Development of Graphene Oxide-Based Anticancer Drug Combination Functionalized with Folic Acid as Nanocarrier for Targeted Delivery of Methotrexate.

Graphene has become a prominent material in cancer research in recent years. Graphene and its derivatives also attract attention as carriers in drug delivery systems. In this study, we designed a graphene oxide (GO)-based methotrexate (MTX)-loaded and folic acid (FA)-linked drug delivery system. MTX and FA were bound to GO synthesized from graphite. MTX/FA/GO drug delivery system and system components were characterized using Fourier transform infrared spectroscopy (FTIR), differential calorimetric analysis (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential analysis, and dimension measurement (DLS) studies. SEM and TEM images confirmed the nanosheet structure of GO synthesized from graphite, and it was shown that MTX/FA binding to GO transformed the two-dimensional GO into a three-dimensional structure. FTIR and DSC graphs confirmed that oxygen atoms were bound to GO with the formation of carboxylic, hydroxyl, epoxide, and carbonyl groups as a result of the oxidation of graphite, and GO was successfully synthesized. Additionally, these analyses showed that MTX and FA bind physicochemically to the structure of GO. The in vitro Franz diffusion test was performed as a release kinetic test. The release kinetics mathematical model and correlation coefficient (R2) of MTX-loaded GO/FA nanomaterials were found to be the Higuchi model and 0.9785, respectively. Stiffness analyses showed that adding FA to this release system facilitated the entry of the drug into the cell by directing the system to target cells. As a result of the stiffness analyses, the stiffness values of the control cell group, free MTX, and MTX/FA/GO applied cells were measured as 2.34 kPa, 1.87 kPa, and 1.56 kPa, respectively. According to these results, it was seen that MTX/FA/GO weakened the cancer cells. Combined use of the MTX/FA/GO drug delivery system had a higher cytotoxic effect than free MTX on the MDA-MB-231 breast cancer cell line. The results showed that the synthesized MTX/FA/GO material has promising potential in cancer cell-specific targeted therapy for MTX as a drug delivery system.

Higher heating value estimation of wastes and fuels from ultimate and proximate analysis by using artificial neural networks.

Higher heating value (HHV) is one of the most important parameters in determining the quality of the fuels. In this study, comparatively large datasets of ultimate and proximate analysis are constructed to be used in HHV estimation of several classes of fuels, including char & fossil fuels, agricultural wastes, manure (chicken, cow, horse, sheep, llama, and pig), sludge (like paper, paper-mil, sewage, and pulp), micro/macro-algae's, wastes (RDF and MSW), treated woods, untreated woods, and others (non-fossil pyrolysis oils) between the HHV range of 4.22-55.55 MJ/kg. The relationships of carbon, hydrogen, and oxygen atomic ratios for fuel classes are illustrated by using ternary plots, and the effects of elemental composition on HHV was analyzed with the extensive dataset. Then, the ultimate (U) and ultimate & proximate (UP) datasets were utilized separately to estimate the HHV by using artificial neural networks (ANN). Hyperparameter optimization was carried out and the best performing ANNs were determined for each dataset, which yielded R2 values of 0.9719 and 0.9715, respectively. The results indicated that while ANNs trained by both datasets perform remarkably well, utilization of U dataset is sufficient for HHV estimation. Finally, the best performing ANN models for both U and UP datasets are given in a directly utilizable format enabling the accurate estimation of HHV of any fuel for optimization of fuel processing and waste management operations.

Three-Dimensional-Printed GelMA-KerMA Composite Patches as an Innovative Platform for Potential Tissue Engineering of Tympanic Membrane Perforations.

