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In contemporary education, game-based learning (GBL) has become a captivating instructional method applied across various academic subjects, including mathematics. The utilization of online GBL in mathematics education constitutes a segment of the activities that mathematics educators can employ during their lessons to teach students and enhance their educational progress. The primary goal of this study was to examine recent research endeavors involving the use of online GBL in mathematics education for Generation Z cohort. To achieve this objective, a systematic review (SR) was carried out to investigate the types of online games employed, analyze previous research methodologies, and explore the educational contexts relevant to mathematics education that align with the needs of Generation Z. An SR process was conducted to gather relevant articles from three databases, namely Science Direct, Scopus, and Springer. Full-text articles were meticulously assessed based on predetermined eligibility criteria. The review revealed many online games suitable for mathematics education, including Augmented Reality, Digital Inquiry Game, E-Rebuild, Math-Island Game, NanoRoboMath, Quizizz, and Wuzzit Trouble. The incorporation of online games in mathematics education offers numerous advantages.

Abstract Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O2) and hydrogen peroxide (H2O2) through the computational simulation and experiments. Considering the short of O2 and H2O2 at the tumor site, we utilize calcium peroxide (CaO2) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O2 provided by CaO2 can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO2-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.

Abstract Despite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.

Traditional high-temperature sterilization of chicken soup can easily lead to adverse effects on product quality and result in a short storage period, which fails to meet the demands for modern convenience and nutritional consumption. In this study, ultra high pressure combined with partial freezing multi-fence technology was applied to preserve chicken soup, aiming to extend its storage period, reduce nutritional loss, and enhance overall quality. The quality of chicken soup was compared and analyzed using pasteurization, high temperature and high pressure treatment, as well as ultra high pressure (400 MPa for 15 min) combined with partial freezing (−2.5 ℃) storage. Freshness indicators (total bacterial count, fat oxidation, protein oxidation), flavor-related parameters (soluble protein content, free amino acid content, inosine acid content, volatile substances), sensory evaluation scores were used to investigate the effects of these three sterilization methods combined with partial freezing technology on the storage stability and freshness of chicken soup. Furthermore, the impact of ultra high pressure combined with partial freezing technology on changes in the quality attributes of chicken soup during storage was explored. Results demonstrated that the group treated with ultra high pressure combined with partial freezing exhibited favorable microbial load values (with a total colony count only at 2.11 log CFU/mL) after being stored for 100 days. Malondialdehyde (MDA) values differed among the three groups subjected to different treatment methods: Higher MDA levels were observed in the high temperature and high pressure group compared to both pasteurization group and ultra high pressure group. Consistently lower MDA values were found in the ultra high pressure group throughout storage stages when compared against other two groups. The soluble protein content in the ultra high pressure group remained consistently higher at 5.22 mg/mL than that in other two groups. Additionally, the ultra high pressure group exhibited significantly higher levels of flavor substances (phenylalanine, proline, inosine, octanaldehyde, 2-heptanone, 2-amylfuran) compared to the other two groups. These findings demonstrate that the combination of ultra high pressure and partial freezing is more effective than traditional heat treatment in minimizing nutrient loss, preserving sensory quality of chicken soup, and extending shelf life.

During the COVID-19 pandemic, educational institutions around the world have closed, affecting more than 60% of students and causing massive disruption to the education system. Taiwan is no exception. For this sudden and dramatic change, teachers, students, and parents all confront significant challenges. In order to make specific suggestions for improvement, the study aims to explore the current state of e-learning in Taiwan and to understand the difficulties faced by teachers, parents, and students. The study conducted in-depth interviews with 20 teachers, 12 parents, and 24 students. The research results show that in New Taipei City, there are barely any online courses for grades 1 and 2, blended learning is mainly for grades 3 and 4, and synchronous e-learning is designed for grades 5 and 6. The main challenges in adopting e-learning in primary schools include, as follows: (i) Teachers, parents, and students are unfamiliar with the user interface of the e-learning platform; (ii) Insufficient hardware and software equipment at home; (iii) Teachers cannot take care of special students; (iv) Communication between teachers and parents is not smooth; (v) Difficulty in assessing learning progress online; and (vi) Students are easily distracted from their studies. Based on the above research results, the researchers put forward specific suggestions for future online teaching practices.

