A Zn-MOF-based mixed matrix membrane as an ultrastable luminescent sensor for selective and visual detection of antibiotics and pesticides in food samples.

The detection of antibiotics and pesticides are of great significance since their residues threaten the health of human beings by accumulation. However, most traditional solid chemical sensors are suffer from the limitations of low sensitivity and economic practicability because of the aggregating nature and unstable of solid sensors. Herein, a new luminescent sensor 1@PMMA (1, [(ZnL)·H2O]n (H2L = 5-(4-(pyridin-4-yl)benzamido)benzene-1,3-dioic acid); PMMA = poly(methyl methacrylate)) was successfully prepared. Notably, the polymer matrix provided the chemical protection for MOF particles. The as fabricated 1@PMMA was stable in milk, honey and egg as well as exhibited strong blue emission under ultraviolet light irradiation, which can act as luminescent probe for detecting antibiotics and pesticides. More interestingly, 1@PMMA exhibited visual, real-time and recyclable detection of antibiotics ornidazole (ODZ) and pesticides 2,6-dichloro-4-nitrobenzenamine (DCN) in real food samples. This work shows that the luminescent MOF-based mixed matrix membranes could be applied as good candidates for sensing analytes in practical application.

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

BACKGROUND: The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). METHODS: A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. RESULTS: In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. CONCLUSIONS: The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

[Application of modified V-Y advancement flap for reconstruction of facial defect].

Objective:To investigate the clinical effect of modified V-Y advancement flap for reconstruction of facial skin defect. Methods:Thirty-eight patients with facial skin tumors underwent individual tumor resection according to pathological type and lesion depth. Based on the defect site and size, appropriate V-Y advancement flap was designed to reconstruct the skin defect in one stage. There were 9 cases of classic subcutaneous tissue pedicle V-Y advancement flap, 24 cases of modified subcutaneous tissue pedicle V-Y advancement flap and 5 cases of perforated V-Y advancement flap in our study. Results:Among the 38 patients, 34 cases had primary healing. Two cases developed necrosis at the edge of the flap and healed after debridement. Local infection occurred in 2 cases, which healed after short-term dressing change. Postoperative mild eyelid ectropion occurred in 2 cases and oral horn displacement in 1 case. The patients were followed up for 6-36 months postoperatively, and the function and appearance recovered well. One case had local recurrence and 3 cases had parotid lymph node metastasis, which were removed again and supplemented with radiotherapy. Conclusion:The improved design of V-Y advancement flap can enlarge the scope of facial defect reconstruction, and achieve good appearance and function.

Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/ß-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma.

Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/ß-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/ß-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.

Elevated O-GlcNAcylation Promotes Malignant Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Stabilizing Nrf2 through Regulation of the PI3K/Akt Pathway.

BACKGROUND AND PURPOSE: O-GlcNAcylation is a significant protein posttranslational modification with O-linked ß-N-acetylglucosamine (GlcNAc) for intracellular signaling. Elevated O-GlcNAcylation contributes to cell proliferation, cell migration, cell apoptosis and signal transduction in various cancers. However, the expression level and functional role of O-GlcNAcylation in Hypopharyngeal Squamous Cell Carcinoma (HSCC) is not clearly elucidated. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a master transcriptional factor that has been found to be aberrantly activated in HSCC. Here, we provide a molecular rationale between O-GlcNAcylation and Nrf2 in HSCC patients. METHODS: The protein levels of O-GlcNAcylation and Nrf2 in HSCC tissues were detected by immunohistochemistry technique and western blot analysis. Then, O-GlcNAcylation knockdown HSCC cells were applied in this study. Cell proliferation was detected by CCK8, colony-forming analysis, and cell cycle assays. Cell migration and invasion ability was evaluated by transwell assays. Cell apoptosis was measured by TUNEL analysis. RESULTS: O-GlcNAcylation was obviously up-regulated in HSCC tissues, which correlated with tumor size and lymph node metastasis. In addition, the protein level of Nrf2 was found to positively correlate with the expression of O-GlcNAcylation both in vivo and in vitro. Knockdown of O-GlcNAcylation significantly inhibited HSCC cell growth, suppressed cell migration, and promoted cell apoptosis, whereas overexpression of Nrf2 reversed these phenotypes. Mechanismly, the upregulation of O-GlcNAcylation promoted the phosphorylation of Akt, leading to the stabilization of Nrf2; this could be attenuated by inhibition of the PI3K/Akt signaling pathway. CONCLUSION: Here, we provide a molecular association between O-GlcNAcylation and Nrf2 in HSCC patients, thus providing valuable therapeutic targets for the disease.

