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Background: The purpose of the current research was to investigate the biological roles of LINC00467 in inducing melanoma deterioration. Methods: Differential level of LINC00467 in melanoma tissues and its prognostic value were analyzed in GEPIA, which were further confirmed in clinical samples we collected. Regulatory effects of LINC00467 on proliferation, migration and invasion capacities of A375 and SKMEL1 cell lines were examined by a series of functional experiments. Potential downstream targets of LINC00467 were identified through dual-luciferase reporter assay, and their synergistic role in melanoma process was finally explored by rescue experiments. Results: LINC00467 was up-regulated in melanoma samples, but it did not have a prognostic potential in melanoma. LINC00467 has the capacities to stimulate proliferation, migration and invasion of A375 and SKMEL1 cell lines. The feedback loop LINC00467/miR-485-5p/PAK1 was identified, which was responsible for inducing melanoma deterioration. Conclusions: LINC00467 stimulates proliferation, migration and invasion capacities of melanoma via targeting miR-485-5p to upregulate PAK1, which provides potential targets for treatment of melanoma.

The C-test is a type of gap-filling test designed to efficiently measure second language proficiency. The typical C-test consists of several short paragraphs with the second half of every second word deleted. The words with deleted parts are considered as items nested within the corresponding paragraph. Given this testlet structure, it is commonly taken for granted that the C-test design may violate the local independence assumption. However, this assumption has not been fully investigated in the C-test research to date, including the evaluation of alternative psychometric models (i.e., unidimensional and multidimensional) to calibrate and score the C-test. This study addressed each of these issues using a large data set of responses to an English-language C-test. First, we examined the local item independence assumption via multidimensional item response theory (IRT) models, Yen’s Q3, and Jackknife Slope Index. Second, we evaluated several IRT models to determine optimal approaches to scoring the C-test. The results support an interpretation of unidimensionality for the C-test items within a paragraph, with only minor evidence of local item dependence. Furthermore, the two-parameter logistic (2PL) IRT model was found to be the most appropriate model for calibrating and scoring the C-test. Implications for designing, scoring, and analyzing C-tests are discussed.

Approximately 60% of patients with melanoma harbor BRAF mutation and targeting BRAF offers enormous advance in the treatment of those patients. Unfortunately, the efficacy of the BRAF inhibitors is usually restricted by the onset of drug resistance. Therefore, better understanding of the adaptive drug resistance mechanisms is essential for the development of alternative therapeutic strategies, and offers more promising measures to promote the short duration of response to BRAF inhibitors. The levels of tumor suppressive long noncoding RNA on chromosome 8p12 (TSLNC8) were evaluated by qPCR. The MTT assay, colony formation assay, apoptosis assay, and in vivo xenograft tumor model were performed to assess the functions of TSLNC8 on drug resistance. Western blotting, RNA pull-down, and RNA immunoprecipitation (RIP) assays were applied to investigate the mechanisms of TSLNC8 in melanoma. Herein, our findings demonstrate that TSLNC8 is significantly downregulated in BRAF inhibitor-resistant melanoma tissues and cells. Moreover, downregulation of TSLNC8 in BRAF inhibitor sensitive cells reduces the toxicity response to BRAF inhibitor PLX4720, and inhibits apoptosis of melanoma cells-treated with PLX4720. Further assay elucidates that TSLNC8 can bind with the catalytic subunit of protein phosphatase 1α (PP1α) to regulate its distribution, and Downregulation of TSLNC8 results in PP1α cytoplasmic accumulation, thus re-activating the MAPK signaling. Eventually, the overexpression of TSLNC8 in BRAF inhibitor PLX4720-resistant melanoma cells restores the sensitive to BRAF inhibitor. Collectively, our research provides a compelling rationale for resistance to BRAF inhibitor in melanoma, and the patient might benefit from the combinatorial therapy of BRAF inhibitors and lncRNA TSLNC8.

