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Background: Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear. Methods: The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats. Results: TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP's nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP's nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement. Conclusions: Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice. [ABSTRACT FROM AUTHOR]

The cervical vertebral maturation (CVM) method is essential to determine the timing of orthodontic and orthopedic treatment. In this paper, a target detection model called DC-YOLOv5 is proposed to achieve fully automated detection and staging of CVM. A total of 1800 cephalometric radiographs were labeled and categorized based on the CVM stages. We introduced a model named DC-YOLOv5, optimized for the specific characteristics of CVM based on YOLOv5. This optimization includes replacing the original bounding box regression loss calculation method with Wise-IOU to address the issue of mutual interference between vertical and horizontal losses in Complete-IOU (CIOU), which made model convergence challenging. We incorporated the Res-dcn-head module structure to enhance the focus on small target features, improving the model's sensitivity to subtle sample differences. Additionally, we introduced the Convolutional Block Attention Module (CBAM) dual-channel attention mechanism to enhance focus and understanding of critical features, thereby enhancing the accuracy and efficiency of target detection. Loss functions, precision, recall, mean average precision (mAP), and F1 scores were used as the main algorithm evaluation metrics to assess the performance of these models. Furthermore, we attempted to analyze regions important for model predictions using gradient Class Activation Mapping (CAM) techniques. The final F1 scores of the DC-YOLOv5 model for CVM identification were 0.993, 0.994 for mAp0.5 and 0.943 for mAp0.5:0.95, with faster convergence, more accurate and more robust detection than the other four models. The DC-YOLOv5 algorithm shows high accuracy and robustness in CVM identification, which provides strong support for fast and accurate CVM identification and has a positive effect on the development of medical field and clinical diagnosis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn’s disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 three‑dimensional (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In mobile crowdsensing activities, it is usually necessary for participants to upload sensing data and related locations. The existing location privacy-preserving mechanisms cannot well protect a user's trajectory privacy because attackers can mine the user's trajectory features through data analysis techniques. Aiming at the trajectory privacy protection problem, this article proposes a differential location privacy-preserving mechanism based on trajectory obfuscation (LPMT). LPMT first extracts the stay points as the features of a trajectory based on the sliding window algorithm, and then obfuscates each stay point to a target obfuscation subregion through the exponential mechanism, and finally performs the Laplace sampling in the target obfuscation subregion to obtain the obfuscated GPS points. Compared with the baseline mechanisms, LPMT can reduce data quality loss by more than 20% while providing the same level of obfuscation quality, which indicates that LPMT has the advantages of strong security and high quality of service. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Keywords: aqueous electrolytes; reversibility; SEI; solvation structure; Zn anodesFront CoverIn article number 2300554, Chen, Passerini, Zhang, and co‐workers emphasize the metrics of anion‐derived interfacial chemistry in aqueous zinc batteries. Electrolyte engineering has been proven to be an efficient strategy for the interphase formation, which provide a new direction for future electrolyte design..By Huihua Li; Zhen Chen; Leilei Zheng; Jian Wang; Henry Adenusi; Stefano Passerini and Huang ZhangReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Background: To examine the influence of mouth breathing on maxillofacial and airway development in children and adolescents with different cervical vertebral maturation stages. Methods: Lateral cephalometric radiograph of a total of 120 children and adolescents, 64 girls and 56 boys (7–15 years old), diagnosed with mouth breathing were examined. Maxillofacial hard tissue, soft tissue and airway measurements were obtained using both manual and digital techniques. Independent samples t-test was performed to compare the difference between the measured indexes and the standard values. Results: As for maxillofacial hard tissue, SNB (CS1–CS5), GoGn (CS1–CS5), ArGoNa (CS1–CS5), ArGo (CS1–CS2) and SNA (CS1–CS2) in mouth breathing children and adolescents were below the standard values (P < 0.05). NGoMe (CS1–CS5), SN-MP (CS1–CS4), SN-PP (CS1–CS4), PP-MP (CS1–CS3) and SN-GoGn (CS1–CS2) in mouth breathing children and adolescents were above the standard values (P < 0.05). As for maxillofacial soft tissue measurements, H angle (CS1–CS5), lower lip length (CS1–CS5), upper lip protrusion (CS1–CS5), upper lip length (CS1–CS4), lower lip protrusion (CS1–CS3), surface Angle (CS2–CS3) and nasolabial angle (CS2) in mouth breathing children and adolescents were above the standard values with statistically significance (P < 0.05). As for airway measurements, PAS (CS1, CS2, CS5) in mouth breathing children and adolescents was above the standard value with statistical significance (P < 0.05). Conclusions: Mouth breathing had a real effect on maxillofacial and airway development, which differed among mouth breathing children and adolescents with different cervical vertebral maturation. [ABSTRACT FROM AUTHOR]

