Search Results (17)

Prodigiosin, a red pigment with diverse biotechnological applications, is produced as a secondary metabolite by Gram-negative bacilli Serratia marcescens. In this study, we implemented an AI-guided hybrid optimization framework combining Response Surface Methodology (RSM) using a Circumscribed Central Composite Design (CCCD) and Artificial Neural Network (ANN) modeling to enhance prodigiosin pigment production. Across 34 experimental runs, we optimized sucrose and peptone concentrations along with inoculum size. The RSM-derived model exhibited a strong correlation (R² = 0.953), while the ANN, trained using a backpropagation algorithm, demonstrated superior predictive power (R² = 0.998; MSE = 0.000414), underscoring the potential of artificial intelligence in modeling complex bioprocesses. Beyond statistical optimization, an induction strategy using 1% of various natural additives (vegetable oils and egg components) identified egg white, rich in albumin, as the most effective enhancer, tripling prodigiosin yield. Further investigation revealed that a 2% egg white concentration maximized production to 1070 mg L⁻¹, a substantial increase compared to the optimized yield of 359.2 ± 12 mg L⁻¹ and predicted value of 391.86 mg L⁻¹. These results highlight the value of integrating machine learning with experimental design and protein-rich inducers to strengthen sustainable microbial pigment production in a cost-effective and scalable manner. Full article

The development of sustainable biorefining processes is essential for increasing the value of lignocellulosic resources and reducing the environmental footprint of the forest-based industry. Birch wood is one of Latvia’s most abundant renewable feedstocks, yet current catalytic technologies for furfural production—primarily based on sulfuric acid (H₂SO₄)—cause extensive cellulose degradation and generate sulfur-containing residues that hinder further valorization. This study proposes an integrated biorefining approach in which orthophosphoric acid (H₃PO₄) is utilized as an alternative catalyst to selectively convert hemicellulose into furfural and acetic acid while preserving cellulose in birch veneer chips (BVC). The experimental plan was based on a full central composite circumscribed (CCC) response surface methodology (RSM) design, which consists of factorial points, axial (star) points, and centre points. In total, 26 experimental runs were performed, including 24 non-centre points (comprising both factorial and axial points (±α)) and two centre points. The optimized conditions enabled high acetic acid yields (6.29–6.48% o.d.m., corresponding to 98–100% of theoretical), furfural yields of 8.75–10.41% o.d.m. (57–68% of theoretical), and exceptional glucan preservation (38.84–40.92% o.d.m., 94–99% of theoretical). Compared with sulfuric acid pretreatment, the H₃PO₄-based process significantly reduced cellulose degradation and improved the suitability of the resulting lignocellulosic residue for subsequent 5-hydroxymethylfurfural (5-HMF) production and other biorefining routes. The findings demonstrate that orthophosphoric acid catalysis is a promising pathway for integrating furfural extraction with cellulose-retentive pretreatment, thereby enhancing the sustainability, efficiency, and circularity of birch veneer chips’ biomass utilization. Full article

Background/Objectives: This research focuses on the development and optimization of polymer–lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selective treatment for different hematological malignancies. Methods: Variations in the mPEG-to-ε-caprolactone ratio influenced both the molecular weight (Mw) of the synthesized co-polymers and their aqueous phase affinity. The ACP-loaded PLHNs (ACP-PLHNs) were optimized using a circumscribed central composite design. The in vivo studies were performed in Wistar rats. Results: The lipophilic mPEG-PCL (Mw = 9817.67 Da) resulted in PLHNs with a particle size of 155.91 nm and 40.08% drug loading, while the hydrophilic mPEG-PCL (Mw = 23,615.84 Da) yielded PLHNs with a relatively larger size (223.46 nm) and relatively higher drug loading (46.59%). The drug release profiles were polymer-grade dependent: lipophilic ACP-PLHNs (lACP-PLHNs) sustained release up to 30 h in pH 7.2 buffer, while hydrophilic ACP-PLHNs (hACP-PLHNs) completed release within 24 h. Stability studies showed greater stability for lACP-PLHNs, likely due to reduced molecular rearrangement from the chemically stable lipophilic co-polymer. Conclusions: Oral administration of both formulations exhibited a 2-fold (p < 0.001) improvement in the C_max and AUC_0-tlast and a 3.9-fold (p < 0.001) increase in the relatively oral bioavailability compared to the conventional ACP suspension in male wistar rats. Full article

