AttentionPert: accurately modeling multiplexed genetic perturbations with multi-scale effects.

MOTIVATION: Genetic perturbations (e.g. knockouts, variants) have laid the foundation for our understanding of many diseases, implicating pathogenic mechanisms and indicating therapeutic targets. However, experimental assays are fundamentally limited by the number of measurable perturbations. Computational methods can fill this gap by predicting perturbation effects under novel conditions, but accurately predicting the transcriptional responses of cells to unseen perturbations remains a significant challenge. RESULTS: We address this by developing a novel attention-based neural network, AttentionPert, which accurately predicts gene expression under multiplexed perturbations and generalizes to unseen conditions. AttentionPert integrates global and local effects in a multi-scale model, representing both the nonuniform system-wide impact of the genetic perturbation and the localized disturbance in a network of gene-gene similarities, enhancing its ability to predict nuanced transcriptional responses to both single and multi-gene perturbations. In comprehensive experiments, AttentionPert demonstrates superior performance across multiple datasets outperforming the state-of-the-art method in predicting differential gene expressions and revealing novel gene regulations. AttentionPert marks a significant improvement over current methods, particularly in handling the diversity of gene perturbations and in predicting out-of-distribution scenarios. AVAILABILITY AND IMPLEMENTATION: Code is available at https://github.com/BaiDing1234/AttentionPert.

Customized planning of the visible maxillary arch width in harmony with interparopia width and smile width for female facial aesthetics.

BACKGROUND: The visible maxillary arch width (VAW) is an important aesthetic-determining feature. To date, there is no well-established methodology to determine the aesthetically optimal VAW in customized treatment planning. METHODS: In this study, the common traits of the dentofacial configuration were investigated in most attractive Asian and Caucasian female smiles. The smiling photo of a subject was digitally modified based on combined variations of VAW, smile width (SW), transverse facial dimensions (TFD), and vertical facial dimensions. These modified photos were assessed for aesthetics. The aesthetically essential parameters were identified, and their mathematic correlations and reference ranges were determined for different vertical facial patterns. Using the obtained results, a mathematic guidance was constructed for customized smile designing. The applicability of this guidance was tested in Asian females. RESULTS: The most attractive Asian and Caucasian female smiles have intraracial and interracial commonalities in the VAW-to-TFD ratios. The interparopia width (IPD) predominated over facial widths in determining well-matched VAW and SW. For optimal smile aesthetics, the VAW and SW were correlated as simulated by the formula 1.92 IPD ≤ VAW + 2.3 SW ≤ 2.17 IPD, plus the VAW-to-IPD ratio within 0.54 to 0.62 and the SW-to-IPD ratio within 0.61 to 0.71, ranges tailored to vertical facial patterns. This constitutes a mathematic guidance for customized planning of the aesthetically optimal VAW. This guidance was preliminarily validated to be applicable to Asian females. CONCLUSIONS: The VAW-to-TFD ratios were essential for Caucasian and Asian female smile aesthetics. The mathematic guidance could serve as a reference for customized smile designs for Asian females.

Assessment tools for stigma in breast cancer patients based on COSMIN guidelines: a systematic review.

OBJECTIVE: The objective of this study was to conduct a systematic review of the measurement properties and methodological quality of stigma assessment tools designed for breast cancer patients. The aim was to provide clinical medical staff with a foundation for selecting high-quality assessment tools. METHODS: A comprehensive computer search was carried out across various databases, including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database(VIP), Embase, PubMed, Web of Science, The Cochrane Library, and Scopus, which were searched from the inception of the databases until March 20, 2023. Literature screening and data extraction were performed independently by two researchers, adhering to predefined inclusion and exclusion criteria. The assessment tools were evaluated using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) systematic evaluation guidelines. RESULTS: In the final analysis, a total of 9 assessment tools were included. However, none of these tools addressed measurement error, cross-cultural validity, criterion validity, and responsiveness. Following the COSMIN guidelines, BCSS and CSPDS were assigned to Class A recommendations, while the remaining tools received Class B recommendations. CONCLUSION: The BCSS and CSPDS scales demonstrated comprehensive assessment in terms of their measurement characteristics, exhibiting good methodological quality, measurement attribute quality, and supporting evidence. Therefore, it is recommended to utilize these scales for evaluating breast cancer stigma. However, further validation is required for the remaining assessment tools.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

OBJECTIVES: Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. MATERIALS AND METHODS: Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6 -methyladenosine (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A inhibition in TMJOA were investigated. RESULTS: Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6 A modification. Moreover, inhibition of m6 A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats. CONCLUSIONS: This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6 A inhibition in TMJOA.