Background: Disruption of brain functional connectivity has been detected after stroke, but whether it also occurs in moyamoya disease (MMD) is unknown. Impaired functional connectivity is always correlated with abnormal white matter fibers. Herein, we used multimodal imaging techniques to explore the changes in brain functional and structural connectivity in MMD patients.Methods: We collected structural images, resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging for each subject. Cognitive functions of MMD patients were evaluated using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Trail Making Test parts A and B (TMT-A/-B). We calculated the functional connectivity for every paired region using 90 regions of interest from the Anatomical Automatic Labeling Atlas and then determined the differences between MMD patients and HCs. We extracted the functional connectivity of paired brain regions with significant differences between the two groups. Correlation analyses were then performed between the functional connectivity and variable cognitive functions. To explore whether the impaired functional connectivity and cognitive performances were attributed to the destruction of white matter fibers, we further analyzed fiber integrity using tractography between paired regions that were correlated with cognition.Results: There was lower functional connectivity in MMD patients as compared to HCs between the bilateral inferior frontal gyrus, between the bilateral supramarginal gyrus, between the left supplementary motor area (SMA) and the left orbital part of the inferior frontal gyrus (IFGorb), and between the left SMA and the left middle temporal gyrus (P < 0.01, FDR corrected). The decreased functional connectivity between the left SMA and the left IFGorb was significantly correlated with the MMSE (r = 0.52, P = 0.024), MoCA (r = 0.60, P = 0.006), and TMT-B (r = -0.54, P = 0.048) in MMD patients. White matter fibers were also injured between the SMA and IFGorb in the left hemisphere and were positively correlated with reduced functional connectivity.Conclusions: Brain functional and structural connectivity between the supplementary motor area and inferior frontal gyrus in the left hemisphere are damaged in MMD. These findings could be useful in the evaluation of disease progression and prognosis of MMD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Globally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs). Methods: Global and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden. Results: Sex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10–24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P < 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P < 0.001; standardized β = 0.300, P < 0.001). Conclusion: Although some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD. [ABSTRACT FROM AUTHOR]

