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Addressing the urgent need to effectively manage landfill leachate as a harmful flow for human health and the environment, this research investigates how electrocoagulation (EC) processes could alleviate the pollution potential of leachate. So far, no experimental study has been carried out on reducing the leachate pollution index (LPI) under the EC process. For this purpose, in this novel research, the LPI was utilized as a key metric to evaluate the efficiency of the treatment process. Central Composite Design (CCD) as a subset of Response Surface Methodology (RSM) was applied to enhance the LPI parameters decreasing percentage. The data were analyzed by analysis of variance and multivariate regression and 3D plots assessed variable interactions. Under optimal conditions, it showed removal of 97.48 % for COD, 91.42 % for BOD5, 98.52 % for N-NH3, and 91.6 % for TDS. Significant reductions were observed in 94.81 % TKN, 87.20 %, 82.80 %, 96.66 %, and 99.28 %, 99.18 %, and 96.56 % for TKN, Cl-, CN-, As, Cr, Zn, and Ni, respectively. Moreover, the kinetics of COD removal indicated that it follows a first-order model. Thus, based on experimental results, the LPI of raw leachate decreased from 38.06 to 7.22 (81 % decrease) under the EC treatment method. The study indicated that the EC treatment method successfully reduced leachate pollution and met the leachate discharge standard.
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Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14-39%). The present investigation aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility. Furthermore, a sustained-release SMEDDS-based gastroretentive floating system was developed and optimized using the Central Composite Design approach of DoE. The optimized SMEDDS-based in situ gelling raft, R-SM-PZH, exhibited minimal floating lag time (3.09 ± 0.8 s), optimal viscosity (1229.4 ± 20.9 cP) and density (0.327 ± 0.15 g/mL) as compared to other formulations under study. Additionally, R-SM-PZH was evaluated for its in vitro dissolution in FaSSGF and FeSSGF, pharmacokinetic profile, and MTT assay (against NCI-H460 lung cancer cells) compared to pure PZH. A 12 h sustained release, three-fold augmentation in dissolution rate and bioavailability, and 15-fold enhancement in cytotoxicity were observed in comparison to pure PZH. Thus, the SMEDDS-based in situ gelling raft presents a promising approach to advancing the developability potential of PZH.
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This study presents the development of eco-friendly cementitious materials for soil stabilization, based on alkaline multi-industrial waste (AMIW), using steel slag (SS), blast furnace slag (BFS), carbide slag (CS), fly ash (FA) and flue gas desulfurization gypsum (FGDG) as the raw materials. The optimal AMIW-based cementitious material composition determined through orthogonal experiments was SS:CS:FGDG:BFS:FA = 15:10:15:44:16. Central composite design (CCD) in response surface methodology (RSM) was employed to optimize the curing process parameters. The maximum 7-day unconfined compressive strength (7d UCS) was achieved under the optimal conditions of 18.51% moisture content, 11.46% curing agent content and 26.48 min of mix-grinding time. The 7d UCS of the AMIW-stabilized soil showed a 24% improvement over ordinary Portland cement (OPC)-stabilized soil. Rietveld refinement results demonstrated that the main hydration products of the stabilized soil were C-S-H and ettringite. After curing for 7 days to 28 days, the C-S-H content increased from 3.31% to 5.76%, while the ettringite content increased from 1.41% to 3.54%. Mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) analysis revealed that with the extension of curing time, the pores of the stabilized soil become smaller and the structure becomes denser, resulting in an improvement in compressive strength.
