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  • 1
    In: Cancers, MDPI AG, Vol. 13, No. 2 ( 2021-01-18), p. 331-
    Abstract: Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4–47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3–5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
    In: Cells, MDPI AG, Vol. 8, No. 12 ( 2019-11-28), p. 1538-
    Abstract: Background: The aim of this study is to elucidate the mechanisms of acquired resistance to pemetrexed in echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer. Methods: We analyzed the sensitivity to pemetrexed and the expression patterns of various proteins after pemetrexed treatment in the cell lines, A549, NCI-H460, NCI-H2228 harboring EML4-ALK variant 3, and NCI-H3122 harboring EML4-ALK variant 1. Pemetrexed-resistant cell lines were also generated through long-term exposure to pemetrexed. Results: The EML4-ALK variant 1 rearranged NCI-H3122 was found to be more sensitive than the other cell lines. Cell cycle analysis after pemetrexed treatment showed that the fraction of cells in the S phase increased in A549, NCI-H460, and NCI-H2228, whereas the fraction in the apoptotic sub-G1 phase increased in NCI-H3122. The pemetrexed-resistant NCI-H3122 cell line showed increased expression of EGFR and HER2 compared to the parent cell line, whereas A549 and NCI-H460 did not show this change. The pan-HER inhibitor afatinib inhibited this alternative signaling pathway, resulting in a superior cytotoxic effect in pemetrexed-resistant NCI-H3122 cell lines compared to that in the parental cells line. Conclusion: The activation of EGFR-HER2 contributes to the acquisition of resistance to pemetrexed in EML4-ALK rearranged non-small cell lung cancer. However, the inhibition of this alternative survival signaling pathway with RNAi against EGFR-HER2 and with afatinib overcomes this resistance.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661518-6
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  • 3
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-03), p. 2500-
    Abstract: Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of PIK3CA mutation status but showed greater efficacy in the PIK3CA mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 4
    In: Polymers, MDPI AG, Vol. 11, No. 11 ( 2019-10-26), p. 1759-
    Abstract: We report the employment of an electrohydrodynamic-jet (EHD)-printed diketopyrrolopyrrole-based copolymer (P-29-DPPDTSE) as the active layer of fabricated organic field-effect transistors (OFETs) and circuits. The device produced at optimal conditions showed a field-effect mobility value of 0.45 cm2/(Vs). The morphologies of the printed P-29-DPPDTSE samples were determined by performing optical microscopy, X-ray diffraction, and atomic force microscopy experiments. In addition, numerical circuit simulations of the optimal printed P-29-DPPDTSE OFETs were done in order to observe how well they would perform in a high-voltage logic circuit application. The optimal printed P-29-DPPDTSE OFET showed a 0.5 kHz inverter frequency and 1.2 kHz ring oscillator frequency at a 40 V supply condition, indicating the feasibility of its use in a logic circuit application at high voltage.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527146-5
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  • 5
    In: Anatomia, MDPI AG, Vol. 1, No. 2 ( 2022-10-01), p. 134-147
    Abstract: EduTech (Education and Technology) has drawn great attention in improving education efficiency for non-face-to-face learning and practice. This paper introduced a blended gross anatomy class using both virtual reality (VR) devices and traditional programs alongside a practice-based cadaver dissection and in-class observation. The class allowed the students to get hands-on experience with both practical practice and VR operations to identify the biochemical aspects of the disease-induced internal organ damage as well as to view the three-dimensional (3D) aspect of human structures that cannot be practiced during the gross anatomy practice. Student surveys indicated an overall positive experience using VR education (satisfaction score over 4 out of 5, Likert scale question). There remains room for improvement, and it was discussed with the results of the essay-based question survey. Formative evaluation results showed that the students who trained in blended anatomy classes with VR set-ups received higher scores (85.28 out of 100, average score) than only cadaver-based anatomy class (79.06 out of 100, average score), and this result represents that the hybrid method could improve the academic efficiency and support the understanding of the 3D structure of the body. At present, VR cannot totally replace actual cadaver dissection practice, but it will play a significant role in the future of medical education if both students and practitioners have more VR devices, practice time, and a more intuitive user-friendly VR program. We believe that our paper will greatly benefit the development of EduTech and a potential new curriculum item for future medical education.
