The clarification conditions and the selection of the clarification agent are pivotal in eliminating the haze components from red grape juice (RGJ) while minimizing the loss of functional color components. In this context, we synthesized a water glass-based APTES functionalized magnesium silica aerogel (MSA-NH3) incorporating 61.44 molecules/nm2 of amine groups, resulting in a positively charged zeta potential value of 33.9 mV (pH 3.4) for clarification of RGJ by targeting negatively charged polyphenols. The optimum clarification conditions using MSA-NH3 were determined as 0.18 g MSA-NH3/L RGJ, 20 °C, and 60 min through the application of Box-Behnken design. Under these conditions, MSA-NH3 exhibited excellent adsorption of haze components (3.61 NTU), outperforming the commercial bentonite-gelatine combination (BGC) (5.45 NTU). Furthermore, it exhibited greater efficacy in preserving anthocyanins while adsorbing browning components. MSA-NH3 has a high potential to serve as a functional alternative clarification agent in the beverage industry due to its promising clarification performance.

The neem tree (Azadirachta indica A. Juss) is grown mainly for shade, fuel, and numerous non-timber forest products using its leaves, fruit, and bark. It produces an essential oil that is used as a source for obtaining bioinsecticides, with a broad spectrum of action in agricultural production. Its bioinsecticidal activity is due to the presence of triterpenes, such as azadirachtin, a product in continued growth of the global biopesticide market. Optimal conditions for neem oil extraction using response surface methodology (RSM) and microwave-assisted extraction (MAE) methods have been defined. However, the extraction conditions for these methods tend to consume high volumes of organic solvent and long extraction times. The aim of the present study is to determine the optimal conditions for the extraction of azadirachtin from neem seeds in a hydroalcoholic medium using MAE and RSM with a Box-Behnken design (BBD). A BBD was applied to evaluate the effects of the factors, magnetron voltage (X1), extraction time (X2), and pH of the extraction medium (X3), on the yield of the azadirachtin extraction process. The effect of each variable on the extraction yield was studied independently, considering the pure coefficients (linear and quadratic) on the three levels that were studied in the experiments. Moreover, the study experiments were conducted in triplicate, data were presented as mean and standard deviation, homogeneity of variances was estimated using Levene\'s test, and a two-way ANOVA with Tukey\'s post hoc analysis was performed to identify the experimental conditions that allowed us to find the highest extraction yield and to analyze whether the response surface model adequately described our data. The most significant effects of the model correspond to quadratic and interaction effects (p < 0.0001); the quadratic terms voltage (X1), extraction time (X2), and pH (X3); and the interaction effects between voltage-pH (X1*X3) and time-pH (X2*X3), which had a significant influence on the model. Moreover, a canonical analysis was performed. The optimal conditions were as follows: 69.22 V, 6.89 min, and a pH value of 4.35, coinciding with the zones shown in the contour plots. Furthermore, the response obtained at the optimal conditions was 37.5 μg of azadirachtin per gram of pretreated seed.

UNASSIGNED: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel.
UNASSIGNED: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed.
UNASSIGNED: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery.
UNASSIGNED: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Baicalin, a flavonoid extracted from traditional Chinese medicine, Scutellaria baicalensis has significant anti-inflammatory effects. Microsponges are drug delivery systems that improve drug stability and slow the release rate. The combination of baicalin and the microsponges produced a new and stable system for its delivery, resulting in a novel formulation of baicalin. Baicalin microsponges (BM) were prepared using the quasi-emulsion solvent diffusion method. Effects of the mass ratio of the polymer (ethylcellulose) to baicalin, the concentration of the emulsifier polyvinyl alcohol (PVA), the stirring speed on the encapsulation efficiency (EE), and yield of the microsponges were investigated by combining the one-factor test and Box-Behnken design (BBD). The preparation process was standardised using 2.61:1 mass ratio of ethyl cellulose to baicalin, 2.17% concentration of PVA, with stirring at 794 rpm. Optimised BM formulations were evaluated for the parameters of EE (54.06 ± 3.02)% and yield of (70.37 ± 2.41)%, transmission electron microscopy (TEM), and in vitro cell evaluation. Results of the in vitro anti-inflammatory assay showed that baicalin microsponges-pretreated-lipopolysaccharide (LPS)-induced RAW264.7, mouse macrophages showed reduced inflammatory response, similar to that seen in baicalin-treated macrophages.

About half of the 1.62 billion cases of anemia are because of poor diet and iron deficiency. Currently, the use of iron-enriched yeasts can be used as the most effective and possible way to prevent and treat anemia due to the ability of biotransformation of mineral compounds into the organic form. In this research, for the first time, Saccharomyces (S.) boulardii was used for iron enrichment with the aim that the probiotic properties of yeast provide a potential iron supplement besides improving the bioavailability of iron. Also, due to its higher resistance than other Saccharomyces strains against stresses, it can protect iron against processing temperatures and stomach acidic-enzymatic conditions. So, the effect of three important variables, including concentration of iron, molasses and KH2PO4 on the growth and biotransformation of yeast was investigated by the Box-Behnken design (BBD). The best conditions occurred in 3 g/l KH2PO4, 20 g/l molasses and 12 mg/l FeSO4 with the highest biotransformation 27 mg Fe/g dry cell weight (DCW) and 6 g/l biomass weight. Such yeast can improve fermented products, provide potential supplement, and restore the lost iron of bread, which is a useful iron source, even for vegetarians-vegans and play an important role in manage with anemia. It is recommended that in future researches, attention should be paid to increasing the iron enrichment of yeast through permeabilizing the membrane and overcoming the structural barrier of the cell wall.

