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Abstract Background Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. Methods Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. Results RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. Conclusions Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.

The stable and efficient operation of rail transit networks (RTNs) is critical for the integrated development of metropolitan areas. However, numerous studies have indicated that RTNs are prone to large-scale cascading failures when subjected to disturbances. To address the limitations of traditional cascading failure models, this paper proposes an innovative cascading failure model for metropolitan areas RTNs, which incorporates nonlinear load fluctuations and the bounded rationality of passengers. This model aims to capture the cascading failure characteristics of RTNs with chaotic properties under 12 combination strategies. A single- and dual-parameter coupling analysis of chaotic evolution parameters and prospect theory parameters are conducted. Taking the RTN in the Chengdu metropolitan area as an example, both the static characteristics and cascading failure features of the network are analyzed. The findings reveal the following: (i) the RTN is a assortativity network and lacks small-world and scale-free properties. (ii) During network disturbances, a higher level of passenger familiarity with the network increases the likelihood of large-scale cascading failures. (iii) When passengers tend to avoid risks, stations with higher carrying capacity are more prone to failures. This study holds significant implications for ensuring the stable and reliable operation of rail transit systems within metropolitan areas.

Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L−1) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of Rhodococcus, Legionella, and Citrobacter) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry.

For the purpose of researching the rules of combustion heat release, ammonium phosphate dry powder extinguishing agent and water-based fire extinguishing agent were utilized before and after the class A fire common wood stack ignition fuel and class B fire anhydrous ethanol ignition fuel fire extinguishing. For wood stack fire, 0.5A wood stack was used for blank combustion test, and the pan fire ignition method for the same type and scale of wood stack fire extinguishing experiment. For absolute ethanol fire, fire suppression was studied using a 13B scale. The change characteristics of the combustion field before and after action of the dry powder extinguishing agent and water system extinguishing agent were measured by thermocouple, heat flow meter and digital camera. The findings of the experiment demonstrated that in the combustion experiment of wood stack, the temperature of 0.5A wood stack of the blank group could reach 800 °C, and the temperature reduction rate of free combustion was 2.62 °C/s. It took an average of 36.5s and 2.25 kg of ammonium phosphate dry powder to put out the fire，and the temperature reduction rate was 4.18 °C/s. The average amount of water-based extinguishing agent used to extinguish a fire was 1.21 kg, yet the average time to do so was just 12.5 s, and the average rate of temperature drop was 10.14 °C/s. In the experiment where an ethanol pool fire was being burned, the typical amount of water-based fire extinguishing chemical used was 3.44 kg, and the typical extinguishing time was 18 s, the maximum temperature drop rate could reach 35.6 °C/s in the initial stage of fire extinguishing, despite the fact that the dry powder fire extinguisher containing ammonium phosphate was used, the fire was not properly controlled.

Platelet extracellular vesicles (PEVs) are an emerging delivery vehi for anticancer drugs due to their ability to target and remain in the tumor microenvironment. However, there is still a lack of understanding regarding yields, safety, drug loading efficiencies, and efficacy of PEVs. In this study, various methods were compared to generate PEVs from clinical-grade platelets, and their properties were examined as vehicles for doxorubicin (DOX). Sonication and extrusion produced the most PEVs, with means of 496 and 493 PEVs per platelet (PLT), respectively, compared to 145 and 33 by freeze/thaw and incubation, respectively. The PEVs were loaded with DOX through incubation and purified by chromatography. The size and concentration of the PEVs and PEV-DOX were analyzed using dynamic light scattering and nanoparticle tracking analysis. The results showed that the population sizes and concentrations of PEVs and PEV-DOX were in the ranges of 120–150 nm and 1.2–6.2 × 1011 particles/mL for all preparations. The loading of DOX determined using fluorospectrometry was found to be 2.1 × 106, 1.7 × 106, and 0.9 × 106 molecules/EV using freeze/thaw, extrusion, and sonication, respectively. The internalization of PEVs was determined to occur through clathrin-mediated endocytosis. PEV-DOX were more efficiently taken up by MDA-MB-231 breast cancer cells compared to MCF7/ADR breast cancer cells and NIH/3T3 cells. DOX-PEVs showed higher anticancer activity against MDA-MB-231 cells than against MCF7/ADR or NIH/3T3 cells and better than acommercial liposomal DOX formulation. In conclusion, this study demonstrates that PEVs generated by PLTs using extrusion, freeze/thaw, or sonication can efficiently load DOX and kill breast cancer cells, providing a promising strategy for further evaluation in preclinical animal models. The study findings suggest that sonication and extrusion are the most efficient methods to generate PEVs and that PEVs loaded with DOX exhibit significant anticancer activity against MDA-MB-231 breast cancer cells.

