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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 This study aims to explore the expression profile of PANoptosis‐related genes (PRGs) and immune infiltration in Alzheimer's disease (AD). Based on the Gene Expression Omnibus database, this study investigated the differentially expressed PRGs and immune cell infiltration in AD and explored related molecular clusters. Gene set variation analysis (GSVA) was used to analyze the expression of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in different clusters. Weighted gene co‐expression network analysis was utilized to find co‐expressed gene modules and core genes in the network. By analyzing the intersection genes in random forest, support vector machine, generalized linear model, and extreme gradient boosting (XGB), the XGB model was determined. Eventually, the first five genes (Signal Transducer and Activator of Transcription 3, Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1B, Interleukin 4 Receptor, Chloride Intracellular Channel 1, TNF Receptor Superfamily Member 10B) in XGB model were selected as predictive genes. This research explored the relationship between PANoptosis and AD and established an XGB learning model to evaluate and screen key genes. At the same time, immune infiltration analysis showed that there were different immune infiltration expression profiles in AD.

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.

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.

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.

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.

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.

Protein binding to bile salts (BSs) reduces cholesterol levels, but the exact mechanism is unclear. In this study, we performed simulated gastrointestinal digestion of egg white protein hydrolysate (EWPHs) and included an unenzyme digestion group (CK) to investigate the changes in BSs binding capacity before and after digestion, as well as the relationship between egg white protein (EWP) structure and BSs binding capacity. In addition, peptidomics and molecular docking were used to clarify EWP's binding mechanism. We found that the BSs binding ability of EWPHs was slightly decreased after digestion, but significantly higher than that of the CK group and the digested CK group (D-CK). Particle size analysis and electrophoresis demonstrated that smaller particles and lower molecular weights exhibited enhanced binding capacity to BSs. Fourier Transform infrared spectroscopy (FTIR) results revealed that a disordered structure favored BS binding ability enhancement. Peptides FVLPM and GGGVW displayed hypocholesterolemic efficacy.

Chemotherapy and radiotherapy in combination with sequence regimens are recognized as the current major strategy for suppressing postoperative tumor recurrence. However, systemic side effects and poor in-field cooperation of the two therapies seriously impair the therapeutic efficacy of patients. The combination of brachytherapy and chemotherapy through innovative biomaterials has proven to be an important strategy to achieve synergistic effects of radiotherapy and chemotherapy in-time and in-field. However, for postoperative chemoradiotherapy, as far as we know, there are few relevant reports. Herein, an injectable pH-responsive polypeptide-polysaccharide depot for concurrent in situ chemotherapy and brachytherapy was developed by encapsulating vincristine into iodine-125 radionuclide labeled hydrogel. This depot hydrogel was prepared by dynamic covalent bonds of Schiff base between aldehydeated hyaluronic acid and polyethylene glycol-polytyrosine. Therefore, this hydrogel enables smart response to tumor acidic microenvironment, rapid release of the encapsulated vincristine and an enhanced uptake effect by tumor cells, which significantly reduces IC50 of vincristine for the anaplasia Wilms' tumor cells in vitro. This depot hydrogel shows excellent stability and biocompatibility, and maintains for 14 days after in situ injection in a postoperative model of anaplasia Wilms' tumor. After injection at the cavity of tumor excision, responsively-released vincristine and the radioactive iodine-125 exerted excellent killing effects on residual tumor cells, inhibiting tumor relapse and liver metastasis of the recurrent tumor. Hence, this study proposes an effective therapeutic strategy for inhibiting anaplasia Wilms’ tumor recurrence, which provides a new approach for concurrent postoperative chemo-radiotherapy and a desirable guidance in regimen execution of pediatric refractory tumors.