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Open AccessArticle
Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy
J. Clin. Med. 2020, 9(1), 64; https://doi.org/10.3390/jcm9010064 (registering DOI) - 26 Dec 2019
Abstract
The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 [...] Read more.
The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradiation (i.e., 5 × 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 µM Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µM and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 µM and 10 Gy and of only 0.9 (both models) after 50 µM and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle
Regional Temperature-Sensitive Diseases and Attributable Fractions in China
Int. J. Environ. Res. Public Health 2020, 17(1), 184; https://doi.org/10.3390/ijerph17010184 (registering DOI) - 26 Dec 2019
Abstract
Few studies have been carried out to systematically screen regional temperature-sensitive diseases. This study was aimed at systematically and comprehensively screening both high- and low-temperature-sensitive diseases by using mortality data from 17 study sites in China located in temperate and subtropical climate zones. [...] Read more.
Few studies have been carried out to systematically screen regional temperature-sensitive diseases. This study was aimed at systematically and comprehensively screening both high- and low-temperature-sensitive diseases by using mortality data from 17 study sites in China located in temperate and subtropical climate zones. The distributed lag nonlinear model (DLNM) was applied to quantify the association between extreme temperature and mortality to screen temperature-sensitive diseases from 18 kinds of diseases of eight disease systems. The attributable fractions (AFs) of sensitive diseases were calculated to assess the mortality burden attributable to high and low temperatures. A total of 1,380,713 records of all-cause deaths were involved. The results indicate that injuries, nervous, circulatory and respiratory diseases are sensitive to heat, with the attributable fraction accounting for 6.5%, 4.2%, 3.9% and 1.85%, respectively. Respiratory and circulatory diseases are sensitive to cold temperature, with the attributable fraction accounting for 13.3% and 11.8%, respectively. Most of the high- and low-temperature-sensitive diseases seem to have higher relative risk in study sites located in subtropical zones than in temperate zones. However, the attributable fractions for mortality of heat-related injuries were higher in temperate zones. The results of this research provide epidemiological evidence of the relative burden of mortality across two climate zones in China. Full article
(This article belongs to the Special Issue (In)Direct Health Effects of Extreme Weather)
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Open AccessReview
A Comprehensive Review of DC–DC Converter Topologies and Modulation Strategies with Recent Advances in Solar Photovoltaic Systems
Electronics 2020, 9(1), 31; https://doi.org/10.3390/electronics9010031 (registering DOI) - 26 Dec 2019
Abstract
Renewable Energy Sources (RES) showed enormous growth in the last few years. In comparison with the other RES, solar power has become the most feasible source because of its unique properties such as clean, noiseless, eco-friendly nature, etc. During the extraction of electric [...] Read more.
Renewable Energy Sources (RES) showed enormous growth in the last few years. In comparison with the other RES, solar power has become the most feasible source because of its unique properties such as clean, noiseless, eco-friendly nature, etc. During the extraction of electric power, the DC–DC converters were given the prominent interest because of their extensive use in various applications. Photovoltaic (PV) systems generally suffer from less energy conversion efficiency along with improper stability and intermittent properties. Hence, there is a necessity of the Maximum power point tracking (MPPT) algorithm to ensure the maximum power available that can be harnessed from the solar PV. In this paper, the most important features of the DC/DC converters along with the MPPT techniques are reviewed and analyzed. A detailed comprehensive analysis is made on different converter topologies of both non-isolated and isolated DC/DC converters. Then, the modulation strategies, comparative performance evaluation are addressed systematically. At the end, recent advances and future trends are described briefly and considered for the next-generation converter’s design and applications. This review work will provide a useful structure and reference point on the DC/DC converters for researchers and designers working in the field of solar PV applications. Full article
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Open AccessArticle
QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor
Molecules 2020, 25(1), 97; https://doi.org/10.3390/molecules25010097 (registering DOI) - 26 Dec 2019
Abstract
Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and para-quinonic indeno[1,2- [...] Read more.
Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical IC50 values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-b]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them (N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit CK2 with an IC50 value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessFeature PaperArticle
Hybrid Material Based on an Amorphous-Carbon Matrix and ZnO/Zn for the Solar Photocatalytic Degradation of Basic Blue 41
Molecules 2020, 25(1), 96; https://doi.org/10.3390/molecules25010096 (registering DOI) - 26 Dec 2019
Abstract
Innovative composites based on an amorphous-carbon matrix containing a second phase ZnO oxide and/or highly dispersed Zn metallic were synthesized via a modified Pechini route, in which a partial pyrolysis method was reached. Studies of adsorption in the dark and the photocatalytic activity [...] Read more.
