[Deep learning-assisted construction of three-dimensional face midsagittal plane based on point clouds].

Objective: To establish an intelligent registration algorithm under the framework of original-mirror alignment algorithm to construct three-dimensional(3D) facial midsagittal plane automatically. Dynamic Graph Registration Network (DGRNet) was established to realize the intelligent registration, in order to provide a reference for clinical digital design and analysis. Methods: Two hundred clinical patients without significant facial deformities were collected from October 2020 to October 2022 at Peking University School and Hospital of Stomatology. The DGRNet consists of constructing the feature vectors of key points in point original and mirror point clouds (X, Y), obtaining the correspondence of key points, and calculating the rotation and translation by singular value decomposition. Original and mirror point clouds were registrated and united. The principal component analysis (PCA) algorithm was used to obtain the DGRNet alignment midsagittal plane. The model was evaluated based on the coefficient of determination (R2) index for the translation and rotation matrix of test set. The angle error was evaluated on the 3D facial midsagittal plane constructed by the DGRNet alignment midsagittal plane and the iterative closet point(ICP) alignment midsagittal plane for 50 cases of clinical facial data. Results: The average angle error of the DGRNet alignment midsagittal plane and ICP alignment midsagittal plane was 1.05°±0.56°, and the minimum angle error was only 0.13°. The successful detection rate was 78%(39/50) within 1.50° and 90% (45/50)within 2.00°. Conclusions: This study proposes a new solution for the construction of 3D facial midsagittal plane based on the DGRNet alignment method with intelligent registration, which can improve the efficiency and effectiveness of treatment to some extent.

[Study on the method of automatically determining maxillary complex landmarks based on non-rigid registration algorithms].

Objective: To explore an automatic landmarking method for anatomical landmarks in the three-dimensional (3D) data of the maxillary complex and preliminarily evaluate its reproducibility and accuracy. Methods: From June 2021 to December 2022, spiral CT data of 31 patients with relatively normal craniofacial morphology were selected from those who visited the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The sample included 15 males and 16 females, with the age of (33.3±8.3) years. The maxillary complex was reconstructed in 3D using Mimics software, and the resulting 3D data of the maxillary complex was mesh-refined using Geomagic software. Two attending physicians and one associate chief physician manually landmarked the 31 maxillary complex datasets, determining 24 anatomical landmarks. The average values of the three expert landmarking results were used as the expert-defined landmarks. One case that conformed to the average 3D morphological characteristics of healthy individuals' craniofacial bones was selected as the template data, while the remaining 30 cases were used as target data. The open-source MeshMonk program (a non-rigid registration algorithm) was used to perform an initial alignment of the template and target data based on 4 landmarks (nasion, left and right zygomatic arch prominence, and anterior nasal spine). The template data was then deformed to the shape of the target data using a non-rigid registration algorithm, resulting in the deformed template data. Based on the unchanged index property of homonymous landmarks before and after deformation of the template data, the coordinates of each landmark in the deformed template data were automatically retrieved as the automatic landmarking coordinates of the homonymous landmarks in the target data, thus completing the automatic landmarking process. The automatic landmarking process for the 30 target data was repeated three times. The root-mean-square distance (RMSD) of the dense corresponding point pairs (approximately 25 000 pairs) between the deformed template data and the target data was calculated as the deformation error of the non-rigid registration algorithm, and the intra-class correlation coefficient (ICC) of the deformation error in the three repetitions was analyzed. The linear distances between the automatic landmarking results and the expert-defined landmarks for the 24 anatomical landmarks were calculated as the automatic landmarking errors, and the ICC values of the 3D coordinates in the three automatic landmarking repetitions were analyzed. Results: The average three-dimensional deviation (RMSD) between the deformed template data and the corresponding target data for the 30 cases was (0.70±0.09) mm, with an ICC value of 1.00 for the deformation error in the three repetitions of the non-rigid registration algorithm. The average automatic landmarking error for the 24 anatomical landmarks was (1.86±0.30) mm, with the smallest error at the anterior nasal spine (0.65±0.24) mm and the largest error at the left oribital (3.27±2.28) mm. The ICC values for the 3D coordinates in the three automatic landmarking repetitions were all 1.00. Conclusions: This study established an automatic landmarking method for three-dimensional data of the maxillary complex based on a non-rigid registration algorithm. The accuracy and repeatability of this method for landmarking normal maxillary complex 3D data were relatively good.

