Coumarins are well-known for their unique chemical structure and a wide range of biological effects. Various substituted coumarin-based compounds have emerged as promising candidates for the development of novel therapeutic agents against numerous diseases. This study was focused on the synthesis of new 4,7-disubstituted coumarin derivatives and investigation of their ability to inhibit the aggregation of Aβ40 peptide, their cytotoxic effect on SH-SY5Y cells, their antioxidant properties, and their ability to penetrate the blood-brain barrier (BBB). The results revealed that the trihydroxy derivatives 5a-c had been the most effective inhibitors of Aβ aggregation, promoting the formation of non-toxic, amorphous aggregates instead. Importantly, no significant decrease in the viability of SH-SY5Y neuroblastoma cells was observed after treatment with the studied coumarins. Among them, coumarin 5a demonstrated the strongest antioxidant activity, while compound 5b also exhibited good antioxidant properties, along with the best inhibition of Aβ aggregation (IC50 = 13.5 μM), and adequate permeability across the blood-brain barrier. These findings suggest that compound 5b is a promising candidate for further investigation in Alzheimer's disease pharmacotherapy.

• Klíčová slova
• Alzheimer's disease, Amyloid aggregation, Antioxidant activity, Aβ peptide, Cell viability assay, Coumarin derivatives,
• MeSH
• amyloidní beta-protein * antagonisté a inhibitory   metabolismus   MeSH
• antioxidancia * farmakologie   chemie   chemická syntéza   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• kumariny * farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• peptidové fragmenty * metabolismus   antagonisté a inhibitory   MeSH
• proteinové agregáty účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidní beta-protein * MeSH
• antioxidancia * MeSH
• coumarin MeSH Prohlížeč
• kumariny * MeSH
• peptidové fragmenty * MeSH
• proteinové agregáty MeSH

Fifty male 90-day-old Hyplus rabbits (PS19 × PS40) were slaughtered (carcass weight: 2126 ± 316.1 g) to determine the effect of post-mortem ageing methods (wet vs dry) and ageing period (7 or 14 days) on the physicochemical characteristics and sensory properties of the longissimus thoracis et lumborum (LTL) muscle. Of the 50 carcasses, 10 were used for physicochemical meat quality assessment on 24 h post-mortem (D1). The remaining carcasses were assigned to either wet ageing (deboned muscles in vacuum-packaging) or dry ageing (whole carcass), for 7 "D7" or 14 "D14" days (n = 10 per treatment combination). Physicochemical and sensory analyses were performed after each ageing period. Results revealed that wet-aged LTLs were lighter in colour (L*) than the dry-aged LTLs, regardless of the ageing period. The wet-aged samples also had the highest a* values (redness) on D14 than all other treatments. Cooking loss percentages were greater in wet- than dry-aged meat on D14, but did not differ on D1 and D7 of wet ageing. Shear force decreased from D1 to D7 of ageing, regardless of the method used, and then stabilised. The dry-aged meat on D14 exhibited the lowest moisture content and the highest ash content, whilst the greatest malondialdehyde concentration was reported on D7 for dry-aged meat corresponding with its higher scores for off-odour intensity by the sensory panel. Whilst no significant differences were noted for overall acceptance on D7, the positive flavour development during dry ageing after 14 days was favourably evaluated by the panellists.

• Klíčová slova
• Cooking loss, Flavour, Malondialdehyde, Off-odour, Vacuum packaging,
• MeSH
• barva MeSH
• chuť MeSH
• kosterní svaly chemie   MeSH
• králíci MeSH
• lidé MeSH
• manipulace s potravinami * metody   MeSH
• maso * analýza   MeSH
• posmrtné změny MeSH
• vaření MeSH
• voda analýza   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• voda MeSH