Reliability and validity of the Chinese version of the trauma-specific frailty index (TSFI) for geriatric trauma patients.

BACKGROUND: Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients. METHODS: A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach's alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value. RESULTS: The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach's alpha coefficient of the C-TSFI was 0.861, Cronbach's alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904-0.96, P < 0.05), the maximum YI was 0.725, the sensitivity was 80.2%, the specificity was 92.3%, and the critical value was 0.31. Kappa value was 0.682 (P < 0.05). CONCLUSIONS: The Chinese version of TSFI could be used as a general assessment tool in geriatric trauma patients, and both its reliability and validity have been demonstrated.

Enhanced virulence of genetically engineered Autographa californica nucleopolyhedrovirus owing to accelerated viral DNA replication aided by inserted ascovirus genes.

Genetic engineering technology is an ideal method to improve insecticidal efficiency by combining the advantages of different pathogenic microorganisms. Thus, six ascovirus genes were introduced into the genomic DNA of Autographa californica nucleopolyhedrovirus (AcMNPV) to possibly transfer the intrinsically valuable insecticidal properties from ascovirus to baculovirus. The viral budded virus (BV) production and viral DNA replication ability of AcMNPV-111 and AcMNPV-165 were significantly stronger than that of AcMNPV-Egfp (used as the wild-type virus in this study), whereas AcMNPV-33 had reduced ones. AcMNPV-111 and AcMNPV-165 also exhibited excellent insecticidal efficiency in the in vivo bioassays: AcMNPV-111 showed a 24.1% decrease in the LT50 value and AcMNPV-165 exhibited a 56.3% decrease in the LD50 value compared with AcMNPV-Egfp against the 3rd instar of Spodoptera exigua larvae, respectively. Furthermore, the size of the occlusion bodies (OBs) of AcMNPV-33, AcMNPV-111, and AcMNPV-165 were significantly increased compared to that of AcMNPV-Egfp. AcMNPV-111 and AcMNPV-165 had stable virulence against the 2nd to 4th instars tested larvae and higher OB yield than AcMNPV-Egfp in the 3rd and 4th instar larvae. Correlation and regression analyses indicated that it is better to use 5 OBs/larva virus to infect the 2nd instar larvae to produce AcMNPV-111 and 50 OBs/larva virus to infect the 3rd instar larvae to produce AcMNPV-165. The results of this study obtained recombinant viruses with enhanced virulence and exhibited a diversity of ascovirus gene function based on the baculovirus platform, which provided a novel strategy for the improvement of baculovirus as a biological insecticide.

Effect of offset on the precision of 3D-printed orthognathic surgical splints.

OBJECTIVE: This study evaluated the effect of offset on the precision of three-dimensional (3D)-printed splints, proposing to optimize the splint design to compensate for systematic errors. MATERIALS AND METHODS: 14 resin model sets were scanned and offset as a whole by given distances (0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, and 0.40 mm). Intermediate splints (ISs) and final splints (FSs) were generated from the non-offset and offset models and grouped correspondingly, named as splint type-offset value, IS-0.05, for instance. Dentitions occluded with the splint were scanned. Translational and rotational deviations of the lower dentition relative to the upper dentition were 3D measured. RESULTS: Deviations of ISs and FSs were more evident in the vertical and pitch dimensions, and were mostly acceptable in other dimensions. ISs with offset ≥ 0.05 mm showed vertical deviations significantly below 1 mm (P < 0.05) while ISs with 0.10- to 0.30-mm offsets had pitch rotations significantly lower than 1° (P < 0.05). The Pitch of IS-0.35 was significantly larger than ISs with 0.15- to 0.30-mm offsets (P < 0.05). Meanwhile, FSs fit better as the offset increased and FSs with offsets ≥ 0.15 mm all had deviations significantly lower than 1 mm (for translation) or 1° (for rotation) (P < 0.05). CONCLUSIONS: Offset affects the precision of 3D-printed splints. Moderate offset values of 0.10 to 0.30 mm are recommendable for ISs. Offset values ≥ 0.15 mm are recommended for FSs in cases with stable final occlusion. CLINICAL RELEVANCE: This study found the optimal offset ranges for 3D-printed ISs and FSs via a standardized protocol.

