Background: A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. Methods: A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. Results: Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. Conclusion: PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.

Background: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. Methods: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. Results: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. Conclusion: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials. Graphical FPHA was successfully prepared through the chemical and thermal process. The immunomodulatory effects of FPHA were investigated through in vitro and in vivo studies, revealing its ability to induce a metabolic shift in macrophages from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This metabolic remodeling resulted in a notable suppression of M1 macrophage polarization and promotion of M2 macrophage polarization. Furthermore, FPHA was found to enhance osteogenic differentiation and facilitate bone repair. These findings underscore the promising potential of FPHA as a biomaterial for bone regenerative applications, providing valuable insights for the development of bioactive materials with metabolic-immunoregulatory properties: Graphical

As an experimental teaching method, emerging learning methods including problem-based learning (PBL), case-based learning, team-based learning and flipped classroom (FC) have been widely applied in dental education. This study aims to evaluate the effect of these teaching methods on dental education performance compared to traditional lecture-based learning (LBL). The search was carried out in April 2024 in PubMed, EMBASE, Web of Science, and Cochrane Library. All randomized controlled trials were included and the methodological quality assessment was based on the guidelines described in the Cochrane Handbook for Systematic Reviews, followed by a meta-analysis using Stata 14.0 software. Using standard mean deviation (SMD) and 95% confidence interval (95% CI) to determine the effectiveness of emerging teaching methods and LBL in all dental disciplines. Meta-regression was used to analyse sources of heterogeneity. Sensitivity analysis was performed to determine the stability, and Begg's analysis was used to determine whether there is publication bias. A total of 29 randomized controlled trials including 3502 students were included. The results indicate that emerging educational methods have a significantly positive effect on achieving higher scores (SMD = 0.48, 95% CI = 0.34-0.62, P < .001), whether it was theoretical scores (SMD = 0.52, 95% CI = 0.32-0.72, P < .001) or skill scores (SMD = 0.45, 95% CI = 0.15-0.76, P < .001). Compared to LBL, PBL (SMD = 0.33, 95% CI = 0.01-0.65, P = .045) and FC (SMD = 0.50, 95% CI = 0.31-0.69, P < .001) can both significantly improve students' academic performance. Compared to LBL, emerging educational methods (PBL, case-based learning, and FC) have significantly improved the learning effectiveness of dental students. These emerging educational methods can be advocated and popularized as routine teaching methods. This study is the first meta-analysis of the effects of emerging teaching methods in dental education which shows great impact of emerging teaching methods on students' development.

Periodontitis is a global inflammatory oral disease, and plaque-induced host excessive immune response is recognized as a major cause of its pathogenesis. In recent years, the relevance of mitochondrial dysfunction to periodontitis has been increasingly investigated, particularly with respect to macrophages, the key immune cells in the periodontal immune microenvironment. Mitochondrial dysfunction drives macrophage M1 polarization and osteoclast differentiation through mechanisms such as metabolic reprogramming, reactive oxygen species release, abnormal mitophagy, abnormal mitochondrial biogenesis and damaged mitochondrial dynamic. In addition, mitochondrial transfer in the periodontitis setting has been reported in several researches. In this review, we highlight the impact of mitochondrial dysfunction on macrophages in the periodontitis setting and summarize emerging therapeutic strategies for targeting mitochondria in periodontitis, including antioxidants, modulators of metabolic reprogramming, nanomaterials and photodynamic therapy.

Oral diseases such as dental caries, periodontitis, and oral cancer are prevalent and present significant challenges to global public health. Although these diseases are typically treated through procedures like dental preparation and resin filling, scaling and root planning, or surgical excision, these interventions are often not entirely effective, and postoperative drug therapy is usually required. Traditional drug treatments, however, are limited by factors such as poor drug penetration, significant side effects, and the development of drug resistance. As a result, there is a growing need for novel drug delivery systems that can enhance therapeutic efficacy, reduce side effects, and improve treatment outcomes. In recent years, drug-loaded vesicles, such as liposomes, polymersomes, and extracellular vesicles (EVs), have emerged as promising drug delivery platforms due to their high drug encapsulation efficiency, controlled release properties, and excellent biocompatibility. This review provides an in-depth examination of the characteristics, advantages, and limitations of liposomes, polymersomes, and extracellular vesicles in the context of oral disease treatment. It further explores the reasons for their advantages and limitations and discusses the specific applications, development prospects, and strategies for optimizing these vesicle-based systems for improved clinical outcomes.

An empirical method is proposed to predict the clinical performance of resin composite dental restorations by using laboratory data derived from simple specimens subjected to chemical degradation and accelerated cyclic fatigue. Three resin composites were used to fill dentin disks (2-mm inner diameter, 5-mm outer diameter, and 2 mm thick) made from bovine incisor roots. The specimens ( n = 30 per group) were aged with different durations of a low-pH challenge (0, 24, and 48 h under pH 4.5) before being subjected to diametral compression with either a monotonically increasing load (fast fracture) or a cyclic load with a continuously increasing amplitude (accelerated fatigue). The data from 1 material were used to establish the relationship between laboratory time (number of cycles) and clinical time to failure (years) via the respective survival probability curves. The temporal relationship was then used to predict the clinical rates of failure for restorations made of the other 2 materials, and the predictions were compared with the clinical data to assess their accuracy. Although there were significant differences in the fast fracture strength among the groups of materials or durations of chemical challenge, fatigue testing was much better at separating the groups. Linear relationships were found between the laboratory and clinical times to failure for the first material ( R² = 0.90, 0.90, and 0.62 for the 0-, 24-, and 48-h low-pH groups, respectively). The clinical life of restorations made of the other 2 materials was best predicted with data from the 48-h low-pH groups. In conclusion, an accelerated fatigue model was successfully calibrated and applied to predict the clinical failure of resin composite restorations, and the predictions based on data obtained from chemically aged specimens provided the best agreement with clinical data.