COVID struggles: undergraduate teaching assistants balance teaching and learning during a pandemic.

Undergraduate teaching assistants (UTAs) have become valuable collaborators with faculty in large undergraduate first-year classes. Their participation requires them to manage their teaching duties and their own learning. The pandemic posed unusual problems for them. Here, two students, along with their instructor, provide an inside look. Throughout the pandemic, UTAs were found to increase their efforts during tutorials in attempts to help ensure that students were more prepared and engaged through the online learning formats. New strategies were implemented to maintain student attendance and participation in class, which greatly increased the workload for UTAs. Students not turning on their cameras and speaking up in online classes made teaching more tiring and stressful, which was compounded by the already present "Zoom fatigue" during online education. UTAs found real challenges in balancing senior year classes and extracurriculars with preparation for tutorials, especially closer to assignment or exam deadlines when the engagement and questions from students would sharply increase. Despite numerous efforts and adaptations made by UTAs to adjust to the impacts of the pandemic, online learning was an immense challenge to both students and teachers in comparison to the in-person formats.NEW & NOTEWORTHY Undergraduate teaching assistants balance teaching others with their own learning during the recent pandemic. Their struggles provide an inside look into a student's plight.

HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.

Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated serine proteases, matriptase and prostasin. Previously, HAI-1 loss in HaCaT human keratinocytes resulted in an expected increase in prostasin proteolysis but a paradoxical decrease in matriptase proteolysis. The paradoxical decrease in shed active matriptase is further investigated in this study with an unexpected discovery of novel functions of fibroblast growth factor-binding protein 1 (FGFBP1), which acts as an extracellular ligand that can rapidly elicit F-actin rearrangement and subsequently affect the morphology of human keratinocytes. This novel growth factor-like function is in stark contrast to the canonical activity of this protein through interactions with FGFs for its pathophysiological functions. This discovery began with the observation that HAI-1 KO HaCaT cells lose the characteristic cobblestone morphology of the parental cells and exhibit aberrant F-actin formation along with altered subcellular targeting of matriptase and HAI-2. The alterations in cell morphology and F-actin status caused by targeted HAI-1 deletion can be restored by treatment with conditioned medium from parental HaCaT cells, in which FGFBP1 was identified by tandem mass spectrometry. Recombinant FGFBP1 down to 1 ng/ml was able to revert the changes caused by HAI-1 loss. Our study reveals a novel function of FGFBP1 in the maintenance of keratinocyte morphology, which depends on HAI-1.

[Preliminary study on three-dimensional morphological reconstruction method for external nose defect based on three-dimensional face template].

