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Different Chiral Ionic Liquids (CIL) based on L-proline have been developed. Simple and efficient synthetic methodologies are used, allowing preparation in good yields for twelve novel CILs using L-proline as a cation or anion combined with suitable counter-ions. A detailed physical and chemical characterization of the CILs was performed to evaluate the influence of counter-ions on the final properties. The most promissory CILs were tested as efficient chiral catalysts in IL media for asymmetric Michael addition reactions of ketones and aldehydes to nitro-olefins. Similar or even better conversions and enantioselectivities (ee up to 95%) compared to the original L-proline were achieved. Additionally, a good product extraction performance using supercritical CO2 processes was obtained. [ABSTRACT FROM AUTHOR]

Precise anticancer therapies employing cytotoxic conjugates constitute a side-effect-limited, highly attractive alternative to commonly used cancer treatment modalities, such as conventional chemotherapy, radiotherapy or surgical interventions. Receptor tyrosine kinases are a large family of N-glycoproteins intensively studied as molecular targets for cytotoxic conjugates in various cancers. At the cell surface, these receptors are embedded in a dense carbohydrate layer formed by numerous plasma membrane glycoproteins. The complexity of the cell surface architecture is further increased by galectins, secreted lectins capable of recognizing and clustering glycoconjugates, affecting their motility and activity. Cell surface N-glycosylation is intensively remodeled by cancer cells; however, the contribution of this phenomenon to the efficiency of treatment with cytotoxic conjugates is largely unknown. Here, we evaluated the significance of N-glycosylation for the internalization and toxicity of conjugates targeting two model receptor tyrosine kinases strongly implicated in cancer: HER2 and FGFR1. We employed three conjugates of distinct molecular architecture and specificity: AffibodyHER2-vcMMAE (targeting HER2), vcMMAE-KCK-FGF1.E and T-Fc-vcMMAE (recognizing different epitopes within FGFR1). We demonstrated that inhibition of N-glycosylation reduced the cellular uptake of all conjugates tested and provided evidence for a role of the galectin network in conjugate internalization. In vitro binding studies revealed that the reduced uptake of conjugates is not due to impaired HER2 and FGFR1 binding. Importantly, we demonstrated that alteration of N-glycosylation can affect the cytotoxic potential of conjugates. Our data implicate a key role for cell surface N-glycosylation in the delivery of cytotoxic conjugates into cancer cells. [ABSTRACT FROM AUTHOR]

Structure, and consequently properties, of ionic liquids can be easily tailored by changing cation/anion combinations and/or attaching functional groups. By grafting enantiopure moieties to the framework of ionic liquid it is possible to prepare bioinspired chiral molecules that can serve as a reaction medium, additive or even asymmetric catalyst. In this context, new chiral ionic liquids (CILs), based on biomolecules, such as aminoacids (l-Cysteine derivatives), have been synthesised and tested in asymmetric aldol condensation of aldehydes and ketones. The best results were obtained for CILs composed of S-methyl-l-cysteine cation and bis(trifluoromethane)sulfonimide anion, in the reaction of 2- or 4-nitrobenzaldehyde with acetone or cyclohexanone, giving the aldol product in moderate yields 70–76% and high ee values (up to 96%). [ABSTRACT FROM AUTHOR]

