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The aim of the article is to determine the features of the relationship between innovative entrepreneurship and external effects arising from the introduction of innovations, from the standpoint of understanding under what conditions the losses that society bears, also the numerous complex risks from the introduction of innovations, can be acceptable, justified and properly compensated. In a complex, dynamic world, innovative technology and entrepreneurship play a crucial role in overall economic development. Along with this, the carried out study of many aspects of the impact of innovation and innovative entrepreneurship on economic growth and development of society has also revealed a significant number of negative external effects that arise at different economic levels and which today are almost not regulated. These external effects accumulate, transform, and give rise to other additional effects. Despite a large number of studies, various attempts by scholars to advance in the elimination of negative externalities have not yet provided an adequate organizational and methodological approach to such an internalization of these effects, which could be considered quite effective. Based on the analysis of scientific sources, one of the main reasons for the imperfect mechanism for eliminating the negative consequences of externalities of innovation activity is the insufficiency of the development of the taxonomy of externalities – due to the lack of progress in the establishment and distribution of property rights to external effects and the appropriate differentiation of possible types of externalities in terms of their significance and scale. The existing institutional possibilities of such regulation are not satisfactory and should be transformed in accordance with the new socioeconomic needs of society. The authors also note that due to the increased complexity and lack of a universal approach to the valuation of external effects, the development of an appropriate mechanism for regulating externalities actualizes the study of a broader issue of management accounting in the context of the above problem.

The article is aimed at defining the peculiarities of the digitalization process in the business environment of the national economy and formalizing the conceptual-methodical approach to assessing the impact of this process on business development. The article studies the actual scientific and practical issue of the impact of digital transformations on the results of economic activity of the business sector as the main driving force of the national economy. The importance of digitalization and the need to understand its multi-aspectuality and peculiarities of the course in socioeconomic systems of different levels are emphasized. Since the process of digital transformation goes beyond the boundaries of individual economic entities and sectors of the national economy, it is concluded that a full and in-depth analysis of the impact of factors of digital transformations on the development of the business sector should be carried out covering the changes that occur at the micro, meso and macro levels. A conceptual-methodical approach to analyzing the results of digital transformation in the economy with an emphasis on the entrepreneurial sector has been proposed. The approach includes the use of a system of indicators to conduct a comprehensive assessment of the progress of digital transformation at each of the above levels. At the micro level, the state of digitalization of the internal environment of economic entities is studied. At the meso level, digital transformations within industry and cross-sectoral interaction are monitored. At the macro level, national processes in the business sector are studied under the influence of the implementation of the State digital strategy and policy. The important role of the State in promoting digital innovations and stimulating the development of new technologies in favor of the national economy is underlined. It is noted that the implementation of the proposed approach requires the creation of a certain information, analytical, and organizational support.

Due to uncontrolled growth of antimicrobial resistance, in the near future humanity may return to the «pre-antibiotic era» with no reliable antimicrobial therapy even for previously easily treatable infectious diseases. One of possible solutions is improved delivery of antibiotics to antibiotic-resistant bacterial strains by conjugating them with siderophores (small molecules secreted by microorganisms to absorb essential Fe(III)). The siderophore-modified antibiotic (sideromycin), like a Trojan horse, permeates the bacterial cell as a complex with Fe(III), allowing the antibiotic to reach its biological target. In this review, we describe the structural diversity of siderophore-antibiotic conjugates with the focus on the structure of sideromycin as well as on the relationship between the structure of sideromycin and its antibacterial activity. We analyze main representatives of various classes of siderophores; the structural diversity of sideromycins and their antibacterial activity discussed in detail.

The content of the article actualizes a number of important issues as to provision of policy in the sphere of supporting innovative entrepreneurship. In the course of their study, the authors note that the socio-economic development of countries is influenced by the degree of innovativeness of the economy. This encourages to consider innovative entrepreneurship as an important resource for the development of innovative processes in the country, and the support of innovative entrepreneurship is considered a key factor in solving the main problems of sustainable socio-economic development of the regions of Ukraine. The country has a fairly strong base for scientific and technical developments, a powerful innovation potential, but there are problems with implementation of the latter due to insufficient focus on the formation of an effective innovative policy and the policy of development of small and medium-sized enterprises (SMEs), which are the main suppliers of innovations in the national innovation system. The results of the study draw attention to the feasibility of integrating innovative policies with the corporate social responsibility development policies and the SME development policies. An integration will allow achieving greater economic return and social benefits through the implementation of a more efficient relationship between the providers of socio-economic development of region on the organization and provision of opportunities for the development of complex regional, interregional and global value-creating networks. This approach also involves taking into account the factors influencing the innovation dynamics with the constant improvement of the system of formation and implementation of the State and regional priorities in the field of regulation of science, investment, innovation, entrepreneurial and socially responsible activities, in accordance with the implementation of the principles of sustainable development.