XGBoost-aided prediction of lip prominence based on hard-tissue measurements and demographic characteristics in an Asian population.

INTRODUCTION: Prediction of lip prominence based on hard-tissue measurements could be helpful in orthodontic treatment planning and has been challenging and formidable thus far. METHODS: A machine learning-based cross-sectional study was conducted on 1549 patients. Hard-tissue measurements and demographic information were used as the input features. Seven popular machine learning algorithms were applied to the datasets to predict upper and lower lip prominence. The algorithm that performed the best was selected for the construction of the prediction model. Evaluation of feature importance was conducted using 3 classical methods. RESULTS: Among the 7 algorithms, the XGBoost model performed the best in the prediction of the distances between labrale superius or labrale inferius to the esthetics plane (UL-EP and LL-EP distances), with root mean square error values of 1.25, 1.49 and r2 values of 0.755 and 0.683, respectively. Among the 14 input features, the L1-NB distance contributed the most to the prominences of the upper and lower lips. A lip prominence predictor was developed to facilitate clinical application by deploying the prediction model into a downloadable tool kit. CONCLUSIONS: The XGBoost model performed well with high accuracy and practicability in predicting upper and lower lip prominence. The artificial intelligence-aided predictor could serve as a reference for orthodontic treatment planning.

Bioheterojunction-Engineered Polyetheretherketone Implants With Diabetic Infectious Micromilieu Twin-Engine Powered Disinfection for Boosted Osteogenicity.

Diabetic infectious micromilieu (DIM) leads to a critical failure rate of osseointegration by virtue of two main peculiarities: high levels of topical glucose and inevitable infection. To tackle the daunting issue, a bioheterojunction-engineered orthopedic polyetheretherketone (PEEK) implant consisting of copper sulfide/graphene oxide (CuS/GO) bioheterojunctions (bioHJs) and glucose oxidase (GOx) is conceived and developed for DIM enhanced disinfection and boosted osseointegration. Under hyperglycemic micromilieu, GOx can convert surrounding glucose into hydrogen peroxide (H2 O2 ). Then, upon infectious micromilieu, the bioHJs enable the catalyzation of H2 O2 to highly germicidal hydroxyl radical (·OH). As a result, the engineered implants massacre pathogenic bacteria through DIM twin-engine powered photo-chemodynamic therapy in vitro and in vivo. In addition, the engineered implants considerably facilitate cell viability and osteogenic activity of osteoblasts under a hyperglycemic microenvironment via synergistic induction of copper ions (Cu2+ ) and GO. In vivo studies using bone defect models of diabetic rats at 4 and 8 weeks further authenticate that bioHJ-engineering PEEK implants substantially elevate their osseointegration through biofilm elimination and vascularization, as well as macrophage reprogramming. Altogether, the present study puts forward a tactic that arms orthopedic implants with DIM twin-engine powered antibacterial and formidable osteogenic capacities for diabetic stalled osseointegration.

Inhibition of osteoclastogenesis by interleukin-33 administration in the periodontal ligament under mechanical loading.

