Denticleless E3 ubiquitin protein ligase (DTL) maintains the proliferation and differentiation of epidermis and hair follicles during skin development.

BACKGROUND: A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. RESULTS: We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL-depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53-independent. CONCLUSION: Our findings indicate that DTL plays a vital role in epidermal malformation during skin development.

Changes of maxillary central incisor and alveolar bone in Class II Division 2 nonextraction treatment with a fixed appliance or clear aligner: A pilot cone-beam computed tomography study.

INTRODUCTION: This retrospective clinical study investigated the clinical changes of maxillary central incisor and alveolar bone in Class II Division 2 nonextraction treatment with fixed appliances or clear aligners on the basis of cone-beam computed tomography. METHODS: Fifty-nine Chinese Han patients with similar demographic characteristics were collected from a conventional bracket group, a self-ligating bracket group, and a clear aligner group. All measurements about root resorption and alveolar bone thickness on the cone-beam computed tomography images were tested. Changes between pretreatment and posttreatment were evaluated by paired-sample t test. The variation among the 3 groups was compared by 1-way analysis of variance. RESULTS: The resistance center of the maxillary central incisor showed upward or forward movement, and the axial inclination was increased in 3 groups (P <0.0001). Root volume loss in the clear aligner group (23.68 ± 4.82 mm3) was significantly less than that in the fixed appliances group (28.24 ± 6.44 mm3 in the conventional bracket group, 28.17 ± 6.07 mm3 in the self-ligating bracket group) (P <0.05). All 3 groups showed a significant decrease in palatal alveolar bone and total bone thickness at all 3 levels at posttreatment. In contrast, labial bone thickness significantly increased except for crestal level l. Among the 3 groups, the clear aligner group had a prominent increase in labial bone thickness at the apical level (P = 0.0235). CONCLUSIONS: Clear aligner treatment for Class II Division 2 malocclusions could effectively reduce the incidence of fenestration and root resorption. Our findings will be beneficial to comprehensively understand the effectiveness of different appliances for Class II Division 2 malocclusions treatment.

Three-dimensional measurement and analysis of mandibular characteristics in subjects with impacted mandibular second molars.

OBJECTIVE: To investigate the morphological characteristics of the mandible in subjects with impacted mandibular second molars by measuring and analysing the mandible in three dimensions. SETTING AND SAMPLE POPULATION: In this retrospective study, the data of a total of 52 609 subjects who underwent cone-beam computed tomography (CBCT) for diagnosis and treatment were reviewed. According to the inclusion and exclusion criteria, 183 subjects with impacted mandibular second molars and 176 age- and sex-matched controls were included. METHODS: A retrospective case-control study was designed. The 183 subjects were divided into two groups: group 1 (G1) comprised 120 patients with unilaterally impacted mandibular second molars, and group 2 (G2) comprised 63 patients with bilaterally impacted mandibular second molars. Group 3 (G3) contained 176 age- and sex-matched controls. The mandible was reconstructed with nineteen landmarks using Mimics software. Twelve linear lengths and 3 angles were measured. RESULTS: The bilateral germination gap, mandibular body width and gonion width in G1 were significantly lower than those in G3 (P < .05), while the gnathion angle and first molar width values in G1 were significantly higher than those in G3 (P < .05). The results in G2 were similar to those in G1, but the differences between G2 and G3 were greater than those between G1 and G3. There were no significant differences in the other measurements among the groups. CONCLUSION: The mandibles of the subjects with impacted second molars were constricted in terms of the sagittal length and transverse width.

Contemporary management of an orthodontic-orthognathic patient with limited time availability in an orthodontic office setting: Case report.

INTRODUCTION: This case report describes the treatment of a 21-year-old man who presented in an orthodontic office for treatment but lived in a city 100 miles away and wanted the orthognathic surgery in another state in America. The patient presented with an anterior open bite and skeletal Class III relationship. METHODS: The treatment plan included: (1) effective and careful communication of the treatment plan with the patient, orthodontist and oral and maxillofacial surgeon; (2) pre-surgical alignment and levelling of the teeth in both arches with Invisalign; (3) a long-distance communication between the orthodontist and the surgeon for surgical plan with virtual surgical planning (VSP Orthognathics; 3D Systems, www.3Dsystem.com) online; (4) maxillary advancement (LeFort I osteotomy) with mandibular set-back (bilateral sagittal split osteotomy); (5) postsurgical correction of the malocclusion with clear brackets and aligners; and (6) retention and final small tooth movement adjustments with aligners/clear retainers. RESULTS: The anterior open bite was treated, crowding was eliminated in the upper and lower anterior segment, correction of skeletal and dental Class III malocclusion was obtained, mandibular plane angle was reduced and facial profile improved. CONCLUSIONS: The results suggest that aesthetic and functional results can be achieved with long-distance communication of two specialties and with the combined use of clear aligners and clear fixed appliances.

