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Virtual Reality (VR) has demonstrated significant advantages in various educational fields as it allows learners to actively learn in high interactivity and realism under their learning pace. However, for low-achieving students, VR learning environments may introduce some challenges, which are problems encountered during their learning process, which lead to difficulties in self-regulating their learning progress and becoming disoriented in the lack of guidance. This study aims to explore the improvement of self-regulated VR learning environment based on the Cognitive Theory of Multimedia Learning and enhance the performance of low-achieving students. We designed a VR course on electronic circuit hardware and programming, providing participants with a series of learning aids in the VR learning environment, including feedback, hints and guidance. Feedback aids provide correct or incorrect feedback after each task or test, guidance aids display progress following each task or test and hint aids offer guidance when inactivity is detected. A quasi-experiment was conducted by using questionnaires and practical tasks to assess the participants' cognitive levels, practical hands-on skills, self-regulated learning abilities and learning engagement after VR learning. The results demonstrated significant improvements in all learning indicators for low-achieving students.

The core purpose of integrating inquiry-based learning strategies into STEM activities is to create a challenging learning environment that stimulates students' active learning, thereby effectively enhancing their interest in learning, thinking skills, and practical application abilities. To achieve these goals, developing more technology-assisted tools and platforms to improve teaching efficiency and enrich the learning experience becomes crucial. Therefore, this research developed InquiryGPT, which guides students through the POEE inquiry process by imposing limitations, facilitating dialogue, and providing feedback, while avoiding over-reliance on ChatGPT. This promotes the cultivation of higher-order thinking skills through interactions with InquiryGPT, thereby enhancing students' knowledge construction and understanding. This study, based on the Technology Acceptance Model (TAM), examined the effectiveness of InquiryGPT. The results showed no significant difference between InquiryGPT and ChatGPT in terms of perceived usefulness and perceived ease of use. Additionally, through analysis of covariance (ANCOVA), the study further analyzed the impact of InquiryGPT on students' higher-order thinking skills and learning scores, proving that it significantly enhances students' creativity, problem-solving abilities, critical thinking, and knowledge construction.

Background: While the integration of robot-based learning in early childhood education has gained increasing attention in recent years, there is still a lack of evidence regarding the impact of AI robots on young children's learning. Objectives: The study explored the effectiveness of two AI education approaches in advancing kindergarteners' computational thinking, sequencing, self-regulation and theory of mind skills. Methods: An experiment was conducted with 90 kindergarteners (ages 5-6) randomly assigned to either a direct instruction (DI), cooperative play (CP) or control group. Results: Results show that (1) children in all three groups had significant improvements on computational thinking, sequencing and self-regulation; (2) both early AI education approaches (CP and DI) significantly enhance young children's computational thinking, sequencing, self-regulation and theory of mind skills; (3) the DI group had significant higher improvement than the CP group on computational thinking; (4) the CP group exhibited greater enhancements in theory of mind skills than the DI group. Conclusion: These findings jointly demonstrate that each AI educational approach has unique strengths, underscoring the significance of designing new pedagogies to expand children's skills.

Reading disability (RD) may be characterized by reduced print-speech convergence, which is the extent to which neurocognitive processes for reading and hearing words overlap. We examined how print-speech convergence changes from children (mean age: 11.07±0.48) to adults (mean age: 21.33±1.80) in 86 readers with or without RD. The participants were recruited in elementary schools and associate degree colleges in China (from 2020 to 2021). Three patterns of abnormalities were revealed: (1) persistent reduction of print-speech convergence in the left inferior parietal cortex in both children and adults with RD, suggesting a neural signature of RD; (2) reduction of print-speech convergence in the left inferior frontal gyrus only evident in children but not adults with RD, suggesting a developmental delay; and (3) increased print-speech convergence in adults with RD than typical adults in the bilateral cerebella/fusiform, suggesting compensations. It provides insights into developmental differences in brain functional abnormalities in RD.

Prolonged digital use is prevalent among young children. Still, it is unclear which parental risk factors contribute to this and whether cultural background (western vs. non-western) and parental role (mother vs. father/parents) could moderate this impact. A systematic literature search identified 52 empirical studies with 54,334 children in a random-effects meta-analysis. The analysis revealed that preschoolers' prolonged digital use was significantly associated with parental digital use (r = 0.24, 95%CI [0.17, 0.30]), low socioeconomic status (r = 0.10, 95%CI [0.08, 0.13]), and passive parenting behavior (r = 0.17, 95%CI [0.10, 0.25]), and significantly but weakly correlated with psychological distress (r = 0.15, 95%CI [0.07, 0.23]). There were effect size differences between the sub-items in both passive parenting behavior and psychological distress factors. In addition, cultural background moderated the associations between preschoolers' digital use and parents' digital use (Q = 8.38, p < 0.01) and passive parenting behaviors (Q = 3.32, p = 0.06). In contrast, the moderating effects of the parental role were not significant (Qs < 4.16, ps > 0.13). These findings suggest that specific items of parental factor, particularly those related to parenting practices, should be considered as the risks of preschoolers' prolonged digital use. Future studies should pay more attention to cultural differences and the roles of fathers.

