Periodontal disease is a common disease and leads to the loss of supporting structures and pathologic tooth migration. In order to achieve a functionally sound and aesthetically satisfactory treatment outcome, combined orthodontic-periodontal therapy may be necessary. In this study, we focus on the anterior tooth movement when designing different thickness of power ridge for patients with periodontal disease and investigate its biomechanical effects during anterior retraction using clear aligners (CAs). Two models of maxillary with different heights of alveolar bone were constructed, and three models of CAs were created with different power ridge designs. This study includes a total of six finite element models, which included alveolar bone, the first premolars extracted maxillary dentition, periodontal ligaments (PDL), attachments, and CAs. And the biomechanical effects were analyzed and compared in each model during anterior retraction using CAs. Compared to the models with normal height of alveolar bone, the patients with alveolar bone loss had more tooth displacement when the retraction distance was the same. And the center of the rotation of the anterior tooth moved towards the root direction. The total displacement of the central incisor increased in models with power ridges, and 0.5 mm power ridges caused the maximum displacement in both normal alveolar bone and reduced alveolar bone height models. In normal alveolar bone models, the crown and root moved in the same direction in 0.7 mm power ridges, but in reduced alveolar bone models, it was 0.5 mm. The von Mises stress values and maximum principal stress values for PDL increased as the depth of power ridges increased, and 0.7 mm power ridges caused concentration of stress in both models with normal alveolar bone or reduced alveolar bone. In patients with periodontal disease, the displacement of the entire maxillary dentition increased in comparison to those with normal alveolar bone. And an appropriate thickness of power ridge is beneficial to achieve torque control of anterior teeth. However, excessive thickness of power ridges is not suitable for anterior tooth retraction because of the stress concentration on the PDL.

Background: Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease characterized by cartilage destruction and subchondral bone remodeling. However, its molecular mechanisms remain incompletely understood, and effective therapeutic targets are still limited. This study aimed to identify candidate targets for TMJ OA through an integrated multi-omics strategy combined with experimental validation. Methods: Multi-layer omics data including expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL) and molecular quantitative trait loci (mQTL) were merged with TMJ OA Genome-Wide Association Study (GWAS) summary stats. Mendelian Randomization (MR) and colocalization analyses were performed to determine whether there was a causal relationship between the genes. The main results were further validated by immune infiltration analysis, pathway enrichment (Gene Set Enrichment Analysis, GSEA), transcription factor and miRNA network analysis, drug prediction (Connectivity Map, CMap), and molecular docking. A rat forced mandibular retrusion (FMR) model was used for in vivo experimental validation. Results: haloacid dehalogenase like hydrolase domain containing 3 (HDHD3) and high mobility group 20B (HMG20B) were prioritized as candidate genes associated with TMJ OA. Colocalization analysis supported shared signals between TMJ OA and the pQTLs of HDHD3 and HMG20B. Transcriptomic validation showed that HDHD3 was significantly upregulated in the diseased group (p < 0.05). Pathway analyses suggested that HDHD3 was associated with glycolysis- and lactylation-related alterations. In the animal model, mechanical stress significantly increased HDHD3 expression and lactylation-related signals (p < 0.05) and was accompanied by cartilage and subchondral bone damage. Folic acid was identified as a candidate compound through drug prediction and molecular docking. Conclusion: This study provides multi-omics and experimental evidence suggesting that HDHD3 and HMG20B are candidate genes associated with TMJ OA. Notably, HDHD3 may be involved in glycolysis- and lactylation-related alterations during TMJ OA progression. Folic acid was identified as a candidate compound, but its therapeutic relevance requires further validation.

IntroductionTo compare the effects of micro-implant (MI) and transpalatal arch (TPA) combined with T-loops of varying gable bend angles on the distalization of mesially impacted canines.MethodsA finite element model of a mesially impacted left maxillary canine was developed using patient CBCT data. Separate models combining MI or TPA with T-loops featuring α-end angulations of 0°, 15°, and 30° were created. A 1 N retraction force was applied, and canine displacement, stress distribution, and rotation were analyzed.ResultsIncreasing the α-end angulation from 0° to 30° changed canine movement from uncontrolled tipping (crown distal/root mesial) to controlled translation (concurrent crown–root distal displacement). The 30°angulation achieved the best root control, minimizing crown–root displacement differences along the X-axis. Among the tested conditions, the 30° angulation showed the most favorable root control pattern in this analysis. Greater angulation also produced lingual root torque and intrusion, maintaining root position within the alveolar bone. Both anchorage systems enabled distalization; however, the TPA group showed slightly greater canine displacement with minor mesial movement and extrusion of anchorage teeth.ConclusionIncreasing the T-loop α-end angulation converts uncontrolled tipping to controlled translation by synchronizing crown and root displacement. Angulations of 15°–30°are recommended for optimal root control. While MI offers greater anchorage stability, TPA remains a practical noninvasive alternative despite some anchorage loss.

