Search

Background and purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. Experimental approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme. The cytotoxic effect of the final compounds on the MCF-7 cell line was evaluated by MTT assay. Findings/Results: The docking results confirmed the optimized electrostatic, H-bonding, and hydrophobic interactions of structures with the key residues of the active site (DG bin < -9Kcal/mol). The derivatives have been obtained in good yield and purity, and their structures were confirmed by different methods (FT-IR, 1 H-NMR, 13 C-NMR, and CHNS analysis). The IC50s of all final derivatives against the MCF-7 cell line were lower than 10 μM, and between all, the IXa from pyrazolo-quinazolinone class (IC 50 : 6.43 µM) with chlorine substitute was the most potent. Furthermore, all derivatives showed negligible cytotoxicity on HUVEC normal cell line which would be a great achievement for a novel cytotoxic agent. Conclusion and implications: Based on the obtained results, pyrazolo[1,5-c] quinazolin-2-one series were more cytotoxic than imidazolinone methyl quinazoline-4(3H)-ones against MCF-7 cells. Chlorine substitute in the para position of the aromatic ring improved the cytotoxicity effect in both classes. It could be related to the polarizability of a chlorine atom and making better intermolecular interactions. Further pre-clinical evaluations are required for the promising synthesized cytotoxic compounds.

In this article, the catalytic conversion of oxygenated compounds (methyl acetate and 4-heptanone) to gasoline has been studied over NH4-ZSM-5 catalyst (Si/Al = 80) at three temperatures of 250, 300, and 390 °C. To determine the crystalline structure and acid sites of the catalyst, X-ray diffraction analysis (XRD) and NH3-TPD analysis were used, respectively. Products selectivity became determined by a GC‐Mass spectrometer. Based on the NH3-TPD analysis, Bronsted acid sites at 390 °C are activating, which the maximum amount of conversion obtained at this temperature. Also, results showed that the distribution of hydrocarbons extremely dependent on the temperature of the reaction, which at 390 °C often products of the reaction include aromatic compounds, while at temperatures below 300 °C aliphatic and olefin compounds have been often produced. Finally, the results from the reaction showed that by controlling the reaction conditions, the amount percentage of benzene, toluene, and xylenes (BTX) compounds is significantly reduced.

Saffron is one of the highly prized spices in the world. This spice is dark-red owing to the accumulation of crocins. Crocins are a group of carotenoid derivatives termed apocarotenoids with various health-promoting properties, especially anticancer and antidepressant ones. The present study aims to investigate the changes in the total crocin content in Crocus sativus stigma under salt stress. Additionally, plant resistance was evaluated by measuring the amounts of proline, soluble and insoluble sugars, potassium, and sodium in leaves. The corms about 80 g were planted in planting boxes under 6 levels of salinity (0, 2, 4, 6, 10 dS/m) in a completely random design with four replications. Results showed that after a relative decrease under electrical conductivities (EC) from 2 to 4 dS/m (49.62 mg/g DW), a sudden increase occurred in the total crocin content at the EC of 6 dS/m (63.07 mg/g DW). The amount of proline significantly increased at the EC of 4 dS/m (18.1 µg/g DW). With increasing levels of salinity, the amount of glucose, calcium, potassium, and sodium gradually increased in the leaves. Therefore, one of the advantages of saffron cultivation in saline areas or with saline water can be an increase in crocin. This not only brings huge economic benefits but also has a beneficial effect on human health.

Introduction: Due to the side effects of drugs, the development of nanoscale drug delivery systems has led to a significant improvement in medicinal therapies due to drug pharmacokinetics changes, decreased toxicity, and increased half-life of the drug. This study aimed to synthesize tamoxifen (TMX)-loaded L-lysine coated magnetic iron oxide nanoparticles as a nano-carrier to investigate its cytotoxic effects and anti-cancer properties against MCF-7 cancer cells. Methods: Magnetic Fe3O4 nanoparticles were synthesized and coated with L-lysine (F-Lys NPs). Then, TMX was loaded onto these NPs. The characteristics of synthesized nanoparticles (F-Lys-TMX NPs) were evaluated by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The drug release was analyzed at pH 5.8 and pH 7.4. The MCF-7 cells were exposed to F-Lys-TMX NPs, F-Lys NPs, and TMX for 24, 48, and 72 hours. To evaluate the cytotoxic potential of designed nanoparticles, MTT and apoptosis assays, real-time PCR, and cell cycle analysis was carried out. Results: The F-Lys-TMX NPs had spherical morphology with a size ranging from 9 to 30 nm. By increasing the nanoparticles concentration and treatment time, more cell proliferation inhibition and apoptosis induction were observed in F-Lys-TMX NPs-treated cells compared to the TMX. The expression levels of ERBB2, cyclin D1, and cyclin E genes were down-regulated and expression levels of the caspase-3 and caspase-9 genes were up-regulated. Studies on the drug release revealed a slow and controlled pH-dependent release of the nanoparticles. Cell cycle analysis indicated that F-Lys-TMX NPs could arrest the cells at the G0/G1 phase. Conclusion: The findings suggest that F-Lys-TMX NPs are more effective and have the potential for cell proliferation inhibition and apoptosis induction compared to the TMX. Hence, F-Lys-TMX NPs can be considered as an anti-cancer agent against MCF-7 breast cancer cells.