Dill (Anethum graveolens), an annual species, was used to study the impact of metallic pollution potentially spreading from the nickel smelter dump in Dolná Streda (Slovakia) by monitoring 55 elements. Despite the proximity of this dump (1 km), only soil Ni (54.8 mg/kg) or Pb (47.3 mg/kg), but not Cr, Mn, Fe or Co (main elements of the dump's sludge) was elevated in given garden soil compared to two control sites. Mainly flowers and/or leaves contained significantly higher amounts of Ni, Cr, Pb, Cu, As, Sb, Sn, V, W, and some rare earth elements at the site close to the dump. Correlation between elements in organs and soil was significant mainly in stem or root but the bioaccumulation factor was typically low (<0.02) for most elements. A positive finding was that the 2022/2024 comparison revealed a decline in most elements in dill leaves, even at the dump site, which may reflect a decrease in the content of air PM particles. Soluble phenols were less accumulated in plants close to the nickel smelter dump, but flavonols showed the opposite trend, and free amino acids were positively correlated with many elements in the stem and root. An evaluation of commercial dill samples revealed variability (e.g., up to 0.7 mg Cd/kg dry weight) but subsequent NCA and PCA analyses clearly separated the dump locality from other samples. However, significant differences in the content of Cd, Ni, Pb, As, and other elements encourage precise control of commercially available dill dry matter.

• Klíčová slova
• Bioaccumulation, Heavy metals, Plant metabolites, Soil pollution, Spice,
• MeSH
• kovy * analýza   MeSH
• látky znečišťující půdu * analýza   metabolismus   MeSH
• monitorování životního prostředí * MeSH
• půda chemie   MeSH
• těžké kovy analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kovy * MeSH
• látky znečišťující půdu * MeSH
• půda MeSH
• těžké kovy MeSH

Sulfamethoxazole (SMX) and its residues exhibit high environmental persistence due to their resistance to conventional degradation processes. The bacterial strain Kocuria rhizophila SA117, isolated from polluted soils, was characterized biochemically, phylogenetically, and -omically. Herein, we describe a complete degradation pathway for SMX and determine two putative pathways: cleavage of the benzene ring and the degradation of the substituted isoxazole, leading to the formation of non-toxic Krebs cycle metabolites. Based on molecular structures containing 13C6-labeled carbons and 2H3 atoms, thirty metabolites were identified by high-resolution tandem mass spectrometry. Genomic and proteomic analysis of strain SA117 revealed its ability to perform a wide range of metabolic activities under sulfamethoxazole selective pressure. These activities include energy and sulfur metabolism, adaptation to stress conditions, and catabolism of aromatic compounds. This study has greatly enhanced the understanding of microbial sulfonamide degradation and highlighted the potential of the bacterium Kocuria in remediation strategies.

• Klíčová slova
• Biodegradation, Genome sequencing, Metabolic profiling, Proteomics, Sulfonamide,
• MeSH
• biodegradace MeSH
• fylogeneze MeSH
• katalýza MeSH
• metabolické sítě a dráhy * MeSH
• Micrococcaceae * metabolismus   genetika   MeSH
• proteomika MeSH
• sulfamethoxazol * metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sulfamethoxazol * MeSH

Anorexigenic neuropeptides have shown a remarkable potential in the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). One of the strong anorexigenic neuropeptides is called cocaine- and amphetamine-regulated transcript peptide (CARTp), which is the third most abundant transcript in the hypothalamus. Previously, we introduced a novel palmitoylated analog of 2-SS-CART(61-102), a specific analog of natural CART(61-102) with two disulfide bridges, with anorexigenic and neuroprotective properties. This study explores the impact of 2-SS-CART(61-102) and its palmitoylated analog, palm-2-SS-CART(61-102), on the early progression of Tau pathology characteristic of AD, utilizing the THY-Tau22 transgenic mouse model. Chronic subcutaneous treatment with CARTp analogs improved short-term spatial memory in the Y-maze, reduced the number of neurofibrillary tangles (NFT) in the hippocampal CA1 region, and decreased the level of GFAP + astrocytes in the hippocampus of THY-Tau22 mice. Furthermore, treatment with CARTp analogs showed increased levels of synaptic markers in the hippocampus. A beneficial effect on these attributes makes CARTp analogs promising for AD therapy.

