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Purpose: This study explores corporate news communication about intangible assets during the COVID-19 crisis in the largest global pharmaceutical companies. Methodology/approach: Computerised lexical content analysis was performed on 297 articles (texts) from 34 companies, amounting to 280,246 words. We generated a bottom-up clustering of the keywords, titles and abstracts. The qualitative data were obtained from the ProQuest textual database by Clarivate. Findings: The research demonstrates that the biggest global pharmaceutical companies focused intensively on intangible assets during the crisis. They disclosed information on three main intangibles: (1) brand, (2) patent and (3) license, covering 78.17% of the entire corpus text. Research limitations: The study limitations include the fact that the sample concerns only the biggest pharmaceutical companies that met our criteria. Further research could cover small and medium-sized companies and other industries. Finally, further analysis could combine quantitative and qualitative methods within the same research. Originality/value: The research article contributes to the current literature on intangible asset narratives, showing how the biggest pharmaceutical companies tend to achieve a competitive advantage, stay successful during a crisis and address messages to their key stakeholders. Considering the high risks and existing uncertainties, these messages could be of the utmost importance.

Reducing agricultural waste through reuse has become one of the most important strategies to minimise impact on the environment—an emerging global issue. Sunflower ranks fourth in the world in the production of vegetable oilseeds and therefore generates large amounts of agricultural waste. The aim of this study was to investigate the phytochemical composition and bioactivity of sunflower crop residues in order to open up new opportunities for waste management. TPC and TFC were determined spectrophotometrically, while the dominant compounds were identified by LC-DAD-ESI-MS as ent-kaur-16-en-19-oic acid (KA) and 6Ac-7OH-dimethylchromone (DMC). Both compounds were present in higher concentrations in the ethyl acetate fraction (245.5 and 16.8 mg/g, respectively) than in the ethanol extract. None of the tested samples showed antimicrobial effects in the microdilution test. DMC showed remarkable antioxidant activity by DPPH, ABTS, FRAP and TRC in vitro assays, while both compounds proved to be promising enzyme inhibitory agents, being particularly efficient in inhibiting anti-neurodegenerative enzymes (IC50 values of DMC and KA were 1.20/1.37 mg/mL and 1.44/1.63 mg/mL for AChE/BChE, respectively) and tyrosinase. The results presented indicate that sunflower crop residues are a good candidate for the extraction of bioactive compounds with potential application in the food, pharmaceutical and cosmetic industries.

Purpose: The purpose of the manuscript is to ascertain whether the introduction of IFRS 16 changed the reliability of financial information in companies in the NACE 77 sector. Benfordʼs Law was applied to identify errors within a selected sample of Euro-pean leasing and rental companies (NACE code 77). Methodology/approach: The study examines accounting manipulations in positive profit and loss (P&L) before tax in 2015 and 2019; Part 2 explores manipulation within negative P&L before tax in 2015 and 2019; Part 3 discovers manipulations in operating revenue in 2015 and 2019. In the empirical part of the study, MAD and Kolmogorov–Smirnov tests were applied. Findings: The study confirmed that the reliability of financial information did not change even though the small differences in the distribution of digits appeared, before and after IFRS adoption. Research limitations: Limitations from this research refers to the sample size; only companies from the leasing and rental industries are included in the study Originality/value: The study adopts Benford's Law in accounting for IFRS leasing adjustments.

Recently, growing interest is devoted to investigation of bioactive secondary metabolites of endophytic fungi. Thus, as an extension to our previous achievements related to antimicrobial potential of endophytic fungi, Phomopsis species isolated from conifer needles was selected as appropriately promising natural source for drug discovery. Its dichloromethane and ethanol extracts considerably inhibited growth of Escherichia coli and Staphylococcus aureus. Moreover, the individual compounds of dichloromethane extract have been separated, collected and purified using semi preparative liquid chromatographic analysis and comprehensively characterized using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). Based on their antimicrobial activity and unique structural characteristics in comparison with well-established drugs from the same therapeutic category, two dominant compounds (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3-(3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-3) and (Z)-(Z)-2-acetoxyprop-1-en-1-yl 3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-5) were recognized as valuable leading structures for future discovery of novel antibiotics.

Enhancing agricultural and other environmental performances has become an essential part of sustainable development policy in countries around the globe. Although Europe is considered as a global leader in the environmental competitiveness, the national economies within Europe region achieve different results in this field. The purpose of this paper is to evaluate current agricultural and other environmental performances of sixteen Central and East European (CEE) countries, but also to identify critical determinants for its improvement in the future period. The research is conducted through comparative analysis, benchmarking method, and correlation analysis. The data basis includes the Environmental Performance Index (2018). The research findings suggest the inferiority of CEE countries in the comparison with the bestranked European countries. The paper contributes to the sustainability literature and could serve as a practical guide in the process of formulating the development policies connected with agricultural and other environmental performances in CEE countries.

Standard versions of blood separators typically use medium-price color sensors for a detection of a boundary level between red blood cells and plasma, at the last gate – at hose clamps. Discrete number of sensors is related to a number of significant levels to be detected thus making blood separation potentially faulty and unreliable. Our target was to make flexible, low cost replacement for level detection system that can be easily integrated into the existing product. We came up with an image processing solution that uses USB web-camera, ARM based off-the-shelf board – BeagleBone black and free OpenCV library. Flexibility is held in much higher, selectable number of levels, freely positioned USB camera and brand-free independent processing platform, as well as semi-automatic calibration system. By adding minimum additional electronics, we managed to integrate our solution into existing Blood processing machine. In conclusion, we added a new value to the machine at lower cost in production, increasing measurement frequency and resolution needed for improvement of blood separation process. Next step is to try to use two USB cameras on a custom-made board, for simultaneous level detection on two-channel blood separator, bringing the system integration to the higher level.

