Self-determination and perceived learning in online learning communities.

This study explores the interplay between Self-Determination (SDT), relatedness, and teaching presence and CoI's presence (teaching, cognitive, and social) in the context of online educational settings within China. Specifically, the study employs the Partial Least Squares Structural Equation Modeling (PLS-SEM) to investigate the interaction between SDT (Self-Determination, relatedness, and competence) and the perceived learning outcomes (autonomy, competence, and perceived learning). The underlying structure of the study's conceptual framework was analyzed through the measurement model and the discriminant validity assessment. The results show that cognitive presence, social presence, and teaching presence are significantly associated with autonomy, competence, relevance, and perceived learning. Moreover, cognitive presence and social presence can potentially augment cognitive processes, amplifying the mediating role of relatedness between cognitive presence and learning outcomes.

Coordinated NREM sleep oscillations among hippocampal subfields modulate synaptic plasticity in humans.

The integration of hippocampal oscillations during non-rapid eye movement (NREM) sleep is crucial for memory consolidation. However, how cardinal sleep oscillations bind across various subfields of the human hippocampus to promote information transfer and synaptic plasticity remains unclear. Using human intracranial recordings from 25 epilepsy patients, we find that hippocampal subfields, including DG/CA3, CA1, and SUB, all exhibit significant delta and spindle power during NREM sleep. The DG/CA3 displays strong coupling between delta and ripple oscillations with all the other hippocampal subfields. In contrast, the regions of CA1 and SUB exhibit more precise coordination, characterized by event-level triple coupling between delta, spindle, and ripple oscillations. Furthermore, we demonstrate that the synaptic plasticity within the hippocampal circuit, as indexed by delta-wave slope, is linearly modulated by spindle power. In contrast, ripples act as a binary switch that triggers a sudden increase in delta-wave slope. Overall, these results suggest that different subfields of the hippocampus regulate one another through diverse layers of sleep oscillation synchronization, collectively facilitating information processing and synaptic plasticity during NREM sleep.

Fostering resilience and post-traumatic growth in overseas Chinese left-behind children: The role of autonomy, competence, and relatedness.

OBJECTIVE: This study examines the impact of parental migration on the psychological well-being and development of left-behind children (LBCs) in Zhejiang, China, within the broader context of the country's rural transformations and urban migration. It investigates how intellectual and relational engagement (RE), autonomy (AUT), competence (COM), and relatedness (RES) contribute to resilience (REL) and post-traumatic growth (PTG) in these children, reflecting on the shift from viewing parental separation merely as a source of trauma to recognizing its potential to foster significant personal growth. METHODS: Utilizing a cross-sectional design, the research was conducted in April and May 2023 with 1348 LBCs from a total sample of 4049 students inZhejiang. A two-step random, stratified, cluster-based sampling strategy was employed, and structural equation modeling was used to examine the hypothesized relationships among the constructs. RESULTS: The statistical analysis demonstrated significant positive effects of intellectual engagement (IE), AUT, COM, and RE on both REL and PTG (p < .05 for all). IE strongly correlated with AUT (r = .68, p < .001) and COM (r = .71, p < .001), enhancing REL and facilitating PTG. Additionally, the presence of secure and consistent relationships was identified as crucial for maintaining psychological well-being, with high correlation coefficients (r > .60) underscoring their importance. Notably, REL was found to moderate the relationships among RES, COM, and PTG, highlighting its critical role in the psychological adaptation of left-behind children. CONCLUSION: The study underscores the importance of nurturing intellectual and REs, AUT, and COM to enhance psychological REL and well-being among LBAs. These elements are crucial for supporting the mental health and developmental needs of children facing the challenges of parental migration. The findings advocate for targeted interventions that can address the unique needs of this vulnerable population, emphasizing the potential for growth and adaptation despite adversities.

Multidimensional impact of sport types on the psychological well-being of student athletes: A multivariate investigation.