Innovative composites based on an amorphous-carbon matrix containing a second phase ZnO oxide and/or highly dispersed Zn metallic were synthesized via a modified Pechini route, in which a partial pyrolysis method was reached. Studies of adsorption in the dark and the photocatalytic activity for the cationic azo-dye, basic blue 41, and degradation were carried out. X-ray diffraction patterns for the carbon matrix and its composite with Zn show characteristics of the amorphous carbon. The infrared in the mid region of the composite prepared with ZnO and Zn exhibit vibrational bands related to bonds zinc oxide. The surface pH of the material is the main factor responsible for the adsorption of the azo-dye, but the contribution of mesopores favored the diffusion of molecules from the bulk of solution to the pore framework. Esters-like functional groups on the surface of carbons hinder the adsorption of the azo-dye. When Zn is embedded within amorphous carbon the photocatalytic activity of the composites showed up to 2.4 higher than neat ZnO. The enhancement in the photocatalytic activity and stability of C/ZnO/Zn and C/Zn composites is discussed in terms of a protector effect by the carbon layers inserted in composites. Carbon layers are responsible to inhibit the lixiviation of ZnO particles along irradiation. Full article
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Open AccessReview
Nanoantioxidants: Recent Trends in Antioxidant Delivery Applications
Antioxidants 2020, 9(1), 24; https://doi.org/10.3390/antiox9010024 (registering DOI) - 26 Dec 2019
Abstract
Antioxidants interact with free radicals, terminating the adverse chain reactions and converting them to harmless products. Antioxidants thus minimize the oxidative stress and play a crucial role in the treatment of free radicals-induced diseases. However, the effectiveness of natural and/or synthetic antioxidants is [...] Read more.
Antioxidants interact with free radicals, terminating the adverse chain reactions and converting them to harmless products. Antioxidants thus minimize the oxidative stress and play a crucial role in the treatment of free radicals-induced diseases. However, the effectiveness of natural and/or synthetic antioxidants is limited due to their poor absorption, difficulties to cross the cell membranes, and degradation during delivery, hence contributing to their limited bioavailability. To address these issues, antioxidants covalently linked with nanoparticles, entrapped in nanogel, hollow particles, or encapsulated into nanoparticles of diverse origin have been used to provide better stability, gradual and sustained release, biocompatibility, and targeted delivery of the antioxidants with superior antioxidant profiles. This review aims to critically evaluate the recent scientific evaluations of nanoparticles as the antioxidant delivery vehicles, as well as their contribution in efficient and enhanced antioxidant activities. Full article
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Open AccessArticle
Thermo-Diffusion and Multislip Effects on MHD Mixed Convection Unsteady Flow of Micropolar Nanofluid over a Shrinking/Stretching Sheet with Radiation in the Presence of Heat Source
Symmetry 2020, 12(1), 49; https://doi.org/10.3390/sym12010049 (registering DOI) - 26 Dec 2019
Abstract
The main purpose of this study is to investigate the multislip effects on the magneto-hydrodynamic (MHD) mixed convection unsteady flow of micropolar nano-fluids over a stretching/shrinking sheet along with radiation in the presence of a heat source. The consequences of multislip and buoyancy [...] Read more.
The main purpose of this study is to investigate the multislip effects on the magneto-hydrodynamic (MHD) mixed convection unsteady flow of micropolar nano-fluids over a stretching/shrinking sheet along with radiation in the presence of a heat source. The consequences of multislip and buoyancy conditions have been integrated. By using the suitable similarity variables are used to solve the governing non-linear partial differential equations into a system of coupled non-linear ordinary differential equations. The transformed equations are solved numerically by using Runge–Kutta fourth-order method with shooting technique. The impacts of the several parameters on the velocity, temperature, micro-rotation, and concentration profiles as well as on the skin friction coefficient, Sherwood number, and Nusselt number are discussed with the help of graphs and tables. Full article
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Open AccessArticle
Continuous Monitoring of Pigs in Fattening Using a Multi-Sensor System: Behavior Patterns
Animals 2020, 10(1), 52; https://doi.org/10.3390/ani10010052 (registering DOI) - 26 Dec 2019
Abstract
In this work, a complete fattening period (81 days) of a total of 30 Landrace pigs housed in two pens of a nucleus in Villatobas (Castilla-La Mancha, Spain) were supervised. The ear skin temperature of each animal was recorded every three minutes. The [...] Read more.