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Agricultural residues are one of the most cost-effective and readily accessible carbon resources for producing commercially significant enzymes. Several enzymes have been used in different industries like pharmaceuticals, foods, textiles, and dyes that can be generated by various species of microbes found in waste from agriculture. The current research investigated laccase production by Aspergillus oryzae utilizing agricultural wastes. Physical and chemical properties, including pH, temperature, sucrose, yeast extract, and copper sulfate levels, were optimized. The utilization of the response surface methodology along with the centralized composite design method, which assesses multiple media parameters and utilizes a two-level experimental approach, aids in determining the variable and its significance in increasing production quality. The centralized composite design enhancement showed that the optimal conditions for highest laccase activity (623.16 U/mL) were pH 7.0, temperature 25 °C, corn cobs as substrate, sucrose (2.0 %), yeast extract (1.0 %), and copper sulfate (0.1 mM) level. The laccase enzyme was optimized using various pH, temperature, metal ions, and inhibitors combinations. The extracted laccase enzyme maximum activity was attained at pH 6.0 and 40 °C. The inclusion of divalent ions can enhance laccase activity, while the use of various inhibitors decreases laccase activity. Under various pH circumstances, the Aspergillus oryzae laccase enzyme can successfully degrade p-chlorophenol. The present study describes statistically validated optimal methodologies for enhancing laccase synthesis, leading to a laccase production technique that is simultaneously highly efficient and economically profitable, with possible use of p-chlorophenol degradation.
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Introduction: Soft pneumatic actuators (SPAs) play a pivotal role in soft robotics due to their unique characteristics of compliance, flexibility, and adaptability. There are plenty of approaches that examine the modeling parameters of SPAs, aiming to optimize their design and, thus, achieve the most advantageous responses. Current optimization methods applied to SPAs are usually performed individually for each design parameter without considering the simultaneous effect all parameters can have on the output performance. This modeling shortcoming is essential to be addressed since customized SPAs are used in a variety of applications, each with different output requirements. Methods: This study provides a generalized design optimization framework for modeling the SPA performance for their motion profiles, the produced strain energy while being deformed, and their stiffness characteristics. Utilizing experimentally validated finite element methods, all geometrical and material parameters of the models are investigated in response surface methodology optimization using the central composite design approach. Results: The results showcase the entire design space of omnidirectional SPAs, along with their output performance, providing guidelines to the end user for design optimization. Discussion: The offering of this modeling process for SPAs can be adapted to the demands of any potential application and ensure the best performance with respect to the required output responses.
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The optimization of floating bifacial solar panels (FBS PV) in tropical freshwater systems is explored by employing response surface methodology (RSM) and central composite design (CCD). Previous studies have yet to explore the long-term durability, environmental impact, economic viability, and performance of FBS PV systems under various climatic conditions. This study addresses this gap by focusing on panel height, water depth, and tilt angle to improve performance. The quadratic model reveals significant non-linear relationships impacting FBS PV power generation with freshwater cooling. Our models demonstrate high explanatory power, with R-squared values of 0.9831 for output power and 0.9900 for Bi-Facial gain. Experimental validation using conventional white surface (CWS) and proposed freshwater surface (PFS) indicates notable improvements in power generation, achieving a 4.34 to 4.86% gain in bifacial efficiency across various irradiation levels. Under 950 W/m2 irradiation, freshwater cooling achieves a 3.19% higher bifacial gain compared to CWS cooling. Panel temperature analysis shows consistent reductions with freshwater cooling, ranging from 1.43 to 2.72 °C, enhancing overall efficiency and longevity. This research highlights the potential of freshwater cooling in optimizing bifacial solar systems, offering actionable insights for sustainable energy solutions in tropical regions.
