Neural Networks Based on Synthesized Training Data for the Automated Detection of Chemical Plumes in Passive Infrared Multispectral Images.

Automated detection of volatile organic compounds in the atmosphere can be achieved by applying pattern recognition analysis to passive infrared (IR) multispectral remote sensing data. However, obtaining analyte-active training data through field experiments is time-consuming and expensive. To address this issue, methodology has been developed for simulating radiance profiles acquired using a multispectral IR line-scanner mounted in a downward-looking position on a fixed-wing aircraft. The simulation strategy used Planck's radiation law and a radiometric model along with the laboratory spectrum of the target compound to compute the upwelling IR background radiance with the presence of the analyte within the instrumental field-of-view. By combining the simulated analyte-active radiances and field-collected analyte-inactive radiances, a synthetic training dataset was constructed. A backpropagation neural network was employed to build classifiers with the synthetic training dataset. Employing methanol as the target compound, the performance of the classifiers was evaluated with field-collected data from airborne surveys at two test fields.

Pattern recognition analysis of marine oil spills in airborne passive infrared multispectral remote sensing images.

Pattern recognition methodology was developed for the automated detection of marine oil spills in passive infrared multispectral remote sensing images. The images employed in this work were collected from the Deepwater Horizon oil spill accident in 2010. The imaging instrument for data collection was a downward-looking infrared line scanner equipped with eight optical bandpass filters in the spectral range of 8-12 µm on a fixed-wing aircraft. Oil slicks may show either positive or negative thermal contrast against the surrounding sea water, depending on the sun glint conditions or the oil thickness. Classifiers were developed separately to detect oil with different contrasts by the application of backpropagation neural networks to the preprocessed radiances. Preprocessing strategies included: (1) assembly of training data through k-means clustering analysis; (2) elimination of variation in radiance magnitudes by a customized temperature correction method; (3) removal of sun glint artifacts in images by polynomial correction; and (4) extraction of the most representative features as inputs for the neural networks by a subset selection approach. The classifiers designed to detect oil with positive and negative thermal contrast relative to water achieved overall classification accuracies of 88.7 and 92.2%, respectively. Composite classification images were generated by integrating classification scores produced by the two classifiers. The prediction performance of the classification system was demonstrated through its application to images not involved during the training of the networks.

HOTAIR/Sp1/miR-199a critically regulates cancer stemness and malignant progression of cutaneous squamous cell carcinoma.

The long non-coding RNA (lncRNA), HOX antisense intergenic RNA (HOTAIR) is a well-characterized oncogene in multiple human cancers, but not in cutaneous squamous cell carcinoma (CSCC). In this study, we focused on investigating the potential role of HOTAIR in stemness of CSCC. By measuring its expression using RT-qPCR in CSCC vs. normal tissues, as well as in CSCC cell lines A431 or SCC13, A431- or SCC13-derived CSCC stem cells (CSCSCs), and normal skin fibroblasts (HSFs), we detected higher expression of HOTAIR in CSCC than in normal tissues, in recurrent than in non-recurrent CSCC tissues, in CSCCs and CSCSCs than in HSFs, and particularly, in CSCSCs than in CSCCs. Kaplan-Meier analysis suggested that higher expression of HOTAIR was positively correlated with worse overall survival of CSCC patients. Functional assays on colony formation, EdU incorporation, sphere formation, western blot on stem-cell biomarkers, and in vivo models showed that HOTAIR was essential in maintaining multiple stem cell phenotypes of CSCSCs in vitro and in vivo xenograft growth as well as metastasis. Mechanistically, HOTAIR directly interacted with and up-regulated Sp1. Sp1 then induced DNMT1-mediated promoter methylation and direct transcriptional repression of miR-199a-5p. Targeting Sp1 or DNMT1 further boosted the in vivo anti-tumor and anti-metastasis activities of targeting HOTAIR. In conclusion, HOTAIR, by up-regulating Sp1 and targeting miR-199a, promotes stemness and progression of CSCC. Targeting HOTAIR, Sp1 or the underlying mechanisms may thus benefit CSCC treatment.

[Retracted] MicroRNA­18b inhibits the growth of malignant melanoma via inhibition of HIF­1α­mediated glycolysis.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Fig. 3, and western blotting assay data shown in Fig. 6F, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 471­479, 2016; DOI: 10.3892/or.2016.4824].

Knockdown of enhancer of rudimentary homolog expression attenuates proliferation, cell cycle and apoptosis of melanoma cells.