Background Acquired reactive perforating collagenosis is a rare skin disease characterized by the discharge of collagen fibers through the epidermis. There is no standard treatment for this disease currently. Here, we report a case of ARPC that has been successfully treated and cured. Case description A 32-year-old man developed severe itching papules on his torso and limbs for 3 months. Skin lesions were keratotic papules scattered on the limbs and trunk, with a diameter of 3 to 12 mm. Some lesions had umbilical recesses and the shape of a crater with positive isomorphic reactions. The patient scratched his severe itching lesions which merged into large ones. This patient had histories of hypertension and dilated cardiomyopathy with mild congestive heart failure. The clinical presentation and histopathology of skin lesions met Faver's diagnostic criteria for ARPC. Treatment Oral Doxycycline 100mg/d, NB-UVB phototherapy 3 times a week with initial dose 400mJ/cm2, gradually increased to 1200mJ/cm2(total cumulative dose 16700J/cm2). Outcomes After a week of treatment, the patient's itching symptoms were significantly reduced and stopped presenting any new skin lesions. Most of the lesions healed in 6 weeks of treatment. Lessons Doxycycline combined with NB-UVB may be an effective treatment for ARPC.

Melanoma is a highly malignant skin cancer with limited treatment options, the mechanism of the occurrence and development of melanoma is still unclear till now. Receptor for activated C kinase 1 (RACK1) is a scaffolding protein that mediates multiple signaling pathways; it interconnects distinct signaling pathways to control essential cellular processes. RACK1 was reported as an oncogene in human tumorigenesis, but little is known about its role in melanoma. This study aimed to investigate the expression of RACK1 in patients with melanoma and to reveal its possible functions in melanoma cells. The expression profiles of RACK1 detected in tumor tissues from melanoma patients showed that RACK1 was higher in tumor tissues, and its expression level was well associated with the clinical progression of melanoma (TNM stage, P=0.009). Furthermore, RNA interfering (RNAi) knockdown of RACK1 could efficiently suppress the proliferation, migration and invasion of A375 and A875 cells and promote their apoptosis. Taken together, these results suggest that RACK1 may be a poor prognostic factor in human melanoma, and it may be a new therapeutic target for melanoma treatment.

In view of the content of bridge condition assessment and health monitoring, this paper is based on the finite element simulation analysis. The uncertain finite element model updating method based on sequential optimization strategy is studied, and the uncertain modal parameter data obtained by health monitoring system are applied to upgrade the uncertain finite element model of cable-stayed bridges, which provides a more accurate finite element model for subsequent reliability analysis. Firstly, the finite element dynamic analysis of the main span structure of the bridge is carried out, and the natural frequencies and modes are obtained. Then the measured natural frequencies of the structure are obtained by estimating the power spectrum of the dynamic monitoring data, and the theoretical values are compared with the measured ones. The dynamic characteristics of the modified two-stayed bridge finite element model are verified by the load test results. The results show that the modified finite element model can simulate the dynamic characteristics of the actual structure well. Most of the measured and calculated displacement increments were within the margin of error. The error is within 5%, which can accurately reflect the true stress state of the structure. The uncertainty model based on the sequential optimization strategy is simple and can be applied to the uncertainty of the finite element model of the actual bridge structure.

Background miRNAs are small noncoding RNAs that function as posttranscriptional regulators during development and disease. Aberrant expression of miRNAs has been associated with various types of malignant tumors. Decreased levels of miR-124 have been observed in human cancers. RACK1 is a scaffold protein that acts as an oncogene in various human cancers. The association between miR-124 and RACK1 in melanoma has not been characterized. Materials and methods Real-time quantitative PCR was used to analyze RACK1 and miR-124 expression in melanoma tissue and cell lines. Dual-Luciferase reporter assay was performed to evaluate the effect of miR-124 inhibition on RACK1 expression. The effects of miR-124 on RACK1 in melanoma cell lines were evaluated using Western blot analysis and immunocytochemical staining. Wound-healing, transwell, and MTT assays, and annexin V-fluorescein isothiocyanate/propidium iodide followed by flow cytometry were used to evaluate the effects of miR-124 on RACK1-mediated proliferation, migration, invasion, and apoptosis of melanoma cells. Results The expression of miR-124 in melanoma tissue was lower than that in normal skin tissue, and the expression of RACK1 was higher in melanoma tissue than that in normal skin tissue. Analysis using Dual-Luciferase reporter assay showed that RACK1 was a direct target of miR-124. Western blot and immunocytochemical staining showed that the expression of RACK1 was significantly inhibited by miR-124 in both A375 and A875 melanoma cells. Furthermore, the results of functional experiments showed that degradation of RACK1 by miR-124 inhibited proliferation, migration, and invasion of melanoma cells, and promoted melanoma cell apoptosis. Conclusion The results suggested that miR-124 affected melanoma cells by directly targeting RACK1. miR-124 and RACK1 may be biomarkers for clinical diagnosis, and prognostic factors of human melanoma. Furthermore, miR-124 and RACK1 may be targets for the treatment of melanoma.