The use of antibiotics in ornamental fish is not regulated, as they are not intended for human consumption. Although antibiotic resistant bacteria have been detected in ornamental fish worldwide, there have been no studies to look at the situation in Hong Kong. Therefore, the present study was conducted to investigate the use of antibiotics in ornamental fish. Ornamental fish were purchased from five local pet fish shops and the antibiotics in carriage water were quantified using liquid chromatography tandem mass spectrometry. Moreover, Aeromonas and Pseudomonas spp. present in carriage water were isolated and their minimum inhibitory concentrations against selected antibiotics were determined. Results indicated that among the twenty antibiotics screened, doxycycline (0.0155–0.0836 µg L−1), oxytetracycline (0.0102–29.0 µg L−1), tetracycline (0.0350–0.244 µg L−1), enrofloxacin (0.00107–0.247 µg L−1), and oxalinic acid (n.d.−0.514 µg L−1) were detected in all sampled shops. Additionally, MIC results revealed that some of the Aeromonas and Pseudomonas spp. isolates were highly resistant to all antibiotics selected. Our findings confirmed that multiple antibiotics are being used in ornamental fish and the associated bacteria are resistant to selected antibiotics, suggesting that this could be a significant transmission route of antibiotic resistant bacteria to household indoor environments.

As an alternative strategy for cancer treatment, the combination of cancer nanomedicine and immunotherapy is promising with regard to efficacy and safety; however, precise modulation of the activation of antitumor immunity remains challenging. Therefore, the aim of the present study was to describe an intelligent nanocomposite polymer immunomodulator, drug-free polypyrrole-polyethyleneimine nanozyme (PPY-PEI NZ), which responds to the B-cell lymphoma tumor microenvironment, for precision cancer immunotherapy. Earlier engulfment of PPY-PEI NZs in an endocytosis-dependent manner resulted in rapid binding in four different types of B-cell lymphoma cells. The PPY-PEI NZ effectively suppressed B cell colony-like growth in vitro accompanied by cytotoxicity via apoptosis induction. During PPY-PEI NZ-induced cell death, mitochondrial swelling, loss of mitochondrial transmembrane potential (MTP), downregulation of antiapoptotic proteins, and caspase-dependent apoptosis were observed. Deregulated AKT and ERK signaling contributed to glycogen synthase kinase-3-regulated cell apoptosis following deregulation of Mcl-1 and MTP loss. Additionally, PPY-PEI NZs induced lysosomal membrane permeabilization while inhibiting endosomal acidification, partly protecting cells from lysosomal apoptosis. PPY-PEI NZs selectively bound and eliminated exogenous malignant B cells in a mixed culture system with healthy leukocytes ex vivo. While PPY-PEI NZs showed no cytotoxicity in wild-type mice, they provided long-term and efficient inhibition of the growth of B-cell lymphoma-driven nodules in a subcutaneous xenograft model. This study explores a potential PPY-PEI NZ-based anticancer agent against B-cell lymphoma.

This study examines the relationship between EFL students' noticing and three written feedback strategies. The convenience sampling method was adopted and four intact classes were randomly assigned into four groups: the model, the error correction, the reformulation, and the control groups. After the completion of picture-cued writing tasks as pretests, three treatment conditions and a noticing log were employed in the respective comparative activities. Focus group interviews were for triangulating the data collected from the log. There was a two-to-four-week interval between the posttest and the delayed posttest to obtain the feedback strategies' short- and long-term effects. An analytical scale was adopted to measure students' writing performance. Johnson Neyman analyses showed a significant difference among the three experimental groups in both posttests as well as that between the reformulation, the error correction, and the control groups in the posttest. Students in the reformulation and the error correction groups reported noticing grammatical problems. Those in the model group declared noticing their inability to develop ideas and describe details. Further analysis showed that learners' noticing contributed to the enhancement of content, grammar, organization, punctuation, and lexis in the model and the error correction groups.pun

