The treatment of triple‐negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)‐nicotinate complex (CNC) as an antitumor as well ...as a proapoptotic agent. In this study, the HCC‐1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein‐1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme‐linked immunosorbent assay technique was used for the detection of phospho‐Chk1 at ser 317 and caspase‐3. Moreover, the gene expression of survivin was identified by real‐time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC‐1806 cells treated with CNC was decreased in a dose‐dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase‐3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis‐mediated mechanism. However, one cannot neglect the abundance of cell necrosis–mediated death of cells via CNC, especially at higher concentrations.
The present study aimed to throw more light on the role of copper (I)‐nicotinate complex (CNC) as an antitumor and a proapoptotic agent. Based on the results of the present study, it could be concluded that the treatment of HCC‐1806 cells, triple‐negative breast cancer (TNBC), with CNC resulted in increased tendency for apoptotic and necrotic mechanisms; the tendency to the first at low concentrations and the latter at high levels.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•This work focuses on the viability of using liquid metal (LM) bonded gap instead of He-gap.•The obtained results show a slight difference in the various neutronic parameters.•In the ...thermal–hydraulic results, a great reduction in the fuel centerline temperature takes place.•The LM bonded gap reduces the fuel outer surface displacement and the Von-Mises stress.•The UO2 overheating problems using He-gap can be solved by applying LM bonded gap.
This work focuses on the viability of using liquid metal bonded gap instead of the traditional helium (He)-gap through investigating its effects on the neutronic, thermal–hydraulic, and solid mechanics analyses. The shortcoming of using a He-gap is the high thermal resistance of helium, which causes overheating and much heat accumulation inside the fuel, and hence causes many problems with the fuel‘s solid mechanics behavior. To reduce both the heat accumulation and overheating inside the fuel material, LM boned gap was applied. The obtained results showed a slight difference in the various neutronic parameters, while in the thermal–hydraulic analysis, an excellent enhancement in the maximum fuel temperature happened, which reduced the heat accumulation in the fuel material. Also, in solid mechanics analysis, the enhancement that came from decreasing the fuel temperature decreased both the thermal expansion of the fuel and the von-Mises stress that acts on it.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Neutronic, thermal-hydraulic, and solid mechanics analyses of different burnable absorber materials.•The standard BPs (ZrB2, Pyrex rods) used in AP-1000 are not optimum in all cases.•Different ...burnable absorbers have been investigated to reach the most optimum one.•WABA rods and Er2O3 presented excellent results in AP-1000 compared to the standard BPs.
Because of the importance of absorber materials in regulating the reactivity of AP-1000, several materials with varied designs have been investigated to find the most optimum absorber materials from the neutronic, thermal-hydraulic, and solid mechanics perspectives. In this work, ZrB2, Er2O3, (SiO2-B2O3) and (Al2O3-B4C) were investigated as burnable absorbers (BAs) and H3BO3, Ag–In–Cd, and SS-304 as non-burnable absorbers. For the investigated BAs, the main neutronic parameters such as the fuel burn-up, axial thermal neutron flux distribution and the pin by pin distribution have been simulated. For the non-burnable absorbers, the control rod worth (CRW) and the boron concentration coefficient have been calculated. In the thermal-hydraulic analysis, the temperature distribution of the fuel, clad, coolant and the minimum departure from nucleate boiling ratio (MDNBR) have been studied. The BAs’ effects on solid mechanics analysis have emerged on both the von-Mises stress and the maximum fuel outer surface displacement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Triple negative breast cancer (TNBC) is a subtype of breast cancer which is characterized by its aggressiveness, poor and short overall survival. In this concept, there is a growing demand for ...metal-based compounds in TNBC therapy as copper complex that have a less toxic effect on normal cells and could stimulate apoptotic cell death. Additionally, Notch1 signaling pathway has received great attention as one of the most important potential targets for developing a novel therapeutic strategy. The present study is an attempt to assess the promising chemotherapeutic activities of copper(I) nicotinate (CNC) through its impact on the expression of downstream genes of Notch1 signaling pathway and the cell fate of TNBC. The co-treatment of TNBC cells with doxorubicin (Doxo) and CNC was also investigated. To approach the objective of the present study, TNBC cell lines; HCC1806 and MDAMB231, were utilized. MTT assay was used to determine the IC
