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In this paper, firstly, according to the conditions of the growth of the tourism industry in the whole region and the requirements of the growth mechanism, the time sequence of the growth of the tourism industry in the whole region is divided into three phases: the initial start-up phase, the mid-growth phase and the late maturity phase, and puts forward the strategy of the growth of the tourism industry in the whole region. Then, on the basis of the transfer matrix model, according to the law of tourism industry development to determine the tourism industry’s independent variable power function, considering the impact of economic policy and monetary policy on the development of the tourism industry, the need to eliminate the direct effect of the tourism industry independent variable, and then construct the transfer matrix based on the spatial distribution of the tourism industry analytical model and hierarchical system analytical model, and the whole region of the tourism industry in Hubei Province for example research and analysis. The results show that on the model analysis, the prediction accuracy of VM and FM varies among five different groups: purchase>tour> food>travel>housing. In the tourism industry, the correlation coefficient between “food and beverage, accommodation, shopping and entertainment” is around 0.95. This study not only contributes to the green and sustainable development of China’s tourism industry but also is an important step in promoting the construction of ecological civilization.

In order to prepare lightweight high entropy alloy (LHEA) with suitable microstructure and excellent properties, Ti3V2NbAlxNiy LHEA with different Al and Ni ratios were prepared on TC4 substrate using laser cladding technology. Its microstructure, friction, and wear properties were studied, and the effect of adding a small amount of MoB ceramic particles on its microstructure and properties was discussed. The results show that the phases of Ti3V2NbAl0.5Ni0.5, Ti3V2NbAl0.5 and Ti3V2NbNi0.5 coatings are composed of a single body-centered cubic crystal (BCC), while the second phase A15 is formed in Ti3V2NbAl0.5Ni0.5/MoB coatings. Compared with the hardness of the matrix, the hardness of four coatings has been improved. The wear forms of four coatings are mainly adhesive wear, with adhesive layer and a small amount of oxide layer distributed in the wear marks, and furrow characteristics caused by slight abrasive wear are also observed in the wear marks. Compared with the matrix, the wear rate of Ti3V2NbAl0.5Ni0.5/MoB coating is greatly reduced, and the wear rate of Ti3V2NbAl0.5Ni0.5/MoB coating is reduced by 51.1%. The LHEA in this paper has good wear resistance and can be used as a protective coating for TC4 parts in aerospace, national defense equipment manufacturing and other fields. [ABSTRACT FROM AUTHOR]

Objective To explore the influence of the SmartClip self-ligating bracket and traditional metal bi-wing brackets on plaque control and to provide a reference for the oral healthcare of orthodontic patients.Methods The patients were divided into the SmartClip self-ligating bracket group, the metal bi-wing bracket group, and the control group, consisting of untreated volunteers, and the patients were examined before treatment, 1 month after the treatment started, 3 months after the treatment started, and when the treatment ended. The oral hygiene status was recorded at four time points, and the plaque index of the following six teeth was compared among the time points: the upper-right central incisor (UR1), the lower-left central incisor (LL1), the upper-right first molar (UR6), the lower-left first molar (LL6), and the upper left canine (UL3) and the lower-right canine (LR3).Results Compared with before treatment, after first month, third month and end of treatment the plaque index of LL1, LR3, LL6 and UR6 in both the SmartClip self-ligating bracket group and the traditional metal bi-wing bracket group was increased, and the difference was statistically significant (P < 0.05). There was no significant difference in PLI index between the end of treatment and 3 months after orthodontic treatment (P > 0.05). There was no statistically significant difference in PLI index in the control group at each time period (P > 0.05). After three months of orthodontic treatment, the plaque index of LL1 and LR3 in the SmartClip self-ligating bracket group was higher than that in the traditional metal bi-wing bracket group, and the difference was statistically significant (P < 0.05).Conclusion Lower anterior and posterior areas are susceptible to plaque accumulation in treatment with fixed orthodontic appliances. The SmartClip self-ligating bracket system has no advantage over the traditional metal bi-wing bracket in terms of oral hygiene.