This article discusses how a new APRS service-learning model was implemented in a new service-learning project in the traditional Chinese medicine (TCM) orthopedics curriculums at three Hong Kong institutions. The APRS model adopting flipped learning approach consists of four cyclic stages, including Application, Practice, Reflection and Self-regulated learning. Qualitative and quantitative findings in this study reveal that TCM students gained confidence in applying discipline knowledge/skills and improved in various areas, including cross-cultural competence, communication, problem-solving and collaboration. Drawing evidence from this study, possible factors contributing to positive impacts on student learning in the APRS model are the "strong connectivity" (including clear alignment with programme, profession, institutional missions and traditional Chinese philosophy "xiushen"), "reinforced motivation" (student autonomy and buy in) and "structured organisation" (strong network among participating parties and use of a centralised electronic platform). The APRS service-learning model is a culture-based approach helping students reconnect Confucian "xiushen" to the discipline knowledge and the real-life application in the Hong Kong context. This model may also be applicable to other Asian contexts where the Confucian culture prevails.

The blood–brain barrier (BBB) is a highly selective cellular barrier that tightly controls the microenvironment of the central nervous system to restrict the passage of substances, which is a primary challenge in delivering therapeutic drugs to treat brain diseases. This study aimed to develop simple surface modifications of mesoporous silica nanoparticles (MSNs) without external stimuli or receptor protein conjugation, which exhibited a critical surface charge and size allowing them to cross the BBB. A series of MSNs with various charges and two different sizes of 50 and 200 nm were synthesized, which showed a uniform mesoporous structure with various surface zeta potentials ranging from +42.3 to −51.6 mV. Confocal microscopic results showed that 50 nm of strongly negatively charged N4-RMSN50@PEG/THPMP (∼−40 mV) could be significantly observed outside blood vessels of the brain in Tg(zfli1:EGFP) transgenic zebrafish embryos superior to the other negatively charged MSNs. However, very few positively charged MSNs were found in the brain, indicating that negatively charged MSNs could successfully penetrate the BBB. The data were confirmed by high-resolution images of 3D deconvoluted confocal microscopy and two-photon microscopy and zebrafish brain tissue sections. In addition, while increasing the size to 200 nm but maintaining the similar negative charge (∼40 mV), MSNs could not be detected in the brain of zebrafish, suggesting that transport across the BBB based on MSNs occurred in charge- and size-dependent manners. No obvious cytotoxicity was observed in the CTX-TNA2 astrocyte cell line and U87-MG glioma cell line treated with MSNs. After doxorubicin (Dox) loading, N4-RMSN50@PEG/THPMP/Dox enabled drug delivery and pH-responsive release. The toxicity assay showed that N4-RMSN50@PEG/THPMP could reduce Dox release, resulting in the increase of the survival rate in zebrafish. Flow cytometry demonstrated N4-RMSN50@PEG/THPMP had few cellular uptakes. Protein corona analysis revealed three transporter proteins, such as afamin, apolipoprotein E, and basigin, could contribute to BBB penetration, validating the possible mechanism of N4-RMSN50@PEG/THPMP crossing the BBB. With this simple approach, MSNs with critical negative charge and size could overcome the BBB-limiting characteristics of therapeutic drug molecules; furthermore, their use may also cause drug sustained-release in the brain, decreasing peripheral toxicity.

Contribution: This research explores the effectiveness of a proposed teaching strategy in blockchain education, finding that it enhances learning outcomes, cognitive well-being, and student engagement in tertiary education, ultimately resulting in a shallower learning curve for STEM knowledge. Background: In the context of Industry 4.0, blockchain technology has emerged as a key driver of transformation in data management and system automation across a range of industrial applications. Despite its significance, the intricate theories and concepts associated with blockchain often serve as a deterrent for novice learners, inhibiting their ability to appreciate the value of industrial blockchain. Consequently, there is a pressing need to develop interactive teaching content that alleviates the steep learning curve. Intended Outcomes: The teaching strategy for the gamification in blockchain education is proposed, which positively influence students' cognitive well-being in terms of knowledge retention, cognitive curiosity, and heightened enjoyment. Application Design: Based on the experimental learning theory, the gamification of blockchain education, namely "BlockTrainHK", is implemented in the experimental learning cycle. Therefore, the gamified learning in experimental learning (GEL) strategy is proposed to examine the effectiveness of concrete experience, reflective observation, abstract conceptualization and active experimentation by two case studies. Findings: The results of the two-year study on the gamified blockchain education are encouraging: test groups using the GEL strategy were better in the cognitive well-being, and students' cognitive well-being is positively proportional to the level of individual technical knowledge and skills.