The present Perspective analyzes the remarkable evolution of the Amyloid Cascade Hypothesis 2.0 (ACH2.0) theory of Alzheimer’s disease (AD) since its inception a few years ago, as reflected in the diminishing role of amyloid-beta (Aβ) in the disease. In the initial iteration of the ACH2.0, Aβ-protein-precursor (AβPP)-derived intraneuronal Aβ (iAβ), accumulated to neuronal integrated stress response (ISR)-eliciting levels, triggers AD. The neuronal ISR, in turn, activates the AβPP-independent production of its C99 fragment that is processed into iAβ, which drives the disease. The second iteration of the ACH2.0 stemmed from the realization that AD is, in fact, a disease of the sustained neuronal ISR. It introduced two categories of AD—conventional and unconventional—differing mainly in the manner of their causation. The former is caused by the neuronal ISR triggered by AβPP-derived iAβ, whereas in the latter, the neuronal ISR is elicited by stressors distinct from AβPP-derived iAβ and arising from brain trauma, viral and bacterial infections, and various types of inflammation. Moreover, conventional AD always contains an unconventional component, and in both forms, the disease is driven by iAβ generated independently of AβPP. In its third, the current, iteration, the ACH2.0 posits that proteolytic production of Aβ is suppressed in AD-affected neurons and that the disease is driven by C99 generated independently of AβPP. Suppression of Aβ production in AD seems an oxymoron: Aβ is equated with AD, and the later is inconceivable without the former in an ingrained Amyloid Cascade Hypothesis (ACH)-based notion. But suppression of Aβ production in AD-affected neurons is where the logic leads, and to follow it we only need to overcome the inertia of the preexisting assumptions. Moreover, not only is the generation of Aβ suppressed, so is the production of all components of the AβPP proteolytic pathway. This assertion is not a quantum leap (unless overcoming the inertia counts as such): the global cellular protein synthesis is severely suppressed under the neuronal ISR conditions, and there is no reason for constituents of the AβPP proteolytic pathway to be exempted, and they, apparently, are not, as indicated by the empirical data. In contrast, tau protein translation persists in AD-affected neurons under ISR conditions because the human tau mRNA contains an internal ribosomal entry site in its 5′UTR. In current mouse models, iAβ derived from AβPP expressed exogenously from human transgenes elicits the neuronal ISR and thus suppresses its own production. Its levels cannot principally reach AD pathology-causing levels regardless of the number of transgenes or the types of FAD mutations that they (or additional transgenes) carry. Since the AβPP-independent C99 production pathway is inoperative in mice, the current transgenic models have no potential for developing the full spectrum of AD pathology. What they display are only effects of the AβPP-derived iAβ-elicited neuronal ISR. The paper describes strategies to construct adequate transgenic AD models. It also details the utilization of human neuronal cells as the only adequate model system currently available for conventional and unconventional AD. The final alteration of the ACH2.0, introduced in the present Perspective, is that AβPP, which supports neuronal functionality and viability, is, after all, potentially produced in AD-affected neurons, albeit not conventionally but in an ISR-driven and -compatible process. Thus, the present narrative begins with the “omnipotent” Aβ capable of both triggering and driving the disease and ends up with this peptide largely dislodged from its pedestal and retaining its central role in triggering the disease in only one, although prevalent (conventional), category of AD (and driving it in none). Among interesting inferences of the present Perspective is the determination that “sporadic AD” is not sporadic at all (“non-familial” would be a much better designation). The term has fatalistic connotations, implying that the disease can strike at random. This is patently not the case: The conventional disease affects a distinct subpopulation, and the basis for unconventional AD is well understood. Another conclusion is that, unless prevented, the occurrence of conventional AD is inevitable given a sufficiently long lifespan. This Perspective also defines therapeutic directions not to be taken as well as auspicious ways forward. The former category includes ACH-based drugs (those interfering with the proteolytic production of Aβ and/or depleting extracellular Aβ). They are legitimate (albeit inefficient) preventive agents for conventional AD. There is, however, a proverbial snowball’s chance in hell of them being effective in symptomatic AD, lecanemab, donanemab, and any other “…mab” or “…stat” notwithstanding. They comprise Aβ-specific antibodies, inhibitors of beta- and gamma-secretase, and modulators of the latter. In the latter category, among ways to go are the following: (1) Depletion of iAβ, which, if sufficiently “deep”, opens up a tantalizing possibility of once-in-a-lifetime preventive transient treatment for conventional AD and aging-associated cognitive decline, AACD. (2) Composite therapy comprising the degradation of C99/iAβ and concurrent inhibition of the neuronal ISR. A single transient treatment could be sufficient to arrest the progression of conventional AD and prevent its recurrence for life. Multiple recurrent treatments would achieve the same outcome in unconventional AD. Alternatively, the sustained reduction/removal of unconventional neuronal ISR-eliciting stressors through the elimination of their source would convert unconventional AD into conventional one, preventable/treatable by a single transient administration of the composite C99/iAβ depletion/ISR suppression therapy. Efficient and suitable ISR inhibitors are available, and it is explicitly clear where to look for C99/iAβ-specific targeted degradation agents—activators of BACE1 and, especially, BACE2. Directly acting C99/iAβ-specific degradation agents such as proteolysis-targeting chimeras (PROTACs) and molecular-glue degraders (MGDs) are also viable options. (3) A circumscribed shift (either upstream or downstream) of the position of transcription start site (TSS) of the human AβPP gene, or, alternatively, a gene editing-mediated excision or replacement of a small, defined segment of its portion encoding 5′-untranslated region of AβPP mRNA; targeting AβPP RNA with anti-antisense oligonucleotides is another possibility. If properly executed, these RNA-based strategies would not interfere with the protein-coding potential of AβPP mRNA, and each would be capable of both preventing and stopping the AβPP-independent generation of C99 and thus of either preventing AD or arresting the progression of the disease in its conventional and unconventional forms. The paper is interspersed with “validation” sections: every conceptually significant notion is either validated by the existing data or an experimental procedure validating it is proposed. Full article

