The performance of artificial intelligence models in generating responses to general orthodontic questions: ChatGPT vs Google Bard.

INTRODUCTION: This study aimed to evaluate and compare the performance of 2 artificial intelligence (AI) models, Chat Generative Pretrained Transformer-3.5 (ChatGPT-3.5; OpenAI, San Francisco, Calif) and Google Bidirectional Encoder Representations from Transformers (Google Bard; Bard Experiment, Google, Mountain View, Calif), in terms of response accuracy, completeness, generation time, and response length when answering general orthodontic questions. METHODS: A team of orthodontic specialists developed a set of 100 questions in 10 orthodontic domains. One author submitted the questions to both ChatGPT and Google Bard. The AI-generated responses from both models were randomly assigned into 2 forms and sent to 5 blinded and independent assessors. The quality of AI-generated responses was evaluated using a newly developed tool for accuracy of information and completeness. In addition, response generation time and length were recorded. RESULTS: The accuracy and completeness of responses were high in both AI models. The median accuracy score was 9 (interquartile range [IQR]: 8-9) for ChatGPT and 8 (IQR: 8-9) for Google Bard (Median difference: 1; P <0.001). The median completeness score was similar in both models, with 8 (IQR: 8-9) for ChatGPT and 8 (IQR: 7-9) for Google Bard. The odds of accuracy and completeness were higher by 31% and 23% in ChatGPT than in Google Bard. Google Bard's response generation time was significantly shorter than that of ChatGPT by 10.4 second/question. However, both models were similar in terms of response length generation. CONCLUSIONS: Both ChatGPT and Google Bard generated responses were rated with a high level of accuracy and completeness to the posed general orthodontic questions. However, acquiring answers was generally faster using the Google Bard model.

Deep analysis of skin molecular heterogeneities and their significance on the precise treatment of patients with psoriasis.

Background: Psoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible. Methods: We performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients. Unsupervised clustering methods were used to identify the skin subtypes. Finally, an Xgboost classifier was utilized to predict the effects of methotrexate and commonly prescribed biologics on skin subtypes. Results: Based on the 163 upregulated differentially expressed genes, psoriasis patients were categorized into three subtypes (subtypes A-C). Immune cells and proinflammatory-related pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate and interleukin-12/23 inhibitors (ustekinumab) but inadequate responses to tumor necrosis factor-α inhibitors and interleukin-17A receptor inhibitors. Contrastly, subtype C exhibited excellent responses to tumor necrosis factor-α inhibitors (etanercept) and interleukin-17A receptor inhibitors (brodalumab) but not methotrexate and interleukin-12/23 inhibitors. Conclusions: Psoriasis patients can be assorted into three subtypes with different molecular and cellular characteristics based on the heterogeneity of the skin's immune cells and the stroma, determining the clinical responses of conventional therapies.

Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019.

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 ß = 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.

Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N6-methyladenosine modification of sclerostin.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. METHODS: Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. RESULTS: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. CONCLUSIONS: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.

PRMT1-mediated arginine methylation promotes postnatal calvaria bone formation through BMP-Smad signaling.

PRMT1 deficiency leads to severely compromised craniofacial development in neural crest cells and profound abnormalities of the craniofacial tissues. Here, we show PRMT1 controls several key processes in calvarial development, including frontal and parietal bone growth rate and the boundary between sutural and osteogenic cells. Pharmacologic PRMT1 inhibition suppresses MC3T3-E1 cell viability and proliferation and impairs osteogenic differentiation. In this text, we investigate the cellular events behind the morphological changes and uncover an essential role of PRMT1 in simulating postnatal bone formation. Inhibition of PRMT1 alleviated BMP signaling through Smads phosphorylation and reduced the deposition of the H4R3me2a mark. Our study demonstrates a regulatory mechanism whereby PRMT1 regulates BMP signaling and the overall properties of the calvaria bone through Smads methylation, which may facilitate the development of an effective therapeutic strategy for craniosynostosis.

Electrolyte Strategies Facilitating Anion-Derived Solid-Electrolyte Interphases for Aqueous Zinc-Metal Batteries.

