Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Highly sensitive dual-function sensor for refractive index and temperature using D-shaped microchannel photonic crystal fiber.

An innovative ultra-sensitive, dual-functional sensor employing a D-shaped microchannel photonic crystal fiber (PCF) for refractive index (RI) and temperature measurements is proposed and comprehensively investigated. Its high-sensitivity is achieved through the incorporation of gold (Au) and magnesium fluoride (MgF2) as plasmonic materials in the micro-rectangular channel. This configuration significantly enhances the interaction between the surface plasmon polaritons (SPPs) field and y-polarized evanescent field on external surfaces. Additionally, the integration of a temperature-sensitive fluid within the sensor allows for precise detection of temperature changes. Our simulations demonstrate a broad detection spectrum, covering RI values from 1.27 to 1.43 and temperatures ranging from 45°C to 100°C. The sensor achieves peak sensitivities of 31800nm/RIU for RI and 49 nm/°C for temperature. Besides, the sensor only has a cladding consisting of three air holes to enhance coupling and reduce the difficulty of preparation. Importantly, the sensor's performance remains robust against minor structural alterations in the PCF, indicating high fault tolerance. Given its high sensitivity, extensive detection range, and strong fabrication stability, this PCF-SPR sensor offers significant potential for applications in biochemical sensing and environmental monitoring.

A Molecular Dynamics Analysis of the Thickness and Adhesion Characteristics of the Quasi-Liquid Layer at the Asphalt-Ice Interface.

The quasi-liquid layer (QLL), a microstructure located between ice and an adhering substrate, is critical in generating capillary pressure, which in turn influences ice adhesion behavior. This study employed molecular dynamics (MD) methods to obtain QLL thickness and utilized these measurements to estimate the adhesive strength between ice and asphalt. The research involved constructing an ice-QLL-asphalt MD model, encompassing four asphalt types and five temperature ranges from 250 K to 270 K. The QLL thickness was determined for various asphalts and temperatures using the tetrahedral order parameter gradient. Additionally, capillary pressure was calculated based on the QLL thickness and other geometric parameters obtained from the MD analysis. These findings were then compared with ice adhesion strength data acquired from pull-off tests. The results indicate that QLL thickness varies with different asphalt types and increases with temperature. At a constant temperature, the QLL thickness decreases in the order of the basal plane, primary prism plane, and secondary prism plane. Furthermore, the adhesion strength of the QLL diminishes as the temperature rises, attributed to the disruption of hydrogen bonds at lower temperatures. The greater the polarity of the asphalt's interface molecules, the stronger the adhesion strength and binding free energy. The MD simulations of the asphalt-ice interface offer insights into the atomic-scale adhesive properties of this interface, contributing to the enhancement in QLL property prediction and calibration at larger scales.

Clinical evaluation on automatic segmentation results of convolutional neural networks in rectal cancer radiotherapy.

Purpose: Image segmentation can be time-consuming and lacks consistency between different oncologists, which is essential in conformal radiotherapy techniques. We aimed to evaluate automatic delineation results generated by convolutional neural networks (CNNs) from geometry and dosimetry perspectives and explore the reliability of these segmentation tools in rectal cancer. Methods: Forty-seven rectal cancer cases treated from February 2018 to April 2019 were randomly collected retrospectively in our cancer center. The oncologists delineated regions of interest (ROIs) on planning CT images as the ground truth, including clinical target volume (CTV), bladder, small intestine, and femoral heads. The corresponding automatic segmentation results were generated by DeepLabv3+ and ResUNet, and we also used Atlas-Based Autosegmentation (ABAS) software for comparison. The geometry evaluation was carried out using the volumetric Dice similarity coefficient (DSC) and surface DSC, and critical dose parameters were assessed based on replanning optimized by clinically approved or automatically generated CTVs and organs at risk (OARs), i.e., the Planref and Plantest. Pearson test was used to explore the correlation between geometric metrics and dose parameters. Results: In geometric evaluation, DeepLabv3+ performed better in DCS metrics for the CTV (volumetric DSC, mean = 0.96, P< 0.01; surface DSC, mean = 0.78, P< 0.01) and small intestine (volumetric DSC, mean = 0.91, P< 0.01; surface DSC, mean = 0.62, P< 0.01), ResUNet had advantages in volumetric DSC of the bladder (mean = 0.97, P< 0.05). For critical dose parameters analysis between Planref and Plantest, there was a significant difference for target volumes (P< 0.01), and no significant difference was found for the ResUNet-generated small intestine (P > 0.05). For the correlation test, a negative correlation was found between DSC metrics (volumetric, surface DSC) and dosimetric parameters (δD95, δD95, HI, CI) for target volumes (P< 0.05), and no significant correlation was found for most tests of OARs (P > 0.05). Conclusions: CNNs show remarkable repeatability and time-saving in automatic segmentation, and their accuracy also has a certain potential in clinical practice. Meanwhile, clinical aspects, such as dose distribution, may need to be considered when comparing the performance of auto-segmentation methods.

