical blockage of the food pathway; moreover, the cause of death was not directly related to eating defects. RNA-sequencing analysis revealed that keap1a;keap1b-double-knockout larvae showed extraordinarily high expression of known Nrf2-target genes as well as decreased expression of visual cycle genes. Finally, trigonelline or brusatol partially rescued the lethality of keap1a;keap1b-double-knockout larvae, suggesting that they can serve as an in vivo evaluation system for Nrf2-inhibiting compounds.

Sleep Quality and Poor Sleep-related Factors Among Healthcare Workers During the COVID-19 Pandemic in Vietnam.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic. METHODS: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher. RESULTS: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95). CONCLUSIONS: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.

Generation and characterization of keap1a- and keap1b-knockout zebrafish.

The Keap1-Nrf2 pathway is an evolutionarily conserved mechanism that protects cells from oxidative stress and electrophiles. Under homeostatic conditions, Keap1 interacts with Nrf2 and leads to its rapid proteasomal degradation, but when cells are exposed to oxidative stress/electrophiles, Keap1 senses them, resulting in an improper Keap1-Nrf2 interaction and Nrf2 stabilization. Keap1 is therefore considered both an "inhibitor" of and "stress sensor" for Nrf2 activation. Interestingly, fish and amphibians have two Keap1s (Keap1a and Keap1b), while there is only one in mammals, birds and reptiles. A phylogenetic analysis suggested that mammalian Keap1 is an ortholog of fish Keap1b, not Keap1a. In this study, we investigated the differences and similarities between Keap1a and Keap1b using zebrafish genetics. We generated zebrafish knockout lines of keap1a and keap1b. Homozygous mutants of both knockout lines were viable and fertile. In both mutant larvae, the basal expression of Nrf2 target genes and antioxidant activity were up-regulated in an Nrf2-dependent manner, suggesting that both Keap1a and Keap1b can function as Nrf2 inhibitors. We also analyzed the effects of the Nrf2 activator sulforaphane in these mutants and found that keap1a-, but not keap1b-, knockout larvae responded to sulforaphane, suggesting that the stress/chemical-sensing abilities of the two Keap1s are different.

Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish.

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7) and 2 enzymes involved in glucose metabolism (pgd and fbp1a) were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates.

Procarcinogens - Determination and Evaluation by Yeast-Based Biosensor Transformed with Plasmids Incorporating RAD54 Reporter Construct and Cytochrome P450 Genes.

In Vietnam, a great number of toxic substances, including carcinogens and procarcinogens, from industrial and agricultural activities, food production, and healthcare services are daily released into the environment. In the present study, we report the development of novel yeast-based biosensor systems to determine both genotoxic carcinogens and procarcinogens by cotransformation with two plasmids. One plasmid is carrying human CPR and CYP (CYP3A4, CYP2B6, or CYP2D6) genes, while the other contains the RAD54-GFP reporter construct. The three resulting coexpression systems bearing both CPR-CYP and RAD54-GFP expression cassettes were designated as CYP3A4/CYP2B6/CYP2D6 + RAD54 systems, respectively and used to detect and evaluate the genotoxic potential of carcinogens and procarcinogens by selective activation and induction of both CPR-CYP and RAD54-GFP expression cassettes in response to DNA damage. Procarcinogens were shown to be predominantly, moderately or not bioactivated by one of the CYP enzymes and thus selectively detected by the specific coexpression system. Aflatoxin B1 and benzo(a)pyrene were predominantly detected by the CYP3A4 + RAD54 system, while N-nitrosodimethylamine only moderately activated the CYP2B6 + RAD54 reporter system and none of them was identified by the CYP2D6 + RAD54 system. In contrast, the genotoxic carcinogen, methyl methanesulfonate, was detected by all systems. Our yeast-reporter system can be performed in 384-well microplates to provide efficient genotoxicity testing to identify various carcinogenic compounds and reduce chemical consumption to about 53% as compared with existing 96-well genotoxicity bioassays. In association with a liquid handling robot, this platform enables rapid, cost-effective, and high-throughput screening of numerous analytes in a fully automated and continuous manner without the need for user interaction.

Subsphaerolaimus minor sp. n. and Micromicron cephalatum Cobb, 1920 (Nematoda) from the Yen River Estuary of Vietnam.

Two nematode species found in Yen River Estuary of Vietnam are described and illustrated. Subsphaerolaimus minor sp. n. is similar to S. lamasus Gerlach, 1956, but differs from it in the shorter body, comparatively shorter pharynx and shorter cephalic setae. A pictorial key for determination of valid species in the genus Subsphaerolaimus Lorenzen, 1978 is given. Micromicron cephalatum Cobb, 1920 is redescribed and reillustrated based on numerous males and females. The genus Micromicron Cobb, 1920 is confirmed as a valid genus with type and only species, M. cephalatum Cobb, 1920.

Electromechanical wave imaging for arrhythmias.

Electromechanical wave imaging (EWI) is a novel ultrasound-based imaging modality for mapping of the electromechanical wave (EW), i.e. the transient deformations occurring in immediate response to the electrical activation. The correlation between the EW and the electrical activation has been established in prior studies. However, the methods used previously to map the EW required the reconstruction of images over multiple cardiac cycles, precluding the application of EWI for non-periodic arrhythmias such as fibrillation. In this study, new imaging sequences are developed and applied based on flash- and wide-beam emissions to image the entire heart at very high frame rates (2000 fps) during free breathing in a single heartbeat. The methods are first validated by imaging the heart of an open-chest canine while simultaneously mapping the electrical activation using a 64-electrode basket catheter. Feasibility is then assessed by imaging the atria and ventricles of closed-chest, conscious canines during sinus rhythm and during right-ventricular pacing following atrio-ventricular dissociation, i.e., during a non-periodic rhythm. The EW was validated against electrode measurements in the open-chest case, and followed the expected electrical propagation pattern in the closed-chest setting. These results indicate that EWI can be used for the characterization of non-periodic arrhythmias in conditions similar to the clinical setting, in a single heartbeat, and during free breathing.