With the rapid growth of traffic, the loads' design of many existing bridges can no longer meet the current vehicle load requirements, and the structural safety is seriously threatened. To ensure the structural safety of the bridge, it is necessary to monitor the bridge health and establish an early warning mechanism to prevent major accidents. The modern concrete bridge structure health monitoring based on damage identification proposed in this paper carried out principal component analysis of modern concrete bridges, and then this paper used principal component analysis (PCA) to locate the nonlinear damage source of the experimental model, which obtained the following conclusions. The maximum shear stress of the steel beam web is about 80 MPa，and the bulk stress of steel is reached at 7.5 MPa. Furthermore, to reduce the original data's dimensionality, PCA effectively retains the characteristic information of the original data; empirical examples from external factor are presented. The major advantage of applying this framework is that the structural damage identification is simple and reliable with its advantages of dimensionality reduction, noise reduction, and exclusion of out-of-bounds interference factors.

This paper shows a more exact and practical finite element model of the steel girder deck pavement. Based on Mindlin thick plate theory, a 12-node solid thick plate element was constituted to analyze the pavement. The computation result was compared with that by traditional 4-node and 8-node thick plate finite element, and is satisfactory. A combined plate beam element method is presented to investigate the stiffened plate. A 6-node solid thin plate element was constituted to analyze the top plate based on Kirchhoff thin plate theory. The stiffeners acting as the vertical supporting function mainly are taken as Euler beam elements. A method of using the linear interpolation to realize the longitudinal displacement and the cubic Hermite interpolation to the vertical displacement is presented to analyze the stiffeners. In addition, it is essential to consider the displacement coordination between the top plate and stiffeners. A node-to-node contact scheme, which is applicable for three-dimensional contact analyses involving large deformations, was used to treat the contact problem between pavement and stiffened plate by Lagrange multiplier methods.

Hedgehog (Hh) signaling has been proved to be closely associated with the occurrence of melanoma. Wogonin is one of the active components of flavonoids that extracts from Scutellariae radix. Previous studies showed that wogonin could inhibit the invasion and migration of B16F10 cells, and suppress the synthesis of melanin in A375 melanoma cells. However, the regulatory effects of Hh signaling in wogonin against melanoma and its potential mechanisms remain largely unknown. The present study aimed to investigate the effect of wogonin on the growth of HT144 melanoma, and to elucidate the role of Hh signaling in wogonin-induced antitumor effects by focusing on inflammation and glycolysis regulation. Wogonin inhibited the proliferation, colony formation and tumor growth of HT144 melanoma cells. Wogonin showed strong anti-inflammatory effect in HT144 melanoma, as shown by the decreased levels of pro-inflammatory factors, the increased level of anti-inflammatory factor and the decreased expression of inflammatory cytokines. Wogonin decreased the glucose consumption and the production of lactic acid and ATP, and decreased the activities of hexokinase (HK), phosphofructokinase(PFK) and pyruvate kinase (PK), and further inhibited the expression of monocarboxylate transporter 1 (MCT-1), MCT-4 and glucosecotransporter-1 (GLUT1), showing potent anti-glycolysis effect against HT144 melanoma. Wogonin inhibited the patched and Smo expression while increased Hhip expression in HT144 cells, suggesting that wogonin blocked the Hh signaling in HT144 cells. The Hh signaling inhibitor cyclopamine, like wogonin, inhibited the colony formation of HT144 cells, however, the inhibitory effect of wogonin on colony formation of HT144 cells was abrogated by the Hh signaling agonist SAG. In addition, SAG abrogated the inhibitory effect of wogonin on the secretion of inflammatory factors and the expression of inflammatory cytokines. Furthermore, SAG abrogated the inhibitory effect of wogonin on several key molecules controlling glycolysis. Overall, these findings suggested that the anti-tumor effect of wogonin can be attributed to the inhibition of Hh signaling-mediated regulation of inflammation and glycolysis in HT144 melanoma.