Rechargeable aqueous zinc-metal batteries (AZBs) are a promising complimentary technology to the existing lithium-ion batteries and the re-emerging lithium-metal batteries to satisfy the increasing demands on energy storage. Despite considerable progress achieved in the past years, the fundamental understanding of the solid-electrolyte interphase (SEI) formation and how its composition influences the SEI properties are limited. This review highlights the functionalities of anion-tuned SEI on the reversibility of zinc-metal anode, with a specific emphasis on new structural insights obtained through advanced characterizations and computational techniques. Recent efforts in terms of key variables that govern the interfacial behaviors to improve the long-term stability of zinc anode, i.e., Coulombic efficiency, plating morphology, dendrite formation, and side-reactions, are comprehensively reviewed. Lastly, the remaining challenges and future perspectives are presented, providing insights into the rational design of practical high-performance AZBs.

The efficacy of concentrated growth factor and platelet-rich fibrin as scaffolds in regenerative endodontic treatment applied to immature permanent teeth: a retrospective study.

BACKGROUND: The aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET). METHODS: Necrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3-6 months), T2 (6-12 months) and T3 (12-24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher's exact test at a significance level of 0.05. RESULTS: The success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance. CONCLUSIONS: Both CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.

Effects of different designs of orthodontic clear aligners on the maxillary central incisors in the tooth extraction cases: a biomechanical study.

BACKGROUND: Controlling the 3D movement of central incisors during tooth extraction cases with clear aligners is important but challenging in invisible orthodontic treatment. This study aimed to explore the biomechanical effects of central incisors in tooth extraction cases with clear aligners under different power ridge design schemes and propose appropriate advice for orthodontic clinic. METHODS: A series of Finite Element models was constructed to simulate anterior teeth retraction or no retraction with different power ridge designs. These models all consisted of maxillary dentition with extracted first premolars, alveolar bone, periodontal ligaments and clear aligner. And the biomechanical effects were analysed and compared in each model. RESULTS: For the model of anterior teeth retraction without power ridge and for the model of anterior teeth no retraction with a single power ridge, the central incisors exhibited crown lingual inclination and relative extrusion. For the model of anterior teeth no retraction with double power ridges, the central incisors tended to have crown labial inclination and relative intrusion. For the model of anterior tooth retraction with double power ridges, the central incisors exhibited a similar trend to the first kind of model, but as the depth of the power ridge increased, there was a gradual decrease in crown retraction value and an increase in crown extrusion value. The simulated results showed that von-Mises stress concentration was observed in the cervical and apical regions of the periodontal ligaments of the central incisors. The clear aligner connection areas of adjacent teeth and power ridge areas also exhibited von-Mises stress concentration and the addition of power ridge caused the clear aligner to spread out on the labial and lingual sides. CONCLUSIONS: The central incisors are prone to losing torque and extruding in tooth extraction cases. Double power ridges have a certain root torque effect when there are no auxiliary designs, but they still cannot rescue tooth inclination during tooth retraction period. For tooth translation, it may be a better clinical procedure to change the one-step aligner design to two-step process: tilting retraction and root control.

Treatment Outcome of Regenerative Endodontic Procedures for Necrotic Immature and Mature Permanent Teeth: A Systematic Review and Meta-Analysis Based on Randomised Controlled Trials.