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α-tocopherol (α-T), ß-sitosterol (ß-S), canolol (CA), and sinapic acid (SA) are the four main endogenous lipid phytochemicals (LP) found in Brassica napus L. seed oil, which possess the bioactivity to prevent the risk of several chronic diseases via antioxidant-associated mechanisms. Discovering the enhancer effects or synergies between LP is valuable for resisting oxidative stress and improving health benefits. The objectives of this study were to identify a potentially efficacious LP combination by central composite design (CCD) and cellular antioxidant activity (CAA) and to investigate its protective effect and potential mechanisms against H2O2-induced oxidative damage in HepG2 cells. Our results indicated that the optimal concentration of LP combination was α-T 10 µM, ß-S 20 µM, SA 125 µM, and CA 125 µM, respectively, and its CAA value at the optimal condition was 10.782 µmol QE/100 g. At this concentration, LP combination exerted a greater amelioration effect on H2O2-induced HepG2 cell injury than either antioxidant (tea polyphenols or magnolol) alone. LP combination could reduce the cell apoptosis rate induced by H2O2, lowered to 10.06%, and could alleviate the degree of oxidative damage to cells (ROS↓), lipids (MDA↓), proteins (PC↓), and DNA (8-OHdG↓). Additionally, LP combination enhanced the antioxidant enzyme activities (SOD, CAT, GPX, and HO-1), as well as the T-AOC, and increased the GSH level in HepG2 cells. Furthermore, LP combination markedly upregulated the expression of Nrf2 and its associated antioxidant proteins. It also increased the expression levels of Nrf2 downstream antioxidant target gene (HO-1, SOD-1, MnSOD, CAT, GPX-1, and GPX-4) and downregulated the mRNA expression levels of Keap1. The oxidative-stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by LP treatment. These results indicate that LP combination protected HepG2 cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE signaling pathways.
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Antioxidantes , Brassica napus , Peróxido de Hidrógeno , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Fitoquímicos , Semillas , Transducción de Señal , Humanos , Células Hep G2 , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Fitoquímicos/farmacología , Antioxidantes/farmacología , Semillas/química , Elementos de Respuesta Antioxidante/efectos de los fármacos , Aceites de Plantas/farmacología , Sitoesteroles/farmacologíaRESUMEN
Despite the large number of works on the synthesis of polylactide-co-glycolide (PLGA) nanoparticles (NP) loaded with antituberculosis drugs, the data on the influence of various factors on the final characteristics of the complexes are quite contradictory. In the present study, a comprehensive analysis of the effect of multiple factors, including the molecular weight of PLGA, on the size and stability of nanoparticles, as well as the loading efficiency and release of the antituberculosis drug rifampicin (RIF), was carried out. Emulsification was carried out using different surfactants (polyvinyl alcohol, Tween 80 and Pluronic F127), different aqueous-to-organic phase ratios, and different solvents (dichloromethane, dimethyl sulfoxide, ethyl acetate). In this research, the PLGA nanoemulsion formation process was accompanied by ultrasonic dispersion, at different frequencies and durations of homogenization. The use of the central composite design method made it possible to select optimal conditions for the preparation of PLGA-RIF NPs (particle size 223 ± 2 nm, loading efficiency 67 ± 1%, nanoparticles yield 47 ± 2%). The release of rifampicin from PLGA NPs was studied for the first time using the flow cell method and vertical diffusion method on Franz cells at different pH levels, simulating the gastrointestinal tract. For the purpose of the possible inhalation administration of rifampicin immobilized in PLGA NPs, their mucoadhesion to mucin was studied, and a high degree of adhesion of polymeric nanoparticles to the mucosa was shown (more than 40% within 4 h). In the example of strain H37Rv in vitro, the sensitivity of Mycobacterium tuberculosis to PLGA-RIF NPs was proven by the complete inhibition of their growth.
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The insulators of overhead power lines play a crucial role in maintaining the reliability of transmission and distribution networks. Because they are exposed to harsh and dynamic environmental conditions, it is essential to investigate the impact of environmental parameters such as pollution, inclined angle with the cross arm, and temperature on the dielectric performance of the insulators of overhead lines. Conventionally, the effect of such parameters can be investigated through experimental measurements of the insulator flashover voltage. However, this approach is costly and time-consuming and calls for the isolation of the lines to conduct the test, causing interruption to the entire grid. As such, there is an essential need to develop a new methodology to quantify the flashover voltage of overhead insulators operating under various environmental conditions, which is the main aim of this paper. The Central Composite Design is employed to develop a mathematical correlation between the insulator flash over voltage as a dependent variable and three environmental parameters: pollution level, inclined angle, and temperature as independent variables. The robustness of the developed equation is validated through extensive experimental measurements of the insulator's flash overvoltage under various conditions. Results reveal a good agreement between the actual and predicted flashover voltage using the developed correlation, as the absolute error for all investigated samples is less than 6%.
