Search Results (1,698)

This study optimized the extraction of polyphenols from Phoenix dactylifera L. kernels by combining hydrated natural deep eutectic solvents (NADESs) with sonotrode ultrasound-assisted extraction (S-UAE), aiming to obtain a ready-to-use antioxidant and antimicrobial liquid extract. A sequential optimization strategy based on Box–Behnken designs identified the solvent-to-solid ratio as the main extraction driver. The optimal conditions were 55% hydrated NADES, a 5 mL/g solvent-to-solid ratio, 60% amplitude, 170 J/mL specific energy, and an 80% duty cycle. Under these conditions, experimental concentrations reached 309.78 mg/L total polyphenols and 265.81 mg/L flavan-3-ols, the predominant phenolic family. Compared with conventional agitation extraction, optimized S-UAE increased total polyphenols by 65.78%, flavan-3-ols by 68.65%, hydroxycinnamic acids by 48.47%, and flavonols by 35.05%. Antioxidant activity was markedly enhanced, reaching 15.47 and 14.70 mg Trolox eq./L in DPPH and FRAP assays, respectively, representing approximately 16-fold and 9-fold improvements over agitation extraction. The extract also showed antibacterial activity, producing inhibition zones of 16.0 mm against Bacillus sp. and 12.0 mm against Pseudomonas fluorescens, while complete inhibition was achieved against several strains in broth assays. These findings demonstrate that hydrated NADESs coupled with S-UAE is an efficient and scalable green strategy for valorizing date kernels into multifunctional polyphenol-rich food additives. Full article

The increasing discharge of pharmaceutical contaminants, particularly antibiotics like metronidazole (MNZ), into water systems poses significant ecological and public health risks due to their high solubility and low biodegradability. This study developed and characterized a highly porous activated carbon derived from maize cob (MC-AC). The synthesized material was characterized using FTIR, FESEM, PXRD, HRTEM, and BET analysis. Batch adsorption experiments were conducted, and the removal efficiency of MC-AC for MNZ was 98.6%. Optimization and modeling of the process variables of pH (3–11), contact time (0–75 min), concentration (0–70 mg/L), temperature (25–35 °C), and adsorbent dosage (0.5–1.5 g/L) were investigated using the Box–Behnken design (BBD) of response surface methodology, and 29 runs were obtained. The BBD model determined an optimal removal efficiency of 94.6 for metronidazole. Furthermore, non-linearized kinetic and isotherm models were used to determine the adsorption mechanism and mode of metronidazole from water. From the investigation, it was observed that both the Freundlich and pseudo-second-order models exhibited high correlation coefficients. The models with the best performance and low error metrics were determined by R², MSE, RMSE, SAE, and SSE. Therefore, the adsorption mode was multilayer heterogeneous, and the mechanism was chemisorption. Therefore, this study provides a unique alternative for using the Box–Behnken design, kinetic, and isotherm models to understand the removal of metronidazole from water using maize cob-activated carbon. Full article

In the leveling process of ultra-high-strength steel plates, sample scarcity—driven by high prototyping costs and small-batch production—coupled with a narrow and unevenly distributed feasible region due to high yield-to-tensile ratios and limited ductility, impedes the balanced optimization of plate shape quality and energy consumption. To address this issue, this paper develops an optimization framework for the balanced trade-off between these two objectives. First, a high-precision response surface model based on Box–Behnken experimental design and finite element simulation was constructed using initial wave height, entry roll reduction, exit roll reduction, and leveling speed as key process parameters; peak residual stress difference (characterizing potential sheet quality) and leveling energy consumption as co-optimization objectives; and post-leveling flatness as a constraint. Next, by introducing the NSGA-II multi-objective genetic algorithm, the Pareto optimal solution set for the quality and energy efficiency objectives was obtained, clearly revealing the trade-off relationship between the two; furthermore, the TOPSIS decision-making method was employed to select the comprehensive optimal process scheme that achieves a balance between quality and energy efficiency from the Pareto solution set. An adaptive recommendation curve for the leveling process parameters of MS1500 ultra-high-strength steel plates was established, covering an initial wave height range of 10.5–14.6 mm, thereby enabling intelligent parameter matching based on different incoming material conditions. Finally, industrial validation demonstrated that this optimized scheme significantly reduced leveling energy consumption while ensuring that post-leveling flatness meets the high-quality requirement of less than 3.5 mm·m⁻¹. This achieves a balanced optimization of quality and energy efficiency. This study provides a reliable theoretical basis and practical engineering solution for the efficient and environmentally friendly leveling production of ultra-high-strength steel. Full article

