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Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Meat aging is an important process that affects the quality of meat and is traditionally used mainly for beef. However, in recent years, there has been an increasing demand for pork products subjected to dry aging. The aim of this study was to compare selected parameters (microbiological quality, instrumental analyses of texture and color of meat, weight loss) of pork neck and loin with bone and skin together subjected to dry aging for 14 days. The microbiological profile (total viable psychrotrophic count, Enterobacteriaceae, psychrotrophic lactic acid bacteria, Pseudomonas spp.) on the surface of the meat with the skin and the lateral cutting surfaces without skin was compared on the first day after slaughter and after 14 days of dry aging. The results of this study demonstrated that dry aging did not significantly deteriorate the microbiological profile. Statistically significant weight losses were observed after 14 days of aging. The dry aging of pork had no significant effect on lightness (L*), redness (a*), and shear force. Significant differences were observed for yellowness (b*) and meat hardness (p < 0.05).

Planting nitrogen-fixing plants in post-mining sites and similar degraded areas is a common approach to speed up soil development and buildup of the nitrogen pool in soil organic matter. The aim of this study was to explore if slower growth of alder seedlings in initial post-mining sites results from adverse soil conditions or lack of microbial symbionts. To address this question, we sampled young soil (age 15 years) and more developed soil (age 70 years) from heaps after coal mining near Sokolov (Czech Republic). Soil samples were sterilized and not inoculated or inoculated with arbuscular mycorrhizal fungi (AMF) or AMF + Frankia, followed by planting with alder (Alnus glutinosa) seedlings germinated and precultured under sterile conditions. The effect of soil age on alder growth appeared to be non-significant. The only significant growth effect was seen with Frankia inoculation, implicating this inoculum as a key factor in later succession in post-mining soils. When the soil was fully inoculated, alder biomass was higher in developed soil supplied with iron (Fe) and phosphorus (P), indicating that iron and phosphorus availability may affect alder growth. In young soil, alder growth was highest with a combination of iron, phosphorus, and sulfur (S), and a positive effect of sulfur in young soil may correspond with a reduced, alkaline soil pH and increased phosphorus and iron availability.

Bcr-Abl is an oncoprotein with aberrant tyrosine kinase activity involved in the progression of chronic myeloid leukemia (CML) and has been targeted by inhibitors such as imatinib and nilotinib. However, despite their efficacy in the treatment of CML, a mechanism of resistance to these drugs associated with mutations in the kinase region has emerged. Therefore, in this work, we report the synthesis of 14 new 2,6,9-trisubstituted purines designed from our previous Bcr-Abl inhibitors. Here, we highlight 11b, which showed higher potency against Bcr-Abl (IC50 = 0.015 μM) than imatinib and nilotinib and exerted the most potent antiproliferative properties on three CML cells harboring the Bcr-Abl rearrangement (GI50 = 0.7–1.3 μM). In addition, these purines were able to inhibit the growth of KCL22 cell lines expressing Bcr-AblT315I, Bcr-AblE255K, and Bcr-AblY253H point mutants in micromolar concentrations. Imatinib and nilotinib were ineffective in inhibiting the growth of KCL22 cells expressing Bcr-AblT315I (GI50 > 20 μM) compared to 11b–f (GI50 = 6.4–11.5 μM). Molecular docking studies explained the structure–activity relationship of these purines in Bcr-AblWT and Bcr-AblT315I. Finally, cell cycle cytometry assays and immunodetection showed that 11b arrested the cells in G1 phase, and that 11b downregulated the protein levels downstream of Bcr-Abl in these cells.

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity. Additionally, we analysed the preliminary anthropometric and laboratory data to test the efficacy of our 12-week intensive program that combines in-person and telemedicine support. The program demonstrated a positive impact on body mass index (BMI) and its z-scores in 21 adolescents, and BMI in 18 participating parents. However, we found no effect on body composition, waist circumference, cardiometabolic parameters, or fitness evaluated via a 6-min walk test in adolescents. In conclusion, the combination of in-person and telemedicine intensive support over 35 h delivered by a multidisciplinary team can be beneficial not only for adolescents with obesity but also for their parents. The ongoing CAMP study serves as a platform for precision medicine in future decisions regarding anti-obesity medication in adolescents with obesity.

Plants can be infected with multiple viruses. High-throughput sequencing tools have enabled numerous discoveries of multi-strain infections, when more than one viral strain or divergent genomic variant infects a single plant. Here, we investigated small interfering RNAs (siRNAs) in a single strawberry plant co-infected with several strains of strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). A range of plants infected with subsets of the initial viral species and strains that were obtained by aphid-mediated transmission were also evaluated. Using high-throughput sequencing, we characterized the small RNA fractions associated with different genotypes of these three viruses and determined small RNA hotspot regions in viral genomes. A comparison of virus-specific siRNA (vsiRNA) abundance with relative viral concentrations did not reveal any consistent agreement. Strawberry mottle virus strains exhibiting considerable variations in concentrations were found to be associated with comparable quantities of vsiRNAs. Additionally, by estimating the specificity of siRNAs to different viral strains, we observed that a substantial pool of vsiRNAs could target all SMoV strains, while strain-specific vsiRNAs predominantly targeted rhabdoviruses, SCV and StrV-1. This highlights the intricate nature and potential interference of the antiviral response within a single infected plant when multiple viruses are present.

SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.

IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.

Advances in high-throughput sequencing methods have boosted the discovery of multistrain viral infections in diverse plant systems. This phenomenon appears to be pervasive for certain viral species. However, our knowledge of the transmission aspects leading to the establishment of such mixed infections is limited. Recently, we reported a mixed infection of a single strawberry plant with strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). While SCV and StrV-1 are represented by two and three molecular variants, respectively, SmoV has three different RNA1 and RNA2 segments. In this study, we focus on virus acquisition by individual adult aphids of the Aphis gossypii, Aphis forbesi and Chaetosiphon fragaefolii species. Single-aphid transmission trials are performed under experimental conditions. Both different viruses and individual virus strains show varying performances in single aphid acquisition. The obtained data suggests that numerous individual transmission events lead to the establishment of multistrain infections. These data will be important for the development of epidemiological models in plant virology.

The aim of this study was to analyse the influence of the contamination level of fresh meat on the bacterial population in raw material before cooking and on the microbiota of cooked hams following heat treatment. The effect of incubation temperatures of 6.5 and 15 °C on the results obtained was also evaluated during the bacteriological investigation. The total viable count (TVC), the number of Enterobacteriaceae and lactic acid bacteria (LAB) were determined in the samples. LAB were isolated from 13 samples out of the 50 fresh meat samples. The species most frequently detected included Latilactobacillus sakei, Leuconostoc carnosum, Enterococcus gilvus, Latilactobacillus curvatus, and Leuconostoc gelidum. The meat sampled after the brine injection and tumbler massaging showed higher bacterial counts compared to fresh meat samples (p < 0.001). The heat treatment destroyed the majority of the bacteria, as the bacterial counts were beneath the limit of detection with a few exceptions. Although the primary cultivation of samples of cooked hams did not reveal the presence of LAB, their presence was confirmed in 11 out of 12 samples by a stability test. Bacteria of the genus Leuconostoc were the most numerous.

To ensure the selection of wheat genotypes that are resilient to future climatic conditions, with drought already being the most significant and acute problem in many areas, twenty winter wheat cultivars were tested for drought stress tolerance from the beginning of stem elongation (DC 30; Zadoks decimal codes) for 49 days (until the stage of grain development, DC 73–75) within an automatic phenotyping platform. The control plants were regularly irrigated to 70% of soil water capacity (SWC), while the drought-stressed plants were subjected to controlled drying until the permanent wilting point (15% of SWC) was reached. Then, the drought-stressed plants were rewatered again to 70% of the maximum SWC. After they recovered, the plants were again exposed to ambient weather conditions. The final yield formation parameters were assessed at the fully ripe stage. Our results showed that the genotypes originating in Western Europe manifested the highest response to the experimentally set drought in the grain number per spike measurement, while the genotypes originating in the warmer regions of southeastern Europe manifested the highest response to the experimental drought mainly in thousand grain weight measurement. Similar response patterns were evident for late- and early-maturing genotypes. The results indicate the potential of selecting genotypes with increased drought resistance even within the existing set of cultivars.

Plants produce specific terpenes, secondary metabolites conferring tolerance to biotic and abiotic stresses. Our study aims to investigate the effects of altitude, light intensity and season on contents of mono- and sesquiterpenes in needles of coniferous Norway spruce (Picea abies). Needles of current shoots representing upper and lower canopy were collected from adult trees growing along an altitudinal gradient (400–1100 m a.s.l.) in summer and autumn. After the extraction in cold heptane, the content of extractable terpenes was determined by gas chromatography coupled with mass spectrometry. Our results show that the total content of terpenes decreases with increasing altitude regardless of canopy position and season. Needles of the upper canopy have a higher total content of terpenes than lower canopy needles, but this difference decreases with increasing altitude in summer. Total content of extractable terpenes increases in autumn when compared to summer particularly in upper canopy needles of trees from high altitudes. Limonene, camphene, α-pinene and myrcene are the most abundant monoterpenes in spruce needles forming up to 85% of total monoterpenes, while germacrene D-4-ol is the most abundant sesquiterpene. Altitude, canopy position and season have a significant interactive effect on most monoterpenes, but not on sesquiterpenes. Terpenoid biosynthesis is thus tightly linked to growth conditions and likely plays a crucial role in the constitution of stress tolerance in evergreen conifers.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition, and migration of cancer cells).

Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes. The chemical, pharmaceutical, and biological properties of flavonoids can be significantly affected by their interaction with transition metal ions, mainly iron. In this review, we explain the interaction of various flavonoid structures with Fe(II) and Fe(III) ions and critically discuss the influence of chelated ions on the flavonoid biochemical properties. In addition, specific biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been included in this review.

We investigated how reduced summer precipitation modifies photosynthetic responses of two model tree species—coniferous Norway spruce and broadleaved sessile oak—to changes in atmospheric CO2 concentration. Saplings were grown under mountainous conditions for two growing seasons at ambient (400 μmol CO2 mol–1) and elevated (700 μmol CO2 mol–1) CO2 concentration. Half were not exposed to precipitation during the summer (June–August). After two seasons of cultivation under modified conditions, basic photosynthetic characteristics including light-saturated rate of CO2 assimilation (Amax), stomatal conductance (GSmax), and water use efficiency (WUE) were measured under their growth CO2 concentrations together with in vivo carboxylation rate (VC) and electron transport rate (J) derived from CO2-response curves at saturating light. An increase in Amax under elevated CO2 was observed in oak saplings, whereas it remained unchanged or slightly declined in Norway spruce, indicating a down-regulation of photosynthesis. Such acclimation was associated with an acclimation of both J and VC. Both species had increased WUE under elevated CO2 although, in well-watered oaks, WUE remained unchanged. Significant interactive effects of tree species, CO2 concentration, and water availability on gas-exchange parameters (Amax, GSmax, WUE) were observed, while there was no effect on biochemical (VC, J) and chlorophyll fluorescence parameters. The assimilation capacity (Asat; CO2 assimilation rate at saturating light intensity and CO2 concentration) was substantially reduced in spruce under the combined conditions of water deficiency and elevated CO2, but not in oak. In addition, the stimulatory effect of elevated CO2 on Amax persisted in oak, but completely diminished in water-limited spruce saplings. Our results suggest a strong species-specific response of trees to reduced summer precipitation under future conditions of elevated CO2 and a limited compensatory effect of elevated CO2 on CO2 uptake under water-limited conditions in coniferous spruce.

The use of photosystem II (PSII) inhibitors allows simulating cascade of defense and damage responses, including the oxidative stress. In our study, PSII inhibiting herbicide metribuzin was applied to the leaf of the model plant species Chenopodium album. The temporally and spatially resolved cascade of defense responses was studied noninvasively at the leaf level by combining three imaging approaches: Raman spectroscopy as a principal method, corroborated by chlorophyll a fluorescence (ChlF) and infrared thermal imaging. ChlF imaging show time-dependent transport in acropetal direction through veins and increase of area affected by metribuzin and demonstrated the ability to distinguish between fast processes at the level of electron transport (1 − Vj) from slow processes at the level of non-photochemical energy dissipation (NPQ) or maximum efficiency of PSII photochemistry (Fv/Fm). The high-resolution resonance Raman images show zones of local increase of carotenoid signal 72 h after the herbicide application, surrounding the damaged tissue, which points to the activation of defense mechanisms. The shift in the carotenoid band indicates structural changes in carotenoids. Finally, the increase of leaf temperature in the region surrounding the spot of herbicide application and expanding in the direction to the leaf tip proves the metribuzin effect on slow stomata closure.

Ectomycorrhizal (ECM) fungi importantly influence seedling growth, nutrition, and survival and create an extensive mycelial network interconnecting tree species and enabling resource redistribution. Due to their symbiotic relationship with trees, they are impacted by forest disturbances, which are of increasing relevance due to climate change. The effect of disturbance on seedling colonization and their morphology is still largely unknown. Seedling growth parameters and the ECM fungal assemblage on the roots of Norway spruce (Picea abies (L.) H. Karst.) seedlings were assessed in mature spruce forests attacked and destroyed by bark beetle and in a mature non-attacked forest as a reference. We did not detect significant differences in number of ECM species on seedling roots among forest types, but ECM species composition changed; Tylospora fibrillosa (Burt) Donk, Meliniomyces variabilis Hambl. & Sigler, and Phialocephala fortinii C.J.K. Wang & H.E. Wilcox were characteristic species in the forest destroyed by bark beetle, whereas Lactarius, Cortinarius, and Russula were in the mature forest. Forest type further significantly influenced the height, root length, and root collar thickness of seedlings and the proportion of exploration types of mycorrhizae.

Bark beetle infestation is a widespread phenomenon in temperate forests, which are facing significant weather fluctuations accompanying climate change. Fungi play key roles in forest ecosystems as symbionts of ectomycorrhizal trees, decomposers, or parasites, but the effect of severe disturbances on their communities is largely unknown. The responses of soil fungal communities following bark beetle attack were determined using Illumina sequencing of soil samples from 10 microsites in a mature forest not attacked by bark beetle, a forest attacked by bark beetle, a forest destroyed by bark beetle, and a stand where all trees were removed after a windstorm. The proportion of ITS2 sequences assigned to mycorrhizal fungal species decreased with increased intensity of bark beetle attack (from 70 to 15%), whereas the proportion of saprotrophs increased (from 29 to 77%). Differences in the ectomycorrhizal (ECM) fungal community was further characterized by a decrease in the sequence proportion of Elaphomyces sp. and Russula sp. and an increase in Piloderma sp., Wilcoxina sp., and Thelephora terrestris. Interestingly, the species composition of the ECM fungal community in the forest one year after removing the windstorm-damaged trees was similar to that of the mature forest, despite the sequence proportion attributed to ECM fungi decreased.