Silk, traditionally acclaimed as the “queen of fiber,” has been widely used thanks to its brilliant performance such as gentleness, smoothness and comfortableness. Owing to its mechanical characteristics and biocompatibility silk has a definitive role in biomedical applications, both as fibroin and fabric. In this work, the simultaneous dyeing and functionalization of silk fabric with pigments from Streptomyces anulatus BV365 were investigated. This strain produced high amounts of orange extracellular pigments on mannitol-soy flour agar, identified as actinomycin D, C2 and C3. The application of purified actinomycins in the dyeing of multifiber fabric was assessed. Actinomycins exhibited a high affinity towards protein fibers (silk and wool), but washing durability was maintained only with silk. Acidic condition (pH5) and high temperature (65°C) facilitated the silk dyeing. The morphologies and chemical components of the treated silk fabrics were analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy. The results showed the pigments bind to the silk through interaction with the carbonyl group in silk fibroin rendering the functionalized, yet surface that does not cause skin irritation. The treated silk exhibited a remarkable antibacterial effect, while the biocompatibility test performed with 3D-reconstructed human epidermis model indicated safe biological properties, paving the way for future application of this material in medicine.

Background/Objectives: The novel pyrazoloquinolinone ligand CW-02-79 shows a unique profile of selective binding to σ2 receptors, but its poor solubility in both water and lipids makes its research and development a burdensome task. We aimed to develop a phospholipid-complex-based nanoemulsion formulation containing CW-02-79 suitable for intravenous administration in preclinical research. Methods: The decorated and undecorated nanoemulsions were formulated and subjected to detailed physiochemical characterization. The delivery and exposure to CW-02-79 from selected nanoemulsions were examined in the in vitro blood–brain barrier model based on human-induced pluripotent stem-cell-derived microvascular endothelial cells, astrocytes, and pericytes, and in vivo neuropharmacokinetic study in rats, respectively. Results: The developed biocompatible nanoemulsions loaded with a CW-02-79—phospholipid complex at a mass ratio of 1:10 exhibited a small droplet size and narrow size distribution, with satisfactory physicochemical stability during steam sterilization and short-term storage at 25 °C. The analysis of protein binding interactions revealed that the PEGylated nanoemulsions had fewer observable interactions compared to the undecorated nanoemulsions, especially when 0.2% DSPE-PEG2000 and 0.1% DSPE-PEG2000-mannose were combined. An in vitro BBB study demonstrated that a substantial part of CW-02-79 present in the applied nanoemulsion is able to permeate the barrier. The quantification of CW-02-79 in plasma/brain homogenate and calculated pharmacokinetic parameters confirmed good systemic and brain availability after intravenous administration. There were subtle differences in the pharmacokinetic parameters in favor of a dual surface-functionalized nanoemulson containing the glucose transporter-1-targeting ligand (mannose). Conclusions: The developed and characterized nanoemulsions enable substantial brain exposure to CW-02-79 as a prerequisite for a pharmacologically and clinically relevant selective modulation of σ2 receptors.

Background/Objectives: Alterations in the actin cytoskeleton correlates to tumor progression and affect critical cellular processes such as adhesion, migration and invasion. Rho-associated coiled-coil-containing protein kinases (ROCK1 and ROCK2), important regulators of the actin cytoskeleton, are frequently overexpressed in various malignancies. The aim of this study was therefore to identify the key structural features of ROCK1/ROCK2 inhibitors using computer-aided drug design (CADD) approaches. In addition, new developed ROCK inhibitors provided a significant framework for the development of multitarget therapeutics—ROCK/HDAC (histone deacetylases) multitarget inhibitors. Methods: 3D-QSAR (Quantitative structure-activity relationship study) and molecular docking study were employed in order to identify key structural features that positively correlate with ROCK inhibition. MDA-MB-231, HCC1937, Panc-1 and Mia PaCa-2 cells were used for evaluation of anticancer properties of synthesized compounds. Results: C-19 showed potent anti-cancer properties, especially enhancement of apoptosis and cell cycle modulation in pancreatic cancer cell lines. In addition, C-19 and C-22 showed potent anti-migratory and anti-invasive effects comparable to the well-known ROCK inhibitor fasudil. Conclusions: In light of the results of this study, we propose a novel multi-target approach focusing on developing dual HDAC/ROCK inhibitors based on the structure of both C-19 and C-22, exploiting the synergistic potential of these two signaling pathways to improve therapeutic efficacy in metastatic tumors. Our results emphasize the potential of multi-target ROCK inhibitors as a basis for future cancer therapies.

Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.

Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditiselegans at concentrations up to 50 µg/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br2, respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski’s “rule of five”, with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.

A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy (Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Serratia marcescens. Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7:2:1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semi-synthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 μg mL-1 and 75 μg mL-1, respectively. None of the di-rhamnolipids exhibited antimicrobial properties at concentrations of up to 500 μg mL-1. Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 μg mL-1. Semi-synthetic amide derivatives showed increased antibacterial activity against S. aureus, and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.