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  • 1
    In: Vaccines, MDPI AG, Vol. 9, No. 7 ( 2021-07-07), p. 754-
    Abstract: Hepatitis B virus (HBV) is a global health burden that causes acute and chronic hepatitis. To develop an HBV-neutralizing antibody that effectively prevents HBV infection, we previously generated a human anti-preS1 monoclonal antibody (1A8) that binds to genotypes A–D and validated its HBV-neutralizing activity in vitro. In the present study, we aimed to determine the fine epitope and paratope of 1A8 to understand the mechanism of HBV neutralization. We performed alanine-scanning mutagenesis on the preS1 (aa 19–34, genotype C) and the heavy (HCDR) and light (LCDR) chain complementarity-determining regions. The 1A8 recognized the three residues (Leu22, Gly23, and Phe25) within the highly conserved receptor-binding motif (NPLGFFP) of the preS1, while four CDR residues of 1A8 were critical in antigen binding. Structural analysis of the epitope–paratope interaction by molecular modeling revealed that Leu100 in the HCDR3, Ala50 in the HCDR2, and Tyr96 in the LCDR3 closely interacted with Leu22, Gly23, and Phe25 of the preS1. Additionally, we found that 1A8 also binds to the receptor-binding motif (NPLGFLP) of infrequently occurring HBV. The results suggest that 1A8 may broadly and effectively block HBV entry and thus have potential as a promising candidate for the prevention and treatment of HBV infection.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2703319-3
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  • 2
    In: Agriculture, MDPI AG, Vol. 13, No. 1 ( 2023-01-11), p. 183-
    Abstract: Proanthocyanidins (PAs) are major phytochemicals in rice, and accumulate abundantly in red pericarp (RP) rice. Consumers and rice breeders are increasingly showing interest in PAs because of their beneficial health effects; however, PA biosynthesis in rice is not well-understood. Therefore, to gain insights into this process, we performed comparative transcriptome analysis of grains harvested at 14 days after flowering (DAF; i.e., the stage at which active PA biosynthesis occurs without pericarp color change) and 28 DAF (the stage of late seed development with pericarp color change) from RP and white pericarp rice. In RP rice at 14 DAF, the expression levels of six structural genes (OsCHS, OsF3H, OsF3′H, OsDFR, OsANS, and OsLAR), one modification gene (OsUGT), and one transport gene (OsGSTU34) were significantly upregulated, along with the activation of Rc, the key regulator of PA accumulation in the pericarp. Functional enrichment analysis of 56 differentially expressed genes specifically upregulated in RP rice at 28 DAF revealed the presence of three laccase genes known to cause the browning reaction through oxidation. These results expand our understanding of PA biosynthesis in rice, and provide a genetic basis that will lead to further studies on the genes and underlying molecular mechanisms associated with this process.
    Type of Medium: Online Resource
    ISSN: 2077-0472
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2651678-0
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  • 3
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 13 ( 2021-06-22), p. 6696-
    Abstract: The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)—which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue—exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 21 ( 2021-10-28), p. 11646-
    Abstract: The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1-knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1-knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 21 ( 2021-10-28), p. 11647-
    Abstract: Selenophosphate synthetase 1 (SEPHS1) plays an essential role in cell growth and survival. However, the underlying molecular mechanisms remain unclear. In the present study, the pathways regulated by SEPHS1 during gastrulation were determined by bioinformatical analyses and experimental verification using systemic knockout mice targeting Sephs1. We found that the coagulation system and retinoic acid signaling were most highly affected by SEPHS1 deficiency throughout gastrulation. Gene expression patterns of altered embryo morphogenesis and inhibition of Wnt signaling were predicted with high probability at E6.5. These predictions were verified by structural abnormalities in the dermal layer of Sephs1−/− embryos. At E7.5, organogenesis and activation of prolactin signaling were predicted to be affected by Sephs1 knockout. Delay of head fold formation was observed in the Sephs1−/− embryos. At E8.5, gene expression associated with organ development and insulin-like growth hormone signaling that regulates organ growth during development was altered. Consistent with these observations, various morphological abnormalities of organs and axial rotation failure were observed. We also found that the gene sets related to redox homeostasis and apoptosis were gradually enriched in a time-dependent manner until E8.5. However, DNA damage and apoptosis markers were detected only when the Sephs1−/− embryos aged to E9.5. Our results suggest that SEPHS1 deficiency causes a gradual increase of oxidative stress which changes signaling pathways during gastrulation, and afterwards leads to apoptosis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 9 ( 2022-05-02), p. 5044-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 9 ( 2022-05-02), p. 5044-
