• Biomolecules & Therapeutics
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• 제23권4호
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• pp.320-326
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• 2015

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

• 생체재료학회지
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• 제22권4호
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• pp.235-248
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• 2018

Background: Injectable hydrogels have been extensively researched for the use as scaffolds or as carriers of therapeutic agents such as drugs, cells, proteins, and bioactive molecules in the treatment of diseases and cancers and the repair and regeneration of tissues. It is because they have the injectability with minimal invasiveness and usability for irregularly shaped sites, in addition to typical advantages of conventional hydrogels such as biocompatibility, permeability to oxygen and nutrient, properties similar to the characteristics of the native extracellular matrix, and porous structure allowing therapeutic agents to be loaded. Main body: In this article, recent studies of injectable hydrogel systems applicable for therapeutic agent delivery, disease/cancer therapy, and tissue engineering have reviewed in terms of the various factors physically and chemically contributing to sol-gel transition via which gels have been formed. The various factors are as follows: several different non-covalent interactions resulting in physical crosslinking (the electrostatic interactions (e.g., the ionic and hydrogen bonds), hydrophobic interactions, ${\pi}$-interactions, and van der Waals forces), in-situ chemical reactions inducing chemical crosslinking (the Diels Alder click reactions, Michael reactions, Schiff base reactions, or enzyme-or photo-mediated reactions), and external stimuli (temperatures, pHs, lights, electric/magnetic fields, ultrasounds, or biomolecular species (e.g., enzyme)). Finally, their applications with accompanying therapeutic agents and notable properties used were reviewed as well. Conclusion: Injectable hydrogels, of which network morphology and properties could be tuned, have shown to control the load and release of therapeutic agents, consequently producing significant therapeutic efficacy. Accordingly, they are believed to be successful and promising biomaterials as scaffolds and carriers of therapeutic agents for disease and cancer therapy and tissue engineering.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.302-310
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• 2019

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.452-458
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• 2019

Objective: The study was carried to determine the interaction effects of pen enrichment and sex on behavioral activities, skin lesions and physiology of Windsnyer pigs. Methods: Forty-eight growing Windsnyer pigs of both sex, with an average initial body weight of 21.6 (${\pm}9.01$) kg were used. Four pigs were randomly assigned to either enriched or barren pens at a stocking density of $0.35m^2/pig$. Enriched pens contained 2 L bottles filled with stones and suspended at head level on ropes stretching across the pens. In addition, two plastic balls (90 mm in diameter) and 500 mL bottles (235 mm long) were placed on the floor of each enriched pen. Results: Pigs in barren environments had higher heart rates (p<0.001) than those in enriched pens. There was an interaction of pen environment and sex on rectal temperature (p<0.001). Females in enriched pens had higher rectal temperatures (p<0.05) than females in barren pens. There was no interaction of pen environment and sex on time spent eating and drinking (p>0.05). Time spent bullying was influenced (p<0.05) by pen environment and sex. Female pigs in barren environment spent more time on bullying than females in enriched pens. There was an interaction of pen environment and sex on time spent lying down and walking (p<0.05). Female pigs in enriched pens spent more time lying down than females in barren pens. Males in barren pens spent more time walking than males in enriched pens while no effect of pen environment was observed in females. There was an interaction of pen environment and sex on the number of skin lesions in the head, neck and shoulder region and other parts of the body (p<0.05). Conclusion: It was concluded that pen enrichment reduced the number of skin lesions and anti-social behaviors, especially for female pigs. There is a need, therefore of housing indigenous pigs under confinement.

