Crystallization is a relevant process in the pharmaceutical industry for product purification and particle production. An efficient crystallization is characterized by crystals produced with the desired attributes. Therefore, modeling this process is a key point to achieve this goal. In this sense, the objective of this work is to propose a hybrid model to describe paracetamol dissolution in ethanol. The universal differential equations methodology is considered in the development of this model, using a neural network to predict the dissolution rate combined with the population balance equations to calculate the moments of the crystal size distribution (CSD) and the concentration. The model was developed using experimental batches. The dataset is composed of concentration measurements obtained using attenuated total reflectance-Fourier transform infrared (ATR-FTIR). The objective function of the optimization problem is to minimize the relative absolute difference between the experiment... [more]

Biomacromolecules have intricate crystallisation behaviour due to their size and many interactions in solution and can often only crystallise in narrow ranges of experimental conditions. High solute concentrations are needed for crystal nucleation and growth, exceeding those eluted upstream and therefore preventing the adoption of crystallisation in downstream separation steps. By promoting molecular aggregation and nucleation via a lowered energy barrier, heterogeneous surfaces or templates can relax the supersaturation requirements and widen the crystallisation operating space. Though templates are promising candidates for process optimisation, their experimental testing has generally been limited to small-volume experiments, and quantification of their impact on process intensification and quality metrics at higher volumes remains unexplored. To address the knowledge gap, a model-based investigation of template-induced protein crystallisation systems through evaluation of key metric... [more]

This work presents a hybrid-modeling approach to monoclonal antibody (mAb) production processes design using automated bioreactor equipment. Experimental data covering a reasonable yet broad range of cultivation conditions was collected by the equipment. Using the data, a model applicable to a wide range of cultivation conditions was developed. In the modeling, a data-driven model was applied to describe complicated/unknown phenomena that could not be captured by previously proposed mechanistic models. In the hybrid model, while maintaining the mass balance of the mechanistic model, coefficients of the equations were estimated with random forest regression. Overall, the model could describe the dynamic concentration profiles of product mAb and quality-relevant impurities depending on the media/glucose feeding conditions. The model was then applied to determine an optimal condition that maximized product mAb concentration and satisfied the impurity constraints. The work can further supp... [more]

Polyhydroxyalkanoates (PHAs) are microbial bioplastics that are fully biodegradable, biocompatible and can be produced by renewable feedstocks through fermentation. These are all desirable attributes for the replacement of current fossil-based plastics. Strong mathematical models describing bioprocesses are invaluable tools that can be used for enhancing bioprocess understanding as well as optimization. In this study, polyhydroxybutyrate (PHB), by Cupriavidus necator DSM 545 was produced using glycerol and ammonium sulphate (AS) as the sole carbon and nitrogen sources, respectively. In addition, a kinetic bioprocess model was developed. The kinetic parameters of the model were calibrated with five fermentation experiments with different initial conditions (e.g. variable glycerol and AS concentrations) in order to properly establish the inhibition regions and provide a generalized model as much as possible. The model was successfully validated by three independent experiments, two with... [more]

The use of metabolic networks is extremely valuable for design and optimisation of bioprocesses as they provide great insight into cellular metabolism. Within bioprocess optimisation, they have enabled better (economic) objective performance through more accurate network-based models. However, one of the drawbacks of using metabolic networks is their underdeterminacy, leading to non-unique flux distributions. Flux Balance Analysis (FBA) reduces this issue by making assumptions on the behaviour of the cell. However, for metabolic networks of higher complexity, can still struggle with underdeterminacy. Metabolic network reduction can remove or greatly reduce this effect but can be difficult, especially when data is limited. Structural analysis of the metabolic network through Elementary Flux Modes (EFM) or Extreme Pathways (EP) can help locate the relevant information within the network. This work presents a metabolic network reduction approach based on the EPs that best explain a small... [more]

In recent years, burgeoning interest in products derived from microbial production across various sectors has significantly propelled the evolution of the field of metabolic engineering. As a Gram-negative bacterium, Vibrio natriegens is characterized by its fast growth, robust metabolic capabilities, and a broad substrate spectrum, making it a promising candidate as a standard biological host for the industrial bioproduction of metabolites. Genome-scale metabolic models (GSMMs) are mathematical representations constructed based on genome annotations and gene-protein-reaction (GPR) associations within a cell. These models enable the computational simulation of intracellular reaction flux distributions. In this study, we developed a hybrid method based on metaheuristic algorithms and the GSMM to optimize metabolism for the production of ethanol and 1,3-propanediol (1,3-PDO) as target products in Vibrio natriegens. The modified GSMM used in this study contains 1195 reactions, 1094 metabo... [more]