Objective To study the relation between the upper first molar root tips and the maxillary sinus floor in patients with different vertical facial patterns using cone⁃beam computed tomography (CBCT) and to explore the refer⁃ ence data for safe clinical orthodontic treatments. Methods Three⁃dimensional images were reconstructed from CBCT data. The CBCT data from 120 adolescents and adults were divided into three groups (low⁃angle group, average⁃angle group, high⁃angle group) based on vertical facial type. For each subject, the distance from the maxillary sinus floor to the upper first molar root tips was measured, and the types of contacts were classified. ANOVA and LSD t tests were used for statistical comparisons and performed using SPSS 19.0. Results Of the 120 samples, only 27% of the upper first molar root tips lost their contacts with the maxillary sinus floor, and the other 73% of the root tips contacted the si⁃ nus to different extents. Significant differences in the distances from the maxillary sinus floor to the upper first molar root tips were found for different vertical facial types (P < 0.05). The high⁃angle group had the lowest sinus floor, rela⁃ tive to the root tips, of the three adult groups (P < 0.05). In the adult group with a low angle, the measured value for the palatal root tips was the lowest and was significantly different from those in the other groups (P < 0.05). Conclusion Seventy⁃three percent of the upper first molar root tips contacted the maxillary sinus floor. The maxillary sinus floor tended to be lower relative to the first molar root tips in patients with a high⁃angle facial pattern than in others. The roots protruded into the sinus to a greater extent.

Background: Extensive patellar tendon ossification is very uncommon and requires surgical intervention when ossification significantly affects knee function. While various approaches and grafts are available for reconstructing ruptured patellar tendons, there is a paucity of literature regarding the management of joint ankylosis due to severely ossified patellar tendons. Case Presentation: This is a case involving an extensively ossified patellar tendon after patellar and tibial tuberosity fracture fixation. Reconstruction of the patellar tendon was performed using ipsilateral semitendinosus and gracilis autografts. At the latest follow‐up of 12 months, the patient achieved knee flexion up to 120° with a slight extension lag and resumed daily activities. Conclusions: Autograft hamstring reconstruction of the patellar tendon is suitable for extensive heterotopic ossification of the patellar tendon, resulting in significant improvement in postoperative knee function. Similar patients may be referred for this reconstruction technique. [ABSTRACT FROM AUTHOR]

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiothoracic surgery or cardiac intervention. Colchicine is an anti-inflammatory agent that was associated with improved cardiovascular outcomes. However, its effect on POAF prevention was inconsistent across studies. Therefore, the aim of this meta-analysis was to evaluate the efficacy of colchicine in prevention of POAF.Methods: We searched PubMed, Embase, ClinicalTrials.gov, Cochrane Library database and Google Scholar for randomized controlled trials (RCTs), using terms "atrial fibrillation" and "colchicine". The primary end point was the occurrence of clinically diagnosed atrial fibrillation. The relative risk (RR) and 95% confidence interval (CI) were evaluated. Estimates were pooled using DerSimonian-Laird random-effects model. We also performed subgroup analyses based on the duration and dose of colchicine treatment.Results: A total of 9 RCTs were included in this meta-analysis, enrolling a total of 2031 patients. Colchicine significantly reduces the incidence of POAF (RR 0.62; 95% CI, 0.52-0.74, P < 0.001, I2 = 0%). Subgroup analyses indicated that the protective effect of colchicine on POAF was slightly stronger in the long-duration group (RR 0.60; 95% CI, 0.48-0.75, P < 0.001, I2 = 0%) than in the short-duration group (RR 0.65; 95% CI, 0.49-0.86, P < 0.001, I2 = 0%).Conclusion: Colchicine is effective in preventing the occurrence of POAF. The efficacy of colchicine can be slightly increased over treatment duration, with no obvious adverse reactions. [ABSTRACT FROM AUTHOR]