Immobilized enzyme reactors (IMERs) are critical tools for developing novel oligosaccharides based on the enzymatic catalysis of polysaccharides. In this paper, a novel glucuronan lyase from Peteryoungia rosettiformans was produced, purified, and then immobilized on a CIM^® CDI disk for cleaving glucuronan. The results showed that around 63.6% of glycuronan lyases (800.9 μg) were immobilized on the disk. The V_max values of immobilized glucuronan lyases did not significantly change (56.9 ± 4.7 μM∙min⁻¹), while the K_m values (0.310 ± 0.075 g∙L⁻¹) increased by 2.5 times. It is worth noting that immobilized glucuronan lyases overcame the catalytic inhibition of free enzymes observed under high glucuronan concentrations (0.5–2 g∙L⁻¹). circumscribed central composite design (CCCD) and response surface methodology (RSM) showed that glucuronan concentration, flow rate, and reaction time significantly affected the yield of oligoglucuronans. The degree of polymerization (DP) of degraded glucuronan ranged from DP 2–8 according to the results obtained by high performance anion exchange chromatography coupled with a pulsed amperometric detector (HPAEC-PAD). The IMER retained 50.9% activity after running 2373 column volumes of glucuronan. Finally, this glucuronan lyase reactor was tentatively connected to an immobilized laccase reactor to depolymerize, and gallic acid (GA) was added to glucuronan. Approximately 8.5 mg of GA was added onto 1 g of initial glucuronan, and the GA–oligoglucuronan conjugates showed notable antioxidant activity. Full article

Metal binder jetting shows great potential for medical technology. This potential can be exploited by integrating binder jetting into existing process routes known from metal injection molding. The biggest challenge here is the flowability and packing behavior of the powders used, due to their low size distributions. This paper investigates different powder-drying strategies to improve flowability using a statistical experimental design. Because of its relevance for medical applications, spherical Ti-6Al-4V powder with a size distribution under 25 µm is dried under various parameters using vacuum and gas purging. The investigated parameters, time and temperature, are selected in a central-composite-circumscribed test plan with eleven tests and three center points. The target parameters—water content, flowability and impurity levels (oxygen, nitrogen)—of the powder are analyzed. For validation, practical test trials are carried out on an industrial binder jetting system with unconditioned powder and conditioning with optimized parameters, comparing the manufactured parts and the powder bed. An optimized drying cycle with a duration of 6 h at 200 °C was determined for the investigated powder. Significant improvements in the dimensional accuracy (from ±1.5 to 0.3%) of the components and the visual impression of the powder bed are demonstrated. Full article