• Asian-Australasian Journal of Animal Sciences
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• 제32권7호
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• pp.966-976
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• 2019

Objective: The methane mitigating potential of various plant-based polyphenol sources is known, but effects of combinations have rarely been tested. The aim of the present study was to determine whether binary and 3-way combinations of such phenol sources affect ruminal fermentation less, similar or more intensively than separate applications. Methods: The extracts used were from Acacia mearnsii bark (acacia), Vitis vinifera (grape) seed, Camellia sinensis leaves (green tea), Uncaria gambir leaves (gambier), Vaccinium macrocarpon berries (cranberry), Fagopyrum esculentum seed (buckwheat), and Ginkgo biloba leaves (ginkgo). All extracts were tested using the Hohenheim gas test. This was done alone at 5% of dry matter (DM). Acacia was also combined with all other single extracts at 5% of DM each, and with two other phenol sources (all possible combinations) at 2.5%+2.5% of DM. Results: Methane formation was reduced by 7% to 9% by acacia, grape seed and green tea and, in addition, by most extract combinations with acacia. Grape seed and green tea alone and in combination with acacia also reduced methane proportion of total gas to the same degree. The extracts of buckwheat and gingko were poor in phenols and promoted ruminal fermentation. All treatments except green tea alone lowered ammonia concentration by up to 23%, and the binary combinations were more effective as acacia alone. With three extracts, linear effects were found with total gas and methane formation, while with ammonia and other traits linear effects were rare. Conclusion: The study identified methane and ammonia mitigating potential of various phenolic plant extracts and showed a number of additive and some non-linear effects of combinations of extracts. Further studies, especially in live animals, should concentrate on combinations of extracts from grape seed, green tea leaves Land acacia bark and determine the ideal dosages of such combinations for the purpose of methane mitigation.

• Nuclear Engineering and Technology
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• 제54권3호
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• pp.1115-1125
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• 2022

Nuclear power plant (NPP) is currently considered as one of the most reliable power sources. However, 182 of them are considered decommissioned and inactive including the one in Bataan, Philippines. The aim of this study was to investigate the acceptance of the reopening of Bataan Nuclear Power Plant (BNPP) by integrating the Theory of Planned Behavior and Protection Motivation Theory. A total of 815 Filipinos answered an online questionnaire which consisted of 37 questions. The Structural Equation Modeling (SEM) indicated that knowledge towards nuclear power plants was the key factor in determining people's acceptance towards NPP reopening. In addition, knowing the benefits would lead to positive perceived behavioral control (PBC) and attitude towards intention. Results showed that PBC and attitude are mediators towards the acceptance of people regarding the reopening of BNPP. If an individual's knowledge gravitates towards the perceived risk, then this can lead to the negative acceptance of the NPP reopening. On the other hand, if an individual's knowledge gravitates towards the perceived benefits, then this will lead to positive acceptance. This study is the first study that explored the acceptance of the reopening BNPP. Finally, the study's model construct would also be very beneficial for researchers, government, and even private sectors worldwide.

• Imaging Science in Dentistry
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• 제52권1호
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• pp.109-115
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• 2022

Purpose: The aim of this study was to evaluate the prevalence of clinically relevant anatomical variations of the ethmoid sinuses and their potential association with ethmoid and maxillary sinus pathologies on cone-beam computed tomography (CBCT) scans. Additionally, potential associations with different sides and demographic factors, including age and sex, were evaluated. Materials and Methods: In total, 273 CBCT scans with complete ethmoid and maxillary sinuses were analyzed to determine the prevalence of Agger nasi cell, supraorbital ethmoid cell, Haller cell, Onodi cell, and ethmomaxillary sinus. In addition, the health or pathology of the ethmoid and maxillary sinuses was also recorded to assess correlations with the aforementioned variations. Results: The prevalence of Agger nasi cell was found to be the highest (95.6%) in this study, followed by Onodi cell (60.4%), Haller cell (29.3%), and supraorbital ethmoid cell (19.4%). Ethmomaxillary sinus was the least common finding (16.5%). Males and persons above 61 years of age had a significantly higher frequency of supraorbital ethmoid cell and Onodi cell, respectively. However, no significant relationships were noted between anatomical variations of the ethmoid sinus and pathologies of the ethmoid or maxillary sinus. Conclusion: There was a high prevalence of ethmoid sinus variations in this Southern Chinese population. The prevalence of Agger nasi cell and Onodi cell was higher than that of other anatomical variations of the ethmoid sinuses. Anatomical variations of the ethmoid sinuses were not associated with ethmoid or maxillary sinus pathologies in this patient cohort.