Early stage or localized melanoma can be surgically resected with satisfactory outcome, whereas advanced malignant melanoma responds to treatment poorly and has a negative prognosis even after surgery, radiotherapy and other comprehensive treatments. Gene therapy targeting various biological signaling pathways has become an increasingly popular area in melanoma research. However, for gene therapy success, it is important to reveal the molecular mechanisms of melanoma tumorigenesis and development. The present study examined the effects of downregulating enhancer of rudimentary homolog (ERH) expression on the proliferation, metastasis and cell cycle of melanoma cells. ERH expression levels in melanoma tissues and cells were determined. Then, ERH gene expression in melanoma cell lines was downregulated or overexpressed by the lentiviral RNA interference technique. Furthermore, we performed cell counting kit-8, clone formation, scratch, transwell migration, subcutaneous tumorigenesis and venous metastasis assays as well as carried out flow cytometry analysis to explore the effects of ERH expression on cell proliferation, cell cycle, apoptosis and metastasis. We found that ERH expression in melanoma tissues and cells was markedly higher than in normal melanin nevus. Suppressing ERH expression by RNA interference in melanoma A375, WM35 and SK28 cell lines inhibited their proliferation and induced cell apoptosis. The cell cycle was also found to be blocked in the G1 phase. However, the metastatic properties of melanoma cells in vitro and in vivo remained largely unaltered by ERH knockdown. Our results show that ERH expression is increased in melanoma. Meanwhile, the proliferation and cell cycle transformation abilities are impaired potentially by downregulating the ERH expression in melanoma cells. Therefore, targeting ERH might serve as a novel therapeutic approach for malignant melanoma.

Identification of differentially expressed proteins involved in fetal scarless wound healing using a rat model of cleft lip.

In early pregnancy, fetal skin wounds can heal quickly and undergo a transition period from scarless healing to scar formation. The aim of the present study was to identify potential biomarkers associated with scarless repair of cleft lips, in order to determine the intrinsic factors leading to scar formation in embryonic tissue. A stable model of cleft lip was established using microsurgery by constructing a wedge­shaped cleft lip­like defect in fetal rats at gestational age (GA) 16.5 and GA18.5. The GA16.5 and GA18.5 groups were used to model scarless healing and scar formation, respectively. The fetuses were returned to the uterus following surgery, then removed 72 h after the procedure. Macroscopic observation of the cleft defect and histological examination were carried out. Reverse transcription­quantitative (RT­q) PCR and parallel reaction monitoring (PRM) were used to detect mRNA and protein expression levels, respectively. The upper­left lip completely healed 72 h after surgery in the GA16.5 group of fetal rats. However, this was not the case in the GA18.5 group. Histological examination indicated new follicles visible under the epidermis of the scarless group (GA16.5). Scarring was visible on the upper­left cleft lip wound of the fetal rats in the GA18.5 group. The expression of some growth and pro­inflammatory factors, including TNF­α, were also different between two groups. Label­free quantification was used to identified differentially expressed proteins and five differentially expressed proteins (Smad4, Fabp5, S100a4, S100a8 and S100a9) were identified. The relative expression of these molecules at the mRNA and protein levels were measured using RT­qPCR and PRM. These molecules may represent potential biomarkers for the scarless repair of fetal rat cleft lip wounds.

Elevated LINC01550 induces the apoptosis and cell cycle arrest of melanoma.

Melanoma is a high-grade malignant subtype of human skin cancer with the highest mortality rate. Here we perform a bioinformatics analysis concerning human melanoma tissues by the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) platform. We found that lncRNA LINC01550 was significantly down-regulated in the melanoma tissues as compared to the normal tissues. The low expression of LINC01550 was tightly associated with shorter overall survival and disease-free survival of patients with melanoma. LINC01550 expression is negatively associated with tumor cell proliferation and invasion abilities in melanoma as evidenced by the single-cell RNA sequencing (scRNA-seq) databases. LINC01550-overexpressing vectors were transferred into melanoma cells (WM35 and WM451). Up-regulation of LINC01550 significantly inhibited proliferation and invasion abilities, as well as induced cell apoptosis and G1 and S phase arrest of the melanoma cells. In conclusion, overexpression of LINC01550 may serve as a potential therapeutic target for melanoma.

Gradient Mineralized and Porous Double-Network Hydrogel Effectively Induce the Differentiation of BMSCs into Osteochondral Tissue In Vitro for Potential Application in Cartilage Repair.

At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.

C16:0 ceramide effect on melanoma malignant behavior and glycolysis depends on its intracellular or exogenous location.