The kynurenine pathway (KP) can be involved in the pathogenesis of neurodegenerative diseases and excessive neurotoxic metabolite production. This study aimed to evaluate the effects of overexpression of murine 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (Acmsd) gene in inflammatory conditions in RAW 264.7 cell line to present more information about the effect of this gene on inflammatory conditions and the KP cycle. The coding sequence of the Acmsd gene was cloned into pCMV6-AC-IRES-GFP expression vector with a green fluorescent protein (GFP) marker. To simulate inflammatory conditions, RAW 264.7 macrophage cells were stimulated by Lipopolysaccharide (LPS) 24 h before transfection, and transfected by Polyethyleneimine (PEI) with constructed plasmids expressing the Acmsd gene. The effect of Acmsd gene expression level on murine Interferon-gamma (Ifn-γ) and murine Indoleamine 2,3-dioxygenase 1 (Ido1) gene expression level was investigated by Real-Time PCR. According to the results of this study, good transfection efficiency was observed 72 h after transfection, and Acmsd expression level increased 29-fold (P

Background We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. Methods We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. Results Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC‐based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative‐associated proteins (Ki67, CD31, and HIF‐1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real‐time polymerase chain reaction results demonstrate up/down‐regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. Conclusion We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy‐treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies., The effect of pure electrostatic charges has been investigated on cultured normal and cancerous breast cell lines for the first time. The selective effect of positive electrostatic charges (PECs) on metastatic cell lines and animal tumors has been reported with no effect on normal tissues. PECs induce apoptosis in metastatic breast cancer cell lines and tumors by suppressing proifration pathways. More than 400 mouse models have been tested to investigate the effects of PECs on cancerous tumors and animal organs by different analyses. Survival analyses depict a high survival rate of treated mice with positive electrostatic charges compared to other conventional cancer treatments such as chemotherapy and radiotherapy.

BACKGROUND Echinacea is a perennial and herbaceous herb containing the most active phenolic compounds and valuable antimicrobial and antioxidant content, such as chicoric acid, which increases the body immune function. The root of this plant is mainly used in pharmaceutical fields to treat inflammation, kidney infections and colds. In the present study, we investigated the drying of echinacea root in an infrared dryer with airborne ultrasonic pretreatment aiming to determine shrinkage, color changes, extraction, total phenolic content, flavonoid content and radical inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH). The experiments were performed in an infrared dryer at three temperature levels of 40, 45 and 50 °C, with ultrasonic pretreatment at frequencies of 2000, 3000 and 4000 Hz and a time duration of 20, 40 and 60 min in three replications. RESULTS Shrinkage and color changes of the samples varied in the range 27.2-6.3% and 39.82-39.64%, respectively. According to all of the evaluated physical and chemical factors, the optimal conditions for echinacea root processing were a drying temperature of 40 °C, a frequency of 3000 Hz and an ultrasound duration of 60 min, in which case shrinkage was 3.35% and color changes were 38.25%. Total phenolic content was 27.41 mg g-1 , flavonoid content was 39.36 mg g-1 and DPPH radical inhibition was 34.87%. CONCLUSION Therefore, the use of airborne ultrasound pretreatment demonstrates increased chemical properties compared to the optimal state when drying the echinacea root with an infrared dryer by 54/21-81/64%. Hence, ultrasound pretreatment preserves the quality and quantity of active ingredients in the therapeutic root of Echinacea. © 2021 Society of Chemical Industry.

An efficient and convenient approach has been developed for the synthesis of naphtho[1,2-f][1,4]oxazepine structures based on the consecutive Betti/Bargellini multicomponent reactions. Aminobenzylnaphthols were prepared from 2-naphthol, aromatic aldehydes, and 2-aminopyridine via the Betti reaction, and then, naphtho[1,2-f][1,4]oxazepine derivatives were synthesized using the Betti reaction products, chloroform, and aliphatic ketones in the presence of sodium hydroxide via Bargellini multicomponent reactions. A significant aspect of this work is the construction of novel oxazepine-based scaffolds with potential pharmaceutical interest from cheap and readily available starting materials in moderate yields.

A carbon quantum dot-based chitosan hydrogel was prepared in this work as a fluorescence sensor for the selective sensing of Hg2+ ions. Among the eight tested metal ions, the prepared hydrogel exhibited remarkable sensing selectivity and sensitivity toward Hg2+. The results demonstrated that a prominent fluorescence quenching at 450 nm was observed in the presence of Hg2+ with a linear response range of 0-100.0 nM and an estimated limit of detection of 9.07 nM. The as-prepared hydrogel demonstrates pH-dependent fluorescence intensity and sensitivity. The highest fluorescence intensity and sensitivity were obtained under pH 5.0. The excellent sensing selectivity could be attributed to a strong interaction between the hydrogel film and Hg2+ ions to form complexes, which provokes an effective electron transfer for fluorescence quenching. Results from density functional theory (DFT) calculation confirm that the interaction energies (ΔIE) of the hydrogel with three toxic metal ions (Hg2+, Cd2+, and Pb2+) are in the following order: Hg2+ > Cd2+ > Pb2+.