In this work, a complete fattening period (81 days) of a total of 30 Landrace pigs housed in two pens of a nucleus in Villatobas (Castilla-La Mancha, Spain) were supervised. The ear skin temperature of each animal was recorded every three minutes. The body weight, the date, the duration, and the amount of feed consumed per animal was monitored via an electronic feeding station. The objective was the identification of animals with different behaviors based on the integration of their thermal and intake patterns. The ear skin temperatures of the animals showed a negative relationship between the mean and the standard deviation (r = 0.83), distinguishing animals with different thermal patterns: individuals with high-temperature values show less thermal variability and vice versa. Feeding parameters showed differences in the feeding strategies of animals, identifying fast-eating animals with a high rate feed intake (60 g/min) and slow eaters (30 g/min). The correlation between the change in the rate of feed intake along with animal growth and feed efficiency reached a significant negative value (−0.57), indicating that animals that do not alter their rate of feed intake along breeding showed higher efficiencies. The difference in temperature of an animal with respect to the averaged group value has allowed us to identify animals with differentiated feeding patterns. Full article
(This article belongs to the Special Issue Information Technology Applied to Animal Management)
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Open AccessArticle
Effects of Equivalent-Oxide-Thickness and Fin-Width Scaling on In0.53Ga0.47As Tri-Gate Metal-Oxide-Semiconductor-Field-Effect-Transistors with Al2O3/HfO2 for Low-Power Logic Applications
Electronics 2020, 9(1), 29; https://doi.org/10.3390/electronics9010029 (registering DOI) - 26 Dec 2019
Abstract
We created tri-gate sub-100 nm In0.53Ga0.47As metal-oxide-semiconductor-field-effect-transistors (MOSFETs) with a bi-layer Al2O3/HfO2 gate stack and investigated the scaling effects on equivalent-oxide-thickness (EOT) and fin-width (Wfin) at gate lengths of sub-100 nm. For [...] Read more.
We created tri-gate sub-100 nm In0.53Ga0.47As metal-oxide-semiconductor-field-effect-transistors (MOSFETs) with a bi-layer Al2O3/HfO2 gate stack and investigated the scaling effects on equivalent-oxide-thickness (EOT) and fin-width (Wfin) at gate lengths of sub-100 nm. For Lg = 60 nm In0.53Ga0.47As tri-gate MOSFETs, EOT and Wfin scaling were effective for improving electrostatic immunities such as subthreshold swing and drain-induced-barrier-lowering. Reliability characterization for In0.53Ga0.47As Tri-Gate MOSFETs using constant-voltage-stress (CVS) at 300K demonstrates slightly worse VT degradation compared to planar InGaAs MOSFET with the same gate stack and EOT. This is due to the effects of both of the etched fin’s sidewall interfaces. Full article
(This article belongs to the Section Microelectronics and Optoelectronics)
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Open AccessArticle
Contact Investigation of Multidrug-Resistant Tuberculosis Patients: A Mixed-Methods Study from Myanmar
Trop. Med. Infect. Dis. 2020, 5(1), 3; https://doi.org/10.3390/tropicalmed5010003 (registering DOI) - 26 Dec 2019
Abstract
There is no published evidence on contact investigation among multidrug-resistant tuberculosis (MDR-TB) patients from Myanmar. We describe the cascade of contact investigation conducted in 27 townships of Myanmar from January 2018 to June 2019 and its implementation challenges. This was a mixed-methods study [...] Read more.
There is no published evidence on contact investigation among multidrug-resistant tuberculosis (MDR-TB) patients from Myanmar. We describe the cascade of contact investigation conducted in 27 townships of Myanmar from January 2018 to June 2019 and its implementation challenges. This was a mixed-methods study involving quantitative (cohort analysis of programme data) and qualitative components (thematic analysis of interviews of 8 contacts and 13 health care providers). There were 556 MDR-TB patients and 1908 contacts, of whom 1134 (59%) reached the health centres for screening (chest radiography and symptoms). Of the latter, 344 (30%) had presumptive TB and of them, 186 (54%) were investigated (sputum microscopy or Xpert MTB/RIF®). A total of 27 TB patients were diagnosed (six bacteriologically-confirmed including five with rifampicin resistance). The key reasons for not reaching township TB centres included lack of knowledge and lack of risk perception owing to wrong beliefs among contacts, financial constraints related to loss of wages and transportation charges, and inconvenient clinic hours. The reasons for not being investigated included inability to produce sputum, health care providers being unaware of or not agreeing to the investigation protocol, fixed clinic days and times, and charges for investigation. The National Tuberculosis Programme needs to note these findings and take necessary action. Full article
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Open AccessArticle
Dual-Functioning Scaffolds for the Treatment of Spinal Cord Injury: Alginate Nanofibers Loaded with the Sigma 1 Receptor (S1R) Agonist RC-33 in Chitosan Films
Mar. Drugs 2020, 18(1), 21; https://doi.org/10.3390/md18010021 (registering DOI) - 26 Dec 2019
Abstract
The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the [...] Read more.