BackgroundCleft lip and palate (CLP) are common congenital craniofacial anomalies associated with substantial health and psychosocial burdens. Although maternal smoking during pregnancy has been linked to CLP, observational studies cannot establish causality because of confounding and reverse causation.MethodsWe performed a two-sample Mendelian randomization (MR) study to investigate the causal effect of maternal smoking on offspring CLP. Genetic variants associated with maternal smoking were used as instrumental variables. Summary statistics were obtained from the UK Biobank (maternal smoking) and the FinnGen consortium (CLP). The primary analysis used the inverse-variance weighted (IVW) method, with MR-Egger and weighted median analyses conducted as sensitivity analyses.ResultsIVW analysis demonstrated a significant causal association between maternal smoking and CLP (b = 5.34, SE = 2.50, p < 0.05). Sensitivity analyses yielded consistent results and showed no evidence of substantial heterogeneity or horizontal pleiotropy, supporting the robustness of the findings.ConclusionsOur findings provide genetic evidence supporting a causal relationship between maternal smoking and CLP. These results reinforce the importance of smoking cessation during pregnancy and support public health strategies aimed at reducing preventable risk factors for CLP. Further studies are warranted to investigate the underlying biological mechanisms and validate these findings in diverse populations.

To evaluate the biomechanical effects on mandibular anterior teeth during second molar protraction using different movement patterns following unilateral mandibular first molar loss. A 3D finite element model was developed to simulate unilateral mandibular first molar absence. Three protraction movement patterns were studied: (A) traction hook, (B) anchorage screw, and (C) anchorage screw with extended arm. A 2 N traction force was applied with an archwire-bracket friction coefficient of 0.2. Tooth displacement and movement direction were analyzed. All three movement patterns affected mandibular anterior teeth differently. The traction hook method showed minimal influence on both anterior teeth and molar displacement. The anchorage screw method demonstrated improved protraction but caused significant displacement of anterior teeth away from the edentulous site and pronounced labial inclination. Adding an extended arm reduced labial inclination and enhanced intrusion of anterior teeth while increasing molar displacement, however, anterior dental movement away from the edentulous site is notably increased. Adverse effects on anterior teeth are inevitable during mandibular second molar protraction, regardless of the space closure technique employed. The traction hook produced minimal displacement overall. The anchorage screw with extended arm effectively reduced anterior teeth labial inclination while enhancing molar protraction, though careful attention to midline control is necessary.

BACKGROUND:Circular RNAs (circRNAs) are increasingly recognized as pivotal factors in the pathogenesis of osteoarthritis (OA). CircPVT1 (ID has_circ_0001821), a circRNA family member, plays a substantial role in the progression of various human diseases; however, its specific function in OA remains to be clarified. This study aims to elucidate the expression patterns and interactions among circPVT1, miR-550a-3p, and CX3CR1 in OA, to establish a circPVT1-miR-550a-3p-CX3CR1 competitive endogenous RNA (ceRNA) network, and to evaluate its role in OA chondrocytes and its potential clinical implications. METHODS:First, a ceRNA network involving circPVT1, miR-550a-3p, and CX3CR1 was constructed using bioinformatics tools. Subsequently, direct targeting relationships between circPVT1 and miR-550a-3p, as well as between miR-550a-3p and CX3CR1, were confirmed through dual-luciferase reporter assays. Lastly, the expression patterns and interactions of circPVT1, miR-550a-3p, and CX3CR1 in OA chondrocytes, as well as their impact on chondrocyte proliferation, apoptosis, inflammatory responses, and extracellular matrix regulation, were studied using techniques such as real-time quantitative PCR, Western blot, CCK-8 cell proliferation assay, flow cytometry, and ELISA. RESULTS:The results indicate that circPVT1 is abnormally upregulated in OA chondrocytes. The aberrant expression of circPVT1 impacts chondrocyte proliferation, apoptosis, inflammatory responses, and the synthesis and degradation of the extracellular matrix. Moreover, circPVT1 upregulates CX3CR1 expression by inhibiting miR-550a-3p, thereby affecting the pathological state of OA chondrocytes. CONCLUSION:Elevated expression of circPVT1 in OA chondrocytes indicates a poor prognosis for OA patients. CircPVT1 acts as a ceRNA, competing with miR-550a-3p and weakening its inhibition of CX3CR1, thus boosting CX3CR1 levels, subsequently affecting chondrocyte growth and cell death, the release of inflammatory mediators, and both the formation and breakdown of the extracellular matrix. These findings suggest that circPVT1 could be an important biomarker and therapeutic target for OA.