It is well-known that near-infrared (NIR) light sources are appropriate to ablate benign tumor irreversibly using heat treatment even in deep tissues. The laser light penetration into the skin in these wavelengths is deep (3–5 mm). Applying new stable materials for emitting NIR wavelengths in tumor positions can help cancer treatment. In this paper, synthesis of the conjugated core-multishell Ag/SiO2/Ag and Au/SiO2/Au quantum dots (QDs) with indocyanine green (ICG) is done and their theoretical and experimental absorptions and emissions in the NIR region are investigated. Thus, heat generation (high-resolution medical imaging capabilities) and emission enhancement are explained and described based on the FRET model for the proposed core-multishell QDs and it is shown that Ag/SiO2/Ag with ICG presents 4 times higher emission rate versus ICG alone in NIR region. Also, because of the plasmon hybridization and also resonance light penetration enhancement, the temperature in tissues increases that is useful for photothermal therapy and NIR high-resolution medical imaging for deep tissues. As an alternative application, these nanoparticles with amazing features are used as a heat source in cancer treatment for shallow and deep tissues. Finally, it is shown that Ag/SiO2/Ag QDs are the best solution for this purpose.

Foaming a polymer not only turns it into a lightweight material but also gives some special properties to it. However, the most important issue is controlling the foaming process to achieve a desirable structure with high cell density and low relative density. In the present study, the extrusion foaming process of polyethylene was studied through stepwise amendments. An innovative extrusion system was designed and implemented to produce extrusion foams under different material and process conditions using N2 as blowing agent. In the first step, the final cooling condition was investigated. The air-cooling condition led to a higher cell density/lower cell size compared to the water-cooling condition although a higher relative density was obtained. In the second step, the effects of the addition of talc and the synergetic effect of talc/nanoclay at different contents were investigated in detail. The hybrid of talc/nanoclay had a noticeably improving effect on the cellular structure. In the third step, the effects of processing parameters including the die temperature and screw speed were studied on the foam properties. Finally, up to 49.4% decrease in the relative density of samples was observed, also cell densities up to 2.5 × 104 cell/cm3 and cell sizes as small as 280 µm were achieved.

Dental pulp stem cells (DPSCs) have been recommended as promising candidate for cell-based therapeutic applications due to high potentials in tissue repair/regeneration and modulation of immune res...

BackgroundPentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens ofLeishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm).ResultThe nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment.ConclusionAccording to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in theleishmaniaaffected patients.

An exceptionally productive and sustainable procedure is described in this paper to fabricate 1-(benzothiazolylamino) methyl-2-naphthols using a novel green nanocomposite of chitosan and diethylenetriamine-modified graphene oxide, supported methanesulfonic acid (Ch@GO-DETA.MSA.). For the synthesis of the nanocomposite, maleic anhydride was first attached to chitosan, and then, graphene oxide was modified by diethylenetriamine (GO@DETA). Subsequently, nanocomposite was prepared from the reaction of chitosan-g-maleic anhydride and GO@DETA. Finally, methane sulfonic acid was added to the nanocomposite to afford Ch@GO-DETA.MSA. Structural properties of the nanocomposite were explored through various techniques including X-ray diffraction (XRD), thermal gravimetric analysis (TGA), FTIR spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). 1-(Benzothiazolylamino) methyl-2-naphthols were efficiently prepared in high to excellent yields through a multicomponent reaction of 2-aminobenzothiazole, aryl aldehydes, and 2-naphthol using Ch@GO-DETA.MSA. nanocomposite under solvent-free conditions. The proposed protocol exhibited superiority over several published protocols due to its nontoxicity and eco-friendly, catalytic ability, short reaction times, generality, efficiency, solvent-free condition, and simple workup.

Human dental pulp stem cells (hDPSCs) have significant potential of immunomodulatory for therapeutic and regenerative biomedical applications compared to other mesenchymal stem cells (MSCs). Nowadays, alteration of gene expression is an important way to improve the performance of MSCs in the clinic. MicroRNAs (miRs) and CD200 are known to modulate the immune system in MSCs. Curcumin is famous for its anti-inflammatory impacts. Phytosomal curcumin (PC) is a nanoparticle synthesized from curcumin that removes the drawbacks of curcumin. The purpose of this research was to assess the effects of PC on the expression of the CD200 and four key miRNAs in immune system. PC (30 μM) treatment of hDPSCs could ameliorate their immunoregulatory property, presented by reduced expressions of miR-21, miR-155 and miR-126, as well as enhanced expressions of miR-23 and CD200. The PC was also able to reduce PI3K\AKT1\NF-κB expressions that were target genes for these miRs and involved in inflammatory pathways. Moreover, PC was more effective than curcumin in improving the immune modulation of hDPSCs. Evidence in this study suggested that PC mediates immunoregulatory activities in hDPSC via miRs and CD200 to regulate PI3K\AKT1\NF-κB signalling pathways, which may provide a theoretical basis for PC in the treatment of many diseases. SIGNIFICANCE OF THE STUDY: Autoimmune diseases or tooth caries are partly attributed to global health problems and their common drug treatments have several side effects. The goal of this study is dentin regeneration and autoimmune diseases treatment via stem cell-based approaches with phytosomal curcumin (PC), for the first time. Because dental pulp stem cells have unique advantages (including higher immunomodulatory capacity) over other mesenchymal stem cells, we considered them the best option for treating these diseases. Using PC, we try to increase the immunomodulatory properties of these cells.