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This study explored the green synthesis of silver nanoparticles (AgNPs) using the extracellular filtrate of Fusarium oxysporum as a reducing agent and evaluated their antitumor potential through in vitro and in silico approaches. The biosynthesis of AgNPs was monitored by visual observation of the color change and confirmed by UV-Vis spectroscopy, revealing a characteristic peak at 418 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses showed spherical nanoparticles ranging from 6.53 to 21.84 nm in size, with stable colloidal behavior and a negative zeta potential of -15.5 mV. Selected area electron diffraction (SAED) confirmed the crystalline nature of the AgNPs, whereas energy-dispersive X-ray (EDX) indicated the presence of elemental silver at 34.35%. A face-centered central composite design (FCCD) was employed to optimize the biosynthesis process, yielding a maximum AgNPs yield of 96.77 µg/mL under the optimized conditions. The antitumor efficacy of AgNPs against MCF-7 and HepG2 cancer cell lines was assessed, with IC50 values of 35.4 µg/mL and 7.6 µg/mL, respectively. Molecular docking revealed interactions between Ag metal and key amino acids of BCL-2 (B-cell lymphoma-2) and FGF19 (fibroblast growth factor 19), consistent with in vitro data. These findings highlight the potential of biologically derived AgNPs as promising therapeutic agents for cancer treatment and demonstrate the utility of these methods for understanding the reaction mechanisms and optimizing nanomaterial synthesis.
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Machine learning and response surface methods for predicting the compressive strength of high-strength concrete have not been adequately compared. Therefore, this research aimed to predict the compressive strength of high-strength concrete (HSC) using different methods. To achieve this purpose, neuro-fuzzy inference systems (ANFISs), artificial neural networks (ANNs), and response surface methodology (RSM) were used as ensemble methods. Using an ANN and ANFIS, high-strength concrete (HSC) output was modeled and optimized as a function of five independent variables. The RSM was designed with three input variables: cement, and fine and coarse aggregate. To facilitate data entry into Design Expert, the RSM model was divided into six groups, with p-values of responses 1 to 6 of 0.027, 0.010, 0.003, 0.023, 0.002, and 0.026. The following metrics were used to evaluate model compressive strength projection: R, R2, and MSE for ANN and ANFIS modeling; R2, Adj. R2, and Pred. R2 for RSM modeling. Based on the data, it can be concluded that the ANN model (R = 0.999, R2 = 0.998, and MSE = 0.417), RSM model (R = 0.981 and R2 = 0.963), and ANFIS model (R = 0.962, R2 = 0.926, and MSE = 0.655) have a good chance of accurately predicting the compressive strength of high-strength concrete (HSC). Furthermore, there is a strong correlation between the ANN, RSM, and ANFIS models and the experimental data. Nevertheless, the artificial neural network model demonstrates exceptional accuracy. The sensitivity analysis of the ANN model shows that cement and fine aggregate have the most significant effect on predicting compressive strength (45.29% and 35.87%, respectively), while superplasticizer has the least effect (0.227%). RSME values for cement and fine aggregate in the ANFIS model were 0.313 and 0.453 during the test process and 0.733 and 0.563 during the training process. Thus, it was found that both ANN and RSM models presented better results with higher accuracy and can be used for predicting the compressive strength of construction materials.
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This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 µM and 7.9 µM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.
