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  • 1
    Online Resource
    Online Resource
    Tivantinib, A c-Met Inhibitor in Clinical Trials, Is Susceptible to ABCG2-Mediated Drug Resistance
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 1 ( 2020-01-12), p. 186-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 1 ( 2020-01-12), p. 186-
    Abstract: Tivantinib, also known as ARQ-197, is a potent non-ATP competitive selective c-Met inhibitor currently under phase 3 clinical trial evaluation for liver and lung cancers. In this study, we explored factors that may lead to tivantinib resistance, especially in regards to its interaction with ATP-binding cassette super-family G member 2 (ABCG2). ABCG2 is one of the most important members of the ATP-binding cassette (ABC) transporter family, a group of membrane proteins that play a critical role in mediating multidrug resistance (MDR) in a variety of cancers, including those of the liver and lung. Tivantinib received a high score in docking analysis, indicating a strong interaction between tivantinib and ABCG2, and an ATPase assay indicated that tivantinib stimulated ABCG2 ATPase activity in a concentration-dependent manner. An MTT assay showed that ABCG2 overexpression significantly desensitized both the cancer cells and ABCG2 transfected-HEK293 cells to tivantinib and that this drug resistance can be reversed by ABCG2 inhibitors. Furthermore, tivantinib upregulated the protein expression of ABCG2 without altering the cell surface localization of ABCG2, leading to increased resistance to substrate drugs, such as mitoxantrone. Altogether, these data demonstrate that tivantinib is a substrate of ABCG2, and, therefore, ABCG2 overexpression may decrease its therapeutic effect. Our study provides evidence that the overexpression of ABCG2 should be monitored in clinical settings as an important risk factor for tivantinib drug resistance.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12010186
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Effect of Electrochemical Interaction between Chalcopyrite and Hexagonal Pyrrhotite on Flotation Separation
    MDPI AG ; 2023
    In:  Minerals Vol. 13, No. 10 ( 2023-10-08), p. 1303-
    Details
    In: Minerals, MDPI AG, Vol. 13, No. 10 ( 2023-10-08), p. 1303-
    Abstract: The mechanism of electrochemical interaction between chalcopyrite and hexagonal pyrrhotite was analyzed via electrochemical interaction, copper ion concentration testing, and X-ray photoelectron spectroscopy (XPS) characterization. Besides, the effect of electrochemical interaction between the two minerals on the flotation separation was investigated using the mineral flotation tests, adsorption capacity tests, and a microcalorimetric test. Our research results showed that chalcopyrite had higher electrochemical activity than hexagonal pyrrhotite, and when the former acted as an anode during the electrochemical interaction of the two, the corrosion current density was three times higher than that when it acted alone, and the surface oxidation corrosion was intensified. At the same time, the interaction between the two minerals was accompanied by a large number of copper ions dissolved and adsorbed on the surface of the hexagonal pyrrhotite, so that adsorption of butyl xanthate intensified, adsorption increased, and flotation recovery increased by 5%–20%. However, owing to the increase in metal defects and the generation of hydrophilic sulfate, the surface of chalcopyrite hindered the adsorption of butyl xanthate on its surface, and the flotation recovery decreased by nearly 10% compared with that before the occurrence of the electrochemical interaction. This action also significantly weakened the inhibition effect of lime on hexagonal pyrrhotite and increased the difficulty of the flotation separation of the two minerals. The research results of this study provide theoretical guidance for the flotation separation of copper–sulfur ores containing pyrrhotite.
