The biodegradation of phenol, p-cresol, and phenol plus p-cresol mixtures was evaluated using Pseudomonas putida ATCC 17484 in aerobic batch reactors. Shake-flask experiments were performed separately using growth medium with initial nominal concentrations of phenol (50−600 mg L−1) and p-cresol (50−600 mg L−1) as well as phenol (50−600 mg L−1) plus p-cresol (50−600 mg L−1). The complete degradation of phenol and p-cresol was achieved within 48 h and 48−56 h, respectively, for all initial concentrations of phenol and p-cresol. The maximum cell growth rate using phenol (μmax,P = 0.45 h−1) was much faster than that using p-cresol (μmax,C = 0.185−1 h). The larger Ki value for phenol (310.5 mg L−1) revealed that the P. putida cells had a higher resistance to phenol inhibition compared with p-cresol (243.56 mg L−1). A mixture of phenol and p-cresol in batch experiments resulted in the complete removal of phenol within 52−56 h for initial phenol concentrations of 50−500 mg L−1. The time neede... [more]

Due to insufficient mass transfer and mixing issues, cells in the industrial-scale bioreactor are often forced to experience glucose feast/famine cycles, mostly resulting in reduced commercial metrics (titer, yield and productivity). Trehalose cycling has been confirmed as a double-edged sword in the Penicillium chrysogenum strain, which facilitates the maintenance of a metabolically balanced state, but it consumes extra amounts of the ATP responsible for the repeated breakdown and formation of trehalose molecules in response to extracellular glucose perturbations. This loss of ATP would be in competition with the high ATP-demanding penicillin biosynthesis. In this work, the role of trehalose metabolism was further explored under industrially relevant conditions by cultivating a high-yielding Penicillium chrysogenum strain, and the derived trehalose-null strains in the glucose-limited chemostat system where the glucose feast/famine condition was imposed. This dynamic feast/famine regim... [more]

Novel technologies such as partial nitritation (PN) and partial denitritation (PDN) could be combined with the anammox-based process in order to alleviate energy input. The former combination, also noted as deammonification, has been intensively studied in a frame of lab and full-scale wastewater treatment in order to optimize operational costs and process efficiency. For the deammonification process, key functional microbes include ammonia-oxidizing bacteria (AOB) and anaerobic ammonia oxidation bacteria (AnAOB), which coexisting and interact with heterotrophs and nitrite oxidizing bacteria (NOB). The aim of the presented review was to summarize current knowledge about deammonification process principles, related to microbial interactions responsible for the process maintenance under varying operational conditions. Particular attention was paid to the factors influencing the targeted selection of AOB/AnAOB over the NOB and application of the mathematical modeling as a powerful tool en... [more]

Due to the poor protein availability of algae in their unprocessed form, development of extraction methods for phycobiliproteins is of great significance. This study aimed to extract phycoerythrin (PE) and phycocyanin (PC) from Porphyra via bacterial enzymatic hydrolysis and to evaluate their bioactivity. To induce enzyme production, Porphyra powder was added into the culture medium of two marine bacterial strains. The pH and enzyme activity of the cultured supernatant, namely crude enzyme solution, were significantly raised. For PE and PC extraction, Porphyra were incubated within crude enzyme solution with homogenization and ultrasonication followed by ultrafiltration process. After distinguishing by fast performance liquid chromatography (FPLC), three major fractions were observed and identified as R-PE, R-PC and small molecular PE by high-performance liquid chromatography (HPLC) and polyacrylamide gel electrophoresis (PAGE) analysis. With respect to bioactivity, these three fractio... [more]

The efficiency of Azadirachta indica (neem leaves) on the removal of Pb(II) ions by adsorption from aqueous solution was investigated in this study. The efficiency of these leaves (without chemical or thermal treatment) for the adsorption of Pb(II) ions has not previously been reported. Batch experiments were performed to study the effect of the particle size, pH, adsorbent dose, contact time, initial Pb(II) ion concentration, and temperature. The maximum removal of 93.5% was achieved from an original Pb(II) ion solution concentration of 50 mg/L after 40 min, at pH 7, with 0.60 g of an adsorbent dose. The maximum adsorption capacity recorded was 39.7 mg/g. The adsorption process was also studied by examining Langmuir, Freundlich, Temkin isotherm, and Dubinin−Radushkevich (D-R) isotherm models. The results revealed that the adsorption system follows the pseudo-second-order model and fitted the Freundlich model. Several thermodynamic factors, namely, the standard free energy (∆G°), entha... [more]