Background: Habituation is considered to have protective and filtering mechanisms. The present study is aim to find the casual relationship and mechanisms of excitatory–inhibitory (E/I) dysfunctions in schizophrenia (SCZ) via habituation. Methods: A dichotic listening paradigm was performed with simultaneous EEG recording on 22 schizophrenia patients and 22 gender- and age-matched healthy controls. Source reconstruction and dynamic causal modeling (DCM) analysis were performed to estimate the effective connectivity and casual relationship between frontal and temporal regions before and after habituation. Results: The schizophrenia patients expressed later habituation onset (p < 0.01) and hyper-activity in both lateral frontal–temporal cortices than controls (p = 0.001). The patients also showed decreased top-down and bottom-up connectivity in bilateral frontal–temporal regions (p < 0.01). The contralateral frontal–frontal and temporal–temporal connectivity showed a left to right decreasing (p < 0.01) and right to left strengthening (p < 0.01). Conclusions: The results give causal evidence for E/I imbalance in schizophrenia during dichotic auditory processing. The altered effective connectivity in frontal–temporal circuit could represent the trait bio-marker of schizophrenia with auditory hallucinations. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess reliability of cone-beam CT (CBCT) for nasolabial soft tissue measurements in patients with skeletal class III malocclusion based on 3-dimensional (3D) facial scanner results. METHODS: CBCT and 3D facial scan images of 20 orthognathic patients are used in this study. Eleven soft tissue landmarks and 15 linear and angular measurements are identified and performed. For qualitative evaluation, Shapiro-Wilk test and Bland-Altman plots are applied to analyze the equivalence of the measurements derived from these two kinds of images. To quantify specific deviation of CBCT measurements from facial scanner, the latter is set as a benchmark, and mean absolute difference (MAD) and relative error magnitude (REM) for each variable are also calculated. RESULTS: Statistically significant differences are observed in regions of nasal base and lower lip vermilion between two methods. MAD value for all length measurements are less than 2 mm and for angular variables < 8°. The average MAD and REM for length measurements are 0.94 mm and 5.64%, and for angular measurements are 2.27° and 3.78%, respectively. CONCLUSIONS: The soft tissue results measured by CBCT show relatively good reliability and can be used for 3D measurement of soft tissue in the nasolabial region clinically. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate three-dimensional soft tissue changes of lips and related jaw changes in patients with skeletal class III malocclusion and facial asymmetry using cone-beam computerized tomography (CBCT). METHOD: This study included 46 CBCT scans of patients with aforementioned character before (T1) and 6–12 months after orthognathic surgery (T2). Subjects were divided into 2 groups according to two types of orthognathic surgery namely, the one-jaw surgery group who underwent bilateral sagittal splint ramus osteotomy (BSSRO) and the two-jaw surgery group who underwent Le Fort I osteotomy and BSSRO. Mimics 19.0 software are used for model reconstruction, landmark location and three-dimensional cephalometric analysis. Descriptive statistics and correlation analyses are used to investigate jaw hard tissue and lip soft tissue changes. RESULTS: In one-jaw group, the mandible shows changes in contour and position (p < 0.05), and the surgery causes changes of lip structure on the deviated side. While in two-jaw group, jaws only show changes in spatial position, and surgery changes contour of bilateral lips and nasolabial angle (p < 0.05). At the same time, lip symmetry increases significantly in both groups postoperatively. CONCLUSIONS: Orthognathic surgery can improve lip aesthetics in patients with skeletal class III malocclusion and facial asymmetry. However, changes induced by two surgical approaches are different. Surgeons should have a clear acquaintance with this difference to deal with different situations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC) and associated with their poor prognosis. However, its underlying mechanisms remain elusive. Here, we developed an ESCC‐induced cachexia mouse model using human xenograft ESCC cell lines and found that ESCC‐derived extracellular vesicles (EVs) containing prolyl 4‐hydroxylase subunit beta (P4HB) induced apoptosis of skeletal muscle cells. We further identified that P4HB promoted apoptotic response through activating ubiquitin‐dependent proteolytic pathway and regulated the stability of phosphoglycerate dehydrogenase (PHGDH) and subsequent antiapoptotic protein Bcl‐2. Additionally, we proved that the P4HB inhibitor, CCF642, not only rescued apoptosis of muscle cells in vitro, but also prevented body weight loss and muscle wasting in ESCC‐induced cachexia mouse model. Overall, these findings demonstrate a novel pathway for ESCC‐induced muscle wasting and advocate for the development of P4HB as a potential intervention target for cachexia in patients with ESCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate skeletal and dental changes in patients with skeletal Class III malocclusion and facial asymmetry after surgical-orthodontic treatment using cone-beam computerized tomography (CBCT). METHODS: This study included forty adult patients diagnosed with skeletal Class III malocclusion and asymmetry who underwent either isolated mandibular surgery or bimaxillary surgery. CBCT scans were taken before treatment (T0), at the completion of presurgical orthodontic treatment (T1) and after treatment (T2). Mimics 17.0 and 3-Matics 7.0 were used to measure skeletal and dental parameters. Skeletal and dental changes within each group from pretreatment to posttreatment were assessed, and Pearson correlation analysis was used to analyze the correlations among skeletal changes. RESULTS: The three-dimensional changes in condylar position were insignificant after surgical-orthodontic treatment in either group (P > 0.05). However, in the one-jaw surgery group, there were significant backward rotations of the condyle and ramus on the nondeviated side (P < 0.05), and the condyle on the deviated side rotated inward and forward significantly in the two-jaw surgery group (P < 0.05) at T2. There were no significant differences in the changes in the total alveolar bone thickness of bilateral first molars during dental decompensation (P > 0.05). The ratio between the buccal and the total bone thickness around the maxillary first molar on the deviated side decreased significantly at T1, as did those around the mandibular first molar on the nondeviated side (P < 0.05). CONCLUSIONS: Condylar angulations were less stable after treatment (7 to 9 months after surgery) in both the one-jaw and the two-jaw surgery groups, while condylar displacements were insignificant. In addition, orthodontists should keep a watchful eye to the relative position of the root in the alveolar bone during tooth decompensation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the skeletal and dental characteristics in skeletal class III patients with facial asymmetry and to analyse the relationships among various parts of the stomatognathic system to provide a theoretical basis for clinical practice. METHODS: Asymmetric cone-beam computed tomography data acquired from 56 patients were evaluated using Mimics 10.0 and 3-Matic software. Skeletal and dental measurements were performed to assess the three-dimensional differences between two sides. Pearson correlation analysis was used to determine the correlations among measurements. RESULTS: Linear measurements, such as ramal height, mandible body length, ramal height above the sigmoid notch (RHASN), maxillary height, condylar height, buccal and total cancellous bone thickness, and measurements of condylar size, were significantly larger on the nondeviated side than on the deviated side (P < 0.05). Crown root ratio and buccolingual angle of mandibular first molar were found to be significantly smaller on the nondeviated side than on the deviated side (P < 0.05). A negative correlation was also discovered between the buccolingual angle of mandibular first molar and the ramal height (P < 0.01). CONCLUSIONS: In patients with facial asymmetry, asymmetries in the mandible, maxilla and condylar morphology, and skeletal canting served as major components of skeletal asymmetry. Furthermore, a reduced thickness of buccal cancellous bone and a larger crown root ratio were found on the deviated side, indicating that orthodontic camouflage has limitations and potential risks. A combination of orthodontics and orthognathic surgery may be the advisable choice in patients with a menton deviation greater than 4 mm. An important association between vertical skeletal disharmony and dental compensation was also observed. [ABSTRACT FROM AUTHOR]