    Type of Medium: Online Resource
    ISSN: 2075-163X
    URL: Article
    DOI: 10.3390/min13101303
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2655947-X
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  • 3
    Online Resource
    Online Resource
    Evidence That DDR1 Promotes Oligodendrocyte Differentiation during Development and Myelin Repair after Injury
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-19), p. 10318-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-19), p. 10318-
    Abstract: Oligodendrocytes generate myelin sheaths vital for the formation, health, and function of the central nervous system. Mounting evidence suggests that receptor tyrosine kinases (RTKs) are crucial for oligodendrocyte differentiation and myelination in the CNS. It was recently reported that discoidin domain receptor 1 (Ddr1), a collagen-activated RTK, is expressed in oligodendrocyte lineage. However, its specific expression stage and functional role in oligodendrocyte development in the CNS remain to be determined. In this study, we report that Ddr1 is selectively upregulated in newly differentiated oligodendrocytes in the early postnatal CNS and regulates oligodendrocyte differentiation and myelination. Ddr1 knock-out mice of both sexes displayed compromised axonal myelination and apparent motor dysfunction. Ddr1 deficiency alerted the ERK pathway, but not the AKT pathway in the CNS. In addition, Ddr1 function is important for myelin repair after lysolecithin-induced demyelination. Taken together, the current study described, for the first time, the role of Ddr1 in myelin development and repair in the CNS, providing a novel molecule target for the treatment of demyelinating diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241210318
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Simultaneous Determination of Eight Alkaloids in Rat Plasma by UHPLC-MS/MS after Oral Administration of Coptis deltoidea C. Y. Cheng et Hsiao and Coptis chinensis Franch
    MDPI AG ; 2016
    In:  Molecules Vol. 21, No. 7 ( 2016-07-14), p. 913-
    Details
    In: Molecules, MDPI AG, Vol. 21, No. 7 ( 2016-07-14), p. 913-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules21070913
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2008644-1
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  • 5
    Online Resource
    Online Resource
    Predictions of Preterm Birth from Early Pregnancy Characteristics: Born in Guangzhou Cohort Study
    MDPI AG ; 2018
    In:  Journal of Clinical Medicine Vol. 7, No. 8 ( 2018-07-27), p. 185-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 7, No. 8 ( 2018-07-27), p. 185-
    Abstract: Preterm birth (PTB, 〈 37 weeks) is the leading cause of death in children 〈 5 years of age. Early risk prediction for PTB would enable early monitoring and intervention. However, such prediction models have been rarely reported, especially in low- and middle-income areas. We used data on a number of easily accessible predictors during early pregnancy from 9044 women in Born in Guangzhou Cohort Study, China to generate prediction models for overall PTB and spontaneous, iatrogenic, late (34–36 weeks), and early ( 〈 34 weeks) PTB. Models were constructed using the Cox proportional hazard model, and their performance was evaluated by Harrell’s c and D statistics and calibration plot. We further performed a systematic review to identify published models and validated them in our population. Our new prediction models had moderate discrimination, with Harrell’s c statistics ranging from 0.60–0.66 for overall and subtypes of PTB. Significant predictors included maternal age, height, history of preterm delivery, amount of vaginal bleeding, folic acid intake before pregnancy, and passive smoking during pregnancy. Calibration plots showed good fit for all models except for early PTB. We validated three published models, all of which were from studies conducted in high-income countries; the area under receiver operating characteristic for these models ranged from 0.50 to 0.56. Based on early pregnancy characteristics, our models have moderate predictive ability for PTB. Future studies should consider inclusion of laboratory markers for the prediction of PTB.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm7080185
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662592-1
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  • 6
    Online Resource
    Online Resource
    Repair of Retinal Degeneration by Human Amniotic Epithelial Stem Cell–Derived Photoreceptor–like Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 15 ( 2022-08-05), p. 8722-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 15 ( 2022-08-05), p. 8722-
    Abstract: The loss of photoreceptors is a major event of retinal degeneration that accounts for most cases of untreatable blindness globally. To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two–step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor–like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non–classical MHC class I molecule HLA–G. Importantly, subretinal transplantation of the hAESCs–derived PR–like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs–derived photoreceptor–like cells could be a promising cell–replacement candidate for therapy of retinal degeneration diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23158722
    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
    Preparation and Performance Study of Radiation-Proof Ultra-High-Performance Concrete
    MDPI AG ; 2023
    In:  Coatings Vol. 13, No. 5 ( 2023-05-11), p. 906-
    Details
    In: Coatings, MDPI AG, Vol. 13, No. 5 ( 2023-05-11), p. 906-
    Abstract: With the continuous development of nuclear technology, it is necessary to urgently solve the nuclear safety problem. γ-rays have a strong penetrating power. The γ-ray-shielding performance of ordinary concrete prepared with natural sand is weak and cannot meet the practical application of engineering. The γ-ray shielding performance of concrete can be effectively improved through the use of titaniferous sand with a better γ-ray protection effect. To prepare ultra-high-performance concrete (UHPC) that can provide radiation protection, the influence law of its performance was investigated. The effects of ilmenite sand on the workability, mechanical properties, durability, and radiation-shielding properties of UHPC were investigated via mix testing, compressive strength and flexural strength testing, and a radiation-shielding simulation. The results show that an appropriate amount of ilmenite sand can improve the ultra-high-performance concrete’s work performance; however, ilmenite sand has little effect on its compressive strength. Although it is not conducive to the development of flexural and tensile strength, the γ-ray shielding performance of the UHPC increases with an increase in the addition of ilmenite sand. When the titanite sand admixture is 70%, the γ-ray linear absorption coefficient of the prepared UHPC is 0.158 cm−1, and the γ-ray shielding performance is significantly improved; meanwhile, its durability performance is excellent.