A new fast, sensitive, and environmentally friendly analytical method has been developed for the simultaneous determination of Ba, Be, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn in wastewater samples using inductively coupled plasma optical emission spectroscopy (ICP OES). A preconcentration step using a magnetic dispersive solid-phase extraction (MDSPE) technique with a new magnetic sorbent was performed. The new sorbent material was a carbon containing magnetic cobalt and nitrogen groups. This material was synthetized using controlled pyrolysis of a zeolitic imidazolate framework (i.e., ZIF-67). In order to optimize the experimental parameters that affect the MDSPE procedure, a multivariate optimization strategy, using Plackett–Burman and circumscribed central composite designs (CCD), was used. The method has been evaluated employing optimized experimental conditions (i.e., sample weight, 10 g; sample pH, 7.6; amount of sorbent, 10 mg; dispersive agent, vortex; complexing agent concentration, 0.5%; ionic concentration, 0%; eluent, HCl; eluent concentration, 0.5 M; eluent volume, 300 μL; elution time, 3 min and extraction time, 3 min) using external calibration. Limits of detection (LODs) in a range from 0.073 to 1.3 μg L⁻¹ were obtained, and the repeatability was evaluated at two different levels, resulting in relative standard deviations below 8% for both levels (n = 5). An increase in the sensitivity was observed due to the high enrichment factors (i.e., 3.2 to 13) obtained compared with direct ICP OES analysis. The method was also validated through carrying out recovery studies that employed a real wastewater sample and through the analysis of a certified reference material (ERM^®-CA713). The recovery values obtained with the real wastewater were between 94 and 108% and between 90 and 109% for the analysis of ERM^®-CA713, showing negligible matrix effects. Full article

In hot and humid climates, asphalt pavements frequently encounter environmental factors such as elevated temperatures and rainfall, leading to rutting deformations and potholes, which can affect pavement performance. The primary objective of this study was to enhance the hydrothermal characteristics of asphalt mixtures through an investigation into the impact of anhydrous calcium sulfate whisker (ACSW) and polyester fiber (PF) on the hydrothermal properties of asphalt mixtures. In this paper, a central composite concatenation design (CCC) was employed to determine the optimal combination of ACSW and PF contents, as well as the asphalt aggregate ratio (AAR). Each influencing factor was assigned three levels for analysis. The evaluation indexes included dynamic stability, retained Marshall stability, and tensile strength ratio. Using the analysis methods of variance and gray correlation degree analysis, the hydrothermal properties of the asphalt mixture were examined in relation to the contents of ACSW, PF, and AAR based on the CCC results. Consequently, the optimal mix design parameters for composite modified asphalt mixture incorporating ACSW and PF were determined. The results indicated that the asphalt mixtures with hydrothermal qualities exhibited optimal performance in terms of 4.1% ARR, 11.84% ACSW, and 0.4% PF. The interaction between AAR and ACSW content had a greater effect on the dynamic stability and tensile strength ratio of the asphalt mixture, whereas the incorporation of ACSW and PF had a greater effect on the retained Marshall stability of the asphalt mixture. Among the three contributing factors, AAR exhibited the strongest relationship with the hydrothermal characteristics of the asphalt mixture, followed by the ACSW content; the correlation of PF content was the lowest. Therefore, to enhance the hydrothermal characteristics of the asphalt mixture, it is important to conduct a full evaluation of the constituents of ACSW and PF, along with the AAR in hot–humid regions. Full article