Abstract Preeclampsia (PE) is a pregnancy complication characterized by high blood pressure and organ damage. This study investigates the differences in the gut microbiota between preterm neonates born to mothers with PE and those born to mothers without PE (PR), aiming to understand how maternal health conditions like PE influence neonatal gut microbiota. The early gut microbiota plays a crucial role in neonatal health, and disturbances in its development can have long-term consequences. Fecal samples were collected from preterm neonates of PE and PR mothers at 2 and 6 weeks postpartum and analyzed using shotgun metagenomic sequencing. We found that PE significantly affected the gut microbial composition of preterm neonates, particularly at 2 weeks postpartum. The gut microbial diversity in the PE_2 group was notably lower compared to the PR_2 group, with no significant difference observed between the PR_6 and PE_6 groups. At the phylum level, Firmicutes and Proteobacteria were predominant, with significant differences observed, particularly a lower abundance of Actinobacteria in the PE_2 group. At the genus level, Escherichia, Enterococcus, and Klebsiella were more prevalent in the PE_2 group, whereas Bifidobacterium and Cutibacterium dominated the PR_2 group. The gut virome analysis showed no significant differences among the groups. Functional analysis revealed distinct metabolic pathway activities across the groups, suggesting that early disturbances due to PE impact the establishment of healthy gut microbiota. These findings underscore the substantial influence of maternal health on the early development of the neonatal gut microbiota and highlight the potential long-term health consequences. Additionally, the differences in metabolic pathways further emphasize the impact of preeclampsia on gut microbiota functionality.

Digital technologies are increasingly integrated into the daily lives of young children. However, disparities in access and use quality, known as the 'digital divide,' persist. Parents play a crucial role in narrowing this divide during early childhood, but the underlying mechanisms remain inconclusive. This study investigates how family socioeconomic status (SES) influences Chinese preschoolers' digital literacy and how parental beliefs and parental mediation mediate this relationship. A sample of 2272 parents of young children from central China completed the "Home Digital Practices Survey" (HDPS). The PROCESS results revealed the following: (1) Family SES, parental beliefs, and parental mediation significantly predicted preschoolers' digital literacy; (2) Parental beliefs and parental mediation co-mediated the impact of family SES on digital literacy; (3) Positive parental beliefs and mediation strategies were associated with better digital literacy outcomes for preschoolers. The findings have implications for parental education and highlight the importance of considering family context in promoting digital literacy among young children.

With the development of science over the years, people have increasingly realized the importance of science communication. Unfortunately, very little research has focused on helping medical students develop the capabilities of science communication. To improve medical students' science communication and evaluate the effectiveness of New Media through mobile clients in health science communication, a competition was held among medical undergraduates. Outstanding works were selected for publication on our official health science communication WeChat account. Furthermore, the participants volunteered to complete a questionnaire survey to help us assess students' awareness of science communication. Our analysis revealed that students had a strong willingness to serve society and to participate in science communication work. Students generally agreed that science communication work had excellent effects on professional knowledge and related skills. In addition, the correlation results showed that the greater students' willingness to participate in health science communication was, the greater their sense of gain. New Media effectively expand the influence of students' popular science works. Our findings suggest that competition in science communication has a positive impact on enhancing students' awareness and capabilities in science communication. In addition, New Media are an effective way to improve students' scientific communication efficiency. However, we also noted that students' participation rate and enthusiasm for scientific communication were not high. Further research is needed to determine the reasons for this situation and potential strategies to further improve students' science communication.

