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Background Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019). Methods Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence. Results Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705–1.706)) and 2019 (RR: 1.602 (1.619–1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910–1.915)) was observed in the age group of 10–14. Relative sex difference had a significant positive relationship with SDI (standardized β = 0.267, P < 0.001). Conclusions Despite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.

Orthodontic tooth movement (OTM) is primarily driven by alveolar bone remodeling, wherein tension-induced osteogenesis plays a central role. Importin7 (IPO7) has been identified as a highly mechanoresponsive nuclear transport receptor (NTR). However, its role in regulating tension-induced osteogenesis during OTM and its underlying mechanism remains elusive. In the present study, cyclic tensile strain and a rat OTM model were used to investigate the role of IPO7. The results revealed that IPO7 was significantly expressed both in vitro and in vivo following exposure to mechanical stretch. Moreover, IPO7 knockdown inhibited tension-induced osteogenesis in BMSCs. Upon mechanical force stimulation, IPO7 translocated from the cytoplasm to the nucleus. Furthermore, immunoprecipitation (IP) coupled with mass spectrometry (MS) was performed and demonstrated that RUNX2 was one of the IPO7-interacting proteins related to osteogenesis. Although RUNX2 has been established to translocate to the nucleus to facilitate osteogenesis, whether it is IPO7 that regulate RUNX2 nuclear input during tension-induced osteogenesis remains to be determined. Then, the interaction between IPO7 and RUNX2 was further validated via co-immunoprecipitation (co-IP) and colocalization assays in BMSCs using immunofluorescence. Taken together, this study demonstrates that IPO7 promotes tension-induced osteogenesis by regulating the nucleoplasmic localization of RUNX2. Thus, targeting IPO7 may represent a prospective therapeutic strategy for enhancing alveolar bone remodeling and the efficacy of orthodontic treatment.

Background Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. Methods An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. Results Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: − 1.63, P  < 0.0001), SNB (MD: − 1.96, P  < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P  < 0.0001), 1. NA (MD: 1.96, P  = 0.009), 1-NA (MD: 0.66, P  = 0.004), and 1-NB (MD: 1.03, P  < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P  = 0.0050), SN-OP (MD: 3.05, P  < 0.0001), PP-MP (MD: 4.92, P  < 0.0001) and SNGoGn (MD: 4.10, P  < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: − 3.48, P  = 0.0009), PAS (MD: − 2.11, P  < 0.0001), and C3-H (MD: − 1.34, P  < 0.0001) were lower in mouth breathing group. Conclusions The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children. Trial registration crd-register@york.ac.uk, registration number CRD42019129198.

Macrophage pyroptosis drives the secretion of IL-1β, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus–periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus–periodontitis in rats, we found that IL-1β and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus–periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1β production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1β secretion. Our study demonstrates that hyperglycemia promotes IL-1β production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus–periodontitis.

•EEG-based multi-scale deep learning predicts individual iTBS response in major depressive disorder.•Two neurophysiological subtypes are identified with distinct baseline symptoms and clinical outcomes.•DCM-PEB analysis reveals subtype-specific frontal–temporal–parietal–motor connectivity patterns.•Connectivity patterns correlate with treatment efficacy, suggesting candidate mechanistic biomarkers. Response to transcranial magnetic stimulation (TMS) in major depressive disorder (MDD) is highly variable, underscoring the need for biomarkers that both predict treatment efficacy and elucidate underlying neural mechanisms. We integrated deep learning and computational modeling to identify subtype-specific responses to intermittent theta-burst stimulation (iTBS) in MDD. Resting-state EEG and event-related potentials were collected from 198 patients across two independent cohorts (training: N = 125; validation: N = 73). A total of 55,476 EEG epochs were analyzed using a multi-scale convolutional recurrent neural network (MCRNN). To probe circuit-level mechanisms, Dynamic Causal Modeling with Parametric Empirical Bayes (DCM-PEB) was applied to assess subtype-specific effective connectivity. The MCRNN achieved robust predictive performance (accuracy = 0.91; 95% CI: 0.85–0.97 in the training cohort; 0.86; 95% CI: 0.76–0.96in the validation cohort), reliably stratifying patients into two neurophysiological subtypes. These subtypes differed in baseline symptom severity and clinical response trajectories. DCM-PEB revealed distinct effective connectivity signatures within frontal–temporal–parietal–motor circuits, with posterior probability exceeding 0.99, linking subtype-specific neural dynamics to treatment outcomes. EEG-based deep learning, combined with biophysically informed connectivity modeling, enables reliable prediction of iTBS outcomes in MDD. Subtype-specific disruptions in frontal–temporal coupling emerge as candidate biomarkers, offering mechanistic insight into neuromodulation response and a framework for personalized TMS interventions.