Aims:Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy. Methods:In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1. Results:Both in vivo and in vitro data revealed that chondrocyte hypertrophic differentiation is promoted by compression. Immunofluorescent and immunoblotting results showed that protein pan-O-GlcNAcylation levels were elevated in these hypertrophic chondrocytes. Pharmacologically inhibiting protein pan-O-GlcNAcylation by OSMI-1 partially mitigated the compression-induced hypertrophic differentiation of chondrocytes. Specifically, runt-related transcription factor 2 (Runx2) and SRY-Box 9 transcription factor (Sox9) were subjected to modification of O-GlcNAcylation under mechanical compression, and pharmacological activation or inhibition of O-GlcNAcylation affected the transcriptional activity of Runx2 but not Sox9. Furthermore, compression-induced protein pan-O-GlcNAcylation in chondrocytes was induced by enhanced expression of glucose transporter 1 (GLUT1), and depletion of GLUT1 by WZB117 dampened the effect of compression on chondrocyte hypertrophy. Conclusion:Our study proposes a novel function of GLUT1-mediated protein O-GlcNAcylation in driving compression-induced hypertrophic differentiation of chondrocytes by O-GlcNAc modification of Runx2, which promoted its transcriptional activity and strengthened the expressions of downstream hypertrophic marker.

Peri-implant inflammation in orthodontic mini-implant may lead to patient discomfort and treatment failure. This study aims to evaluate the effects of diode laser application on the health of mini-implant, preventing peri-implantitis and promoting healing. A randomized controlled trial was conducted involving 30 orthodontic patients (12 males and 18 females, aged 18-32) who had mini-implants implanted on both sides of the maxilla for anterior teeth retraction. One side of each patient was assigned to either an experimental group receiving diode laser irradiation (650 nm, 25 mW) at specific postoperative intervals or a control group receiving simulated radiation. Clinical assessments included plaque index, modified sulcus bleeding index, probing depth, and incidence of peri-implant mucositis and implant mobility, measured at 1, 4, and 12 weeks post-implantation. Additionally, interleukin-1 beta (IL-1\b{eta}) levels in peri-implant fluid were analyzed via enzyme-linked immunosorbent assay (ELISA). Results indicated that the experimental group exhibited significantly lower plaque indices, sulcus bleeding indices, and probing depths (p < 0.05) compared to the control group. Moreover, the experimental group had fewer cases of peri-implant mucositis (p < 0.05), while differences in implant stability were not statistically significant (p > 0.05). IL-1\b{eta} levels were consistently lower in the experimental group throughout the study duration (p < 0.05). In conclusion, adjunctive diode laser therapy appears to enhance peri-implant health and reduce complications associated with orthodontic mini-implants, suggesting a promising direction for improving patient outcomes in orthodontics. Future research should explore long-term effects and the mechanisms underlying these benefits.

Conventional anti-biofilm strategies for periodontitis predominantly focus on bacterial populations, often inadvertently facilitating the resurgence of fungi and aggravating the persistence of biofilms. Here, we report a pH-responsive copper-gallic acid core-shell nanoplatform (CGC@HSAF NP) that eradicates drug-resistant fungal-bacterial biofilms through cross-kingdom synergy, marking a significant advancement over traditional species-specific methodologies. The calcium carbonate shell facilitates an acid-triggered release of the antifungal agent HSAF, which selectively disrupts fungal membranes by inhibiting ceramide synthase. This mechanism not only fractures the biofilm scaffolds but also preserves the viability of dental follicle stem cells (113% viability compared to only 2% for free HSAF). Such disruption creates penetration channels for bactericidal Cu2+ ions, leading to significantly enhanced biofilm removal efficacy compared to monotherapy approaches. Importantly, this dual microbial annihilation effectively halts the metabolic cross-feeding that drives biofilm reformation, thereby addressing the persistent kill-recolonize cycle that plagues existing treatments. Concurrently, gallic acid serves as a potent scavenger of reactive oxygen and nitrogen species and mitigates pro-inflammatory cytokine production, thereby remodeling the pathogenic microenvironment favorably. In a rat model of periodontitis, when delivered via a thermosensitive hydrogel, the CGC@HSAF NPs not only eliminated biofilms but also stimulated alveolar bone regeneration. This work redefines the design of antimicrobial agents by emphasizing the disruption of ecological networks rather than merely targeting isolated species, heralding a novel paradigm in the battle against biofilm-associated infections.

