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1.
J Proteome Res ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917576

RESUMO

Ankylosing Spondylitis (AS) is a systemic, chronic and inflammatory rheumatic disease that affects 0.2% of the population. Current diagnostic criteria for disease activity rely on subjective Bath Ankylosing Spondylitis Disease Activity Index scores. Here, we aimed to discover a panel of serum protein biomarkers. First, TMT-based quantitative proteomics was applied to identify differential proteins between 15 pooled active AS and 60 pooled healthy subjects. Second, cohort 1 of 328 humans, including 138 active AS and 190 healthy subjects from 2 independent centers, was used for biomarker discovery and validation. Finally, biomarker panels were applied to differentiate among active AS, stable AS and healthy subjects from cohort 2, which enrolled 28 patients with stable AS, 26 with active AS and 28 healthy subjects. From the proteomics study, a total of 762 proteins were identified, and 46 proteins were up-regulated and 59 proteins were down-regulated in active AS patients compared to healthy persons. Among them, C-reactive protein (CRP), Complement factor H-related protein 3 (CFHR3), alpha-1-acid glycoprotein 2 (ORM2), serum amyloid A1 (SAA1), fibrinogen gamma (FG-γ) and fibrinogen beta (FG-ß) were the most significantly up-regulated inflammation-related proteins; S100A8, fatty acid-binding protein 5 (FABP5) and thrombospondin 1 (THBS1) were the most significantly down-regulated inflammation-related proteins. From cohort 1 study, the best panel for diagnosis of active AS vs healthy subjects is combination of CRP and SAA1. The area under the receiver operating characteristic (ROC) curve was nearly 0.900. The sensitivity was 0.970 and the specificity was 0.805 at a 95% confidence interval from 0.811 to 0.977. Using 0.387 as the cut-off value, the predictive values reached 92.00% in the internal validation set (62 with active AS vs 114 healthy subjects) and 97.50% in the external validation phase (40 with active AS vs 40 healthy subjects). From cohort 2 study, a panel of CRP and SAA1 can differentiate well among active AS, stable AS and healthy subjects. For active AS vs stable AS, the area under the ROC curve was 0.951, the sensitivity was 96.43%, the specificity was 88.46% at a 95% confidence interval from 0.891 to 1, and the coincidence rate was 92.30%. For stable AS vs healthy humans, the area under the ROC curve was 0.908, the sensitivity was 89.29%, the specificity was 78.57% at a 95% confidence interval from 0.836 to 0.980, and the coincidence rate was 83.93%. For active AS vs healthy subjects, the predictive value was 94.44%. The results indicated that the CRP and SAA1 combination can potentially diagnose disease status, especially for active or stable AS, which will be conducive to treatment recommendation for patients with AS.

2.
Inflammation ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912281

RESUMO

The original version of this article was published with incorrect Fig. 1B. The correct Fig. 1B is now presented in Fig. 1 shown at the next page.

3.
Protein Expr Purif ; 168: 105567, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31904423

RESUMO

Rabies is a fatal zoonosis which could affect all mammals. Glycoprotein (G protein) from the rabies virus plays an important role in the binding of virus to target cells. However, expression of the G protein with native conformation has been a great challenge for many years. In this study, we solved this problem by replacing the original signal peptide of rabies virus G protein with the one from the heavy chain of human IgG. The expression levels of recombinant G protein dramatically increased from a few µg/L to 50 mg/L in the culture supernatants. The identity of the recombinant G protein was confirmed by western blotting using both 6XHis mAb 6E2 and rabies G protein mAb 7G3. The correct conformation of the recombinant G protein was shown by using rabies virus neutralizing antibodies. In addition, the recombinant G protein had immune-reactivities with mice sera raised against rabies vaccines and vice versa. Taken together, our data suggested that by replacing the signal peptide, the expression level of the G protein with native conformation could be significantly improved. This would help the development of a rabies subunit vaccine, structural studies of rabies G protein, elucidation of the signal pathway of RABV infection.