This study's aim is to determine the consistency of student opinions regarding the importance of individual skills in three areas—people, practice, and perspective—with expert assessment. The study group consisted of five-year students accredited by IPMA Poland. The team of experts was comprised of recruiters, project management lecturers, assessors, and information technology (IT) industry project managers. Our research shows divergences in the approach to key competence that a project manager should have. This is understandable, given the specifics of the comparison. However, the analysis that has been conducted and presented will allow the curricula to be revised. The subsequent evaluation of curricula should address the changes in the labor market. Education should provide key competences, especially as modern project management requires a full spectrum of competences and approaches. Besides experience, project management is the most frequently pursued competence that is required in terms of staff recruitment criteria. The research resulting figures may be useful for recruiters, certification institutions, and universities. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute signaling circuits that transmit signals across the plasma membrane, regulating pivotal cellular processes like differentiation, migration, proliferation, and apoptosis. The malfunction of FGFs/FGFRs signaling axis is observed in numerous developmental and metabolic disorders, and in various tumors. The large diversity of FGFs/FGFRs functions is attributed to a great complexity in the regulation of FGFs/FGFRs-dependent signaling cascades. The function of FGFRs is modulated at several levels, including gene expression, alternative splicing, posttranslational modifications, and protein trafficking. One of the emerging ways to adjust FGFRs activity is through formation of complexes with other integral proteins of the cell membrane. These proteins may act as coreceptors, modulating binding of FGFs to FGFRs and defining specificity of elicited cellular response. FGFRs may interact with other cell surface receptors, like G-protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). The cross-talk between various receptors modulates the strength and specificity of intracellular signaling and cell fate. At the cell surface FGFRs can assemble into large complexes involving various cell adhesion molecules (CAMs). The interplay between FGFRs and CAMs affects cell–cell interaction and motility and is especially important for development of the central nervous system. This review summarizes current stage of knowledge about the regulation of FGFRs by the plasma membrane-embedded partner proteins and highlights the importance of FGFRs-containing membrane complexes in pathological conditions, including cancer. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptors (FGFRs) in response to fibroblast growth factors (FGFs) transmit signals across the cell membrane, regulating important cellular processes, like differentiation, division, motility, and death. The aberrant activity of FGFRs is often observed in various diseases, especially in cancer. The uncontrolled FGFRs' function may result from their overproduction, activating mutations, or generation of FGFRs' fusion proteins. Besides their typical subcellular localization on the cell surface, FGFRs are often found inside the cells, in the nucleus and mitochondria. The intracellular pool of FGFRs utilizes different mechanisms to facilitate cancer cell survival and expansion. In this review, we summarize the current stage of knowledge about the role of FGFRs in oncogenic processes. We focused on the mechanisms of FGFRs' cellular trafficking—internalization, nuclear translocation, and mitochondrial targeting, as well as their role in carcinogenesis. The subcellular sorting of FGFRs constitutes an attractive target for anti-cancer therapies. The blocking of FGFRs' nuclear and mitochondrial translocation can lead to the inhibition of cancer invasion. Moreover, the endocytosis of FGFRs can serve as a tool for the efficient and highly selective delivery of drugs into cancer cells overproducing these receptors. Here, we provide up to date examples how the cellular sorting of FGFRs can be hijacked for selective cancer treatment. [ABSTRACT FROM AUTHOR]

In the rapidly developing field of targeted cancer therapy there is growing interest towards therapeutics combining two or more compounds to achieve synergistic action and minimize the chance of cancer resistance to treatment. We developed a fibroblast growth factor 2 (FGF2)-conjugate bearing two cytotoxic drugs with independent mode of action: α-amanitin and monomethyl auristatin E. Drugs are covalently attached to the targeting protein in a site-specific manner via maleimide-thiol conjugation and Cu(I)-catalyzed alkyne-azide cycloaddition. The dual warhead conjugate binds to FGF receptor 1 (FGFR1) and utilizes receptor-mediated endocytosis for selective internalization into cancer cells with FGFR1. The developed conjugate displays high cytotoxicity towards all tested FGFR1-positive cell lines. Most importantly, the improved cytotoxic effect of both drugs is observed for lung cancer cell line NCI-H446. The single drug-FGF2 conjugates have no impact on the viability of NCI-H446 cells, whereas the dual warhead-FGF2 conjugate selectively and efficiently kills these FGFR1 positive cancer cells. Due to the diversified mode of action the dual warhead-FGF2 conjugate may overcome the potential acquired resistance of FGFR1-overproducing cancer cells towards single cytotoxic drugs. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) fused to highly cytotoxic drugs (warheads). The efficiency of ADC strategy largely depends on the internalization of cytotoxic conjugate into cancer cells. Here, we have studied an interplay between affinity of anti-FGFR1 antibodies and efficiency of their cellular uptake. We have developed a unique set of engineered anti-FGFR1 antibodies that bind the same epitope in the extracellular part of FGFR1, but with different affinities. We have demonstrated that these antibodies are effectively taken up by cancer cells in the FGFR1-dependent manner. Interestingly, we have found that efficiency, defined as rate and level of antibody internalization, largely depends on the affinity of engineered antibodies towards FGFR1, as high affinity antibody displays fastest internalization kinetics. Our data may facilitate design of therapeutically relevant targeting molecules for selective treatment of FGFR1 overproducing cancers. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine how different doses of phytase in diets with extruded soybean seeds and rapeseed meal affected pigs' growth performance, meat quality, bone mineralization, and fatty acid profiles. Sixty pigs were divided into three treatments by sex and body mass. Pigs were divided into starter (25 days), grower (36 days), and finisher (33 days) periods and fed with mash diets. No phytase was used in the control group diet, whereas in Phy1 and Phy2, 100 g and 400 g of phytase per ton of mixture were used, respectively. The feed conversion ratio and meat color were significantly correlated with phytase. Phytase supplementation had no effect on the growth of pigs, but total phosphorus was significantly increased in the bones and meat of the pigs. The enzyme additive reduced the C22:4 n-6 acid content in the meat, whereas other results were not significantly affected. The data suggest that the addition of phytase at a dosage of 100 g/ton to diets with extruded full-fat soya seeds and rapeseed meal can be valuable, as it reduces the FCR and increases the P content in the meat and bones. [ABSTRACT FROM AUTHOR]