Airborne particulate matter (PM) pollution often occurs in the wintertime in northern China, posing a potential threat to human health. To date, there are limited studies about the metals and inorganic ions to link source apportionments and health risk assessments in the different size-segregated PM samples. In this study, our samples were collected by a high-volume air sampler from 26 December 2018 to 11 January 2019 in a high population residential area (Beijing). Water-soluble inorganic ions, metal elements in the different size-segregated PM samples were determined for health risk assessments by inhalation of PM. During the sampling period in Beijing, the average concentrations of PM1.1 and PM1.1−2.0 were 39.67 ± 10.66 μg m−3 and 32.25 ± 6.78 μg m−3. Distinct distribution profiles characterized the different elements. The markers of coal combustion Pb, As, and Se had >52% of their mass concentration in PM1.1. The average mass ratios of (NO3− + NO2−)/SO42−, Cl−/Na+, Cl−/K+, and Cl−/... [more]

This research examines a case study on the implementation of an effective approach to advanced Lean Six Sigma problem-solving within a pharmaceutical manufacturing site which manufactures acetaminophen (paracetamol containing pain relief) tablets. Though this study was completed in a single manufacturing company, the implementation of this study delivers important application and results that can be deployed in other such manufacturing companies. The manufacturing site faced backlogs in customer orders due to increased demand. Increased demand is due to brand popularity and recognition, product efficacy and a COVID 19 pandemic that intensified the demand for pain relief tablets in an already very busy site. With increased demand, to ensure timely deliveries, customer satisfaction and minimize delays, sources of site productivity losses and wastes needed to be analyzed and reduced or eliminated. Manufacturing Packaging line downtime was identified as one area of concern. The goal of the... [more]

The increasing clinical use of artificial medical devices raises the issue of microbial contamination, which is a risk factor for the occurrence of biofilm-associated infections. A huge amount of scientific data highlights the promising potential of essential oils (EOs) to be used for the development of novel antibiofilm strategies. We aimed to review the relevant literature indexed in PubMed and Embase and to identify the recent directions in the field of EOs, as a new modality to eradicate microbial biofilms. We paid special attention to studies that explain the mechanisms of the microbicidal and antibiofilm activity of EOs, as well as their synergism with other antimicrobials. The EOs are difficult to test for their antimicrobial activity due to lipophilicity and volatility, so we have presented recent methods that facilitate these tests. There are presented the applications of EOs in chronic wounds and biofilm-mediated infection treatment, in the food industry and as air disinfecta... [more]

Pesticide by-products found in soil are usually more toxic and persistent than the pesticides themselves. For example, Endosulfan lactone (EL) (a by-product of the organochloride pesticide endosulfan). EL is created by the enzymatic activity (and related oxidative processes) of microorganisms in the soil. A sustainable method of EL removal is the introduction of Eisenia fetida earthworm. In this paper, it will be demonstrated the impact of vermicomposting process related to Eisenia fetida earthworm on EL by measuring initial and final concentrations of the compound and overall enzymatic activity in sterile and non-sterile solid substrate over 56 days. As a baseline, it be observed there were higher EL removals in non-sterile solid substrate (90.86%) at day 5 than in sterile solid substrate (83.86%) at day 14. In samples with Eisenia fetida, the presence of EL in non-sterile solid substrate was 36%, however in sterile solid substrate it was only 18% at day 1 and 7, with a maximum enzyme... [more]

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.