The results of a study of gelation peculiarities in chitosan solutions in the presence of a cross-linking agent of natural origin and biocompatible properties of films obtained on the basis of the chitosan-solution-genipin gelling system are presented. The possibility of controlling the swelling degree of the films from 300 to 1800% are shown. [ABSTRACT FROM AUTHOR]

The influence of the conditions of the formation of chitosan hydrogels crosslinked with glutaraldehyde ( GA) or genipin (the polysaccharide molecular weight, pH level, and concentration of the chitosan solution) on the gel time and the properties of biopolymer scaffolds for tissue engineering obtained by the freeze-drying of hydrogels was studied. The resulting scaffolds had different structures (morphology, degree of anisotropy, average pore size) and moisture-retaining capacities. The cytotoxicity of biodegradable scaffolds based on chitosan with a low content of genipin and GA was studied for the first time. Using the L929 mouse fibroblasts model line, we demonstrated that scaffolds based on chitosan with a molecular weight of 320 and 190 kDa crosslinked with genipin and GA (0.005 and 0.01 mol/mol of chitosan amino groups) are biocompatible. Using confocal laser microscopy, we demonstrated that the cells are uniformly distributed in all scaffold samples and they successfully grew and proliferated when cultured in vitro for 4 days. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is one of the most serious global health threats. Therefore, there is a need to develop antimicrobial agents with new mechanisms of action. Targeting of bacterial cystathionine γ-lyase (bCSE), an enzyme essential for bacterial survival, is a promising approach to overcome antibiotic resistance. Here, we described a series of (heteroarylmethyl)benzoic acid derivatives and evaluated their ability to inhibit bCSE or its human ortholog hCSE using known bCSE inhibitor NL2 as a lead compound. Derivatives bearing the 6-bromoindole group proved to be the most active, with IC 50 values in the midmicromolar range, and highly selective for bCSE over hCSE. Furthermore, none of these compounds showed significant toxicity to HEK293T cells. The obtained data were rationalized by ligand-based and structure-based molecular modeling analyses. The most active compounds were also found to be an effective adjunct to several widely used antibacterial agents against clinically relevant antibiotic-resistant strains of such bacteria as Staphylococcus aureus , Klebsiella pneumoniae , and Pseudomonas aeruginosa . The most potent compounds, 3h and 3i, also showed a promising in vitro absorption, distribution, metabolism, and excretion (ADME) profile. Finally, compound 3i manifested potentiating activity in pneumonia, sepsis, and infected-wound in vivo models.

An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC 50  = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.

A novel 3,4-dihydroisoquinol-1-one-4-carboxamide scaffold was designed as the basis for the development of novel inhibitors of poly(ADP-ribose) polymerase (PARP). Synthesis of 3,4-dihydroisoquinol-1-one-4-carboxylic acids was achieved using the previously developed protocol based on the modified Castagnoli-Cushman reaction of homophthalic anhydrides and 1,3,5-triazinanes as formaldimine synthetic equivalents. Employment of 2,4-dimethoxy groups on the nitrogen atom of the latter allowed preparation of 2,3-unsubatituted 3,4-dihydroquinolone core building blocks. Iterative synthesis and in vitro biological testing of the amides resulting from the amidation of these carboxylic acids allowed not only drawing important structure-activity generalisations (corroborated by in silico docking simulation) but also the identification of the lead compound, 4-([1,4'-bipiperidine]-1'-carbonyl)-7-fluoro-3,4-dihydroisoquinolin-1(2 H )-one, as the candidate for further preclinical development. The lead compound as well as its des-fluoro analog were compared to the approved PARP1 inhibitor, anticancer drug Olaparib, in terms of their molecular characteristics defining druglikeness as well as experimentally determined ADME parameters. The newly developed series demonstrated clear advantages over Olaparib in terms of molecular weight, hydrophilicity, human liver microsomal and plasma stability as well as plasma protein binding. Further preclinical investigation of the lead compound is highly warranted.

