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Reversible cholinesterase (ChE) inhibitors are widely used drugs for the therapy of various cognitive and neurodegenerative disorders. The development of a "universal drug" with easily tunable ChE inhibition activity is a relevant interdisciplinary problem. Here we propose for the first time the design of novel "fine-tuned" ChE inhibitors based on dendrimers with a thiacalix[4]arene core (PAMAM-calix-dendrimers). A series of first-generation PAMAM-calix-dendrimers with different terminal fragments were designed and synthesized. The human acetylcholinesterase and butyrylcholinesterase inhibition by PAMAM-calix-dendrimers was confirmed by molecular docking and in vitro studies. PAMAM-calix-dendrimers were found to have IC 50 values for acetylcholinesterase and butyrylcholinesterase in the range of 0.076-5400 μM. Relationships between the structure of PAMAM-calix-dendrimers and the ChE inhibitory activity were established. The conformation of the macrocyclic core and the nature of the terminal groups were found to exert a direct impact on the inhibitory activity of dendrimers. We anticipate our study to be a starting point for creation of "universal drug" with tunable ChE inhibitory activity to specific therapeutic targets, and more sophisticated in vivo studies of such systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

D-Mannose 2-epimerase (MEase) catalyzes the bioconversion between D-glucose and D-mannose. It is an important potential biocatalyst for large-scale production of D-mannose, a functional monosaccharide used in pharmaceutical and food industries. In this study, a new microbial MEase was characterized from Runella zeae DSM 19591. The enzyme was purified by one-step nickel-affinity chromatography and determined to be a dimeric protein with two identical subunits of approximately 86.1 kDa by gel filtration. The enzyme showed the highest activity at pH 8.0 and 40 °C, with a specific activity of 2.99 U/mg on D-glucose and 3.71 U/mg on D-mannose. The melting temperature (T m ) was 49.4 °C and the half-life was 115.14 and 3.23 h at 35 and 40 °C, respectively. The purified enzyme (1 U/mL) produced 115.7 g/L of D-mannose from 500 g/L of D-glucose for 48 h, with a conversion ratio of 23.14 %. It was successfully expressed in Bacillus subtilis WB600 via pP43NMK as the vector. The highest fermentation activity was 10.58 U/mL after fed-batch cultivation for 28 h, and the whole cells of recombinant B. subtilis produced 114.0 g/L of D-mannose from 500 g/L of D-glucose, with a conversion ratio of 22.8 %., Competing Interests: Declaration of Competing Interest The authors declare that they have no known financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bacillus licheniformis 24 (BL24) is an efficient, non-pathogenic producer of 2,3-butanediol (2,3-BD). However, during inulin fermentation, the strain produces large amounts of exopolysaccharides (EPS), which interfere with the process' performance. The present study aims to investigate the effect that inactivation of the sacB gene, encoding levansucrase in BL24, has on 2,3-BD production efficiency. Knockout of the sacB gene was accomplished via insertional inactivation. The sacB -knockout variant formed 0.57 g/L EPS from sucrose and 0.7-0.8 g/L EPS from glucose and fructose, a 15- and 2.5-fold reduction relative to the wild type, respectively. Likewise, during batch fermentation with soluble inulin Frutafit ® CLR, the mutant BLΔ sacB produced significantly less EPS than the wild type, allowing the maintenance of pH at values favoring 2,3-BD synthesis. At pH 6.50, BLΔ sacB reached a record titer of 128.7 g/L 2,3-BD, with productivity of 1.65 g/L/h, and a yield of 85.8% of the theoretical maximum. The obtained concentration of 2,3-BD is two-fold higher compared to that of the wild type. Subsequent RT-qPCR assays confirmed a successful sacB knockout. Three of the genes involved in inulin hydrolysis ( sacA , sacC , and fruA ) maintained their expression levels compared to the wild type, while that of levB increased. Although total EPS accumulation could not be completely eliminated via sacB gene knockout alone, the overall reduction in EPS content has enabled the highest yield of 2,3-BD from inulin to date, a promising result for the industrial production from inulin-rich substrates.