The correlation between sports participation and psychological well-being is well-documented, revealing a complex interplay influenced by competition level and cultural context. This is particularly relevant in Korea, where the university sports culture significantly impacts student life. This study evaluates how competitive versus non-competitive sports affect Korean university students' psychological well-being using a quantitative approach with SmartPLS 4 for multi-group analysis. Findings reveal that competitive sports significantly enhance mental toughness and stress management through structured coping mechanisms and robust social support, improving coping strategy effectiveness by 34 % compared to non-competitive sports. Conversely, participants in non-competitive sports experience greater general well-being with a 40 % higher use of informal support. These insights suggest that university sports programs could benefit from targeted interventions incorporating specific coping strategies and social support frameworks tailored to the competitive context. This research underscores the need for precise stress management techniques and resilience-building exercises in sports curricula to optimize psychological well-being across different sports environments in Korean universities.

Epilepsy lesion localization method based on brain function network.

Objective: In the past, the localization of seizure onset zone (SOZ) primarily relied on traditional EEG signal analysis methods. However, due to their limited spatial and temporal resolution, accurately pinpointing neural activity was challenging, thereby restricting their clinical applicability. Compared with traditional EEG signals, SEEG signals have superior spatial and temporal resolution, and can more accurately record neural activity near epileptic foci, making them better suited for studying SOZ. In addition, the traditional EEG signal analysis methods still have limitations, mainly focusing on the analysis of local signal features, while ignoring the complexity and interconnection of the overall brain network. How to more accurately locate SOZ is still not well resolved. The purpose of this study is to develop an effective positioning method for more accurate positioning. Method: To overcome these limitations, this study proposed a model integrating brain functional network analysis with nonlinear dynamics. We utilized weighted phase lag index (WPLI) to construct brain functional network, epilepic network connectivity strength (ENCS) as the feature, and introduced persistence entropy (PE) for feature fusion, subsequently employing support vector machine (SVM) classification. Results: The proposed method was verified on the HUP-iEEG dataset, our solution identified the SOZ with 0.9440 accuracy, 0.9848 precision, 0.8974 recall rate, 0.9340 F1 score and 0.9697 area under the ROC curve across patients, which outperforms the existing approaches. It exhibits a 2.30 percentage point enhancement in localisation accuracy along with a 2.97 percentage points in AUC compared to others. Conclusion: Our method consider the interactions between nodes in brain network connections, as well as the inherent nonlinear and non-stationary properties of neural signals, to be more robust.

Investigating the Mechanism of Cadmium-Tolerant Bacterium Cellulosimicrobium and Ryegrass Combined Remediation of Cadmium-Contaminated Soil.

Cadmium (Cd) pollution has been rapidly increasing due to the global rise in industries. Cd not only harms the ecological environment but also endangers human health through the food chain and drinking water. Therefore, the remediation of Cd-polluted soil is an imminent issue. In this work, ryegrass and a strain of Cd-tolerant bacterium were used to investigate the impact of inoculated bacteria on the physiology and biochemistry of ryegrass and the Cd enrichment of ryegrass in soil contaminated with different concentrations of Cd (4 and 20 mg/kg). The results showed that chlorophyll content increased by 24.7% and 41.0%, while peroxidase activity decreased by 56.7% and 3.9%. In addition, ascorbic acid content increased by 16.7% and 6.3%, whereas glutathione content decreased by 54.2% and 6.9%. The total Cd concentration in ryegrass increased by 21.5% and 10.3%, and the soil's residual Cd decreased by 86.0% and 44.1%. Thus, the inoculation of Cd-tolerant bacteria can improve the antioxidant stress ability of ryegrass in Cd-contaminated soil and change the soil's Cd form. As a result, the Cd enrichment in under-ground and above-ground parts of ryegrass, as well as the biomass of ryegrass, is increased, and the ability of ryegrass to remediate Cd-contaminated soil is significantly improved.

A prospective and consecutive study assessing short-term clinical and radiographic outcomes of Chinese domestically manufactured 3D printing trabecular titanium acetabular cup for primary total hip arthroplasty: evaluation of 236 cases.

Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

Preschool Teachers' Emotional Competence and Teacher Self-Efficacy towards Preschool Performance in Zhejiang Province of China.