Machine learning algorithms have led to the development of numerous vector embeddings for biological entities such as metabolites, proteins, genes, and enzymes. However, these embeddings often lack contextual information due to their specialized focus on individual omics. Disease progression and biosynthesis pathways are increasingly understood through complex, multi-layered networks that integrate diverse omics data and intricate signaling and reaction sequences. Capturing these relationships in a meaningful way requires embeddings that account for both functional and multi-modal dependencies. We propose an embedding approach that unifies these different biological modalities by treating them as directions in a shared space rather than as isolated data types. Similar to how word embeddings in natural language processing reveal meaningful relationships (e.g., Tokyo – Japan + UK = London, indicating a directional representation of capitals), we can model genes and proteins in a way that... [more]

Individual-based modeling (IbM) has emerged as a powerful approach for studying microbial populations, offering a bottom-up framework to simulate cellular behaviors and their interactions. Unlike continuum-based models, IbM explicitly captures the heterogeneity and emergent dynamics of microbial communities, making it invaluable for studying spatially structured phenomena such as nutrient competition, biofilm formation, and colony interactions. However, IbM faces significant computational challenges, particularly in resolving spatial overlaps during simulations of large microbial populations. Traditional approaches, such as pairwise comparisons or kd-trees, are computationally expensive and scale poorly with population size. The Discretized Overlap Resolution Algorithm (DORA) introduces a novel grid-based solution to overcome these limitations. By encoding spatial information into an occupancy matrix, DORA achieves a time complexity of O(N), enabling efficient resolution of overlaps wh... [more]

TLC (thin-layer chromatography) and HPTLC (high-performance thin-layer chromatography) in normal (NP) and reversed (RP) phase systems were combined with densitometry to analyze caffeine, propyphenazone, and paracetamol. This work aims to check whether comparable limit of detection (LOD) values can be obtained on TLC and HPTLC plates. Analyses were performed on five (NP) or four (RP) different stationary phases (chromatographic plates), testing, in both cases, three mobile phases. It is shown that by using both TLC and HPTLC plates, it is possible to develop chromatographic conditions that enable the detection of compounds analyzed in amounts ranging from a dozen to several dozen µg/spot. In the RP system, lower LOD values for all tested compounds were obtained using TLC than HPTLC. However, performing analyses in the NP, similar (of the same order) LOD values were obtained for caffeine, propyphenazone, and paracetamol when using both TLC and HPTLC plates. For example, during the NP-HPT... [more]

Nature is an amazing source of natural bioactive compounds derived from numerous species of plants, marine bacteria, and fungi [...]

The optimization of cell disruption is a critical step in microalgal biorefineries. We used the same batch of Tetraselmis suecica culture to compare two mechanical cell disruption techniques, focusing on the extraction yield of water-soluble molecules. The conditions for high-pressure homogenization (HPH) studied were two passes at a moderate pressure of 300 bars. For ultrasound (US) treatment, we used an amplitude of 20% (equivalent to 100 W) for 25 min. These conditions were chosen on the basis of a preliminary screen of extraction conditions. HPH extracted proteins and pigments more efficiently than US, whereas US was superior for uronic acid extraction. Interestingly, the two methods had similar extraction yields for carbohydrates under the studied conditions. We also analyzed the kinetics of molecule release by considering the centrifugation time lag for HPH and applying a first-order kinetic model for US. HPH outperformed US in terms of the immediate extraction and release of mol... [more]

Nowadays, heavy metal pollution in soil caused by human production activities is increasingly serious. The heavy metal ions in soil inhibit plant growth and endanger human health as they can disrupt the physicochemical properties of soil. However, the elimination of heavy metals in soil is so difficult that more and more researchers are studying effective soil conditioners. The negatively charged groups in microbial communities can bind with heavy metal ions in the soil to remove them. In this paper, Cr- and Cd-polluted soils were used to simulate heavy-metal-polluted soil, and microbial compound fertilizer (MOF) was used as a soil conditioner for removing Cr and Cd in soil. The effects of different additive amounts of MOF on the physicochemical properties, the concentration of metal binding forms in soil and the enzyme activity of soil were investigated. The results showed that when the addition amount of fertilizer was 10%, the improvement effect on Cr- and Cd-polluted soils was the... [more]

causes plant diseases and is included in the list of microorganisms subject to export control. Janthinobacterium lividum is capable of synthesizing a pigment with antagonistic potential. The purpose of the study was to evaluate the activity of J. lividum VKM B-3705D and the pigment fraction against C. michiganensis VKM Ac-1402. The results of spectrophotometric and nuclear magnetic resonance analysis showed that the pigment synthesized by the J. lividum VKM B-3705D corresponds to violacein. The J. lividum strain demonstrated potential bacteriostatic activity against C. michiganensis VKM Ac-1402 when both strains were co-cultured. Compared to the control (DMSO), the violacein solution suppressed the specific growth of Clavibacter by 57.7%. The mechanism of suppression of the growth of Clavibacter is discussed. One of the ways to suppress the growth of C. michiganensis may be the inhibition of key enzymes. Violacein inhibited the activity of adenosine triphosphatase (ATPase, EC 3.6.1.3)... [more]