Downregulation of microRNA­423­5p suppresses TGF­ß1­induced EMT by targeting FOXP4 in airway fibrosis.

Airway fibrosis (AF) is a common disease that can severely affect patient prognosis. Epithelial­mesenchymal transition (EMT) participates in the pathophysiological development of AF and several studies have demonstrated that some microRNAs (miRNAs) contribute to the development of EMT. The aim of this study was to investigate the function of miR­423­5p in the EMT process and its possible underlying mechanism in BEAS­2B cells. The present study utilized the BEAS­2B cell line to model EMT in AF. Online tools, fluorescence in situ hybridization analysis and an RNA pull­down assay were used to identify potential target genes of miR­423­5p. In addition, immunohistochemistry, wound healing assays, Transwell migration assays, flow cytometry, enzyme­linked immunosorbent assay, reverse transcription­quantitative PCR, western blot analysis and immunofluorescence staining were used to determine the function of miR­423­5p and its target gene in the EMT process in AF. The results indicated that the miR­423­5p expression in AF tissues and BEAS­2B cells stimulated with 10 ng/ml TGF­ß1 for 24 h was significantly increased compared with that in the control group. Overexpression of miR­423­5p facilitated TGF­ß1­induced EMT in BEAS­2B cells; by contrast, downregulation of miR­423­5p suppressed TGF­ß1­induced EMT in BEAS­2B cells. Furthermore, forkhead box p4 (FOXP4) was identified as a potential target gene of miR­423­5p and changes in the miR­423­5p and FOXP4 expression were shown to significantly affect the expression of PI3K/AKT/mTOR pathway members. In summary, overexpression of miR­423­5P promoted the EMT process in AF by downregulating FOXP4 expression and the underlying mechanism may partly involve activation of the PI3K/AKT/mTOR pathway.

Left Main Bronchus Stenosis Lesion, Neutrophil Count, and Platelet Count Are Predictors of Post-Tuberculosis Bronchomalacia.

BACKGROUND Post-tuberculosis bronchomalacia (PTBM) is one of the main conditions occurring in patients after tracheobronchial tuberculosis (TBTB), and is also associated with the recurrence of symptoms. The present study aimed to investigate the predictors of PTBM in patients who had been undergoing appropriate TB treatment. MATERIAL AND METHODS Clinical data of 104 patients with symptomatic airway stenosis after TBTB between January 01, 2019 and June 31, 2020 were recorded and analyzed. The association between baseline clinical characteristics, laboratory results, and PTBM was calculated with logistical regression. The time from onset of bronchoscopic intervention was examined by Kaplan-Meier estimates; differences between the 2 groups were tested by the log-rank test. RESULTS Fifty-seven patients (54.81%) had PTBM. In the multivariate logistical analysis, the left main bronchus stenosis lesion (odds ratio [OR]=3.763), neutrophil (NEUT) count (OR=1.527), and platelet (PLT) (OR=1.010) count were predictors of PTBM. During follow-up, patients with BM had a significantly longer duration from onset of bronchoscopic intervention than patients without BM (hazard ratio=2.412, P<0.0001). Further, all patients needing long-term bronchoscopic intervention therapy were subsequently identified as having PTBM. Additionally, blood PLT counts were significantly decreased to normal levels in the non-BM group (P<0.05), but not in the BM group (P>0.05). CONCLUSIONS PTBM is most likely to occur in the left main bronchus. The inflammatory and immune responses associated with NEUT and PLT may represent therapeutic targets of PTBM. Our study is the first to report that decreased blood PLT count has the potential to monitor the treatment response.