Simple Summary: Plants store phosphorus mainly in phytate form, which is slightly digestible by pigs due to the lack of native phytase. Some thermal processes, such as extrusion and exogenous phytase additives, can reduce phytate content in the diet, but the effectivity of the enzyme in diets including processed and unprocessed legume seeds needs to be better recognized. This study aims to investigate the effect of the addition of two phytase dosages to a diet containing raw lupine seeds and full-fat extruded soya seeds on the performance of growing pigs in terms of their carcasses, pork quality, and bone mineralization. Phytase significantly improved the pigs' growth and feed utilization in the starter period and affected some meat, fat, and bone parameters. Higher phytase dosages did not improve the pigs' performance, but only increased calcium deposition in their bones. This study aims to determine how different doses of phytase in diets including extruded soya and lupine seeds affect fatteners' performance, meat quality, bone mineralization, and fatty acid profile. Sixty pigs were divided into three treatment groups. The control group was offered a diet without phytase, whereas the Phy100 and Phy400 groups were provided with 100 g and 400 g of phytase per ton of their diet, respectively. The animals from both experimental groups were characterized by a significantly (p < 0.05) higher body weight gain and lower feed efficiency in the starter period than the control group. Unfortunately, their meat had lower (p < 0.05) fat content, gluteal muscle thickness, and water-holding capacity. In the meat, a higher phosphorus content (p < 0.05) was found, and in the bones, a higher calcium (for Phy400) content was found when phytase was added to the pigs' diet. The pigs from the Phy100 group tended to have higher mean backfat thickness and C18:2 n-6 content in their fat, but lower C22:5 n-3 content, than the other groups. A higher dosage of phytase is not necessary for the diets of fatteners with extruded full-fat soya and lupin seeds. [ABSTRACT FROM AUTHOR]

This study aimed to assess the applicability of eleven different products of solid-state fermentation of rapeseed cakes with commercial enzyme additives. Ground rapeseed cakes were mixed with water (1:2) and the enzymatic preparation (0.1%) according to the different variants and fermented at 25 °C for 24 h under anaerobic conditions. For fermentation, different enzymes were used: (1) α-amylase, (2) endo 1,4-β-xylanase, (3) endo-1,3(4)β-glucanase, (4) endo 1,4-β-xylanase, endo-1,3(4)β-glucanase, (5) α-amylase, endo-1,3(4)β-glucanase, (6) 6-phytase, (7) RONOZYME HiPhos 6-phytase, (8) liquid exogenous-6-phytase; and mixed combinations: (9) endo 1,4-β-xylanase, endo-1,3(4)β-glucanase, liquid exogenous-6-phytase, (10) α-amylase, endo-1,3(4)β-glucanase, liquid exogenous-6-phytase, and (11) α-amylase, endo 1,4-β-xylanase, endo-1,3(4)β-glucanase, liquid exogenous-6-phytase. After fermentation, the crude protein content in the products was similar, but the true protein content was significantly higher than in nonfermented rapeseed cakes (p < 0.05). Fermentation significantly reduced (p < 0.05) the levels of phytate phosphorous, raffinose family oligosaccharides, and glucosinolates in the products. In the next step, the most advantageous fermentation product obtained using liquid exogenous-6-phytase was selected in terms of nutritional value, produced on the technical scale, and incorporated into the diets for broilers. Six diets containing 12, 17, or 22% raw or fermented rapeseed cakes, respectively, were prepared. Up to 22% fermented rapeseed cakes did not adversely affect broiler production rates. Replacing raw rapeseed cakes with fermented products improved body weight gain in the grower phase, lowered feed intake in the finisher phase, and lowered the feed conversion ratio in all periods. A level of 22% of naturally fermented rapeseed cakes with liquid exogenous-6-phytase in the diet of broilers could be recommended. [ABSTRACT FROM AUTHOR]

