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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.
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Manose , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica , Serina-Treonina Quinases TOR , Animais , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Manose/farmacologia , Manose/metabolismo , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
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 49â 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.
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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.
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Broncopatias/epidemiologia , Broncomalácia/epidemiologia , Constrição Patológica/epidemiologia , Neutrófilos/imunologia , Tuberculose Pulmonar/complicações , Adulto , Brônquios/diagnóstico por imagem , Brônquios/patologia , Broncopatias/sangue , Broncopatias/imunologia , Broncopatias/patologia , Broncomalácia/imunologia , Broncomalácia/microbiologia , Broncoscopia , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/imunologia , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
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.
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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.
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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.
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Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead , MicroRNAs , Fibrose Pulmonar , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Fibrose , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/genética , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
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.
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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.
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Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo , Células A549 , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Fibrose Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
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.
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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.