In this present study, a three-factor Box-Behnken, response surface methodology (RSM) design was employed to optimize the skimmed milk powder (SMP)/whey protein concentrate (WPC) ratio (0.25-0.75%w/v) as a source of milk protein, inulin (1-2%w/v), and honey (4-6%w/v) for production of high-quality goat milk yoghurt (GMY). The resulting ANOVA and response surface equations revealed the significant effect (p < 0.05) of these variables on the various attributes such as total solid (%), pH, titratable acidity [(LA) % by weight], syneresis (%), DPPH (% inhibition), viscosity (m.Pa⋅s), whiteness index (WI), and overall acceptability (OA). The coefficient of determination (R2) for all response variables ranged from 0.88 to 0.99. Lack-of-fit tests resulted in non-significant F-values. The optimal conditions were determined as SMP/WPC at 0.36%w/v, inulin at 1.00%w/v, and honey at 6.00%w/v. The optimum values for total solid, pH, titratable acidity, syneresis, DPPH, viscosity, WI, and OA were 22.03, 4.46, 0.77, 6.34, 25.20, 182.30, 76.29 and 8.37, respectively with desirability value of 0.95.

Nowadays, large numbers of organizations may opt for Aspect-Oriented Programming (AOP), which is an enhancement to Object-Oriented Programming (OOP). This is due to the addition of a number of concepts that have assisted in the production of more flexible and reusable components. One of the most important elements added by AOP is software reuse, which is based on reusability attributes. These attributes indicate the possibility of reusing one or more components in the development of a new system. It is one of the most essential attributes to evaluate the quality of a system\'s components. Thus far, little attention has been paid to the process of measuring AOP reusability, and it has not yet been standardized. The objective of the current study is to come up with a reasonable measurement for AOP software reuse, which is simultaneously a significant topic for researchers while offering several advantages for organizations. Although numerous models have been built to estimate the reusability of software, most of them are not dedicated to Aspect-Oriented Software (AOS). In this study, a model has been designed for AOS reusability estimation and measurement based on a new equation depending on five attributes that have a range of positive and negative impacts on AOS reusability. Three of those attributes, namely coupling, cohesion, and design size, have been included in previous studies. This study proposes complexity and generality as two new attributes to be considered. Each of these attributes was measured based on the metrics also proposed in this study. A new equation to calculate AOS reusability was constructed based on the most important reusability attributes and metrics. Seven aspect projects were employed as a case study to apply the proposed equation. After the proposed equation was applied to the selected projects, we obtained new values of reusability to compare with the values that resulted from applying the previous equation. The fact that new values emerged indicates that the proposed reusability metrics and attributes had a significant effect.

New and innovative nanomedicines have been developed and marketed over the past half-century, revolutionizing the prognosis of many human diseases. Although a univocal regulatory definition is not yet available worldwide, the term \"nanomedicines\" generally identifies medicinal products that use nanotechnology in their design or production. Due to the intrinsic high structural complexity of these products, the scientific and regulatory communities are reflecting on how to revise the regulatory framework to provide a more appropriate benefit/risk balance to authorize them on the market, considering the impact of their peculiar physicochemical features in the evaluation of efficacy and safety patterns. Herein, a critical perspective is provided on the current open issues regarding regulatory qualification and physicochemical characterization of nanosystems considering the current European regulatory framework on nanomedicine products. Practicable paths for improving their quality assurance and predicting their fate in vivo are also argued. Strengthening the multilevel alliance among academic institutions, industrial stakeholders, and regulatory authorities seems strategic to support innovation by standard approaches (e.g., qualification, characterization, risk assessment), and to expand current knowledge, also benefiting from the new opportunities offered by artificial intelligence and digitization in predictive modelling of the impact of nanomedicine characteristics on their fate in vivo.

Protein A chromatography is widely used for isolation of monoclonal antibodies (mAbs) from cell culture components. In this study, the effect of different process parameters of the Protein A purification namely, binding pH, elution pH, flow rate, neutralization pH and tween concentration, on the concentration and quality of the purified mAb were evaluated. Using design of experiments approach, the critical process parameters of protein A chromatography were identified and experimentally optimized. Their impact on quality attributes, such as size variants and charge variants, of the mAb was studied. Multivariate data analysis was subsequently performed using multiple linear regression and partial least squares regression methods. It was observed that the elution pH primarily governed the concentration of the purified mAb and the content of monomers and aggregates, while the tween concentration primarily influenced the main peak of the charge variants. This is the first study that evaluates the impact of tween concentration in buffers on the protein A chromatography purification step. These studies helped in identifying the design space and defining the target robust and optimal setpoints of the responses, which were subsequently verified experimentally. These setpoints not only passed the target criteria but also resulted in the highest recoveries during the investigation. Through this statistically-aided approach, an optimized and robust protein A chromatography process was rationally developed for purification of mAbs, while achieving the desired product quality. This study highlights the influence of multiple parameters of the protein A purification process on critical quality attributes of mAbs, such as the size and charge variants, which has been a very scarcely explored area.