Background and Purpose: The free fatty acid receptor 1 (FFAR1) plays an important role in glucose-stimulated insulin secretion making it an attractive anti-diabetic target. This study characterizes the pharmacological profile of HWL-088 (2-(2-fluoro-4-((2'-methyl-[1,1'- biphenyl]-3-yl)methoxy)phenoxy)acetic acid), a novel highly potent FFAR1 agonist in vitro and in vivo. Moreover, we investigated the long-term effects of HWL-088 alone and in combination with metformin in diabetic mice.Experimental Approach: In vitro effects of HWL-088 on FFAR1 and PPARα/γ/δ were studied in cell-based assays. Glucose-dependent insulinotropic effects were evaluated in MIN6 cell line and in rats. Long-term effects on glucose and lipid metabolism were investigated in ob/ob mice.Key Results: HWL-088 is a highly potent FFAR1 agonist (EC50 = 18.9 nM) with moderate PPARδ activity (EC50 = 570.9 nM) and promotes glucose-dependent insulin secretion in vitro and in vivo. Long-term administration of HWL-088 exhibited better glucose control and plasma lipid profiles than those of another FFAR1 agonist, TAK-875, and synergistic improvements were observed when combined with metformin. Moreover, HWL-088 and combination therapy improved β-cell function by up-regulation of pancreas duodenum homeobox-1, reduced fat accumulation in adipose tissue and alleviated fatty liver in ob/ob mice. The effect of HWL-088 involves a reduction in hepatic lipogenesis and oxidative stress, increased lipoprotein lipolysis, glucose uptake, mitochondrial function and fatty acid β-oxidation.Conclusion and Implications: These data indicate that long-term treatment with HWL-088, a highly potent FFAR1 agonist, improves glucose and lipid metabolism and may be useful for the treatment of diabetes mellitus by mono-therapy or combination with metformin. [ABSTRACT FROM AUTHOR]

Background and Purpose: Non‐small‐cell lung cancer (NSCLC) accounts for up to 80–85% of all lung cancers and has a disappointing prognosis. Flavonoids exert anticancer properties, mostly involving stimulation of ROS production without significant toxicity to normal cells. This study was aimed to delineate the effect of diosmetin, a natural flavonoid, on NSCLC cells and its ability to enhance the antitumour activity of paclitaxel. Experimental Approach NSCLC cells, normal cell lines HLF‐1 and BEAS‐2B, and immunodeficient mice were chosen as models to study the effects of diosmetin. Changes in cell viability, apoptosis, and ROS were analysed by MTT assay, flow cytometry assay, and fluorescent probe DCFH‐DA. Expression of proteins and mRNA was determined by Western blotting and real‐time RT‐PCR. Growth of xenografted tumours was measured. Spleens and other vital organs were analysed with histological and immunohistochemical techniques. Key Results: Diosmetin induced selective apoptotic death in NSCLC cells but spared normal cells, via ROS accumulation. Diosmetin induced ROS production in NSCLC cells probably via reducing Nrf2 stability through disruption of the PI3K/Akt/GSK‐3β pathway. The in vitro and in vivo xenograft studies showed that combined treatment of diosmetin and paclitaxel synergistically suppressed NSCLC cells. Histological analysis of vital organs showed no obvious toxicity of diosmetin, which matched our in vitro findings. Conclusions and Implications: Diosmetin selectively induced apoptosis and enhanced the efficacy of paclitaxel in NSCLC cells via ROS accumulation through disruption of the PI3K/Akt/GSK‐3β/Nrf2 pathway. Therefore, diosmetin may be a promising candidate for adjuvant treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Distinctive exosomal contents could be useful for cancer diagnosis and prognosis. However, little is known about whether serum exosomal heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) mRNA is a satisfactory biomarker for hepatocellular carcinoma (HCC). Methods: Two hundred and ninety-one participants divided into four age- and gender-matched groups, including a HCC group (n=88), a liver cirrhosis (LC) group (n=67), a chronic hepatitis B (CHB) group (n=68) and a healthy control group (n=68), were enrolled. Serum exosomal hnRNPH1 mRNA and GAPDH mRNA were measured using TaqMan real-time PCR, and the relative expression levels were calculated. Receiver operating characteristic (ROC) curves were constructed to evaluate the effectiveness of hnRNPH1 mRNA alone and in combination with α-fetoprotein (AFP) in the diagnosis of HCC. The correlation between hnRNPH1 mRNA levels and clinicopathological characteristics and overall survival (OS) in HCC was determined. Results: The serum exosomal hnRNPH1 mRNA levels in HCC patients were remarkably higher than in the other groups (p<0.05). The hnRNPH1 mRNA discriminated HCC from CHB with an area under the ROC curve (AUC) of 0.865, with sensitivity of 85.2% and specificity of 76.5% at cut-off value of 0.670. The AUC for hnRNPH1 mRNA in combination with AFP was further improved. The exosomal hnRNPH1 mRNA levels in HCC patients were associated with the Child-Pugh classification, portal vein tumor emboli, lymph node metastasis, TNM stage and OS (p<0.05). Conclusions: These findings suggested that serum exosomal hnRNPH1 mRNA could be an effective marker for HCC in high HBV prevalence areas. [ABSTRACT FROM AUTHOR]

