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  • Online-Ressource  (168)
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  • 1
    Online-Ressource
    Online-Ressource
    Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 5 ( 2021-04-28), p. 629-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 5 ( 2021-04-28), p. 629-
    Kurzfassung: Sorafenib, an oral multikinase inhibitor, exhibits a highly variable absorption profile due to enterohepatic reabsorption and poor solubility. SYO-1644 improved the solubility of sorafenib by nanoparticulation technology leading to enhanced bioavailability. To evaluate the pharmacokinetically equivalent dose of SYO-1644 to the reference Nexavar® 200 mg, a randomized, open-label, replicated two-period study was conducted in healthy volunteers. A total of 32 subjects orally received a single dose of the following assigned treatment under a fasted state in the first period and repeated once more in the second period with a two-week washout: SYO-1644 100, 150 and 200 mg and Nexavar® 200 mg. Pharmacokinetic (PK) samples were collected up to 168 h post-dose. The PK profile was evaluated by both non-compartmental analysis and population PK method. With the final model, 2 × 2 crossover trial scenarios with Nexavar® 200 mg and each dose of SYO-1644 ranging from 100 to 150 mg were repeated 500 times by Monte Carlo simulation, and the proportion of bioequivalence achievement was assessed. Transit absorption compartments, followed by a one-compartment model with first-order elimination and enterohepatic reabsorption components were selected as the final model. The simulation results demonstrated that the SYO-1644 dose between 120 and 125 mg could yielded the highest proportion of bioequivalence.
    Materialart: Online-Ressource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13050629
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2527217-2
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Fabrication of 30 µm Sn Microbumps by Electroplating and Investigation of IMC Characteristics on Shear Strength
    MDPI AG ; 2022
    In:  Electronics Vol. 12, No. 1 ( 2022-12-28), p. 144-
    Details
    In: Electronics, MDPI AG, Vol. 12, No. 1 ( 2022-12-28), p. 144-
    Kurzfassung: In this paper, we prepared a pure Sn microbump with a diameter of 30 µm using an electroplating method for a solder cap on a Cu post/Ni barrier and then determined its IMC characteristics and shear strength according to reflow recovery. In order to secure uniformity of the bump height, it was optimized through WID and WIW evaluation methods. Using an optimized plating system, bumps with a diameter of 30 µm, a height of 40 µm, and a space of 50 µm were formed on a 4-inch wafer. Shear strength was measured according to the number of reflows. IMC was evaluated through cross-sectional and plane analyses of bumps. Its correlation with shear strength according to the number of reflows was derived. The Sn plating system optimized each process condition according to the Sn concentration, current density, and temperature. The shape, surface condition, and height uniformity of the bump were quantified by a 3D profiler and FIB analysis. Height uniformity (WID) according to the concentration was confirmed to be approximately 2% when the Sn concentration was 60 g/L. WID according to the additive was confirmed to be 2% when the Sn concentration was 60 mL/L. WID according to the plating temperature was excellent in the shape of the bump at 30 °C, and a value of 2% was confirmed. The WIW for the Sn plating thickness on a 4-inch wafer was confirmed to have a value of ±3.88%. A shear test between the Cu and Sn junction was conducted to verify the shear strength of the manufactured bump. At this time, reflow was performed 1, 3, 5, 7, and 10 times for each sample. It was confirmed that as the number of flows increased, shear strength first increased. It then decreased sharply. It was confirmed that as the number of reflows increased, the thickness and cross-section area of the IMC first increased. They then gradually became saturated. The IMC between Cu and Sn was created in island form at the beginning of the reflow, resulting in increased roughness and shear strength. However, as the number of reflows increased, the roughness decreased since the IMC generated by the island was combined. The shear strength also decreased sharply.
    Materialart: Online-Ressource
    ISSN: 2079-9292
    URL: Article
    DOI: 10.3390/electronics12010144
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2662127-7
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Closed-Form Analysis of Thin-Walled Composite Beams Using Mixed Variational Approach
    MDPI AG ; 2022
    In:  Aerospace Vol. 9, No. 10 ( 2022-10-04), p. 576-
    Details
    In: Aerospace, MDPI AG, Vol. 9, No. 10 ( 2022-10-04), p. 576-
    Kurzfassung: An analytical methodology is developed for thin-walled composite beams with arbitrary geometries and material distributions. The approach uses a mixed variational theorem which sets the shell displacements, and the shear stress resultants and hoop moments as the unknowns to obtain the stiffness constants at the level of Timoshenko–Vlasov beam. All the field equations and the continuity conditions that should be satisfied over the shell wall are derived in closed form as the part of the analysis. Numerical simulations are conducted to show the validity of the proposed analysis. The comparison of the predicted stresses and the stiffness constants indicates close correlation with those of the detailed finite element (FE)-based analysis and up-to-date beam approaches. Symbolically generated stiffness constants and the sectional warping deformation modes of coupled composite beams are presented explicitly to illustrate the strength of the proposed theory.