Most oil reservoirs are first saturated with water and become oil-wet gradually due to oil migration and accumulation. Previous studies reported that the adsorption of hydrocarbon components onto the rock surface during a considerable time caused wettability alteration from primarily water-wet to oil-wet. However, few studies fundamentally reviewed the effects of the ionic composition of formation water on the process of the rock surface wettability alteration from water-wet to oil-wet using advanced surface analysis tools. In this research, wettability alteration of calcite surface from water-wet to oil-wet and (in the next step) from oil-wet to water-wet was studied using a specific carboxylic acid (stearic acid), normal decane, and three single salt aqueous phases. During this research, the surface was analyzed using contact angle and scanning electronic microscopy. Results showed that using deionized water as an aqueous phase caused maximum surface adsorption of carboxylic components and minimum adsorption occurred in the presence of the MgCl2 aqueous phase. The carboxylic acid adsorption onto the calcite surface was controlled by interactions of negative ions formed during dissociation of carboxylic acids and positive salt ions present in brine solvents.

Introduction: Herbal products are beneficial compounds with many applications in human life. In this study the chemical composition and cytotoxic activity of the essential oil of the aerial parts of Dorema aucheri were assessed. Methods: The essential oil was extracted by hydrodistillation after drying the aerial parts of D. aucheri, collected from the mountains around Yasuj city in the South-West of Iran. The oil composition was determined by GC/MS. To evaluate in vitro cytotoxic activity, the apoptotic effects of the essential oil were investigated against SW48 and SW1116 colorectal cancer cell lines by (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium) bromide (MTT) assay and flow cytometry. Results: The essential oil yield was obtained 0.02% (W/W). Twenty-five compounds were identified in the oil, and the main constituents were caryophyllene (E) (31.29%), Phytol (14.92%), gurjunene (β-) (9.84%), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (8.7%), and n-hexadecanoic acid (8.09%). The MTT assay showed that the IC50 values of the essential oil for SW48 and SW1116 cell lines were 1.4 and 1.2 mg/mL, respectively. The results of flow cytometry showed that the essential oil significantly increased the apoptosis in SW48 cell line compared with the vincristine (P < 0.05). It also increased the apoptosis in SW1116 cells compared with the vincristine, but this difference is not significant. Conclusion: The essential oil of D. aucheri consisted of high amounts of caryophyllene and showed significant cytotoxic effects against SW48 and SW1116 cancerous cell lines.

An efficient and straightforward approach has been established for the preparation of a new class of depsipeptide structures via isocyanide-based consecutive Bargellini–Passerini multicomponent reactions. 3-Carboxamido-isobutyric acids bearing an amide bond were obtained via Bargellini multicomponent reaction from isocyanides, acetone, and chloroform in the presence of sodium hydroxide. Next, via a Passerini multicomponent-reaction strategy, a new class of depsipeptides was synthesized using the Bargellini reaction products, isocyanides, and aldehydes. The depsipeptides thus prepared have more flexible structures than their pseudopeptidic analogues.

The mathematical models were used to predict the conversion, molecular weights, and polydispersity in atom transfer radical polymerization (ATRP) of styrene with mono- and bi-functional initiators. The moment and population balance models can predict monomer conversion, averaged-number molecular weight which increased linearly and narrow polydispersity index of synthesized polystyrene. The modeling calculating results were in good agreement with the experimental results. Comparison of the results of these two methods with the experimental data showed that the accuracy of population balance method for prediction of polymer polydispersity index in low conversions is more than the moment method. In addition, the new numerical simulation basis of population balance model can predict the full molecular weight distribution of the polystyrene in all the reaction time.

Renal clearance of many drugs is mediated by renal organic anion transporters OAT1/3 and inhibition of these transporters may lead to drug‐drug interactions (DDIs). Pyridoxic acid (PDA) and homovanillic acid (HVA) were indicated as potential biomarkers of OAT1/3. The objective of this study was to develop a population pharmacokinetic model for PDA and HVA to support biomarker qualification. Simultaneous fitting of biomarker plasma and urine data in the presence and absence of potent OAT1/3 inhibitor (probenecid, 500 mg every 6 h) was performed. The impact of study design (multiple vs. single dose of OAT1/3 inhibitor) and ability to detect interactions in the presence of weak/moderate OAT1/3 inhibitors was investigated, together with corresponding power calculations. The population models developed successfully described biomarker baseline and PDA/HVA OAT1/3‐mediated interaction data. No prominent effect of circadian rhythm on PDA and HVA individual baseline levels was evident. Renal elimination contributed greater than 80% to total clearance of both endogenous biomarkers investigated. Estimated probenecid unbound in vivo OAT inhibitory constant was up to 6.4‐fold lower than in vitro values obtained with PDA as a probe. The PDA model was successfully verified against independent literature reported datasets. No significant difference in power of DDI detection was found between multiple and single dose study design when using the same total daily dose of 2000 mg probenecid. Model‐based simulations and power calculations confirmed sensitivity and robustness of plasma PDA data to identify weak, moderate, and strong OAT1/3 inhibitors in an adequately powered clinical study to support optimal design of prospective clinical OAT1/3 interaction studies.

A mathematical model for the formation of condensation aerosols from highly supersaturated vapor-air mixtures is presented. The model is suitable for systems with very high nucleation rates that re...