Surface electromyography (sEMG) is a kind of biological signal that records muscle activity noninvasively, which is of great significance in advanced human-computer interaction, prosthetic control, clinical therapy, and biomechanics. However, the number of hand gestures that can be recognized is limited and the recognition accuracy needs to be further improved. These factors lead to the fact that sEMG products are not widely used in practice. The main contributions of this paper are as follows. Firstly, considering the increasing number of gestures to be recognized and the complexity of gestures, an extensible two-stage machine learning lightweight framework was innovatively proposed for multi-gesture task recognition. Secondly, the multivariate variational mode decomposition (MVMD) is applied to extract the spatial–temporal features from the multiple channels to the EMG signals, and the separable convolutional neural network is used for modelling. In this work, the experimental results for 52 hand gestures recognition task show that the average accuracy on each stage is about 90%. The potential movement information is mainly contained in the low-frequency oscillator of the sEMG signal, and the model performs better with the low-frequency oscillation from the MVMD algorithm on the second stage classification than that of other decomposition methods. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) overdose-induced acute liver damage is mostly due to overwhelmingly increased oxidative stress. Nuclear factor-erythroid 2-related factor2 (Nrf2) plays an important role in alleviating APAP hepatic toxicity. Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells. Nevertheless, whether SHK protects against APAP-induced liver toxicity remains undefined. This study found SHK defended APAP-induced liver toxicity, as well as reversed the levels of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, and reactive oxygen species (ROS), while it enhanced the liver glutathione (GSH) level in APAP-treated mice. SHK rescued the cell viability and GSH depletion, but neutralized oxidative stress in APAP-treated human normal liver L-02 cells. Mechanically, SHK increased Nrf2 expression in the exposure of APAP at the protein level but not at the mRNA level. Inhibition of Nrf2 blocked the SHK effect in APAP-treated hepatocytes. Furthermore, SHK improved Nrf2 stability through stimulating PI3K/Akt pathway, thus inhibiting GSK-3β. In vivo studies confirmed the close correlation of liver protection of SHK against APAP and Akt/GSK-3β/Nrf2 pathway. In conclusion, this study reveals that SHK prevents APAP hepatotoxicity by upregulation of Nrf2 via PI3K/Akt/GSK-3β pathway. Therefore, SHK may be a promising candidate against APAP-induced liver injury. [ABSTRACT FROM AUTHOR]

Objective. Since early diagnosis is very important for treating gastric cancer (GC), we aimed to detect serum small proline-rich protein2A (SPRR2A) to verify its diagnostic value for GC patients. Methods. Serum samples were collected from 200 patients with GC, 100 patients with gastritis, 40 patients with rectal cancer (RC), 50 patients with colon cancer (CC), and 100 healthy controls. An enzyme-linked immunosorbent assay (ELISA) detection kit was applied to measure serum SPRR2A concentration. The correlations between serum SPRR2A and carcinoembryonic antigen (CEA), clinical pathological parameters of GC, and receiver operating characteristic (ROC) curve were also analyzed. Results. The median serum SPRR2A concentration in GC patients was significantly higher than those in healthy controls and gastritis or colorectal cancer patients (P < 0.001). Serum SPRR2A concentration at a cut-off value of 80.7 pg/ml yielded an AUC of 0.851, with 75.7% sensitivity and 74.5% specificity for discriminating GC patients from healthy people. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.876, with 79.7% sensitivity and 78.7% specificity. Similarly, serum SPRR2A discriminated GC patients from gastritis patients with an AUC of 0.820, with 90.5% sensitivity and 61.7% specificity. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.848, with 87.8% sensitivity and 68.1% specificity. The serum SPRR2A levels in GC patients were associated with lymph node metastasis and the tumor-node-metastasis (TNM) stage (P < 0.05). There was an obvious difference in serum SPRR2A expression between GC patients before and after surgery (P < 0.0001). Conclusion. These results suggest that serum SPRR2A can be used as an effective marker for GC. [ABSTRACT FROM AUTHOR]

