IFRD1 promotes tumor cells "low-cost" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.

CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR-1246/PEG3 signaling.

Ischemia‒reperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.

Construction of Fu brick tea polysaccharide-cold plasma modified alginate microgels for probiotic delivery: Enhancing viability and colonization.

Emerging food processing technologies provide broader avenues for enhancing probiotic delivery systems. In this study, the new Fu brick tea polysaccharide (FBTP) was extracted and combined with cold plasma-modified alginate nano-montmorillonite (AMT) to prepare microgels by ionic gelation to improve the viability of encapsulated Lactobacillus kefiranofaciens JKSP109. Results showed that cold plasma treatment for 3 min changed the surface charge of AMT biopolymer solution, and FBTP addition reduced the particle size to the lowest of 223 ± 5.50 nm. Morphological analysis showed that the AMT treated with cold plasma for 3 min and FBTP (C3AMT + FBTP) formed a dense microgel through electrostatic interaction, and the probiotics were randomly distributed in their internal polysaccharide network, as well as the interlayer and surrounding of nanoparticles. The probiotics immobilized in C3AMT + FBTP microgel exhibited the highest viability (8.48 ± 0.03 log CFU/g) and colonic colonization after exposure to simulated gastrointestinal conditions. In addition, the good antioxidant activity of FBTP reduced the loss of probiotic viability during storage, with only 2.58 log CFU/g decreased after 4 weeks. Therefore, such probiotic products enriched with natural bioactive ingredients can be developed as a potential functional food additive.

Gated CNN-Transformer Network for Automatic Cardiovascular Diagnosis using 12-lead Electrocardiogram.

12-lead electrocardiogram (ECG) is a widely used method in the diagnosis of cardiovascular disease (CVD). With the increase in the number of CVD patients, the study of accurate automatic diagnosis methods via ECG has become a research hotspot. The use of deep learning-based methods can reduce the influence of human subjectivity and improve the diagnosis accuracy. In this paper, we propose a 12-lead ECG automatic diagnosis method based on channel features and temporal features fusion. Specifically, we design a gated CNN-Transformer network, in which the CNN block is used to extract signal embeddings to reduce data complexity. The dual-branch transformer structure is used to effectively extract channel and temporal features in low-dimensional embeddings, respectively. Finally, the features from the two branches are fused by the gating unit to achieve automatic CVD diagnosis from 12-lead ECG. The proposed end-to-end approach has more competitive performance than other deep learning algorithms, which achieves an overall diagnostic accuracy of 85.3% in the 12-lead ECG dataset of CPSC-2018.

Prediction of drug permeation through microneedled skin by machine learning.

Stratum corneum is the outermost layer of the skin preventing external substances from entering human body. Microneedles (MNs) are sharp protrusions of a few hundred microns in length, which can penetrate the stratum corneum to facilitate drug permeation through skin. To determine the amount of drug delivered through skin, in vitro drug permeation testing is commonly used, but the testing is costly and time-consuming. To address this issue, machine learning methods were employed to predict drug permeation through the skin, circumventing the need of conducting skin permeation experiments. By comparing the experimental data and simulated results, it was found extreme gradient boosting (XGBoost) was the best among the four simulation methods. It was also found that drug loading, permeation time, and MN surface area were critical parameters in the models. In conclusion, machine learning is useful to predict drug permeation profiles for MN-facilitated transdermal drug delivery.

The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia.

Microtia is a congenital deformity of the ear with an incidence of about 0.8-4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

The psc-CVM assessment system: A three-stage type system for CVM assessment based on deep learning.

BACKGROUND: Many scholars have proven cervical vertebral maturation (CVM) method can predict the growth and development and assist in choosing the best time for treatment. However, assessing CVM is a complex process. The experience and seniority of the clinicians have an enormous impact on judgment. This study aims to establish a fully automated, high-accuracy CVM assessment system called the psc-CVM assessment system, based on deep learning, to provide valuable reference information for the growth period determination. METHODS: This study used 10,200 lateral cephalograms as the data set (7111 in train set, 1544 in validation set and 1545 in test set) to train the system. The psc-CVM assessment system is designed as three parts with different roles, each operating in a specific order. 1) Position Network for locating the position of cervical vertebrae; 2) Shape Recognition Network for recognizing and extracting the shapes of cervical vertebrae; and 3) CVM Assessment Network for assessing CVM according to the shapes of cervical vertebrae. Statistical analysis was conducted to detect the performance of the system and the agreement of CVM assessment between the system and the expert panel. Heat maps were analyzed to understand better what the system had learned. The area of the third (C3), fourth (C4) cervical vertebrae and the lower edge of second (C2) cervical vertebrae were activated when the system was assessing the images. RESULTS: The system has achieved good performance for CVM assessment with an average AUC (the area under the curve) of 0.94 and total accuracy of 70.42%, as evaluated on the test set. The Cohen's Kappa between the system and the expert panel is 0.645. The weighted Kappa between the system and the expert panel is 0.844. The overall ICC between the psc-CVM assessment system and the expert panel was 0.946. The F1 score rank for the psc-CVM assessment system was: CVS (cervical vertebral maturation stage) 6 > CVS1 > CVS4 > CVS5 > CVS3 > CVS2. CONCLUSIONS: The results showed that the psc-CVM assessment system achieved high accuracy in CVM assessment. The system in this study was significantly consistent with expert panels in CVM assessment, indicating that the system can be used as an efficient, accurate, and stable diagnostic aid to provide a clinical aid for determining growth and developmental stages by CVM.

