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A multi-enzyme-like activity exhibiting nanozyme hydrogel with oxidase and catalase-like activity was designed for wound healing, which exhibited excellent antibacterial performance. The catalase-like activity of the nanozyme provides adequate O2 for hypoxia abatement.

The schematic representation of the colorimetric sensors for glyphosate detection.

Methylmercury (MeHg

(1) To identify improvements when bulk compressive creep testing of dental resin composite materials to reduce the sensitivity to the surface morphology and parallelism of specimens, to generate more accurate strain (displacement) measurement values. (2) To investigate the effect of loading rate on the creep and recovery behavior under bulk compressive creep test.Cylindrical composite resin specimens were subjected to bulk compressive creep test with conventional and modified methodology (with/without introduction of stainless steel hemisphere and preload process). Furthermore, specimens undertook different loading rates ranging from 1 N/s to 50 N/s. Maximum deformation, creep deformation, permanent set as well as percentage of recovery during the creep and recovery procedure were compared, and surface topography changes before and after preload process was evaluated by laser scanning confocal. Burgers model was used to investigate the effect of improvements to each part of viscoelastic deformation of resin specimens.(1) The influence of surface evenness of resin specimens could be reduced by addition of preload process before the bulk compressive creep test resulting in significantly decreased permanent set (p = 0.002), and increased recovery to 91.7 % (p 0.001). While the standard deviation of maximum deformation, permanent set and percentage of recovery had the smallest values when hemisphere was introduced to loading chain. (2) With increasing loading rate of bulk compressive creep tests, creep deformation increased and this trend became statistically significant when the loading rate reached 50 N/s.The accuracy of deformation measurement during bulk compressive creep test could be improved by means of introducing stainless steel hemisphere to the loading chain, and adding preload process to loading protocol.

In this paper, a hydrophobic substrate as concentrators including an inner layer of polytetrafluoroethylene (PTFE) and an outer layer covered a thin layer of perfluoropolyether (PFPE) was constructed to achieve a higher sensitivity for acetamiprid (AC) SERS detection. The condensation effect of the PTFE-PFPE hydrophobic substrate-induced aggregation of gold nanoparticles (Au NPs) result ''hot spots'' for SERS. The hydrophobic substrate is better reproducibility (RSD 5%) compared with that on a conventional silicon wafer. A further application of the hydrophobic substrate was demonstrated by the detection of AC in tea samples within a detection range of 0.03 mg/L to 3 mg/L. The hydrophobic substrate eliminates the problem of solution diffusion to avoid the "coffee ring" effect (When a droplet adheres to a solid surface, the suspended molecular particles usually deposit on the edge of the droplet to form a ring).

Single-atom nanozymes (SAzymes) show distinct advantages in catalytic activity and selectivity owing to their stability and special characteristic of maximum atomic utilization. Inspired by the structure of natural horseradish peroxidase (HRP), we developed a simple method for specific determination of both propyl gallate (PG) and formaldehyde (HCHO) by utilizing the intrinsic peroxidase mimics activity of hemin (hem) loaded Zn-nitrogen-carbon single-atom nanozymes (Zn-N-C@hem SAzymes). Zn-N-C@hem was prepared via a salt-template strategy and self-assembly, where hemin exhibits enhancing peroxidase-like activity can catalyze oxidation of colorless PG to yellow product. Upon introduction of HCHO into Zn-N-C@hem/PG system, complete suppression of PG oxidation was showed, resulting in distinguished decrease in absorbance. The colorimetric sensors of PG and HCHO based on Zn-N-C@hem/PG were developed at their respective linear range of concentration 1.25-200 mg/kg and 5-250 mg/kg. The practicability of the rapid analysis of PG and HCHO in food samples has been verified with reliable results.

An Au-based nanozyme composite (AuNPs/Cu,I) was constructed by using Cu,I-doped carbon dots (Cu,I-CDs) as the reducing agent as well as the nanozyme. Notably, AuNPs/Cu,I nanozyme not only possessed the intrinsic activity of mimicking enzymes of superoxide dismutase, peroxidase, and catalase at different conditions but was also employed as surface-enhanced Raman spectroscopy (SERS) enhancer. The combination of Cu,I-CDs and AuNPs promoted the electron transferability, leading to increased peroxidase-like activity and superoxide-like activity. Compared to the individual Cu,I-CDs and AuNPs nanozyme, the AuNPs/Cu,I composite demonstrated promising peroxidase-like activity by transferring electrons instead of generating OH. Interestingly, the multienzyme-like activity of AuNPs/Cu,I nanozyme could be finely tuned by changing the composition of Cu