To investigate the role of C16:0 ceramide in melanoma metastatic behavior and glycolysis, five common long-chain ceramides (C16:0, C18:0, C20:0, C22:0, C24:0) were tested in melanocyte and melanoma cell lines by LC-MS. We then treated non-metastatic and metastatic melanoma cells with PDMP and exogenous C16:0 to explore their effects on proliferation, migration, and glycolysis. The long-chain ceramide was also analyzed by LC-MS after treatment. C16:0 ceramide showed the highest levels in melanocyte and melanoma cells, with all melanomas higher than melanocytes. PDMP inhibited malignant behavior and glycolysis in melanoma, and caused the accumulation of intracellular C16:0. Exogenous C16:0 promoted melanoma glycolysis, but not malignant behavior, and decreased intracellular C16:0. Finally, pyruvate kinase (PK), hexokinase (HK), and lactic acid dehydrogenase (LDH) activity, key enzymes in glycolysis, were altered after treatment with PDMP and exogenous C16:0.

MiR-199a-5p represses the stemness of cutaneous squamous cell carcinoma stem cells by targeting Sirt1 and CD44ICD cleavage signaling.

Tumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitro and in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8.

Studies on the treatment of melanoma with folate acid conjugated dextran and lauryl alcohol loaded with IMD0354.

Background: IMD-0354 is a kind of hydrophobic small molecule inhibitor of IKKß, which can effectively inhibit the NF-κB pathway. Besides, IMD-0354 can inhibit a variety of tumor cells in culture, but its poor water solubility and low utilization have limited its clinical application. Methods: In this study, IMD-0354 was synthesized through esterifying the folate acid (FA) conjugated dextran (Dex) as well as the lauryl alcohol (LA). Results:The particle (IMD/FA-Dex-LA) size was 212.13±10.62nm, the encapsulation efficiency was 89.27±6.51%, and the drug loading was 4.25±0.42%. Cell viability studies indicated that the IMD/FA-Dex-LA effectively inhibited survival of B16F10 cells in culture. Meanwhile, Western Blotting results showed that the nuclear transport of NF-κB was reduced after blocking the IKK pathway, which would thereby suppress melanoma cell division and proliferation. Moreover, subcutaneous tumor implantation experiment revealed that, the drug-loading complex had an obvious effect on suppressing melanoma cells. Findings of this study demonstrated that the IMD-0354 loaded FA-Dex-LA was more effective than IMD-0354 alone. Conclusion: In summary, FA-Dex-LA has been successfully synthesized in this study, which can serve as a carrier for hydrophobic drug. Further, it is believed the FA-Dex-LA can potentially applied in cancer treatment.

LncRNA TUG1 regulates FGF1 to enhance endothelial differentiation of adipose-derived stem cells by sponging miR-143.

Adipose-derived stem cells (ADSCs) have emerged as a cell source for regeneration medicine. ADSCs possess the capacity to differentiate into endothelial cells and serve an essential role in vascular development and function. LncRNA taurine upregulated gene 1 (TUG1) has recently been linked with angiogenesis in hepatoblastoma. However, the roles of TUG1 in endothelial differentiation of ADSCs remain unidentified. Human adipose-derived stem cells (hADSCs) were obtained and characterized by flow cytometry, Oil red O and Alizarin Red staining. HADSCs were maintained in the endothelial differentiation medium and the expressions of TUG1, miR-143, and FGF1 were examined by qRT-PCR. To assess endothelial differentiation, the expressions of CD31, von Willebrand factor (vWF), VE-cadherin were examined by Western blot analysis, qRT-PCR, and immunofluorescence. Tube formation in Matrigel was examined. The interactions between TUG1 and miR-143, miR-143 and FGF1 were validated by luciferase assays. During the endothelial differentiation process, TUG1 and FGF1 were upregulated, whereas miR-143 was downregulated. TUG1 overexpression downregulated miR-143, upregulated FGF1, CD31, vWF, and VE-cadherin, and enhanced capillary tube formation. Luciferase assays showed that TUG1 interacted with miR-143, and FGF1 was a direct target of miR-143. Furthermore, the enhancement of endothelial differentiation induced by TUG1 overexpression was abolished by miR-143 overexpression. Our findings implicated that lncRNA TUG1 promoted endothelial differentiation of ADSCs by regulating the miR-143/FGF1 axis.

MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis.