BackgroundEndogenous biomarkers are promising tools to assess transporter-mediated drug–drug interactions early in humans.MethodsWe evaluated on a common and validated in vitro system the selectivity of 4-pyridoxic acid (PDA), homovanillic acid (HVA), glycochenodeoxycholate-3-sulphate (GCDCA-S) and taurine towards different renal transporters, including multidrug resistance-associated protein, and assessed the in vivo biomarker sensitivity towards the strong organic anion transporter (OAT) inhibitor probenecid at 500 mg every 6 h to reach close to complete OAT inhibition.ResultsPDA and HVA were substrates of the OAT1/2/3, OAT4 (PDA only) and multidrug resistance-associated protein 4; GCDCA-S was more selective, having affinity only towards OAT3 and multidrug resistance-associated protein 2. Taurine was not a substrate of any of the investigated transporters under the in vitro conditions tested. Plasma exposure of PDA and HVA significantly increased and the renal clearance of GCDCA-S, PDA and HVA decreased; the magnitude of these changes was comparable to those of known clinical OAT probe substrates. PDA and GCDCA-S were the most promising endogenous biomarkers of the OAT pathway activity: PDA plasma exposure was the most sensitive to probenecid inhibition, and, in contrast, GCDCA-S was the most sensitive OAT biomarker based on renal clearance, with higher selectivity towards the OAT3 transporter.ConclusionsThe current findings illustrate a clear benefit of measuring PDA plasma exposure during phase I studies when a clinical drug candidate is suspected to be an OAT inhibitor based on in vitro data. Subsequently, combined monitoring of PDA and GCDCA-S in both urine and plasma is recommended to tease out the involvement of OAT1/3 in the inhibition interaction.

The application of 3,5-bis(trifluoromethyl)phenylammonium triflate (BFPAT) as a convenient new organocatalyst for the synthesis of quinoxaline derivatives is described. In the presence of BFPAT, one-pot synthesis of a wide variety of quinoxaline derivatives was achieved by the reaction of various o-phenylenediamines and 1,2-dicarbonyl compounds in water.

According to laboratory data, the thermal conductivity ratio of an antifreeze-based hybrid nanofluid containing graphene oxide (GO) and Copper oxide (CuO) was modeled using mathematical methods, one is based on an artificial brain structure model, and the other is based on curve-fitting method. A two-variable empirical based correlation (R2 = 0.996) as a function of temperature and volume fraction suggested from the curve-fitting method. In the brain structure-based section, an artificial neural network employed by applying temperature and concentration as input variables and thermal conductivity ratio as the desired output. The correlation coefficient (R) values of designed ANN are 0.999963, 0.999409, and 0.999103 for train, validation and test, respectively. Mean squared errors (MSE) values of designed ANN are 1.01743e-6, 5.01019e-5, and 2.90237e-5 for train, validation and test, respectively. The findings indicated that the artificial neural network and the proposed correlation can predict the thermal conductivity ratio of GO-CuO (50:50%)/EG-Water (50:50%) hybrid nanofluid with high accuracy.

The natural convection heat tranfer in annulate region confined between two homocentric cylinders were numerically studied in the present work. The annulus was filled by ethylene glycol / water based Titania nanofluid. Both internal and external cylinders are presereved at an isothermal hot and cold temperatures respectively, whereas, the upper and lower walls are adiabatic. The numerical solution is obtained by applying the finite volume method along with the SIMPLER, and TDMA algorithms. In the current study, the solid volumetric fraction is varied as (0 % ? ? ? 3 %), the volume ratios of EG to water are varied as (0:100 %, 40 : 60 %, 100:0 %), while both the Rayleigh number and radii ratio are considered fixed at (Ra = 104 and ? = 2). The obtained results indicated that, the average Nusselt number increases as the solid volumetric fraction and the volume ratio of ethylene glycol in the base fluid increase. Moreover, the velocity profiles reach their maximum value in the half region adjacent the internal hot wall when TiO2 – water nanofluid is used. Also, the temperature profiles decrease along the radial distance for all considered values of volume ratios of EG to water.

To improve the low photocatalytic efficiency, powerful UV light activation, and facile electron transport of ZnFe2O4–CuO the combination of different C3N4 and N/B/RGO nanosheets in ZnFe2O4–CuO–C3N4 and ZnFe2O4–CuO-N/B/RGO ternary nanoheterojunction fabricated that lead to decrease recombination of electron/hole pairs and high photocatalytic efficiency for degradation of MO organic pollutants. The ZnFe2O4, ZnFe2O4-N/B/RGO, CuO-N/B/RGO, ZnFe2O4–CuO, ZnFe2O4–CuO-N/RGO, ZnFe2O4–CuO-B/RGO, ZnFe2O4–CuO-RGO, ZnFe2O4–CuO-N/B/RGO and ZnFe2O4–CuO–C3N4 photocatalysts were fabricated by sol–gel technique using melamine, zinc nitrate, ferric nitrate and copper nitrate hexahydrate as precursors. The prepared ZnFe2O4–CuO–C3N4 photocatalysts have a narrower bandgap than that of ZnFe2O4–CuO-N/B/RGO ternary heterojunction, resulting in higher photocatalytic activity for Fenton-type photodecomposition of methyl orange (MO). The activity of the compounds as a photocatalyst can be attributed to an electron transfer process on the surface of the photocatalyst, where the ZnFe2O4–CuO–C3N4 is a powerful electron donor and electron acceptor for the oxidized MO under ultra-violet (UV) light irradiation. ZnFe2O4–CuO–C3N4 ternary heterojunction photocatalyst show a red shift (lowest bandgap) in absorption and excellent photocatalytic degradation of MO. The particle sizes of ZnFe2O4 and CuO nanoparticles (NPs) were in the ranges of ~ 650–750 and ~ 50–150 nm, respectively. The CuO and ZnFe2O4 samples were displayed spherical and cubic morphology in FESEM images, respectively. Among the as-prepared nanostructures ZnFe2O4–CuO–C3N4 show the highest photocatalytic activity and eliminate 95.84% (80 min) of methyl orange under UV light irradiation.