Epilepsy is a common chronic neurological disorder characterized by recurrent seizures. Gastrodia elata, the dried tuber of G. elata Bl. (Orchidaceae), is a valuable medicinal and edible botanical resource. This study optimized the preparation of Yellow Rice Wine-Processed G. elata (YPGE) and investigated its antiepileptic effects and underlying mechanisms in a pentylenetetrazol (PTZ)-kindled rat model. Processing parameters were optimized using single-factor experiments combined with an analytic hierarchy process (AHP)-entropy weight method (EWM) weighting strategy and Box–Behnken design–response surface methodology. The optimal parameters were determined as 18% alcohol by volume, 72 °C drying temperature, and 32 h drying time. Compared with unprocessed G. elata (GE), YPGE exhibited 0.54-, 0.13-, 1.87-, and 3.58-fold increases in the contents of gastrodin (GAS), G. elata polysaccharides (GEPs), p-hydroxybenzyl alcohol (p-HBA), and total parishins (TP), respectively, and demonstrated significantly enhanced in vitro antioxidant activity (IC50 values of 2.604, 2.719, and 4.046 mg/mL for DPPH, ABTS, and hydroxyl radicals). In vivo, both GE and YPGE significantly reduced seizure severity, decreased inflammatory cytokines (TNF-α, IL-1β), alleviated oxidative stress (increased SOD and GSH-Px, decreased MDA), and modulated neurotransmitter balance (reduced Glu, increased GABA) in brain tissues. YPGE also upregulated P-glycoprotein expression and reduced neuronal apoptosis in the hippocampal CA1 region by upregulating Bcl-2 and downregulating Bax. These findings suggest that YPGE exerts multi-target antiepileptic effects through synergistic anti-inflammatory, antioxidant, and anti-apoptotic actions, providing experimental evidence for the development of novel antiepileptic therapies based on processed G. elata. Full article

Aerobic ceramic membrane bioreactors (AeCeMBR) have shown great potential in treating wastewater (WW) from the textile industry; however, their operation faces challenges such as process variability, membrane contamination, and the need for accurate prediction of treated water quality under varying conditions. In this study, chemical oxygen demand (COD) and turbidity were selected as key indicators, as they directly reflect organic load removal and solids separation efficiency in MBR systems. The effect of four operational parameters: hydraulic retention time (HRT), organic loading rate (OLR), mixed liquor suspended solids (MLSS), and transmembrane pressure (TMP), was investigated using a response surface methodology (RSM) based on a Box–Behnken design. A random forest (RF) model coupled with Monte Carlo simulation (MC) was also developed using 174 experimental data points to enhance predictive power and quantify uncertainty. The RSM model showed strong agreement with experimental results (coefficient of determination (R²) > 0.95), achieving approximately 96% removal for both COD and turbidity, with validation errors of less than 2%. MC simulation (10,000 iterations) was applied to assess the effect of ±10% variance under operating conditions, providing a probabilistic view of system performance. The RF-MC framework demonstrated high predictive accuracy, with strong correlations between predicted and observed values (R² = 0.92 for COD and 0.97 for turbidity) and low uncertainty. Overall, this study proposes an integrated RSM, RF–MC approach for AeCeMBR systems, providing a robust and uncertainty-aware framework for process optimization and performance prediction under changing operating conditions. Full article

Ellagic acid (EA) possesses various biological activities, including anti-inflammatory, whitening, and antioxidant properties. Its practical application is limited by poor aqueous solubility and susceptibility to degradation. To overcome these limitations, this study prepared EA liposomes using the thin-film hydration–ultrasonication method, followed by surface modification with low-molecular-weight chitosan (LM-CS) and medium-molecular-weight chitosan (MM-CS), yielding EA liposomes modified with LM-CS (EA-L-LC) and MM-CS (EA-L-MC), respectively. The formulation and preparation process were optimized using a Box–Behnken design combined with response surface methodology. Under optimal conditions, the mean particle size (MPS), polydispersity index (PDI), Zeta-potential, and encapsulation efficiency (EE) of the different liposomes (unmodified EA-L, EA-L-LC, and EA-L-MC) were determined. Morphological observation and functional group characterization were conducted via transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR), respectively. The stability of the various liposomes was compared under different environmental conditions, and their stability and the released amount of EA were evaluated during in vitro digestion. The in vitro antioxidant activity and tyrosinase inhibitory effects of the different liposomes were investigated. After process optimization, the encapsulation efficiency of EA liposomes was effectively enhanced following modification with chitosan of different molecular weights. TEM and FTIR results confirmed that EA was effectively encapsulated, and chitosan was successfully coated onto the outer layer of the liposomes. Compared to unmodified EA liposomes (EA-L), the chitosan-modified liposomes (EA-L-LC and EA-L-MC) exhibited enhanced in vitro antioxidant activity and sustained, slow-release tyrosinase inhibitory effects, along with superior stability across multiple conditions. In vitro digestion experiments demonstrated that EA-L-MC and EA-L-LC achieved slower release rates in simulated gastric fluid compared to EA-L, thereby improving the digestive stability of EA. Full article