values of CNC and Doxo. After treatment, microtubule-associated protein light chain3 (LC3) were determined by flow cytometry. Additionally, qRT-PCR technique was used to detect the changes in genes levels that are involved Notch1 signaling pathway. Moreover, autophagosomes were monitored and imaged by Transmission electron microscopy. Treatment of TNBC cells with CNC modulated Notch1 signaling pathway in different manners with respect to the type of cells and the applied dose of CNC. The observed effects of CNC may reflect the possible anti-cancer activities of CNC in both types of TNBC. However, cell type and CNC dose should be considered.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neutronic, thermal-hydraulics, and solid mechanics computations were used to study the different VVER-1000 reactors' operational conditions for the steady-state and the transient state. The main ...objective of these studies is to investigate the safe operating conditions, which is essential in determining the reactor safety limits. The coupling between different physics enables a better understanding of reactor phenomena and enhanced accuracy by reducing the assumption needed for separate calculations for different physics. MCNPX code is used to provide the source power distribution for two themes of calculations. The first theme is the analytical solution using MATLAB software, and the second theme is the finite element coupled physics using COMSOL Multiphysics. Analytical solutions using MATLAB software and results from COMSOL-Multiphysics were used to simulate the uncoupled analytical models and coupled models, respectively. The coupled theme provide feedbacks between different physics by iterating the solution between different physics; such as solving the heat transfer with taking into consideration the variation of the coolant velocity along the coolant channel and solving solid mechanics with taking into consideration the change of either the fuel and the clad temperatures distribution (thermal load) or the change in the coolant pressure (pressure load). While in the uncoupled solutions, certain assumptions reflect an average behavior for the effect of other physics on the physics under concern, such as the average pressure of the coolant and the average value for the coolant velocity. The obtained results are verified by comparing it to WIMS D-4 for neutronic calculations and COPERA-EN code for the thermal-hydraulic analytical solution. Also, thermal-hydraulic results by both coupled and uncoupled themes are verified against results from the final safety analysis report. The Departure from Nucleate Boiling Ratio (DNBR) and the Minimum Departure from Nucleate Boiling Ratio (MDNBR) were applied for the investigation of VVER-1000 reactor safety parameters. Solid mechanics, fluid dynamics and heat transfer were used to compute the maximum stress/maximum volumetric strain acting on both fuel and cladding material. Results from both methods satisfied the limits addressed by the designer and shows a good agreement with the other published works that used WIMS D-4 for neutronic calculations and COBRA-EN code for thermal-hydraulic calculations analytically. in addition, the maximum stress occurring on the fuel and clad materials didn't exceed the yield stress. Furthermore, the fuel material displacement didn't exceed the Helium gap thickness, which means the surface contact between the fuel and the clad material is impossible that prevents the chemical interaction between both fuel and clad at 1135 K.
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•MCNPX code is used to calculate the power distribution of VVER-1000.•Analytical solutions of heat transfer, CFD, and solid mechanics were performed using MATLAB software.•Finite element calculations are done using COMSOL Multiphysics to couple heat transfer with CFD and solid mechanics.•Results from analytical and finite element coupled solutions are compared to results from other codes and the final safety analysis report.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Applying Uranium Nitride (UN) and Uranium Carbide (UC) as accident-tolerant fuels.•The proposed accident-tolerant fuels have been applied on VVER-1000/UTVS.•Neutronic, thermal–hydraulic, and solid ...mechanics analyses have been done for the proposed fuels.•MCNPX 2.7 code and COMSOL-Multiphysics software were used to make an integrated analysis.