    Materialart: Online-Ressource
    ISSN: 2226-4310
    URL: Article
    DOI: 10.3390/aerospace9100576
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2756091-0
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Effects of Irradiance and Temperature on the Photosynthesis of the Crustose Coralline Algae Pneophyllum fragile (Corallinales, Rhodophyta) in the Coastal Waters of Korea
    MDPI AG ; 2022
    In:  Journal of Marine Science and Engineering Vol. 10, No. 7 ( 2022-06-22), p. 851-
    Details
    In: Journal of Marine Science and Engineering, MDPI AG, Vol. 10, No. 7 ( 2022-06-22), p. 851-
    Kurzfassung: We investigated the photosynthetic characteristics of the crustose coralline alga Pneophyllum fragile (Corallinales, Rhodophyta) according to elevated water temperature and irradiance on the coast of Jeju in 2018. P. fragile was cultured under different temperature (11 °C, 21 °C, 26 °C, and 31 °C) and irradiance (0–1250 μmol photon m−2 s−1) conditions. Oxygen (O2) concentrations at the P. fragile mat–water interface (MWI) were measured using an O2 microsensor. At the MWI, the diffusive boundary layer thicknesses ranged from 200 to 400 μm. The O2 concentrations at the mat surface increased in response to increasing irradiance, and reached 344% air saturation. The maximum photosynthesis capacity (Pmax) and respiration rate in the dark (Rd) at 31 °C were about 3 times higher than those recorded at 11 °C. The compensation irradiance (Ec) and saturation irradiance (Ek) increased with increasing water temperature. The Pmax, Rd, and Ec were statistically correlated with temperature (p 〈 0.05). The Ek increased up to 833 μmol photon m−2 s−1 at 31 °C and exhibited a strong dependence on irradiance at high temperatures. The adaptability of P. fragile to high temperatures and strong irradiance was distinct from that observed for coralline algae in other temperate waters.
    Materialart: Online-Ressource
    ISSN: 2077-1312
    URL: Article
    DOI: 10.3390/jmse10070851
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2738390-8
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    Therapeutic Efficacy of ABN401, a Highly Potent and Selective MET Inhibitor, Based on Diagnostic Biomarker Test in MET-Addicted Cancer
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 6 ( 2020-06-15), p. 1575-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 6 ( 2020-06-15), p. 1575-
    Kurzfassung: The receptor tyrosine kinase c-MET regulates processes essential for tissue remodeling and mammalian development. The dysregulation of c-MET signaling plays a role in tumorigenesis. The aberrant activation of c-MET, such as that caused by gene amplification or mutations, is associated with many cancers. c-MET is therefore an attractive therapeutic target, and inhibitors are being tested in clinical trials. However, inappropriate patient selection criteria, such as low amplification or expression level cut-off values, have led to the failure of clinical trials. To include patients who respond to MET inhibitors, the selection criteria must include MET oncogenic addiction. Here, the efficacy of ABN401, a MET inhibitor, was investigated using histopathologic and genetic analyses in MET-addicted cancer cell lines and xenograft models. ABN401 was highly selective for 571 kinases, and it inhibited c-MET activity and its downstream signaling pathway. We performed pharmacokinetic profiling of ABN401 and defined the dose and treatment duration of ABN401 required to inhibit c-MET phosphorylation in xenograft models. The results show that the efficacy of ABN401 is associated with MET status and they highlight the importance of determining the cut-off values. The results suggest that clinical trials need to establish the characteristics of each sample and their correlations with the efficacy of MET inhibitors.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12061575
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 6
    Online-Ressource
    Online-Ressource
    Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 15 ( 2022-07-25), p. 8170-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 15 ( 2022-07-25), p. 8170-
    Kurzfassung: Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23158170
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Diagnostic Blood Biomarkers in Alzheimer’s Disease
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 1 ( 2022-01-13), p. 169-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 1 ( 2022-01-13), p. 169-
    Kurzfassung: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1–42 (Aβ1–42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aβ1–42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aβ1–42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson’s correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aβ1–42 concentrations decreased. The plasma and CSF NFL/Aβ1–42 were strongly correlated (r = 0.558). Plasma NFL/Aβ1–42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aβ1–42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aβ1–42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aβ1–42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.