BACKGROUND AND OBJECTIVES: The molecular mechanisms mediating external root resorption are poorly understood. Interleukin-33 (IL-33) expression increased remarkably in the periodontal ligament (PDL) under orthodontic loading. The IL-33-driven responses are delicately cell type- and tissue context-dependent. It is unknown how IL-33 act on osteoclastogenesis in the context of root surface. This study aimed to investigate the effect of IL-33 on osteoclastogenesis in the PDL under mechanical loading. MATERIALS AND METHODS: C57BL/6J mice were treated with injections of phosphate buffer saline (PBS) or recombinant mouse IL-33 (rmIL-33, 6 µl, 30 µg/ml), and subjected to models of orthodontic tooth movement. Tartrated resistant acid phosphates (TRAP)-positive cells and IL-33 expressions were examined in the PDL. IL-33 release from human PDL cells (hPDLCs) was detected by ELISA. Cementoblast-like (OCCM-30) cells were cultured in the presence of rmIL-33 to examine the release of osteoclast-regulatory proteins. The effects of rmIL-33 on osteoclastogenesis were examined in vitro in cultures of bone marrow macrophages (BMMs) and in BMMs-OCCM-30 cocultures. Expressions of osteoclast-specific or -related genes and proteins were investigated in BMMs-OCCM-30 cocultures treated with or without rmIL-33, in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody. RESULTS: Interleukin-33 expressions were upregulated in the PDL under orthodontic loading. Static compressive force enhanced expression and release of IL-33 from hPDLCs. Administration of rmIL-33 resulted in reduced number of TRAP-positive cells in the PDL, and inhibited osteoclast differentiation from BMMs in vitro. OCCM-30 cells had varied osteoprotegerin (OPG) / receptor activator for nuclear factor-κB ligand (RANKL) secretion and increased release of GM-CSF under rmIL-33 stimulation. Treatment with rmIL-33 in BMMs-OCCM-30 cocultures resulted in inhibited differentiation and decreased activity of osteoclasts, and these effects were partially reversed by GM-CSF neutralizing antibody. CONCLUSIONS: Interleukin-33 inhibits osteoclastogenesis in the PDL under orthodontic loading. The anti-osteoclastogenic effects were mediated partly by directly affecting osteoclast precursors and partly by cementoblast-mediated release of GM-CSF.

Methods to assess tooth gingival thickness and diagnose gingival phenotypes: A systematic review.

OBJECTIVE: Measurement of the periodontal soft tissue dimension is crucial for clinical decision-making and aesthetic prognosis. However, the effectiveness of different measuring methods remains unclear. This systematic review aimed to explore the diagnostic accuracy of two non-invasive methods (namely CBCT and ultrasound) for gingival thickness measurement at different tooth positions. MATERIALS AND METHODS: A systematic search was performed using PubMed (including Medline), PubMed Central, OVID, Cochrane Library, LILACS and OpenGrey. Studies focusing on comparisons between CBCT, ultrasound and direct transgingival probing were included. The means, SDs and correlation coefficients with 95% confidence intervals were extracted and analyzed using Review Manager and R software. RESULTS: Twelve studies were selected. No significant difference was found between CBCT measurement and transgingival probing in the anterior and posterior dentition, and a moderate correlation was observed between these two methods (r = 0.41). A weak correlation was found between ultrasound measurement and transgingival probing (r = 0.32), and a slight but statistically significant difference was found when comparing ultrasonic devices and transgingival probing in the posterior area. CONCLUSION: CBCT can be considered a relatively reliable method for gingival thickness measurement in both the anterior and posterior areas compared with direct probing. Ultrasonic devices provide limited accuracy in the posterior area but are relatively comparable with direct clinical assessments in the anterior area. CLINICAL SIGNIFICANCE: Measurement location may affect the diagnostic accuracy and repeatability of gingival thickness measurements. Appropriate method selection in different clinical scenarios is crucial to aesthetic outcome prediction and decision-making.

Orthodontic correction of a skeletal Class II malocclusion with severe gummy smile by total intrusion of the maxillary dentition.

A 22-year-old woman visited the hospital complaining of lip protrusion, crowded teeth, and a gummy smile. The clinical examination showed a convex profile with a hyperdivergent mandible and a severe gummy smile in both anterior and posterior regions. The unstable mandible position was considered during treatment planning, and a targeted mechanic system was carefully designed. Temporary skeletal anchorage devices in the posterior dental region and a transpalatal arch were introduced as anchorage for the intrusion of the entire maxillary dentition and controlled retraction of the anterior teeth. Based on effective and simple mechanisms, we successfully eliminated the severe gummy smile and improved the facial aesthetics with the aid of conventional appliances. This approach provided an alternative option to orthognathic surgery or bulky invasive miniscrews for treatment of skeletal Class II malocclusion with severe gummy smile.

The lower bow-shaped curve as a novel reference frame to determine the lateral limit of the maxillary anterior arch for smile esthetics.