Downregulation of miR­483­5p inhibits TGF­ß1­induced EMT by targeting RhoGDI1 in pulmonary fibrosis.

Transforming growth factor­ß1 (TGF­ß1)­induced epithelial­mesenchymal transition (EMT) serves a significant role in pulmonary fibrosis (PF). Increasing evidence indicates that microRNAs (miRNAs or miRs) contribute to PF pathogenesis via EMT regulation. However, the role of miR­483­5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR­483­5p on TGF­ß1­induced EMT in PF. It was found that the expression of miR­483­5p was upregulated in both PF tissue and A549 cells treated with TGF­ß1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR­483­5p mimic transfection promoted TGF­ß1­induced EMT; by contrast, miR­483­5p inhibitor inhibited TGF­ß1­induced EMT. Also, miR­483­5p mimic decreased RhoGDI1 expression, whereas miR­483­5p inhibitor increased RhoGDI1 expression. Furthermore, dual­luciferase reporter gene assay indicated that miR­483­5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR­483­5p inhibitor on TGF­ß1­induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway. In conclusion, these data indicated that miR­483­5p inhibition ameliorated TGF­ß1­induced EMT by targeting RhoGDI1 via the Rac1/PI3K/Akt signaling pathway in PF, suggesting a potential role of miR­483­5p in the prevention and treatment of PF.

Clinical significance of serum transforming growth factor-ß1 and procollagen type I N-propeptide in post-tuberculosis tracheobronchial stenosis.

Non-invasive strategies for monitoring post-tuberculosis (TB) tracheobronchial stenosis (PTTS) are clinically important but currently lacking. Transforming growth factor-ß1 (TGF-ß1) and procollagen type I N-propeptide (PINP) have been identified as markers of fibrosis. The present study aimed to investigate the clinical significance of serum TGF-ß1 and PINP in PTTS. Serum samples were collected from 119 patients with tracheobronchial TB after the condition was treated for at least 6 months (59 patients with airway stenosis and 60 patients with no stenosis). Serum TGF-ß1 and PINP levels were measured using ELISA and compared between the groups. Relationships between serum TGF-ß1 and PINP levels and clinical characteristics, interventional bronchoscopy and outcomes of airway stenosis were analysed. The correlation between TGF-ß1 and PINP, and their diagnostic efficacy for airway stenosis were also analysed. The TGF-ß1 and PINP levels in the airway stenosis group were higher than those in the non-stenosis group. Furthermore, airway stenosis with atelectasis or mucus plugging was associated with higher TGF-ß1 levels, and airway stenosis with atelectasis, mucus plugging, right main bronchus stenosis or severe airway tracheal stenosis was associated with higher PINP levels. In addition, TGF-ß1 and PINP levels increased after interventional bronchoscopy therapy and airway stenosis with recurrent stenosis was associated with higher baseline levels of both markers. Finally, TGF-ß1 levels were positively correlated with PINP levels in patients with airway stenosis. The area under the receiver operating characteristic curve of TGF-ß1 and PINP for distinguishing airway stenosis from non-stenosis cases was 0.824 (95% CI: 0.748-0.900) and 0.863 (95% CI: 0.796-0.930), respectively. Therefore, TGF-ß1 and PINP are potential biomarkers that may be useful for diagnosing and monitoring PTTS.

Laboratory Investigation of Aging Resistance for Rubberized Bitumen Modified by Using Microwave Activation Crumb Rubber and Different Modifiers.