In the present study we explored the different patterns of volumetric atrophy in hippocampal subregions of patients with left and right mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Meanwhile, the memory impairment patterns in Chinese-speaking TLE-HS patients and potential influencing factors were also determined. TLE-HS patients (21 left and 17 right) and 21 healthy controls were recruited to complete T2-weighted imaging and verbal/nonverbal memory assessment. The results showed that both left and right TLE-HS patients had overall reduced hippocampal subregion volumes on the sclerotic side, and cornu ammonis sectors (CA1) exhibited maximum atrophy. The verbal memory of left TLE-HS patients was significantly impaired (P < 0.001) and was not associated with the volumes of the left hippocampal subregions. Verbal or nonverbal memory impairment was not found in the patients with right TLE-HS. These results suggested that the atrophy of hippocampal subregion volumes cannot account for the verbal memory impairment, which might be related to the functional network. [ABSTRACT FROM AUTHOR]

ABSTRACT MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow stromal cells (BMSCs) isolated from transgenic mice displayed higher mRNA expression of osteogenic markers than wild-type mice BMSCs cultures. Protein expression of Runx2 and Osx was also upregulated in BMSC cultures of transgenic mice upon osteogenic induction, whereas that of DKK1 was downregulated. Most important, BMSCs from transgenic mice were able to repair craniofacial bone defects as shown by μCT analysis, H&E staining, and osteocalcin (OCN) immunohistochemistry of newly formed bone in defects treated with BMSCs. Taken together, our results demonstrate constitutive overexpression of miR-335-5p driven by an osterix promoter in the osteoblast lineage induces osteogenic differentiation and bone formation in mice and support the potential application of miR-335-5p-modified BMSCs in craniofacial bone regeneration. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Hyperglycemia is one of the most important pathogenesis of diabetic osteopathy. Several lines of studies indicate Runx2 plays a critical role in the process of osteogenic differentiation. However, little studies have analyzed the effect of Runx2 on osteoblast differentiation of rat bone mesenchymal stem cells (rBMSCs) in high-glucose condition. In this study, the effect of Runx2 on osteoblast differentiation in high-glucose condition was evaluated by the expression of osteogenesis-related maker including Runx2, ALP, OC, and OPN, as well as ALP staining, ALP activity, and Alizarin red S staining. Western blot analysis was performed to detect the protein expression levels of p-AKT, AKT, p-GSK3β, GSK3β, and β-catenin. Immunofluorescence staining analysis was performed to detect subcellular localization of β-catenin. Our results revealed that high glucose significantly inhibited osteogenic differentiation, hyperosmolarity did not cause a suppression. In addition, Runx2 could upregulate the expression of osteogenic-related genes and increase matrix mineralization, while applying 10 µM PI3K/AKT inhibitor LY294002 abolished the beneficial effect. Collectively, these results indicate that Runx2 alleviates high glucose-induced inhibition of osteoblast differentiation by modulating PI3K/AKT/GSK3β/β-catenin pathway. [ABSTRACT FROM AUTHOR]

DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity, and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 −/−) compared with that of Runx2 +/− and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation, and repairing in calvarial defects with the siRNA targeting DICER group. In conclusion, our results suggest that DICER is specifically regulated by osteogenic master gene Runx2 that binds to the DICER promoter. Consequently, DICER cleaves precursors of miR-335-5p and miR-17-92 cluster to form mature miRNAs, which target and decrease the Dickkopf-related protein 1 (DKK1), and proapoptotic factor BIM levels, respectively, leading to an enhanced Wnt/β-catenin signaling pathway. These intriguing results reveal a central mechanism underlying lineage-specific regulation by a Runx2/DICER/miRNAs cascade during osteogenic differentiation and bone development. Our study, also suggests a potential application of modulating DICER expression for bone tissue repair and regeneration. J. Cell. Physiol. 232: 182-191, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A new biomimetic nanointerface was constructed by facile grafting the bioactive arginylglycylaspartic acid (RGD) peptide on the graphene oxide (GO) surface through carbodiimide and N-hydroxysuccinimide coupling amidation reaction. The formed RGD-GO nanocomposites own unique two-dimensional structure and desirable electrochemical performance. The linked RGD peptides could improve GO’s biocompatibility and support the adhesion and proliferation of human periodontal ligament fibroblasts (HPLFs) on RGD-GO biofilm surface. Furthermore the biologically active RGD-GO nanocomposites were demonstrated as a potential biomimetic nanointerface for monitoring cell biobehaviors by electrochemical impedance spectroscopy (EIS). By analysis of the data obtained from equivalent circuit-fitting impedance spectroscopy, the information related to cell membrane capacitance, cell-cell gap resistance, and cell-electrode interface gap resistance in the process of cell adhesion and proliferation could be obtained. Besides, this proposed impedance-based cell sensor could be used to assess the inhibition effect of the lipopolysaccharide (LPS) on the HPLFs proliferation. Findings from this work suggested that RGD peptide functionalized GO nanomaterials may be not only applied in dental tissue engineering but also used as a sensor interface for electrochemical detection and analysis of cell behaviors in vitro. [ABSTRACT FROM AUTHOR]

This study was to investigate the association of psychological characteristics and functional dyspepsia treatment outcome. 109 patients who met the criteria for FD were enrolled. Eysenck Personality Questionnaire (EPQ), Symptom Checklist 90 (SCL90), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure personality, psychological symptoms, and sleep quality in our patients. Leeds Dyspepsia Questionnaire (LDQ) was used to assess dyspeptic symptoms at baseline and after eight weeks of treatment. The LDQ scores change after therapy, and the degraded rate of LDQ was used to assess the prognosis of patients. Logistic regression model was used to assess the effect of the personality, psychological symptoms, and sleep quality on the prognosis of patients. Our result revealed that poor sleep quality (OR=7.68, 95% CI 1.83–32.25) and bad marriage status (OR=1.22, 95% CI 1.10–1.36) had the negative effect on the prognosis of FD, while extroversion in personality traits (OR=0.86, 95% CI 0.76–0.96) had positive effect on the prognosis of FD. We should pay attention to the sleep quality, the personality, and the marriage status of FD patients; psychological intervention may have benefit in refractory FD. [ABSTRACT FROM AUTHOR]