PURPOSE: To analyse whether the stage of apical development affects the effectiveness of regenerative endodontic treatment by comparing the outcomes for necrotic mature and immature permanent teeth treated with regenerative endodontic procedures. MATERIALS AND METHODS: Multiple databases (PubMed, Cochrane Library, Web of Science, EMBASE and OpenGrey databases) were searched through February 17th, 2022. Inclusion criteria were randomised controlled trials that included treatment of necrotic immature or mature permanent teeth using any regenerative endodontic procedures (REPs) that aimed to achieve pulp revascularisation or regeneration. The Cochrane Risk of Bias 2.0 tool was used to assess risk of bias. The included indicators were asymptomatic sign, success, pulp sensitivity, and discolouration. The extracted data were expressed by percentage for statistical analysis. The random effect model was used to explain the results. Comprehensive Meta-Analysis Version 2 was used to perform the statistical analyses. RESULTS: Twenty-seven RCTs were eligible for inclusion in the meta-analysis. The success rates of necrotic immature and mature permanent teeth were 95.6% (95% CI, 92.4%-97.5%; I2=34.9%) and 95.5% (95%CI, 87.9%-98.4%; I2=0%), respectively. The asymptomatic rates of necrotic immature and mature permanent teeth were 96.2% (95%CI, 93.5%-97.9%; I2=30.1%) and 97.0% (95%CI, 92.6%-98.8%; I2=0%), respectively. The treatment of immature and mature necrotic permanent teeth with REPs yields high success rates and low symptomatic rates. The incidence of positive sensitivity response for electric pulp testing in necrotic immature permanent teeth (25.2% [95% CI, 18.2%-33.8%; I2=0%]) was lower than that in necrotic mature permanent teeth (45.4% [95% CI, 27.2%-64.8%; I2=75.2%]), and this difference was statistically significant. The restoration of pulp sensitivity seems to be more evident in necrotic mature permanent teeth than in necrotic immature permanent teeth. The crown discolouration rate of immature permanent teeth was 62.5% (95% CI, 49.7%-73.8%; I2=76.1%). Necrotic immature permanent teeth have a considerable crown discolouration rate. CONCLUSION: REPs for both immature and mature necrotic permanent teeth yield high success rates and promote root development. The vitality responses seem to be more evident in necrotic mature permanent teeth than in necrotic immature permanent teeth.

The effect of early versus delayed space closure on the rate of orthodontic tooth movement: a systematic review and meta-analysis.

BACKGROUND: Orthodontic space closure of extraction sites can be initiated early, within 1-week post-extraction, or it can be delayed for a month or more. OBJECTIVE: This systematic review aimed to evaluate the effect of early versus delayed initiation of space closure after tooth extraction on the rate of orthodontic tooth movement. SEARCH METHODS: Unrestricted search of 10 electronic databases was conducted until September 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) investigating the initiation time of space closure of extraction sites in patients undergoing orthodontic treatment were included. DATA COLLECTION AND ANALYSIS: Data items were extracted using a pre-piloted extraction form. The Cochrane's risk of bias tool (ROB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation approach were used for quality assessment. Meta-analysis was undertaken if there are at least two trials reporting the same outcome. RESULTS: Eleven RCTs met the inclusion criteria. Meta-analysis revealed that early canine retraction resulted in a statistically significant higher rate of maxillary canine retraction when compared to delayed canine retraction [mean difference (MD); 0.17 mm/month, 95% CI: 0.06 to 0.28, P = 0.003, 4 RCTs, moderate quality]. Duration of space closure was shorter in the early space closure group, but not statistically significant (MD; 1.11 months, 95% CI: -0.27 to 2.49, P = 0.11, 2 RCTs, low quality). The incidence of gingival invaginations was not statistically different between early and delayed space closure groups (Odds ratio; 0.79, 95% CI: 0.27 to 2.29, 2 RCTs, P = 0.66, very low quality). Qualitative synthesis found no statistically significant differences between the two groups regarding anchorage loss, root resorption, tooth tipping, and alveolar bone height. CONCLUSIONS: Based on the available evidence, early traction within the first week after tooth extraction has a minimal clinically significant effect on the rate of tooth movement compared to delayed traction. Further high-quality RCTs with standardized time points and measurement methods are still needed. REGISTRATION: PROSPERO (CRD42022346026).

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis.

Macrophage pyroptosis drives the secretion of IL-1ß, 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-1ß 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-1ß 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-1ß secretion. Our study demonstrates that hyperglycemia promotes IL-1ß 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.

Erratum: Transcriptional Downregulation of miR-4306 serves as a New Therapeutic Target for Triple Negative Breast Cancer: Erratum.

[This corrects the article DOI: 10.7150/thno.30701.].

Three-dimensional analysis of the relationship between mandibular retromolar space and positional traits of third molars in non-hyperdivergent adults.