4.
Carbohydr Polym ; 230: 115726, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887919

RESUMO

The study tried to investigate whether apple polysaccharide (AP) could prevent colitis associated colorectal cancer (CACC) through the regulation of intestinal microbiota disorders. 10 % AP (w/v) was administrated to ICR mice by gavage for 15 wk. It was found that AP treatment protected against CACC in mice effectively. The level of Lactobacillus in the intestine of AOM/DSS-treated mice was significantly decreased and that of Fusobacterium increased; while AP could reverse this trend and increase the intestinal microbiota diversity. The number of T cells and macrophages in the colon tissue of mice in AOM/DSS group elevated; while AP could reduce the number of these cells significantly. AP suppressed nuclear aggregation of ß-catenin, inhibited the activation of Wnt pathway in colon tissues. These data suggest that AP prevented ICR mice from CACC at least in part through regulating intestinal flora disorder and Wnt pathway.

5.
Plant Signal Behav ; : 1706024, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900029

RESUMO

Plant leaf margins produce small outgrowths or teeth causing serration in a regular arrangement, which is specified by auxin maxima. In Arabidopsis, the spatiotemporal pattern of auxin dependents on both, the transcription factor CUC2 and the signal peptide EPFL2, a ligand of the growth-promoting receptor kinase ERECTA (ER). Ectopic expression of CUC2 can have contrary effects on leaf growth. Ubiquitous expressed CUC2 suppresses growth in the whole leaf, whereas cuc2-1D mutants have enlarged leaves, through ER-dependent cell proliferation in the teeth. Here we investigated the growth dynamics of cuc2-1D leaves and the growth restricting the function of CUC2 using the ubiquitous inducible CUC2-GR transgene. In time courses, we dissected the serration promoting the function of CUC2 in the leaf margin and ectopic growth inhibition by CUC2 in the leaf plate. We found that CUC2 limits growth rather by cell cycle inhibition than by cell size control. Furthermore, endogenous CUC2 was rapidly induced by CUC2-GR indicating a possible auto-inducible feedback. In contrast, EPFL2 was quickly decreased by transient CUC2 induction but increased in cuc2-3 mutant leaves suggesting that CUC2 can also counteract the EPFL2-ER pathway. Therefore, tooth growth promotion and growth inhibition by CUC2 involve partially the same mechanism but in contrary ways.

6.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3921-3930, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31833706

RESUMO

Soil microorganisms would reproduce rapidly and migrate directionally under the applied electric field. In this study, tetradecane-degrading bacteria were added at different locations in soil, and 1 V·cm-1 unidirectional DC electric field was applied to investigate the migration, distribution, and degradation characteristics of target bacteria in soil. The results showed that microorga-nisms migrated to the cathode and anode by electrodialysis and electrophoresis, respectively. The number of microorganisms migrated by electrodialysis was 3.5 times of that by electrophoresis. The application of electric field could make the soil environment spatially heterogeneous to affect the growth of microorganisms. The average number of soil microorganisms under electric field was 1.16×108 CFU·g-1(6 days), which was 2.3 times of that without electric field. S2 to S4 were the efficient growth areas of microorganisms, with the average number after 30-day electric treatment being 2.8-3.5 times of that on the anode and cathode, and 2.1 times of that in the control. There was a significant positive correlation between the tetradecane degradation rate and the number of microorganisms (r=0.895, P<0.05). The optimal tetradecane degradation region was near the cathode (S4), where its degradation rate reached 94.6%. Based on these results, a model modified by environmental factors was established to simulate the spatial distribution of microorganisms under the combined effect of electrokinetic stimulation and transportation. According to the model, the number distribution of microorganisms could be deduced when exogenous bacteria were added in a fixed section. The results provide a theoretical basis for the efficient import of exogenous functional bacteria in electrokinetic-bioremediation of organic contaminated soil.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1979-1985, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839070