This paper presents an integrated study about some accident-tolerant fuels compared to the standard fuel in trying to find an alternative fuel that enhances the safety, competitiveness, and economics of commercial nuclear power. The neutronic, thermal–hydraulic and solid mechanics analysis of Uranium Nitride (UN) and Uranium Carbide (UC) were performed in a single fuel assembly of the VVER-1000 nuclear power reactor and compared with that of Uranium dioxide (UO2). MCNPX 2.7 computer code and COMSOL-Multiphysics computer software were used to make a deep analysis for the investigated fuel types. In the neutronic analysis, the fuel burn-up, the safety parameters and the power peaking factor (PPF) for the hot channel were simulated. The thermal–hydraulic and solid mechanics analyses were performed on the hot channel to make sure that the maximum temperature of the clad and the coolant would not exceed the safety limits.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adventitious root formation is the key to successful propagation of olives through cuttings. Etiolation, as an eco-friendly practice, can modulate the plant’s endogenous phytohormone, which plays an ...important role in stimulation of rooting of cuttings. Therefore, this study was aimed to investigate the effect of etiolation on the rooting behavior of both ‘Manzanillo’ and ‘Picual’ olive cuttings (terminal and sub-terminal) treated with IBA (0, 4000 ppm). The results indicated that sub-terminal cuttings in both cultivars were more effective in olive propagation than terminal cuttings as they recorded increased leaves number, C/N ratio, total carbohydrates, total indoles, IAA, IAA/GA ratio, and total phenols. Etiolation of both olive cultivars for both terminal and sub-terminal cuttings significantly decreased rooting percent, roots number, IAA, and IAA/GA ratio; while, it increased GA and GA/IAA. Moreover, etiolation decreased total sugars, IAA, IAA/GA ratio, and indole/phenol ratio in both sub-terminal cuttings. Terminal ‘Manzanillo’ cuttings achieved a higher rooting percent than terminal ‘Picual’ cuttings by 5.83% and 202.2% as mean of both seasons for untreated and IBA-treated cuttings, which was accompanied by significant increase in vascular bundle%, total phenol, phenol/indole ratio, IAA, and IAA/GA ratio by 21.48%, 49.2%, 44.72%, 12.9%, and 22.9%, respectively. Also, terminal ‘Manzanillo’ cuttings recorded lower GA by 7.98% and GA/IAA ratio by 18.21% and pith by 6.13% than terminal ‘Picual’ cuttings. This study proved that olive plants need exposure to full sunlight to propagate easily by cuttings since etiolation had negative effects on IBA-treated cuttings.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The epidemy of metabolic syndrome (MetS) is typically preceded by adoption of a "risky" lifestyle (e.g., dietary habit) among populations. Evidence shows that those with low socioeconomic status ...(SES) are at an increased risk for MetS. To investigate this, we recruited 123 obese subjects (body mass index BMI ≥ 30) from Chicago. Multi-omic data were collected to interrogate fecal microbiota, systemic markers of inflammation and immune activation, plasma metabolites, and plasma glycans. Intestinal permeability was measured using the sugar permeability testing. Our results suggest a heterogenous metabolic dysregulation among obese populations who are at risk of MetS. Systemic inflammation, linked to poor diet, intestinal microbiome dysbiosis, and gut barrier dysfunction may explain the development of MetS in these individuals. Our analysis revealed 37 key features associated with increased numbers of MetS features. These features were used to construct a composite metabolic-inflammatory (MI) score that was able to predict progression of MetS among at-risk individuals. The MI score was correlated with several markers of poor diet quality as well as lower levels of gut microbial diversity and abnormalities in several species of bacteria. This study reveals novel targets to reduce the burden of MetS and suggests access to healthy food options as a practical intervention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Squamous cell cancer is a heterogeneous aggressive disease, therefore, its treatment is challenging. Increased attention has been paid to metal complexes as anticancer drugs. However, new insights ...towards autophagy have been recognized due to its role in tumor cell death or survival.
To clarify the antitumor activity of copper (I) nicotinate complex (CNC) as new therapeutic agent and understand the role of autophagy modulation as a prospective target for the advancement of efficient therapeutic agent for treatment.
Viability of MDA-MB-231 and HCC1806 cells and IC50 values of CNC for both cell lines were assessed by MTT assay. Also, the viability and IC50 values of Torin1 and Chloroquine (CQ) were assessed only in HCC1806 cells by MTT assay. The level of microtubule-associated protein 1 light chain 3 (LC3) was assessed by ELISA. Real time PCR was used to detect the changes in NBR1 gene expression. Cell cycle distribution and quantitative detection of acid vesicular organelles (AVOs) were determined by flow cytometry. Fluorescence microscope was used for qualitative detection of AVOs. Modulation of autophagy was carried out by Torin1 as inducer and CQ as inhibitor.
CNC restrained the growth, in a dose-dependent manner, and induced cell death in human HCC1806 cell line. In addition, the CNC treated cells displayed inhibition of autophagy, as indicated by reduction of AVOs, decrease in LC3 protein level and up regulation of NBR1 gene expression.
CNC, as an autophagy inhibitor and pro-apoptotic agent, could be a promising anti-cancer agent either alone or in combination with other therapeutic drugs.