    Abstract: Hydrogels capable of stimuli-responsive deformation are widely explored as intelligent actuators for diverse applications. It is still a significant challenge, however, to “program” these hydrogels to undergo highly specific and extensive shape changes with precision, because the mechanical properties and deformation mechanism of the hydrogels are inherently coupled. Herein, two engineering strategies are simultaneously employed to develop thermoresponsive poly(N-isopropyl acrylamide) (PNIPAm)-based hydrogels capable of programmable actuation. First, PNIPAm is copolymerized with poly(ethylene glycol) diacrylate (PEGDA) with varying molecular weights and concentrations. In addition, graphene oxide (GO) or reduced graphene oxide (rGO) is incorporated to generate nanocomposite hydrogels. These strategies combine to allow the refined control of mechanical and diffusional properties of hydrogels over a broad range, which also directly influences variable thermoresponsive actuation. It is expected that this comprehensive design principle can be applied to a wide range of hydrogels for programmable actuation.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  Energies Vol. 16, No. 11 ( 2023-06-03), p. 4505-
    In: Energies, MDPI AG, Vol. 16, No. 11 ( 2023-06-03), p. 4505-
    Abstract: Recently, the conversion of livestock manure to solid fuel via torrefaction has brought more attention to moving forward to a carbon neutral society. A proper design of livestock manure to solid fuel is key for sustainable waste management. In this study, cow manure, as a representative of livestock manure, was examined for solid fuel production, focusing on enhancing the heating value. The torrefaction process was adopted as a main solid fuel generation process and compared to simple drying. The heating value of the torrefied cow manure was increased as the torrefaction temperature increased from 200 °C to 300 °C. The heating value was nearly saturated at around 30 min when the torrefaction temperature was increased from 20 min to 40 min. The heating value was further increased when the cow manure was mixed with sawdust or rice straw. The sawdust, which originally possessed a higher heating value, showed its potential as a candidate for additives to the torrefaction of cow manure. Compared to simple drying, torrefaction showed a higher heating value and energy density, successfully converting to stable carbon material.
    Type of Medium: Online Resource
    ISSN: 1996-1073
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2437446-5
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2017
    In:  Sensors Vol. 17, No. 8 ( 2017-08-10), p. 1850-
    In: Sensors, MDPI AG, Vol. 17, No. 8 ( 2017-08-10), p. 1850-
    Abstract: Most of the commercial nighttime pedestrian detection (PD) methods reported previously utilized the histogram of oriented gradient (HOG) or the local binary pattern (LBP) as the feature and the support vector machine (SVM) as the classifier using thermal camera images. In this paper, we propose a new feature called the thermal-position-intensity-histogram of oriented gradient (TPIHOG or T π HOG) and developed a new combination of the T π HOG and the additive kernel SVM (AKSVM) for efficient nighttime pedestrian detection. The proposed T π HOG includes detailed information on gradient location; therefore, it has more distinctive power than the HOG. The AKSVM performs better than the linear SVM in terms of detection performance, while it is much faster than other kernel SVMs. The combined T π HOG-AKSVM showed effective nighttime PD performance with fast computational time. The proposed method was experimentally tested with the KAIST pedestrian dataset and showed better performance compared with other conventional methods.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2052857-7
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  • 9
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  Applied Sciences Vol. 10, No. 23 ( 2020-12-04), p. 8656-
    In: Applied Sciences, MDPI AG, Vol. 10, No. 23 ( 2020-12-04), p. 8656-
    Abstract: Wheat (Triticum aestivum Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, T. aestivum hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (1) and seven flavonolignans (2–8). Compounds 2–8 have not yet been isolated from Triticum species. All compounds were evaluated for their LPS-induced NO production inhibition, and 1, 2, 4, 6, and 8 exhibited inhibitory effects with IC50 values ranging from 24.14 to 58.95 μM. These results suggest the potential of using T. aestivum hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704225-X
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  • 10
    In: Polymers, MDPI AG, Vol. 13, No. 21 ( 2021-10-28), p. 3715-
    Abstract: Polyimides (PIs) are widely utilized polymeric materials for high-temperature plastics, adhesives, dielectrics, nonlinear optical materials, flexible hard-coating films, and substrates for flexible electronics. PIs can be facilely mass-produced through factory methods, so the industrial application value is limitless. Herein, we synthesized a typical poly(amic acid) (PAA) precursor-based solution through an industrialized reactor for mass production and applied the prepared solution to form thin films of PI using thermal imidization. The deposited PI thin films were successfully applied as gate dielectrics for organic field-effect transistors (OFETs). The PI layers showed suitable characteristics for dielectrics, such as a smooth surface, low leakage current density, uniform dielectric constant (k) values regardless of frequency, and compatibility with organic semiconductors. Utilizing this PI layer, we were able to fabricate electrically stable operated OFETs, which exhibited a threshold voltage shift lower than 1 V under bias-stress conditions and a field-effect mobility of 4.29 cm2 V−1 s−1. Moreover, integrated logic gates were manufactured using these well-operated OFETs and displayed suitable operation behavior.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527146-5
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