Multivariate control charts (MCC) are widely used to detect out-of-control (OOC) situations in interrelated processes; however, they do not directly provide information about the source(s) of these signals. Although various methods for signal decomposition and interpretation have been proposed in the literature, most of them are limited to statistical interpretation and do not support automated signal classification. To overcome this limitation, an intelligent decision-support approach combining MCCs and machine learning for OOC signal classification has been developed. Interrelated cost and schedule performance indicators obtained through earned value analysis (EVA) were monitored by a Hotelling T² control chart. When an OOC signal occurred, the associated variable(s) were identified using the Mason–Young–Tracy (MYT) decomposition method, and the resulting MYT classifications were used as class labels for supervised learning of an artificial neural network (ANN). The Box–Behnken experimental design was used to determine the optimal network architecture and training hyperparameters of the ANN. The findings showed that the optimized ANN model achieved 93.33% classification accuracy, and the optimization model explained 85.14% of the variation in Mean Squared Error (MSE). The main contribution of this study is the integration of statistical signal decomposition and machine learning into a learning-based decision-support mechanism for the automated interpretation of MCC signals. The developed approach provides a systematic, practical decision-support tool for identifying which EVA-based performance parameter(s) are associated with an OOC signal in the monitoring of complex processes. Full article

Jackfruit seeds, a by-product of the jackfruit processing industry, comprise a substantial proportion of starch. As a result, jackfruit seeds are emerging as a viable source of fermentable sugars for fermentation processes. In this study, α-amylase from Bacillus licheniformis TKU004 was employed to hydrolyze gelatinized jackfruit seed starch slurry, and the hydrolysis conditions were systematically optimized using the Box–Behnken design (BBD) coupled with response surface methodology (RSM). Three independent variables, including incubation temperature (40–60 °C), enzyme-to-substrate ([E]/[S]) ratio (5–10 U/g), and reaction time (2–6 h), were evaluated, with dextrose equivalent (DE, %) as the response. The optimal hydrolysis parameters were determined to be 47 °C, an [E]/[S] ratio of 10 U/g, and a reaction time of 5.1 h, yielding a predicted DE of 31.72%. Experimental validation confirmed a DE of 32.85 ± 1.12%, in close agreement with the model prediction. HPLC (high-performance liquid chromatography) analysis of the hydrolysate revealed a composition of 14.20% glucose, 56.51% maltose, and 29.29% maltooligosaccharides, indicating that this process is well-suited for producing high-maltose syrup. In short, this study demonstrates the feasibility of valorizing jackfruit seed waste into value-added carbohydrate products through enzymatic hydrolysis with B. licheniformis α-amylase. Full article

In this study, an ultrasound-assisted extraction (UAE) method combined with ion chromatography (IC) was developed, optimized and validated for the determination of benzoate in Northern Thai green chili dip. Four extraction variables were optimized using response surface methodology (RSM) based on a Box–Behnken design (BBD). The optimal conditions were a sample mass of 5.0 g, water volume of 20.0 mL, extraction temperature of 70 °C, and extraction time of 20 min. The validated method showed good linearity in the range of 0.5 to 100 mg L⁻¹, limits of detection (LOD) and quantification (LOQ) of 0.305 and 1.070 mg L⁻¹, respectively, precision in the range of 0.31 to 6.37% (%RSD, n = 11), and spiked recovery in the range of 85.50 to 107.80%, all of which were within the acceptable criteria. The AGREE score of the developed method was 0.45, which was higher than that of the conventional LLE-HPLC-UV method (0.27) due to the use of only deionized water as the extracting solvent and no generation of organic waste. The developed method was sensitive, validated, and environmentally friendly, and was successfully applied to the determination of benzoate in traditional condiment products. The proposed method may serve as an alternative approach for routine food analysis and quality control. Full article