    Materialart: Online-Ressource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10010169
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2720867-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Effect of Renal Ischemia Reperfusion on Brain Neuroinflammation
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 11 ( 2022-11-21), p. 2993-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 11 ( 2022-11-21), p. 2993-
    Kurzfassung: Acute kidney injury (AKI) is an inflammatory sequence. It can lead to distant organ injury, including damage to the central nervous system (CNS), mediated by increased circulating cytokines and other inflammatory mediators. It can also lead to increased blood–brain barrier (BBB) permeability. However, the effect of AKI on the inflammatory response of the brain has not yet been investigated. Therefore, we observed the effect of AKI on BBB permeability, microglia and astrocyte activation, and neuronal toxicity in the brain. The striatum and ventral midbrain, known to control overall movement, secrete the neurotransmitter dopamine. The activation of microglia and astrocytes present in this area causes neuro-degenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The activation of astrocytes and microglia in the hippocampus and cerebral cortex, which are responsible for important functions, including memory, learning, concentration, and language, can trigger nerve cell apoptosis. The activation of astrocytes and microglia at this site is also involved in the inflammatory response associated with the accumulation of beta-amyloid. In the situation of kidney ischemia reperfusion (IR)-induced AKI, activation of microglia and astrocytes were observed in the striatum, ventral midbrain, hippocampus, and cortex. However, neuronal cell death was not observed until 48 h.
    Materialart: Online-Ressource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10112993
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2720867-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Metabolic and Lipidomic Profiling of Vegetable Juices Fermented with Various Probiotics
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 5 ( 2020-05-06), p. 725-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 5 ( 2020-05-06), p. 725-
    Kurzfassung: Fermented vegetable juices have gained attention due to their various beneficial effects on human health. In this study, we employed gas chromatography–mass spectrometry, direct infusion-mass spectrometry, and liquid chromatography–mass spectrometry to identify useful metabolites, lipids, and carotenoids in vegetable juice (VJ) fermented with Lactobacillus plantarum HY7712, Lactobacillus plantarum HY7715, Lactobacillus helveticus HY7801, and Bifidobacterium animalis ssp. lactis HY8002. A total of 41 metabolites, 24 lipids, and 4 carotenoids were detected in the fermented and non-fermented VJ (control). The lycopene, α-carotene, and β-carotene levels were higher in VJ fermented with L. plantarum strains (HY7712 and HY7715) than in the control. Proline content was also elevated in VJ fermented with HY7715. Uracil, succinic acid, and α-carotene concentration was increased in VJ fermented with HY7801, while glycine and lycopene levels were raised in VJ fermented with HY8002. This study confirmed that each probiotic strain has distinctive characteristics and produces unique changes to metabolic profiles of VJ during fermentation. Our results suggest that probiotic-fermented VJ is a promising functional beverage that contains more beneficial metabolites and carotenoids than commercial non-fermented VJ.
    Materialart: Online-Ressource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10050725
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2701262-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Inhaled Corticosteroids and COVID-19 Risk and Mortality: A Nationwide Cohort Study
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 11 ( 2020-10-23), p. 3406-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 11 ( 2020-10-23), p. 3406-
    Kurzfassung: Inhaled corticosteroids (ICS) could increase both the risk of coronavirus disease 2019 (COVID-19) and experiencing poor outcomes. To compare the clinical outcomes between ICS users and nonusers, COVID-19-related claims in the Korean Health Insurance Review and Assessment database were evaluated. To evaluate susceptibility to COVID-19 among patients with COPD or asthma, a nested case-control study was performed using the same database. In total, 7341 patients were confirmed to have COVID-19, including 114 ICS users and 7227 nonusers. Among 5910 patients who were hospitalized, death was observed for 9% of ICS users and 4% of nonusers. However, this association was not significant when adjusted for age, sex, region, comorbidities, and hospital type (aOR, 0.94; 95% CI, 0.43–2.07). The case-control analysis of COPD compared 640 cases with COVID-19 to 2560 matched controls without COVID-19, and the analysis of asthma compared 90 cases with COVID-19 to 360 matched controls without COVID-19. Use of ICS was not significantly associated with COVID-19 among patients with COPD (aOR, 1.02; 95% CI, 0.46–2.25) or asthma (aOR, 0.38; 95% CI, 0.13–1.17). Prior ICS use was not significantly associated with COVID-19 in patients with COPD or asthma, nor with clinical outcomes among patients with COVID-19.
    Materialart: Online-Ressource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9113406
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2662592-1
    Standort Signatur Einschränkungen Verfügbarkeit
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