RESUMO

OBJECTIVE: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of malignant hematopathy and its influencing factors. METHODS: The clinical data of 300 cases received hematopoietic stem cell transplantation due to malignant hematological diseases in Zhu Jiang Hospital of Southern Medical University from January 2010 to June 2018 were analyzed retrospectively, and the factors affecting hematopoietic reconstruction, disease-free survival (DFS) and overall survival (OS) were compared between haploidentical HSCT and HLA matched HSCT. RESULTS: The hematopoietic reconstitution rate, incidence of GVHD, posttransplant recurrence rate and disease-free survival (DFS) were not statistically different between HLA-metched and haploidentical colorts. However, compared with HLA-matched HSCT group the time of platelet implantation was prolonged, the recurrence-related mortality was higher, and the overall survival (OS) rate was lower in the haploidentical HSCT group. Univariate analyses showed that non-remission before transplantation, and grade Ⅲ, Ⅳ aGVHD were the risk factors for OS in both groups (P<0.05). The age than 40 years old at the time of transplantation and unrelated donors were risk factors for OS in haploidentical HSCT group (P<0.05). Multivariate analysis showed that non-remission before transplantation and grade Ⅲ, Ⅳ aGVHD were independent prognostic indictor for OS with relative risk (RR) of 4.4 (95% CI,1.5-13.4), 9.3 (95% CI,2.3-37.0), 11.0 (95% CI,3.2-37.3) (P<0.05) in HLA-matched HSCT group. Unrelated donor, high-risk group, and gradeⅣaGVHD were independent prognostic indictors for OS with relative risk (RR) of 7.4 (95% CI,2.3-23.1), 2.4 (95% CI,1.3-4.5), 4.1(95% CI,1.6-10.5) (P<0.05) in haploidentical HSCT group. CONCLUSION: The comprehensive curative effect of HLA-matched HSCT is better than the haploidentical HSCT in hematological malignancies. In haploidentical HSCT the selecting related donor is better than unrelated donors, which required more platelet transfusion support.

8.
Database (Oxford) ; 20192019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31819989

RESUMO

Therapeutic vaccines represent a promising immunotherapeutic modality against cancer. Discovery and validation of antigens is the key to develop effective anti-cancer vaccines. Neoantigens, arising from somatic mutations in individual cancers, are considered as ideal cancer vaccine targets because of their immunogenicity and lack of expression in normal tissues. However, only few databases support convenient access to these neoantigens for use in vaccines. To address this gap, we developed a web-accessible database, called NeoPeptide, which contains most of the important characteristics of neoantigens (such as mutation site, subunit sequence, major histocompatibility complex restriction) derived from published literature and other immunological resources. NeoPeptide also provides links to resources for further characterization of the novel features of these neoantigens. NeoPeptide will be regularly updated with newly identified and published neoantigens. Our work will help researchers in identifying neoantigens in different cancers and hasten the search for appropriate cancer vaccine candidates.

9.
Front Immunol ; 10: 2664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798590

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy is highly effective in the treatment of B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoma, providing alternative therapeutic options for patients who failed to respond to conventional treatment or relapse. Moreover, it can bridge other therapeutic strategies and greatly improve patient prognosis, with broad applicable prospects. Even so, 30-60% patients relapse after treatment, probably due to persistence of CAR T-cells and escape or downregulation of CD19 antigen, which is a great challenge for disease control. Therefore, understanding the mechanisms that underlie post-CAR relapse and establishing corresponding prevention and treatment strategies is important. Herein, we discuss post-CAR relapse from the aspects of CD19-positive and CD19-negative and provide some reasonable prevention and treatment strategies.