The worldwide surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and led governments to control spread of the virus and provide care for the population affected by the infection. Although, in children, COVID-19 is usually asymptomatic or mild (except PIMS), the pandemic affected the whole socioeconomic system and led to the overwhelming of healthcare facilities. We report retrospective observations of the prevalence of various infectious diseases during the SARS-CoV-2 pandemic in a tertiary multidisciplinary pediatric center in Southern Poland. We retrospectively evaluated the impact of the SARS-CoV-2 pandemic on the number of other infections diagnosed in a pediatric tertiary care referral center. Our analysis included the period from the beginning of February to the end of April 2020 (spring pandemic wave), and from the beginning of September to the end of November 2020 (autumn pandemic wave). We compared them to the appropriate periods of 2019. The evaluation included blood, urine, stool and lover respiratory tract cultures as well as virological investigations. Additionally, the costs of antibiotics and antifungal drugs in selected departments were assessed. Our analysis showed considerable reduction in the majority of common infections except for influenza A and B. The microbiological data correspond with economical summary of antibiotic costs, which were significantly lower during the pandemic. One exception was the number of positive blood cultures, which increased even though the overall number of tests was lower. A general reduction of the number of infections diagnosed in children could result from the implemented preventative measures associated with the pandemic and the generally increased awareness of the risk of infection among parents and guardians. The treatment of the most serious diseases continued as it did before the pandemic. To our knowledge, this study is the first attempt to assess the impact of the COVID-19 pandemic on the prevalence of infections in a large pediatric center. Further research on the impact of the COVID-19 pandemic on the healthcare systems is necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Faba beans could be a valuable raw material in pigs' diets, but the presence of anti-nutritional factors limits their wide use. The aim of the study was to investigate how the extrusion of faba bean seeds and/or the addition of protease to pigs' diets affected the animals' growth parameters, digestibility of nutrients, selected physiological parameters of the digestive tract, and biochemical blood parameters. Our research showed that extrusion increased the nutritional value of faba bean seeds, especially by reducing antinutritional factors, but in comparison with raw seeds, it did not improve the pigs' growth performance, digestibility of nutrients, intestinal structure, and physiology when the content of faba beans in the diet was below 10%. Thanks to protease supplementation in our study, protein and oil levels in the diet were reduced while maintaining the same pigs' performance, which cut the cost of feeding. The extrusion and enzyme additives did not improve the pigs' growth performance in this experiment, but protease appears to be highly promising in the commercial nutrition of pigs. The aim of the study was to investigate how the extrusion of faba bean seeds (var. Albus) and/or the addition of protease to pigs' diets affected the animals' growth parameters, digestibility of nutrients, selected physiological parameters of the digestive tract, and biochemical blood parameters. A 28-day experiment was conducted on 32 pigs weighing 9 ± 0.2 kg. The animals were allocated to four treatments in a 2 × 2 factorial arrangement with the main effects of extrusion (raw or extruded) and effects of protease supplementation (0 and 0.05%). Extrusion reduced the levels of neutral detergent fibre, trypsin inhibitor, phytate-P, and resistant starch but did not improve the digestibility of protein and dry matter in faba bean seeds. The pigs' growth performance, ileal digestibility, enzyme activity, and morphometric parameters of the ileum were not significantly affected by extrusion, except for a higher feed intake between the 15th and 28th day of the experiment. The protease supplementation gave comparable results as the diet without protease, except the feed conversion ratio (in the periods of 15–28th day and 0–28th day), which was higher than in the groups without protease. The extrusion and protease increased acetate and acetoacetate contents in the cecal digesta, but propionate, butyrate, and isovalerate concentrations in the digesta of the pigs in this group were lower. Thanks to protease supplementation, protein and oil levels in the diet were reduced, which cut the cost of feed mixtures. The extrusion and protease additive combined together did not improve the pigs' growth performance in this experiment. [ABSTRACT FROM AUTHOR]

