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Supplementary Figures S1-S3 from Transforming Growth Factor-β1 Induces Tissue Inhibitor of Metalloproteinase-1 Expression via Activation of Extracellular Signal-Regulated Kinase and Sp1 in Human Fibrosarcoma Cells

In this study, we investigated the physicochemical characteristics and antioxidant activity of fermented vinegar using onion and black onion. When the onion and black onion were fermented in alcohol for 8 days, the alcohol content in both onion vinegar (OV) and black onion vinegar (BV) increased, whereas their sugar content decreased. The alcohol content was higher in OV than that in BV. When the onion and black onion were fermented in acetic acid for 20 days, the pH of both OV and BV decreased, whereas their total acidity increased. After fermentation, the main free sugars of OV and BV were fructose and glucose, and they were higher in BV than in OV. The major organic acids in OV and BV were acetic acid and malic acid, and the content of acetic acid was higher in BV than that in OV. In addition, OV and BV increased 1,1’-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) radical scavenging activities in a dose-dependent manner. Furthermore, DPPH and ABTS+ radical scavenging activities were greater in black onion juice than in onion juice. The BV showed a higher DPPH and ABTS+ radical scavenging activities than OV. Therefore, BV is the more suitable antioxidant functional vinegar through radical scavenging activity.

This study was conducted to investigate the effects of supplementing different ratios of phytogenic feed additives (PFA) to weaned pigs challenged with pathogenic Escherichia coli on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response, and to determine the optimal mixing ratio for post-weaning diarrhea (PWD) prevention. A total of 48 4-wk-old weaned pigs with initial body weight of 8.01 ± 0.39 kg were placed in individual metabolic cages, and then randomly assigned to eight treatment groups. The eight treatments were as follows: a basal diet without E. coli challenge (negative control, NC), a basal diet with E. coli challenge (positive control, PC), PC with supplementing 0.1% mixture of 20% bitter citrus extract (BCE), 10% microencapsulated blend of thymol and carvacrol (MEO), and 70% excipient (T1), PC with supplementing 0.1% mixture of 10% MEO, 20% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient (T2), PC with supplementing 0.1% mixture of 10% BCE, 10% MEO, 10% PGE, and 70% excipient (T3), PC with supplementing 0.1% mixture of 20% BCE, 20% MEO, and 60% excipient (T4), PC with supplementing 0.1% mixture of 20% MEO, 20% PGE, and 60% excipient (T5), and PC with supplementing 0.1% mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipient (T6). The experiments progressed in 16 days, including 5 days before and 11 days after the first E. coli challenge (day 0). In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F 18 for three consecutive days from day 0 postinoculation (PI). Compared with the PC group, the PFA2 and PFA6 groups significantly increased (P < 0.05) feed efficiency and decreased (P < 0.05) diarrhea during the entire period. At day 11 PI, the PFA6 group significantly improved (P < 0.05) gross energy digestibility compared to the PFA1 group. The PFA6 group significantly decreased (P < 0.05) tumor necrosis factor α (TNF-α) and interleukin-6 in serum and increased (P < 0.05) the villus height to crypt depth ratio (VH:CD). The PFA2 significantly decreased (P < 0.05) the relative protein expression of calprotectin in the ileum. In conclusion, improvements in growth performance, diarrhea reduction, and immunity enhancement are demonstrated when 10% BCE, 20% MEO, 10% PGE, and 60% excipient are mixed.

While poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) film is an excellent piezoelectric material for mechanical energy harvesting, the piezoelectric output varies considerably with the spin coating conditions. Herein, we reported a systematic evaluation of the structural, electrical, mechanical, and microstructural properties of spin-coated P(VDF-TrFE) films obtained at various distances from the center, as well as under different rotational speeds. With increasing distance, the remnant polarization, dielectric constant, and crystallinity of the films increased, which resulted in enhanced piezoelectric power at the largest distance. With increasing rotational speed, the remnant polarization, dielectric constant, and crystallinity of the films initially increased and then decreased, while the Young’s modulus continuously increased. This resulted in an enhanced piezoelectric power at a given rotational speed. The piezoelectric power is proportional to the remnant polarization and inversely proportional to the Young’s modulus. The highest (2.1 mW) and lowest (0.5 mW) instantaneous powers were obtained at the largest (1.09 μC/cm2·GPa−1) and smallest (0.60 μC/cm2·GPa−1) value of remnant polarization over Young’s modulus, respectively. We explain these behaviors in terms of the centrifugal force-induced shear stress and grain alignment, as well as the thickness-dependent β-phase crystallization and confinement. This work implies that the spin coating conditions of distance and rotational speed should be optimized for the enhanced power output of spin-coated P(VDF-TrFE)-based piezoelectric nanogenerators.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.

Glioblastoma (GBM) is the most malignant brain tumor with profound genomic alterations. Tumor suppressor genes regulate multiple signaling networks that restrict cellular proliferation and present barriers to malignant transformation. While bona fide tumor suppressors such as PTEN and TP53 often undergo inactivation due to mutations, there are several genes for which genomic deletion is the primary route for tumor progression. To functionally identify putative tumor suppressors in GBM, we employed in vivo RNAi screening using patient-derived xenograft models. Here, we identified PIP4K2A, whose functional role and clinical relevance remain unexplored in GBM. We discovered that PIP4K2A negatively regulates phosphoinositide 3-kinase (PI3K) signaling via p85/p110 component degradation in PTEN-deficient GBMs and specifically targets p85 for proteasome-mediated degradation. Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. Our results unravel a novel tumor-suppressive role of PIP4K2A for the first time and support the feasibility of combining oncogenomics with in vivo RNAi screen.

BackgroundGastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments.MethodsTo address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers.ResultsWe identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors inALK-mutant tumors, a significant association betweenPIK3CA-E542K mutation and AZD5363 response, and transcriptome expression ofRNF11as a potential predictor of response to gefitinib.ConclusionsCollectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Arrays of high-index dielectric nanoparticles supporting both electrical and magnetic resonances have gained increasing attention for their excellent light-trapping (LT) effects, thus greatly improving the performance of ultrathin solar cells. This work explores front-located, high-index dielectric subwavelength nanosphere arrays as an efficient and broadband LT structure patterned on top of an ultrathin perovskite solar cell (PSC) for a greatly enhanced absorption. Combined strong light scattering and anti-reflection properties achieved by optimized geometrical parameters of the LT structure lead to a broadband absorption enhancement in the ultrathin thickness of a photoactive layer (100 nm) yielding the short-circuit current density (Jsc) of 18.7 mA/cm2, which is 31.7% higher than that of a planar counterpart. Moreover, effects of the LT structure on far-field radiation patterns, scattering cross-sections, multipoles’ contributions, and asymmetry parameters along with the incidence angle and polarization dependence are investigated. The present strategy could be applied to diverse applications, such as other ultrathin or semitransparent solar cells, absorbers and photodetectors.

1990년대 초반 나선특구 지정을 시작으로 추진한 북한의 경제특구 개발전략이 아직까지 이렇다 할 성과를 내고 있지 못한 이유는 무엇인가? 북한은 중국 베트남의 '점진적' 개혁 개방 또는 경제개발에 성공할 수 있을 것인가? 그러기 위한 조건은 무엇인가? 이 연구는 중국, 베트남, 북한의 경제특구 사례를 '맥락과 목적',...

The purpose of this study is to analyze cognition of applicants about the national sports coaching certificate examination. In order to collect data an online survey was conducted against those who attended the practical and oral examination for the sports coaching certificate. SPSS Version 18.0 was used to analyze frequency of the collected 2,895 samples, the factors of measuring methods in the study, difference of applicants` cognition on the certificate system, and difference of applicants` cognition on the practical and oral examination. Results from this study indicates that the applicants` cognition on the sports coaching certificate system differs according to ages, educational levels, and sports related majors at college, and that the applicants` cognition on the practical and oral examination for the sports coaching certificate is also different according to gender, age, educational level, and sports related majors at college. This study suggests development directions for the future sports coaching system by comprehending of the study results.

This study examined the relationship among dropout, organizational trust, and intention to transfer in the department affiliated with Physical Education. Data were collected from 480 students in the department affiliated with Physical Education from 6 institutions of a 4-year university located in Seoul, Gyeonggi-do, Incheon, and ChungChong-do. For the research model analysis, a structural equation model and bootstrapping were conducted. Results indicated that the academic domain, the social domain, and the environmental domain of dropout had a positive effect on organizational trust. But the only the academic domain in the relationship between dropout and intention to transfer affected intention to transfer positively. The social domain and the environmental domain were not statistically significant on intention to transfer. Moreover, organizational trust had a positive effect on intention to transfer. Finally, organizational trust partially mediated the path between the academic domain and intention to transfer. It fully mediated the paths between the social domain and the environmental domain and intention to transfer.

CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.

[Purpose] This study was conducted to determine whether acute aerobic exercise (climbing) is associated with changes in the dietary intake pattern. [Subjects and Methods] Food intake and physical activity data for 15 female college students were sampled for 3 days and categorized according to routine activity or high-intensity activity such as hiking. Nutrient intake based on the data was analyzed using a nutrition program. [Results] Carbohydrate and protein intake was significantly decreased after exercise compared to before acute aerobic exercise, but lipid intake showed no significant difference. Calorie intake was significantly decreased after exercise compared to before exercise; however, calorie consumption was significantly increased after exercise. [Conclusion] Aerobic exercise causes a decrease in total calories by inducing reduction in carbohydrate and protein intake. Therefore, aerobic exercise is very important for weight (body fat) control since it causes positive changes in the food intake pattern in female students.

Background/aims Surgical site infection (SSI) is a major complication after radical neck dissection (RND) in patients with head and neck cancer (HNC). We investigated the incidence, risk factors, and etiology of SSI among patients who underwent RND. Methods A retrospective cohort study was performed on HNC patients, excluding those with thyroid cancer, who underwent first RND at a teaching hospital between January 2006 and June 2010. Medical records were collected and analyzed to evaluate the risk factors and microbiological etiologies. Results A total of 370 patients underwent first RND. The overall incidence of SSI was 19.7% (73/370). Multivariate analysis showed that male sex (odds ratio [OR], 4.281; p = 0.004), cardiovascular diseases (OR, 1.941; p = 0.020), large amount of blood loss during surgery (OR, 4.213; p = 0.001), and surgery lasting longer than 6 hours (OR, 4.213; p = 0.002) were significantly associated with SSI. The most common causative pathogen was Staphylococcus aureus (32.6%), and 93.2% of S. aureus isolates were methicillin-resistant. Klebsiella pneumoniae (13/92, 14.1%), Pseudomonas aeruginosa (11/92, 12.0%), and Enterococcus species (11/92, 12.0%) were also frequently detected. Conclusions Based on our results, we predict that certain groups of patients are at high risk for SSIs after major HNC surgery. Preventive measures or close monitoring in these patients may be required to reduce the likelihood of postoperative SSIs. Furthermore, even though additional research is required, we would consider changing the prophylactic antibiotic regimens according to the causative organisms.

Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive inter-tumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscape of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared to the traditional long-term cultured cancer cell-line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. In present study, we provide unprecedented insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors and potential repurposing of ibrutinib (currently being used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present potential implementation of PDC-derived drug sensitivities for prediction of clinical response to targeted therapeutics using retrospective clinical studies.