BACKGROUND: The anatomical position of the mandibular third molars (M3s) is located in the distal-most portions of the molar area. In some previous literature, researchers evaluated the relationship between retromolar space (RS) and different classifications of M3 in three­dimensional (3D) cone-beam computed tomography (CBCT). METHODS: Two hundred six M3s from 103 patients were included. M3s were grouped according to four classification criteria: PG-A/B/C, PG-I/II/III, mesiodistal angle and buccolingual angle. 3D hard tissue models were reconstructed by CBCT digital imaging. RS was measured respectively by utilizing the fitting WALA ridge plane (WP) which was fitted by the least square method and the occlusal plane (OP) as reference planes. SPSS (version 26) was used to analyze the data. RESULTS: In all criteria evaluated, RS decreased steadily from the crown to the root (P < 0.05), the minimum was at the root tip. From PG-A classification, PG-B classification to PG-C classification and from PG-I classification, PG-II classification to PG-III classification, RS both appeared a diminishing tendency (P < 0.05). As the degree of mesial tilt decreased, RS appeared an increasing trend (P < 0.05). RS in classification criteria of buccolingual angle had no statistical difference (P > 0.05). CONCLUSIONS: RS was associated with positional classifications of the M3. In the clinic, RS can be evaluated by watching the Pell&Gregory classification and mesial angle of M3.

Flash-free and conventional adhesive ceramic brackets in patients undergoing orthodontic treatment: A systematic review and meta-analysis.

To investigate whether flash-free adhesive ceramic brackets (FFA) have a better clinical performance than conventional adhesive ceramic brackets (CVA) in patients undergoing multi-bracket orthodontic treatment. PubMed, CENTRAL, Web of Science, Scopus, Embase, CNKI and Grey-literature were searched without restrictions up to January 2022. Both randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Risk of bias assessment was performed using the RoB 2.0 and ROBINS-I cochrane risk of bias tools. Eight articles, for seven studies, were included in this systematic review, and four split-mouth trials (SMT) were included in the meta-analysis. A random-effects meta-analysis found a statistically significant faster bonding time with FFA (mean difference [MD] = -93.85 seconds/quadrant, P = .002, 2 SMT), and no statistically significant difference regarding bracket failure rate at 6 months (risk ratio [RR] = 1.05; P = .93, 3 SMT), adhesive removal time (MD = -18.26 seconds/quadrant, P = .50, 2 SMT), and amount of remnant adhesive (MD = -0.13/bracket, P = .72, 2 SMT) between FFA and CVA. No difference (P > .05, 3 SMT) was found in enamel demineralization and periodontal measurements. CVA showed a statistically significant higher debonding pain score (P = .004, 1 SMT). Both flash-free and conventional adhesive ceramic brackets had a similar clinical performance, except for the faster bonding with FFA. Further, well-designed clinical trials are still required.

MiR-134-5p/Stat3 Axis Modulates Proliferation and Migration of MSCs Co-Cultured with Glioma C6 Cells by Regulating Pvt1 Expression.

Mesenchymal stem cells (MSCs) are critical in regenerating tissues because they can differentiate into various tissue cells. MSCs interact closely with cells in the tissue microenvironment during the repair of damaged tissue. Although regarded as non-healing wounds, tumors can be treated by MSCs, which showed satisfactory treatment outcomes in previous reports. However, it is largely unknown whether the biological behaviors of MSCs would be affected by the tumor microenvironment. Exploring the truth of tumor microenvironmental cues driving MSCs tumor "wound" regeneration would provide a deeper understanding of the biological behavior of MSCs. Therefore, we mimicked the tumor microenvironment using co-cultured glioma C6 cells and rat MSCs, aiming to assess the proliferation and migration of MSCs and the associated effects of Stat3 in this process. The results showed that co-cultured MSCs significantly exhibited enhanced tumorigenic, migratory, and proliferative abilities. Both up-regulation of Stat3 and down-regulation of miR-134-5p were detected in co-cultured MSCs. Furthermore, miR-134-5p directly regulated Stat3 by binding to the sequence complementary to microRNA response elements in the 3'-UTR of its mRNA. Functional studies showed that both the migration and proliferation abilities of co-cultured MSCs were inhibited by miR-134-5p, whereas Stat3 gain-of-function treatment reversed these effects. In addition, Pvt1 was confirmed to be regulated by miR-134-5p through Stat3 and the suppression of Pvt1 reduced the migration and proliferation abilities of co-cultured MSCs. To sum up, these results demonstrate a suppressive role of miR-134-5p in tumor-environment-driven malignant transformation of rat MSCs through directly targeting Stat3, highlighting a crucial role of loss-of-function of miR-134-5p/Stat3 axis in the malignant transformation, providing a reference to the potential clinic use of MSCs.