Dental follicle cells (DFCs) are the precursor cells of periodontium. Under certain differentiation conditions, DFCs can be induced to differentiate into chondrogenic, osteogenic and adipogenic cells. However, DFCs has limited lifespan in vitro, so it’s difficult to harvest enough cells for basic research and translational application. pMPH86 is a piggyBac transposon-mediated vector which contains SV40 T-Ag cassette that can be removed by flippase recognition target (FRT) recombinase. Here we demonstrated the pMPH86 can effectively amplify human DFCs through reversible immortalization. The immortalized DFCs (iDFCs) exhibit higher proliferate activity, which can be reversed to its original level before immortalization when deimmortalized by FLP recombinase. The iDFCs and deimmortalized DFCs (dDFCs) express most DFC markers and maintain multiple differentiation potential in vitro as they can be induced by BMP9 to differentiate into chondrogenic, osteogenic and adipogenic cells evidenced by gene expression and protein marker. We also proved telomerase activity of iDFCs are significantly increased and maintained at a high level, while the telomerase activity of primary DFCs was relatively low and decreased with every passage. After SV40 T-Ag was removed to deimmortalize the cells, telomerase activity was reduced to its original level before immortalization and decreased with passages just the same as primary DFCs. These results suggest that piggyBac immortalization system could be a potential strategy to amplify primary cells, which is critical for regenerative research and further clinical application. [ABSTRACT FROM AUTHOR]

Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor cell mobilization from the bone marrow for tissue repair and remodeling. In this study, we found that APN regulates the mobilization and recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to participate in tissue repair and regeneration. APN facilitated BMSCs migrating from the bone marrow into the circulation to regenerate bone by regulating stromal cell-derived factor (SDF)−1 in a mouse bone defect model. More importantly, we found that systemic APN infusion ameliorated diabetic mobilopathy of BMSCs, lowered glucose concentration, and promoted bone regeneration in diet-induced obesity mice. In vitro studies allowed us to identify Smad1/5/8 as a novel signaling mediator of APN receptor (AdipoR)−1 in BMSCs and osteoblasts. APN stimulation of MC3T3-E1 osteoblastic cells led to Smad1/5/8 phosphorylation and nuclear localization and increased SDF-1 mRNA expression. Although APN-mediated phosphorylation of Smad1/5/8 occurred independently from adaptor protein, phosphotyrosine interaction, pleckstrin homology domain, and leucine zipper containing 1, it correlated with the disassembly of protein kinase casein kinase 2 and AdipoR1 in immunoprecipitation experiments. Taken together, this study identified APN as a regulator of BMSCs migration in response to bone injury. Therefore, our findings suggest APN signaling could be a potential therapeutic target to improve bone regeneration and homeostasis, especially in obese and T2D patients. S tem C ells 2015;33:240-252 [ABSTRACT FROM AUTHOR]

Background: The exact mechanism behind auditory hallucinations in schizophrenia remains unknown. A corollary discharge dysfunction hypothesis has been put forward, but it requires further confirmation. Electroencephalography (EEG) of the Deutsch octave illusion might offer more insight, by demonstrating an abnormal cerebral activation similar to that under auditory hallucinations in schizophrenic patients. Methods: We invited 23 first-episode schizophrenic patients with auditory hallucinations and 23 healthy participants to listen to silence and two sound sequences, which consisted of alternating 400- and 800-Hz tones. EEG spectral power and coherence values of different frequency bands, including theta rhythm (3.5-7.5 Hz), were computed using 32 scalp electrodes. Task-related spectral power changes and task-related coherence differences were also calculated. Clinical characteristics of patients were rated using the Positive and Negative Syndrome Scale. Results: After both sequences of octave illusion, the task-related theta power change values of frontal and temporal areas were significantly lower, and the task-related theta coherence difference values of intrahemispheric frontal-temporal areas were significantly higher in schizophrenic patients than in healthy participants. Moreover, the task-related power change values in both hemispheres were negatively correlated and the task-related coherence difference values in the right hemisphere were positively correlated with the hallucination score in schizophrenic patients. Limitations: We only tested the Deutsch octave illusion in primary schizophrenic patients with acute first episode. Further studies might adopt other illusions or employ other forms of schizophrenia. Conclusion: Our results showed a lower activation but higher connection within frontal and temporal areas in schizophrenic patients under octave illusion. This suggests an oversynchronized but weak frontal area to exert an action to the ipsilateral temporal area, which supports the corollary discharge dysfunction hypothesis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Understanding how cerebral regions are synchronized when hearing illusions might help to explain some of the mechanisms of hallucination in psychiatric disorders. EEG theta coherence in response to the octave illusion in healthy volunteers might be used for this purpose. Methods: Right-handed healthy volunteers were invited to hear silence, normal and reversed sequences of the octave illusion. Results: After hearing both normal and reversed sequences of the octave illusion, 11 people reported hearing the high tone in the left ear (RL) and 18 in the right (RR). The task-related power change in the right frontal and temporal areas and the task-related coherence difference in the right medial frontal and temporal areas were significantly increased in the RR group compared to the RL group. Conclusion: When processing the octave illusion, the right ear predominance was linked to a higher reactivity in the right frontal and right temporal areas in healthy right-handers. [ABSTRACT FROM AUTHOR]