The low solubility of α-tocopherol in water and its susceptibility to photodegradation make it difficult for biological systems to absorb this natural antioxidant. To overcome these limitations, α-tocopherol was encapsulated in low-toxicity nanocontainers, namely, niosomes based on Tween 80 and cholesterol. The niosomes were modified with cationic surfactants containing a carbamate fragment. The size and charge of the particles were determined and their stability was assessed using dynamic and electrophoretic light scattering methods. It was found that the introduction of cationic surfactants to niosome formulations significantly improved their physicochemical properties and increased stability due to a positive charge of up to +40 mV being generated. Modified niosomes loaded with α-tocopherol were characterized by a hydrodynamic diameter of 100-120 nm, a narrow particle size distribution, and a high encapsulation efficiency of more than 90%. Testing the photochemical stability of α-tocopherol using a spectrophotometric method demonstrated that niosomes were able to protect this substance from UV irradiation. Luminescence analysis showed that the inclusion of α-tocopherol in niosomes increased their antioxidant activity by 30%. An acute toxicity study has demonstrated the safety of the systems. The LD 50 value for niosomes modified with carbamate-containing surfactants and loaded with α-tocopherol exceeded 10,000 mg·kg -1 (mice, intraperitoneal and oral administration).

The natural auxiliary function (NAF) approach is an approximation to decrease the size of the auxiliary basis set required for quantum chemical calculations utilizing the density fitting technique. It has been proven efficient to speed up various correlation models, such as second-order Møller-Plesset (MP2) theory and coupled-cluster methods. Here, for the first time, we discuss the theory of analytic derivatives for correlation methods employing the NAF approximation on the example of MP2. A detailed algorithm for the gradient calculation with the NAF approximation is proposed in the framework of the method of Lagrange multipliers. To assess the effect of the NAF approximation on gradients and optimized geometric parameters, a series of benchmark calculations on small and medium-sized systems was performed. Our results demonstrate that, for MP2, sufficiently accurate gradients and geometries can be achieved with a moderate time reduction of 15-20% for both small and medium-sized molecules.

Antinutrients, also known as anti-nutritional factors (ANFs), are compounds found in many plant-based foods that can limit the bioavailability of nutrients or can act as precursors to toxic substances. ANFs have controversial effects on human health, depending mainly on their concentration. While the positive effects of these compounds are well documented, the dangers they pose and the approaches to avoid them have not been discussed to the same extent. There is no dispute that many ANFs negatively alter the absorption of vitamins, minerals, and proteins in addition to inhibiting some enzyme activities, thus negatively affecting the bioavailability of nutrients in the human body. This review discusses the chemical properties, plant bioavailability, and deleterious effects of anti-minerals (phytates and oxalates), glycosides (cyanogenic glycosides and saponins), polyphenols (tannins), and proteinaceous ANFs (enzyme inhibitors and lectins). The focus of this study is on the possibility of controlling the amount of ANF in food through fermentation. An overview of the most common biochemical pathways for their microbial reduction is provided, showing the genetic basis of these phenomena, including the active enzymes, the optimal conditions of action, and some data on the regulation of their synthesis.