Despite the significant progress in anticancer drug development over recent years, there is a vital need for newer agents with unique, but still effective, mechanisms of action in order to treat the disease, particularly the highly aggressive and drug-resistant types. Alkylating agents, in particular nitrogen-based alkylators, are commonly used to treat hematological and solid malignancies; they exert their antineoplastic effects at all phases of the cell cycle and prevent reproduction of tumor cells. Certain alkylating agents have been designed to be more lipophilic, enabling the compound to penetrate the cell and enhance its alkylating activity against tumors. This review details the evolution of currently available alkylating agents and their profiles, with a focus on nitrogen-based alkylating agents, as important anticancer therapy strategies.

Lipophilicity is one of the most important parameters determining the pharmacodynamic and pharmacokinetic properties, as well as the toxicity of many compounds. The subject of the research was to determine the lipophilicity of betulin-1,4-quinone hybrids using thin layer chromatography in reverse phase system and computer programs to calculate its theoretical models. The correlation between the experimental and theoretical values of lipophilicity was analyzed. Lipinski’s and Veber’s rules, as well as penetration through the blood−brain barrier were also determined using computer programs. For all of the analyzed values, a similarity analysis was performed. The dendrograms for the experimental and theoretical lipophilicity show that there is a correlation between them. However, the dendrograms for the experimental lipophilicity and pharmacokinetic parameters indicate that there is no correlation between the structure and the pharmacological properties. Hybrids exhibit a high biological... [more]

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Growing evidence shows that EVs have great potential to serve as effective drug carriers. Since EVs can not only transfer biological information, but also effectively deliver hydrophobic drugs into cells, the application of EVs as a novel drug delivery system has attracted considerable scientific interest. Recently, EVs loaded with siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, or therapeutic drugs show improved delivery efficiency and drug effect. In this review, we summarize the methods used for the cargo loading into EVs, including siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, and therapeutic drugs. Furthermore, we also include t... [more]

Plasmin (Plm), a trypsin-like serine protease, is responsible for fibrinolysis pathway and pathologic events, such as angiogenesis, tumor invasion, and metastasis, and alters the expression of cytokines. A growing body of data indicates that a Plm inhibitor is a potential candidate as an anti-inflammatory and anti-cancer agent. A class of active site-directed plasmin inhibitors containing tranexamic acid residue has been designed. As evidenced by docking studies, the inhibitor binds to the active site not to the lysine binding site (LBS) in plasmin, thus preventing plasmin from digesting the substrate. Further optimization of the series, concerning both activity and selectivity, led to the second generation of inhibitors. This review focuses on the Plm inhibitory activity-structure relationship of Plm inhibitors with the goal of realizing their design and clinical application.

In this work was evaluated the effect of sequential inoculum of Hanseniaspora uvarum AS27 strain and a commercial Saccharomyces cerevisiae yeast on the physical−chemical and organoleptic features of Aglianico, a traditional red wine of Southern Italy. Four fermentation treatments on a pilot scale were performed. In fermentation treatment A, the alcoholic fermentation was spontaneously conducted by the indigenous yeasts present in grape must. In the fermentation treatments B and C were inoculated respectively S. cerevisiae FE and H. uvarum AS27 strains, as a single starter. The fermentation treatment D was initially inoculated with H. uvarum AS27, and S. cerevisiae strain was added after 72 h (sequential inoculation). Microbiological, physical−chemical parameters and sensory profiles of the wines have been defined. The results showed that the use of H. uvarum AS27, in sequential inoculum with S. cerevisiae FE, influenced the wine composition, enriching it in polyphenolic and volatile co... [more]

Studying cell metabolism serves a plethora of objectives such as the enhancement of bioprocess performance, and advancement in the understanding of cell biology, of drug target discovery, and in metabolic therapy. Remarkable successes in these fields emerged from heuristics approaches, for instance, with the introduction of effective strategies for genetic modifications, drug developments and optimization of bioprocess management. However, heuristics approaches have showed significant shortcomings, such as to describe regulation of metabolic pathways and to extrapolate experimental conditions. In the specific case of bioprocess management, such shortcomings limit their capacity to increase product quality, while maintaining desirable productivity and reproducibility levels. For instance, since heuristics approaches are not capable of prediction of the cellular functions under varying experimental conditions, they may lead to sub-optimal processes. Also, such approaches used for bioproc... [more]