The catalytic oxidation of phenethoxybenzene as a lignin model compound with a β-O-4 bond was conducted using the Keggin-type polyoxometalate nanocatalyst (TBA)₅[PMo₁₀V₂O₄₀]. The optimization of the process’s operational conditions was carried out using response surface methodology. The statistically significant variables in the process were determined using a fractional factorial design. Based on this selection, a central circumscribed composite experimental design was used to maximize the phenethoxybenzene conversion, varying temperature, reaction time, and catalyst load. The optimal conditions that maximized the phenethoxybenzene conversion were 137 °C, 3.5 h, and 200 mg of catalyst. In addition, under the optimized conditions, the Kraft lignin catalytic depolymerization was carried out to validate the effectiveness of the process. The depolymerization degree was assessed by gel permeation chromatography from which a significant decrease in the molar mass distribution Mw from 7.34 kDa to 1.97 kDa and a reduction in the polydispersity index PDI from 6 to 3 were observed. Furthermore, the successful cleavage of the β-O-4 bond in the Kraft lignin was verified by gas chromatography–mass spectrometry analysis of the reaction products. These results offer a sustainable alternative to efficiently converting lignin into valuable products. Full article

Principles of quality by design and design of experiments are acquiring more importance in the discovery and application of new drug carriers, such as solid lipid nanoparticles. In this work, an optimized synthesis of solid lipid nanoparticles loaded with Triamcinolone Acetonide is presented using an approach that involves Stearic Acid as a lipid, soy PC as an ionic surfactant, and Tween 80 as a nonionic surfactant. The constructed circumscribed Central Composite Design considers the lipid and nonionic surfactant quantities and the sonication amplitude in order to optimize particle size and Zeta potential, both measured by means of Dynamic Light Scattering, while the separation of unentrapped drug from the optimized Triamcinolone Acetonide-loaded solid lipid nanoparticles formulation is performed by Size Exclusion Chromatography and, subsequently, the encapsulation efficiency is determined by HPLC-DAD. The proposed optimized formulation—with the goal of maximizing Zeta potential and minimizing particle size—has shown good accordance with predicted values of Zeta potential and dimensions, as well as a high value of encapsulated Triamcinolone Acetonide. Experimental values obtained from the optimized synthesis reports a dimension of 683 ± 5 nm, which differs by 3% from the predicted value, and a Zeta potential of −38.0 ± 7.6 mV (12% difference from the predicted value). Full article

The efficiency of annular-nozzle ejectors serving as components of complex technical systems interacting with high-temperature media in engines and in the field of energy technologies is not linearly related to the gas-dynamic characteristics of the flows formed in the device. In this paper, we have analyzed the results of numerical and experimental studies of gas jets in an annular-nozzle air ejector. The regression equations built according to the circumscribed central composite design described the relationship between a pressure drop and the structural parameters of the nozzle with the speed and mass flow rates of the airflows, including error rates of no more than 15 percent. A two-factor optimization based on Harington’s generalized desirability function was performed to obtain a relatively accurate estimate of the ejector efficiency under the influence of the structural and operating parameters. An optimization method based on the combination of response surface methodology and the desirability function approach, allowing simultaneous consideration of all responses, made it possible to simultaneously optimize multiple conflicting objectives. Full article

In order to improve the properties of calcium sulfate anhydrous whisker (ACSW) and polyester fiber composite reinforced asphalt mixture (ACPRA) to meet the service requirements of pavement materials in low-temperature environments, the central composite circumscribed design (CCC), a kind of response surface methodology, was chosen to optimize the design parameters. Three independence variables, asphalt aggregate ratio, ACSW content, and polyester fiber content were adopted to evaluate the design parameters. Four responsive variables, air voids, Marshall stability, splitting tensile strength, and failure tensile strain, were chosen to study the volumetric and mechanical characteristics, and the low-temperature behavior of ACPRA by the Marshall test and indirect tensile test at −10 °C. The results showed that, taking low-temperature behavior optimization as the objective, the CCC method was practicable to optimize design of ACPRA, and the optimization design parameters were asphalt aggregate ratio of 4.0%, ACSW content of 10.8%, and polyester fiber content of 0.4%. Furthermore, the impact of three independence variables interactions on four response variables was also discussed, and it was identified that the interaction between asphalt aggregate ratio and ACSW content, and between asphalt aggregate ratio and polyester fiber content, has greater bearing on the splitting tensile strength and failure tensile strain of APCRA. Meanwhile, ACSW and polyester fiber enhancing the low-temperature behavior of APCRA was primarily connected with their contents. Full article