Simple Summary: Fermented feed in growing pig nutrition may influence microbiota of the gastrointestinal tract, improve utilization of nutrients from the diet, and reduce the level of excreted ammonia and phosphorus released into the environment. In the research, fermentation of narrow-leafed lupine seeds was provided and fermented seeds were added to the pigs' diet. In the 28-day experiment, 24 male pigs were divided into three groups. The control group was fed a soybean meal diet, whereas in the experimental diets, 50% of soybean meal (SBM) protein was replaced by raw or fermented lupine seeds. The influence of fermentation on performance results, gut environment and physiology, and selected blood metabolic parameters in young pigs, were analyzed. Fermentation did not affect pigs' performance, metabolic, microbial and most gastrointestinal tract parameters, but influenced crypt depth, concentrations of short chain fatty acids and p-cresole in the proximal colon segment, and significantly lowered the pH of the middle colon digesta and ammonia contents. Fermentation improved the chemical composition of seeds, but due to the lack of a significant improvement in the performance, the results may prove to be economically unviable. The aim of this study was to: (1) provide controlled fermentation of narrow-leafed lupine seeds; (2) monitor seed composition, and (3) determine the influence of fermentation on the performance, gut environment and physiology, and selected blood metabolic parameters, in young pigs. Firstly, the effect of 24 h lupine seed fermentation by bacteria and yeast on seed chemical composition was determined. It increased contents of crude protein, crude fiber and ash, but reduced nitrogen-free extractive levels. The amino acid profile of fermented lupine (FL) was similar to that of raw lupine (RL) seeds, whereas the contents of oligosaccharides and P-phytate decreased significantly, in contrast to alkaloids. In fermented feed, pH dropped from 5.5 to 3.9. In the 28-day experiment, 24 male pigs were divided into three groups. The control group was fed a soybean meal diet (SBM), whereas in the experimental diets, 50% of SBM protein was replaced by RL or FL. Afterwards, eight pigs from each group were euthanized and their digesta and blood samples were collected. The FL use did not affect pigs' performance, nor their metabolic, microbial and most gastrointestinal tract parameters, but influenced crypt depth. Fermentation affected concentrations of short chain fatty acids and p-cresole in the proximal colon segment. In the small intestine, the levels of acetate and butyrate decreased, and, in the caecum, the propionate level decreased. Fermentation significantly lowered the pH of the middle colon digesta and ammonia contents compared to RL. A part of SBM may be successfully replaced by RL and FL in young pigs' diets. [ABSTRACT FROM AUTHOR]

Simple Summary: Soy is the major source of protein in animal feeds worldwide. In Europe, only GMO-free varieties may be cultivated. Their chemical composition, contamination by fungi and yeast and the acceptable level in the diet of pigs have not been fully determined yet. This work comprised extensive analyses, both chemical (the composition of amino acids and anti-nutritional factors) and microbiological, also including mycotoxins. Moreover, digestibility and performance parameters were studied in 48 male post-weaning piglets for 28 days using diets, in which soybean meal was replaced by 0%, 5%, 10%, 15%, 20% and 25% soybean seed addition. The chemical composition of soybean seeds differed in terms of crude protein, ether extract, neutral detergent fibre and antinutrient contents. Seeds were also contaminated (but to varying intensity, which may have been influenced by the weather conditions during the seed harvest period) with fungi, yeast and mycotoxins, mainly zearalenone and deoxynivalenol. The digestibility coefficients of crude protein and dry matter in the diet were similar. Pigs' performance parameters were reduced strongly with increasing amounts of raw seeds in their diets, so a 5% of raw soy seed supplementation in pigs' diet is recommended. The aim of this study was to compare the chemical composition of European soy seeds. A mycological and toxigenic screening was carried out on 18 varieties of soy seeds harvested in Poland. Moreover, the level of soybean meal (SBM) substitution by raw soybean seeds was analysed in terms of its effect on young pigs' performance (body weight gain, feed intake, feed utilisation) along with apparent total tract digestibility (ATTD) of dry matter and crude protein in the diets. In a 28-day trial, 48 male pigs were tested using a marker method with TiO2. In their diets, SBM was replaced by soy seeds in the amounts of 0%, 5%, 10%, 15%, 20% and 25%. In the last 3 days of the experiment, samples of excreta from each animal separately were collected three times per day. The chemical composition of soybean seeds differed in terms of their contents of crude protein, ether extract, neutral detergent fibre and raffinose family oligosaccharides, as well as the trypsin inhibitor activity. Seeds were also contaminated with fungi, yeast and mycotoxins, mainly zearalenone and deoxynivalenol. The ATTD of crude protein ranged from 70.6% to 77.6% and that of dry matter from 93.5% to 94.6%, with no differences between the groups being found (p > 0.05). Pigs' performance parameters were reduced strongly with increasing amounts of raw seeds in the diets (p < 0.05). The results indicate that only a 5% addition of raw soy seeds in pigs' diet is recommended. [ABSTRACT FROM AUTHOR]