Objective: To provide a new solution for the digital design of nasal prostheses, this study explores the three-dimensional (3D) facial morphology completion method for external nasal defects based on the non-rigid registration process of 3D face template. Methods: A total of 20 male patients with tooth defect and dentition defect who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to December 2022 were selected, age 18-45 years old. The original 3D facial data of patients were collected, and the 3D facial data of the external nose defect was constructed in Geomagic Wrap 2021 software. Using the structured 3D face template data constructed in the previous research of the research group, the 3D face template was deformed and registered to the 3D facial data of external nose defect (based on the morphology of non-defective area) by non-rigid registration algorithm (MeshMonk program), and the personalized deformed data of the 3D face template was obtained, as the complemented facial 3D data. Based on the defect boundary of the 3D facial data of the external nose defect, the complemented external nose 3D data can be cut out from the complemented facial 3D data. Then the nasofacial angle and nasolabial angle of the complemented facial 3D data and the original 3D facial data was compared and analyzed, the ratio between the nose length and mid-face height, nose width and medial canthal distance of the complemented facial 3D data was measured, the edge fit between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was evaluated, and the morphological difference of the nose between the complemented external nose 3D data and the original 3D facial data was analyzed. Results: There was no significant statistically difference (t=-0.23, P=0.823; Z=-1.72, P=0.086) in the nasofacial angle (28.2°±2.9°, 28.4°±3.5° respectively) and nasolabial angle [95.4°(19.2°), 99.9°(9.5°) respectively] between the 20 original 3D facial data and the complemented facial 3D data. The value of the ratio of nose length to mid-face height in the complemented facial 3D data was 0.63±0.03, and the value of the ratio of nose width to medial canthal distance was 1.07±0.08. The curve deviation (root mean square value) between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was (0.37±0.09) mm, the maximum deviation was (1.14±0.32) mm, and the proportion of the curve deviation value within±1 mm was (97±3)%. The distance of corresponding nose landmarks between the complemented facial 3D data and the original 3D facial data were respectively, Nasion: [1.52(1.92)] mm; Pronasale: (3.27±1.21) mm; Subnasale: (1.99±1.09) mm; Right Alare: (2.64±1.34) mm; Left Alare: (2.42± 1.38) mm. Conclusions: The method of 3D facial morphology completion of external nose defect proposed in this study has good feasibility. The constructed complemented external nose 3D data has good facial coordination and edge fit, and the morphology is close to the nose morphology of the original 3D facial data.

[The design method of the digital sequential tooth-sectioning guide for the extraction of mandibular impacted third molars].

Objective: To explore a method for digitally designing and fabricating a sequential tooth-sectioning guide that can assist in the extraction of mandibular horizontal impacted third molars, preliminarily evaluate its feasibility and provide a reference for clinical application. Methods: Twenty patients with mandibular low level impacted third molars who visited the Department of General Dentistry, Peking University School and Hospital of Stomatology from March 2021 to January 2022 were selected. Cone-beam CT showed direct contact between the roots and mandibular canal, and full range impressions of the patients' intraoral teeth were taken and optical scans of the dental model were performed. The patients' cone-beam CT data and optical scan data were reconstructed in three dimensions, anatomical structure extraction, registration fusion, and the design of the structure of the guide (including crown-sectioning guide and root-sectioning guide) by Mimics 24.0, Geomagic Wrap 2021, and Magics 21.0 software, and then the titanium guide was three dimension printed, and the guide was tried on the dental model. After confirmation, the guide was used to assist the dentist in the operation. We observed whether the guide was in place, the number of tooth splitting, the matching of tooth splitting with the preoperative design, the operation time, and whether there were any complications. Results: In this study, 20 sectioning guides were successfully printed, all of them were well fitted in the patients' mouth, the average number of section was 3.4 times, the tooth parts was better matched with the preoperative design, and the average operative time of the guides was (29.2±9.8) minutes without complications such as perforation of the bone cortex. Conclusions: The use of sequential sectioning guides to assist in the extraction of mandibular impacted third molars was initially validated to accurately replicate the preoperative sectioning design, and is expected to provide a digital solution to improve surgical precision and ensure safety. Further studies with larger sample sizes are needed to evaluate its accuracy and safety.

[Preliminary evaluation of the trueness of 5 chairside 3D facial scanning techniques].