Food waste (FW), piggery waste (PW), and activated sludge (AS) were investigated as potential organic feeds for bioelectricity generation in laboratory-scale microbial fuel cells (MFCs). The MFCs fed by FW gained the highest maximum power density at 7.25 W/m3, followed by those fed by PW at 3.86 W/m3 and AS at 1.54 W/m3. The tCOD removal in the FW-, PW-, and AS-MFCs reached 76.9%, 63.9%, and 55.22%, respectively, within a 30-day retention time. Food waste, which resulted in the highest power density and tCOD removal, was selected for a series of following tests to investigate the effects of some physicochemical properties of organic feed on the performance of MFCs. The effect of feed particle size was tested with three controlled size ranges (i.e., 3, 1, and <1 mm) in MFCs. A smaller feed particle size provided a higher power density of 7.25 W/m3 and a tCOD removal of 76.9% compared to the MFCs fed with organic waste with a larger particle size. An increment in feed moisture from 70... [more]

Several studies have shown that lactic acid bacteria (LAB) fermentation plays an important role in the development and application of soy-based products and could increase their nutritional values and content of bioactive substances. Lactiplantibacillus plantarum LP95 has shown in previous studies to be a promising candidate as a probiotic and microbial culture in fermented soymilk production. In this study, the suitability of Lp. plantarum LP95 as a functional starter culture in tofu production was verified, with a focus on evaluating the isoflavone and amino acid content in the final product after 21 days of storage at 4 °C. Lp. plantarum LP95 was found able to ferment monosaccharides and disaccharides naturally present in soymilk (D-glucose, D-fructose, D-galactose and D-sucrose) after 24 h while leaving the content of galacto-oligosaccharides (stachyose and raffinose) unaffected. The rich amino acid profile of tofu has undergone some quantitative but not qualitative variations comp... [more]

Ester 2 was produced by reacting thiourea derivative 1 with ethyl 2-chloro-3-oxobutanoate in MeOH containing piperidine. Hydrazide 3 was produced by reacting the latter ester with hydrazine hydrate in EtOH at reflux. By reacting hydrazide 3 with aromatic/heterocyclic aldehydes, twelve derivatives of hydrazide hydrazone 5a−l were produced. Spectral measurements and elemental analysis verified the molecular structure. Compounds 2, 5a, 5c, 5d, and 5f had strong effects on all the pathogenic bacterial strains according to an evaluation of the antimicrobial qualities of the synthetic compounds. With inhibitory zone diameters ranging from 16 to 20.4 mm, hydrazide hydrazone 5f exhibited the strongest activity. Additionally, the minimum inhibitory concentration (MIC) was assessed. The best outcomes were found with hydrazones 5c and 5f. For B. subtilis, the MIC of 5c was 2.5 mg/mL. For E. coli and K. pneumoniae, the MIC of 5f was 2.5 mg/mL. The molecular mechanics-generalized born surface area... [more]

Essential oils are emerging as alternatives to conventional pest control chemicals. Lippia graveolens Kunth (Mexican oregano) is a source of essential oils and during conventional extraction, the biomass generated is discarded as waste; however, reports show that this biomass is still a rich source of essential oils. Conventional essential oil extraction causes contamination and utilizes toxic solvents. Deep eutectic solvents (DESs) offer low toxicity, biodegradability, high selectivity, and yields comparable to organic solvents. This study obtained essential oil from Lippia graveolens biomass via hydrodistillation with ultrasound-assisted DES pretreatment. This research aimed to optimize the extraction of essential oil from Lippia graveolens biomass using ultrasound-assisted DESs and assess its in vitro and in vivo inhibitory effect on C. asianum. The response variables were extraction yield and total reducing capacity. Optimal conditions were determined using a central composite rota... [more]

Brain-derived neurotrophic factor (BDNF) plays a vital role in supporting neuronal survival, differentiation, and promoting synaptogenesis, thereby facilitating synaptic plasticity in the central nervous system. Administration of exogenous BDNF is a crucial approach for treating central nervous system injuries. However, the inability of sustained drug release to match disease activity often leads to insufficient drug accumulation in the injured area (ineffectiveness) and severe side effects induced by the drug (toxicity). Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are typically upregulated after tissue damage, and their upregulated expression levels represent the degree of disease activity. In this study, we utilized bioengineering techniques to prepare a BDNF that can specifically bind to collagen and be released in response to MMP substrate cleavage (collagen binding domain tissue inhibitor of matrix metalloproteinases brain-derived neurotrophic factor, CBD-TIMP-BD... [more]

