Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.

BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

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.

Interactive and lag effects of environmental factors on the density of schistosome-transmitting Oncomelania hupensis: A twelve-year monthly repeated survey.

Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum. We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.

Prediction on the spatial distribution of the seropositive rate of schistosomiasis in Hunan Province, China: a machine learning model integrated with the Kriging method.

Schistosomiasis remains a formidable challenge to global public health. This study aims to predict the spatial distribution of schistosomiasis seropositive rates in Hunan Province, pinpointing high-risk transmission areas and advocating for tailored control measures in low-endemic regions. Six machine learning models and their corresponding hybrid machine learning-Kriging models were employed to predict the seropositive rate. The optimal model was selected through internal and external validations to simulate the spatial distribution of seropositive rates. Our results showed that the hybrid machine learning-Kriging model demonstrated superior predictive performance compared to basic machine learning model and the Cubist-Kriging model emerged as the most optimal model for this study. The predictive map revealed elevated seropositive rates around Dongting Lake and its waterways with significant clustering, notably in the central and northern regions of Yiyang City and the northeastern areas of Changde City. The model identified gross domestic product, annual average wind speed and the nearest distance from the river as the top three predictors of seropositive rates, with annual average daytime surface temperature contributing the least. In conclusion, our research has revealed that integrating the Kriging method significantly enhances the predictive performance of machine learning models. We developed a Cubist-Kriging model with high predictive performance to forecast the spatial distribution of schistosomiasis seropositive rates. These findings provide valuable guidance for the precise prevention and control of schistosomiasis.

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.

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.

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.

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.