Coagulation–flocculation is widely recognized as a fundamental step in wastewater treatment, as it promotes the aggregation and removal of suspended particles and organic contaminants following the addition of a coagulant. In this study, a bio-based coagulant was prepared from prickly pear (Opuntia ficus-indica) seed residues obtained after essential oil extraction. The extraction process for bioactive agents was successfully modeled using Central Composite Design (CCD)-based Response Surface Methodology (RSM). Optimal extraction was reached at pH 13, PPSM of 7.5 g, 0.75 M NaCl, and 40 min of stirring, providing maximum yields of 69.63 g proteins, 217.075 g total sugars, and 81.416 g polyphenols. The optimized extract was subsequently used as a bio-coagulant for the treatment of wastewater collected from the Chalghoum El Aid–Oued El Athmania wastewater treatment plant (Mila, Algeria). The effects of three operating parameters, initial turbidity, solution pH, and bio-coagulant dosage, on the coagulation–flocculation performance were investigated using a Box–Behnken design (BBD). Process efficiency was evaluated in terms of turbidity, chemical oxygen demand (COD), and organic matter (OM) removal. The raw wastewater exhibited initial values of 200 NTU for turbidity, 640 mg/L for COD, and 25 for organic matter. Statistical analysis revealed that the developed quadratic models were highly significant (p ≤ 0.05) and showed excellent predictive performance, with coefficients of determination (R² ≥ 0.97). Optimal treatment conditions were identified at pH 7, a bio-coagulant dosage of 1 mL/L, and an initial turbidity of 200 NTU. Under these conditions, removal efficiencies exceeded 98% for turbidity and COD and reached 88.08% for organic matter. Furthermore, Fourier-Transform Infrared (FTIR) Spectroscopy analysis confirmed the presence of functional groups responsible for the coagulation activity of the bio-coagulant. These findings highlight the potential of prickly pear seed residues as an effective, sustainable, and low-cost alternative to conventional chemical coagulants in wastewater treatment. Full article

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R² based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R² ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules. Full article

Background: Conventional transdermal drug delivery systems are often limited by poor skin permeability and low drug loading efficiency, necessitating the development of advanced delivery platforms. Objectives: This study aimed to develop and optimize photopolymerizable bioinks (PBs) for liquid crystal display (LCD)-based 3D printing of crosslinked hydrogel microneedles (cHMNs) to enhance transdermal delivery of estradiol valerate (E2V). Methods: A Box–Behnken design (BBD) was used to optimize the effects of Gantrez™ S-97, Jurymer™, and polyvinyl alcohol (PVA) on viscosity, exposure time, hardness, and elasticity, with strong predictive performance (R² = 0.9702–0.9907). Results: Estradiol valerate-loaded nanoparticles (E2V-NPs) were prepared via ionotropic gelation, exhibiting a particle size of 698.33 (0.78) nm, PDI of 0.50 (0.06), zeta potential of −39.09 (7.32) mV, and high encapsulation efficiency (86.87 (0.78)%). The optimized PBs enabled fabrication of uniform cHMNs (~800 µm height) with adequate mechanical strength (hardness 20.45 (1.23) N; elasticity 2.97 (0.49) MPa) and effective insertion capability. The E2V-NPs-loaded cHMNs exhibited sustained drug release over 12 days (~56.92 (4.27)%). Skin permeation studies showed a significantly enhanced flux (10.81 (4.55) µg/cm²/h) and cumulative permeation (12.94 (2.06) µg/cm²) compared to topical E2V-NPs and suspension, along with increased skin accumulation (38.55 (0.10) µg). Cytotoxicity studies confirmed that E2V and E2V-NPs were biocompatible (>80% viability), while PBs showed concentration-dependent cytotoxicity. Conclusions: Overall, this integrated platform combining design of experiment, nanoparticles, microneedles, and LCD 3D printing offered a promising strategy for enhancing transdermal drug delivery efficiency and reproducibility. Full article