Background Oral submucous fibrosis (OSF) is a potentially malignant lesion characterized by epithelial-mesenchymal transition (EMT). Bone morphogenetic protein 4 (BMP4) promotes EMT in fibrotic diseases, but the underlying mechanisms and its potential role in OSF are unclear. This study investigates whether BMP4 plays a role in the pathogenesis of OSF and explores the underlying mechanisms. Methods The expression of BMP4 and the EMT proteins E-cadherin and vimentin was investigated in OSF specimens by immunohistochemical staining. Pearson's correlation analysis was conducted to explore the correlation between BMP4 and the EMT markers. Western blotting and RT-PCR assays were used to analyze the effect of arecoline (a known EMT-promoting pathogenic factor in OSF) on BMP4 and identify the transcription factor involved. Confocal microscopy was used to observe the intracellular sublocalization of the identified transcription factor, Yes-associated protein 1 (YAP1). Finally, siRNA silencing of BMP4 was used to determine its effect on YAP1 activation and arecoline-induced EMT. Results BMP4 is overexpressed in OSF and plays a role in EMT, as its expression correlates with the expression of E-cadherin and vimentin. Arecoline induces BMP4 expression via the activation of YAP1 (through its nuclear translocation). Furthermore, the YAP1/BMP4 mechanism is the main molecular event in arecoline-induced EMT, as knockdown of BMP4 expression affects expression of the EMT markers and inhibits extracellular matrix accumulation. Conclusions Arecoline induces EMT in OSF via the YAP1/BMP4 pathway. Thus, BMP4 could be considered as a potential therapeutic target for the treatment of OSF.

Oral submucous fibrosis (OSF) is a potentially malignant disorder. Current studies have shown that chewing areca nut is considered the main cause of OSF, and endothelial-mesenchymal transformation (EndMT) participates in the occurrence and development of the fibrotic lesion. However, the specific molecular mechanisms and treatments remain unclear. Here, we report the mechanism of arecoline-induced EndMT and the importance of this mechanism in OSF, and we also identify potential therapeutics for decreasing OSF incidence. We demonstrate the overexpression of Yes-associated protein (YAP) in human samples and that it was significantly associated with OSF pathologic stage. Arecoline activated YAP by increasing reactive oxygen species levels and inducing the PERK pathway (eukaryotic translation initiation factor 2 alpha kinase 3), resulting in the initiation of EndMT and leading to OSF. Verteporfin, a YAP–TEA domain pathway inhibitor, suppressed EndMT and decreased collagen accumulation, resulting in the alleviation of OSF in mice. These data indicate that arecoline regulates the activity of YAP and highlight an alternative method for treating OSF.

Background: Hepatitis B virus X-interacting protein (HBXIP) is associated with a variety of tumors. The purpose of this study was to investigate the clinicopathological significance of HBXIP expression in pancreatic ductal adenocarcinoma (PDAC) and to explore its potential as a biomarker for PDAC. Methods: Immunohistochemical (IHC) staining was performed on 126 PDAC tissues, 36 paraneoplastic tissues and 22 normal pancreatic tissues. The relationship between high levels of HBXIP expression and pathological features of PDAC patients was evaluated by chi-squared values. Results:The positive rate of HBXIP protein in PDAC tissues was 85.7% (108/126), which was significantly higher than that of adjacent pancreatic tissue (41.7%, 15/36) and normal pancreas (18.2%, 4/22). In addition, strong positive expression of HBXIP was associated with tumor size, positive lymph node metastasis, clinical stage and 80-month overall survival. Patient's age, gender, degree of differentiation, Ki-67 expression index, and calcification were, however, not associated with high levels of HBXIP expression. Conclusions:We present association between HBXIP expression and the pathological features of patients with PDAC.

Various research groups have been paying huge attention to tune the metal states in metal–carbon hybrid materials. Herein, a mixed-valence copper-iodine co-doped carbon dots (Cu,I-CDs, Cu2+/Cu+/Cu0) were prepared through a one-step hydrothermal method, which displayed an intrinsic reduction performance under given conditions. Moreover, AuNPs/Cu,I-CDs composite was fabricated using Cu,I-CDs as reductant and stabilizer. Among them, the AuNPs/Cu,I-CDs composite exhibited the highest oxidase- and peroxidase-like activities, which was used for the colorimetric detection of tert-butyl hydroquinone (TBHQ), with the detection limits of 23.45 μg/kg. Interestingly, the catalytic oxidation of TBHQ to oxidized TBHQ (TQ) could be inhibited by formaldehyde (HCHO). Therefore, a colorimetric sensor for HCHO was developed with the detection limit 0.335 mg/L. The catalytic mechanism for TBHQ was investigated by employing scavengers of different reactive species, indicating the significant roles of •O2− in the catalytic process. Therefore, it is believed that the as-prepared AuNPs/Cu,I-CDs nanozyme has promising potential applications in the fields of biomedicine and food safety.