• Klíčová slova
• Alzheimer's disease, Anorexigenic neuropeptides, CART peptide, Neuroinflammation, THY-Tau22 mice, Tau pathology,
• MeSH
• astrocyty účinky léků   patologie   metabolismus   MeSH
• bludiště - učení účinky léků   MeSH
• hipokampus * účinky léků   patologie   metabolismus   MeSH
• kokainem a amfetaminem regulovaný transkript MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• neurofibrilární klubka patologie   metabolismus   účinky léků   MeSH
• neuroprotektivní látky * farmakologie   terapeutické užití   MeSH
• prostorová paměť účinky léků   MeSH
• proteiny nervové tkáně * farmakologie   terapeutické užití   chemie   MeSH
• proteiny tau * genetika   metabolismus   MeSH
• tauopatie * patologie   farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kokainem a amfetaminem regulovaný transkript MeSH
• neuroprotektivní látky * MeSH
• proteiny nervové tkáně * MeSH
• proteiny tau * MeSH

The CE-MS/MS method for the analysis of boswellic acids, natural compounds with anti-inflammatory activity, and nonsteroidal anti-inflammatory drugs (NSAIDs) as potential adulterants of dietary supplements with Boswellia serrata extract is presented for the first time. An aqueous-organic background electrolyte comprising 40 mmol/L ammonium acetate (pH 8.5), methanol, and acetonitrile (5:1:4, v/v/v) was used for the separation of boswellic acids and thirteen NSAIDs in negative electrospray ionization mode. Design-of-experiments-guided optimization of Agilent Jet Stream ion source parameters and adjustments to the sheath liquid composition were conducted to improve sensitivity and prevent capillary breakage inside the nebulizer. The CE-MS/MS method was validated for diclofenac, flurbiprofen, ibuprofen, ketoprofen, phenylbutazone, salicylic acid, and carprofen, meeting the ICH M10 guideline requirements for accuracy, precision, matrix effects, and recovery. The lower limits of quantification ranged from 0.04 to 4 μg/mL for all NSAIDs, providing sufficient sensitivity to detect adulteration. The application of the method to dietary supplements revealed no evidence of NSAID adulteration while highlighting quantitative variations in boswellic acid profiles. Further analysis using CE-HRMS with data-dependent acquisition workflow enabled the identification of additional natural triterpenoids and undeclared compounds, such as citric acid and ascorbic acid.

• Klíčová slova
• Adulteration, Boswellia, Boswellic acids, Capillary electrophoresis, Dietary supplements, Mass spectrometry, NSAID,
• MeSH
• antiflogistika nesteroidní * analýza   MeSH
• Boswellia * chemie   MeSH
• elektroforéza kapilární metody   MeSH
• kontaminace léku * MeSH
• potravní doplňky analýza   MeSH
• rostlinné extrakty * chemie   analýza   MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• triterpeny * analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika nesteroidní * MeSH
• boswellic acid MeSH Prohlížeč
• rostlinné extrakty * MeSH
• triterpeny * MeSH

We revisit the classic situation in functional data analysis in which curves are observed at discrete, possibly sparse and irregular, arguments with observation noise. We focus on the reconstruction of individual curves by prediction intervals and bands. The standard approach consists of two steps: first, one estimates the mean and covariance function of curves and observation noise variance function by, e.g. penalized splines, and second, under Gaussian assumptions, one derives the conditional distribution of a curve given observed data and constructs prediction sets with required properties, usually employing sampling from the predictive distribution. This approach is well established, commonly used and theoretically valid but practically, it surprisingly fails in its key property: prediction sets constructed this way often do not have the required coverage. The actual coverage is lower than the nominal one. We investigate the cause of this issue and propose a computationally feasible remedy that leads to prediction regions with a much better coverage. Our method accounts for the uncertainty of the predictive model by sampling from the approximate distribution of its spline estimators whose covariance is estimated by a novel sandwich estimator. Our approach also applies to the important case of covariate-adjusted models.