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A simple and effective ultrasound-assisted dispersive micro solid-phase extraction (UA-dµSPE) method was developed for the spectrophotometric determination of traces maneb in food and water. In this study, a new hybrid block copolymer poly (vinyl benzyl chloride-b-dimethyl aminoethyl methacrylate) (Pvb-DMA) was synthesized and characterized using techniques such as FTIR, SEM-EDX. The synthesized Pvb-DMA was used as an adsorbent for the extraction of maneb for first time in this study. The effects of different experimental variables such as pH, adsorbent amount, sample volume, eluent type were optimized. The statistical toll factorial design was applied to estimate the individual and combined impact of parameters on the extraction of maneb. The applicability of different solvents such as acetone, methanol, ethanol, tetrahydrofuran, acetonitrile for maneb recovery from adsorbent was tested. The detection and quantification limits were found to be 3.3 ng mL-1 and 10.0 ng mL-1, respectively. In addition, the preconcentration factor and linear range was obtained 300 and 10-500 ng mL-1. The extraction recovery and relative standard deviation were found to be 95 % and 2.8 %, respectively.
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Istamycins (ISMs) are 2-deoxyfortamine-containing aminoglycoside antibiotics (AGAs) produced by Streptomyces tenjimariensis ATCC 31603 with broad-spectrum bactericidal activities against most of the clinically relevant pathogens. Therefore, this study aimed to statistically optimize the environmental conditions affecting ISMs production using the central composite design (CCD). Both the effect of culture media composition and incubation time and agitation rate were studied as one factor at the time (OFAT). The results showed that both the aminoglycoside production medium and the protoplast regeneration medium gave the highest specific productivity. Results also showed that 6 days incubation time and 200 rpm agitation were optimum for their production. A CCD quadratic model of 17 runs was employed to test three key variables: initial pH, incubation temperature, and concentration of calcium carbonate. A significant statistical model was obtained including, an initial pH of 6.38, incubation temperature of 30 ËC, and 5.3% CaCO3 concentration. This model was verified experimentally in the lab and resulted in a 31-fold increase as compared to the unoptimized conditions and a threefold increase to that generated by using the optimized culture media. To our knowledge, this is the first report about studying environmental conditions affecting ISM production as OFAT and through CCD design of the response surface methodology (RSM) employed for statistical optimization. In conclusion, the CCD design is an effective tool for optimizing ISMs at the shake flask level. However, the optimized conditions generated using the CCD model in this study should be scaled up in a fermenter for industrial production of ISMs by S. tenjimariensis ATCC 31603 considering the studied environmental conditions that significantly influence the production proces.
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Antibacterianos , Medios de Cultivo , Fermentación , Streptomyces , Temperatura , Streptomyces/metabolismo , Streptomyces/crecimiento & desarrollo , Medios de Cultivo/química , Concentración de Iones de Hidrógeno , Antibacterianos/biosíntesis , Antibacterianos/farmacología , Carbonato de Calcio/metabolismo , Aminoglicósidos/farmacología , Microbiología Industrial , Reactores Biológicos/microbiologíaRESUMEN
Osteoarthritis (OA) is a chronic joint disease that results in biomechanical and morphological changes that contribute to cartilage degradation. Ketoprofen (KP), used in the treatment of OA, is a selective inhibitor of cyclooxygenase-2 (COX-2). Topical administration of KP bypasses gastric irritation as well as first-pass metabolism and increases localized delivery. The research intricates fabrication and optimization of KP-loaded transethosomes (KP-TEs) via Taguchi orthogonal array design and Central composite design (CCD). The optimized KP-TEs depicted an average vesicle size of 110.0 ± 1.70 nm, poly dispersibility index (PDI) of 0.103 ± 0.01, zeta potential -6.08 ± 0.27 mV, and conductivity of 0.049 ± 0.0001 mS/cm. The optimized KP-TEs were loaded in composite hyaluronic acid (HA) and poloxamer 407 (Px407) for an improvement of osteotrophic and chondroprotective transethosomal gel. The drug content of KP-TEs-HA/Px407 gel was found to be 90.08 ± 1.25 %. Preclinical research has been carried out by using the monosodium iodoacetate to develop model for osteoarthritis in male wistar rats. The X-ray imaging of KP-TEs-HA/Px407 gel treated group showed intact meniscus, healthy articular joint, and normal synovial lining same as the healthy control group. The IL - 1ß IL-6, IL-22, TNF-α, and IL-10, levels, X-ray imaging, and studies on histopathology demonstrated the effectiveness of transethosomal gel in reducing pain and inflammation.