Transcriptome analysis of tongue cancer based on high­throughput sequencing.

Tongue cancer is one of the most common types of cancer, but its molecular etiology and pathogenesis remain unclear. The aim of the present study was to elucidate the pathogenesis of tongue cancer and investigate novel potential diagnostic and therapeutic targets. Four matched pairs of tongue cancer and paracancerous tissues were collected for RNA sequencing (RNA­Seq), and the differentially expressed genes were analyzed. The RNA­Seq data of tongue cancer tissues were further analyzed using bioinformatics and reverse transcription­quantitative PCR analysis. The sequenced reads were quantified and qualified in accordance with the analysis demands. The transcriptomes of the tongue cancer tissues and paired paracancerous tissues were analyzed, and 1,700 upregulated and 2,249 downregulated genes were identified. Gene Ontology analysis uncovered a significant enrichment in the terms associated with extracellular matrix (ECM) organization, cell adhesion and collagen catabolic processes. Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that these differentially expressed genes were mainly enriched in the focal adhesion pathway, ECM­receptor interaction pathway, phosphoinositide 3­kinase (PI3K)­Akt pathway, and cell adhesion molecules. Comprehensive analyses of the gene tree and pathway network revealed that the majority of cell cycle genes were upregulated, while the majority of the genes associated with intracellular response, cell adhesion and cell differentiation were downregulated. The ECM­receptor interaction, focal adhesion kinase (FAK) and PI3K­Akt pathways were closely associated with one another and held key positions in differential signaling pathways. The ECM­receptor, FAK and PI3K­Akt signaling pathways were found to synergistically promote tongue cancer occurrence and progression, and may serve as potential diagnostic and therapeutic targets for this type of cancer.

MiR-143-3p suppresses cell proliferation, migration, and invasion by targeting Melanoma-Associated Antigen A9 in laryngeal squamous cell carcinoma.

Previously we found that melanoma-associated antigen-A9 (MAGE-A9) was a significantly upregulated biomarker in laryngeal squamous cell carcinoma (LSCC). A high expression of MAGE-A9 indicates an unfavorable survival outcome, and the MAGE-A9 expression level is an independent prognostic factor of LSCC. To explore the mechanism of MAGE-A9 upregulation, several predicted regulatory microRNAs were screened and validated in LSCC cells. In the current study, we found that miR-143-3p (MAGE-A9 related miRNAs) expression levels correlated negatively with the MAGE-A9 protein expression in LSCC tissues. Dual-luciferase reporter assays and Western blot analysis revealed MAGE-A9 to be a direct target of miR-143-3p. Furthermore, a series of in vitro gain- and loss-of-function assays revealed that miR-143-3p inhibited LSCC cell proliferation, migration, and invasion. Also, miR-143-3p suppressed LSCC tumorigenesis in vivo. These effects were clinically relevant, as a lower expression of miR-143-3p occurred in severer clinical stages and represented poor overall survival in patients with LSCC. Taken together, these results suggest that downregulation of miR-143-3p contributes to tumor progression through upregulation of MAGE-A9. The expression level of these two key molecules maintained LSCC progression, thus, highlighting the potential of miR-143-3p as a therapeutic target for human LSCC.

Role of natural killer cells in liver transplantation treatment of liver cancer.

Liver cancer caused by diet or life style is a significant public health problem. Liver transplantation (LT) is a commonly used method of treatment for the liver cancer. The present study aimed to determine whether assessing the net state of natural killer (NK) cell function following LT distinguishes patients at risk for transplantation rejection. A total of 53 patients were involved; all underwent LT for hepatocellular carcinoma with (n=13) or without (n=40) transplantation rejection. The density of interferon-γ (IFN-γ) in blood serum was examined and patients were divided into two groups: Higher (H) and lower (L), on the basis of IFN-γ density. The percentage of NK cells and their producing cytokines was detected using fluorescence-activated cell sorting in peripheral blood and liver samples. As evaluation indexes of liver function, aspartate transaminase (AST) and alanine transaminase (ALT) were detected in blood serum. NK cell activation of the H-group was observed to be higher than the L-group, specifically the expression of NK group 2D, cluster of differentiation 69 and IFN-γ were higher than the L-group. The H-group exhibited a higher level of AST and ALT, which indicates the potential for acute transplantation rejection. The results of the present study indicate that NK cells and NK-derived IFN-γ serve an important function in regulating the rejection of LT and tumor metastasis in response to LT.