The influence of the conditions of the formation of chitosan hydrogels crosslinked with glutaraldehyde (GA) or genipin (the polysaccharide molecular weight, pH level, and concentration of the chitosan solution) on the gel time and the properties of biopolymer scaffolds for tissue engineering obtained by the freeze-drying of hydrogels was studied. The resulting scaffolds had different structures (morphology, degree of anisotropy, average pore size) and moisture-retaining capacities. The cytotoxicity of biodegradable scaffolds based on chitosan with a low content of genipin and GA was studied for the first time. Using the L929 mouse fibroblasts model line, we demonstrated that scaffolds based on chitosan with a molecular weight of 320 and 190 kDa crosslinked with genipin and GA (0.005 and 0.01 mol/mol of chitosan amino groups) are biocompatible. Using confocal laser microscopy, we demonstrated that the cells are uniformly distributed in all scaffold samples and they successfully grew and proliferated when cultured in vitro for 4 days.

In this paper, characterization is given of clinical and biochemical features of VH B course against the background of narcomania. Recordable in such patient populations are high percentage of delta hepatitis (14.2%), unusual severity of the intoxication syndrome, protracted course with exacerbations (12.2%) and recurrences (8%), outcome being a chronic hepatitis (14.2%), slower normalization of biochemical indicators, persistently low ratio of AIAT activity in diluted and whole blood sera. The persistence of viral markers in drug addicts discharged from the hospital (68%) is fraught with danger of spreading viral hepatitis of prophylactic measures are not strictly observed.

Intestinal excretion of free bile acids (BA), i.e. of cholic, chenodeoxycholic, deoxycholic, lithocholic, and of conjugated BA, i.e. of glycocholic, glycodeoxycholic together with glycochenodeoxycholic, taurocholic, taurodeoxycholic together with taurochenodeoxycholic acids, was examined in patients with viral hepatitides (VH), chronic hepatitis (CH), biliary cirrhosis of the liver (BCL), and acute dysentery (AD), as were the effects of therapy on these acid levels. The findings evidence that fecal levels of free BA are significantly reduced during the acute period of VH, CH, AD, and BCL, whereas the levels of conjugated acids are elevated in all the examinees except the BCL patients, in whom these acids are unchanged. Study of BA excretion in VH patients treated with prednisolone has demonstrated a normalizing effect of this therapy on the spectrum of excreted free BA. Furazolidone and erythromycin therapy resulted in disordered transformation of 'primary' BA into 'secondary' ones and to deconjugation of BA, this being possibly related to these drugs effects on intestinal microflora.

Total activity and isoenzymic spectrum of the blood serum and liver alkaline phosphatase were studied with experimental obstructive jaundice beginning from the first hours of its development till 30 days. Changes in the activity of alkaline phosphatase and its isoenzymic spectrum are shown to have their characteristic features at different times of obstructive jaundice.

The activity and isoenzymic spectrum of alkaline phosphatase of the blood serum and liver under cholemia caused by deoxycholic acid were compared in healthy animals and in animals with the affected liver. It is shown, that under conditions of the bile acids higher content in the organism due to deoxycholic acid, the total activity increases considerably and there appears an isoenzyme absent in the blood serum of healthy animals. Changes in the activity and isoenzymic spectrum of alkaline phosphatase under experimental cholemia developing against a background of the healthy and affected liver are characterized by certain peculiarities.

Activity of alanine and aspartate aminotransferase, alkaline phosphatase, adenosine, desaminase and AMP-aminohydrolase was determined in rats in the process of the liver regeneration under acute and chronic lesion with CCl4. It is shown that under chronic lesion of the liver with CCl4, in contrast to the acute one, changes in the aminotransferase activity in blood serum are not expressed in the liver, the activity is essentially decreased. A steady increase was observed in the activity of adenosine desaminase, AMP-aminohydrolase and alkaline phosphatase in the liver and blood serum. It is concluded that the normal regenerative process is accompanied by short-term shifts of the enzymes activity in the liver and blood serum. The development of a chronic process results in a characteristic increase in the activity of adenosine desaminase, AMP-aminohydrolase and alkaline phosphatase in the liver and blood serum.

After partial hepatoectomy of the rat normal liver a maximum three-fold increase in the activity of alkaline phosphatase is observed in the blood serum, on the second-third day, and by the 14th day becomes almost normal; the activity of adenosine desaminase, AMP-aminohydrolase and 5'-nucleotidase becomes 30-60% as high for one-two days. The activity of the alkaline phosphatase in the liver becomes four times as high and reaches normalcy by the sixth day. The activity of adenosine desaminase and AMP-aminohydrolase increases to a less extent for a fortnight. The activity of 5'-nucleotidase decreases in the first day, then rises and a fortnight later becomes normal. After partial hepatoectomy of the liver injured with deoxicholic acid the activity of all the enzymes in blood serum anr a longer period of time; in the 5'-nucleotidase activity there is no initial drop and its earlier subsequent increase is observed.