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Drugs with lower permeability and water solubility provide major challenges for producing safe and efficient formulations. The current work aims to prepare ICs of the drug phenothiazine and ß-cyclodextrin via physical, microwave, freeze-drying, and kneading methods. Many analytical methods, such as 1H NMR, ROESY, FT-IR, DSC, SEM, and XRD, were then used to confirm the formation of inclusion complexes. The natural polysaccharide-based hydrogel comprising pectin and pullulan was synthesized in air and optimized through various parameters. In order to maximize the reaction parameters, Response Surface Methodology design was employed for experimental optimization. We use FT-IR, TGA, SEM, EDX, and XRD to investigate hydrogel formation. At 37 °C, an investigation was carried out on the in vitro controlled release of PN at pH 2, 7, and 7.4. The analysis of drug release data revealed that PM and KM exhibited an initial burst release of drugs, with the MW and FD method proving to be the most suitable approach for achieving precise ICs of PN and ß-CD for sustained drug release. The kinetics of drug release were evaluated using various kinetic models, with the Riteger-Peppas and Peppas-Sahlin models demonstrating the best fit for drug release in all instances.
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Preparaciones de Acción Retardada , Liberación de Fármacos , Glucanos , Hidrogeles , Pectinas , Fenotiazinas , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Pectinas/química , Glucanos/química , Hidrogeles/química , Concentración de Iones de Hidrógeno , Fenotiazinas/química , Cinética , Portadores de Fármacos/química , Espectroscopía Infrarroja por Transformada de Fourier , SolubilidadRESUMEN
Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA's therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood-brain barrier (BBB). This work aimed to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with folic acid (FA), as its receptor is overexpressed in BBB and GBM cells, for GA delivery to enhance its therapeutic efficacy. The preparation of NPs was optimized by a central composite design (CCD). The obtained NPs showed physicochemical features suitable for drug internalization in BBB and tumor cells (sizes below 200 nm, monodispersity, and negative surface charge) and the ability to maintain a slow and sustained release for 40 days. In vitro studies using a human GBM cell line (U215) revealed the NPs' ability to accumulate in the target cells, further promoting GA antiproliferative activity by inducing the production of intracellular reactive oxygen species (ROS). Furthermore, GA encapsulation in the developed nanosystems conferred higher protection to healthy cells.
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Global warming, driven by greenhouse gases like CH4 and CO2, necessitates efficient catalytic conversion to syngas. Herein, Ni containing different molecular sieve nanomaterials are investigated for dry reforming of methane (DRM). The reduced catalysts are characterized by surface area porosity, X-ray diffraction, Raman infrared spectroscopy, CO2 temperature-programmed desorption techniques, and transmission electron microscopy. The active sites over each molecular sieve remain stable under oxidizing gas CO2 during DRM. The reduced 5Ni/CBV10A catalyst, characterized by the lowest silica-alumina ratio, smallest surface area and pore volume, and narrow 8-ring connecting channels, generated the maximum number of active sites on its outer surface. In contrast, the reduced-5Ni/CBV3024E catalyst, with the highest silica-alumina ratio, more than double the surface area and pore volume, 12-ring sinusoidal porous channels, and smallest Ni crystallite, produced the highest H2 output (44%) after 300 min of operation at 700 °C, with a CH4:CO2 = 1:1, P = 1 atom, gas hour space velocity (GHSV) = 42 L gcat-1 h-1. This performance was achieved despite having 25% fewer initial active sites, suggesting that a larger fraction of these sites is stabilized within the pore channels, leading to sustained catalytic activity. Using central composite design and response surface methodology, we successfully optimized the process conditions for the 5Ni/CBV3024E catalyst. The optimized conditions yielded a desirable H2 to CO ratio of 1.00, with a H2 yield of 91.92% and a CO yield of 89.16%, indicating high efficiency in gas production. The experimental results closely aligned with the predicted values, demonstrating the effectiveness of the optimization approach.