OBJECTIVE: To quantitatively evaluate the trueness of five chairside three-dimensional facial scanning techniques, and to provide reference for the application of oral clinical diagnosis and treatment. METHODS: The three-dimensional facial data of the subjects were collected by the traditional professional three-dimensional facial scanner Face Scan, which was used as the reference data of this study. Four kinds of portable three-dimensional facial scanners (including Space Spider, LEO, EVA and DS-FScan) and iPhone Ⅹ mobile phone (Bellus3D facial scanning APP) were used to collect three-dimensional facial data from the subjects. In Geomagic Studio 2013 software, through data registration, deviation analysis and other functions, the overall three-dimensional deviation and facial partition three-dimensional deviation of the above five chairside three-dimensional facial scanning technologies were calculated, and their trueness performance evaluated. Scanning time was recorded during the scanning process, and the subject's comfort was scored by visual analogue scale(VAS). The scanning efficiency and patient acceptance of the five three-dimensional facial scanning techniques were evaluated. RESULTS: DS-FScan had the smallest mean overall and mean partition three-dimensional deviation between the test data and the reference data, which were 0.334 mm and 0.329 mm, respectively. The iPhone Ⅹ mobile phone had the largest mean overall and mean partition three-dimensional deviation between the test data and the reference data, which were 0.483 mm and 0.497 mm, respectively. The detailed features of the three-dimensional facial data obtained by Space Spider were the best. The iPhone Ⅹ mobile phone had the highest scanning efficiency and the highest acceptance by the subject. The average scanning time of the iPhone Ⅹ mobile phone was 14 s, and the VAS score of the subjects' scanning comfort was 9 points. CONCLUSION: Among the five chairside three-dimensional face scanning technologies, the trueness of the scan data of the four portable devices had no significant difference, and they were all better than the iPhone Ⅹ mobile phone scan. The subject with the iPhone Ⅹ scanning technology had the best expe-rience.

[Automatic determination of mandibular landmarks based on three-dimensional mandibular average model].

OBJECTIVE: To explore an efficient and automatic method for determining the anatomical landmarks of three-dimensional(3D) mandibular data, and to preliminarily evaluate the performance of the method. METHODS: The CT data of 40 patients with normal craniofacial morphology were collected (among them, 30 cases were used to establish the 3D mandibular average model, and 10 cases were used as test datasets to validate the performance of this method in determining the mandibular landmarks), and the 3D mandibular data were reconstructed in Mimics software. Among the 40 cases of mandibular data after the 3D reconstruction, 30 cases that were more similar to the mean value of Chinese mandibular features were selected, and the size of the mandibular data of 30 cases was normalized based on the Procrustes analysis algorithm in MATLAB software. Then, in the Geomagic Wrap software, the 3D mandibular average shape model of the above 30 mandibular data was constructed. Through symmetry processing, curvature sampling, index marking and other processing procedures, a 3D mandible structured template with 18 996 semi-landmarks and 19 indexed mandibular anatomical landmarks were constructed. The open source non-rigid registration algorithm program Meshmonk was used to match the 3D mandible template constructed above with the tested patient's 3D mandible data through non-rigid deformation, and 19 anatomical landmark positions of the patient's 3D mandible data were obtained. The accuracy of the research method was evaluated by comparing the distance error of the landmarks manually marked by stomatological experts with the landmarks marked by the method of this research. RESULTS: The method of this study was applied to the data of 10 patients with normal mandibular morphology. The average distance error of 19 landmarks was 1.42 mm, of which the minimum errors were the apex of the coracoid process [right: (1.01±0.44) mm; left: (0.56±0.14) mm] and maximum errors were the anterior edge of the lowest point of anterior ramus [right: (2.52±0.95) mm; left: (2.57±1.10) mm], the average distance error of the midline landmarks was (1.15±0.60) mm, and the average distance error of the bilateral landmarks was (1.51±0.67) mm. CONCLUSION: The automatic determination method of 3D mandibular anatomical landmarks based on 3D mandibular average shape model and non-rigid registration algorithm established in this study can effectively improve the efficiency of automatic labeling of 3D mandibular data features. The automatic determination of anatomical landmarks can basically meet the needs of oral clinical applications, and the labeling effect of deformed mandible data needs to be further tested.

Binary effects of intravascular laser irradiation of blood on motor recovery and homocysteine reduction in a case with ischemic hemiparesis: portrayed with brain perfusion images.