The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the site of SCI, was developed. RC-33-loaded fibers, containing alginate (ALG) and a mixture of two different grades of poly(ethylene oxide) (PEO), were prepared by electrospinning. After ionotropic cross-linking, fibers were incorporated in chitosan (CS) films to obtain a drug delivery system more flexible, easier to handle, and characterized by a controlled degradation rate. Dialysis equilibrium studies demonstrated that ALG was able to form an interaction product with the cationic RC-33 and to control RC-33 release in the physiological medium. Fibers loaded with RC-33 at the concentration corresponding to 10% of ALG maximum binding capacity were incorporated in films based on CS at two different molecular weights—low (CSL) and medium (CSM)—solubilized in acetic (AA) or glutamic (GA) acid. CSL- based scaffolds were subjected to a degradation test in order to investigate if the different CSL salification could affect the film behavior when in contact with media that mimic SCI environment. CSL AA exhibited a slower biodegradation and a good compatibility towards human neuroblastoma cell line. Full article
(This article belongs to the Special Issue Marine Biopolymers and Drug Delivery)
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Open AccessCommunication
Generalized Stacking Fault Energy of Al-Doped CrMnFeCoNi High-Entropy Alloy
Nanomaterials 2020, 10(1), 59; https://doi.org/10.3390/nano10010059 (registering DOI) - 26 Dec 2019
Abstract
Using first-principles methods, we investigate the effect of Al on the generalized stacking fault energy of face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy as a function of temperature. Upon Al addition or temperature increase, the intrinsic and extrinsic stacking fault energies increase, whereas the [...] Read more.
Using first-principles methods, we investigate the effect of Al on the generalized stacking fault energy of face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy as a function of temperature. Upon Al addition or temperature increase, the intrinsic and extrinsic stacking fault energies increase, whereas the unstable stacking fault and unstable twinning fault energies decrease monotonously. The thermodynamic expression for the intrinsic stacking fault energy in combination with the theoretical Gibbs energy difference between the hexagonal close packed (hcp) and fcc lattices allows one to determine the so-called hcp-fcc interfacial energy. The results show that the interfacial energy is small and only weakly dependent on temperature and Al content. Two parameters are adopted to measure the nano-twinning ability of the present high-entropy alloys (HEAs). Both measures indicate that the twinability decreases with increasing temperature or Al content. The present study provides systematic theoretical plasticity parameters for modeling and designing high entropy alloys with specific mechanical properties. Full article
(This article belongs to the Special Issue Computational Quantum Physics and Chemistry of Nanomaterials)
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Open AccessEditorial
Marine Compounds and Cancer: The First Two Decades of XXI Century
Mar. Drugs 2020, 18(1), 20; https://doi.org/10.3390/md18010020 (registering DOI) - 26 Dec 2019
Abstract
In 2019, the scientific and medical community celebrated the 50th anniversary of the introduction of the very first marine-derived drug, Cytarabine, into clinics [...] Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessArticle
Superconducting HfO2-YBa2Cu3O7?δ Nanocomposite Films Deposited Using Ink-Jet Printing of Colloidal Solutions
Coatings 2020, 10(1), 17; https://doi.org/10.3390/coatings10010017 (registering DOI) - 26 Dec 2019
Abstract
To reduce the fabrication costs while maximizing the superconducting and pinning properties of YBa2Cu3O7−δ (YBCO) nanocomposite films, the drop-on-demand ink-jet printing technique was used to deposit colloidal YBCO inks onto LaAlO3 substrates. These inks containing preformed HfO [...] Read more.
To reduce the fabrication costs while maximizing the superconducting and pinning properties of YBa2Cu3O7−δ (YBCO) nanocomposite films, the drop-on-demand ink-jet printing technique was used to deposit colloidal YBCO inks onto LaAlO3 substrates. These inks containing preformed HfO2 nanocrystals were carefully adjusted, prior to the jettability, as the droplet formation depends on the rheological properties of the inks themselves. After carefully adjusting printing parameters, 450-nm thick pristine YBCO films with a self-field critical current density (Jc) of 2.7 MA cm² at 77 K and 500-nm thick HfO2-YBCO nanocomposite films with a self-field Jc of 3.1 MA·cm² at 77 K were achieved. The final HfO2-YBCO nanocomposite films contained dispersed BaHfO3 particles in a YBCO matrix due to the Ba2+ reactivity with the HfO2 nanocrystals. These nanocomposite films presented a more gradual decrease of Jc with the increased magnetic field. These nanocomposite films also showed higher pinning force densities than the pristine films. This pinning enhancement was related to the favorable size and distribution of the BaHfO3 particles in the YBCO matrix. Full article
(This article belongs to the Special Issue Superconducting Films and Nanostructures)
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