Fixed orthodontic appliances cause pain and disturbance in somatosensory function.

This study aimed to assess the short-term effects of orthodontic pain on quantitative sensory testing (QST) in subjects receiving fixed orthodontic treatment. Twenty patients and 12 healthy volunteers (as controls) participated. All 20 patients had bonded AO self-ligating brackets, with a 0.014 super elastic nickel-titanium arch wire placed in the brackets. Pain [self-reported on a visual analog scale (VAS)], and thermal and mechanical thresholds, were tested at six time points--before (baseline), and 2 h, 24 h, 7 d, 14 d, and 30 d after, force application--in the treatment group. The attached gingiva adjacent to the left upper central incisor (21 gingiva) was hypersensitive to cold stimuli (i.e. increased cold detection thresholds were detected) in the treatment group. The pressure pain thresholds of the left upper central incisor (21) and 21 gingiva were significantly reduced. Our results suggest clear signs of sensitization of the trigeminal nociceptive system up to 1 month after force application and orthodontic pain. Quantitative assessment of somatosensory function may help to provide a better understanding and profiling of the underlying neurobiological mechanisms related to orthodontic pain.

Development and assessment of an online virtual orthodontic curriculum.

INTRODUCTION: Due to break space and time limits, an entirely new online curriculum of orthodontic education with online evaluation system has been structured and developed in the dental school, based on virtual reality simulation. CURRICULUM: At Nanjing Medical University, a new online orthodontic curriculum with programmatic assessment process was constructed and implemented based on competency-based education (CBE). It was consisted of the online orthodontic theoretical lectures based on the National Open Online Course "Orthodontics," the online journal club via the online "flipped classroom," and the online orthodontic pre-clinical training via the virtual learning network platform. In order to evaluate this curriculum, 94 Year 4 dental students took part to complete the online orthodontic curriculum. The mean total score of all the students was 91.99, and the element scores of the online theoretical lectures, journal club, virtual pre-clinical training, and online final examination were respectively 96.83, 79.49, 96.00, and 87.02, which showed a good performance. According to the student feedback toward this curriculum via the online questionnaire, nearly 98% of the students showed agreement or strong agreement that the online orthodontic curriculum has enhanced their orthodontic theoretical understanding and orthodontic practical ability. CONCLUSION: As a student-centered CBE, this online orthodontic curriculum with online evaluation system could provide both orthodontic theory and practice teaching for all the dental students at all times and places based on the online virtual mode, which enriched learners' critical thinking, problem solving, and assessment skills.

Novel quat/di-N-halamines silane unit with enhanced synergism polymerized on cellulose for development of superior biocidability.

A silane unit with enhanced synergism that is realized using one cationic quaternary ammonium salt (QAS) to draw anionic bacteria to two N-halamine functionalities was designed and polymerized on cellulose for superior biocidability. A monomer containing one tertiary amine, one amide N-H, and one imide N-H, was synthesized via alcoholysis of 3-triethoxysilylpropyl succinic anhydride with 2-(dimethylamino)ethan-1-ol and following esterification with 5-(4-hydroxyphenyl)hydantoin. The triethoxysilyl groups of the monomer were hydrolyzed to silanol groups to condense with counterparts in different hydrolyzates and with hydroxyl groups on cellulose to form a polymeric modifier. Each silane unit of the modifier has one QAS and two N-halamine functionalities (quat/di-N-halamines) after quaternization of the tertiary amine and chlorination of the amide and imide hydrogens. The resultant cellulose suppressed (7 logs) both Staphylococcus aureus and Escherichia coli within 3 min, demonstrating an enhanced synergism since the inactivation rate is faster than counterparts decorated with only N-halamine and with synergistic units of one cationic center and one N-halamine. The modifier exhibited promising stability and rechargeability toward washings, UV irradiation, and long-term storage. The proved enhanced synergism from the integration of one cationic center with multiple N-halamines directs the synthesis of more powerful biocides for developing antibacterial polymers.

[Three-dimensional analysis of the mandible with impacted mandibular second molar].