10.
Animals (Basel) ; 9(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810299

RESUMO

Mutations are heritable changes at the base level of genomic DNA. Furthermore, mutations lead to genetic polymorphisms and may alter animal growth phenotypes. Our previous study found that mutations in the bovine Actin-like protein 8 (ACTL8) gene may be involved in muscle growth and development. This study explored several mutations of the ACTL8 gene and their influence on body size in Chinese beef cattle, as well as tested the tissue expression profile of the ACTL8 gene in Qinchuan cattle at different ages. Five single nucleotide polymorphisms (SNPs) (including one synonymous mutation (c.2135552895G > A)) and two insertion/deletion polymorphisms (indels) were identified in the ACTL8 gene from 1138 cattle by DNA-seq, RFLP and other methods. Then, the expression profile of the ACTL8 gene in Qinchuan cattle showed that it was expressed in heart, spleen, lung, liver, muscle, and fat tissues. Moreover, the expression level of ACTL8 was increased with cattle growth (p < 0.01). The ACTL8 mRNA expression level in kidney and muscle tissues was the highest in the calves, while lowest in the fetal stage. Overall, we showed that the mutations could act as markers in beef molecular breeding and selection of the growth traits of cattle.

11.
Exp Cell Res ; : 111801, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31877304

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoimmune-mediated platelet destruction and impaired platelet production, which can lead to an increased risk of bleeding. The clinical management of ITP currently remains a challenge for hematologists. We explored the role of interleukin-9 (IL-9) in the treatment of CD41-induced ITP, and investigated its underlying mechanisms in a CD41-induced ITP mouse model. IL-9 treatment increased the numbers of mature megakaryocytes (CD41+CD42d+) and CD41+Sca-1+ cells in the bone marrow in these model mice, while IL-9 receptor (IL-9R) small interfering RNA (siRNA) inhibited the process. Moreover, phosphorylated signal transducer and activator of transcription 5 (STAT5), as a downstream molecule of IL-9R, was increased after IL-9 treatment. We next investigated the source of IL-9 in bone marrow, osteoblasts produced the highest level of IL-9. These results confirmed that IL-9 could prevent CD41-induced ITP in BALB/c mice by regulating osteoblasts and activating IL-9R/STAT5 signaling in megakaryocytes, thus providing further evidence for IL-9 as a promising therapeutic agent for the treatment of ITP.

12.
Emerg Microbes Infect ; 8(1): 1584-1592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682199

RESUMO

The genetic and/or antigenic differences between street rabies virus (RABV) and vaccine strains could potentially affect effectiveness of rabies vaccines. As such, it is important to continue monitoring the glycoprotein (G) of the street isolates. All RABVG sequences in public database were retrieved and analysed. Using a pseudovirus system, we investigated 99 naturally occurring mutants for their reactivities to well-characterized neutralizing monoclonal antibodies (mAbs) and vaccine-induced antisera. A divergence in G sequences was found between vaccine strains and recent street isolates, with mutants demonstrating resistance to neutralizing mAbs and vaccine-induced antibodies. Moreover, antigenic variants were observed in a wide range of animal hosts and geographic locations, with most of them emerging since 2010. As the number of antigenic variants has increased in recent years, close monitoring on street isolates should be strengthened.

13.
Neural Netw ; 122: 253-272, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726331

RESUMO

Artificial neural networks have been used as a powerful processing tool in various areas such as pattern recognition, control, robotics, and bioinformatics. Their wide applicability has encouraged researchers to improve artificial neural networks by investigating the biological brain. Neurological research has significantly progressed in recent years and continues to reveal new characteristics of biological neurons. New technologies can now capture temporal changes in the internal activity of the brain in more detail and help clarify the relationship between brain activity and the perception of a given stimulus. This new knowledge has led to a new type of artificial neural network, the Spiking Neural Network (SNN), that draws more faithfully on biological properties to provide higher processing abilities. A review of recent developments in learning of spiking neurons is presented in this paper. First the biological background of SNN learning algorithms is reviewed. The important elements of a learning algorithm such as the neuron model, synaptic plasticity, information encoding and SNN topologies are then presented. Then, a critical review of the state-of-the-art learning algorithms for SNNs using single and multiple spikes is presented. Additionally, deep spiking neural networks are reviewed, and challenges and opportunities in the SNN field are discussed.