PURPOSE:To screen the stress-sensitive genes in myoblasts and reveal the potential target genes and their regulatory mechanisms of facial muscle remodeling induced by functional orthopaedic force. METHODS:The procedure involved the use of gene microarray technology to identify the differentially expressed genes(DEGs) in myoblasts. DEGs were then categorized by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Furthermore, real-time quantitative PCR(qRT-PCR) was used to verify the DEGs. Western blot, transmission electron microscopy(TEM), and confocal laser scanning microscope(CLSM) were employed to detect the effect of stress on autophagy in myoblasts. The data were analyzed by SPSS 17.0 software package. RESULTS:A total of 1 410 DEGs were identified in stretched myoblasts, with 788 up-regulated and 622 down-regulated genes. GO enrichment analysis indicated that DEGs were primarily involved in signal transduction, biopolymer metabolic process, and protein metabolic process. KEGG analysis revealed that DEGs were primarily associated with ECM-receptor interaction, pathway in cancer, MAPK signaling pathway, focal adhesion and lysosome. Both TEM and CLSM showed that stress could promote the formation of autophagosomes, and Western blot demonstrated that stress could promote the expression of autophagy-related molecules Beclin-1 and LC3-II. Rapamycin could enhance all the above processes, while 3-MA could inhibit them. CONCLUSIONS:Autophagy may play an important role in the regulation of myoblast fate induced by cyclic tensile stress.

This study integrates human cohorts (n=60, 30 high-altitude [4300m] vs. 30 low-altitude [50m]) and C57BL/6 mouse models to elucidate regulatory mechanisms of metabolic adaptation via serum exosomal miRNAs under hypoxic stress. High-altitude exposure significantly improved metabolic health in humans (reduced BMI, FBG, HOMA-IR, Tch, TG, LDL-C; increased HDL-C) and mice (decreased weight gain, insulin, FBG, HOMA-IR, FFA, TG; p<0.05). High-throughput sequencing identified 57 differentially expressed miRNAs (22↑/35↓) in hypoxic mice, enriched in Ras/MAPK signaling and metabolic networks. Cross-species validation confirmed hsa-miR-5100 (AUC=0.9089), hsa-miR-184-3p (AUC=0.8233), and hsa-miR-122-5p (AUC=0.7521) as diagnostic biomarkers. We propose the first "exosomal miRNA-signaling pathway-metabolic phenotype" trinity framework, providing novel targets for hypoxia adaptation and metabolic disease intervention.

OBJECTIVES:The objective of this investigation was to assess the stress and displacement pattern of the craniomandibular complex by employing finite element methodology to simulate diverse angulations of inclined planes that are incorporated in the Twin Block appliance. METHODS:A 3D finite element representation was established by use of Cone Beam Computed Tomography (CBCT) scans. This comprehensive structure included craniofacial skeletal components, the articular disc, a posterior disc elastic layer, dental elements, periodontal ligaments, and a Twin Block appliance. This investigation is the first to incorporated inclined planes featuring three distinct angulations (45, 60, and 70°) as the study models. Mechanical impacts were evaluated within the glenoid fossa, tooth, condylar, and articular disc regions. RESULTS:In all simulations, the stress generated by the Twin Block appliance was distributed across teeth and periodontal ligament, facilitating the anterior movement of mandibular teeth and the posterior displacement of maxillary teeth. Within the temporomandibular joint region, compressive forces on the superior and posterior facets of the condyle diminished, coinciding with the stress configuration that fosters condylar and mandibular growth. Stress dispersion homogenized in the condylar anterior facet and articular disc, with considerable tensile stress in the glenoid fossa's posterior aspect conforming to stress distribution that promote fossa reconfiguration. The 70° inclined plane exerts the highest force on the tissues. The condyle's maximum and minimum principal stresses are 0.36 MPa and -0.15 MPa, respectively, while those of the glenoid fossa are 0.54 MPa and -0.23 MPa. CONCLUSION:Three angled appliances serve the purpose of advancing the mandible. A 45° inclined plane relative to the occlusal plane exerts balanced anteroposterior and vertical forces on the mandibular arch. Steeper angles yield greater horizontal forces, which may enhance forward growth and efficient repositioning.