OBJECTIVE: To study the developmental and morphological characteristics of the mandible in patients with impacted mandibular second molar and to predict the possible trend of mandibular development via three-dimensional (3D) measurement and analysis. METHODS: A total of 88 cases of impacted group and 88 cases of control group were screened out. 3D measurements were performed by using Mimics software. A total of 23 landmark points and 17 measurements were determined. The measurements were analyzed by t-test. RESULTS: The mandible length, the space between the first molars, the space between mandibular angles, and the width between the first molars in the impacted group were lower than those in the control group (P<0.05). Moreover, the value of the submandibular angle was higher than that in the control group (P<0.05). CONCLUSIONS: The impacted mandible of patients with mandibular second molar showed lack of sagittal and width development, and the impacted mandibular second molar was a manifestation of its degeneration.

Three-Dimensional Culture Promotes the Differentiation of Human Dental Pulp Mesenchymal Stem Cells Into Insulin-Producing Cells for Improving the Diabetes Therapy.

INTRODUCTION: Diabetes is a metabolic disease with a high incidence and serious harm to human health. Islet ß-cell function defects can occur in the late stage of type 1 diabetes and type 2 diabetes. Studies have shown that stem cell is a promising new approach in bioengineering regenerative medicine. In the study of stem cell differentiation, three-dimensional (3D) cell culture is more capable of mimicking the microenvironment of cell growth in vivo than two-dimensional (2D) cell culture. The natural contact between cells and cells, and cells and extracellular matrix can regulate the development process and promote the formation of the artificial regenerative organs and organization. Type IV, VI collagen and laminin are the most abundant extracellular matrix components in islets. Matrigel, a basement membrane matrix biomaterial rich in laminin and collagen IV. MATERIALS AND METHODS: We used Matrigel biomaterial to physically embed human dental pulp stem cells (hDPSCs) to provide vector and 3D culture conditions for cells, and we explored and compared the preparation methods and preliminary mechanisms of differentiation of hDPSCs into insulin-producing cells (IPCs) under 2D or 3D culture conditions.We first designed and screened the strategy by mimicking the critical events of pancreatogenesis in vivo, and succeeded in establishing a new method for obtaining IPCs from hDPSCs. Activin A, Noggin, and small molecule compounds were used to synergistically induce hDPSCs to differentiate into definitive endoderm-like cells, pancreatic progenitor like cells and IPCs step by step under 2D culture conditions. Then, we used Matrigel to simulate the microenvironment in vivo, induced hDPSCs to differentiate into IPCs in Matrigel, evaluated and compared the efficiency between 2D and 3D culture conditions. RESULTS: The results showed that the synergistic combination of growth factors and small molecule compounds and 3D culture promoted the differentiation of hDPSCs into IPCs, significantly enhancing the release of insulin and C-peptide from IPCs. DISCUSSION: Significant support is provided for obtaining a large number of functional IPCs for disease modeling and final cell therapy in regenerative medicine.

[Advances in surgical techniques of periodontal corticotomy].

The number of adults seeking orthodontic treatment is increasing. Shortening the course of orthodontic treatment has become a research hotspot in recent years. Methods of accelerating tooth movement have been reported. Theoretical and clinical studies have confirmed that periodontal corticotomy is effective in accelerating tooth movement and increasing osteogenic potential. Many surgical techniques of periodontal corticotomy have been developed. This review summarizes the history of periodontal corticotomy and the development of the surgical techniques in recent years, thereby providing references for the clinical application of corticotomy.

Effect of corticision on orthodontic tooth movement in a rat model as assessed by RNA sequencing.

Corticision is a common technique to accelerate orthodontic tooth movement; however, not much is known about the underlying mechanisms. In this study, we investigated the mechanism of alveolar tissue remodeling after corticision in a rat model of tooth movement (TM) by analyzing the differential transcriptome. A total of 36 male rats were equally divided into TM and TM with corticision (TM+C) groups. Alveolar bone response was examined using micro-computed tomography (micro-CT). Osteoclasts and osteoblasts were quantified on tartrate-resistant acid phosphatase (TRAP) and Goldner's trichrome staining. The transcriptomes of alveolus around the left maxillary first molar were determined on RNA sequencing (RNA-Seq), and the expression of selected differentially expressed genes (DEGs) validated on quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Immunohistochemical examination of alveolar tissue was performed to examine the expressions of correlative proteins of the selected signaling pathway in the TM and TM+C groups. The ratio of bone volume to total volume (BV/TV), and the trabecular number (Tb.N) were significantly decreased, while the movement distance and the trabecular separation (Tb.Sp) was significantly increased in the TM+C group. However, no significant between-group difference in trabecular thickness (Tb.Th) was observed. On histomorphometric analysis, a significant increase in the number of osteoclasts and increased bone resorption was observed in the TM+C group. A total of 399 DEGs were identified on RNA-SEq. Eleven selected genes were confirmed on qRT-PCR, which included components of the Ras signaling pathway. Four proteins of the Ras signaling pathway showed a higher expression in the TM+C group. Our findings indicate that corticision may speed up orthodontic tooth movement by accelerating osteoclastogenesis mediated via the Ras signaling pathway.