BACKGROUND: Stroke is a burdensome cerebral eventthat affects many aspects of daily activities such as motion, speech, memory, vision, and cognition. Intravascular laser irradiation of blood (ILIB) is a novel therapy, going beyond conventional rehabilitation modalities, that is effective in stroke recovery. Homocysteine ​​is an important risk factor associated with stroke. However, there are few studies that examine the relationship between ILIB treatment and the level of homocysteine. In recent years, researchers use the single-photon emission computed tomography (SPECT) scan of the brain to evaluate stroke patients and patients with a neurologicdeficit. The present report investigates the clinical effect of ILIB treatment on the level of serum homocysteine, the perfusion change of impaired brain region via SPECT, and the patient's neurologic appearance. CASEPRESENTATION: We focus on a case of a 62-year-old man with subacute stroke accompanied with left hemiparesis and hyperhomocysteinemia, who showed dramatic improvement in muscle power, a decreasing level of homocysteine, and increased blood flow of the right cerebral after three-courseILIB treatment. CONCLUSION: We found that ILIB is effective in lowering serum levels of homocysteine and facilitating cerebral circulation for the patient with subacute stroke.

Network Pharmacology-Based Strategy for Exploring the Pharmacological Mechanism of Honeysuckle (Lonicer japonica Thunb.) against Newcastle Disease.

Objective: Newcastle disease causes huge economic losses in the global poultry industry. An efficient treatment is needed to deal with the variable immunogenicity of the Newcastle disease virus (NDV). This study utilized network pharmacology to study the potential therapeutic targets of Honeysuckle (Lonicer japonica Thunb.) against Newcastle disease. Methods: Venny online analysis was used to analyze the potential overlapping targets of Honeysuckle and Newcastle disease. Hub genes were obtained using the STRING database and Cytoscape 3.8.2 software. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis using the DAVID online tool were performed on these targets. Results: Twenty-five overlapping targets were identified. The PPI network construction results included 23 nodes of 25 genes and 95 edges. It was found that the IL-6 node had the largest degree. STAT1 and IRF1, CASP9, and CASP3 had the same as well as strongest interaction strengths. GO functions, such as "cytokine activity," had a regulatory effect on NDV. The "Toll-like receptor signaling Pathway" "Nod-like receptor signaling pathway," "RIG-I-like receptor signaling pathway," and "Apoptosis," which were obtained using KEGG analysis, also indicated that these pathways can act on NDV to enhance immune function. Conclusions: In this study, the potential targets and mechanisms of action of Honeysuckle against Newcastle disease were explored through network pharmacology, which provided a theoretical basis for the treatment of Newcastle disease and provided new ideas for the development of traditional Chinese medicine for the poultry industry.

[Preliminary study on the method of automatically determining facial landmarks based on three-dimensional face template].

Objective: To explore the establishment of an efficient and automatic method to determine anatomical landmarks in three-dimensional (3D) facial data, and to evaluate the effectiveness of this method in determining landmarks. Methods: A total of 30 male patients with tooth defect or dentition defect (with good facial symmetry) who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to August 2021 were selected, and these participants' age was between 18-45 years. 3D facial data of patients was collected and the size normalization and overlap alignment were performed based on the Procrustes analysis algorithm. A 3D face average model was built in Geomagic Studio 2013 software, and a 3D face template was built through parametric processing. MeshLab 2020 software was used to determine the serial number information of 32 facial anatomical landmarks (10 midline landmarks and 22 bilateral landmarks). Five male patients with no mandibular deviation and 5 with mild mandibular deviation were selected from the Department of Orthodontics or Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June to August 2021. 3D facial data of patients was collected as test data. Based on the 3D face template and the serial number information of the facial anatomical landmarks, the coordinates of 32 facial anatomical landmarks on the test data were automatically determined with the help of the MeshMonk non-rigid registration algorithm program, as the data for the template method to determine the landmarks. The positions of 32 facial anatomical landmarks on the test data were manually determined by the same attending physician, and the coordinates of the landmarks were recorded as the data for determining landmarks by the expert method. Calculated the distance value of the coordinates of facial anatomical landmarks between the template method and the expert method, as the landmark localization error, and evaluated the effect of the template method in determining the landmarks. Results: For 5 patients with no mandibular deviation, the landmark localization error of all facial anatomical landmarks by template method was (1.65±1.19) mm, the landmark localization error of the midline facial anatomical landmarks was (1.19±0.45) mm, the landmark localization error of bilateral facial anatomical landmarks was (1.85±1.33) mm. For 5 patients with mild mandibular deviation, the landmark localization error of all facial anatomical landmarks by template method was (2.55±2.22) mm, the landmark localization error of the midline facial anatomical landmarks was (1.85±1.13) mm, the landmark localization error of bilateral facial anatomical landmarks was (2.87±2.45) mm. Conclusions: The automatic determination method of facial anatomical landmarks proposed in this study has certain feasibility, and the determination effect of midline facial anatomical landmarks is better than that of bilateral facial anatomical landmarks. The effect of determining facial anatomical landmarks in patients without mandibular deviation is better than that in patients with mild mandibular deviation.