BACKGROUND:Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. METHODS:An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. In vitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. RESULTS:Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. In vitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. CONCLUSION:Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, often associated with a poor prognosis for patients. One of the major challenges in managing PDAC is the difficulty in early diagnosis, owing to the limited and invasive nature of current diagnostic methods. Recent studies have identified the oral microbiome as a potential source of non-invasive biomarkers for diseases, including PDAC. In this study, we focused on leveraging the differential expression of virulence factors (VFs) encoded by the oral microbiome to create a diagnostic tool for PDAC. We observed a higher alpha diversity in VF categories among PDAC patients compared to healthy controls. We then identified a panel of VF categories that were significantly upregulated in PDAC patients, these being associated with bacterial adherence, exoenzyme production, and nutritional/metabolic processes. Moreover, Streptococcus-derived VFs were notably enriched in PDAC patients. We developed a diagnostic model using random forest analysis based on the levels of these VFs. The model's diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.88, indicating high accuracy in differentiating PDAC patients from healthy controls. Our findings suggest that VFs encoded by the oral microbiome hold potential as diagnostic tools for PDAC, offering a non-invasive approach that could significantly enhance early detection and prognosis, ultimately leading to improved patient outcomes.

BACKGROUND:Mesenchymal stem cells (MSCs) derived from the synovium, known as synovium mesenchymal stem cells (SMSCs), exhibit significant potential for articular cartilage regeneration owing to their capacity for chondrogenic differentiation. However, the microRNAs (miRNAs) governing this process and the associated mechanisms remain unclear. While mechanical stress positively influences chondrogenesis in MSCs, the miRNA-mediated response of SMSCs to mechanical stimuli is not well understood. OBJECTIVE:This study explores the miRNA-driven mechano-transduction in SMSCs chondrogenesis under mechanical stress. METHODS:The surface phenotype of SMSCs was analysed by flow cytometry. Chondrogenesis capacities of SMSCs were examined by Alcian blue staining. High throughput sequencing was used to screen mechano-sensitive miRNAs of SMSCs. The RNA expression level of COL2A1, ACAN, SOX9, BMPR2 and miR-143-3p of SMSCs were tested by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-143-3p and TLR4 was confirmed by luciferase reporter assays. The protein expression levels of related genes were assessed by western blot. RESULTS:High-throughput sequencing revealed a notable reduction in miR-143-3p levels in mechanically stressed SMSCs. Gain- or loss-of-function strategies introduced by lentivirus demonstrated that miR-143-3p overexpression hindered chondrogenic differentiation, whereas its knockdown promoted this process. Bioinformatics scrutiny and luciferase reporter assays pinpointed a potential binding site for miR-143-3p within the 3'-UTR of bone morphogenetic protein receptor type 2 (BMPR2). MiR-143-3p overexpression decreased BMPR2 expression and phosphorylated Smad1, 5 and 8 levels, while its inhibition activated BMPR2-Smad pathway. CONCLUSION:This study elucidated that miR-143-3p negatively regulates SMSCs chondrogenic differentiation through the BMPR2-Smad pathway under mechanical tensile stress. The direct targeting of BMPR2 by miR-143-3p established a novel dimension to our understanding of mechano-transduction mechanism during SMSC chondrogenesis. This understanding is crucial for advancing strategies in articular cartilage regeneration.