Abstract Objective Recent studies highlight the role of H-type vasculature in bone regeneration. This study, based on single-cell RNA sequencing (scRNA-seq), aims to explore the changes in H-type vasculature endothelial cells (H_ECs) in osteonecrosis of the femoral head (ONFH) and hip osteoarthritis (HOA), focusing on the death modes such as ferroptosis, pyroptosis, and parthanatos. Methods We re-analyzed the scRNA-seq data of femoral head samples publicly available in 2022. This study selected nine femoral head samples (3 each from HOA, ONFH stage 3 A, and ONFH stage 4). CD31 + EMCN + endothelial cells were classified as H_ECs. Molecular differences were assessed using Gene Ontology and KEGG analysis. Hypoxia, ferroptosis, pyroptosis, and parthanatos indices were calculated, and transcription factors were predicted using SENIC. Cell communication was analyzed with CellChat. Results After integrating the 9 samples, 14 cell types were identified: B cells, Mesenchymal stem cells, Osteoblasts, Endothelial cells, Monocytes, T cells, NK cells, Fibroblasts, Macrophages, Common myeloid progenitors, Chondrocytes, Myelocytes, Osteoclasts, and Pericytes. The number of endothelial cells and H_ECs decreased with necrosis severity. H_ECs showed higher angiogenic capacity but lower stress resistance compared to other endothelial cells. Angiogenic capacity decreased in necrotic samples, accompanied by an elevation in inflammation levels. The hypoxia index was higher, with ferroptosis increased in stage 3 A and parthanatos in stages 3 A and 4. No change was observed in pyroptosis. Cell communication analysis revealed downregulation of SLIT3-ROBO4 signaling during necrosis. Conclusion H_ECs show molecular differences compared to other endothelial cells. Ferroptosis and parthanatos contribute to the demise of H_ECs in ONFH, with pericytes and fibroblasts supporting H_EC angiogenesis.

Abstract Background Diabetic encephalopathy (DE) is considered as one of the complications of diabetes,which is associated with cognitive impairment in the pathological process of development. Up to now, phospholipid phosphatase related 4 (Plppr4), also known as plasticity related gene 1 (PRG-1) has been revealed its important role in neuroplasticity. However, the underlying mechanisms of Plppr4 on the basis of diabetic-induced cognitive dysfunction (DCD) are still unknown. The aim of current study was to provide insight into molecular mechanism and cellular heterogeneity underlying DCD, and investigate the functional role of PRG-1 involved in this process. Methods Combined Single-cell RNA sequencing (scRNA-seq) and RNA transcriptome analysis, the distinct sub-populations, functional heterogeneity as well as potential enriched signaling pathways of hippocampal cells could be elucidated. Results We identified the sub-cluster of type I spiral ganglion neurons expressed marker gene as Amigo2 in cluster8 and Cnr1 in cluster 9 of hippocampal cells from DCD and the effect of those on neuronal cells interaction. We also found that PRG-1 was involved in the synaptic plasticity regulation of hippocampus via NGF\BDNF-Trkb signaling pathway. In high glucose induced HT22 cells injury model in vitro, we investigated that down-regulated PRG-1 along with down-regulated BDNF and also decreased expression of synapsin-1, PSD-95, SYN which are related to synaptic plasticity; Meanwhile, the Prg-1 targeted miR-18a-LncRNA NONRATG-022419 pairs related with significantly down-regulated expression of PRG-1. Conclusion This study revealed the synaptic plasticity regulation of PRG-1 in DCD, and might provide the therapeutic target and potential biomarkers for early interventions in DCD patients.

Abstract Background There is growing evidence that the pathogenesis of Alzheimer's disease is closely linked to the resident innate immune cells of the central nervous system, including microglia and astrocytes. Mitochondrial dysfunction in microglia has also been reported to play an essential role in the pathogenesis of AD and other neurological diseases. Therefore, finding the mitochondrial and immune-related gene (MIRG) signatures in AD can be significant in diagnosing and treating AD. Methods In this study, the intersection of the differentially expressed genes (DEGs) from the GSE109887 cohort, immune-related genes (IRGs) obtained from WGCNA analysis, and mitochondria-related genes (MRGs) was taken to identify mitochondria–immune-related genes (MIRGs). Then, using machine learning algorithms, biomarkers with good diagnostic value were selected, and a nomogram was constructed. Subsequently, we further analyzed the signaling pathways and potential biological mechanisms of the biomarkers through gene set enrichment analysis, prediction of transcription factors (TFs), miRNAs, and drug prediction. Results Using machine learning algorithms, five biomarkers (TSPO, HIGD1A, NDUFAB1, NT5DC3, and MRPS30) were successfully identified, and a nomogram model with strong diagnostic ability and accuracy (AUC > 0.9) was constructed. In addition, single-gene enrichment analysis revealed that NDUFAB1 was significantly enriched in pathways associated with diseases, such as Alzheimer's and Parkinson's, providing valuable insights for future clinical research on Alzheimer's in the context of mitochondrial–immune interactions. Interestingly, brain tissue pathology showed neuronal atrophy and demyelination in AD mice, along with a reduction in Nissl bodies. Furthermore, the escape latency of AD mice was significantly longer than that of the control group. After platform removal, there was a notable increase in the path complexity and time required to reach the target quadrant, suggesting a reduction in spatial memory capacity in AD mice. Moreover, qRT-PCR validation confirmed that the mRNA expression of the five biomarkers was consistent with bioinformatics results. In AD mice, TSPO expression was increased, while HIGD1A, NDUFAB1, NT5DC3, and MRPS30 expressions were decreased. However, peripheral blood samples did not show expression of HIGD1A or MRPS30. These findings provide new insights for research on Alzheimer's disease in the context of mitochondrial–immune interactions, further exploring the pathogenesis of Alzheimer's disease and offering new perspectives for the clinical development of novel drugs. Conclusions Five mitochondrial and immune biomarkers, i.e., TSPO, HIGD1A, NDUFAB1, NT5DC3, and MRPS30, with diagnostic value in Alzheimer's disease, were screened by machine-learning algorithmic models, which will be a guide for future clinical research of Alzheimer's disease in the mitochondria–immunity-related direction.