    Type of Medium: Online Resource
    ISSN: 2813-0545
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3117607-0
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  • 6
    In: Biology, MDPI AG, Vol. 12, No. 10 ( 2023-10-09), p. 1317-
    Abstract: The mitogenomic evolution of the Psettodes flatfishes is still poorly known from their range distribution in eastern Atlantic and Indo-West Pacific Oceans. The study delves into the matrilineal evolutionary pathway of these primitive flatfishes, with a specific focus on the complete mitogenome of the Psettodes belcheri species, as determined through next-generation sequencing. The mitogenome in question spans a length of 16,747 base pairs and comprises a total of 37 genes, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. Notably, the mitogenome of P. belcheri exhibits a bias towards AT base pairs, with a composition of 54.15%, mirroring a similar bias observed in its close relative, Psettodes erumei, which showcases percentages of 53.07% and 53.61%. Most of the protein-coding genes commence with an ATG initiation codon, except for Cytochrome c oxidase I (COI), which initiates with a GTG codon. Additionally, four protein-coding genes commence with a TAA termination codon, while seven others exhibit incomplete termination codons. Furthermore, two protein-coding genes, namely NAD1 and NAD6, terminate with AGG and TAG stop codons, respectively. In the mitogenome of P. belcheri, the majority of transfer RNAs demonstrate the classical cloverleaf secondary structures, except for tRNA-serine, which lacks a DHU stem. Comparative analysis of conserved blocks within the control regions of two Psettodidae species unveiled that the CSB-II block extended to a length of 51 base pairs, surpassing the other blocks and encompassing highly variable sites. A comprehensive phylogenetic analysis using mitochondrial genomes (13 concatenated PCGs) categorized various Pleuronectiformes species, highlighting the basal position of the Psettodidae family and showed monophyletic clustering of Psettodes species. The approximate divergence time (35−10 MYA) between P. belcheri and P. erumei was estimated, providing insights into their separation and colonization during the early Miocene. The TimeTree analysis also estimated the divergence of two suborders, Psettodoidei and Pleuronectoidei, during the late Paleocene to early Eocene (56.87 MYA). The distribution patterns of Psettodes flatfishes were influenced by ocean currents and environmental conditions, contributing to their ecological speciation. In the face of climate change and anthropogenic activities, the conservation implications of Psettodes flatfishes are emphasized, underscoring the need for regulated harvesting and adaptive management strategies to ensure their survival in changing marine ecosystems. Overall, this study contributes to understanding the evolutionary history, genetic diversity, and conservation needs of Psettodes flatfishes globally. However, the multifaceted exploration of mitogenome and larger-scale genomic data of Psettodes flatfish will provide invaluable insights into their genetic characterization, evolutionary history, environmental adaptation, and conservation in the eastern Atlantic and Indo-West Pacific Oceans.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661517-4
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  • 7
    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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  • 8
    In: Genes, MDPI AG, Vol. 11, No. 3 ( 2020-03-21), p. 337-
    Abstract: The radish is a highly self-incompatible plant, and consequently it is difficult to produce homozygous lines. Bud pollination in cross-fertilization plants should be done by opening immature pollen and attaching pollen to mature flowers. It accordingly takes a lot of time and effort to develop lines with fixed alleles. In the current study, a haploid breeding method has been applied to obtain homozygous plants in a short period of time by doubling chromosomes through the induction of a plant body in the haploid cells, in order to shorten the time to breed inbred lines. We constructed genetic maps with an F1 population derived by crossing parents that show a superior and inferior ability to regenerate microspores, respectively. Genetic maps were constructed from the maternal and parental maps, separately, using the two-way pseudo-testcross model. The phenotype of the regeneration rate was examined by microspore cultures and a quantitative trait loci (QTL) analysis was performed based on the regeneration rate. From the results of the culture of microspores in the F1 population, more than half of the group did not regenerate, and only a few showed a high regeneration rate. A total of five significant QTLs were detected in the F1 population, and five candidate genes were found based on the results. These candidate genes are divided into two classes, and appear to be related to either PRC2 subunits or auxin synthesis.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
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  • 9
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 20 ( 2020-10-09), p. 7444-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 20 ( 2020-10-09), p. 7444-
    Abstract: In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL)-treated human kidney proximal tubule epithelial (HK-2) cells. ApoE knockout (KO) mice underwent uninephrectomy to induce CKD, and were fed a normal diet or high-cholesterol (HC) diet along with the XO inhibitor topiroxostat (1 mg/kg/day). HK-2 cells were treated with LDL (200 µg/mL) and topiroxostat (5 µM) or small interfering RNA against xanthine dehydrogenase (siXDH; 20 nM). In uninephrectomized ApoE KO mice, the HC diet increased cholesterol accumulation, oxidative stress, XO activity, and kidney damage, while topiroxostat attenuated the hypercholesterolemia-associated renal dysfunction. The HC diet induced cholesterol accumulation by regulating the expressions of genes involved in cholesterol efflux (Nr1h3 and Abca1) and synthesis (Srebf2 and Hmgcr), which was reversed by topiroxostat. Topiroxostat suppressed the expressions of genes related to hypercholesterolemia-associated inflammation and fibrosis in the unilateral kidney. LDL stimulation evoked changes in the cholesterol metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and NF-κB pathways in HK-2 cells, which were mitigated by XO inhibition with topiroxostat or siXDH. These findings suggest that XO inhibition exerts renoprotective effects against hypercholesterolemia-associated kidney injury. XO could be a novel therapeutic target for hypercholesterolemia-associated kidney injury in uninephrectomized patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    In: Foods, MDPI AG, Vol. 12, No. 1 ( 2022-12-22), p. 43-
    Abstract: This study investigated the effects of the aging period on the black elephant garlic (Allium ampeloprasum L.) manufacturing process. Black elephant garlic is a processed elephant garlic product prepared by high-temperature and high-humidity treatment for 40 days. The proximate composition (moisture, crude lipid, crude protein, carbohydrate, and ash), minerals, color values, reducing sugars, pH, total polyphenol contents, total flavonoid contents and antioxidant activities of elephant garlic and black elephant garlic were evaluated. The browning intensity of elephant garlic increased with the aging period, but the browning reaction terminated after aging for 30 days, exhibiting the same browning level. Reducing sugars increased over the aging period until 20 days, and then decreased with the aging period, in contrast to the pH, which decreased from 6.47 to 3.68 over the aging period. Antioxidant components, including the total polyphenol and total flavonoid contents of black elephant garlic, increased significantly until day 30 of aging. From the metabolite profiles determined through GC/MS analysis, it was confirmed that primary metabolites related to antioxidant components, such as lactic acid and 5-hydroxymethyl-2-furoic acid, were generated during the aging process of elephant garlic.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704223-6
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