Different modification methods, such as adding modifiers and pretreating crumb rubber, have been developed to achieve decent engineering properties and reduce the viscosity of rubberized bitumen. This study evaluated the influence of the modification methods on the aging resistance for rubberized bitumen. Two types of crumb rubber-a 40-mesh crumb rubber and a microwave-pretreated crumb rubber-and two kinds of modifiers-Sasobit and Trans-polyoctenamer-were selected to prepare rubberized bitumen. The samples were subjected to a Thin-Film Oven Test for the simulation of the short-term aging condition, while a Pressure-Aging-Vessel test was used to simulate the long-term aging condition. The indexes of rubberized bitumen, including softening point, elastic recovery ratio, maximum load, ductility, fracture energy, phase angle, and dynamic modulus, were tested before and after aging. The result showed that trans-polyoctenamer displayed the best resistance to short-term aging, while Sasobit significantly improved the fracture energy of rubberized bitumen after short-term aging. Microwave pretreated partially destroyed the internal structure of crumb rubber, leading to a decrease of short-term aging resistance for rubberized bitumen. Compared with short-term aging, the changing trends of various indexes were basically same, except the discrepancy of properties indexes was reduced after long-term aging.

Clinical application of an interaction retention method for multi-implant-supported fixed bridges in posterior teeth / 口腔疾病防治

Objective @#To research the feasibility and preliminary clinical effect of an implant-supported fixed bridge based on interactions with the posterior interocclusal space deficiency. @*Methods@#Four patients with multiple implant-supported fixed-bridge restorations for interocclusal space deficiency in posterior teeth were included in this study. The 8 total implant sites had an average interocclusal space size of 3.3 mm. Two abutments with an undercut area were performed, the fixed bridge was placed by rotating it without a common path of insertion, and the abutment screw was then tightened. In the production process, the interaction retention concept and methods were fully communicated to the technician. The abutments and bridges on the implants were placed, and the clinical effect was observed. @*Results@#The prosthesis was fixed well and presented appropriate functioning. At the 3-month and 18-month follow-up examination, the prosthesis and abutments were not loose, and the abutments did not release or break. No swelling or tenderness was observed in the margin of the implants.@*Conclusion @#The interaction retention is a good method of resolving the problem of interocclusal space deficiencies in the posterior teeth.

Clinical application of custom all-ceramic crown based on CT data in maxillary anterior implant tooth / 口腔疾病防治

Objective @#To evaluate the clinical outcomes of custom all-ceramic crown fabricated in zirconia based on CT data in maxillary anterior implant tooth. @*Methods@#15 patients with single anterior tooth missing were applied to this treatment. Crown remodeling according to the opposite tooth, fabrication of the all-ceramic crown was finished based on the data capture via CT scan. The observation period extended 2-7 years on average.@*Results@#The survival and success rates were 100%. Soft tissue was stabile in follow up photos. All of the patients were satisfied with the restorations. @*Conclusion @#The custom all-ceramic crown based on CT data showed good interface friendship with both of the hard and soft tissues and the aesthetics result is predictable.

Clinical significance of serum transforming growth factor-ß1 in lung cancer.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-ß1 levels in patients with lung cancer and analyze the relationship between TGF-ß1 and existing tumor markers for lung cancer. METHODS: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-ß1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-ß1 was assessed alone and in combination with existing tumor markers for lung cancer. RESULTS: Serum TGF-ß1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6 × 10(5) (0.4 × 10(5), 0.9 × 10(5))pg/ml vs 0.5 × 10(5) (0.3 × 10(5), 0.7 × 10(5))pg/ml, P=0.040]. Although there was a positive correlation between serum TGF-ß1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P=0.116). The ability of serum TGF-ß1 to discriminate lung cancer at a cutoff value of 79,168 pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-ß1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R=0.308, P=0.020) and neuron-specific enolase (NSE; R=0.558, P=0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-ß1 levels. CONCLUSION: Quantification of serum TGF-ß1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.