This study investigates the interplay between emotional competence, self-efficacy, and teaching experience in determining preschool teachers' performance. Drawing on Bandura's Theory of Self-Efficacy, Goleman's Emotional Intelligence Theory, and Bronfenbrenner's Ecological Systems Theory, the research employs a quantitative approach, analyzing responses from preschool teachers in Zhejiang province, China. Key findings reveal that emotional competence significantly predicts teachers' performance and self-efficacy, with self-efficacy further mediating this relationship. Interestingly, while teaching experience moderates the impact of emotional competence on self-efficacy, it does not significantly influence the relationship between self-efficacy and teaching performance. The study underscores the critical role of emotional competence in teaching efficacy and highlights the complexity of how teaching experience interacts with these dynamics. These insights are crucial for developing targeted interventions in teacher training programs, emphasizing emotional skills and self-belief as key drivers of effective teaching in early-childhood education.

Inoculation of cadmium-tolerant bacteria to regulate microbial activity and key bacterial population in cadmium-contaminated soils during bioremediation.

The perennial ryegrass Lolium perenne can be used in conjunction with cadmium (Cd)-tolerant bacteria such as Cdq4-2 (Enterococcus spp.) for bioremediation of Cd-contaminated soil. In this study, a theoretical basis was provided to increase the efficiency of L. perenne remediation of Cd-contaminated soil using microorganisms to maintain the stability of the soil microbiome. The experimental design involved three treatment groups: CK (soil without Cd addition) as the control, 20 mg·kg-1 Cd-contaminated soil, and 20 mg·kg-1 Cd-contaminated soil + Cdq4-2, all planted with L. perenne. The soil was collected on day 60 to determine the soil microbial activity and bacterial community structure and to analyze the correlation between soil variables, the bacterial community, available Cd content in the soil, Cd accumulation, and L. perenne growth. The soil microbial activity and bacterial community diversity decreased under Cd stress, and the soil microbial community composition was changed; while inoculation with Cdq4-2 significantly increased soil basal respiration and the activities of urease, invertase, and fluorescein diacetate (FDA) hydrolase by 83.65%, 79.72%, 19.88%, and 96.15% respectively; and the stability of the community structure was also enhanced. The Actinobacteriota biomass, the amount of available Cd, and the above- and belowground Cd content of L. perenne were significantly negatively correlated with the total phosphorus, total potassium, and pH. The activity of urease, invertase, and FDA hydrolase were significantly positively correlated with the biomasses of Acidobacteriota and L. perenne and significantly negatively correlated with the Chloroflexi biomass. Further, the available soil Cd content and the above- and belowground Cd levels of L. perenne were significantly positively correlated with the Actinobacteriota biomass and significantly negatively correlated with the Gemmatimonadetes biomass. Overall, inoculating Cd-tolerant bacteria improved the microbial activity, diversity, and abundance, and changed the microbial community composition, facilitating the remediation of Cd-contaminated soil by L. perenne.

Cadmium levels and soil pH drive structure and function differentiation of endophytic bacterial communities in Sedum plumbizincicola: A field study.

Sedum plumbizincicola is a promising hyperaccumulator for heavy metal phytoremediation. It grows in heavy metal polluted soil and stores specific endophyte resources with heavy metal tolerance or growth promotion characteristics. In this study, the endophyte communities of S. plumbizincicola, growing naturally in the field (two former mining locations and one natural location) were investigated, and their structure and function were comparatively studied. The bioaccumulation and translocation characteristics of cadmium (Cd) and selenium (Se) in S. plumbizincicola were also evaluated. The results showed that the heavy metal pollution reduced the richness and diversity of endophyte communities. Soil pH and Cd concentration could be the key factors affecting the composition of the endophyte community. Co-occurrence network analysis identified that 22 keystone taxa belonging to Actinobacteriota, Firmicutes, Myxococcota and Proteobacteria were positively correlated with Cd bioaccumulation and translocation. The predicted endophyte metabolic pathways were enriched in physiological metabolism, immune system, and genetic Information processing. These findings may help to understand how endophytes assist host plants to enhance their adaptability to harsh environments, and provide a basis for further exploration of plant-endophyte interactions and improvement in phytoremediation efficiency.

Limiting resources for soil microbial growth in climate change simulation treatments in the subarctic.