[Deep learning-assisted construction of three-demensional facial midsagittal plane].

OBJECTIVE: To establish a deep learning algorithm that can accurately determine three-dimensional facial anatomical landmarks, multi-view stacked hourglass convolutional neural networks (MSH-CNN) and to construct three-dimensional facial midsagittal plane automatically based on MSH-CNN and weighted Procrustes analysis algorithm. METHODS: One hundred subjects with no obvious facial deformity were collected in our oral clinic. Three-dimensional facial data were scanned by three-dimensional facial scanner. Experts annotated twenty-one facial landmarks and midsagittal plane of each data. Eighty three-dimensional facial data were used as training set, to train the MSH-CNN in this study. The overview of MSH-CNN network architecture contained multi-view rendering and training the MSH-CNN network. The three-dimensional facial data were rendered from ninety-six views that were fed to MSH-CNN and the output was one heatmap per landmark. The result of the twenty-one landmarks was accurately placed on the three-dimensional facial data after a three-dimensional view ray voting process. The remaining twenty three-dimensional facial data were used as test set. The trained MSH-CNN automatically determined twenty-one three-dimensional facial anatomical landmarks of each case of data, and calculated the distance between each MSH-CNN landmark and the expert landmark, which was defined as position error. The midsagittal plane of the twenty subjects' could be automatically constructed, using the MSH-CNN and Procrustes analysis algorithm. To evaluate the effect of midsagittal plane by automatic method, the angle between the midsagittal plane constructed by the automatic method and the expert annotated plane was calculated, which was defined as angle error. RESULTS: For twenty subjects with no obvious facial deformity, the average angle error of the midsagittal plane constructed by MSH-CNN and weighted Procrustes analysis algorithm was 0.73°±0.50°, in which the average position error of the twenty-one facial landmarks automatically determined by MSH-CNN was (1.13±0.24) mm, the maximum position error of the orbital area was (1.31±0.54) mm, and the minimum position error of the nasal area was (0.79±0.36) mm. CONCLUSION: This research combines deep learning algorithms and Procrustes analysis algorithms to realize the fully automated construction of the three-dimensional midsagittal plane, which initially achieves the construction effect of clinical experts. The obtained results constituted the basis for the independent intellectual property software development.

Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.