This study aimed to investigate the inherent asymmetry of mandibular functional units and to compare the degree of asymmetry between adults with different sagittal skeletal patterns. Ninety CBCTs scans of normodivergent adults with a normal degree of chin deviation, representing different sagittal skeletal patterns (Classes I, II, and III) were included; 30 each. Three-dimensional mandibular models were generated, and volumetric and linear bilateral measurements were obtained for the hemimandible and the condylar, coronoid, ramus, angular, alveolar, body, and chin units. The degree of asymmetry was presented using the asymmetry index (AI) and between groups measurements were compared using ANOVA test and GEE model. The mean AI values were significantly higher than 0% across all measurements for all sagittal skeletal patterns. Volumetric measurements yielded higher overall AI values than linear measurements (3.55 ± 3.6 vs 1.83 ± 1.74, P < 0.001). Negative and positive correlation values were found between mandibular units, thus supporting the theory of compensatory mechanism of the mandible. In all groups, the coronoid process volume and angular unit length exhibited the highest degree of asymmetry, whereas the total body length and hemimandibular volume showed the lowest. No significant differences were found in the AI of volumetric or linear measurements between sagittal skeletal patterns (P > 0.05). Mandibular functional units exhibited a degree of asymmetry in adults from different sagittal skeletal patterns. Clinical Relevance : This study quantifies the inherent asymmetry and compensatory mechanisms in mandibular functional units of adults with normal chin deviation.

Hypoxemia is a common complication associated with anesthesia in painless gastroscopy. With the aging of the social population, the number of cases of hypoxemia among middle-aged and elderly patients is increasing. However, tools for predicting hypoxemia in middle-aged and elderly patients are lacking. In this study, we investigated the risk factors for hypoxemia in middle-aged and elderly outpatients undergoing painless gastroscopy based on machine learning and constructed a risk prediction model. In this retrospective study, we included the data on 1,348 outpatients undergoing painless gastroscopy. In total, 26 characteristic variables, including demographic information, past medical history, and clinical data of the patients were included, and BorutaShap was used for feature selection. Five machine learning algorithm models, including logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGB), and light gradient boosting machine (LightGBM), were selected. The best models were selected based on the area under the receiver operating characteristic curve (AUROC). Model feature importance was explained and analyzed using Shapley Additive Explanations (SHAP). The endpoint event of this study was considered to be hypoxemia during the procedure, defined as at least one occurrence of pulse oxygen saturation below 90% without probe misalignment or interference from the beginning of anesthesia induction to the end of painless gastroscopy. In the final cohort of 984 patients, 11% of patients (108/984) experienced hypoxemia during the painless gastroscopy procedure. The AUROCs of the five models were as follows: Logistic Regression (AUROC = 0.893, 95CI: 0.881–0.899), SVM (AUROC = 0.855, 95CI: 0.812–0.884), Random Forest (AUROC = 0.914, 95CI: 0.889–0.924), XGB (AUROC = 0.902, 95CI: 0.865–0.919), and LightGBM (AUROC = 0.891, 95CI: 0.847–0.917). Regarding the explanation of the importance of SHAP features, preoperative variables (baseline SpO2, body mass index, and micrognathia) and intraoperative variables (operating time of gastroscopy, induction dose of etomidate and propofol mixture, append anesthetic, cough, and repeated pharyngeal irritation) significantly contributed to the model. We identified eight potential risk factors related to the occurrence of hypoxemia in middle-aged and elderly patients undergoing painless gastroscopy, based on machine learning feature engineering. Among the five machine learning algorithms, RF exhibited the best predictive performance in the internal test set and had a certain degree of generalization ability in the external validation set, which indicated that the RF model was more suitable for the data framework of this study. This model was more likely to enhance the accuracy of hypoxemia prediction in middle-aged and elderly patients undergoing painless gastroscopy, and thus, it is suitable for assisting anesthesiologists in clinical decision-making.

Background External root resorption (ERR) during orthodontic treatment is a common concern, and accurate quantification is crucial for assessing outcomes and minimizing long-term complications. This study aims to quantify ERR using automated root extraction from cone beam computed tomography (CBCT), combined with a novel root partitioning method and enhanced through the integration of intraoral scans for improved accuracy. Methods Thirty-six patients with malocclusion were included and divided into two groups. Root extraction was performed on CBCT images using artificial intelligence (AI), Simultaneously, crown data from intraoral scans were integrated to create composite dental models in Geomagic software. Pre- and post-treatment models were aligned based on crowns. A novel partitioning method was then used to analyze root volume changes in three dimensions. Finally, these changes were analyzed according to age, tooth region, and extraction treatment using SPSS software. Results A statistically significant reduction in root volume was observed post-treatment in both groups ( P  < 0.001). Anterior teeth exhibited greater ERR, especially in the upper anterior teeth of Group II (extraction treatment, P  < 0.05). Posterior maxillary teeth in Group I showed less ERR ( P  < 0.05). ERR was more pronounced in the apical third of the root ( P  < 0.001). Group II experienced greater overall ERR, particularly in the apical third, whereas Group I showed more ERR at the cervical third ( P  < 0.05). Conclusion This 3D quantification method provides a novel assessment of ERR, with distribution influenced by age, tooth position, extraction treatment, and root region.

