One of the biggest challenges for EFL (English as Foreign Language) students to learn English is the lack of practicing environments. Although language researchers have attempted to conduct flipped ...classrooms to increase the practicing time in class, EFL students generally have difficulties interacting with peers and teachers in English in class. The advancement of Artificial Intelligence (AI) provides an opportunity to address this problem. With AI technologies, computer systems, in particular in the form of AI chatbots, are able to identify the meanings of users' statements and make responses accordingly. In the research design, AI-based chatbots were employed in the in-class and out-of-class activities for facilitating the students' speaking performance and interactions during the learning process in a university flipped English speaking classroom. The experimental results show that the mind map-guided AI chatbot approach (MM-AI) promoted the students' English speaking performances more than did the conventional AI chatbot approach (C-AI). Moreover, the MM-AI also promoted the students' learning performance and organized the interaction between the robots and humans more than the C-AI did. The findings could be a valuable reference for language educators and researchers who intend to conduct AI-supported flipped classrooms in language learning.
Flipped classrooms have been widely adopted and discussed by school teachers and researchers in the past decade. However, few studies have been conducted to formally evaluate the effectiveness of ...flipped classrooms in terms of improving EFL students' English oral presentation, not to mention investigating factors affecting their flipped learning outcomes. In this study, an online community-based flipped learning approach was proposed for an EFL oral presentation course; moreover, a learning analytics approach was used to analyze factors affecting the students' oral presentation outcomes. An 18-week research design was implemented with the online community-based flipped classroom using Facebook as the platform for facilitating and recording peer-to-peer interactions during the flipped learning process. In addition, the students' learning performance and perceptions were collected in 3 learning stages during the 18 weeks. The experimental results reveal positive effects of the online community-based flipped instruction over the conventional video-based instruction. That is, first, the online community-based flipped instruction using mobile devices can enhance students' English oral performance. Moreover, it was found that the high improvers had a significantly higher frequency of online participation, as well as more interactive behaviors and greater satisfaction with the flipped classroom than the low improvers. These results imply that the online community flipped classroom could not only provide learning materials and out-of-class learning for students, but could also help them become more responsible and autonomous in their learning and communication. These findings could be valuable references for those who intend to conduct effective flipped classrooms with an online community to facilitate students' before-class learning participation and to improve their in-class learning performance.
Ferroptosis is a specialized iron-dependent cell death that is associated with lethal lipid peroxidation. Modulation of ferroptosis may have therapeutic potential since it has been implicated in ...various human diseases as well as potential antitumor activities. However, much remains unknown about the underlying mechanisms and genetic determinants of ferroptosis. Given the critical role of kinases in most biological processes and the availability of various kinase inhibitors, we sought to systemically identify kinases essential for ferroptosis. We performed a forward genetic-based kinome screen against ferroptosis in MDA-MB-231 cells triggered by cystine deprivation. This screen identified 34 essential kinases involved in TNFα and NF-kB signaling. Unexpectedly, the DNA damage response serine/threonine kinase ATM (mutated in Ataxia-Telangiectasia) was found to be essential for ferroptosis. The pharmacological or genetic inhibition of ATM consistently rescued multiple cancer cells from ferroptosis triggered by cystine deprivation or erastin. Instead of the canonical DNA damage pathways, ATM inhibition rescued ferroptosis by increasing the expression of iron regulators involved in iron storage (ferritin heavy and light chain, FTH1 and FTL) and export (ferroportin, FPN1). The coordinated changes of these iron regulators during ATM inhibition resulted in a lowering of labile iron and prevented the iron-dependent ferroptosis. Furthermore, we found that ATM inhibition enhanced the nuclear translocation of metal-regulatory transcription factor 1 (MTF1), responsible for regulating expression of Ferritin/FPN1 and ferroptosis protection. Genetic depletion of MTF-1 abolished the regulation of iron-regulatory elements by ATM and resensitized the cells to ferroptosis. Together, we have identified an unexpected ATM-MTF1-Ferritin/FPN1 regulatory axis as novel determinants of ferroptosis through regulating labile iron levels.
Creation of sizable subintima during intervention for chronic total occlusions (CTO) could lead to the key selection preference of metallic stents rather than bioresorbable vascular scaffolds (BVS) ...and then possibly deviate the outcome comparisons in real-world studies. By including recanalized CTO with true lumen tracking, we tested if any selection preference remained and compared the outcomes between everolimus-eluting stent (EES) and BVS implantation.Among 211 consecutive CTO interventions with true lumen tracking from August 2014 to April 2018 when BVS was available, we compared the clinical and interventional features between 28 patients with BVS and 77 patients with EES implantation. With propensity score matching and a median follow-up of 50.5 (37.3-60.3) months, we further assessed 25 patients with BVS and 25 with EES for target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target lesion revascularization).Multivariate analyses showed that BVS was still favored in the presence of LAD CTO (odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.0-11.7) and an average scaffold/stent size ≥ 3 mm (OR = 10.5, 95% CI = 3.0-37.3). EES was preferred for lesions with a J-CTO score ≥ 3 (OR = 19.3, 95% CI = 3.4-110.8) and multivessel intervention necessary at index procedure (OR = 11.3, 95% CI = 1.9-67.3). With matched comparisons, the TVF-free survival of EES was better than that of BVS for CTO recanalization (P = 0.049 by log-rank test) at long-term follow-up.Even with true lumen tracking techniques, selection bias remained substantial when determining either device for CTO implantation. The matched comparison of outcomes suggested the unfavorable longer-term impacts of the first generation of BVS on CTO lesions.
