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Sheet metal channels with variable sections or local features have been widely used in automobile and construction industries, and novel forming techniques, such as flexible roll forming process, flexibly-reconfigurable roll forming process, Deakin’s flexible forming facility and chain-die forming recently have been developed to manufacture those channels. In this paper, the feasibility of chain-die forming technique to manufacture channels with variable sections are systematically investigated through experiment and finite element simulation by taking 6 types of channel products as demonstration, including three variable-width and three variable-depth profiles. The forming process of the channels shows a combination of roll forming and stamping, and this roll-stamp mode is greatly potential in manufacturing a wide variety of channels with variable cross-sections. The formability for roll-stamp forming variable-depth channels is evaluated through finite element simulation and forming limit diagram. The roll-stamp mode can be discomposed into roll forming longitudinally and stamping vertically, and can achieve a reduction in forming load by the maximum of 33.9% compared with the conventional stamping in forming the flange step product. The forming direction sensitivity of the variable-width feature is discussed from the aspect of web arch height development.

As STEM (Science, Technology, Engineering and Mathematics) education gets more and more attention from society, students' attitudes towards STEM are increasingly concerned. However, there was scant research that has empirically documented the relations among STEM attitude, learning motivation and metacognition. This research used Structural Equation Modeling to examine the above relations. Data were collected from 845 primary school students from grade 4 to 6, regarding their STEM attitude, learning motivation, metacognition, and their sociodemographic characteristics (family socioeconomic status). The results showed that metacognition played a mediating role in the effect of learning motivation on STEM attitude. The family socioeconomic status played a moderating role in the effect of metacognition on STEM attitude, and students with higher family socioeconomic status had a stronger effect on STEM attitude. This research also suggested that it is worth considering the improvement of students' learning motivation to facilitate STEM attitude through promoting their metacognitive skills, meanwhile balancing the gap between students under the difference of socioeconomic level in STEM education. Keywords: learning motivation, metacognition, STEM attitude, Structural Equation Modeling

Dynamic communication within adipose tissue depends on highly vascularized structural characteristics to maintain systemic metabolic homoeostasis. Recently, it has been noted that adipose endothelial cells (AdECs) act as essential bridges for biological information transmission between adipose-resident cells. Hence, paracrine regulators that mediate crosstalk between AdECs and adipose stromal cells were summarized. We also highlight the importance of AdECs to maintain adipocytes metabolic homoeostasis by regulating insulin sensitivity, lipid turnover and plasticity. The differential regulation of AdECs in adipose plasticity often depends on vascular density and metabolic states. Although choosing pro-angiogenic or anti-angiogenic therapies for obesity is still a matter of debate in clinical settings, the growing numbers of drugs have been confirmed to play an anti-obesity effect by affecting vascularization. Pharmacologic angiogenesis intervention has great potential as therapeutic strategies for obesity., Graphical abstract

BACKGROUND AND OBJECTIVE: EBV-associated gastric cancer (EBVaGC) is a distinct subtype of GC, and EBV plays an important role in tumor progress. The standard method to identify EBV-positive tumor is determined by in situ hybridization for EBV-encoded EBERs in tumor tissues. The present study aims to detect the serological expression of EBV-related antibodies and ET-1 axis to provide a noninvasive method for diagnosis of EBVaGC. METHODS: The content of EBV-related antibodies and ET-1 axis in preoperative peripheral blood of GC was performed by Chemiluminescence and ELISA assay. The EBV DNA copy number was measured by qRT-PCR. RESULTS: The results showed that the levels of anti-EBV early antigen (EA) IgG, viral capsid antigen (VCA) IgA, nuclear antigen (NA) IgG, and EBV DNA copy number were significantly higher in EBVaGC. The ET-1 axis level was much lower in EBVaGC than EBVnGC. CONCLUSIONS: The combined detection of specific anti-EBV antibodies and ET-1 axis might provide new molecular markers for the identification of EBVaGC.

Evidence of the short-term effects of ambient sulfur dioxide (SO

Aim: The purpose of this study is to investigate the polymorphism and distribution characteristics of BALF2 gene in Epstein–Barr virus (EBV)-associated tumors (gastric cancer, nasopharyngeal carcinoma and lymphoma). Materials & methods: DNA sequences of 349 EBV-related samples were analyzed by nested PCR combined with DNA sequencing. Results: According to the phylogenetic tree, BALF2 was divided into six genotypes ( BALF2-A–F). Statistically, the incidence of BALF2-E in nasopharyngeal carcinoma was higher than that in healthy people, and the incidence of BALF2-E in nasopharyngeal carcinoma in South China was higher than that in North China (p = 0.001). Conclusion: BALF2 variants in EBV-associated samples are not only tumor-specific, but also differ between northern and southern regions.