14.
Int J Biol Macromol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730960

RESUMO

Xyloglucan endotransglycosylase/hydrolase (XTH) belongs to the GH16 subfamily of the glycoside hydrolases of carbohydrate active enzymes and plays an important role in the structure and function of plant cell walls. In this study, 11 members of the XTH gene family were cloned from Populus tomentosa. A bioinformatics analysis revealed that 11 PtoXTHs could be classified into three groups, where PtoXTH27 and PtoXTH34 were most likely to exhibit XTH activity. Biochemical analyses of purified PtoXTHs demonstrated that PtoXTH27 and PtoXTH34 had detectable xyloglucan endotransglucosylase (XET) activity, while the others did not exhibit XET or XEH activity. Moreover, enzymatic assays revealed that the optimum reaction temperature of both PtoXTH27 and PtoXTH34 was 37 °C, while their optimum pH values differed, such that PtoXTH27 was 6.0 and PtoXTH34 was 5.0. Enzyme kinetic parameters indicated that PtoXTH34 had higher affinity for the receptor substrate, XXXG, implying that PtoXTH34 and PtoXTH27 in plants have different substrate structure specificity. Finally, heterologous expression of XTH significantly increased intracellular total sugar content and osmotolerance of yeast cells, indicating that PtoXTH27 and PtoXTH34 are potentially involved in osmotic stress responses. These results clearly demonstrate the enzymatic characteristics and putative role of XTH in osmotic stress responses.

15.
Materials (Basel) ; 12(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731493

RESUMO

In this study, the influence of rotary-die equal channel angular pressing (RD-ECAP) processing on the mechanical properties and rolling formability of AZ91 alloys was investigated. The as-cast and pre-homogenized AZ91 alloys were pre-processed by RD-ECAP for 16 passes at 573 K and subjected to post-ECAP rolling at 573 K with a rolling speed of 10 m/min. The microstructure and deformation characteristics of the AZ91 alloys were characterized. Results demonstrated that fine-grained AZ91 alloys with improved strength and ductility were obtained via the high-pass RD-ECAP processing, indicating a good plastic formability. The ECAP-ed alloys were easily rolled at 573 K from 4.5 mm to 1.1 mm in thickness without edge cracking. After rolling, heterogeneous grain structures were observed with large numbers of twins and shear bands that created strong basal textures. The rolled AZ91 alloys exhibited higher tensile strength and appropriate elongation. The post-ECAP rolling was successfully used in the high productivity of AZ91 rolled plates with good mechanical properties.

16.
Int J Biol Macromol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759005

RESUMO

It is widely accepted that regulating microbiome could improve human health. We previously observed apple polysaccharide (AP) reversed high-fat-induced microbial dysbiosis, but the mechanism remains to be elucidated. In this study, the function of AP in vitro was evaluated in Bifidobacterium longum (B. longum) and Lactobacillus rhamnosus (L. rhamnosus). The effects of AP on the composition of fecal bacteria of normal SD rats were investigated by qPCR, TA cloning and 16S sequencing. 0.125-2% AP showed no significant effect on the growth of B. longum and L. rhamnosus. DNA concentration of fecal bacteria cultured with 1% AP was significantly higher than that of control group. qPCR revealed that the number of Bifidobacterium and Lactobacillus in fecal flora incubated by 1% AP was significantly higher than that of control group. Three strains of escherichia coli (E. coli) in fecal bacteria were screened out and analyzed. AP can be utilized by one E. coli and the metabolic products of AP could enhance the proliferation of B. longum. These data suggest that AP could promote the growth of B. longum indirectly, and provide another basis to understand the health care function of apple.