A fast online questionnaire for screening mental illness symptoms during the COVID-19 pandemic.

The COVID-19 pandemic has caused massive effects on the situation of public mental health. A fast online questionnaire for screening and evaluating mental symptoms is urgent. In this work, we developed a new 19-item self-assessment Fast Screen Questionnaire for Mental Illness Symptoms (FSQ-MIS) to quickly identify mental illness symptoms. The FSQ-MIS was validated on a total of 3828 young adult mental disorder patients and 984 healthy controls. We applied principal component analysis (PCA), receiver operating characteristic (ROC) curve, and general log-linear analysis (GLA) to evaluate the construct and parallel validity. Results demonstrate that the proposed FSQ-MIS shows high test-retest reliability (0.852) and split-half reliability (0.844). Six factors obtained using PCA explained 54.3% of the variance and showed high correlations with other widely used scales. The ROC results (0.716-0.983) revealed high criterion validity of FSQ-MIS. GLA demonstrated the advantage of FSQ-MIS in predicting anxiety and depression prevalence in COVID-19, supporting the efficiency of FSQ-MIS as a tool for research and clinical practice.

Erratum: Co-culture with Endothelial Progenitor Cells promotes the Osteogenesis of Bone Mesenchymal Stem Cells via the VEGF-YAP axis in high-glucose environments: Erratum.

[This corrects the article DOI: 10.7150/ijms.52316.].

Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products.

Advanced glycation end products (AGEs) aggregation and macrophages polarization are identified as the main factors contributing to bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to elucidate the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. Firstly, AGEs-treated RAW264.7 macrophages were observed to up-regulate the release of nitric oxide (NO), the expression of M1-associated genes and the surface antigen marker CD86. The detection of osteoclast-related markers and TRAP staining revealed that the osteoclastogenic ability of M1 macrophages was markedly enhanced by AGEs. Further, AGEs were found to effectively activate the transduction of Notch signaling pathway and promote the nuclear translocation of NICD1. In addition, with the signals transduction of Notch pathway blocked by γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J, AGEs-induced M1 polarization was significantly mitigated. Collectively, we defined a critical role for AGEs in inducing M1 polarization and osteoclastogenesis of macrophages, and further identified Notch/NICD/RBP-J signaling axis as an essential mechanism regulating AGEs-mediated M1 polarization.

Moyamoya Disease With Initial Ischemic or Hemorrhagic Attack Shows Different Brain Structural and Functional Features: A Pilot Study.

Objective: Cerebral ischemia and intracranial hemorrhage are the two main phenotypes of moyamoya disease (MMD). However, the pathophysiological processes of these two MMD phenotypes are still largely unknown. Here, we aimed to use multimodal neuroimaging techniques to explore the brain structural and functional differences between the two MMD subtypes. Methods: We included 12 patients with ischemic MMD, 10 patients with hemorrhagic MMD, and 10 healthy controls (HCs). Each patient underwent MRI scans and cognitive assessment. The cortical thickness of two MMD subtypes and HC group were compared. Arterial spin labeling (ASL) and diffusion tensor imaging (DTI) were used to inspect the cerebral blood flow (CBF) of cortical regions and the integrity of related white matter fibers, respectively. Correlation analyses were then performed among the MRI metrics and cognitive function scores. Results: We found that only the cortical thickness in the right middle temporal gyrus (MTG) of hemorrhagic MMD was significantly greater than both ischemic MMD and HC (p < 0.05). In addition, the right MTG showed higher ASL-CBF, and its associated fiber tract (arcuate fasciculus, AF) exhibited higher fractional anisotropy (FA) values in hemorrhagic MMD. Furthermore, the cortical thickness of the right MTG was positively correlated with its ASL-CBF values (r = 0.37, p = 0.046) and the FA values of right AF (r = 0.67, p < 0.001). At last, the FA values of right AF were found to be significantly correlated with cognitive performances within patients with MMD. Conclusions: Hemorrhagic MMD shows increased cortical thickness on the right MTG in comparison with ischemic MMD and HCs. The increased cortical thickness is associated with the higher CBF values and the increased integrity of the right AF. These findings are important to understand the clinical symptoms and pathophysiology of MMD and further applied to clinical practice.