A gastroretentive in situ oral gel containing metformin hydrochloride (Met HCl) was prepared based on sodium alginate (Sod ALG), calcium carbonate, and hydroxyethylcellulose (HEC). The optimal composition of the formulation was explored based on the design of experiments (DoE). First, a 3² full factorial design was used for formulation E1 to determine proper composition of Sod ALG and calcium carbonate. Second, a circumscribed central composite design was employed to add HEC as a thickening agent (formulation E2). The dissolution rates at 15, 30, 60, 120, and 240 min were used as responses. Partial least squares regression analysis indicated the effect of each component in delaying the release of Met HCl in the oral gel formulation. The optimized formulation E2-08 consisting of 1.88% Sod ALG, 0.63% HEC, and 1.00% calcium carbonate and two more formulations, E2-10 and E2-12 conformed to USP monograph for extended release. Other physicochemical properties, including floating lag time and duration, viscosity, and pH, measured for each batch and FT-IR spectrometry analysis showed no unexpected interaction between Met HCl and excipients. The current study suggests the potential use of a gastroretentive in situ oral gel for Met HCl helping patient compliance. This study highlights that a systematic approach based on DoE allows the formulation optimization. Full article

Sargassum muticum is an invasive brown macroalga in Galicia (Spain). Thus, exploitation of this biomass for the extraction of bioactive compounds could be an interesting strategy to add value to food supplements and functional foods. Among these compounds, fucoxanthin (Fx) has been gaining attention for its promising biological activities, such as its antioxidant, antimicrobial, anticancer, antihypertensive, anti-inflammatory, anti-diabetic, anti-obesity, neuroprotective, anti-angiogenic and photoprotective properties. Fucoxanthin is the most abundant and characteristic pigment in brown algae, accounting for approximately 10% of the total carotenoids in nature. The aim of this study was to optimize the extraction yield (grams extract per 100 g of macroalgae dried weight, g E/100 g Ma dw) and Fx content (mg Fx/g E) from Sargassum muticum using ultrasound-assisted extraction (UAE). For this purpose, a response surface methodology (RSM) study with a five-level circumscribed central composite design (28 independent experiments) was applied to optimize three main UAE variables: ethanol concentration (S, 35–100%), time (t, 5–55 min) and power (p, 100–500 W). A second-order polynomial model was used to fit the experimental data (obtained in triplicate). Based on the model prediction (R² = 0.965), the optimal conditions that individually maximized extraction yield were 29.98 ± 1.03 g E/100 g Ma dw at a t-value of 45.00 ± 3.35 min, an S-value of 37.50 ± 3.06% and a p-value of 409.46 ± 10.12 W. Meanwhile, for maximizing the Fx content (R² = 0.8199), the response was optimal at 0.93 ± 0.10 mg Fx/g Ma dw at a t-value of 45.00 ± 3.35 min, an S-value of 84.22 ± 4.59% and a p-value of 339.73 ± 9.22 W. Full article

Olive pomace, an environmentally detrimental residue generated during olive oil extraction, contains bioactive compounds in demand by the food industry. To valorize this waste product a suitable yield for the extraction process is required. Heat-assisted extraction of bioactive compounds from olive pomace was optimized by a circumscribed central composite design and response surface methodology. Our previous studies indicated that irradiation could improve 2.4-fold the extractability of the main phenolic compounds from olive pomace. The effect of extraction time, temperature and solvent concentration on the yield of polyphenols from irradiated olive pomace at 5 kGy was tested. Hydroxytyrosol-1-β-glucoside, hydroxytyrosol, tyrosol and caffeic acid were quantified by High Performance Liquid Chromatography to calculate the total polyphenol content. The optimal general conditions by RSM modeling were extraction time of 120 min, temperature of 85 °C, and 76% of ethanol in water. Using these selected conditions, 19.04 ± 1.50 mg/g dry weight, 148.88 ± 8.73 mg/g extract of total polyphenols were obtained, representing a yield of 13.7%, which was consistent with the value predicted by the model. This work demonstrated the potential of residues from the olive oil industry as a suitable alternative to obtain compounds that could be used as ingredients for the food industry. Full article