Frictional resistance, typically provided by the bottom and sides of saddle, is essential for counterpoising unbalanced cable tension between adjacent spans. In most practices, however, the friction from the saddle sides is ignored due to the lack of an effective calculation method of lateral forces, giving rise to serious anti-slip issues, especially for multi-tower suspension bridges. For this reason, the lateral forces between the main cable and saddle are studied in this paper. A similar formula of lateral force in specification is first investigated to reveal its theoretical basis and limitations. Considering each cable wire as an individual discrete body, an analytical model with recursive algorithm is then developed, which allows to calculate the contact forces layer by layer. Based on this, the effects of possible errors are quantified, and the sensitivity of lateral forces to key parameters, such as friction coefficient, extra pressure, arrangement and diameter of the wires, is subsequently discussed in detail. The results show that the existing formula evolved from the Janssen theory is insufficient for anti-slip assessment of the main cable. The transverse gap of saddle trough has a limited increase effect on the lateral force. As the wire arrangement widens, the lateral force grows rapidly and then approaches a certain value. The lateral force is negatively related with the friction coefficient, and the extra pressure can create great yet regular influence on the distribution of lateral pressure. Finally, the Taizhou Yangtze River Bridge is taken as a case example for an application of the proposed model. It is found that 32.2% of the total friction comes from the lateral friction when two vertical friction plates are used, confirming that the anti-slip capacity of cable-saddle system can be greatly improved by adequately utilizing the lateral friction.

Research on examinees’ response changes on multiple-choice tests over the past 80 years has yielded some consistent findings, including that most examinees make score gains by changing answers. This study expands the research on response changes by focusing on a high-stakes admissions test—the Verbal Reasoning and Quantitative Reasoning measures of the GRE revised General Test. We analyzed data from 8,538 examinees for Quantitative and 9,140 for Verbal sections who took the GRE revised General Test in 12 countries. The analyses yielded findings consistent with prior research. In addition, as examinees’ ability increases, the benefit of response changing increases. The study yielded significant implications for both test agencies and test takers. Computer adaptive tests often do not allow the test takers to review and revise. Findings from this study confirm the benefit of such features.

It has been demonstrated that numerous types of metastatic cancer overexpress vacuolar-type H+ (V)-ATPases. It may be possible to inhibit the growth and metastasis of human cancer cells by inhibiting V-ATPases. It was previously reported that diphyllin, a novel V-ATPase inhibitor, can inhibit the migration and invasion of SGC7901 human gastric cancer cells; however, the effects of cleistanthin A (CA), a diphyllin glycoside, on melanoma cells has not been demonstrated. The present study aimed to investigate the effect of CA as a V-ATPase inhibitor and its effects on the invasion and metastasis of A375 cells. The results of an MTT assay in the present study indicated that the growth inhibition of A375 cells by CA was induced in a dose- and time-dependent manner; however, A375 cell viability was not significantly affected by low concentrations (0.03, 0.1 and 0.3 µM) after 24 h. Similar results were obtained by viable cell counting with trypan blue. Therefore, these concentrations of CA were selected for the treatment of A375 cells in further experiments. It was demonstrated that CA inhibited the expression of V-ATPases in a dose-dependent manner and decreased the internal pH level of A375 cells. Alterations to the lysosomal pH were associated with the CA concentration. Furthermore, CA treatment induced a significant decrease in cell migration and invasion, as demonstrated with wound-healing and Transwell assays. Gelatin zymography and western blot analysis demonstrated that the expression levels of matrix metallopeptidase (MMP)-2 and −9 decreased following CA treatment. Therefore, CA can be characterized as a novel V-ATPase inhibitor for the treatment of melanoma that may inhibit invasion and metastasis by downregulating the expression of MMP-2 and −9.

Cutaneous horns were first reported in London in 1588.1 Unlike a true animal horn that has bony core, a cutaneous horn is a conical projection made up of cornified material. The length of this lesion varies from a few millimeters to 38 cm in some reported cases.2 Cutaneous horns are usually skin colored or erythematous, and they may present as white with a fine scale.3 Approximately 30% of cutaneous horns appear in sun-exposed areas, such as upper face and scalp.1 However, chronic irritation can also give rise to cutaneous horns on other areas of the body, even on the penis.4 People ages 50 to 89 years are the group most affected.5 Cutaneous horns are a morphologic designation rather than a pathologic diagnosis, and they can be derived from many benign or malignant diseases, such as seborrheic keratoses, basal cell carcinoma, and squamous cell carcinoma (SCC).