INTRODUCTION: Smile analysis in horizontally angled views is indispensable for esthetic assessment and could reveal teeth-to-lip disharmony, which might escape discovery in the frontal and profile views. However, evidence is lacking on where the anterior teeth should be positioned for esthetics in angled smiles. METHODS: Based on 3-dimensional facial image processing and geometric analysis, the lip edges were projected to the horizontal plane, and the horizontal teeth-to-lip relation was simplified and represented by the distances from dental landmarks to lower bow-shaped curves (LBSC), with the distance from facial-axis (FA) point of the canine to LBSC (FA-tangent line [TL] distance) identified as the key parameter. Using photographic modification and esthetic assessment, the effect of FA-TL distances on the attractiveness of 45° angled smiles was tested, with esthetic ranges identified. A simplified method was developed to obtain the estimative LBSC and FA-TL distances using 2-dimensional photographs and geometric analysis to facilitate clinical application. RESULTS: The FA-TL distance remarkably affected the esthetics of 45° angled smiles. Smiles were attractive when the FA-TL distance ranged from -1.0 to 1.5 mm perceived by orthodontists and from -1.5 to 1.5 mm perceived by laypersons. The 2-dimensional photograph-derived estimative FA-TL distance was not significantly different from that obtained in a 3-dimensional image, validating the simplified method. CONCLUSIONS: The LBSC could serve as a reference frame to determine the lateral limit of the maxillary anterior arch for the esthetics of 45° angled smiles. The FA-TL distance, which represented the spatial relation of the maxillary canine with the lower lip, was an esthetically essential parameter. For females aged 20-30 years, the FA point of the maxillary canines should be positioned no more than 1.5 mm labial or lingual to the LBSC.

Integrating maxillary dentition and 3D facial photo using a modified CAD/CAM facebow.

BACKGROUND: Accurate integration of the dentitions with the face is essential in dental clinical practice. Here we introduce a noninvasive and efficient protocol to integrate the digitized maxillary dentition with the three-dimensional (3D) facial photo using a prefabricated modified computer-aided design/computer-aided manufacture (CAD/CAM) facebow. METHODS: To integrate the maxillary dentition with the 3D facial photo, the CAD/CAM facebow protocol was applied to 20 patients by taking a series of 3D facial photos in the clinic and integrating them in the laboratory. The integration accuracy of this protocol was compared with that of a valid 3D computed tomography (CT)-aided protocol concerning translational deviations of the landmarks representing maxillary incisors and maxillary first molars as well as the rotational deviation of the maxillary dentition. The intra- and inter-observer reproducibility was assessed, and the time of clinical operation and laboratory integration was recorded. RESULTS: This facebow-aided protocol generated 3D fused images with colored faces and high-resolution dentitions, and showed high reproducibility. Compared with the well-established CT-aided protocol, the translational deviations ranged from 0 to 1.196 mm, with mean values ranging from 0.134 to 0.444 mm, and a relatively high integration error was found in the vertical dimension (Z) with a mean ± standard deviation (SD) of 0.379 ± 0.282 mm. Meanwhile, the rotational deviations ranged from 0.020 to 0.930°, with mean values less than 1°, and the most evident deviation was seen in pitch rotation with a mean ± SD of 0.445 ± 0.262°. The workflow took 4.34 ± 0.19 min (mins) for clinical operation and 11.23 ± 0.29 min for laboratory integration. CONCLUSION: The present radiation-free protocol with the modified CAD/CAM facebow provided accurate and reproducible transfer of the digitized maxillary dentition to the 3D facial photo with high efficiency.

Effect of occlusal coverage depths on the precision of 3D-printed orthognathic surgical splints.