Objective Osseointegration of orthodontic microscrew implant is influenced by tooth extraction. This study aims to evaluate the safety margin of the osseointegration of orthodontic implants by investigating the healing process of the implant-bone interface through histopathological studies and quantitative determination. Methods Twelve male beagles were selected and randomly divided into four groups. An orthodontic microscrew was implanted beside the tooth extraction area. Animals were killed in 1, 3, 8, and, 12 weeks to investigate tissue response. Histomorphological observation and bone implant contact ratio (BIC) tests were performed at different healing time after implantation. Results A new bone was formed on the implant-bone interface of the control group. Bone resorptions were also detected in the experimental group 3 weeks after implantation. The BIC level of the control groups increased during the first 8 weeks; no change was observed anymore after the 8th week. On the other hand, the BIC value in the experimental group decreased in the first 3 weeks. It then increased rapidly and reached its peak of 80.08% in the 8th week. No significant difference was found between the experimental and control groups in the first 3 weeks. After the 3rd week, the BIC value of the experimental group (44.35%) was lower than that of the control group (55.46%) (P<0.01). Conclusion The healing process after implantation was influenced by tooth extraction. Bone resorption was detected at an early stage. However, vigorous bone remodeling was observed subsequently. [ABSTRACT FROM AUTHOR]

The production of ligninolytic enzymes by the fungus Schizophyllum sp. F17 using a cost-effective medium comprised of agro-industrial residues in solid-state fermentation (SSF) was optimized. The maximum activities of the enzymes manganese peroxidase (MnP), laccase (Lac), and lignin peroxidases (LiP) were 1,200, 586, and 109 U/L, respectively, on day 5 of SSF. In vitro decolorization of three structurally different azo dyes by the extracellular enzymes was monitored to determine its decolorization capability. The results indicated that crude MnP, but not LiP and Lac, played a crucial role in the decolorization of azo dyes. After optimization of the dye decolorization system with crude MnP, the decolorization rates of Orange IV and Orange G, at an initial dye concentration of 50 mg/L, were enhanced to 76 and 57%, respectively, after 20 min of reaction at pH 4 and 35°C. However, only 8% decolorization of Congo red was observed. This enzymatic reaction system revealed a rapid decolorization of azo dyes with a low MnP activity of 24 U/L. Thus, this study could be the basis for the production and application of MnP on a larger scale using a low-cost substrate. [ABSTRACT FROM AUTHOR]

Recent studies have shown that F-box proteins constitute a large family in eukaryotes, and play pivotal roles in regulating various developmental processes in plants. However, their functions in monocots are still obscure. In this study, we characterized a recessive mutant dwarf and deformed flower 1-1 ( ddf1-1) in Oryza sativa (rice). The mutant is abnormal in both vegetative and reproductive development, with significant size reduction in all organs except the spikelet. DDF1 controls organ size by regulating both cell division and cell expansion. In the ddf1-1 spikelet, the specification of floral organs in whorls 2 and 3 is altered, with most lodicules and stamens being transformed into glume-like organs and pistil-like organs, respectively, but the specification of lemma/palea and pistil in whorls 1 and 4 is not affected. DDF1 encodes an F-box protein anchored in the nucleolus, and is expressed in almost all vegetative and reproductive tissues. Consistent with the mutant floral phenotype, DDF1 positively regulates B-class genes OsMADS4 and OsMADS16, and negatively regulates pistil specification gene DL. In addition, DDF1 also negatively regulates the Arabidopsis LFY ortholog APO2, implying a functional connection between DDF1 and APO2. Collectively, these results revealed that DDF1, as a newly identified F-box gene, is a crucial genetic factor with pleiotropic functions for both vegetative growth and floral organ specification in rice. These findings provide additional insights into the molecular mechanism controlling monocot vegetative and reproductive development. [ABSTRACT FROM AUTHOR]