Most cells within the human body interact with neighboring cells and extracellular matrix (ECM) components to establish a unique 3D organization. These cell−cell and cell−ECM interactions form a complex communication network of biochemical and mechanical signals critical for normal cell physiology. The behavior of cells in a 3D environment is fundamentally different from that of cells in monolayer culture. Aggregation can affect cell−cell interactions, being more representative of the normal tissue microenvironment. Therefore, 3D cell culture technologies have been developed. The general method for cell aggregate is a physical method; it is difficult to control the size and number of cell aggregates. In any case, no chemical method has been discovered yet, so a new method to solve these problems is needed. In this paper, we describe the induction of a cell aggregate of the newly discovered (Lys-Pro)12(KP24) peptide. Since it was revealed that KP24 had cell aggregate-inducing activity,... [more]

The aim of the study was to determine oxidation potential of selected persistent, environmentally relevant antibiotics (Amoxicillin, Levofloxacin, and their mixture with Vancomycin) to reduce their environmental emissions. Ozonation (O3) and indirect ozonation at pH 9.5 (O3/pH9.5) were catalytically enhanced by addition of Fe2+ (O3/Fe2+) and photocatalytic ozonation in combination with Fe2+ and UV-A black light (O3/Fe2+/UV) at two temperatures using total organic carbon (TOC) and chemical oxygen demand (COD) to identify formation of by-products. Oxidative degradation followed pseudo-first order consecutive reactions. Initial phase of oxidation was more intensive than mineralisation at 21 and 40 °C: up to 57.3% and 69.2%, respectively. After 120 min mineralization at 21 °C was up to 64.9% while at 40 °C it was up to 84.6%. Oxidation reached up to 86.6% and 93.4% at 21 °C and 40 °C, respectively. The most efficient processes were indirect ozonation at pH 9.5 (O3/pH9.5) (up to 93.4%) and... [more]

Tripartite motif 21 (TRIM21) plays an important role in hepatocellular carcinoma (HCC). However, the gene polymorphisms of TRIM21 in HCC is not as well known. In this study, two single nucleotide polymorphisms (SNPs) in the TRIM21 gene, rs4144331, and re915956, were selected to investigate correlations between these SNPs and susceptibility to HCC. Two SNPs of the TRIM21 gene from 1196 controls without cancer and 394 HCC patients were analyzed using real-time polymerase chain reaction. These results were further analyzed to expound the associations between these TRIM21 polymorphisms and the risk of HCC as well as the impact of these SNPs on clinicopathological characteristics of HCC. After adjustment for other covariants, we observed that that younger patients (<65 years) with the TRIM21 rs915956 A allele had a probability of HCC (AOR = 3.153, 95% CI: 1.315−7.516, p = 0.010). Moreover, patients with a smoking habit who carried the T allele of rs4144331 had more probability of HCC (AO... [more]

Supercritical carbon dioxide + ethanol (SC-CO2+EtOH) extraction, was employed as a deflavoring method to improve the sensory properties of pea flours. Furthermore, the impacts of particle size along with extraction on volatile profile and sensory attributes of pea flours were investigated using multiple approaches. These included headspace solid-phase microextraction-gas chromatography (HS-SPME-GC), GC-olfactometry (GC-O), and quantitative descriptive analysis (QDA) using a trained sensory panel. Total volatile contents of non-deflavored and deflavored whole pea flour and its fractions were in the range of 7.1 ± 0.3 to 18.1 ± 1.0 µg/g and 0.4 ± 0.1 to 2.7 ± 0.4 µg/g, respectively. The GC-O system showed that the total volatile intensity was in the range of 14.5 to 22.0 and 0 to 3.5, for non-deflavored and deflavored pea flours, respectively. Volatile analyses indicated that 1-hexanol, 1-octanol, 1-nonanol, nonanal, and 2-alkyl methoxypyrazines were major off-aroma compounds. Most off-a... [more]