Allergic rhinitis (AR), a globally prevalent allergic airway disorder, fundamentally involves CD4+T cell subset imbalance, notably T helper 2 (Th2) hyperpolarization. As critical antigen-presenting cells bridging innate and adaptive immunity, dendritic cells (DCs) contribute to the pathogenesis of AR by presenting antigens, modulating T cell differentiation, and regulating inflammatory responses. Emerging research highlights epigenetic alterations within DCs-encompassing DNA methylation, histone modifications, and non-coding RNAs (ncRNAs)-as central molecular mechanisms governing their function and contributing to AR-related immune dysregulation. DNA methylation dynamically regulates promoter regions, influencing DC migration, maturation, and T cell polarization, while also potentially contributing to transgenerational susceptibility to AR, though evidence in humans remains limited. By altering chromatin structure, histone modifications reprogram gene expression networks. This epigenetic remodeling modulates the transcription of inflammation-associated genes within DCs, thereby influencing the balance between immune tolerance and activation. ncRNAs post-transcriptionally regulate DC developmental trajectories, activation thresholds, and signaling pathways, thus impacting Th1/Th2 immune balance. This study aims to systematically review recent advances in research on epigenetic modifications in DCs, provide an in-depth analysis of their mechanistic role in the immune dysregulation of AR, elucidate the molecular basis of their function as both an “environment-gene bridge” and a “transgenerational inheritance vector”, identify current research limitations, and suggest future directions. The goal is to offer a theoretical framework focused on DC epigenetic regulation for understanding AR pathogenesis and developing novel intervention strategies. Unlike previous reviews on epigenetics in allergic diseases, which broadly discuss various immune cells, this study specifically focuses on DCs. This focus is justified because DCs are pivotal initiators and regulators of type 2 immune responses, and their epigenetic status directly dictates the initiation strength and duration of allergic reactions. Furthermore, we clarify the molecular logic of the dual mechanisms mentioned above: DC epigenetics serves both as a molecular translator converting environmental signals into gene regulatory outcomes and as a mechanism for transmitting allergic susceptibility across generations without altering the DNA sequence. Finally, we analyze the barriers to the clinical translation of DC epigenetics-targeted therapies, thereby offering a new perspective from translational medicine for shifting the treatment paradigm of AR from symptomatic control toward immune remodeling.

Background Despite the importance of dentoalveolar compensation in orthodontic treatment, the inclination of alveolar bone and its relationship with the incisors remain unclear in patients with different skeletal malocclusions. This study aimed to assess anterior alveolar bone inclination (ABI), tooth inclination (TI), and the angulation between them in patients with different skeletal patterns, using a novel method to define ABI, and explore skeletal parameters correlated with ABI. Methods Based on cone-beam computed tomography images of 79 adult patients, the ABI, TI, and the angulation between them were measured in the central incisor region. The subjects were classified into skeletal Class I, Class II division 1, Class II division 2, and Class III groups, and hypodivergent, normodivergent, and hyperdivergent groups. One-way analysis of variance was performed for intergroup comparison. Craniofacial skeletal parameters were also measured to evaluate correlations with ABI through correlation analysis. Results The ABI and TI were smallest in skeletal Class II division 2 patients in maxilla and decreased gradually in skeletal Class II, I, III patients in mandible ( P  < 0.01). In terms of vertical skeletal patterns, the ABI in maxilla and the ABI and TI (related to the mandibular plane) in mandible decreased in hypodivergent, normodivergent, and hyperdivergent patients ( P  < 0.01). The angulation between ABI and TI in maxilla was smaller in hyperdivergent patients and largest in skeletal Class II division 2 patients ( P  < 0.05). Correlation analyses revealed that the ABI had correlations with TI, ANB, SN-MP, FHI, gonial angle, Y-axis angle, etc. Conclusions The anterior ABI and TI, as well as the angulation between them, show significant variations across different skeletal patterns. ABI also exhibits correlations with several skeletal parameters. These variations should be considered in orthodontic treatment planning to reduce the risk of iatrogenic complications.