Estrogen depletion in postmenopausal women and animal models of ovariectomy is associated with some undesirable alternations in lipid metabolism, the adverse impacts of which could be improved through regular exercise training; however, molecular mechanisms underlying this process are not fully understood. In this study, the impacts of an 8-week moderate aerobic exercise training on plasma lipid profile, liver enzymes, and some gene expression involved in cholesterol metabolism were investigated in ovariectomized rats. Forty female Wistar rats were randomly divided into four groups including sham-control, exercise training, ovariectomized-control (OVX), and ovariectomized + Exercise training (OVX + E). Three weeks after ovariectomy, the animals began their training on the treadmill (25 m/min, 5 sessions/week) for 8 weeks. The hepatic expression of Fansoid X receptor (FXR), Cholesterol-1-alphahydroxylase 1 (CYP7A1), and Small heterodimeric protein (SHP) along with lipid profile and liver enzymes were assessed. The hepatic expression of FXR, CYP7A1 and SHP genes were down-regulated in OVX rats compared to the exercise group. The levels of triglyceride (TG) and total cholesterol (TC) were significantly increased in OVX and OVX + E rats in comparison to sham and exercise groups. The levels of liver enzymes were also increased in OVX rats. However, exercise did not alter liver enzymes, despite a decrease in total cholesterol in OVX rats. Although ovariectomy could down-regulate the hepatic gene expressions involved in cholesterol metabolism, our exercise protocol could not alter the expression of these genes in OVX rats. These effects may occur due to other variables such as some regulatory mechanisms which are not the subject of the present research.

Aberrant protein aggregation and the formation of amyloid deposits are associated with numerous neuro- and non-neurodegenerative disorders. Thus, one potential strategy is to eliminate these deposits by halting amyloid aggregation. Selenium nanoparticles (Se-NPs) have great potential in biomedicine for various therapeutic and diagnostic purposes and also have the ability to inhibit amyloid fibrillation. Herein, Hen Egg White Lysozyme (HEWL) was chosen as a protein model, and rod-like Se-NPs with diameters ranging from 90 to 120 nm were synthesized and the influence of shape and concentration of the particles on HEWL fibrillation was investigated. The effect of the nanoparticles on HEWL amyloid formation was analyzed using thioflavin T and Congo red binding assays, atomic force microscopy, and cytotoxicity assays. In the present study, it has been observed that these particles have a dual function in various concentrations. Using lower concentrations of Se-NPs ranging from 3-30 μg/ml, the Thioflavin T (ThT) fluorescence intensity decreased significantly by 60%, with an increased lag time compared to that of the control. While HEWL fibrillation substantially increased upon co-incubation with a higher concentration of these particles (300-2400μg/ml), and these results were verified by AFM, Congo red, and MTT assay. We showed that inhibitory or inductive influences of Se-NPs on the hen egg-white lysozyme (HEWL) amyloid aggregation are achieved via different independent mechanisms. These results demonstrate that dual-activity of Se-NPs might be a valuable targeting system for inhibiting amyloid aggregation, and thus, may play a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.

Comprehensive investigation of the synergistic effect of incorporating Fe and Ga into ZSM-5 in cracking of hexane.

Background and purpose: Alzheimer’s disease is considered one of the lead causes of elderly death around the world. A significant decrease in acetylcholine level in the brain is common in most patients with Alzheimer’s disease, therefore acetylcholinesterase (AChE) inhibitors such as donepezil and rivastigmine are widely used for patients with limited therapeutic results and major side effects. Experimental approach: A series of isoindoline-1,3-dione -N-benzyl pyridinium hybrids were designed, synthesized and evaluated as anti-Alzheimer agents with cholinesterase inhibitory activities. The structure of the compounds were confirmed by various methods of analysis such as HNMR, CNMR, and FT-IR. Molecular modeling studies were also performed to identify the possible interactions between neprilysin and synthesized compounds. Findings/Results: The biological screening results indicated that all synthesized compounds displayed potent inhibitory activity with IC 50 values ranging from 2.1 to 7.4 µM. Among synthesized compounds, para-fluoro substituted compounds 7a and 7f exhibited the highest inhibitory potency against AChE (IC 50 = 2.1 µM). Molecular modeling studies indicated that the most potent compounds were able to interact with both catalytic and peripheral active sites of the enzyme. Also, some of the most potent compounds (7a, 7c, and 7f) demonstrated a neuroprotective effect against H 2 O 2 -induced cell death in PC12 neurons. Conclusion and implications: The synthesized compounds demonstrated moderate to good AChE inhibitory effect with results higher than rivastigmine.

Core-shell particles were synthesized employing seeded suspension polymerization. Suspension polystyrene (PS) particles were used as seeds, and poly(methyl methacrylate) (PMMA) was synthesized in the presence of polystyrene seeds. A combination of solvent extraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy techniques were employed to study the structure and morphology of synthesized particles. The results suggested a core-inner shell-outer shell structure for the synthesized particles in which the PS core was covered by a PMMA-rich inner shell and a very thin PS-rich outer shell. The size and concentration of PMMA domains decreased from the outer shell toward the core of the particle, and particle morphology was mainly controlled by the limitations to the diffusion of MMA through the polymer particle.

The viscosity of liquid mixtures in e-vapor products (EVPs) is key to their performance and is sensitive to mixture composition and temperature. To date, no accurate model exists for the viscositie...