• Nuclear Engineering and Technology
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• 제55권8호
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• pp.3054-3070
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• 2023

Nuclear Power Plants (NPP) are widely utilized around the globe from different base forms as it is one of the most dependable renewable resources that technological advancements have offered. However, different perceptions of the usage of NPPs emerged from different generations. The purpose of this study was to investigate the acceptance of nuclear energy as an alternative source of energy among Generation Z in the Philippines by utilizing an extended Theory of Planned Behavior (TPB) approach. An online questionnaire which consisted of 31 items was distributed using a purposive sampling approach and 450 respondents of Generation Z voluntarily answered. Structural Equation Modeling (SEM) showed that the knowledge regarding NPP had significant effects on risk perception and benefit perception which subsequently led to subjective norms. In addition, perceived behavioral control and subjective norms had significant effects on behavioral intention which led to nuclear acceptance. Interestingly, the respondents perceived the benefit of NPP as slightly higher than the perceived risk. With these, it was clear that the commissioning Nuclear Power Plant must consider as an alternative source of electric energy in the Philippines. Moreover, this study is one of the first studies that investigated the acceptance of NPP among Generation Z. Lastly, the model could be a basis to strengthen the acceptance strategy of opening NPP among Generation Z, particularly in developing countries.

• Structural Engineering and Mechanics
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• 제88권3호
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• pp.221-238
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• 2023

This paper developed and examined a novel passive vibration isolator (i.e., "X-inerter") motivated by combining a bio-inspired structure and a rack-pinion inerter. The bio-inspired structure provided nonlinear stiffness and damping owing to its geometric nonlinearity. In addition, the behavior was further enhanced by a gear inerter that produced a special nonlinear inertia effect; thus, an X-inerter was developed. As a result, the X-inerter can achieve both high-static-low-dynamic stiffness (HSLDS) and quasi-zero stiffness (QZS), obtaining ultra-low frequency isolation. Furthermore, the installed inerter can produce a coupled nonlinear inertia and damping effect, leading to an anti-resonance frequency near the resonance, wide isolation region, and low resonance peak. Both static and dynamic analyses of the proposed isolator were conducted and the structural parameters' influence was comprehensively investigated. The X-inerter was proven to be comparatively more stable in the ultra-low frequency than the benchmarking QZS isolator due to the nonlinear damping and inertia properties. Moreover, the inertia effect could suppress the bio-inspired structure's super- and sub-harmonic resonance. Therefore, the X-inerter isolator generally possesses desirable nonlinear stiffness, nonlinear damping, and unique nonlinear inertia, designed to achieve the ultra-low natural frequency, the anti-resonance property, and a wide isolation region with a low resonance peak.

• Journal of Electrochemical Science and Technology
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• 제15권1호
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• pp.67-95
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• 2024

Direct alcohol fuel cells (DAFCs) have gained much attention as promising energy conversion devices due to their ability to utilize alcohol as a fuel source. In this regard, Molybdenum-based electrocatalysts (Mo-ECs) have emerged as a substitution for expensive Pt and Ru-based co-catalyst electrode materials in DAFCs, owing to their unique electrochemical properties useful for alcohol oxidation. The catalytic activity of Mo-ECs displays an increase in alcohol oxidation current density by several folds to 1000-2000 mA mg_Pt^-1, compared to commercial Pt and PtRu catalysts of 10-100 mA mg_Pt^-1. In addition, the methanol oxidation peak and onset potential have been significantly reduced by 100-200 mV and 0.5-0.6 V, respectively. The performance of Mo-ECs in both acidic and alkaline media has shown the potential to significantly reduce the Pt loading. This review aims to provide a comprehensive overview of the bifunctional mechanism involved in the oxidation of alcohols and factors affecting the electrocatalytic oxidation of alcohol, such as synthesis method, structural properties, and catalytic support materials. Furthermore, the challenges and prospects of Mo-ECs for DAFCs anode materials are discussed. This in-depth review serves as valuable insight toward enhancing the performance and efficiency of DAFC by employing Mo-ECs.