Adolescence is a critical period during which youth develop and shape their behaviors. Because differences between youths are strongly connected to environmental factors, we aimed to elucidate possible pathways from home-school regulation and atmosphere to youths' prosocial and antisocial behaviors. Data were derived from the China Education Panel Survey. This study involved a total of 9291 students aged 14-15 years (4834 boys, 4457 girls). We used structural equation modeling (SEM) with LISREL 8.80 and Monte Carlo resampling with R to conduct the analysis strategy. In the home-school regulation, parental supervision on the one hand and teacher criticism on the other hand have direct positive and negative predictive effects on youths' prosocial behaviors, respectively, while their direct effects on antisocial behavior are the opposite; teachers praise does not directly affect adolescents' prosocial and antisocial behaviors. In the home-school atmosphere, family interaction and perceived good class climate directly positively affect youths' prosocial behaviors, while the direct effects of both on antisocial behavior are not significant. The SEM results reveal that academic self-efficacy and depressive symptoms may be underlying mediating mechanisms through which home-school regulation and atmosphere during adolescence affect students' prosocial and antisocial behaviors. Intervention programs targeting home-school supportive environments and prevention programs targeting positive emotion and self-awareness may yield benefits for proper social behavior in adolescents. For example, by enhancing the way and frequency of parent-child interaction, teachers and students jointly create a good class climate of care and friendship to strengthen a home-school supportive environment. Improve adolescents' positive emotions such as contentment, optimism, and hope to reduce the possibility of depression.

The purpose of this study is to investigate the relations among children's symbolic functioning at 15 months, joint attention at 24 months, expressive communication at 24 and 36 months, and executive functioning at 36 months. With the sample from rural areas in the United States collected by the Family Life Project (N = 1,008), a longitudinal data analysis was conducted. The results of structural equation modeling suggested that children's symbolic functioning at 15 months and children's executive functioning at 36 months was directly related to each other. These two variables were also indirectly related to each other through joint attention at 24 months and expressive communication at 24 and 36 months. Psychological distancing and verbal and nonverbal communication were used to explain the role symbolic functioning plays in the development of executive functioning during the second and the third years of children's lives.

This paper discusses the factors affecting the behaviours for coping with fake news among young people. The data were collected from a survey conducted in late 2019, which sampled 2112 secondary school students from 21 partnering schools. This study aims to understand the opinions and behaviours of teenagers towards disinformation when fake news was prevalent during the anti-extradition bill protests in Hong Kong. It finds that awareness of the problem alone had limited influence in facilitating coping strategies. Civic awareness and interaction with social media were useful predictors of internal and external coping behaviours, respectively. Confidence about one's ability to detect fake news was a crucial factor, yet a concern for the value of truth stood out as the strongest predictor of fake news coping behaviours.

This study explores the mechanisms that underlie the effect of school marketing strategies on parents' perceived school attractiveness, particularly emphasizing the mediating role of parents' perceptions of being welcomed in urban schools. Additionally, we investigated how schools' marketing strategies work differently among parents with different value orientations toward schooling. Structural Equation Modeling and Cluster Analysis Data were applied to analyze 510 questionnaires collected from parents. Two experiential marketing strategies, namely, one-way disseminating materials and interactive social networking, impacted parents' perceived attractiveness of schools differently with the feeling of being welcomed mediating the relationship between parents and schools. Additionally, parents' value orientations toward schooling could be classified into three profiles. The results suggest that schools should consider parents' needs and preferences concerning their children's schooling and employ appropriate marketing strategies to engage different types of parents. To facilitate this outcome, individualized interaction is necessary to accommodate the diverse needs of parents. The overall structural equation model validates the mechanism of experiential marketing in influencing parental perceptions, and the cluster analysis underscores the need to explore the complex relationship between parents' educational priorities and their interpretation of marketing strategies.