The intestinal epithelium represents a natural barrier against harmful xenobiotics, whilst facilitating the uptakeof nutrients and other substances. Understanding the interaction of chemicals with constituents of theintestinal epithelium and their fate in the body requires quantitative measurement of relevant proteins in invitro systems and intestinal epithelium. Recent studies have highlighted the mismatch between mRNA andprotein abundance for several drug-metabolising enzymes and transporters in the highly dynamic environmentof the intestinal epithelium; mRNA abundances cannot therefore be used as a proxy for protein abundances inthe gut, necessitating direct measurements. The objective was to determine the expression of a wide rangeproteins pertinent to metabolism and disposition of chemicals and nutrients in the intestinal epithelium. Ileumand jejunum biopsy specimens were obtained from 16 patients undergoing gastrointestinal elective surgery.Mucosal fractions were prepared and analysed using targeted and global proteomic approaches. A total of 29enzymes, 32 transporters, 6 tight junction proteins, 2 adhesion proteins, alkaline phosphatase, thioredoxin, 5markers and 1 regulatory protein were quantified; 60 for the first time. The global proteomic methodidentified a further 5222 proteins, which are retained as an open database for interested parties to explore. Thisstudy significantly expand our knowledge of a wide array of proteins important for xenobiotic handling in theintestinal epithelium. Quantitative systems biology models will benefit from the novel systems data generatedin the present study and the translation path offered for in vitro to in vivo translation.

In this work, the biosynthesis of Ag or Pd nanoparticles (NPs) supported on Fe3O4/bentonite using an aqueous Salix aegyptiaca leave extract in the role of reducing and stabilizing agent was reported. Techniques of fourier transform infra-red spectroscopy, X-ray diffraction, field emission scanning electron microscope (FESEM), X-ray spectroscopy (EDX), and vibrating sample magnetometer were used for characterization of structures or properties of the prepared nanocomposites. The average particle sizes of well-dispersed spherical Ag and Pd NPs supported on the surface of Fe3O4/bentonite obtained from FESEM were below 70 nm. The magnetically recoverable Ag or Pd NPs/Fe3O4/bentonite nanocomposites exhibited remarkable catalytic activity for the reduction reaction of rhodamine B (RhB), methylene blue (MB), and methyl orange (MO) azo dyes in the presence of aqueous NaBH4 with good reusability. The obtained nanocomposites showed the dyes reduction rates in an order of Pd/Fe3O4/bentonite > Ag/Fe3O4/bentonite > Fe3O4/bentonite. The reduced form of MO under the reduction process cannot be converted to the original oxidized form; nevertheless, the products of the reduction reactions of RhB and MB can be oxidized again to the original form.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

To promote the low photocatalytic efficiency caused by the recombination of electron/hole pairs and widen the photo-response wavelength window, ZnFe2O4@ZnO-N/B/RGO and ZnFe2O4@ZnO-C3N4 ternary heterojunction nanophotocatalysts were designed and successfully prepared through a sol–gel technique. In comparison to bare ZnFe2O4 and ZnO, the ZnFe2O4-ZnO@N/B/RGO and ZnFe2O4@ZnO-C3N4 ternary products showed highly improved photocatalytic properties in the degradation of methyl orange (MO) under ultra-violet (UV) and visible light irradiation. Various physicochemical properties of the photocatalysts were evaluated through field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX) analysis, X-ray diffraction (XRD), UV–visible diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) techniques. The observations indicated that the ternary heterojuncted ZnFe2O4@ZnO-N/B/RGO absorbs lower energy visible light wavelengths, which is an enhancement in the photocatalytic properties of ZnFe2O4@ZnO loaded on reduced graphene oxide (RGO) nanosheets and graphite-like carbon nitride (g-C3N4). This gives the catalyst photo-Fenton degradation properties.

A CuO-ZnO@graphitic carbon nitride (Cu/Zn/g) triplex heterojunction nanocomposite was prepared through a multistep ultrasound-assisted hydrothermal procedure. XRD, SEM, EIS, EDX, BET, FT-IR, EDS, U...

Today, mesenchymal stem cells (MSCs) are candidates for various autoimmune disease treatments due to immunomodulatory activity in these cells. Much research has recently been done to improve the im...

A novel and efficient procedure for the generation of quinazolinone phosphonate derivatives employing the reaction of euparin, isatin or its derivatives, primary amines, dialkyl acetylenedicarboxylates, trimethyl phosphite or triphenyl phosphite, and acidic solution of hydrogen peroxide in aqueous media at ambient temperature under ultrasonic irradiation was developed. Without ultrasonic irradiation, the reaction does not proceed and agitation of the reaction mixture is difficult. Some advantages of this procedure are: short time of reaction, high yields of products, easy isolation of products.

In this study, the effects of incorporating of SiO2 nanoparticles into the ethylene glycol on the viscosity were examined. Many samples were prepared by two-step method to investigate the effects of temperature (5–65 ℃ ), mass fraction (0.005−5 wt.%), shear rate (3–110 1 s ) and sonication time (15−60 min) on viscosity. Rheological analysis revealed that despite the EG Newtonian behavior, it was found that SiO2/EG conforms to the non-Newtonian shear-thinning model. However, as the shear rate raised, the behavior tends to Newtonian. For all samples, the viscosity of SiO2/EG was higher than EG viscosity. At higher temperature as well as mass fraction and the lowest shear rate, the maximum intensification in viscosity was reported to be 133.7%. The sonication energy diminishes clustering length and consequently reduces the viscosity. It was found that the increase in sonication time from 15 min to 60 min, diminished the viscosity up to 14%.