Epidermal differentiation and barrier function require well-controlled matriptase and prostasin proteolysis, in which the Kunitz-type serine protease inhibitor HAI-1 represents the primary enzymatic inhibitor for both proteases. HAI-1, however, also functions as a chaperone-like protein necessary for normal matriptase synthesis and intracellular trafficking. Furthermore, other protease inhibitors, such as antithrombin and HAI-2, can also inhibit matriptase and prostasin in solution or in keratinocytes. It remains unclear, therefore, whether aberrant increases in matriptase and prostasin enzymatic activity would be the consequence of targeted deletion of HAI-1 and so subsequently contribute to the epidermal defects observed in HAI-1 knockout mice. The impact of HAI-1 deficiency on matriptase and prostasin proteolysis was, here, investigated in HaCaT human keratinocytes. Our results show that HAI-1 deficiency causes an increase in prostasin proteolysis via increased protein expression and zymogen activation. It remains unclear, however, whether HAI-1 deficiency increases "net" prostasin enzymatic activity because all of the activated prostasin was detected in complexes with HAI-2, suggesting that prostasin enzymatic activity is still under tight control in HAI-1-deficient keratinocytes. Matriptase proteolysis is, however, unexpectedly suppressed by HAI-1 deficiency, as manifested by decreases in zymogen activation, shedding of active matriptase, and matriptase-dependent prostasin zymogen activation. This suppressed proteolysis results mainly from the reduced ability of HAI-1-deficient HaCaT cells to activate matriptase and the rapid inhibition of nascent active matriptase by HAI-2 and other yet-to-be-identified protease inhibitors. Our study provides novel insights with opposite impacts by HAI-1 deficiency on matriptase versus prostasin proteolysis in keratinocytes.

Matriptase and prostasin proteolytic activities are differentially regulated in normal and wounded skin.

Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin.

The intracellular seven amino acid motif EEGEVFL is required for matriptase vesicle sorting and translocation to the basolateral plasma membrane.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

[A method for constructing three-dimensional face symmetry reference plane based on weighted shape analysis algorithm].

OBJECTIVE: To establish a novel method based on three-dimensional (3D) shape analysis and weighted Procrustes analysis (WPA) algorithm to construct a 3D facial symmetry reference plane (SRP), automatically assigning weight to facial anatomical landmarks. The WPA algorithm suitability for commonly observed clinical cases of mandibular deviation were analysed and evaluated. METHODS: Thirty patients with mandibular deviation were recruited for this study. The 3D facial SRPs were extracted independently based on original-mirror alignment method. Thirty-two anatomical landmarks were selected from the overall region by three times to obtain the mean coordinate. The SRP of experimental groups 1 and 2 were using the standard Procrustes analysis (PA) algorithm and WPA algorithm, respectively. A reference plane defined by experts based on regional iterative closest point (ICP) algorithm, served as the ground truth. Three experts manually selecting facial regions with good symmetry for original model, and common region was included in the study. The angle error values between the SRP of WPA algorithm in the experimental group 1 and the truth plane were evaluated in this study, and the SRP of PA algorithm of experimental group 2 was calculated in the same way. Statistics and measurement analysis were used to comprehensively evaluate the clinical suitability of the WPA algorithm to calculate the SRP. A paired t-test analysis (two-tailed) was conducted to compare the angles. RESULTS: The average angle error between the SRP of WPA algorithm and the ground truth was 1.53°±0.84°, which was smaller than that between the SRP of PA and the ground truth (2.06°±0.86°). There were significant differences in the angle errors among the groups (P < 0.05). For the patients with severe mandibular deviation that the distance between pogonion and facial midline greater than 12 mm, the average angle error of the WPA algorithm was 0.86° smaller than that of the PA algorithm. CONCLUSION: The WPA algorithm, based on weighted shape analysis, can provide a more adaptable SRP than the standard PA algorithm when applied to mandibular deviation patients and preliminarily simulate the diagnosis strategies of clinical experts.

Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.