With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a ...Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl⁻) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium. To test the hypothesis that WNK4 senses the intracellular concentration of Cl⁻ physiologically, we generated knockin mice carrying Cl⁻-insensitive mutant WNK4. These mice displayed hypertension, hyperkalemia, hyperactive NCC, and other features fully recapitulating human and mouse models of PHAII caused by gain-of-function WNK4. Lowering plasma potassium levels by dietary potassium restriction increased NCC activity in wild-type, but not in knockin, mice. NCC activity in knockin mice can be further enhanced by the administration of norepinephrine, a known activator of NCC. Raising plasma potassium by oral gavage of potassium inactivated NCC within 1 hour in wild-type mice, but had no effect in knockin mice. The results provide compelling support for the notion that WNK4 is a bona fide physiological intracellular Cl⁻ sensor and that Cl⁻ regulation of WNK4 underlies the mechanism of regulation of NCC by extracellular potassium.
Despite recent advances, the poor outcomes in renal cell carcinoma (RCC) suggest novel therapeutics are needed. Ferroptosis is a form of regulated cell death, which may have therapeutic potential ...toward RCC; however, much remains unknown about the determinants of ferroptosis susceptibility. We found that ferroptosis susceptibility is highly influenced by cell density and confluency. Because cell density regulates the Hippo-YAP/TAZ pathway, we investigated the roles of the Hippo pathway effectors in ferroptosis. TAZ is abundantly expressed in RCC and undergoes density-dependent nuclear or cytosolic translocation. TAZ removal confers ferroptosis resistance, whereas overexpression of TAZS89A sensitizes cells to ferroptosis. Furthermore, TAZ regulates the expression of Epithelial Membrane Protein 1 (EMP1), which, in turn, induces the expression of nicotinamide adenine dinucleotide phosphate (NADPH) Oxidase 4 (NOX4), a renal-enriched reactive oxygen species (ROS)-generating enzyme essential for ferroptosis. These findings reveal that cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for RCC and other TAZ-activated tumors.
Display omitted
•Ferroptosis susceptibility can be affected by cell density•TAZ is activated in renal cell carcinoma cell lines and early-passage tumor cells•The activation status of TAZ regulates the susceptibility of RCC to ferroptosis•TAZ regulates ferroptosis through affecting EMP1-NOX4 expression
Yang et al. show that ferroptosis sensitivity in renal cell carcinoma (RCC) is regulated by cell density through the TAZ-EMP1-NOX4 pathway. These findings reveal TAZ as a genetic determinant of ferroptosis in RCC. In addition, ferroptosis may hold therapeutic potential for RCC and other TAZ-activated tumors.
English business writing is an important and challenging course for English as Foreign Language (EFL) students since it is not only related to English writing skills, but also to business knowledge. ...Context-game-based learning seems to be a good approach to situating students in a meaningful and interesting practicing environment, which could improve their learning motivation and interest. However, without interacting with the teacher and peers, the effectiveness of game-based learning could be limited. In this study, a flipped contextual game-based learning approach was proposed to cope with this problem: moreover, a mixed methods research approach was used to analyze the writing performance, writing errors, and reflective content of the students who learned with the proposed approach and those learning with conventional contextual game-based learning. The experimental results revealed that the flipped contextual game-based instruction was able to enhance the students' English writing performance. It was also found that those students with the flipped learning approach had fewer writing errors than those learning with the conventional approach. Moreover, by analyzing the students' reflective content, the benefits and challenges of flipping the classroom are reported. These findings could be valuable references for those who intend to conduct effective flipped contextual game-based learning with learning management systems to motivate students' game-based learning and to improve their language learning performance.
To situate students in authentic English learning and practicing contexts so as to facilitate their writing performance, in this study, a mind mapping-based contextual gaming approach was proposed. A ...quasi-experiment was implemented by recruiting two English tourism classes of students from a university of science and technology in northern Taiwan. One class was scheduled to learn with the proposed approach, and the other was arranged to learn with the conventional contextual gaming approach. The students’ writing performance, learning perceptions and generative uses were measured to evaluate the effectiveness of the proposed approach. It was found that, compared to the control group students; the experimental group students who learned with the proposed learning approach had better writing performance in the aspects of fluency and elaboration with a small effect size. Additionally, it was found that most students considered the game to be beneficial and interesting, and they were in favor of the mind mapping strategy. Moreover, it was also found that the proposed learning approach is more likely to help students produce positive thoughts and feelings, generate diverse ideas, create a sense of exoticism and express actions or intent of actions. Finally, the limitations of the study and some suggestions for improvement of this proposed gaming learning environment and approaches are provided.
•A mind mapping-based contextual gaming approach was proposed.•An experiment was conducted to evaluate the performance of the proposed approach.•The approach has been applied to an English tourism course.•The approach improved the students' writing performance and language use.•Some suggestions for improvement of this proposed approach are provided.
Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, ...and insulin sensitivity in overweight/obese children.
We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits.
Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%).
Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.
Causal analysis largely influences the effectiveness of decision-making and the productivity of actions. The complex relationship between cause and effect as well as the fuzzy nature of human life ...make the casual analysis difficult. In this paper, we develop a fuzzy DEMATEL method for group decision-making to gather group ideas and analyze the cause–effect relationship of complex problems in fuzzy environments. Procedures of the fuzzy DEMATEL method are then proposed. Using the fuzzy DEMATEL procedures, the involved criteria of a system (or subsystem) are separated into the cause and effect groups for helping decision-makers focus on those criteria that provide great influence. An empirical study applies the proposed fuzzy DEMATEL method to the R&D project selection of a Taiwanese company. The result shows that, within the cause group, the criterion of “probability of technical success” is the most important factor for R&D project selection, whereas the “strategic fit” and “potential size of market” have the best effect on the other criteria. By contrast, the “net present value” is the most easily improved of the effect group criteria.
PDF