Effects of ACEI/ARB or CCB use on atrial fibrillation in hypertensive patients following permanent pacemaker implantation.

Aims: Permanent pacemaker implantation (PPI) combined with hypertension leads to a higher risk of new-onset atrial fibrillation (NOAF) for patients. Hence, it is essential to study how to reduce this risk. Currently, the effects of the two common anti-hypertensive drugs, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and calcium channel blockers (CCB), on the risk of NOAF for such patients remain unknown. This study aimed to investigate this association. Methods: This single-center retrospective study included hypertensive patients with PPI and without prior history of AF/atrial flutter, heart valve disease, hyperthyroidism, etc. Patients were classified into ACEI/ARB group and CCB group based on their exposure drug information. The primary outcome was NOAF events that occurred within 12 months after PPI. The secondary efficacy assessments were the changes from baseline to follow-up in blood pressure and transthoracic echocardiography (TTE) parameters. A multivariate logistic regression model was used to verify our aim. Results: A total of 69 patients were finally included (51 on ACEI/ARB and 18 on CCB). Both univariate analysis [odds ratio (OR) 0.241, 95% confidence interval (CI) 0.078-0.745] and multivariate analysis (OR: 0.246, 95% CI: 0.077-0.792) demonstrated that ACEI/ARB were associated with a lower risk of NOAF compared to CCB. The mean reduction in left atrial diameter (LAD) from baseline was greater in ACEI/ARB group than in CCB group (P = 0.034). There was no statistical difference between groups in blood pressure and other TTE parameters after treatment. Conclusion: For patients with PPI combined with hypertension, ACEI/ARB may be superior to CCB in selecting anti-hypertensive drugs, as ACEI/ARB further reduces the risk of NOAF. One reason for this may be that ACEI/ARB improves left atrial remodelling such as LAD better.

Recent progress and clinical applications of advanced biomaterials in cosmetic surgery.

Materials of different allogeneic or xenogeneic or autologous origins are widely used as soft-tissue fillers or structural scaffolds in the field of cosmetic surgery, while complications including prosthesis infection, donor site deformity and filler embolization have always been difficult problems for plastic surgeons. The application of novel biomaterials may bring in hopeful solutions for these problems. Recently, some advanced biomaterials, such as regenerative biomaterials can effectively promote the repair of defective tissues, which have been proven to have good therapeutic as well as cosmetic effects in cosmetic surgery. Therefore, biomaterials with active compounds have drawn significant attention for the tissue regeneration of reconstructive and esthetic treatment. Some of these applications have achieved better clinical outcomes than traditional biological materials. This review summarized recent progress and clinical applications of advanced biomaterials in cosmetic surgery.

Comparison of risk of complication between neuraxial anaesthesia and general anaesthesia for hip fracture surgery: a systematic review and meta-analysis.

BACKGROUND: Controversy remains over the choice of anaesthetic technique for patients undergoing surgery for hip fracture. AIM: The aim was to compare the risk of complication of neuraxial anaesthesia with that of general anaesthesia in patients undergoing hip fracture surgery. METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and was registered at PROSPERO (CRD42022337384). The study included eligible randomised controlled trials published before February 2022. Data synthesis was performed to compare the differences between general and neuraxial anaesthesia. Meta-regression analysis was performed to investigate the influence of the publication year. A subgroup analysis was performed based on patient age and the anaesthetic technique used. A grading of recommendations, assessment, development and evaluations assessment was performed to assess the quality of each outcome. RESULTS: Twenty randomised controlled trials and 4802 patients were included. Data synthesis revealed significant higher risk of acute kidney injury in the general anaesthesia group ( P =0.01). There were no significant differences between the two techniques in postoperative short-term mortality ( P =0.34), delirium ( P =0.40), postoperative nausea and vomiting ( P =0.40), cardiac infarction ( P =0.31), acute heart failure ( P =0.34), pulmonary embolism ( P =0.24) and pneumonia ( P =0.15). Subgroup analysis based on patient age and use of sedative medication did not reveal any significant differences. Meta-regression analysis of the publication year versus each adverse event revealed no statistically significant differences. CONCLUSION: A significantly higher risk of postoperative acute kidney injury was found in patients receiving general anaesthesia. This study revealed no significant differences in terms of postoperative mortality and other complications between general and neuraxial anaesthesia. The results were consistent across the age groups.