    Type of Medium: Online Resource
    ISSN: 2079-6412
    URL: Article
    DOI: 10.3390/coatings13050906
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662314-6
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  • 8
    Online Resource
    Online Resource
    Coupling Effect of Expansion Agent and Internal Curing Aggregate on Shrinkage of High-Modulus Ultra-High-Performance Concrete
    MDPI AG ; 2023
    In:  Coatings Vol. 13, No. 9 ( 2023-09-08), p. 1571-
    Details
    In: Coatings, MDPI AG, Vol. 13, No. 9 ( 2023-09-08), p. 1571-
    Abstract: In the realm of bridge structural engineering, it is customary to meticulously contemplate the material’s strength and rigidity attributes during the dimensioning phase. In recent years, there has been a burgeoning interest in employing Ultrahigh-Performance Concrete (abbreviated as UHPC) for the construction of bridge decks and wet joints. However, the large self-shrinkage of UHPC can easily lead to shrinkage cracking and affect its service life. This study delves into the utilization of a blend of basalt coarse aggregate and high-modulus aggregate (HMA) in the formulation of Ultrahigh-Performance Concrete (UHPC) with the objectives of achieving exceptional strength ( 〉 180 MPa), superior modulus of elasticity ( 〉 56 GPa), and synergistic effect of using prewetted internal curing aggregate (ICA), metallurgical ore sand (MOS), and calcium–magnesium composite-based expansion agent (EA) to reduce the shrinkage of UHPC. Furthermore, the mechanical properties, shrinkage, hydration process, and microstructure of UHPC prepared with EA and ICA were studied. The results show that UHPC prepared with both 3% EA and 20% ICA had the optimal volume stability (the shrinkage was only 273 με at 180 d). In contrast, the 180 d shrinkage of UHPC with 3% EA and 20% ICA separately was 287 με and 373 με, respectively. In addition, the incorporation of EA and ICA can effectively improve the flexural strength of UHPC, although it affects the compressive strength and modulus of elasticity of UHPC (small decrease).
    Type of Medium: Online Resource
    ISSN: 2079-6412
    URL: Article
    DOI: 10.3390/coatings13091571
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662314-6
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  • 9
    Online Resource
    Online Resource
    Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 21, No. 1 ( 2019-12-24), p. 131-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 1 ( 2019-12-24), p. 131-
    Abstract: Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax–caspase-3 axis and the inhibition of the NF-κB signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21010131
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    An Integration Method for Regional PM2.5 Pollution Control Optimization Based on Meta-Analysis and Systematic Review
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 1 ( 2021-12-29), p. 344-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 1 ( 2021-12-29), p. 344-
    Abstract: PM2.5 pollution in China is becoming increasingly severe, threatening public health. The major goal of this study is to evaluate the mortality rate attributed to PM2.5 pollution and design pollution mitigation schemes in a southern district of China through a two-objective optimization model. The mortality rate is estimated by health effect evaluation model. Subjected to limited data information, it is assumed that the meta-analysis method, through summarizing and combining the research results on the same subject, was suitable to estimate the percentage of deaths caused by PM2.5 pollution. The critical parameters, such as the total number of deaths and the background concentration of PM2.5, were obtained through on-site survey, data collection, literature search, policy analysis, and expert consultation. The equations for estimating the number of deaths caused by PM2.5 pollution were established by incorporating the relationship coefficient of exposure to reaction, calculated residual PM2.5 concentration of affected region, and statistical total base number of deaths into a general framework. To balance the cost from air quality improvement and human health risks, a two-objective optimization model was developed. The first objective is to minimize the mortality rate attributable to PM2.5 pollution, and the second objective is to minimize the total system cost over three periods. The optimization results demonstrated that the combination of weights assigned to the two objectives significantly influenced the model output. For example, a high weight value assigned to minimizing the number of deaths results in the increased use of treatment techniques with higher efficiencies and a dramatic decrease in pollutant concentrations. In contrast, a model weighted more toward minimizing economic loss may lead to an increase in the death toll due to exposure to higher air pollution levels. The effective application of this model in the Nanshan District of Shenzhen City, China, is expected to serve as a basis for similar work in other parts of the world in the future.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19010344
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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