Abstract Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive. ATP6AP2, an accessory subunit of V-ATPase, plays important roles in multiple cell types/organs and multiple signaling pathways. However, little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation. Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions. Conditionally knocking out (CKO) ATP6AP2 in the OB-lineage cells (Atp6ap2 Ocn-Cre ) reduced trabecular, but not cortical, bone formation and bone mass. Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs, but not osteocytes. Additional in vitro and in vivo studies revealed impaired β-catenin signaling in ATP6AP2-KO BMSCs and OBs, but not osteocytes, under both basal and Wnt stimulated conditions, although LRP5 was decreased in ATP6AP2-KO osteocytes, but not BMSCs. Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression of β-catenin phosphorylation, but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane, thus preventing their degradation. Expression of active β-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs. Taken together, these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability, and thus regulating β-catenin levels, demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

Abstract Background Transport accidents are one of the leading causes of child morbidity and mortality worldwide and represent a significant public health burden. This study aimed to investigate the hospitalization information and burden of pediatric inpatients in transport accidents in China. Methods In this study, we collected the cover page of the medical records of pediatric inpatients in transport accidents using the Futang Research Center of Pediatric Development (FRCPD) database from January 1, 2016 to December 31, 2021. Then, we extracted the epidemiological characteristics, including demographic characteristics, cases distribution, disease information, and hospitalization burden. Results Among 36,455 included inpatients, males, aged 1–3 years, East China, July were dominant in different subgroups. In transport accidents, pedestrians were the most frequently type of injury (65.69%). Of all known lesions, craniocerebral/nerve injury was the more common results in pediatric inpatients in transport accidents (33.93%). In addition to pedal cyclists more susceptible to sport system injury, other types of injured person with transport accidents were mainly craniocerebral/nerve injury. In terms of the type of discharge, occupant of heavy transport vehicle or bus and people with craniocerebral/nerve injury had the highest mortality rate after hospitalization in all type and lesion of injured person groups, respectively. The largest hospitalization burden in the type of injured person was occupant of heavy transport vehicle or bus. Conclusions This study revealed that epidemiological characteristics and the main factor influencing the hospitalization information and burden of children with traffic accidents in China.

Utilizing excess vacancy to form effective solute clusters has been considered as a potential strategy to strengthen Al alloys. Herein, we designed a cryogenic submerged friction stir processing, by the one-step process in a short time, to realize the coexistence of grain refinement, high-density clusters, and nanoprecipitates, thus enhancing strength and ductility simultaneously. The atomic information showed the unique formation of high-density clusters (1 ∼ 2 nm), which was related to the strain-induced migration of solute atoms. This study may provide a new strategy for alloys with low alloying content that can be enhanced by forming solute clusters.

Increasing child engagement and improving social-communication (SC) and play skills for young children with autism spectrum disorder (ASD) may provide a foundation for future academic and social development; yet preschool practitioners may not have the resources to successfully identify and target these skills for all children in their classrooms. With intentional collaboration, applying evidence-based strategies accompanied by specific Advancing Social-communication and Play (ASAP) resources such as the play and SC hierarchies may help address this need, thus increasing engagement of all children in classroom learning opportunities.

Abstract Only microstructures are used to improve the sensitivity of iontronic pressure sensors. By modulating the compressive modulus, a breakthrough in the sensitivity of the iontronic pressure sensor is achieved. Furthermore, it allows for programmatic tailoring of sensor performance according to the requirements of different applications. Such a new strategy pushes the sensitivity up to a record‐high of 25 548.24 kPa−1 and expands the linear pressure range from 15 to 127 kPa. Additionally, the sensor demonstrates excellent mechanical stability over 10 000 compression‐release cycles. Based on this, a well‐controlled robotic hand that precisely tracks the pressure behavior inside a balloon to autonomously regulate the gripping angle is developed. This paves the way for the application of iontronic pressure sensors in precise sensing scenarios.

Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family and involved in embryonic development and cardiac repair. This study aimed to explore the role of FGF20 in cardiac hypertrophy and the underlying molecular mechanisms. FGF20 improved cardiac hypertrophy in vivo and in vitro. Furthermore, FGF20 increased expression of erythroblastic leukemia viral oncogene homolog 2 (ErbB2), which was negatively correlated with expression of the cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In addition, FGF20 effectively protected cardiomyocytes against apoptosis and oxidative stress. To further investigate whether protective effect of FGF20 is mediated by ErbB2, neonatal rat cardiomyocytes (NRCMs) were treated with lapatinib, an inhibitor of ErbB2. Lapatinib largely abrogated the anti-hypertrophic effect of FGF20, accompanied by increases in cardiomyocyte apoptosis and oxidative stress. In summary, this study reveals that FGF20 prevents cardiac hypertrophy by inhibiting apoptosis and oxidative stress via activating ErbB2 and may be a promising therapeutic strategy for cardiac hypertrophy.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.

Abstract Background Individuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS). Methods The present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits. Genetic correlation analysis was conducted between osteoarthritis and other traits through cross-trait bivariate linkage disequilibrium score regression. Subsequently, latent causal variable analysis was performed to explore the causal association when there was a significant genetic correlation. Genetic correlation and latent causal variable analysis were conducted on the Complex Traits Genomics Virtual Lab platform ( https://vl.genoma.io/ ). Results We found 133 unique phenotypes showing causal relationships with osteoarthritis. Our results confirmed several well-established risk factors of osteoarthritis, such as obesity, weight, BMI, and meniscus derangement. Additionally, our findings suggested putative causal links between osteoarthritis and multiple factors. Socioeconomic determinants such as occupational exposure to dust and diesel exhaust, extended work hours exceeding 40 per week, and unemployment status were implicated. Furthermore, our analysis revealed causal associations with cardiovascular and metabolic disorders, including heart failure, deep venous thrombosis, type 2 diabetes mellitus, and elevated cholesterol levels. Soft tissue and musculoskeletal disorders, such as hallux valgus, internal derangement of the knee, and spondylitis, were also identified to be causally related to osteoarthritis. The study also identified the putative causal associations of osteoarthritis with digestive and respiratory diseases, such as Barrett’s esophagus, esophagitis, and asthma, as well as psychiatric conditions including panic attacks and manic or hyperactive episodes. Additionally, we observed osteoarthritis causally related to pharmacological treatments, such as the use of antihypertensive medications, anti-asthmatic drugs, and antidepressants. Conclusion Our study uncovered a wide range of traits causally associated with osteoarthritis. Further studies are needed to validate and illustrate the detailed mechanism of those causal associations.

Abstract Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.

Low-fat conversion of high-fat products met consumers' pursuit of health, and was one of the future development directions of meat products. In this study, the effects of two forms of tea seed oil (TSO) and nano tea seed oil microcapsules (NTM) on the physical and chemical properties of pork mince products were investigated, with no tea seed oil fat replacing pork mince as the control group. The water retention, cooking yield, water distribution, texture, microstructure, and fat oxidation level of different fat replacing pork mince products were studied. The results showed that the addition of 50% and 70% NTM could improve the water retention ability of pork minced meat products caused by TSO replacement. The T21 relaxation time and proportion of the NTM replacement group were not significantly different from those of the non-replacement control group (P>0.05), while the proportion of non-flowable water in the TSO replacement group was significantly decreased (P

Abstract Background Culturally sensitive care has been identified as a best-practice approach for improving health outcomes. Hemodialysis patients require culturally sensitive care because it involves totally changing their previous life. The purpose of this study was to explore the subjective experiences of hemodialysis nurses in providing culturally sensitive care to hemodialysis patients. Methods A qualitative study was carried out in the hemodialysis center of a teaching hospital in northern Taiwan. Purposive sampling and semi-structured interview guidelines were employed to interview 23 hemodialysis nurses. The interviews were recorded and transcribed verbatim, and the resulting data were analyzed and summarized using content analysis by constant comparative methods. Results Hemodialysis nurses exhibited the characteristics for delivering culturally sensitive care, which comprised five aspects: finding the true meaning of the behavior of the participants, recognizing and honoring individual psychological states, culturally sensitive communication in line with patients’ values, customizing care content through cultural transformation strategies, and empowerment rather than prohibition. Conclusions The findings of this study on the culturally sensitive care provided by hemodialysis nurses can be utilized by nursing educators and administrators as a reference to develop and enhance the nursing education related to culturally sensitive care for hemodialysis professionals.