Tympanic membrane (TM) perforations, primarily induced by middle ear infections, the introduction of foreign objects into the ear, and acoustic trauma, lead to hearing abnormalities and ear infections. We describe the design and fabrication of a novel composite patch containing photocrosslinkable gelatin methacryloyl (GelMA) and keratin methacryloyl (KerMA) hydrogels. GelMA-KerMA patches containing conical microneedles in their design were developed using the digital light processing (DLP) 3D printing approach. Following this, the patches were biofunctionalized by applying a coaxial coating with PVA nanoparticles loaded with gentamicin (GEN) and fibroblast growth factor (FGF-2) with the Electrohydrodynamic Atomization (EHDA) method. The developed nanoparticle-coated 3D-printed patches were evaluated in terms of their chemical, morphological, mechanical, swelling, and degradation behavior. In addition, the GEN and FGF-2 release profiles, antimicrobial properties, and biocompatibility of the patches were examined in vitro. The morphological assessment verified the successful fabrication and nanoparticle coating of the 3D-printed GelMA-KerMA patches. The outcomes of antibacterial tests demonstrated that GEN@PVA/GelMA-KerMA patches exhibited substantial antibacterial efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, cell culture studies revealed that GelMA-KerMA patches were biocompatible with human adipose-derived mesenchymal stem cells (hADMSC) and supported cell attachment and proliferation without any cytotoxicity. These findings indicated that biofunctional 3D-printed GelMA-KerMA patches have the potential to be a promising therapeutic approach for addressing TM perforations.

Serial progesterone levels more accurately predict the time of ovulation in subfertile women: a prospective cohort study.

PURPOSE: To predict ovulation in subfertile women using serial follicular growth (FG) and serum hormone measures (estradiol (E2), luteinizing hormone (LH), and progesterone (P) levels) in mathematical models. METHODS: This was a prospective observational study of 116 subfertile women aged between 18 and 40 years. FG was assessed by serial transvaginal ultrasonography starting from cycle days 8-12, depending on cycle length. Once the dominant follicle reached 15-16 mm, hormone levels were assessed daily. The primary outcome measure was ovulation (Ov), with a serum LH level ≥15 IU/l defining the start of the LH surge (the day prior to ovulation) and a serum P level >1 µg/ml concurrent with a drop in serum E2 levels indicating Ov. To determine Ov, mathematical models were generated using FG, LH, E2, and P measurements. RESULTS: A mathematical model was constructed using exponential regression to relate days until and after ovulation with P levels. The Ov(P) model was found to be superior to the Ov(LH) model in the prediction of Ov, with high R2 and low RMSE values of 0.9983 and 0.2454, respectively. In the range of [-2, 2] days, the net accuracy of the Ov(P) model was 63.0%, while with an allowed one-day error, the accuracy was 99.6%. CONCLUSION: Serum P levels display a highly predictable linear curve in natural cycles, which enables the prediction of ovulation. The Ov(P) model can be independently used to schedule embryo transfer in natural frozen-thaw cycles and could therefore replace the Ov(LH) model in clinical practice.

Characterization, optimization, and evaluation of preservative efficacy of carboxymethyl cellulose/hydromagnesite stromatolite bio-nanocomposite.

Currently, researchers are focusing on the development of nano-additive preservatives during the worldwide COVID-19 pandemic. This research aimed to constitute a small sized preservative nano-formulation which emerges from the biopolymer carboxymethyl cellulose (a green stabilizing agent) and hydromagnesite stromatolite (a fossilized natural additive). In this study, we investigated the optimization of the experimental design of carboxymethyl cellulose/hydromagnesite stromatolite (CMC/HS) bio-nanocomposites using a green and one-step sonochemical method at room temperature. In addition, we constructed a mathematical model which relates the intrinsic viscosity with all operating variables, and we carried out statistical error analysis to assess the validity of the proposed model. The characterization and chemical functional groups of CMC/HS bio-nanocomposites were determined by different advanced techniques such as SEM, HRTEM, DLS, FTIR, XRD, and BET. The challenge test was used to show the preservative efficacy of CMC/HS bio-nanocomposites against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus brasiliensis. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltrazolium bromide (MTT) assay was performed on L929 cells to evaluate the in vitro cytotoxicity of CMC/HS bio-nanocomposites. According to the results, we showed that the synthesized CMC/HS bio-nanocomposites have no cytototoxic effects on L929 fibroblast cells and could be considered to be an alternative green nano-additive preservative against pathogenic microorganisms.