Cranial base characteristics in anteroposterior malocclusions: A meta-analysis.

OBJECTIVE: To investigate cranial base characteristics in malocclusions with sagittal discrepancies. MATERIALS AND METHODS: An electronic search was performed in PubMed, Embase, Web of Science, and the Cochrane Library. A fixed- or random-effect model was applied to calculate weighted mean difference with 95% confidence intervals (CIs) according to statistical heterogeneity. Outcome measures were anterior, posterior, and total cranial base length and cranial base angle. Sensitivity analysis and publication bias were conducted. RESULTS: Twenty studies that together included 1121 Class I, 1051 Class II, and 730 Class III cases qualified for the final analysis. Class III malocclusion demonstrated significantly reduced anterior (95% CI: -1.74, -0.53; P < .001 vs Class I; 95% CI: -3.30, -2.09; P < .001 vs Class II) and total cranial base length (95% CI: -3.33, -1.36; P < .001 vs Class I; 95% CI: -7.38, -4.05; P < .001 vs Class II). Further, Class II patients showed significantly greater anterior and total cranial base length than did Class I patients (95% CI: 0.51, 1.87; P < .001 for SN; 95% CI: 2.20, 3.30; P < .001 for NBa). Cranial base angle was significantly smaller in Class III than in Class I (95% CI: -3.14, -0.93; P < .001 for NSBa; 95% CI: -2.73, -0.68; P  =  .001 for NSAr) and Class II malocclusions (95% CI: -5.73, -1.06; P  =  .004 for NSBa; 95% CI: -6.11, -1.92; P < .001 for NSAr) and greater in Class II than in Class I malocclusions (95% CI: 1.38, 2.38; P < .001 for NSBa). CONCLUSIONS: This meta-analysis showed that anterior and total cranial base length and cranial base angle were significantly smaller in Class III malocclusion than in Class I and Class II malocclusions, and that they were greater in Class II subjects compared to controls.

Structure and properties of phospholipid-peptide monolayers containing monomeric SP-B(1-25) I. Phases and morphology by epifluorescence microscopy.

Epifluorescence microscopy was used to study the structure and phase behavior of phospholipid films containing a human-sequence monomeric SP-B(1-25) synthetic peptide (mSP-B(1-25)). Measurements were done directly at the air-water (A/W) interface on films in a Langmuir-Whilhelmy balance coupled to a fluorescence microscope and real-time detection system to yield an approximate optical resolution of 1 mum. Fluorescence was achieved by laser excitation of 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)-1-hexadecanoyl-sn-glycero-3-PC (BODIPY-PC, concentration

Structure and properties of phospholipid-peptide monolayers containing monomeric SP-B(1-25) II. Peptide conformation by infrared spectroscopy.

The conformation and orientation of synthetic monomeric human sequence SP-B(1-25) (mSP-B(1-25)) was studied in films with phospholipids at the air-water (A/W) interface by polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS). Modified two-dimensional infrared (2D IR) correlation analysis was applied to PM-IRRAS spectra to define changes in the secondary structure and rates of reorientation of mSP-B(1-25) in the monolayer during compression. PM-IRRAS spectra and 2D IR correlation analysis showed that, in pure films, mSP-B(1-25) had a major alpha-helical conformation plus regions of beta-sheet structure. These alpha-helical regions reoriented later during film compression than beta structural regions, and became oriented normal to the A/W interface as surface pressure increased. In mixed films with 4:1 mol:mol acyl chain perdeuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPC-d(62):DOPG), the IR spectra of mSP-B(1-25) showed that a significant, concentration-dependent conformational change occurred when mSP-B(1-25) was incorporated into a DPPC-d(62):DOPG monolayer. At an mSP-B(1-25) concentration of 10 wt.%, the peptide assumed a predominantly beta-sheet conformation with no contribution from alpha-helical structures. At lower, more physiological peptide concentrations, 2D IR correlation analysis showed that the propensity of mSP-B(1-25) to form alpha-helical structures was increased. In phospholipid films containing 5 wt.% mSP-B(1-25), a substantial alpha-helical peptide structural component was observed, but regions of alpha and beta structure reoriented together rather than independently during compression. In films containing 1 wt.% mSP-B(1-25), peptide conformation was predominantly alpha-helical and the helical regions reoriented later during compression than the remaining beta structural components. The increased alpha-helical structure of mSP-B(1-25) demonstrated here by PM-IRRAS and 2D IR correlation analysis in monolayers of 4:1 DPPC:DOPG containing 1 wt.% (and, to a lesser extent, 5 wt.%) peptide may be relevant for the formation of the intermediate order 'dendritic' surface phase observed in similar surface films by epi-fluorescence.