The unique properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable their use as magnetic biosensors, targeted drug delivery, magnetothermia, magnetic resonance imaging, etc. Today, SPIONs are the only type of metal oxide nanoparticles approved for biomedical application. In this work, we analyzed the cellular response to the previously reported luminescent silica coated SPIONs of the two cell types: M-HeLa cells and primary motor neuron culture. Both internalization pathways and intracellular fate of SPIONs have been compared for these cell lines using fluorescence and transmission electron microscopy. We also applied a pharmacological approach to analyze the endocytosis pathways of SPIONs into the investigated cell lines. The penetration of SPIONs into M-HeLa cells is already noticeable within 30 s of incubation through both caveolin-dependent endocytosis and micropinocytosis. However, incubation for a longer time (1 h at least) is required for the internalization of SPIONs into motor neuron culture cells provided by dynamin-dependent endocytosis and macropinocytosis. The intracellular colocalization assay reveals that the lysosomal internalization pathway of SPIONs is also dependent on the cell type. The lysosomal pathway is much more pronounced for M-HeLa cells compared with motor neurons. The emphasized differences in cellular responses of the two cell lines open up new opportunities in the application of SPIONs in the diagnostics and therapy of cancer cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Food availability determines the amount of energy animals can acquire and allocate to reproduction and other necessary functions. Female animals that are food limited thus experience reduced energy available for reproduction. When this occurs, females may reduce frequency of reproductive events or the number or size of offspring per reproductive bout. We assessed how maternal diet affects reproductive output in adult female Murray River short-necked turtles, Emydura macquarii, from four wetlands in Victoria. We previously found that turtle diets differ in the composition of plants and animals between our study wetlands. In this study, we tested whether differences in turtle diet composition (i.e. plants and animals) at these wetlands were associated with differences in clutch mass, individual egg mass, bulk egg composition and hatching success. We found total clutch mass increased with maternal body size at each site. At sites where filamentous green algae were scarce and E. macquarii were carnivorous, females produced smaller clutches relative to body size compared to females from sites where algae were abundant, and turtles were more herbivorous. Individual egg mass, bulk egg composition and hatching success did not differ across wetlands. Isotopic analysis revealed significant positive relationships between the carbon and nitrogen isotopes (δ 13 C, δ 15 N) of the eggs and those of the mothers, indicating that mothers allocated ratios of carbon and nitrogen isotopes to their eggs similar to those present in their tissues. Our study suggests that at sites where females are more carnivorous due to a relative absence of algae, females produce smaller clutches, but other aspects of their reproduction are not significantly impacted. The reduction in clutch size associated with differences in the availability of dietary plants and animals may have long-term consequences for E. macquarii and other freshwater turtle species that are experiencing population declines., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press and the Society for Experimental Biology.)

The number of victims with damage to the great vessels has increased in recent years due to escalation of armed conflicts. Vascular damages comprise 3% of traumatic injuries in peacetime, and their incidence increases to 15% during hostilities. False aneurysms and traumatic arteriovenous fistulas follow vascular injury in 48.9-68.7% of cases. We present open surgical treatment of traumatic arteriovenous fistulas. The issues of diagnosis, surgical tactics, algorithm of intervention and options for successful treatment are described.

Objective: Assessment of plasma and salivary acetylcholinesterase (AChE) activity in patients with amyotrophic lateral sclerosis (ALS) and in an animal model of the disease., Material and Methods: We studied 41 participants, aged 31 to 71 years, including 17 patients with diagnosed ALS (ALS group, average age 62.3±2.2), 9 patients with ALS mimics (disease control, average age 58.1±2.9), and 15 healthy people (normal control, average age 57.7±2.3). Plasma and salivary AChE activity was measured by using the Ellman colorimetric method. ALS severity was assessed using the ALSFRS-R scale. The King's College staging system and the Milano-Torino Scale (MiToS) were used to determine the stage of the disease. Transgenic FUS-mice were used as ALS model., Results: Plasma AChE activity in the ALS group did not significantly differ from the control groups. There was also no significant correlation between plasma AChE activity and disease parameters such as the stage, duration, rate of progression, and severity. In transgenic FUS-mice plasma AChE activity also did not differ from wild-type mice. However, it has been shown that patients with ALS have significantly higher saliva AChE activity compared to normal controls. However, patients with the bulbar form of ALS had significantly higher values of salivary AChE activity compared to healthy controls., Conclusion: In patients with the bulbar form of ALS, an increase in salivary AChE activity was noted, which can be used for diagnostic and prognostic purposes. There is no significant change in plasma AChE activity in ALS patients.