• Klíčová slova
• 62G99, 62M99, Coverage, curve reconstruction, functional data analysis, noisy discrete observation, prediction set, spline smoothing,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The integration of robotic technology into surgical procedures has gained considerable attention for its promise to enhance a variety of clinical outcomes. Robotic deep inferior epigastric perforator (DIEP) flap harvest has emerged as a novel approach for autologous breast reconstruction. This systematic review aims to provide a comprehensive overview of the current techniques, outcomes, and complications of robotic DIEP flap surgery. METHODS: A systematic literature search was conducted after PRISMA 2020 guidelines across databases including PubMed, Embase, Google Scholar, and Web of Science from 2000 to 2023. Articles exploring robotic DIEP flap harvest for breast reconstruction were assessed to compare operative techniques, clinical outcomes, and complications. The risk of bias was evaluated using ROBINS-I and the Newcastle-Ottawa scale. RESULTS: Fourteen studies involving 108 patients were included. Three studies used a totally extraperitoneal (TEP) technique, whereas 11 studies used a transabdominal preperitoneal (TAPP) approach. Preoperative planning utilized computed tomography angiography and magnetic resonance angiography imaging. The mean robotic operative time was 64 minutes, with total operative times averaging 574 minutes for TAPP and 497 minutes for TEP. The mean length of stay was 5 days, and the mean fascial incision length was 3 cm. Overall complication rate was 14.9%, with no significant difference compared with conventional DIEP flap procedures. CONCLUSION: Robotic DIEP flap harvest is a promising technique that may reduce postoperative pain and limiting abdominal donor site morbidity. Potential limitations include longer operative times, variable hospital stays, and increased costs.

• MeSH
• arteriae epigastricae * transplantace   MeSH
• délka operace * MeSH
• délka pobytu MeSH
• lidé MeSH
• mamoplastika * metody   MeSH
• odběr tkání a orgánů metody   MeSH
• perforátorový lalok * krevní zásobení   MeSH
• pooperační komplikace prevence a kontrola   MeSH
• roboticky asistované výkony * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

Slipping motions of magnetic field lines are a distinct signature of three-dimensional magnetic reconnection, a fundamental process driving solar and stellar flares. While being a key prediction of numerical experiments, the rapid super-Alfvénic field line slippage driven by the 'slip-running' reconnection has remained elusive in previous observations. New frontiers into exploring transient flare phenomena were introduced by recently designed high cadence observing programs of the Interface Region Imaging Spectrograph (IRIS). By exploiting high temporal resolution imagery (~2 s) of IRIS, here we reveal slipping motions of flare kernels at speeds reaching thousands of kilometres per second. The fast kernel motions are direct evidence of slip-running reconnection in quasi-separatrix layers, regions where magnetic field strongly changes its connectivity. Our results provide observational proof of theoretical predictions unaddressed for nearly two decades and extend the range of magnetic field configurations where reconnection-related phenomena can occur.

• Klíčová slova
• Astrophysical magnetic fields, Astrophysical plasmas, Solar physics,
• Publikační typ
• časopisecké články MeSH

The study aims to present a case study of a patient with supratherapeutic serum gentamicin concentration. An 83-year-old male was admitted to the Department of Internal Medicine for persistent loss of appetite, decompensated heart failure, and pneumonia. He was treated with 240 mg gentamicin daily alongside ampicillin/sulbactam penicillin antibiotic. The trough gentamicin concentrations and estimated glomerular filtration rate from creatinine (eGFRcrea) and cystatin C (eGFRcys) were performed. The patient had the supratherapeutic trough gentamicin concentration of 2.5 mg/L. eGFRcrea was 62 mL/min/1.73m2 and eGFRcys was 25 mL/min/1.73m2. The difference between eGFRcrea and eGFRcys was 148%. Falsely high eGFRcrea in elderly patient led to the supratherapeutic gentamicin concentration even after the standard 240 mg gentamicin dose.

• Klíčová slova
• creatinine, cystatin C, drug overdose, gentamicins, glomerular filtration rate,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH