Identification and functional study of a novel variant of PAX9 causing tooth agenesis.

OBJECTIVES: To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis. MATERIALS AND METHODS: A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes. RESULTS: A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed ß-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05). CONCLUSIONS: This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-ß/BMP pathway, which may contribute to tooth agenesis in this family.

Interleukin-13 contributes to the occurrence of oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is a chronic progressive fibrosis disease that affects in oral mucosal tissues. Interleukin (IL)-13 has been implicated in the development of fibrosis in multiple organs. Indeed, it contributes to diseases such as pulmonary fibrosis, liver cirrhosis among others. Currently, its expression in OSF and the specific mechanisms are not well understood. The aim of this study was to investigate the role of IL-13 in OSF and further explore whether IL-13 regulates-polarization of M2-macrophages in OSF. Initially, in the tissues of patients with OSF, we observed a high expression of M2-macrophages and IL-13 protein. Additionally, we found a correlation between the expression of IL-13 and the stage of OSF. Arecoline inhibited the proliferation of fibroblasts (FBs) and promoted IL-13 production in vitro. Furthermore, our observations revealed that M2-macrophages increased upon co-culturing M0-macrophages with supernatants containing the IL-13 cytokine. In conclusion, our study demonstrated that arecoline stimulates FBs leading to increased secretion of IL-13, which in turn IL-13 leads to polarization of M2-macrophages and promotes the occurrence of OSF. This suggests that IL-13 may be a potential therapeutic target of OSF.

Evaluation of phase-adjusted interventions for COVID-19 using an improved SEIR model.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2-5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

The preliminary exploration of immune microenvironment in oral leukoplakia concomitant with oral submucosal fibrosis: A comparative immunohistochemical study.

BACKGROUND: Oral leukoplakia concomitant with oral submucous fibrosis is a high-risk oral potentially malignant disorder, but little is known about its immune microenvironment. METHODS: Thirty samples of oral leukoplakia concomitant with oral submucous fibrosis, 30 oral leukoplakia samples, and 30 oral submucous fibrosis samples were collected from two hospitals. Immunohistochemistry was performed to analyze expression of T cell biomarkers [CD3, CD4, CD8, and Forkhead box P3 (Foxp3)], a B cell biomarker (CD20), macrophage biomarkers (CD68 and CD163), an immune inhibitory receptor ligand (PD-L1), and Ki-67. RESULTS: The numbers of CD3+ (p < 0.001), CD4+ (p = 0.018), and CD8+ (p = 0.031) cells in oral leukoplakia concomitant with oral submucous fibrosis were less than those in oral leukoplakia. The number of CD4+ cells (p = 0.035) in oral leukoplakia concomitant with oral leukoplakia was higher than that in oral submucous fibrosis. More CD3+ (p < 0.001), CD4+ (p < 0.001), Foxp3+ (p = 0.019), and CD163+ (p = 0.029) cells were found in oral leukoplakia than in oral submucous fibrosis. CONCLUSION: Various levels of immune infiltration were observed among oral leukoplakia concomitant with oral submucous fibrosis, oral leukoplakia, and oral submucous fibrosis. Characterization of the immune microenvironment may contribute to personalized immunotherapy.

The mechanism of IL-13 targeting IL-13Rα2 in regulating oral mucosal FBs through PI3K/AKT/mTOR.

OBJECTIVE: The objective of this investigation was to examine the presence of interleukin (IL)-13 and its receptor IL-13Rα2 in the tissues of oral submucous fibrosis (OSF), investigate their biological functions, and explore the underlying mechanisms involved in the development of OSF. MATERIALS AND METHODS: The expression of IL-13 and IL-13Rα2 in the oral mucosa of patients with OSF and normal individuals was determined through immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary fibroblasts (FBs) were extracted through enzymatic digestion and then cultured. Immunofluorescence was employed to identify the FB cultures and the location of IL-13Rα2. The effects of IL-13/IL-13Rα2/PI3K/AKT/mTOR on the migration, proliferation, and secretion of fiber-related proteins of FBs were explored via the wound healing assay, CCK-8 assay, EDU assay, and RT-qPCR. The impact of IL-13Rα2 silencing and PI3K/AKT inhibition on the effect of IL-13 on FBs was analyzed by RT-qPCR and Western blotting. RESULTS: IL-13 and IL-13Rα2 were highly expressed in OSF. Primary FBs were successfully extracted and cultured. IL-13Rα2 was found to be localized in myofibroblasts. IL-13 promoted the proliferation, migration, and secretion of fibril-associated proteins in FBs. The proliferation, migration, and secretion of fibril-associated proteins of FBs were decreased following IL-13Rα2 silencing and inhibition of the PI3K/AKT/mTOR pathway. CONCLUSION: IL-13 may promote the proliferation, migration, and secretion of fiber-related proteins of FBs through the PI3K/AKT/mTOR pathway by targeting IL-13Rα2.

A Significant Fluorescence Turn-On Probe for the Recognition of Al3+ and Its Application.

An easy prepared probe, BHMMP, was designed and synthesized, which displayed a significant fluorescence enhancement (over 38-fold) and obvious color change in the recognition of Al3+. The binding ratio of probe BHMMP to Al3+ was determined as 1:1, according to Job plot. The binding mechanism was fully clarified by the experiments, such as FT-IR spectrum, ESI-MS analysis, and 1H NMR titration. A DFT study further confirmed the binding mode of BHMMP to Al3+. The limit of detection (LOD) for Al3+ was determined as low as 0.70 µM, based on the fluorescence titration of BHMMP. Moreover, the results from real sample experiments, including real water samples, test papers, and cell images, well-demonstrated that BHMMP was capable of sensing Al3+ in environmental and biological systems.

Research progress on the effect of autophagy-lysosomal pathway on tumor drug resistance.

Autophagy is an intracellular degradation pathway that is highly conserved during the evolution of eukaryotes and is based on lysosome. Under nutritional deficiencies or stress, cells can clear damaged and necrotic organelles and proteins through autophagy to maintain the homeostasis of cells and organisms. Studies have found that abnormal autophagy is closely related to the occurrence and development of neurodegenerative diseases and tumors. In order to further understand the relationship between lysosomes and autophagy, tumorigenesis and drug resistance, the role of autophagy-lysosomal pathway in tumor resistance and related mechanisms and the relationship between drug resistance and hypoxia-induced autophagy are discussed in this paper.

High precision measurement for the chamfered hole radius and spacing of a large-size workpiece based on binocular vision combined with plane dynamic adjustment.

A novel, to the best of our knowledge, hole radius and spacing measurement method is presented based on binocular vision combined with dynamic local plane for the large-size workpiece with plane feature. The novel method overcomes the problem of the ariable working distance and large location error of an abrupt edge for conventional methods. Its measurement principle and model are introduced. Then, a chamfered inner edge extraction method based on the shrinkage of an elliptical band and an adaptive weight optimal calculation based on redundant measurement data are presented to improve the measurement accuracy. Experiments are carried out to validate the presented method, and a high measurement accuracy with a standard deviation of 0.017 mm in the hole radius and 0.021 mm in hole spacing have eventually been achieved for the actual measurement workpieces, respectively. Compared with the common method, the measurement accuracy is improved by at least 77% and 53% in radius and spacing, respectively.

The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction.

BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in the immune remodeling of tumor microenvironments (TME) in oral squamous cell carcinoma (OSCC) remains controversial. In this study, we pursued a comprehensive characterization of the repertoire of TILs and then analyzed its clinical significance and potential prognostic value. METHODS: Fresh tumor tissue samples and peripheral blood from 83 OSCC patients were collected to comprehensively characterize the phenotypes and frequencies of TILs by flow cytometry. Archived paraffin-embedded tissues derived from 159 OSCC patients were analyzed by immunohistochemistry to further assess the TIL repertoire. The clinical significance of TILs and their potential prognostic value were further analyzed. RESULTS: A series of unique features of TILs were observed. IL-17 was highly expressed in betel nut chewers, and CD20 was abundantly expressed in patients who did not drink alcohol; high expression of CD138, PD-L1, and Foxp3 was associated with poor prognosis. The Th17/Treg ratio was an independent prognostic factor for patient survival with greater predictive accuracy for overall survival. CONCLUSIONS: Our results suggest an antigen-driven immune response; however, the immune dysfunction within the microenvironment in OSCC and the Th17/Treg balance may play important roles in the modulation of antitumor immunity.

Phase-modulation combined deflectometry for small defect detection.

Deflectometry has been widely used to detect defects on specular surfaces. However, it is still very challenging to detect defects on semispecular or diffuse surfaces because of the low contrast and low signal-to-noise ratio. To address this challenge, we proposed a phase-modulation combined method for accurate defect detection. Based on the phase and modulation of captured fringes, a dual-branch convolutional neural network is employed to simultaneously extract geometric and photometric features from the phase-shifting pattern sequence and modulation, which improves the defect detection performance significantly. Compared to state-of-the-art methods, we believe the results demonstrated the proposed method's effectiveness and capability to reduce false positives.

Micro-Frequency Shifting Projection Technique for Inter-Reflection Removal.

Inter-reflection removal is vital for complex-scene reconstruction. However, most methods assume that the tested surface is a diffuse, and are limited to removal of inter-reflection caused only by diffuse reflections. For all kinds of inter-reflections caused by diffuse and specular reflections, a micro-frequency shifting (MFS) projection technique is presented. Because the modulation variation with frequency in inter-reflection regions is larger than that of other regions, we use the MFS technique to detect inter-reflections, where patterns with specifically designed frequency-shifts and base frequencies are projected. Inter-reflections are detected through large variations in modulation, and removed using a regional-projection technique. Experimental results validate the effectiveness for diffuse and specular inter-reflection removal.

Heterodyne interferometer with two parallel-polarized input beams for high-resolution roll angle measurement.

We have proposed an improved heterodyne interferometric roll measurement system with enhanced resolution in this paper. Two beams with different frequencies but with the same polarization state input to the interferometer are provided by two acousto-optic modulators. A quarter-wave plate is employed in each path before the two beams are combined to generate a beat frequency. A mathematical model for the measurement system is established based on Jones' calculus. The measurement resolution is doubled because the sensitive areas of the two beams appear simultaneously. Experimental results show that in the range of 0.1° the gain coefficient reaches 229 which is twice that of the traditional method.

Oral submucous fibrosis: A clinicopathological study of 674 cases in China.

BACKGROUND: Oral submucous fibrosis (OSF) has been reported frequently in India and other countries in South Asia. There are few reports on the clinicopathological features of OSF in China, where OSF is an epidemic. This study analyses the clinicopathological features of OSF in Hunan Province, China. METHODS: A total of 674 cases of OSF were collected from July 2013 to August 2018 in Xiangya Stomatological Hospital, Central South University, and gender, age, site, pathological stage, habits, symptoms and associated lesions were recorded. RESULTS: The male to female ratio was 32.7:1. The average age was 35.23 ± 10.08. The buccal mucosa was the most common site. A total of 99.85% of OSF cases chewed areca nut. Pale mucosa, restricted mouth opening, burning and fibrous bands were common clinical manifestations. Oral leukoplakia (OLK) was the most common associated lesion. The extended duration of chewing areca nut increased the risk of associated lesions (P < 0.05). The risk of OSF associated with OLK decreased with increasing OSF stage (P < 0.05). CONCLUSION: The prevalence of OSF in males was higher than that in females, the buccal mucosa was most affected, and chewing areca nut is the most common habit of OSF patients.

Distant metastases in newly diagnosed tongue squamous cell carcinoma.

OBJECTIVE: To characterize the incidence and survivals of patients with distant metastases in newly diagnosed tongue squamous cell carcinoma. MATERIALS AND METHODS: Patients with distant metastases in newly diagnosed tongue squamous cell carcinoma were collected from the Surveillance, Epidemiology, and End Results database. Data were classified by sex, age, race, insurance status, T stage, N stage and grade. Multivariable logistic and Cox regression were used to demonstrate risk factors of the presence of distant metastases and hazards related to mortality, respectively. RESULTS: We found 92 patients with distant metastases in newly diagnosed tongue squamous cell carcinoma, including lung, bone, liver, and brain, representing 1.08% of the entire cohort. 69 were male and 23 were female. Median survival among patients with distant metastases was 4.0 months. CONCLUSION: The study describes the incidence and prognosis of patients with distant metastases in newly diagnosed tongue squamous cell carcinoma based on population estimates. The findings lend support to closely monitor the development of distant metastases among patients with predictors at the time of diagnosis of tongue squamous cell carcinoma.

Resolution-enhanced heterodyne laser interferometer with differential configuration for roll angle measurement.

A high resolution roll measurement heterodyne interferometer with differential configurations is proposed in this paper. The proposed interferometer is composed of a pair of measurement beams providing environmental noise immunity. The structure is designed and the mathematic model based on Jones' matrix for measuring the roll angle is established. Sensitivity is enhanced dramatically because of the opposite phase shift directions of two signals. An experimental setup is built and an amplification factor of 270 is obtained. Correspondingly, a roll angle resolution of 0.13 arcsec is attained using a phase meter with detecting resolution of 0.01°.

Error of image saturation in the structured-light method.

In the phase-measuring structured-light method, image saturation will induce large phase errors. Usually, by selecting proper system parameters (such as the phase-shift number, exposure time, projection intensity, etc.), the phase error can be reduced. However, due to lack of a complete theory of phase error, there is no rational principle or basis for the selection of the optimal system parameters. For this reason, the phase error due to image saturation is analyzed completely, and the effects of the two main factors, including the phase-shift number and saturation degree, on the phase error are studied in depth. In addition, the selection of optimal system parameters is discussed, including the proper range and the selection principle of the system parameters. The error analysis and the conclusion are verified by simulation and experiment results, and the conclusion can be used for optimal parameter selection in practice.

STAT3 mediates multidrug resistance of Burkitt lymphoma cells by promoting antioxidant feedback.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

Multiple Roles of WNT5A in Breast Cancer.

Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A. WNT signaling molecules are potent targets for treatment of cancer. Therefore, understanding the role of WNT5A in breast cancer may provide new ideas and methods for breast cancer treatment. We review the evidence concerning WNT5A and breast cancer involving the signaling pathways and the molecular-targeted therapy of WNT5A. Our results show that the role WNT5A plays depends on the availability of key receptors and intercellular interactions among different cell types.

Analysis and Compensation for Lateral Chromatic Aberration in a Color Coding Structured Light 3D Measurement System.

While color-coding methods have improved the measuring efficiency of a structured light three-dimensional (3D) measurement system, they decreased the measuring accuracy significantly due to lateral chromatic aberration (LCA). In this study, the LCA in a structured light measurement system is analyzed, and a method is proposed to compensate the error caused by the LCA. Firstly, based on the projective transformation, a 3D error map of LCA is constructed in the projector images by using a flat board and comparing the image coordinates of red, green and blue circles with the coordinates of white circles at preselected sample points within the measurement volume. The 3D map consists of the errors, which are the equivalent errors caused by LCA of the camera and projector. Then in measurements, error values of LCA are calculated and compensated to correct the projector image coordinates through the 3D error map and a tri-linear interpolation method. Eventually, 3D coordinates with higher accuracy are re-calculated according to the compensated image coordinates. The effectiveness of the proposed method is verified in the following experiments.

Modeling and Analysis of Phase Fluctuation in a High-Precision Roll Angle Measurement Based on a Heterodyne Interferometer.

Heterodyne interferometry is a high-precision method applied in roll angle measurements. Phase metering is essential for high precision. During a high-precision measurement, a phase fluctuation appears even when the roll angle does not vary, which has never been analyzed before. Herein, the reason for the phase fluctuation is revealed, which results from the frequency-difference fluctuation and time difference between measurement and reference beams. A mathematical model of that phase-fluctuation mechanism is established, and that model provides a theoretical basis for analyzing and reducing the phase fluctuation. The impact that the main factors have on the phase metering is analyzed quantitatively, and experiments are carried out to validate the model. Finally, the phase fluctuation decreases to 0.02° by frequency reduction, which conversely verifies the theoretical model.