AIM: To investigate the effect of 0.01% atropine sulphate eye gel on myopia progression and axial elongation in a 6-month treatment in children. METHODS: Totally 185 children aged 6-12y with binocular myopia of 3.0 D or less in both eyes were enrolled in this prospective cohort study. The atropine group (n=125) received one drop of 0.01% atropine sulphate eye gel in each eye before bedtime daily. The control group included 60 matched children without drug intervention during the same period. The spherical equivalent and axial length was recorded at baseline and the sixth month of treatment. The efficacy was evaluated by the change of the spherical equivalent and axial length. Adverse events were also recorded. RESULTS: The average spherical equivalent and axial length at baseline were not statistically significant between the atropine group (-1.64±0.80 D, 24.13±0.76 mm) and the control group (-1.59±0.94 D, 24.06±0.77 mm, P>0.05). After 6mo, there was significantly difference in the spherical equivalent progression between the atropine and the control group (-0.27±0.33 vs -0.60±0.35 D, P

DNA barcoding and metabarcoding have been increasingly used in species delimitation and species diversity assessment, respectively, and the molecular markers used in animals are mainly derived from mitochondrial DNA. It is well known that the phenomenon of multiple mitochondrial haplotypes within the same specimen (hereafter referred to as "mitotype diversity") may have a negative impact on the proper assessment of biodiversity by metabarcoding. However, few studies have focused on the incidence of this phenomenon and its effects on metabarcoding results using different sample preparation strategies, such as mock community construction using pooled high-throughput sequencing (HTS) data, DNA-pooling and Tissue-pooling. In this study, we investigated mitotype diversity and its influence on metabarcoding based on 398 specimens from 66 species of Insecta and 82 specimens from 16 species of Arachnida by HTS of the mitochondrial cox1 gene fragment. The results revealed that mitotype diversity was common in the studied taxa and significantly increased the number of operational taxonomic units (OTUs) using the three sample preparation strategies. The results also showed that the bioinformatics pipeline based on authentic amplicon sequence variants was more reliable than the pipeline based on OTUs. Regarding the sample preparation strategies of DNA-pooling and Tissue-pooling commonly used in metabarcoding, our results revealed that their results of metabarcoding were quite similar, and the Tissue-pooling strategy was therefore preferred because of its simplicity. Our study calls for additional attention to the interference of mitotype diversity on the results of DNA metabarcoding in biodiversity assessment.

Background A high incidence of hepatocellular carcinoma (HCC), the most frequently diagnosed form of liver cancer, is observed in Africa and Asia. SYVN1 is upregulated in HCC; however, the biological roles of SYVN1 in immune evasion remain unclear. Methods RT-qPCR and western blot were employed to detect the expression levels of SYVN1 and the key molecules in HCC cells and tissues. Flow cytometry was used to determine the proportion of T cells, and an ELISA assay was used to determine the amount of IFN-γ secreted. Cell viability was monitored by CCK-8 and colony formation assays. The metastatic properties of HCC cells were detected by Transwell assays. Bioinformatics analysis, ChIP, and luciferase assays were used to study the transcriptional regulation of PD-L1. Co-IP was used to detect direct interaction between SYVN1 and FoxO1, as well as the ubiquitination of FoxO1. The in vitro findings were validated in xenograft and lung metastasis models. Results In HCC cells and tissues, SYVN1 was upregulated while FoxO1 was downregulated. SYVN1 knockdown or FoxO1 overexpression reduced PD-L1 expression, and inhibited immune evasion, cell growth, and metastasis in HCC cells. Mechanistically, FoxO1 regulated PD-L1 transcription in a β-catenin-independent or -dependent manner. Functional studies further showed that SYVN1 promoted immune evasion, cell proliferation, migration and invasion via facilitating ubiquitin-proteasome-dependent degradation of FoxO1. In vivo investigations showed that silencing of SYVN1 inhibited immune evasion and metastasis of HCC cells, possible via the FoxO1/PD-L1 axis. Conclusion SYVN1 regulates FoxO1 ubiquitination to stimulate β-catenin nuclear translocation and promotes PD-L1-mediated metastasis and immune evasion in HCC.