The huge utilization of hydroxychloroquine in autoimmune infections led to an abnormal increment in its concentration in wastewater, which can pose a real risk to the environment, necessitating the development of a pretreatment technique. To do this, we are interested in researching how hydroxychloroquine degrades in contaminated water. The main goal of this investigation is to optimize the operating conditions for the sono-photodegradation of hydroxychloroquine in water using an ultrasound-assisted Fe(0)/ S 2 O 8 2 - /UV system. To get adequate removal of HCQ, a chemometric method based on the Box-Behnken design was applied to optimize the influence of the empirical parameters selected, including Fe(0) dose, S 2 O 8 2 - concentration, pH, and initial HCQ concentration. The quadratic regression model representing the HCQ removal rate (η(%)) was evolved and validated by ANOVA. The optimal conditions as a result of the above-mentioned trade-off between the four input variables, with η(%) as the dependent output variable, were captured using RSM methodology and the composite desirability function approach. For HCQ full decomposition, the optimal values of the operating factors are as follows: S 2 O 8 2 - dose, 194.309 mg/L; Fe(0) quantity, 198.83 mg/L; pH = 2.017, and HCQ initial dose of 296.406 mg/L. Under these conditions, the HCQ removal rate, achieved after 60 min of reaction, attained 98.95%.

Enzymatic hydrolysis is an essential step in the lignocellulosic biorefining process. In this paper, Box-Behnken was used to optimize the enzymatic hydrolysis process of corn stalk, and the promotion effect of three typical surfactants on the enzymatic hydrolysis process was investigated. The experimental results showed that the total reducing sugar yield reached 67.6% under the best-predicted conditions. When the concentration of Tween 80 is 0.1%, it could be increased to 80.2%. In addition, the Impeded Michaels Model (IMM) is introduced in this study to describe the enzymatic hydrolysis process of corn stalks. Finally, the initial contact coefficient between the enzyme and cellulose (Kobs,0) and the gradual loss coefficient of enzyme activity (ki) caused by reaction obstruction were obtained by fitting data, which successfully verified the rationality of the model.

Plant extracts have been shown to effectively inhibit metal corrosion. Using the Box-Behnken design, gravimetric, and electrochemical techniques, analyses were designed to investigate the anti-corrosion potential of okra in a 1M HCl medium. The inhibition performances derived from the various methods were in good agreement, demonstrating that physio-chemisorption was effective and adhered to the Langmuir isotherm model. The efficiency of okra mucilage extract was 96% at a much lower concentration compared to 91.2% and 88.4% for the unsieved extract and gelly-okra filtrate, respectively. FTIR results showed the presence of several functional groups in the okra mucilage extract that are associated with adsorption, and TGA analysis revealed that the extract has high thermal stability. FESEM analysis also supported evidence of adsorption. It was determined that corrosion inhibition by okra mucilage extract was primarily influenced by temperature, followed by extract concentration, with immersion time having the least effect. From the model optimization, it was observed that okra mucilage extract at 200 ppm, 60°C, and 24 h gave an inhibition efficiency of 89.98% and high desirability. These results demonstrate the high capacity of natural okra as an efficient biodegradable corrosion inhibitor.

BACKGROUND: The interconnection between different fields of research has gained interest due to its cutting-edge perspectives in solving scientific problems. Terminalia arjuna is indigenously used in India for curing several diseases, and its pharmacological activities are being revisited in recent drug-repurposing research.
OBJECTIVE: Efficient ultrasound-assisted extraction of phytochemicals from the bark of Terminalia arjuna is highlighted in this study. Following the optimization of the extraction process, the crude hydroethanolic extract is subjected to phytochemical profiling and an in-silico investigation of its anti-cancer properties.
METHODS: A three-level four-factor Box-Behnken design is exploited to optimize four operational parameters, namely extraction time, ultrasonic power, ethanol concentration (as the extracting solvent) and solute (in g): solvent (in mL) ratio. At the optimum parametric condition, the crude extract is obtained, and its GC-MS analysis is carried out. An analysis of network pharmacology (by constructing and visualizing biological networks using Cytoscape) combined with molecular docking reveals the potential antineoplastic targets of the crude extract.
RESULTS: The ANOVA table exhibits the significance, adequacy and reliability of the proposed second-order polynomial model with the R² value of 0.917 and adjusted R² of 0.865. Experimental results portray the significant antioxidant potential of the prepared extract in its crude form. The GC-MS analysis of the crude extract predicts the extracted phytochemicals, while the constructed biological networks highlight its multi-targeted activity in colorectal cancer.
CONCLUSIONS: The study identifies three phytochemicals viz. luteolin, β-sitosterol and arjunic acid as potent anti-cancer agents and can be extended with in-vitro and in-vivo experiments to validate the in-silico results, thus establishing lead phytochemicals in multi-targeted colorectal cancer therapies.