We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation. Endogenous ATF1 was spontaneously down-regulated after d 1-3 of neural induction. By double-knockdown experiments, up-regulation of SOX2 was critical for the increase of PAX6 and SOX1 expression in shRNA targeting Atf1 hESCs. Using the luciferase reporter assay, we identified ATF1 as a negative transcriptional regulator of Sox2 gene expression. A novel function of ATF1 was discovered, and these findings contribute to a broader understanding of the very first steps in regulating NE differentiation in hESCs.-Yang, S.-C., Liu, J.-J., Wang, C.-K., Lin, Y.-T., Tsai, S.-Y., Chen, W.-J., Huang, W.-K., Tu, P.-W. A., Lin, Y.-C., Chang, C.-F., Cheng, C.-L., Lin, H., Lai, C.-Y., Lin, C.-Y., Lee, Y.-H., Chiu, Y.-C., Hsu, C.-C., Hsu, S.-C., Hsiao, M., Schuyler, S. C., Lu, F. L., Lu, J. Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.

All-optical inhibitory dynamics in photonic neuron based on polarization mode competition in a VCSEL with an embedded saturable absorber.

An all-optical spike inhibition scheme based on polarization-mode competition (PMC) in a vertical-cavity surface-emitting laser (VCSEL) with an embedded saturable absorber is proposed and investigated numerically. The inhibitory dynamics is characterized by spike amplitude and first-spike latency (FSL) for the first time, to the best of our knowledge. The effects of time differences between inhibitory and excitatory inputs, inputs strengths, bias current, as well as noise on the spike amplitude and FSL are examined. The results show that a spike can be triggered in the y-polarization mode by excitatory input and can be inhibited in the presence of inhibitory input due to PMC.

Clinical study on the early application and ideal dosage of urokinase after surgery for hypertensive intracerebral hemorrhage.

OBJECTIVE: The objective of the present study was to investigate the clinical efficacy of early application and ideal dosage of urokinase after minimally invasive surgery for hypertensive intracerebral hemorrhage (HICH). PATIENTS AND METHODS: We consecutively enrolled 132 patients with HICH who underwent CT-guided stereotactic intubation of the hematoma combined with dissolution using urokinase, where the urokinase was injected at 24 h after intubation. The 40 patients in the low-dosage group received 10-30 thousand units of urokinase; the 46 patients in the moderate-dosage group received 40-60 thousand units of urokinase; and the 46 patients in the high-dosage group received 70-100 thousand units of urokinase. After the drainage tubes were clamped for 4-6 h, clamps were removed for drainage for 24 h, and the intubated tubes were maintained for 3-5 d. Patients in all groups were followed up for 6 months, and the clinical outcomes were compared. RESULTS: The clearance of hematomas in the high-dosage group was significantly improved compared with the other two groups (p<0.05), and the occurrence rates of complications in the moderate- and high-dosage groups were significantly higher than in the low-dosage group (p<0.05). During follow-up, the Chinese stroke scale and Barthel index scores in the high-dosage group were higher than those in the other two groups (p<0.05). The serum levels of matrix metalloproteinase-9 (MMP-9) and neuron-specific enolase (NSE) in the high-dosage group were lower than those in the other two groups (p<0.05). CONCLUSIONS: CT-guided stereotactic intubation of the hematoma combined with dissolution using urokinase is effective for eliminating the hematoma for treatment of HICH with few complications. For recovery of neurological functions and improvement of regular life skills, it is considered to be associated with decreases in the serum levels of MMP-9 and NSE.

Bayesian Analysis of the Association between Family-Level Factors and Siblings' Dental Caries.

We conducted a Bayesian analysis of the association between family-level socioeconomic status and smoking and the prevalence of dental caries among siblings (children from infant to 14 y) among children living in rural and urban Northern Appalachia using data from the Center for Oral Health Research in Appalachia (COHRA). The observed proportion of siblings sharing caries was significantly different from predicted assuming siblings' caries status was independent. Using a Bayesian hierarchical model, we found the inclusion of a household factor significantly improved the goodness of fit. Other findings showed an inverse association between parental education and siblings' caries and a positive association between households with smokers and siblings' caries. Our study strengthens existing evidence suggesting that increased parental education and decreased parental cigarette smoking are associated with reduced childhood caries in the household. Our results also demonstrate the value of a Bayesian approach, which allows us to include household as a random effect, thereby providing more accurate estimates than obtained using generalized linear mixed models.