Among renewable energies, using photovoltaic systems to convert solar energy into electricity without noise, toxin production and release of greenhouse gases has become increasingly important. These panels are diversely used on building roofs in urban areas, which exposes them to problems such as rapid deposition of dust and pollution that reduces light transmittance and cell efficiency. The present study aimed to enhance the self-cleaning ability of the glass surface of the solar cells. Therefore, titanium dioxide (TiO2) coating was applied for ultraviolet light section. TiO2 doped with nitrogen (N-TiO2) and four metals including copper (Cu-TiO2), cobalt (Co-TiO2), iron (Fe-TiO2) and silver (Ag-TiO2) coating were applied for visible light section. The surfaces were prepared by nanosol/dip-coating method. Using an ultraviolet–visible (UV–Vis) spectrometer, self-cleaning of glass surface, removal of methylene blue (MB) and light transmittance was investigated. Moreover, the prepared samples were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM) and Atomic force microscopy (AFM) analysis.

A conceptually simple route has been designed for the preparation of flexible plate by utilization of biodegradable cellophane film through addition of NaHCO3 powder into structure of Polypyrrole-Multiwalled carbon nanotube-Cellophane (PMC) composite and then by chemical treatment in acidic solution. A homogeneous conductive-porous structure was formed as a result of release of NaHCO3 from the composite bulk in acidic solution as well as CO2 (g) evolution. The porous PMC plate exhibited a specific capacitance of 244 mF cm−2 at a current density of 0.5 mA cm−2 and favorite rate capability. The assembled symmetric supercapacitor device showed a high areal capacitance of 309 mF cm−2 at 2.5 mA cm−2, excellent flexibility and a long cycle lifetime (89% capacitance retention after 5000 cycles). The strategy presented in this work opens a new door for environmentally friendly preparation of flexible-biodegradable supercapacitor devices with high mechanical strength.

Purpose The purpose of this study was to evaluate the possibility of using conductive polymers such as polyaniline (PANI) as corrosion inhibitors for metals. Design/methodology/approach In this study, the effect of the addition of praseodymium (Pr3+) cations on the corrosion inhibition performance of PANI for AZ31 magnesium alloy was appraised through electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization tests. Findings The results of EIS and potentiodynamic polarization tests indicated the improvement of corrosion resistance of AZ31 during different immersion times. Research limitations/implications This anti-corrosion ability of PANI/Pr3+ composite applies as non-toxic environmentally friendly corrosion inhibitor on the self-healing corrosion protection properties. Practical implications The conductive polymers are interested for many industries. The reported data can be used by the formulators working in the R&D departments. Social implications The anti-corrosion ability of PANI/Pr3+ composite present a novel and high effective route against metal corrosion besides application of toxic corrosion. Originality/value The application of titanium dioxide coating in the field of architectural heritage is a great challenge. Therefore, the main objective of this study is to study the synthesis, characterization and corrosion inhibition performance of Pr3+ cations doped PANI nano-fibers as an anti-corrosion additive for AZ31 magnesium alloy in 3.5 Wt.% NaCl solution.

In this article, for the first time, a hybrid plasmonic (HP) ring resonator uni-traveling carrier pin-photodetector was numerically presented that offers a high responsivity of 0.68 A/W, a high bandwidth of over 125 GHz, and low footprint. This device has the capability of monolithic integration with HP-passive devices on the InP platform at an optical communication wavelength of 1550 nm.

In this research, thermal conductivity of a hybrid nanofluid containing multi-walled carbon nanotubes (MWCNTs) and titanium dioxide (TiO2) has been examined. Many samples were prepared by loading MWCNTs and TiO2 at 50:50 mass% into the ethylene glycol (EG) to measure the thermal conductivity at temperatures within 25–50 °C and solid volume fractions of 0–1%. The amount of positive nanoparticles incorporation efficacy on the thermal conductivity was influenced by the volume fraction as well as the temperature. As the temperature augmented from 25 to 50 °C, the EG thermal conductivity was intensified by 9.6%, while this figure for nanofluid at 1 vol.% was 18.2%. Therefore, it is concluded that the loading nanoparticles amplified the thermal conductivity sensitivity to temperature. Statistical analysis showed that the positive effects of loading nanoparticles on thermal conductivity are amplified by rising temperature. At 25 °C, loading nanoparticles (1 vol.%) can amplify the thermal conductivity by 16%, while at 50 °C, this figure was 25.18% (maximum thermal conductivity enhancement). A correlation was developed using response surface methodology (RSM), and the input parameters significance was specified applying analysis of variance (ANOVA). Finally, using 28 machine learning-based algorithms, the hybrid nanofluid thermal conductivity has been predicted and compared with the RSM outputs.

A novel nanosheet-structured material, namely graphene oxide anchored with sulfonic acid-functionalized glycerin (GO@Gl-SO3H), was prepared and characterized by FTIR, EDS, FESEM, TEM and XRD analyses. Afterward, its catalytic performance was examined for the synthesis of N,N′-alkylidene bisamides through the reaction of benzamide (2 eq.) and arylaldehydes (1 eq.) under solvent-free conditions. GO@Gl-SO3H was a highly effective catalyst for the reaction and afforded the products in high yields and short reaction times.