17.
Plants (Basel) ; 8(10)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623210

RESUMO

Watermelon (Citrullus lanatus (Thunb.) Matsum. &Nakai) is an economic crop, which is widely cultivated around the world. The ploidy study of watermelon has an important role in field breeding and production, therefore, timely and convenient ploidy detection is necessary to accelerate its application. Traditionally, the ploidy of watermelon was determined by a series of time-consuming, expensive, and less efficient methods. In this study, we developed a more efficient method to simplify and accelerate the polyploidy identification in watermelons. We first confirmed the ploidy of watermelon by traditional tetraploid morphological features and well-established flow cytometry (FCM). Then we developed a reliable real-time quantitative PCR (qPCR) technique by quantifying the highly conserved 5S rDNA sequence and its copy numbers. This technique requires less sample collection and has comparable accuracy to FCM, it accelerates the analysis process and provides a new method for the identification of polyploidy of watermelon.

18.
Am J Cancer Res ; 9(8): 1622-1634, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497346

RESUMO

Epidermal growth factor receptor pathway substrate 8 (EPS8), which acts as an oncoprotein in various carcinomas, is associated with tumor progression. However, its impact on multiple myeloma (MM) has not been determined. Here, we investigate the role of EPS8 in MM and consider the potential of EPS8 as an anti-MM target. We confirmed overexpression of EPS8 in MM cells compared with plasma cells derived from healthy volunteers. Knockdown of EPS8 significantly abrogated MM cell survival, migration and invasion. Moreover, depletion of EPS8 overcomes drug resistance. TNFα or bone marrow stromal cell culture supernatants induce EPS8, which is blocked by the IKKß inhibitor MLN120B, suggesting that EPS8 is regulated by NF-κB signaling in MM cells. Mithramycin (MTM), a selective EPS8 inhibitor, suppressed MM cell proliferation and exerted potent anti-MM activity in xenograft tumor models. A synergistic effect of MTM and bortezomib (BTZ) was also observed in vitro and in vivo. Mechanistically, treatment of MM cells with MTM reduced the expression of EPS8 and related pathways. Additionally, the EPS8-knockdown phenotype can be rescued by shRNA-resistant EPS8. Taken together, we describe overexpression of EPS8 in MM by highlighting its role as a potential target and reveal therapeutic targeting of EPS8 by MTM as a novel therapy for MM.

20.
Cancer Biother Radiopharm ; 34(10): 614-620, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560562

RESUMO

Objective: To explore the role of diffusional kurtosis imaging (DKI) in evaluating the efficacy of transcatheter arterial chemoembolization (TACE) in patients with liver cancer. Materials and Methods: A total of 54 patients with primary liver cancer underwent TACE were selected as the study subjects. Magnetic resonance imaging and DKI scans were carried out before and after TACE, and the relevant parameters were analyzed. Results: Compared with those before TACE, the values of radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) of tumor tissues in the patients after TACE were significantly increased, whereas the values of axial kurtosis (Ka), fractional anisotropy of kurtosis (FAk), hepatic blood volume (HBV), hepatic blood flow (HBF), and hepatic artery perfusion (HAP) were notably decreased (p < 0.05). There were no significant changes regarding FA, radial kurtosis (Kr), mean kurtosis (MK), hepatic arterial fracture (HAF), permeability-surface area product (PS), mean transit time (MTT), and portal vein perfusion (PVP) (p > 0.05). The differences in apparent diffusion coefficients (ADCs) of different liver cancer tissues in patients under different b values after operation were statistically significant, and the ADC values of liver cancer tissues were evidently higher than those of other tumor tissues (p < 0.05). Conclusion: DKI is characterized with advantages such as fastness, simpleness, high resolution, and impregnability of the density of lipiodol. It can not only directly reflect the changes in blood perfusion at the lesion but also accurately and efficiently evaluate the remnants, necrosis, and recurrence of tumor tissues based on changes in ADC under different b values. It provides certain clinical assistance for the evaluation of the efficacy before and after TACE.

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