Prickly pear (Opuntia ficus-indica (L.) Mill.) generates substantial agro-industrial by-products, such as press cake, seed, and oil, that remain underexploited despite their recognized phytochemical richness. This study reports the systematic optimization, characterization, and bioactivity profiling of flavonoid-rich extracts recovered from these three matrices. A Box–Behnken design (BBD) coupled with response surface methodology (RSM) was applied to optimize the ultrasound-assisted extraction (UAE) of total flavonoid content (TFC) from press cake using a natural deep eutectic solvent (NADES: fructose–glycerol–sorbitol–water and FGSH), selected through an initial screening of fifteen solvent systems. The quadratic polynomial model showed excellent fit (R² = 0.9852; R²adj = 0.9687; MAPE = 1.31%; Durbin–Watson = 1.857), and optimal extraction conditions were established at 37.6 min extraction time, 35.6% ultrasonic power, and 29.4 °C, yielding a maximum predicted TFC of 54.78 ± 0.49 mg quercetin equivalents (QE)/mL. HPLC-DAD analysis of the press cake extract revealed five isorhamnetin derivatives as the dominant flavonoids, with isorhamnetin-3-O-glucoside (23.18 ± 0.12 mg/g DW) and isorhamnetin-3-O-rutinoside (13.80 ± 0.28 mg/g DW) as the most abundant. Comprehensive bioactivity assessment demonstrated significant antioxidant capacities (CUPRAC: 191.35 ± 3.22 µM AAE; ORAC: 184.44 ± 3.44 µM TE; DPPH: 103.47 ± 9.98 µM TE for press cake extract), potent in cellulo ROS/RNS suppression in a yeast UV-stress model (85.9 ± 1.0% inhibition for press cake), and differential tyrosinase inhibition across fractions (press cake: 32.8%; seed: 57.5%; oil: 83.8%), highlighting the oil as a potent anti-melanogenic ingredient. In silico safety prediction (ProTox-II/pkCSM) confirmed the favorable toxicity profiles of all identified isorhamnetin derivatives (LD₅₀ > 5000 mg/kg; Toxicity Class V). These results collectively position Opuntia ficus-indica by-products as high-value natural sources of bioactive flavonoids with applications in cosmetic, nutraceutical, and dermatological formulations. Full article

This study investigates the process optimization and predictive modeling of femtosecond laser precision milling for commercial poly(methyl methacrylate) (PMMA) slices, with emphasis on surface roughness R_a and milling depth h. Three-dimensional surface morphology was measured using a laser confocal microscope, and the measurement methods for R_a and h were defined based on stable regions of interest and reference-plane correction. The effects of pulse energy, scanning line speed, scanning line spacing and pulse repetition frequency on milling quality were systematically analyzed. The results show that pulse energy and repetition frequency promoted material removal and increased milling depth, whereas scanning line speed and scanning line spacing reduced milling depth by decreasing the effective energy deposition per unit area. Surface roughness was influenced by both energy input and scanning uniformity, showing non-monotonic responses to scanning line speed and scanning line spacing. Quadratic response surface models were established using the Box–Behnken design. The ANOVA results indicate that both the R_a and h models were statistically significant, with R² values of 0.9970 and 0.9982, respectively. The validation results show that the average relative errors of the R_a and h models were 6.51% and 2.62%, respectively. These results demonstrate that the proposed models can effectively predict femtosecond laser milling quality and provide guidance for parameter selection and surface-quality control of commercial PMMA slices. Full article

Mung bean (Vigna radiata (L.) Wilczek) seed coat (MBSC) is an underutilized by-product rich in vitexin and isovitexin, but its potential as a source of spray-dried functional powders has not been systematically evaluated. This study investigated the spray drying of MBSC extract using three structurally distinct polysaccharide-based carriers—maltodextrin, trehalose, and inulin—to compare their effects on process yield, powder quality, and the content of phenolic compounds, flavonoids, and antioxidant activity. Response surface methodology (RSM) with a Box–Behnken design was employed to examine the influence of inlet temperature (130–160 °C) and carrier concentration. Maltodextrin provided the highest process yield (84.85%), while trehalose and inulin formulations exhibited stronger antioxidant activity, with the lowest DPPH IC₅₀ values of 0.096 mg/mL and 0.100 mg/mL, respectively (expressed per mg of spray-dried powder). Trehalose yielded the highest total phenolic content (TPC = 28.12 mg GAE/g extract) and acceptable flowability (Carr’s index = 20.72%). Inulin gave the highest total flavonoid content (TFC = 126.8 mg QE/g extract) but showed greater variability, attributed to its polymeric network and higher hygroscopicity. The RSM models showed high predictive accuracy for TPC (R² > 0.98) and DPPH antioxidant activity (R² ≈ 1.00). These findings offer a multi-objective optimization framework that links carrier structure to powder performance, providing practical guidance for selecting polysaccharide carriers in the development of spray-dried nutraceutical and functional food ingredients. However, direct measurement of encapsulation efficiency, particle morphology, and storage stability was beyond the scope of this study and warrants further investigation. Full article