Eight treatments of edible coatings and nets including liquid smoke (SP and 24P) and xanthan gum (XG) were used to evaluate their effectiveness at controlling mite growth on dry-cured hams. Mite growth was controlled (P < 0.05) in both coating and netting treatments of 1% SP + 1% XG. Increasing SP concentration from 1% to 2% in the SP only treatments without XG did not control mite growth (P > 0.05) in the coating but controlled mite growth (P < 0.05) when infused in the nets. Both coating and netting treatments with 2% 24P + 1% XG controlled mite growth (P < 0.05), and ham cubes with 1% and 2% 24P in infused nets had mite numbers of 4.6 and 9.4, respectively. SP did not impact the sensory attributes of the ham. Results indicate that liquid smoke can potentially be added in coatings or ham nets to control mites and used in an integrated pest management program for dry-cured hams.

Fruit quality attributes interrelate with their dielectric properties, but such interrelationships in sea buckthorn berries under differing freezing regimes remain uninvestigated. Sea buckthorn (Hipophae rhamnoides L., cv. Shenqiuhong) berries were frozen at different temperatures (-13, -30, -35 and -40 °C) and stored for different periods (15, 30, 45, 60, 75 and 90 d). Seven quality attributes and nine dielectric parameters were measured to evaluate the effect of different frozen storage regimes on those attributes and parameters. The results showed that shorter time and lower temperature contributed to the preservation of berries quality. The dielectric parameters values increased with decreasing temperature and with the increase of freezing duration. The quality prediction models were established by the principal component analysis of the dielectric properties at characteristic frequency. The results are expected to provide a way to evaluate quality of frozen sea buckthorn berries by dielectric properties.

In the development of therapeutic monoclonal antibodies (mAbs), it is essential to characterize the modifications causing structural heterogeneity because certain modifications are associated with safety and efficacy. However, the rapid structural analysis of mAbs remains challenging due to their structural complexity. The multi-attribute method (MAM) is a structural analytical method based on peptide mapping using LC/MS, and has drawn attention as a new quality control method for therapeutic mAbs instead of conventional structural heterogeneity analyses using several chromatographic techniques. Peptide mapping, which is regarded as an identification test method, is used to confirm that the amino acid sequence corresponds to that deduced from the gene sequence for the desired product. In contrast, MAM is used for simultaneously monitoring the modification rates of individual amino acid residues of therapeutic mAbs, indicating that MAM is used as quantitative test rather than identification test. In this review, we summarized the typical structural heterogeneities of mAbs and the general scheme of MAM. We also introduced our optimized sample preparation method for MAM, and examples of simultaneous monitoring of several modifications including deamidation, oxidation, N-terminal pyroglutamination, C-terminal clipping and glycosylation by our MAM system.

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Chinese hamster ovary (CHO) cells are the most widely used mammalian host cells for the commercial production of therapeutic proteins. Fed-batch culture is widely used to produce therapeutic proteins, including monoclonal antibodies, because of its operational simplicity and high product titer. Despite technical advances in the development of culture media and cell cultures, it is still challenging to maintain high productivity in fed-batch cultures while also ensuring good product quality. In this review, factors that affect the quality attributes of therapeutic proteins in recombinant CHO (rCHO) cell culture, such as glycosylation, charge variation, aggregation, and degradation, are summarized and categorized into three groups: culture environments, chemical additives, and host cell proteins accumulated in culture supernatants. Understanding the factors that influence the therapeutic protein quality in rCHO cell culture will facilitate the development of large-scale, high-yield fed-batch culture processes for the production of high-quality therapeutic proteins.

The effects of vacuum package combined with 0.1% ε-polylysine and 0.2% rosemary extract (V + RP) on the quality attributes and microbial communities of large yellow croaker (Pseudosciaena crocea) during ice storage were investigated. The quality was evaluated by chemical characteristics (total volatile basic nitrogen (TVB-N), K-value and biogenic amines (BAs)), microbiological indexes (Total viable counts (TVC), Shewanella bacteria counts, Pseudomonas bacteria counts, Psychrophilic bacteria counts (PBC)), changes in microbial composition were analyzed using high-throughput sequencing. Results showed that the increase of TVB-N, K-value, microorganisms and BAs could be inhibited by V + RP. Psychrobacter and Pseudomonas were detected in all samples. Shewanella increases rapidly in the middle of storage. Vagococcus and Shewanella were related to the decomposition of ATP, the formation of BAs, and TVB-N, respectively. In conclusion, V + RP presented the optimal effects, which could extend the shelf life of large yellow croaker for another 9 days compared with the control.