Abstract Background Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drug-loaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed. Methods PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at − 80 °C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay. Results 15~36 × 106 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX. Conclusions Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.

With the rapid economic development, urban areas are seeing more and more vehicles, leading to frequent urban traffic congestion. To solve this problem, the forecasting of traffic parameters is essential, in which, road operating speed (hereinafter referred to as “road speed”) is a key parameter for forecasting road congestion. This paper proposes a hybrid radial basis function (RBF) neural network algorithm for forecasting road speed. First, it proposes a fuzzy RBF neural network structure by combining the fuzzy logic system with the RBF neural network. Then, it incorporates factors such as weather, holidays and road grades into the input layer. Considering the uncertainty and sensitivity of the initial centre of the traditional membership function layer, it uses fuzzy C-means clustering to determine the centre and other parameters of the membership function layer. Then using the gradient descent method, it trains the weights between the fuzzy inference layer and the output layer. Finally, this paper trains the proposed hybrid RBF neural network with the traffic road network data and weather data of a city, and uses the trained hybrid neural network to predict the road speed and the congestion status. The prediction results show that, compared with simplex prediction methods, such as BP neural network, time series method, and RBF neural network, the hybrid RBF neural network has a higher forecasting accuracy, with the mean absolute percentage error (MAPE) being reduced to 6.4%. Experimental results verify the accurate forecasting, enhanced learning feature and mapping capability of this method in short-term road speed forecasting, indicating that it can provide reliable predicted values to help solve urban congestion problems.

Abstract Introduction Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics. Methods In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems. Results In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only. Conclusions Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.

Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T4) stimulates cancer cell proliferation via a receptor on integrin αvβ3 of plasma membranes. It also induces the expression of programmed death-ligand 1 (PD-L1) and cell proliferation in cancer cells. Thyroid hormone also activates β-catenin-dependent cell proliferation in cancer cells. However, the relationship between PD-L1 and cancer proliferation is not fully understood. In the current study, we investigated the role of inducible thyroid hormone-induced PD-L1-regulated gene expression and proliferation in oral cancer cells. Thyroxine bound to integrin αvβ3 to induce PD-L1 expressions via activation of ERK1/2 and signal transducer and activator of transcription 3 (STAT3). Inactivated STAT3 inhibited PD-L1 expression and nuclear PD-L1 accumulation. Inhibition of PD-L1 expression reduced β-catenin accumulation. Furthermore, nuclear PD-L1 formed a complex with nuclear proteins such as p300. Suppression PD-L1 expression by shRNA blocked not only expression of PD-L1 and β-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin αvβ3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and β-catenin-related growth in oral cancer cells.

Biomedical engineering is critical in improving people's lives through innovative solutions to biological and medical challenges. In the face of today's rapidly evolving climate, the field of biomedical engineering encounters numerous pressures that demand up-to-date skills and competencies. The (re-)development of curricula aligning with industry and societal needs, students' expectations, and academics' expertise while outlining graduates' knowledge (that) and abilities (how) becomes indispensable despite the challenges and complexities presented by conflicting priorities, tight timelines, and scarce resources. This paper presents a qualitative study conducted by a biomedical engineering graduate school at an Australian university. The study engaged four key stakeholders--industry partners, recent graduates, current academics, and students--in a self-auditing process of an existing biomedical engineering curriculum. This exercise aimed to identify priorities for the future development of the curriculum. The findings reveal the perspectives from the four stakeholder groups, with industry partners and recent graduates focusing on technical and transferable skills and current students and academic staff advocating for breadth and a more practice-oriented curriculum, where transdisciplinarity should inform biomedical engineering education. We propose that this evidence-based and bottom-up approach with multiple stakeholders holds potential implications for fields beyond biomedical engineering education. It provides valuable guidance to educational institutions seeking to (re-)develop their curricula to align with evolving industry and society demands.