The integration of real time release testing into an advanced process control (APC) concept in combination with digital twins accelerates the process towards autonomous operation. In order to implement this, on the one hand, measurement technology is required that is capable of measuring relevant process data online, and on the other hand, a suitable model must be available to calculate new process parameters from this data, which are then used for process control. Therefore, the feasibility of online measurement techniques including Raman-spectroscopy, attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), diode array detector (DAD) and fluorescence is demonstrated within the framework of the process analytical technology (PAT) initiative. The best result is achieved by Raman, which reliably detected mAb concentration (R2 of 0.93) and purity (R2 of 0.85) in real time, followed by DAD. Furthermore, the combination of DAD and Raman has been investigated, which... [more]

Although many benefits drawn from beer consumption are claimed, the epidemiological records are contradictory with respect to cancer prevention. The purpose of this study was to investigate the possible health-related activities involving genome safety and the ageing processes of two types of lyophilised ale beers (blond and stout), as well as two of their bioactive compounds (tyrosol and iso-alpha humulone). A multipurpose trial set of in vivo toxicity, antitoxicity, mutagenicity, antimutagenicity, lifespan and healthspan assays using Drosophila melanogaster were used. In parallel, several in vitro assays were designed using the cancer cell line HL-60 in order to establish the possible chemopreventive activity of the selected substances, where epigenetic modulation of DNA methylation changes, clastogenic activity and tumour cell inhibition growth were evaluated. The safety of the four substances was confirmed: lyophilised blond ale beer (LBAB), lyophilised stout ale beer (LSAB), tyros... [more]

Cubing machines in food processing have evolved over the years, which have made products like Star®, Knorr®, and Chicken® bouillon cubes become commercially available today, even in many parts of Africa. On the other hand, the fermented mesquite seed “okpeye” food condiment, traditionally produced by well-trained artisans and widely utilised in Nigeria, requires further product development in order to compete with bouillon cubes. Quality comparisons between the cubed “okpeye” condiment and commercially available bouillon cube products have not yet been reported. Therefore, cubing fabrication/costing and machine performance on African fermented “okpeye” condiment quality attributes, compared with commercial bouillon types, were done. The processing of mesquite seeds into the “okpeye” condiment resembled those of artisans. Bouillon cube products involved the Star®, Knorr®, and Chicken® types. Quality attributes involved proximate, micronutrient, phytochemical, and microbial aspects. Resu... [more]

This study proposes a reliable inline PAT concept for the simultaneous monitoring of different product components after chromatography. The feed for purification consisted of four main components, IgG monomer, dimer, and two lower molecular weight components of 4.4 kDa and 1 kDa molecular weight. The proposed measurement setup consists of a UV−VIS diode-array detector and a fluorescence detector. Applying this system, a R2 of 0.93 for the target component, a R2 of 0.67 for the dimer, a R2 of 0.91 for the first side component and a R2 of 0.93 for the second side component is achieved. Root mean square error for IgG monomer was 0.027 g/L, for dimer 0.0047 g/L, for side component 1 0.016 g/L and for the side component 2 0.014 g/L. The proposed measurement concept tracked component concentration reliably down to 0.05 g/L. Zero-point fluctuations were kept within a standard deviation of 0.018 g/L for samples with no IgG concentration but with side components present, allowing a reliable det... [more]

The valorization of Spirulina as a potential biosorption material to treat contaminated wastewater was evaluated. Batch experiments were conducted to study the influence of pH value and ionic strength on the biosorption capacity of Spirulina. Higher removal capacity was observed at pH 5.2, while higher ionic strength was found to result in lower adsorption capacity, which suggests that ion exchange is a relevant mechanism for Pb (II) adsorption on Spirulina. The immobilization of Spirulina on alginate beads was found not only to increase the adsorption capacity, but also to overcome limitations such as unacceptable pressure drops on column systems. The Langmuir model was the most appropriate model to describe the biosorption equilibrium of lead by free and immobilized Spirulina. The experimental breakthrough curves were evaluated using the Thomas, Bohart-Adams, and dose-response models. The experimental results were most properly described by the dose-response model, which is consisten... [more]