The study presents a spectrofluorimetric method for the determination of Cr(III) based on 2,3-diaminophenazine (DAP) as fluorescent nano sensor. With the peroxidase-mimicking activity of copper-doped carbon dots (Cu-CDs), colorless o-phenylenediamine (OPD) was oxidized to fluorescent DAP in the presence of H2O2 via generation of hydroxyl radicals. The Cr(III) was found to decrease the fluorescent intensity of the Cu-CDs-mediated OPD oxidation system. Cr(VI) species were reduced to Cr(III) by employing 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) as the reductant, and a novel spectrofluorimetric method for the highly sensitive detection of speciation Cr(VI) and Cr(III) was developed. The Cu-CDs nanozyme was prepared from ethylenediaminetetraacetic acid copper disodium salt (Na2[Cu (EDTA)]) by one-step pyrolysis method. Under optimal conditions, the fluorescence intensity of DAP is linearly proportional to the Cr(III) ion concentration in the range of 5 × 10−6 to 1.5 × 10−4 mol L−1 and the detection limit is 1.2 × 10−7 mol L−1. The method has a good anti-interference performance against some metal ions, such as, Hg2+, Co2+, Cu2+, Mg2+, Ba2+, K+, Mn2+, Ni2+, Al3+, and Fe3+. The proposed method was successfully applied in the determination of Cr(VI) and Cr(III) in water samples.

Cdkn1c, a member of the Cip/Kip cyclin-dependent kinase inhibitor family, is critically involved in regulating cell cycle and cellular differentiation during development in mammals. However, the functional role of Cdkn1c and the underlying mechanisms by which Cdkn1c affects odontogenesis remain largely unknown. In our study, we found that Cdkn1c expression dynamically changes from embryonic day 11.5 (E11.5) to postnatal day 3 (P3), and exhibits tissue-specific expression profiles. Evaluation of CDKN1C protein by immunohistochemistry and western blot, revealed that CDKN1C protein expression peaks at P3 and then is reduced at P5 and P7. Interestingly, we observed that CDKN1C expression is higher in immature odontoblasts than preodontoblasts, is lower in mature odontoblasts, and is practically absent from ameloblasts. We evaluated cell cycle progression to further investigate the mechanisms underlying CDKN1C-mediated regulation of odontogenesis, and found that pRB, cyclin D1 and CDK2 expression decreased from P1 to P3, and reduced at P5 and P7. In addition, we observed increased methylation of KvDMR1 at P1 and P3, and reduced KvDMR1 methylation at P5 and P7. However, the methylation levels of Cdkn1c-sDMR were relatively low from P1 to P7. In summary, we demonstrated that Cdkn1c expression and methylation status may be involved in early postnatal tooth development through regulating the cell cycle inhibition activity of Cdkn1c. Notably, Cdkn1c expression and methylation may associate with cell cycle exit and differentiation of odontoblasts.

Background: Myocardial Infarction (MI), a kind of heart deficiency, is the main cause of death and disability. Autophagy, a metabolic process for the degradation of damaged proteins or organelles, is important for cardiac functions and regulated by several miRNAs including miRNA- 101. The aim of this research was to investigate the effects of miR-101 in myocardial infarctioninduced injury and the related mechanisms. Methods: MI model was induced by ligation of the left coronary artery. The in vitro model was established by hypoxia-induced H9c2 cells (rat myocardial cells). The overexpression of miR-101 was achieved by transfection. The expression of associated proteins was analyzed by Western blotting. The level of miR-101 was analyzed by reverse transcription-polymerase chain reaction (RTPCR). The target genes for miR-101 and the target sites were analyzed by TargetScan. Results: The results showed that miR-101 was decreased in MI mice (P Conclusion: This research suggested that miR-101 attenuated- MI-induced injury by targeting DDIT4 to regulate autophagy, which indicated that miR-101 or DDIT4 may be potential therapeutic targets for heart injury.