During the sexual phase of Neurospora crassa, unpaired genes are subject to a silencing mechanism known as meiotic silencing by unpaired DNA (MSUD). MSUD targets the transcripts of an unpaired gene and utilizes typical RNA interference (RNAi) factors for its process. Using a reverse genetic screen, we have identified a meiotic silencing gene called sad-9, which encodes a DEAD-box RNA helicase. While not essential for vegetative growth, SAD-9 plays a crucial role in both sexual development and MSUD. Our results suggest that SAD-9, with the help of the SAD-2 scaffold protein, recruits the SMS-2 Argonaute to the perinuclear region, the center of MSUD activity.

Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL).Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL.Results: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts.Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies.Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. Cancer Epidemiol Biomarkers Prev; 21(4); 664–72. ©2012 AACR.

Supplementary Figure S1. CircPRMT5 is upregulated in UCB cells. Supplementary Figure S2. CircPRMT5 promotes migration and invasion of UCB cells. Supplementary Figure S3. CircPRMT5 contains multiple target sites of miRNAs. Supplementary Figure S4. CircPRMT5 promotes migration and invasion of UCB cells by reducing the inhibitory effect of miR-30c via sponge activity. Supplementary Figure S5. SNAIL1 is a target of miR-30c. Supplementary Figure S6. Representative images of SNAIL1 and E-cadherin expressions examined by IHC in UCB tissues with high (left) and low (right) expression of circPRMT5. Supplementary Figure S7. The correlation between expressions of SNAIL1 and miR-200 family in UCB tissues derived from TCGA database. Supplementary Figure S8. CircPRMT5 was secreted into exosomes derived from serum and urine of UCB patients. Supplementary Table S1. Correlation between expression of circPRMT5 and patients' clinicopathological variables in UCB patients Supplementary Table S2. The up-regulated and down-regulated circRNAs in UBCs Supplementary Table S3. Correlation of miR-30c expression with patients' clinicopathological variables in TCGA UCB cohorts Supplementary Table S4. Correlation of circPRMT5 expression in serum exosomes with patients' clinicopathological variables in 71 cases of UCB

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Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

PDF file - 687KB, Supplemental Figures S1-S9. S1 shows MTBP induces proliferation. S2 shows peptides in TIP48 and TIP49 identified by mass spectrometry. S3 shows Mtbp increases the pro-proliferative and transforming functions of Myc. S4 shows increased MTBP and MYC express correlates with poor colon and lung cancer survival. S5 shows the location of MTBP and MYC on 8q24. S6 shows Mtbp knockdown inhibits Myc-mediated transcription. S7 shows MTBP knockdown inhibits proliferation. S8 shows the C-terminus of Mtbp inhibits breast cancer cell expansion. S9 shows the working model of MTBP function.

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TIP30 is a tumor suppressor whose expression is altered in human liver, prostate, lung, colon, and breast cancers. Mice lacking TIP30 spontaneously developed hepatocellular carcinomas (HCC) and other tumors at a higher incidence than wild-type mice. Somatic missense mutations in the TIP30 gene were identified in human HCC tissue specimens, which resulted in instability or abnormal cellular distribution of TIP30 protein in cells. Here, we show that TIP30 mutants are able to promote cell growth and invasion and inhibit cisplatin-induced apoptosis in the HCC cell line HepG2 negative for endogenous TIP30. Moreover, one of the TIP30 mutants can dramatically accelerate tumor formation in immunodeficient mice. Analysis of gene expression in HepG2 cells, ectopically expressing either wild-type TIP30 or mutant TIP30, by Affymetrix GeneChip array, real-time quantitative PCR, and Western blotting assays reveals that TIP30 mutants can alter expression of genes involved in the regulation of tumorigenesis. This includes up-regulation of expression of N-cadherin and c-MYC and down-regulation of expression of p53 and E-cadherin. N-cadherin knockdown with small interfering RNA in HepG2 cells expressing mutant TIP30 resulted in a profound reduction in cell viability. Taken together, our data indicate that somatic mutations in the TIP30 gene may abolish its native tumor-suppressor activity and gain oncogenic activities partially through up-regulation of N-cadherin, thereby potentiating the pathogenesis of HCC in patients. [Cancer Res 2007;67(8):1–9]

Supplementary Figure 1 from TIP30 Mutant Derived from Hepatocellular Carcinoma Specimens Promotes Growth of HepG2 Cells through Up-Regulation of N-cadherin

Supplementary Figure 1 Legend, Methods and Materials from TIP30 Mutant Derived from Hepatocellular Carcinoma Specimens Promotes Growth of HepG2 Cells through Up-Regulation of N-cadherin

Supplementary Figures 1-2 from Tip30 Deletion in MMTV-Neu Mice Leads to Enhanced EGFR Signaling and Development of Estrogen Receptor–Positive and Progesterone Receptor–Negative Mammary Tumors