Abstract Background Current data indicate that supplements such as folic acid play a significant role in treating chronic atrophic gastritis (CAG). However, no meta-analysis article evaluates its efficacy comprehensively. Therefore, we conducted a meta-analysis to compare the effectiveness and safety of folic acid in the treatment of CAG with Helicobacter pylori (H. pylori) infection. Methods Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. A comprehensive search of the literature was conducted from all years up to June 2024. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Vip, and Wanfang databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.4 and STAT15.1. Efficacy and safety outcomes were evaluated using risk ratio (RR) and 95% confidence intervals (CI). Results 16 randomized controlled trials with 1364 patients were included. Compared with conventional therapy, folic acid therapy had a higher total effective rate (95.09% vs.79.06%, pooled RR = 1.19, 95% CI: 1.12–1.26, p

Abstract Age-related long-term disability is attracting increasing attention due to the growing ageing population worldwide. However, the current understanding of the senescent spinal cord remains insufficient. Bulk RNA sequencing reveals that 526 genes are upregulated and 300 genes are downregulated in senescent spinal cords. Pathway enrichment analysis of differentially expressed genes shows that senescence in spinal cords is related to phagosome function, neuroinflammation, ferroptosis, and necroptosis. Prediction of upstream transcription factors and interactome analysis identify Spi1 as a transcription factor that potentially plays a core role in senescent spinal cords. Spatial transcriptomics illustrates the spatial distribution of the transcriptomic landscape in both young and senescent spinal cords and identifies distinct neuronal and glial subtypes. The ferroptosis-associated gene Fth1 is upregulated in aged spinal cords. Flow cytometry reveals increased accumulation of free Fe2+ and ROS in senescent mixed glial cells; however, CCK-8 assays reveal that these cells are resistant to ferroptosis. SiRNA and lentivirus experiments indicate that the overexpression of Fth1 in normal mixed glial cells reduces their sensitivity to ferroptosis, whereas Fth1 knockdown increases their sensitivity to ferroptosis. In summary, spatial and bulk transcriptomics elucidate the transcriptional characteristics of young versus senescent spinal cords, thus highlighting the role of Fth1 in mediating ferroptosis resistance in senescent mixed glial cells.

Abstract Purpose Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Methods Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Results Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Abnormally high expression of Golgi protein 73 (GP73) and pyruvate kinase M2 (PKM2) is intimately associated with HCC progression. However, as secreted proteins, the role of their extracellular secretions in HCC progression remains unclear. Here, we demonstrated that the expression of extracellular GP73 was positively correlated with extracellular PKM2. GP73 interacted with PKM2 to promote SUMO1 modification of PKM2, which in turn enhanced the interaction of GP73 and PKM2. This process continuously promoted the transfer of PKM2 from the cytoplasm to the membrane in HCC cells, and finally secretion. Extracellular PKM2 and GP73 synergistically promoted angiogenesis and polarization of M2-type macrophages, thereby leading to malignant progression and sorafenib resistance in HCC. Sorafenib combined with shikonin, a specific inhibitor of PKM2, has a strong anti-tumor effect. This study reveals the role of GP73 in enhancing PKM2 and GP73 secretion in promoting HCC progression, providing a theoretical basis and drug targets for HCC therapy.

The malicious infestations of Android malware caused huge economic losses to users over the past few years. Machine learning-based malware detection enhances the accuracy and partially mitigates these security threats. However, when the static or dynamic features cannot effectively represent software behavior, the accuracy of the model will be reduced. For this issue, a multi-features hybrid malware detection and category classification method HGDetector is proposed, this approach provides a more comprehensive representation of software behavior. HGDetector first extracts the software static function call graph and constructs the network behavior function call graph, then applies the dynamic network traffic features of the software to build the node interaction graph and edge-node graph; Subsequently, these features were fused and converted into a vector representation employing graph embedding method; Finally, combined with the proposed HGDetector, different classifiers were used to test the accuracy of malware detection and category classification. The experimental results demonstrate that the fusion of hybrid features can enhance malware detection accuracy by approximately 4 % when network traffic features effectively capture APP's behavior. Conversely, in cases where network traffic features alone are insufficient to represent software's network behavior, the application of hybrid features can improve malware detection accuracy by 21 %-26 %.