Background Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma with an unsatisfactory prognosis. The aim of this study was to identify potential prognostic mRNA biomarkers of OSCC based on analysis of The Cancer Genome Atlas (TCGA). Methods Expression profiles and clinical data of OSCC patients were collected from TCGA database. Univariate Cox analysis and the least absolute shrinkage and selection operator Cox (LASSO Cox) regression were used to primarily screen prognostic biomarkers. Then multivariate Cox analysis was performed to build a prognostic model based on the selected prognostic mRNAs. Nomograms were generated to predict the individual’s overall survival at 3 and 5 years. The model performance was assessed by the time-dependent receiver operating characteristic (ROC) curve and calibration plot in both training cohort and validation cohort (GSE41613 from NCBI GEO databases). In addition, machine learning was used to assess the importance of risk factors of OSCC. Finally, in order to explore the potential mechanisms of OSCC, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was completed. Results Three mRNAs (CLEC3B, C6 and CLCN1) were finally identified as a prognostic biomarker pattern. The risk score was imputed as: (−0.38602 × expression level of CLEC3B) + (−0.20632 × expression level of CLCN1) + (0.31541 × expression level of C6). In the TCGA training cohort, the area under the curve (AUC) was 0.705 and 0.711 for 3- and 5-year survival, respectively. In the validation cohort, AUC was 0.718 and 0.717 for 3- and 5-year survival. A satisfactory agreement between predictive values and observation values was demonstrated by the calibration curve in the probabilities of 3- and 5- year survival in both cohorts. Furthermore, machine learning identified the 3-mRNA signature as the most important risk factor to survival of OSCC. Neuroactive ligand-receptor interaction was most enriched mostly in KEGG pathway analysis. Conclusion A 3-mRNA signature (CLEC3B, C6 and CLCN1) successfully predicted the survival of OSCC patients in both training and test cohort. In addition, this signature was an independent and the most important risk factor of OSCC.

Background Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the understanding of the ceRNA network in tongue squamous cell carcinoma (TSCC) remains limited. Methods Expression profile data regarding mRNAs, miRNAs and lncRNAs as well as clinical information on 122 TSCC tissues and 15 normal controls from The Cancer Genome Atlas (TCGA) database were collected. We used the edgR package to identify differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) between TSCC samples and normal samples. In order to explore the functions of DEmRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Subsequently, a ceRNA network was established based on the identified DElncRNAs–DEmiRNAs and DEmiRNAs–DEmRNAs interactions. The RNAs within the ceRNA network were analyzed for their correlation with overall disease survival. Finally, lncRNAs were specifically analyzed for their correlation with clinical features in the included TSCC patient samples. Results A total of 1867 mRNAs, 828 lncRNAs and 81 miRNAs were identified as differentially expressed in TSCC tissues (—log 2fold change— ≥ 2; adjusted P value P P Conclusion Our study deepens the understanding of ceRNA network regulatory mechanisms in TSCC. Furthermore, we identified ten lncRNAs (PART1, LINC00261, AL163952.1, C2orf48, FAM87A, LINC00052, LINC00472, STEAP3-AS1, TSPEAR-AS1 and ERVH48-1) as novel, potential prognostic biomarkers and therapeutic targets for TSCC.

In this work, a spectrofluorimetric method combined with magnetic solid-phase extraction purification was utilized for the nicotine detection in shredded tobacco. The copper and nitrogen doped carbon dots (Cu-NCDs) with a high quantum yield (30%) was prepared via facile microwave method and used as fluorescent probe for nicotine assay. Fe3O4 nanoparticles were used to remove the coexisting substances in the tobaccos by physical adsorption. The Cu-NCDs showed two fluorescence emission peaks at 294 nm and at 580 nm under a single excitation wavelength of 270 nm, and could be obviously quenched by nicotine at the same time. Herein, highly sensitive detection of nicotine in shredded tobacco was developed. Under optimal conditions, the fluorescence intensity of Cu-NCDs was linearly proportional to the nicotine concentration in the range of 0.1 to 10 μg mL−1, with the detection limit of 0.01 μg mL−1. The combination of Fe3O4 adsorbent and fluorescent probe showed improved anti-interference performance in comparison to fluorescent probe alone. Based on results from the study, the method could be utilized as a fluorescent probe for the practical determination of nicotine.

Risk of bias summary: review authorsâ judgements about each risk of bias item for each included study. (DOCX 35 kb)

Sensitivity analysis. (DOCX 16 kb)

Search strategy used in PubMed/MEDLINE. (DOCX 14 kb)

Data extraction table of this network meta-analysis. (DOCX 16 kb)

Search strategy used in PubMed/MEDLINE. (DOCX 14 kb)

Sensitivity analysis for informative uniform distribution. (DOCX 24 kb)

Forest plot of changes in FPG. (DOCX 172 kb)

Sensitivity analysis of outcomes by excluding trials with a high risk of bias. (DOCX 148 kb)

Evaluation of model fit. (DOCX 14 kb)

Forest plot on the effect size of subgroups. (DOCX 688 kb)

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. (DOCX 342 kb)

Outcomes of studies included in the network meta-analysis. (DOCX 22 kb)

Background Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice. Methods We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane’s risk of bias tool was used to assess the risk of bias. Results Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI − 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11). Conclusion The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results. Electronic supplementary material The online version of this article (10.1186/s12903-019-0829-y) contains supplementary material, which is available to authorized users.