Nanomolar Benzothiazole-Based Inhibitors of 17β-HSD10 with Cellular Bioactivity.

Multifunctional mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a potential drug target for the treatment of various pathologies. The most discussed is the pathology associated with Alzheimer's disease (AD), where 17β-HSD10 overexpression and its interaction with amyloid-β peptide contribute to mitochondrial dysfunction and neuronal stress. In this work, a series of new benzothiazole-derived 17β-HSD10 inhibitors were designed based on the structure-activity relationship analysis of formerly published inhibitors.

BODIPY-labelled acetylcholinesterase reactivators can be encapsulated into ferritin nanovehicles for enhanced bioavailability in the CNS.

The BODIPY-labelled oxime reactivator was prepared and used to study its biodistribution into central nervous system. The newly synthesized oxime was found to be weak inhibitor of acetylcholinesterase and strong inhibitor of butyrylcholinesterase. Its reactivation ability for organophosphate inhibited acetylcholinesterase was found similar to a parent oxime.

Evaluation of Mechanical Properties and Filler Interaction in the Field of SLA Polymeric Additive Manufacturing.

The paper deals with research focused on the use of fillers in the field of polymeric materials produced by additive technology SLA (stereolithography). The aim of the research is to evaluate 3D printing parameters, the mechanical properties (tensile strength, hardness), and the interaction of individual phases (polymer matrix and filler) in composite materials using SEM analysis. The tested fillers were cotton flakes and ground carbon fibres in different proportions.

[Development of chronic venous disease].

Introduction: Chronic venous disease is known to gradually worsen in the course of years. However, little clinical data is available. The patient group and methods: We used the set of our patients with completed clinical examination, duplex sonography and photoplethysmography and selected 160 patients examined at our office after 10 and more years.

STAT3 inhibitor Stattic and its analogues inhibit STAT3 phosphorylation and modulate cytokine secretion in senescent tumour cells.

Signal transducer and activator of transcription 3 (STAT3) signalling serves an important role in carcinogenesis and cellular senescence, and its inhibition in tumour cells represents an attractive therapeutic target. Premature cellular senescence, a process of permanent proliferative arrest of cells in response to various inducers, such as cytostatic drugs or ionizing radiation, is accompanied by morphological and secretory changes, and by altered susceptibility to chemotherapeutic agents, which can thereby complicate their eradication by cancer therapies. In the present study, the responsiveness of proliferating and docetaxel (DTX)‑induced senescent cancer cells to small molecule STAT3 inhibitor Stattic and its analogues was evaluated using tumour cell lines.

Identification of and discrimination between the complex and complex directly from sputum using quadruplex real-time PCR.

. Cystic fibrosis (CF) is a serious disease with multisystemic clinical signs that is easily and frequently complicated by bacterial infection. Recently, the prevalence of nontuberculous mycobacteria as secondary contaminants of CF has increased, with the complex (MAC) and complex (MABSC) being the most frequently identified.

Modified Lymphoscintigraphy in Primary Lymphatic Insufficiency of the Lower Limb.

Primary lymphedema of the foot and toes could be sometimes misdiagnosed by lymphoscintigraphy as a whole lower limb lymphatic insufficiency (LLLI). This is caused by using standard lymphoscintigraphic protocol based on one interstitial injection of radiotracer applied into the first interdigital space followed by image analysis of lower limb lymphatic vessels and lymph nodes. Here, we show that a modification of the lymphoscintigraphic protocol and introduction of a second dose of radiotracer right above the inner ankle to the clinically healthy tissue can more accurately describe morphological abnormalities of the superficial lymphatic system at the lower limb and thereby refine the diagnosis of the LLLI.

Research on Low-Cycle Fatigue Engineered Hybrid Sandwich Ski Construction.

This research is aimed at evaluating the effect of low-cycle fatigue on a newly designed hybrid sandwich ski structure to determine the changes that may occur due to cyclic loading and thus affect its use. This is primarily concerned with the fatigue behavior of the tested ski over different time intervals simulating its seasonal use and its effect on the mechanical properties of the ski, i.e.

Halogen substituents enhance oxime nucleophilicity for reactivation of cholinesterases inhibited by nerve agents.