In higher education, it is challenging to cultivate non-computer science majors' programming concepts. This study used the GAME model (gamification, assessment, modeling, and enquiry) in a programming education course to enhance undergraduates' self-efficacy and performance of basic programming concepts. There were 83 undergraduates taking part in this study, which adopted a quasi-experimental research design. Students in the experimental group (n = 43) experienced a course in which the GAME model was used to design the block-based programming course. The control group (n = 40) was given a general information education course covering similar learning concepts without the game-based learning strategy. The analysis of covariance (ANCOVA) was adopted to investigate the effect of the GAME model on students' learning outcomes for the quantitative data. In the qualitative analysis, students' responses to the course perception questionnaire were coded and analyzed. The results showed that students in the experimental group outperformed their counterparts regarding self-efficacy and basic programming concepts. The experimental treatment resulted in a small to medium effect size difference between the two groups. The results showed that incorporating the GAME model into block-based programming teaching helped improve undergraduates' self-efficacy and performance of basic programming concepts. In addition, these experimental group undergraduates also perceived the pedagogic GAME model positively. Several research suggestions are proposed based on the findings of the present study.

The relationship between Information and Communication Technology (ICT) and academic performance is a controversial issue that has attracted increasing attention from administrators, policymakers, and researchers. The relationship between perceived ICT competence and the academic performance of rural students deserves particular attention. Although a small but growing body of research has examined the relationship between perceived ICT competence and student academic performance, few studies have viewed perceived ICT competence as a multilevel construct. This study aimed to fill this gap by examining the relationship between multilevel perceived ICT competence (i.e., student- and school-level perceived ICT competence) and student academic performance using a sample of 5530 students from 156 schools in rural China. Two-level hierarchical linear modeling results indicated that student- and school-level perceived ICT competence could predict academic performance. Furthermore, school-level perceived ICT competence could moderate the relationship between student-level ICT competence and academic outcomes. Specifically, the role of student-level perceived ICT competence showed heterogeneity across schools. Academic performance was strongly correlated with student-level perceived ICT competence in schools with a low level of perceived ICT competence; in contrast, this outcome was not observed in schools with a high level of perceived ICT competence. The findings suggest that administrators and policymakers in China should pay special attention to rural schools where perceived ICT competence is low and consider providing services for students in these schools to promote educational equity.

Background: The school is one of the most salient developmental contexts for children. However, little is known about the associations linking the school environment to child adjustment in a non-Western context, not to mention the potential processes that may mediate these associations. Aims: This study examined the associations of school- and classroom-level characteristics with child adjustment and tested whether these associations were mediated by teacher-child relationship qualities. Sample: Cross-sectional data were collected on a representative sample of 1777 children (mean age = 55.14 months; 50% of them were girls) from 100 kindergartens in Hong Kong, China. Methods: Using self-reported questionnaires, teachers rated their school-level environments, their classroom chaos, their closeness and conflict with children and children's socioemotional competence and academic ability. Meanwhile, parents rated children's behavioural problems. Results: Multilevel structural equation modelling revealed that the school-level environment and classroom chaos were uniquely associated with children's socioemotional, behavioural and academic adjustment. Moreover, the associations of the school-level environment and classroom chaos with child socioemotional and academic adjustment were mediated by teacher-child closeness and conflict, whereas the associations of the school-level environment and classroom chaos with child behavioural problems were mediated by teacher-child conflict only. Conclusions: Findings indicated how school- and classroom-level characteristics may be uniquely associated with child adjustment and how teacher-child relationships may be implicated in the underlying mechanism, highlighting the potential utility of targeting school- and classroom-level environments and teacher-child relationships in promoting child development.

Differentiated instruction is much demanded yet quite challenging in face of the growing student diversity in today's K-12 classrooms. One major challenge is the provision of differentiated materials to students. Automated text simplification (ATS) tools fueled by natural language processing may serve as a useful assistant for teachers. However, little is known about teachers' contextualized use of ATS over time. This case study traced two teachers' use of ATS systems over a semester. Drawing upon three semi-structured interviews and teacher-generated materials with ATS, we identified an evolving pattern of teachers' engagement with ATS systems, a progression from a blind reliance on the tool to a more critical and coordinated use of the tool over time. We further revealed that teachers' evolving understanding of DI, positioning of the role of ATS systems and human instructors, and interpretation of DI need in specific teaching situations interplayed to shape their particular ways of engagement. Overall, this study contributes to the understanding of teachers' contextualized use of ATS technology for DI. By revealing the influencing factors, the findings hold significant pedagogical implications to inform the design of ATS tools and the creation of favorable conditions to maximize the potential of ATS tools for DI and language teaching and learning in general.