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Gummy candy is one of the main snacks for children, and conventional samples with high calorie illustrate no nutritional value; therefore, the aim of present research was to develop functional product on priority. Celery (Apium graveolens) puree (25%-50%), boswellia gum (10%-20%), lemon essential oil (0.25%-0.50%), and sugar (10%-20%) in two levels were considered for vegan gummy candy production. Based on central composite design, the 30 types of gummy candies were prepared; afterward, response surface methodology was applied to optimize results determined by texture (hardness, springiness, adhesiveness, gumminess, chewiness, and elasticity characteristics), physicochemical attributes (pH, sugar content, water activity, antioxidant function, and calorie restriction), and also sensory evaluation. In general, elevated concentration of celery puree and boswellia gum-enhanced hardness, chewiness, and also gumminess for treated products. On the other hand, higher sugar with lemon essential oil improved adhesion, springiness, and elasticity features. More boswellia gum, celery, lemon essential oil, and reduction in sugar elevated water activity and also declined pH for treated samples. The celery puree, boswellia gum, and lemon essential oil significantly enhanced antioxidant function of treated gummy candies. According to attained results, sugar had a remarkable influence on acceptability and in treated samples calorie decreased. Based on all investigated factors, optimal formulation was achieved including 25% celery puree, 20% boswellia gum, 0.450% lemon essential oil, and 13.55% sugar. Regarding the results, obtained gummy candy with high nutritional value and low calorie demonstrated the potential to produce extensively in food sector.
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Treatment-induced ototoxicity and accompanying hearing loss are a great concern associated with chemotherapeutic or antibiotic drug regimens. Thus, prophylactic cure or early treatment is desirable by local delivery to the inner ear. In this study, we examined a novel way of intratympanically delivered sustained nanoformulation by using crosslinked hybrid nanoparticle (cHy-NPs) in a thermoresponsive hydrogel i.e. thermogel that can potentially provide a safe and effective treatment towards the treatment-induced or drug-induced ototoxicity. The prophylactic treatment of the ototoxicity can be achieved by using two therapeutic molecules, Flunarizine (FL: T-type calcium channel blocker) and Honokiol (HK: antioxidant) co-encapsulated in the same delivery system. Here we investigated, FL and HK as cytoprotective molecules against cisplatin-induced toxic effects in the House Ear Institute - Organ of Corti 1 (HEI-OC1) cells and in vivo assessments on the neuromast hair cell protection in the zebrafish lateral line. We observed that cytotoxic protective effect can be enhanced by using FL and HK in combination and developing a robust drug delivery formulation. Therefore, FL-and HK-loaded crosslinked hybrid nanoparticles (FL-cHy-NPs and HK-cHy-NPs) were synthesized using a quality-by-design approach (QbD) in which design of experiment-central composite design (DoE-CCD) following the standard least-square model was used for nanoformulation optimization. The physicochemical characterization of FL and HK loaded-NPs suggested the successful synthesis of spherical NPs with polydispersity index < 0.3, drugs encapsulation (> 75%), drugs loading (~ 10%), stability (> 2 months) in the neutral solution, and appropriate cryoprotectant selection. We assessed caspase 3/7 apopototic pathway in vitro that showed significantly reduced signals of caspase 3/7 activation after the FL-cHy-NPs and HK-cHy-NPs (alone or in combination) compared to the CisPt. The final formulation i.e. crosslinked-hybrid-nanoparticle-embedded-in-thermogel was developed by incorporating drug-loaded cHy-NPs in poloxamer-407, poloxamer-188, and carbomer-940-based hydrogel. A combination of artificial intelligence (AI)-based qualitative and quantitative image analysis determined the particle size and distribution throughout the visible segment. The developed formulation was able to release the FL and HK for at least a month. Overall, a highly stable nanoformulation was successfully developed for combating treatment-induced or drug-induced ototoxicity via local administration to the inner ear.