Bioengineered MSC-derived exosomes in skin wound repair and regeneration.

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis.

The identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-series gene expression data in a zebrafish osteoporosis model, which revealed that cyclin-dependent kinase inhibitor 1 A (cdkn1a) is a core DNB. We found that cdkn1a negatively regulates osteogenesis, as evidenced by loss-of-function and gain-of-function studies. Specifically, CRISPR/Cas9-mediated cdkn1a knockout in zebrafish significantly altered skeletal development and increased bone mineralization, whereas inducible cdkn1a expression significantly contributed to osteoclast differentiation. We also found several mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. To summarize, in this study, we provided new insights into the dynamic nature of osteoporosis and identified cdkn1a as an early-warning signal of osteoporosis onset.

Secrecy Energy Efficiency Enhancement in UAV-Assisted MEC System.

A secrecy energy efficiency optimization scheme for a multifunctional unmanned aerial vehicle (UAV) assisted mobile edge computing system is proposed to solve the computing power and security issues in the Internet-of-Things scenario. The UAV can switch roles between a computing UAV and jamming UAV based on the channel conditions. To ensure the security of the content and the system energy efficiency in the process of offloading computing tasks, the UAV trajectory, uplink transmit power, user scheduling, and offload task are jointly optimized, and an updated-rate assisted block coordinate descent (BCD) algorithm is used. Simulation results show that this scheme efficiently improves the secrecy performance and energy efficiency of the system. Compared with the benchmark scheme, the secrecy energy efficiency of the scheme is improved by 38.5%.

Anatomical Guidelines for Thigh Lipoplasty Based on Cadaveric Dissection of the Superficial Fascial System in the Thigh.

BACKGROUND: Although widely accepted as an optimal procedure in thigh contouring, liposuction can result in complications, such as skin irregularity or aspiration inadequacy. A main cause might be insufficient knowledge of the superficial fascial system (SFS). The authors aimed to explore the characteristics of the SFS in the thigh and propose anatomical guidelines and new zoning for liposuction-assisted thigh contouring. METHODS: A total of 20 fresh female thighs were dissected from the skin to deep fascia to observe and compare changes in the SFS from the medial to the lateral side and from the proximal to the distal end. RESULTS: The thigh was divided into four units, namely, the medial (three subunits: upper, middle, and lower), anterior, posterior (three subunits: upper medial, upper lateral, and middle lower parts), and lateral thigh. The authors found that the form of the SFS has regional variations. Therefore, based on these varied features, four anatomical scenarios (degrees I to IV) and one functional section (hip-contour support) were devised from the eight subunits. Five different liposuction methods were formulated to manage these subunits: all-layer mass liposuction, normal aspiration, border feather-out, restricted lipoplasty, and anchor. CONCLUSIONS: The SFS of the thigh showed a regional variation pattern, based on which the authors proposed a series of new anatomy-based liposuction approaches. A well-sculpted thigh with its different sections presented in harmony can be safely obtained using these approaches.

The Superficial Fascia System: Anatomical Guideline for Zoning in Liposuction-Assisted Back Contouring.

BACKGROUND: Dorsal contour deformity presents with different manifestations in each part of the back, such as back rolls, iliac crest deposit, and buffalo hump. However, scant current literature exists on the anatomical basis of dorsal contour deformity. The aim of this study was to better understand the anatomical characteristics of the back, and to propose evidence-based zoning principles for liposuction-assisted back contouring. METHODS: A total of 12 fresh cadavers were dissected for observation of each hierarchy in the vertical order (skin to deep fascia) and transverse comparison of the superficial fascial system (SFS) in the scapular-infrascapular-lumbar triangle region. Full-dorsum vectorial sections were used for the study of suprascapular fat deposits. RESULTS: The SFS acts as a bridge connecting all levels of the dorsal subcutaneous tissue. Macroscopically, it is denser in the scapular and lumbar triangle regions and looser in the infrascapular region; microscopically, the ultrastructure of the retinaculum cutis consists of loose interlobular fascia and stiff functional fascia. CONCLUSIONS: The regional variation pattern of the SFS in the back was consistent with observed back contour deformities in Asian female patients. A better understanding of the topographic anatomy of the back applied to evidenced zoning is the basis for improving surgical precision and avoiding dorsal contour deformity.