The biocompatibility of calcium phosphate cements containing alendronate-loaded PLGA microparticles in vitro.

The composite of poly-lactic-co-glycolic acid (PLGA) and calcium phosphate cements (CPC) are currently widely used in bone tissue engineering. However, the properties and biocompatibility of the alendronate-loaded PLGA/CPC (APC) porous scaffolds have not been characterized. APC scaffolds were prepared by a solid/oil/water emulsion solvent evaporation method. The morphology, porosity, and mechanical strength of the scaffolds were characterized. Bone marrow mesenchymal stem cells (BMSCs) from rabbit were cultured, expanded and seeded on the scaffolds, and the cell morphology, adhesion, proliferation, cell cycle and osteogenic differentiation of BMSCs were determined. The results showed that the APC scaffolds had a porosity of 67.43 ± 4.2% and pore size of 213 ± 95 µm. The compressive strength for APC was 5.79 ± 1.21 MPa, which was close to human cancellous bone. The scanning electron microscopy, cell counting kit-8 assay, flow cytometry and ALP activity revealed that the APC scaffolds had osteogenic potential on the BMSCs in vitro and exhibited excellent biocompatibility with engineered bone tissue. APC scaffolds exhibited excellent biocompatibility and osteogenesis potential and can potentially be used for bone tissue engineering.

[Establishment and biomechanical analysis of three-dimensional nonlinear finite element model of three-pieces segment arch].

OBJECTIVE: To reconstruct a three-dimensional nonlinear finite element model of mandibular teeth with three-pieces segment arch, and analyze the mechanical properties of intrusive arch and the biomechanical characteristics of three-pieces segment arch. METHODS: Three-dimensional nonlinear finite element model of mandible with three-pieces segment arch was reconstructed by multi-slice spiral CT scanning, Mimics, CATIA and Anasys software. Then, the mechanical properties of intrusive arch, the movement trend and stress distribution of three-pieces segment arch were calculated by Anasys software. RESULTS: In the range of 5 degrees-25 degrees, with the degree of intrusive arch increased, the force of intrusive arch also increased rapidly. The maximal force was 0.604 8 N in 30 degrees; the force was about 0.59 N in 30 degrees-65 degrees range. In condition of three-pieces segment arch mechanics, lateral incisor tipped labially and intruded; the first moral tipped distally and rotating; other teeth did not move clearly. The largest stress distribution in the whole arch was in the one-third labial cervical area of the lateral incisor root and the root bifurcations of first moral. CONCLUSION: Under an appropriate intrusive force, three-pieces segment arch can intrude incisors and control the extrusion of posterior teeth. It can be used to correct the deep overbite, especially with high mandibular planes, gummy smile or adult patients.

[Comparative evaluation of two kinds of micro-implant system with different size].

OBJECTIVE: To offer some reference for micro-implant's development and population by analyzing clinical application of two kinds of micro-implant systems. METHODS: 38 patients treated with MIA (micro-implant anchorage) and 28 patients treated with SDIA (self-driven titanium implant for orthodontic anchorage) were included. Analyzing the rate of lost implants, the gum's reactivity and the efficiency of moving teeth summarized the excellences and shortcomings of two systems. RESULTS: 1) Six of MIA implants fell off after being inserted. Seven of SDIA implants lost when they had been implanted for a month. But they were stable after being inserted again. 2) The gum around 12 SDIA implants got inflammation symptom, but the gum around MIA implants was normal. 3) Both MIA implants and SDIA implants could move teeth effectively and persistently when they were stable. CONCLUSION: When we apply micro-implant in clinic, we should prevent it from closing roots of teeth and choose the small tip micro-implant. The embedded position should be in area of attachment gum. At the same time, the areas around the tip of micro-implant should be keeping clean.