We read and discussed with great interest the manuscript by Zhang et al (Zhang Y, Zheng X, Zhang Q, He Z, Huang W, Yan X, et al. Clinical finite element analysis of mandibular displacement model treated with Twin-block appliance. Am J Orthod Dentofacial Orthop 2023;164:p395–405) published in the September 2023 issue. Clinical finite element analysis of mandibular displacement model treated with Twin-block applianceAmerican Journal of Orthodontics and Dentofacial OrthopedicsVol. 164Issue 3PreviewThe mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates. Full-Text PDF Authors’ responseAmerican Journal of Orthodontics and Dentofacial OrthopedicsVol. 164Issue 4PreviewThank you for your comments and suggestion concerning our manuscript. The comments and suggestions are valuable and helpful for revising and improving our paper and the important guiding significance of our research. We have carefully studied these comments and responded, hoping for your approval. We have replied below to your 9 comments and/or questions. Full-Text PDF

Objective > The modified clear twin-block aligner (CTBA) was developed to provide a mandibular advancement appliance for the treatment of mandibular retrognathia. The objective of this study was to analyse the stress distribution changes of CTBA with 45 degrees, 60 degrees and 70 degrees bite blocks. Material and methods > A three-dimensional model of the craniomaxillofacial bones and teeth was generated from a spiral computed tomography (CT) scan. The models of the articular disc, capsule, periodontal ligament and CTBA were constructed mathematically. After assigning the appropriate material properties and the boundary condition using ABAQUS software, we simulated the CTBA with different bite blocks to analyse the mechanical effects. Results > In the temporomandibular joint (TMJ) region, the posterior aspect of the condyle and glenoid fossa experienced tensile stress that was approximately about 22 times greater at 70 degrees than at 45 degrees. The Von Mises stress distribution on the articular disc tended to be uniform. The strain direction of the condyle was backward. In the maxillary bone, the stress on the labial alveolar bone was about 5.83 MPa at 70 degrees and greater than that on the lingual side. The resulting displacement of the dentition revealed a tendency for the upper teeth to shift backward and the lower teeth to move forward by 0.46 to 0.49 mm. The foregoing stress and displacement rose as the angle of the bite blocks increased. Conclusions > CTBA with 70 degrees bite blocks constituted an advantageous biomechanical setting for the treatment of mandibular retrognathia in teenagers and provided a superior therapeutic effect.

The 3' untranslated region (3'UTR) of mRNA plays a key role in the post-transcriptional regulation of gene expression. Most eukaryotic protein-coding genes express 3'UTR isoforms owing to alternative cleavage and polyadenylation (APA). The 3'UTR isoform expression profile of a cell changes in cell proliferation, differentiation, and stress conditions. Here, we review the emerging theme of regulation of 3'UTR isoforms in cell metabolic reprogramming, focusing on cell growth and autophagy responses through the mTOR pathway. We discuss regulatory events that converge on the Cleavage Factor I complex, a master regulator of APA in 3'UTRs, and recent understandings of isoform-specific m6A modification and endomembrane association in determining differential metabolic fates of 3'UTR isoforms.

Objective: Mandibular growth that is induced by functional appliances is closely associated with skeletal and neuromuscular adaptation. Accumulating evidence has proved that apoptosis and autophagy have a vital role in adaptation process. However, little is known about the underlying mechanisms. This study sought to determine whether ATF-6 is involved in stretch-induced apoptosis and autophagy in myoblast. The study also sought to uncover the potential molecular mechanism. Materials and methods: Apoptosis was assessed by TUNEL and Annexin V and PI staining. Autophagy was detected by transmission electron microscopy (TEM) analysis and immunofluorescent staining for autophagy-related protein light chain 3 (LC3). Real time-PCR and western blot were performed to evaluate the expression level of mRNA and proteins that were associated with endoplasmic reticulum stress (ERS), autophagy and apoptosis. Results: Cyclic stretch significantly decreased the cell viability and induced apoptosis and autophagy of myoblasts time-dependently. Stretching stimuli activated ATF-6 pathway and induced ERS-mediated apoptosis. Moreover, using 4-PBA significantly inhibited ERS-related apoptosis, as well as partially decreasing autophagy. In addition, inhibition of autophagy by 3-MA enhanced apoptosis by affecting the expression of CHOP and Bcl-2. However, it had no obvious effects on ERS-related proteins of GRP78 and ATF-6. More importantly, knockdown ATF-6 effectively weakened apoptosis and autophagy. It did so by regulating the expression of Bcl-2, Beclin1 and CHOP, but not cleaved Caspase-12, LC3II and p62 in stretched myoblast. Conclusion: ATF-6 pathway was activated in myoblast by mechanical stretch. ATF-6 may regulate the process of stretch-induced myoblast apoptosis and autophagy via CHOP, Bcl-2 and Beclin1 signaling.