The fluorinated bis-pyridinium oximes were designed and synthesized with the aim of increasing their nucleophilicity and potential to reactivate phosphorylated human recombinant acetylcholinesterase (AChE) and human purified plasmatic butyrylcholinesterase (BChE) in relation to chlorinated and non-halogenated oxime analogues. Compared to non-halogenated oximes, halogenated oximes showed lower pK of the oxime group (fluorinated < chlorinated < non-halogenated) along with higher level of oximate anion formation at the physiological pH, and had a higher binding affinity of both AChE and BChE. The stability tests showed that the fluorinated oximes were stable in water, while in buffered environment di-fluorinated oximes were prone to rapid degradation, which was reflected in their lower reactivation ability.

Application of Sol-Gels Modified with Natural Plants Extracts as Stationary Phases in Open-Tubular Capillary Electrochromatography.

Ethanol extracts of three widely growing plants were added to silica sol-gel solutions, which were subsequently applied as wall surface modifiers in inner quartz capillaries. Modified capillaries were used for open-tubular capillary electrochromatographic separation of nucleotides and amino groups containing biological compounds (neurotransmitters, amino acids and oligopeptides). The experiments were performed at physiological pH 7.

Charged pyridinium oximes with thiocarboxamide moiety are equally or less effective reactivators of organophosphate-inhibited cholinesterases compared to analogous carboxamides.

The organophosphorus antidotes, so-called oximes, are able to restore the enzymatic function of acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) via cleavage of organophosphate from the active site of the phosphylated enzyme. In this work, the charged pyridinium oximes containing thiocarboxamide moiety were designed, prepared and tested. Their stability and p properties were found to be analogous to parent carboxamides (K027, K048 and K203).

Chemical and Structural Analysis of Newly Prepared Co-W-Al Alloy by Aluminothermic Reaction.

This article is devoted to the characterization of a new Co-W-Al alloy prepared by an aluminothermic reaction. This alloy is used for the subsequent preparation of a special composite nanopowder and for the surface coating of aluminum, magnesium, or iron alloys. Due to the very high temperature (2000 °C-3000 °C) required for the reaction, thermite was added to the mixture.

Temperature-induced changes in egg white antimicrobial concentrations during pre-incubation do not influence bacterial trans-shell penetration but do affect hatchling phenotype in Mallards.

Microbiome formation and assemblage are essential processes influencing proper embryonal and early-life development in neonates. In birds, transmission of microbes from the outer environment into the egg's interior has been found to shape embryo viability and hatchling phenotype. However, microbial transmission may be affected by egg-white antimicrobial proteins (AMPs), whose concentration and antimicrobial action are temperature-modulated.

Inter-annual repeatability and age-dependent changes in plasma testosterone levels in a longitudinally monitored free-living passerine bird.

While seasonal trends in testosterone levels are known from cross-cohort studies, data on testosterone inter-annual individual repeatability in wild birds are rare. Also, our understanding of hormonal age-dependent changes in testosterone levels is limited. We assessed plasma testosterone levels in 105 samples originating from 49 repeatedly captured free-living great tits (Parus major) sampled during the nesting to investigate their relative long-term repeatability and within-individual changes.

Ultrasonic Pulsating Water Jet Peening: Influence of Pressure and Pattern Strategy.

Peening techniques are nowadays attracting more research attention due to their association with the extending of the service life and improving surface texture of engineering components. Ultrasonic pulsating water jet peening represents a new way of mechanical surface treatment. Accelerated water droplets via hammer effect cause small elastic-plastic deformations on the surface.

Longitudinal evidence for immunosenescence and inflammaging in free-living great tits.

The first-line effector mechanisms of immune defence, including inflammation and oxidative burst, contribute significantly to host-pathogen resistance. Whether these immune responses undergo age-related changes in birds remains unknown. Here, we tracked selected inflammatory parameters in 54 free-living great tits (Parus major) of known age, captured repeatedly over three consecutive years, with the aims to investigate long-term repeatability and age-dependent changes in cellular oxidative burst responsiveness upon in vitro stimulation with bacterial lipopolysaccharide (LPS), and to identify its relationships with leukotriene B4 (LTB4) levels and haematological traits.

Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes.

Cytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1.

Design, synthesis, and evaluation of BP-1-102 analogs with modified hydrophobic fragments for STAT3 inhibition.

Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range.

Differences in the growth rate and immune strategies of farmed and wild mallard populations.

Individuals reared in captivity are exposed to distinct selection pressures and evolutionary processes causing genetic and phenotypic divergence from wild populations. Consequently, restocking with farmed individuals may represent a considerable risk for the fitness of free-living populations. Supportive breeding on a massive scale has been established in many European countries to increase hunting opportunities for the most common duck species, the mallard (Anas platyrhynchos).

Open-tubular capillary electrochromatographic application of a sol-gel matrix with chilli peppers, garlic, or synthetic additives.

This article describes a possible combination of two promising fields of analytical chemistry-the preparation of sol-gel matrices with varying additives and their application in capillary electrochromatography. The inner surfaces of capillaries were coated with the sol-gel solution containing either pure synthetic chemical additive-alliin or capsaicin-or an extract of their natural sources-garlic and chilli pepper, respectively. The modified capillaries were tested for interaction with two neurotransmitters, oligopeptides and nucleotides under conditions of open-tubular capillary electrochromatography.

Crayfish plague in Czechia: Outbreaks from novel sources and testing for chronic infections.

The crayfish plague pathogen Aphanomyces astaci, which is among the most studied pathogens of aquatic invertebrates, co-evolved with North American crayfish species but threatens crayfish on other continents. The pathogen causes mass mortalities, particularly in Europe. In this study we document 12 crayfish plague outbreaks that occurred from 2014 to 2019 in Czechia and, by using available molecular techniques (microsatellite and mtDNA markers), we reveal the A.

Longitudinally monitored lifetime changes in blood heavy metal concentrations and their health effects in urban birds.

Urban heavy metal pollution can impair the health of humans and other organisms inhabiting cities. While birds are suggested as one of the appropriate bioindicators for essential and non-essential trace element monitoring, the process of particular elements' accumulation in blood and its possible adverse health effects during ageing of individuals remain unexplored. We have investigated lifetime changes in blood lead (Pb), cadmium (Cd), arsenic (As) and zinc (Zn) concentrations and searched for links to health-related traits in sub-urban free-living great tit (Parus major) population monitored over a long period of time.

Modification of human pericardium by chemical crosslinking.

Autologous and allogenic human pericardia used as biomaterials for cardiovascular surgery are traditionally crosslinked with glutaraldehyde. In this work, we have evaluated the resistivity to collagenase digestion and the cytotoxicity of human pericardium crosslinked with various concentrations of glutaraldehyde in comparison with pericardium crosslinked by genipin, nordihydroguaiaretic acid, tannic acid, and in comparison with unmodified pericardium. Crosslinking retained the wavy-like morphology of native pericardium visualized by second harmonic generation microscopy.

Determination of thermodynamic acidity constants and limiting ionic mobilities of weak electrolytes by capillary electrophoresis using a new free software AnglerFish.

Thermodynamic acidity constants (acid or acid-base dissociation constants, sometimes called also as ionization constants) and limiting ionic mobilities (both of them at defined temperature, usually 25°C) are the fundamental physicochemical characteristics of a weak electrolyte, that is, weak acid or weak base or ampholyte. We introduce a novel method for determining the data of a weak electrolyte by the nonlinear regression of effective electrophoretic mobility versus buffer composition dependence when measured in a set of BGEs with various pH. To correct the experimental data for zero ionic strength we use the extended Debye-Hückel model and Onsager-Fuoss law with no simplifications.

Socio-Economic and Environmental Factors Related to Spatial Differences in Human Non-Tuberculous Mycobacterial Diseases in the Czech Republic.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that can induce pulmonary and non-pulmonary diseases in susceptible persons. It is reported that the prevalence of NTM diseases is increasing in developed countries, but this differs by regions and countries. NTM species distribution and the rate of diseases caused by NTM vary widely in the historical territories of Moravia and Silesia (Czech Republic).