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction.

Aims: At present, the effects of Glucagon-Like Peptide 1 Receptor agonists (GLP-1RAs) on arrhythmia in patients with type 2 diabetes mellitus (T2DM) and myocardial infarction (MI) are still unclear. Hence, this systematic review and meta-analysis aimed to investigate this association. Methods and results: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) that compared GLP-1RAs with placebo and met the critical criterion of a proportion of patients with T2DM and MI > 30% were included to verify our purpose indirectly. The outcomes of interest included atrial arrhythmias, ventricular arrhythmias, atrioventricular block (AVB), sinus arrhythmia, and cardiac arrest. Relative risk (RR) and 95% confidence intervals (CI) were pooled using a random-effects model. We included five RCTs with altogether 31,314 patients. In these trials, the highest proportion of patients with T2DM and MI was 82.6%, while the lowest was 30.7%. Compared to placebo, GLP-1RAs were associated with a lower risk of atrial arrhythmias (RR 0.81, 95% CI 0.70-0.95). There was no significant difference in the risk of ventricular arrhythmias (RR 1.26, 95% CI 0.87-1.80), AVB (RR 0.95, 95% CI 0.63-1.42), sinus arrhythmia (RR 0.62, 95% CI 0.26-1.49), and cardiac arrest (RR 0.97, 95% CI 0.52-1.83) between groups. Conclusion: GLP-1RAs may be associated with reduced risk for atrial arrhythmias, which seems more significant for patients with T2DM combined with MI. More studies are needed to clarify the definitive anti-arrhythmic role of this drug.

Novel insights into nanomaterials for immunomodulatory bone regeneration.

Bone defect repair caused by trauma, congenital malformation, tumors, infection or systemic diseases remains the focus of attention in regeneration medicine. Recent advances in osteoimmunology indicate that immune cells and correlative cytokines modulate the delicate balance between osteoblasts and osteoclasts and induce a favorable microenvironment for bone regeneration. With superior attributes that imitate the three-dimensional architecture of natural bone, excellent fabricability, mechanical and biological properties, nanomaterials (NMs) are becoming attractive in the field of bone tissue engineering. Particularly, it could be an effective strategy for immunomodulatory bone regeneration by engineering NMs involved in composition nature, nanoarchitectural morphology, surface chemistry, topography and biological molecules, whose mechanisms potentially refer to regulating the phenotype of high-plastic immune cells and inducing cytokine secretion to accelerate osteogenesis. Despite these prominent achievements, the employment of NMs is poorly translated into clinical trials due to the lack of knowledge about the interaction between NMs and the immune system. For this reason, we sketch out the hierarchical structure of bone and its natural healing process, followed by discussion about the effects of immune cells on bone regeneration. Novel horizons focusing on recent progressions in the architectural and physicochemical performances of NMs and their impacts on the body defence mechanism are also emphasized, hoping to provide novel insights for the fabrication of bone graft materials in tissue engineering.

Effects of the advanced mandibular spring on mandibular retrognathia treatment: a three-dimensional finite element study.

BACKGROUND: The Advanced Mandibular Spring (AMS) was newly developed as a dentofacial orthopedic appliance in conjunctive use of clear aligners to treat Class II malocclusion with mandibular retrognathia in adolescents. This study aimed to launch a biomechanical assessment and evaluate whether the stress patterns generated by AMS promote mandibular growth. METHODS: A three-dimensional finite element model was constructed using images of CBCT and spiral CT. The model consisted of craniomaxillofacial bones, articular discs, retrodiscal elastic stratum, masticatory muscle, teeth, periodontal ligament, aligner and AMS. Mechanical effects were analyzed in three types of models: mandibular postural position, mandibular advancement with AMS, and mandibular advancement with only muscular force. RESULTS: The stress generated by AMS was distributed to all teeth and periodontal ligament, pushing mandibular teeth forward and maxillary teeth backward. In the temporomandibular joint area, the pressure in the superior and posterior aspects of the condyle was reduced, which conformed to the stress pattern promoting condylar and mandibular growth. Stress distribution became even in the anterior aspect of the condyle and the articular disc. Significant tensile stress was generated in the posterior aspect of the glenoid fossa, which conformed to the stress pattern stimulating the remodeling of the fossa. CONCLUSIONS: AMS created a favorable biomechanical environment for treating mandibular retrognathia in adolescents.