BACKGROUND: Precise orthognathic surgical splints are important in surgical-orthodontic treatment. This study aimed to propose a standardized protocol for three-dimensional (3D)-printed splints and assess the precision of splints with different occlusal coverage on the dentition (occlusal coverage depth, OCD), thus optimizing the design of 3D-printed splints to minimize the seemingly unavoidable systematic errors. METHODS: Resin models in optimal occlusion from 19 patients were selected and scanned. Intermediate splints (ISs) and final splints (FSs) with 2-mm, 3-mm, 4-mm, and 5-mm OCDs were fabricated and grouped as IS-2, IS-3, IS-4, IS-5, FS-2, FS-3, FS-4, and FS-5, respectively. The dentitions were occluded with each splint and scanned as a whole to compare with the original occlusion. Translational and rotational deviations of the lower dentition and translational deviations of the landmarks were measured. RESULTS: For vertical translation, the lower dentitions translated inferiorly to the upper dentition in most of the splints, and the translation increased as OCD got larger. Vertical translations of the dentitions in 89.47% of IS-2, 68.42% of IS-3, 42.11% of IS-4, 10.53% of IS-5, 94.74% of FS-2, 63.16% of FS-3, 26.32% of FS-4, and 21.05% of FS-5 splints were below 1 mm, respectively. For pitch rotation, the lower dentitions rotated inferiorly and posteriorly in most groups, and the rotation increased as OCD got larger. Pitch rotations of the dentitions in 100% of IS-2, 89.47% of IS-3, 57.89% of IS-4, 52.63% of IS-5, 100.00% of FS-2, 78.95% of FS-3, 52.63% of FS-4, and 47.37% of FS-5 splints were below 2°, respectively. On the other hand, the transversal and sagittal translations, roll and yaw rotations of most groups were clinically acceptable (translation < 1 mm and rotation < 2°). The deviations of ISs and FSs showed no statistical significance at all levels of coverage (P > 0.05). CONCLUSIONS: A protocol was proposed to generate 3D-printed ISs and FSs with normalized basal planes and standardized OCDs. Deviations of the ISs and FSs were more evident in the vertical dimension and pitch rotation and had a tendency to increase as the OCD got larger. ISs and FSs with both 2-mm and 3-mm OCD are recommendable regarding the precision relative to clinical acceptability. However, considering the fabrication, structural stability, and clinical application, ISs and FSs with 3-mm OCD are recommended for accurate fitting.

Proteoglycans in the periodontium: A review with emphasis on specific distributions, functions, and potential applications.

Proteoglycans (PGs) are largely glycosylated proteins, consisting of a linkage sugar, core proteins, and glycosaminoglycans (GAGs). To date, more than 40 kinds of PGs have been identified, and they can be classified as intracellular, cell surface, pericellular, and extracellular PGs according to cellular locations. To illustrate, extracellular PGs are known for regulating the homeostasis of the extracellular matrix; cell-surface PGs play a role in mediating cell adhesion and binding various growth factors. In the field of periodontology, PGs are implicated in cellular proliferation, migration, adhesion, contractility, and anoikis, thereby exerting a profound influence on periodontal tissue development, wound repair, the immune response, biomechanics, and pathological process. Additionally, the expression patterns of some PGs are dynamic and cell-specific. Therefore, determining the roles and spatial-temporal expression patterns of PGs in the periodontium could shed light on treatments for wound healing, tissue regeneration, periodontitis, and gingival overgrowth. In this review, close attention is paid to the distributions, functions, and potential applications of periodontal PGs. Related genetically modified animal experiments and involved signal transduction cascades are summarized for improved understanding of periodontal PGs. To date, however, there is a large amount of speculation on this topic that requires rigorous experiments for validation.

Expression of an active Gαs mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance.

Fibrous dysplasia (FD) is a disease caused by postzygotic activating mutations of GNAS (R201C and R201H) that encode the α-subunit of the Gs stimulatory protein. FD is characterized by the development of areas of abnormal fibroosseous tissue in the bones, resulting in skeletal deformities, fractures, and pain. Despite the well-defined genetic alterations underlying FD, whether GNAS activation is sufficient for FD initiation and the molecular and cellular consequences of GNAS mutations remains largely unresolved, and there are no currently available targeted therapeutic options for FD. Here, we have developed a conditional tetracycline (Tet)-inducible animal model expressing the GαsR201C in the skeletal stem cell (SSC) lineage (Tet-GαsR201C/Prrx1-Cre/LSL-rtTA-IRES-GFP mice), which develops typical FD bone lesions in both embryos and adult mice in less than 2 weeks following doxycycline (Dox) administration. Conditional GαsR201C expression promoted PKA activation and proliferation of SSCs along the osteogenic lineage but halted their differentiation to mature osteoblasts. Rather, as is seen clinically, areas of woven bone admixed with fibrous tissue were formed. GαsR201C caused the concomitant expression of receptor activator of nuclear factor kappa-B ligand (Rankl) that led to marked osteoclastogenesis and bone resorption. GαsR201C expression ablation by Dox withdrawal resulted in FD-like lesion regression, supporting the rationale for Gαs-targeted drugs to attempt FD cure. This model, which develops FD-like lesions that can form rapidly and revert on cessation of mutant Gαs expression, provides an opportunity to identify the molecular mechanism underlying FD initiation and progression and accelerate the development of new treatment options.

Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration.

Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are seldom reported. In the current study, TMJ condyles were extracted from young (4-month-old), middle-aged (10-month-old), and old-aged (20-month-old) adults to detect the morphology and circadian oscillation changes in TMJ condyles with aging. The transcriptome profile of Bmal1-deleted bone-marrow mesenchymal stem cells (BMSCs) and controls were explored to reveal the circadian-related differences at the molecular level. Furthermore, the reparative effects of Bmal1-overexpressed BMSCs-based cytotherapy in aged TMJ condyles were investigated in vitro and in vivo. Aged TMJ condyles displayed damaged tissue structure and an abolished circadian rhythm, accompanied by a progressively decreasing chondrogenesis capability and bone turnover activities. The deletion of Bmal1 significantly down-regulated chondrogenesis-related genes Prg4, Sox9, and Col7a1. Bmal1-overexpressed BMSCs presented improved migration capability ex vivo and attenuated age-related TMJ condylar degeneration in vivo. These data demonstrate the crucial role of circadian timing in the maintenance of osteochondral homeostasis, and indicate the potential clinical prospects of circadian-modified MSCs therapy in tissue regeneration.

Diagnostic and treatment protocol for a patient with temporomandibular disorder using a stabilization splint and temporary anchorage devices.

Treatment of orthodontic patients with temporomandibular disorder (TMD) is challenging for orthodontists because of the TMD signs and symptoms and unstable mandible position, which may lead to improper diagnosis and treatment design. This case report presents a 22-year-old woman with proclined maxillary incisors and TMD. First, stabilization splint therapy was implemented to eliminate temporomandibular joint pain and to obtain the stable adapted centric posture. Subsequently, orthodontic treatment was initiated on the basis of a definitive diagnosis made from the postsplint records. Temporary anchorage devices were used to intrude maxillary molars and distalize the maxillary dental arch. Favorable soft tissue, skeletal, and dental relationship were accomplished after 12 months of comprehensive orthodontic treatment. Functional occlusion was established with teeth as well as vacuum-formed retainers. Excellent posttreatment stability was maintained after a 20-month retention.

Transcriptome analysis of genes related to gonad differentiation and development in Muscovy ducks.

BACKGROUND: Sex-related genes play a crucial role in gonadal differentiation into testes or ovaries. However, the genetic control of gonadal differentiation in Muscovy ducks remains unknown. Therefore, the objective of our study was to screen new candidate genes associated with ovarian and testicular development. RESULTS: In this study, 24 males before gonadal differentiation (MB), 24 females before gonadal differentiation (FB), 24 males after gonadal differentiation (MA) and 24 females after gonadal differentiation (FA) were selected from Putian Muscovy ducks, forming 4 groups. RNA-Seq revealed 101.76 Gb of clean reads and 2800 differentially expressed genes (DEGs), including 46 in MB vs FB, 609 in MA vs FA, 1027 in FA vs FB, and 1118 in MA vs MB. A total of 146 signalling pathways were enriched by KEGG analysis, among which 20, 108, 108 and 116 signalling pathways were obtained in MB vs FB, MA vs MB, MA vs FA and FA vs FB, respectively. In further GO and KEGG analyses, a total of 21 candidate genes related to gonad differentiation and development in Muscovy ducks were screened. Among these, 9 genes were involved in the differentiation and development of the testes, and 12 genes were involved in the differentiation and development of the ovaries. In addition, RNA-Seq data revealed 2744 novel genes. CONCLUSIONS: RNA-Seq data revealed 21 genes related to gonadal differentiation and development in Muscovy ducks. We further identified 12 genes, namely, WNT5B, HTRA3, RSPO3, BMP3, HNRNPK, NIPBL, CREB3L4, DKK3, UBE2R2, UBPL3KCMF1, ANXA2, and OSR1, involved in the differentiation and development of ovaries. Moreover, 9 genes, namely, TTN, ATP5A1, DMRT1, DMRT3, AMH, MAP3K1, PIK3R1, AGT and ADAMTSL1, were related to the differentiation and development of testes. Moreover, after gonadal differentiation, DMRT3, AMH, PIK3R1, ADAMTSL1, AGT and TTN were specifically highly expressed in males. WNT5B, ANXA2 and OSR1 were specifically highly expressed in females. These results provide valuable information for studies on the sex control of Muscovy ducks and reveal novel candidate genes for the differentiation and development of testes and ovaries.