Our study explores the potential of a novel microwave plasma source for enhancing wound healing in BALB-C mouse models. Chronic wounds, particularly in diabetic individuals, present significant challenges due to impaired regenerative capacity. Cold Atmospheric Plasma (CAP) has emerged as a promising approach, offering diverse therapeutic benefits. However, its specific efficacy in the context of diabetic wounds remains underexplored. We developed and characterized a microwave plasma source optimized for wound treatment, inducing acute wounds and treating them with CAP in a controlled experimental setup. The treated group exhibited accelerated wound closure compared to controls, suggesting CAP’s potential to enhance the healing process. Our findings underscore CAP’s multifaceted impact on the wound healing cascade, highlighting its ability to promote angiogenesis, modulate inflammatory responses, and exhibit antimicrobial properties. These results position CAP as a promising interventio... [more]

Fungal diseases of plants are one of the key factors causing global crop losses. In this study, we isolated a Bacillus velezensis strain VC3, which was found to have a broad-spectrum inhibitory effect on a variety of phytopathogenic fungi through in vitro and in planta experiments, especially on Magnaporthe oryzae and Colletotrichum gloeosporioides. Further genomic and transcriptomic analyses revealed that the B. velezensis VC3 has multiple functional gene clusters encoding for the synthesis of a variety of antifungal secondary metabolites, including antimicrobial peptides (AMPs) and lipopeptides (LPs). In addition, AMPs and LPs were isolated and purified from B. velezensis VC3 fermentation broth and their antifungal activities were verified in this study. AMPs and LPs significantly inhibited spore germination, appressorium formation, and disease development, and AMPs have a better potential for controlling M. oryzae and C. gloeosporioides than LPs. These findings open new avenues for... [more]

During the last few decades, water pollution has become a growing concern at international level. To date, only a few Candida parapsilosis strains were successfully used in environmental remediation. In the present article, the strain C. parapsilosis CMGB-YT was studied for its ability to assimilate hydrophobic substrates and to produce biosurfactants with antimicrobial activity and positive effects on heavy metal removal from contaminated wastewaters. The strain C. parapsilosis CMGB-YT was grown on yeast peptone (YP) media with 1% n-decane, n-dodecane, n-tetradecane, n-hexadecane, as well as commercial sunflower and olive oils. The production of the biosurfactant was evaluated using the emulsification index (E24%). The surface properties and emulsifying stability of the biosurfactant were determined. The effect of the biosurfactant on the cell growth of two strains of Rhodotorula mucilaginosa and on their removal capacity of lead (0.032 g/L) and cadmium (0.030 g/L) ions from synthetic... [more]

The Processes Editorial Office retracts the article titled “A Review on Insights for Green Production of Unconventional Protein and Energy Sources Derived from the Larval Biomass of Black Soldier Fly” [...]

Grapes and grape products are rich in secondary metabolites such as phenolic compounds and anthocyanins, which have antioxidant properties. These compounds possess health-promoting attributes, including cardioprotective, antimicrobial, and anticancer effects. In recent years, biotechnological methods have been employed to produce high quantities and purity of secondary metabolites under in vitro conditions, aiming to elucidate their complex functions and optimize production methods. However, the potential effects of harpin proteins on the accumulation of secondary compounds in callus cultures have not been investigated thus far. Harpin proteins, encoded by the hrp gene clusters in Gram-negative phytopathogens, are known to trigger defense responses in various plant species by promoting the accumulation of secondary compounds. These findings suggest that harpin proteins may have the potential to enhance secondary metabolite accumulation in callus cultures. This study therefore investiga... [more]

The Processes Editorial Office retracts the article titled “RETRACTED: In-Situ Yeast Fermentation Medium in Fortifying Protein and Lipid Accumulations in the Harvested Larval Biomass of Black Soldier Fly” [...]

Incorporating anthocyanins, valuable natural pigments, into a powder can improve their stability, but exposure to high temperatures during processing can cause them to degrade. The purpose of this study was to investigate how the inlet air temperature during spray drying affects the physical and chemical characteristics as well as the flowability of a grape pomace anthocyanin powder obtained through ultrasound-assisted extraction using acidified water as the solvent. An anthocyanin solution containing 13% (w/v) maltodextrin was subjected to spray drying at temperatures ranging from 120 to 170 °C. Tukey’s test was applied to compare the means of the samples. The samples dried at temperatures between 130 and 170 °C were adequate, with a moisture content < 5% and a water activity < 0.3, indicating that the powder was stable. The highest anthocyanin retention (91.94 ± 1.59%) and process yield (50.00 ± 3.06%) were achieved at 140 °C, while higher temperatures resulted in anthocyanin degr... [more]