MicroRNAs (miRs) have been demonstrated to play critical roles in the development and progression of malignant melanoma (MM). However, the exact role and underlying mechanism of miR-18b in MM growth remains unclear. In the present study, real-time PCR data indicated that miR-18b was significantly downregulated in MM tissues compared to their matched adjacent non-tumor tissues. Low miR-18b expression was significantly associated with the tumor thickness and stage, although no significant association was observed between the miR-18b expression and the age, gender, or lymph node metastasis. Besides, miR-18b was also significantly downregulated in MM B16 and A375 cells compared to normal skin HACAT cells. Ectopic expression of miR-18b decreased the proliferation of A375 and B16 cells, while induced a remarkable cell cycle arrest at G1 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1α, a key regulator in glycolysis, was then identified as a target gene of miR-18b, and its expression was negatively mediated by miR-18b in A375 and B16 cells. Overexpression of HIF-1α rescued the suppressive effect of miR-18b on MM cell proliferation and glycolysis. In vivo study further showed that overexpression of miR-18b inhibited the MM growth as well as the tumor-related death, accompanied with HIF-1α downregulation. Taken together, the present study suggests that miR-18b inhibits the growth of MM cells in vitro and in vivo through directly targeting HIF-1α.

Identification of FLOT2 as a novel target for microRNA-34a in melanoma.

PURPOSE: To confirm whether flotillin 2 (FLOT2) is a direct target of miR-34a and miR-34a/FLOT2 pathway plays a key role in melanoma proliferation and metastasis. METHODS: First, miR-34a and FLOT2 expressions were both detected in human tissues and cell lines by qRT-PCR. Then, after transfection of mimics/inhibitor of miR-34a into melanoma cell lines, MTT, colony formation, scratch migration assays and transwell invasion assays were performed to evaluate the impact of miR-34a on cell proliferation and metastasis. Western blot, qRT-RCR and dual luciferase reporter gene assays were carried out to confirm whether FLOT2 is a direct target gene of miR-34a. In functional recovery experiments, proliferation and metastasis ability of WM35 and WM451 was tested after being co-transfected with miR-34a inhibitor/si-FLOT2 or miR-34a mimics/FLOT2 cDNA to confirm that FLOT2 is downregulated by miR-34a. RESULTS: The miR-34a significantly lower-expressed in metastasis melanoma tissues compared to in situ melanoma, nevi and normal skin whereas FLOT2 has an opposite trend. The level of miR-34a and FLOT2 in different melanoma cell lines was also tested and found that metastatic melanoma cell lines has lower miR-34a expression and higher FLOT2 expression compare to in situ melanoma cell line. MiR-34a overexpression profoundly inhibits WM451 cell proliferation and metastasis, whereas miR-34a reduction had a promoting effect to proliferation and metastasis of WM35. Results of Western blot, qRT-RCR and dual luciferase reporter gene assays revealed that FLOT2 is a direct target gene of miR-34a. Furthermore, overexpression/blockage of FLOT2 could attenuate effect of miR-34a overexpression/inhibition which indicated miR-34a suppresses melanoma biological behavior partially through FLOT2 inhibition. CONCLUSIONS: Our study confirmed that miR-34a is involved in the tumor inhibition of melanoma by directly targeting FLOT2 gene. This finding provides potential novel strategies for therapeutic interventions of melanoma.

Thrombocytopenia induces multiple intracranial hemorrhages in patients with severe burns: A review of 16 cases.

The aim of this study was to explore the etiology and diagnosis of multiple intracranial hemorrhages (ICHs) following severe burns, with a retrospective review of 16 cases of severe burns further complicated by multiple ICHs. Using cranial CT scans of the brains, we identified that all patients presented with low platelet counts and coagulation abnormalities prior to intracranial hemorrhaging. Following conventional treatment and various supporting treatments, five cases succumbed following a progressive reduction in blood platelet levels and the ICHs were cured in 11 cases following the restoration of normal platelet levels. We conclude that low platelet counts and coagulation abnormalities may cause multiple ICHs following severe burns and early diagnosis and treatment is the key to successful treatment.

Giant neurofibroma in the right lower limb of a 26-year-old woman: report of a case.

Neurofibromatosis (NF) is a genetically inherited, autosomal-dominant disease with an incidence of 1 in 3000 live births. There are two types of NF, NF 1 and NF 2, and NF 1 is the most common. This study reports on the diagnosis, treatment, and related family medical history of a rare case with NF-1 in the right lower limb.

Clinical features and pedigree report of a patient with giant neurofibroma.

Neurofibromatosis (NF) is a genetically inherited, autosomal-dominant disease with an incidence of 1/3,000 in live births. There are two types of NF, NF 1 and NF 2, and NF 1 is the most common type. This study reports on the diagnosis, treatment, and related family medical history of a rare case with NF-1 in the right lower leg.