Current extraction methods often extract DNA and RNA separately, and few methods are capable of co-extracting DNA and RNA from sputum. We established a nucleic acid co-extraction method from sputum based on magnetic beads and optimized the method by evaluating influencing factors, such as the guanidinium thiocyanate (GTC) and dithiothreitol (DTT) concentrations, magnetic bead amount, incubation temperature, lysis buffer pH and RNA carrier type. The feasibility of the simultaneous nucleic acid co-extraction method was evaluated by amplifying DNA and RNA viruses from a single clinical specimen with a multiplex RT-qPCR method. Both DNA and RNA were most efficiently extracted when the GTC and DTT concentrations were 2.0 M and 80 mM, respectively, 20 μl magnetic beads were added, the incubation temperature was 80 °C, the pH was 8 or 9, and RNA carrier A was used. Therefore, we established a simple method to extract nucleic acids from two important respiratory viruses compared with other commercial kits. This magnetic beads-based co-extraction method for sputum followed by a multiplex RT-qPCR can rapidly and precisely detect DNA and RNA viruses from a single clinical specimen and has many advantages, such as decreased time, low cost, and a lack of harmful chemicals. [ABSTRACT FROM AUTHOR]

This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC) curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC) for RASSF1A methylation (0.718) was better than the corresponding AUC for AFP (0.609) in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, P=0.028), and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses. [ABSTRACT FROM AUTHOR]

Graphical abstract Aiming to exploring potent XO inhibitor with optimal heterocycle, we have identified a new 2-phenylthiazole-4-carboxylic acid scaffold by evaluating 5 heterocycle scaffolds unexplored in this field, exemplified by the potent and orally bioavailable XO inhibitor 8. Highlights • 2-Phenylthiazole-4-carboxylic acid was identified as a novel scaffold of xanthine oxidase inhibitors. • Compound 8 revealed equivalent XO inhibitory activities with the analog of Febuxostat (compound 7). • Compound 8 exhibited significantly hypouricemic effect in hyperuricemic mice. Abstract The xanthine oxidase (XO) plays an important role in producing uric acid, and therefore XO inhibitors are considered as one of the promising therapies for hyperuricemia and gout. We have previously reported a series of XO inhibitors with pyrazole scaffold to extend the chemical space of current XO inhibitors. Herein, we describe further structural optimization to explore the optimal heterocycle by replacing the thiazole ring of Febuxostat with 5 heterocycle scaffolds unexplored in this field. All of these efforts resulted in the identification of compound 8 , a potent XO inhibitor (IC 50 = 48.6 nM) with novel 2-phenylthiazole-4-carboxylic acid scaffold. Moreover, lead compound 8 exhibited hypouricemic effect in potassium oxonate-hypoxanthine-induced hyperuricemic mice. These results promote the understanding of ligand-receptor interaction and might help to design more promising XO inhibitors. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor receptors (PDGFRs) are abundantly expressed by stromal cells in the non-small cell lung cancer (NSCLC) microenvironment, and in a subset of cancer cells, usually with their overexpression and/or activating mutation. However, the effect of PDGFR inhibition on lung cancer cells themselves has been largely neglected. In this study, we investigated the anticancer activity of CP-673451, a potent and selective inhibitor of PDGFRβ, on NSCLC cell lines (A549 and H358) and the potential mechanism. The results showed that inhibition of PDGFRβ by CP-673451 induced a significant increase in cell apoptosis, accompanied by ROS accumulation. However, CP-673451 exerted less cytotoxicity in normal lung epithelial cell line BEAS-2B cells determined by MTT and apoptosis assay. Elimination of ROS by NAC reversed the CP-673451-induced apoptosis in NSCLC cells. Furthermore, CP-673451 down-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) probably through inhibition of PI3K/Akt pathway. Rescue of Nrf2 activity counteracted the effects of CP-673451 on cell apoptosis and ROS accumulation. Silencing PDGFRβ expression by PDGFRβ siRNA exerted similar effects with CP-673451 in A549 cells, and when PDGFRβ was knockdowned by PDGFRβ siRNA, CP-673451 produced no additional effects on cell viability, ROS and GSH production, Nrf2 expression as well as PI3K/Akt pathway activity. Specifically, Nrf2 plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and we found that combination of CP-673451 and cisplatin produced a synergistic anticancer effect and substantial ROS production in vitro . Therefore, these results clearly demonstrate the effectiveness of inhibition of PDGFRβ against NSCLC cells and strongly suggest that CP-673451 may be a promising adjuvant chemotherapeutic drug. [ABSTRACT FROM AUTHOR]