Abstract. Background:. Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers. Methods:. We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients' survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3). Results:. A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P

Although paternal age has been linked to certain psychiatric disorders, the nature of any causal relationship remains elusive. Here, we aimed to comprehensively assess the magnitude of a wide range of offsprings psychiatric risk conferred by paternal age, leveraging a pedigree inferred from covered-insurance relationship (accuracy >98%) in Taiwans single-payer compulsory insurance program. We also examined whether there is an independent role of paternal age and explored the potential effect of parental age difference. A total cohort of 7,264,788 individuals born between 1980 and 2018 were included; 5,572,232 with sibling(s) were selected for sibling-comparison analyses and 1,368,942 and 1,044,420 children with information of paternal-grandparents and maternal-grandparents, respectively, were selected for multi-generation analyses. Using inpatient/outpatient claims data (1997-2018), we identified schizophrenia, autism, bipolar disorder (BPD), attention deficit-hyperactivity disorder (ADHD), major depressive disorder (MDD), eating disorder (ED), substance use disorder (SUD), mental retardation (MR), tic disorder, obsessive-compulsive disorder (OCD), anxiety, and somatoform disorder. We identified suicides using death certificates. Logistic regression analysis was used to estimate the paternal/maternal/grand-paternal age association with psychiatric risk in the offspring. The total cohort and sibling-comparison cohort resulted in similar estimates. Paternal age had a U-shaped relationship with offsprings MDD, ED, SUD, and anxiety. A very young maternal age (25 years) was linearly associated with offsprings schizophrenia, autism, BPD, ADHD, MDD, ED, SUD, MR, OCD, anxiety, and suicide. Older grand-paternal age was linearly associated with offsprings schizophrenia, autism, ADHD, and MR. Dissimilar parental age was positively associated with offsprings ADHD, MDD, SUD, MR, anxiety, and suicide, and negatively associated with offsprings OCD. This comprehensive assessment provides solid evidence for the independent role of paternal age in psychiatric risk in the offspring and clarifies the significance of both early parenthood and delayed paternity.

With the rapid development of technology, online writing instruction (OWI) has become an integral part of all writing instruction. However, one of the challenges encountered by OWI instructors has been to select an appropriate online learning platform or learning management system (LMS) aligning with writing pedagogies. This study developed a small-scale fully online writing course -- a college-level English composition MOOC using Google Classroom, a free and easy-to-use online learning platform, to (a) explore the potential of using Google Classroom in teaching composition MOOCs and (b) examine students' learning effectiveness in the composition MOOC. Participants were 33 EFL students who learnt knowledge and skills needed to write a literature review assignment in this 6-week, theme-based composition MOOC. Results demonstrated that the composition MOOC was well received by the participants and was effective in teaching writing given that students made improvement on both knowledge of citation practices and final written product. Specifically, features of Google Classroom allowed teachers to create different types of learning materials, assignments, and assessment that make online writing courses engaging and interactive. Most importantly, its collaborative features, such as file sharing and the real-time communication technology, empowered teachers to give timely feedback and create communicative activities that writing pedagogies value, making Google Classroom a good platform for OWI.

Purpose: The purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. Methods: This study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values

Abstract Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel “two birds with one stone” technique for amplifying enzyme‐mediated tumor apoptosis and enzyme‐promoted metabolic clearance is proposed and achieved using GOx‐functionalized rhenium nanoclusters‐doped polypyrrole (Re@ReP‐G). Re@ReP‐G reduces ATP production while increasing H2O2 concentrations in the tumor microenvironment through GOx‐induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti‐apoptotic Bcl‐2 proteins, the upregulation of pro‐apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser‐induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, H2O2 catalyzes the conversion of rhenium nanoclusters in Re@ReP‐G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP‐G‐based “two birds with one stone” therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.