The microbial use of resources to sustain life and reproduce influences for example, decomposition and plant nutrient provisioning. The study of "limiting factors" has shed light on the interaction between plants and their environment. Here, we investigated whether carbon (C), nitrogen (N), or phosphorus (P) was limiting for soil microorganisms in a subarctic tundra heath, and how changes in resource availability associated with climate change affected this. We studied samples in which changes in resource availability due to climate warming were simulated by the addition of birch litter and/or inorganic N. To these soils, we supplied factorial C (as glucose), N (as NH4 NO3 ), and P (as KH2 PO4 /K2 HPO4 ) additions ("limiting factor assays," LFA), to determine the limiting factors. The combination of C and P induced large growth responses in all soils and, combined with a systematic tendency for growth increases by C, this suggested that total microbial growth was primarily limited by C and secondarily by P. The C limitation was alleviated by the field litter treatment and strengthened by N fertilization. The microbial growth response to the LFA-C and LFA-P addition was strongest in the field-treatment that combined litter and N addition. We also found that bacteria were closer to P limitation than fungi. Our results suggest that, under a climate change scenario, increased C availability resulting from Arctic greening, treeline advance, and shrubification will reduce the microbial C limitation, while increased N availability resulting from warming will intensify the microbial C limitation. Our results also suggest that the synchronous increase of both C and N availability might lead to a progressive P limitation of microbial growth, primarily driven by bacteria being closer to P limitation. These shifts in microbial resource limitation might lead to a microbial targeting of the limiting element from organic matter, and also trigger competition for nutrients between plants and microorganisms, thus modulating the productivity of the ecosystem.

The Mediating Role of Brand Trust and Brand Love between Brand Experience and Loyalty: A Study on Smartphones in China.

Smartphones have become increasingly essential in people's daily lives. Studying the enablers that influence students' smartphone buying intentions can inform technology-enhanced learning development, whereas research on brand loyalty and experience is important for marketing strategies. While prior research has acknowledged the importance of brand experience and customer loyalty, little literature has investigated the specific dimensions of brand loyalty and their connection to brand love and trust. This study investigates the effects of brand attributes on loyalty and word-of-mouth engagement in choosing smartphones in China, including the mediating role of brand trust and brand love between brand experience and loyalty. The study adopted a research framework based on the previous literature and tested it empirically. The study adopted a cross-sectional survey method, collecting 369 questionnaires from Chinese students in mainland China. The collected data were analyzed with the help of structural equation modelling by applying AMOS software version 26. The results showed that brand experience had a significant influence on brand trust, brand love, attitudinal loyalty, and word-of-mouth, except for behavioral loyalty. Likewise, the link between brand trust and attitudinal loyalty, behavioral loyalty, and brand love was found to be significant. The effect of brand love on attitudinal loyalty and behavioral loyalty became significant. Additionally, the study confirmed that behavioral trust and brand love significantly mediates the relationship between brand experience-attitudinal loyalty, and brand experience-behavioral loyalty, respectively. The study results provide numerous theoretical and managerial implications to help academicians and practitioners provide better customer and brand relationship management.

Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1.

Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence-read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.

Study of Neuronal Apoptosis ceRNA Network in Hippocampal Sclerosis of Human Temporal Lobe Epilepsy by RNA-Seq.

Hippocampal sclerosis (HS) is one of the most common pathological type of intractable temporal lobe epilepsy (TLE), often characterized by hippocampal atrophy, neuronal apoptosis, and gliogenesis. However, the molecular mechanisms of neuronal apoptosis in patients with HS are still not fully understood. We therefore conducted a pilot study focusing on the neuronal apoptosis ceRNA network in the sclerotic hippocampus of intractable TLE patients. In this research, RNA sequencing (RNA-seq) was utilized to quantify the expression levels of lncRNAs, miRNAs, and mRNAs in TLE patients with HS (HS-TLE) and without HS (non-HS-TLE), and reverse transcription-quantitative PCR (qRT-PCR). The interactions of differential expression (DE) lncRNAs-miRNAs or DEmiRNAs-mRNAs were integrated by StarBase v3.0, and visualized using Cytoscape. Subsequently, we annotate the functions of lncRNA-associated competitive endogenous RNA (ceRNA) network through analysis of their interactions with mRNAs. RNA-seq analyses showed 381 lncRNAs, 42 miRNAs, and 457 mRNAs were dysregulated expression in HS-TLE compared to non-HS-TLE. According to the ceRNA hypothesis, 5 HS-specific ceRNA network were constructed. Among them, the core ceRNA regulatory network involved in neuronal apoptosis was constituted by 10 DElncRNAs (CDKN2B-AS1, MEG3, UBA6-AS1, etc.), 7 DEmiRNAs (hsa-miR-155-5p, hsa-miR-195-5p, hsa-miR-200c-3p, etc.), and 3 DEmRNAs (SCN2A, DYRK2, and MAPK8), which belonging to apoptotic and epileptic terms. Our findings established the first ceRNA network of lncRNA-mediated neuronal apoptosis in HS-TLE based on transcriptome sequencing, which provide a new perspective on the disease pathogenesis and precise treatments of HS.