The prognostic implications of growth-related gene product ß in laryngeal squamous cell carcinoma.

Growth-related gene product ß (GROß) is an angiogenic chemokine that belongs to the CXC chemokine family, and a number of studies have suggested that GROß is associated with tumor development and progression. However, a number of studies have investigated the association between GROß expression and the clinical attributes of laryngeal squamous cell carcinoma (LSCC). In the present study, one-step quantitative polymerase chain reaction and immunohistochemistry analysis were used to detect GROß expression and evaluate the association between its expression and the clinicopathological characteristics of LSCC. The results demonstrated that the GROß mRNA and protein expression levels were significantly increased in LSCC compared with the corresponding non-cancerous tissues. GROß protein expression in LSCC was associated with tumor-node-metastasis stage, lymph node metastasis and histopathological grade. The Kaplan-Meier method and Cox multi-factor analysis indicated that high GROß expression, lymph node metastasis and histopathological grade were significantly associated with poor survival of patients with LSCC. These data indicated that GROß may be a novel prognostic biomarker of LSCC.

LTBP2 is a prognostic marker in head and neck squamous cell carcinoma.

Latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) belongs to the fibrillin/LTBP extracellular matrix glycoprotein superfamily. It plays vital roles in tumorigenesis through regulating TGFß activity, elastogenesis and maintenance of the extracellular matrix (ECM) structure. In this study, we determined the expression levels of LTBP2 mRNA and protein in head and neck squamous cell carcinoma (HNSCC) tissues and adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. LTBP2 protein levels in cancer tissues were correlated with HNSCC patients' clinical characteristics and overall survival. Both LTBP2 mRNA and protein levels were significantly higher in HNSCC tissues than in adjacent normal tissues. High LTBP2 protein level was associated with lymph node metastasis and higher pTNM stages. High LTBP2 protein level is an independent prognostic marker in HNSCC. Our data suggest that LTBP2 acts as an oncogene in HNSCC development and progression. Detection of LTBP2 expression could be a useful prognosis marker and targeting LTBP2 may represent a novel strategy for cancer treatment through regulating activities of TGFß.

[Necessity of central lymph node dissection in management of papillary thyroid microcarcinoma].

OBJECTIVE: The objective of this study was to identify the risk factors for central lymph node metastasis (CLNM) of papillary thyroid microcarcinoma(PTMC) and to explore the necessity of central lymph node dissection (CLND). METHOD: Clinical data of 85 patients with PTMC, who had undergone surgical treatment between January 2004 and May 2012, were retrospected. Risk factors for CLNM were identified by univariate analysis and multivariate analysis,which can provide the basis for elective performance of CLND. RESULT: Of 85 patients,66 patients underwent ipsilateral CLND,while 19 patients received bilateral CLND. Concurrent cervical lymph node dissection was performed in 3 patients. The incidence of central and cervical lymph node metastasis was 38.8% and 3.53%, respectively. Univariate analysis showed that CLNM was correlated with tumor size > 5 mm, extrathyroidal extension, multifocality, bilaterality and intraoperatively suspected lymph node, but not related to gender and age. Upon multivariate analysis, tumor size > 5 mm (OR = 3.862, P < 0.05) and extrathyroidal extension (OR = 3.885, P < 0.05) were independent risk factors for CLNM. CONCLUSION: Patients presenting tumor size > 5 mm and/or extrathyroidal extension may have an increased risk of central lymph node metastasis,and it is necessary to perform central lymph node dissection for them.

Treatment of nanowaste via fast crystal growth: with recycling of nano-SnO2 from electroplating sludge as a study case.

The treatment of industrial sludge containing amorphous/nanophase metal oxides or hydroxides is one of the vital issues in hazardous waste disposal. In this work, we developed a strategy to recycle nano-SnO(2) from tinplate electroplating sludge. It revealed that the major components of this sludge were acid soluble Sn and Fe amorphous phases. By introducing NaOH as a mineralizer, a fast growth of amorphous Sn compound into acid-insoluble SnO(2) nanowires was achieved selectively. Thus, the as-formed nano-SnO(2) could be recycled via dissolving other solid compositions in the sludge by using acid. The role of NaOH on accelerating both the Oriented Attachment (OA) and Ostwald Ripening (OR) growth of SnO(2) was discussed, which was regarded as a critical factor for treating the sludge. A pilot-scale experiment was conducted to treat 2.3 kg original sludge and the recycling of about 90 g nano-SnO(2) was achieved. We anticipate this work can provide a good example for the recycling of valuable metals from industrial sludge containing fine metal oxides or hydroxides.