Methyl-CpG-Binding Domain Protein 3 Promotes Seizures by Recruiting Methyltransferase DNMT1 to Enhance TREM2 Methylation.

Epilepsy represents a hazardous neurological disorder, underpinned by a pathophysiological process that is yet to be fully understood. Here, we aimed to elucidate the effect of methyl-CpG-binding domain protein 3 (MBD3) on hippocampal neuronal damage in epileptic mice by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. The expression of MBD3 was determined by Western blot in a hippocampal neuronal culture (HNC) epileptic model established using the low Mg2+ECF culture method. The interaction between MBD3 and DNA methyltransferase 1 (DNMT1) was determined via co-immunoprecipitation and mass spectrometry analysis. Bisulfite modification and sequencing was performed to evaluate the degree of methylation of triggering receptor expressed on myeloid cells 2 (TREM2). The viability and apoptosis of hippocampal neurons were detected by CCK-8 and TUNEL assays, respectively. Finally, the effect of MBD3 was verified in vivo. MBD3 was highly expressed in the HNC model of epilepsy, with its interaction with DNMT1 found to promote the hypermethylation of TREM2 at site cg25748868. Additionally, decreased TREM2 and inhibited PI3K/Akt pathway was observed in the HNC epileptic model. Simultaneous inhibition of MBD3 and DNMT1 decreased the methylation level at cg25748868, up-regulated TREM2 expression, and activated the PI3K/Akt pathway, thereby arresting neuronal damage. Inhibition of MBD3 reduced the level of epileptic seizures, down-regulated cg25748868 methylation, activated TREM2-mediated signaling pathways, and alleviated hippocampal neuronal damage in the acute seizure mouse models. The present study unveiled that MBD3 and DNMT1 synergistically enhanced hypermethylation of cg25748868 in TREM2, and promoted the onset of epilepsy via inhibition of the PI3K/Akt pathway.

GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma.

BACKGROUND: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas. METHODS: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells. RESULTS: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration. CONCLUSIONS: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

Differential DNA Methylation Profiles in Patients with Temporal Lobe Epilepsy and Hippocampal Sclerosis ILAE Type I.

Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.

Dysregulation of Glutamate Transport Enhances Treg Function That Promotes VEGF Blockade Resistance in Glioblastoma.

Anti-VEGF therapy prolongs recurrence-free survival in patients with glioblastoma but does not improve overall survival. To address this discrepancy, we investigated immunologic resistance mechanisms to anti-VEGF therapy in glioma models. A screening of immune-associated alterations in tumors after anti-VEGF treatment revealed a dose-dependent upregulation of regulatory T-cell (Treg) signature genes. Enhanced numbers of Tregs were observed in spleens of tumor-bearing mice and later in tumors after anti-VEGF treatment. Elimination of Tregs with CD25 blockade before anti-VEGF treatment restored IFNγ production from CD8+ T cells and improved antitumor response from anti-VEGF therapy. The treated tumors overexpressed the glutamate/cystine antiporter SLC7A11/xCT that led to elevated extracellular glutamate in these tumors. Glutamate promoted Treg proliferation, activation, suppressive function, and metabotropic glutamate receptor 1 (mGlutR1) expression. We propose that VEGF blockade coupled with glioma-derived glutamate induces systemic and intratumoral immunosuppression by promoting Treg overrepresentation and function, which can be pre-emptively overcome through Treg depletion for enhanced antitumor effects. SIGNIFICANCE: Resistance to VEGF therapy in glioblastoma is driven by upregulation of Tregs, combined blockade of VEGF, and Tregs may provide an additive antitumor effect for treating glioblastoma.