Bacterial oxygen sensing embodies a fascinating interplay between evolutionary pressures and physiological adaptations to varying oxygen levels. Throughout Earth's history, the composition of the atmosphere has undergone significant changes, from anoxic conditions to the gradual accumulation of oxygen. In response, microbial life has evolved diverse strategies to cope with these shifting oxygen levels, ranging from anaerobic metabolism to oxygen-dependent pathways crucial for energy production and cellular processes typical for eukaryotic, multicellular organisms. Of particular interest is the role of iron in bacterial oxygen sensing systems, which play pivotal roles in adaptation to changing oxygen levels. Only free iron, heme-iron, and non-heme iron directly sense oxygen. These iron-containing proteins, such as heme-containing sensors and iron-sulfur cluster proteins, regulate the expression of genes and activity of enzymes involved in oxidative stress defence, virulence, and biofilm formation, highlighting their significance in bacterial pathogenesis and environmental adaptation. Special attention in the review is paid to the mechanisms of oxygen detection and signal transduction from heme-containing sensing to functional domains in the case of bacterial heme-based oxygen sensors.

• Keywords
• Heme-based sensor, Intramolecular catalytic regulation, Oxygen sensing, Signal transduction,
• MeSH
• Bacteria * metabolism   genetics   MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Bacterial Physiological Phenomena * MeSH
• Heme * metabolism   MeSH
• Hemeproteins metabolism   MeSH
• Oxygen * metabolism   MeSH
• Gene Expression Regulation, Bacterial MeSH
• Signal Transduction MeSH
• Iron * metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Heme * MeSH
• Hemeproteins MeSH
• Oxygen * MeSH
• Iron * MeSH

Spices are a rich source of vitamins, polyphenols, proteins, dietary fiber, and minerals such as calcium, magnesium, iron, and zinc, all of which play an important role in biological functions. Since ancient times, spices have been used in our kitchen as a food coloring agent. Spices like cinnamon and turmeric allegedly contain various functional ingredients, such as phenolic and volatile compounds. Therefore, this review aims to summarize the current knowledge about the nutritional profiles of cinnamon and turmeric, as well as to analyze the clinical studies on their extracts and essential oils in animals and humans. Furthermore, their enrichment applications for food products and animal feed have also been investigated in terms of safety and toxicity. Numerous studies have shown that cinnamon and turmeric have various health benefits, including the reduction of insulin resistance and insulin signaling pathways in diabetic patients, the reduction of inflammatory biomarkers, and the maintenance of gut microflora in both animals and humans. The food and animal feed industries have taken notice of these health benefits and have begun to promote cinnamon and turmeric as healthy foods. This has resulted in the development of new food products and animal feeds that contain cinnamon and turmeric as primary ingredients, which have been deemed an effective means of promoting cinnamon and turmeric's health benefits.

• Keywords
• Cinnamon, enrichment, functional feed, functional food, turmeric,
• MeSH
• Curcuma * chemistry   MeSH
• Food, Fortified * MeSH
• Functional Food * analysis   MeSH
• Spices analysis   MeSH
• Animal Feed * analysis   MeSH
• Humans MeSH
• Nutritive Value MeSH
• Oils, Volatile analysis   MeSH
• Plant Extracts MeSH
• Cinnamomum zeylanicum * chemistry   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Oils, Volatile MeSH
• Plant Extracts MeSH

Since late 2022, an increase in Streptococcus pyogenes (Group A Streptococcus, GAS) infections, both non-invasive and invasive (iGAS), has been reported globally. This study investigates iGAS cases complicated by recurrent infection (rGAS). From January to September 2023, four adults with severe iGAS suffered from rGAS. Clinical and whole-genome sequencing data were analysed. All patients required ICU admission and surgical debridement during their initial iGAS. The median interval between the initial iGAS and rGAS was 25.5 days, with a median duration of antibiotic treatment of 25 and 17.5 days, respectively. Patients A (female, age 69) and B (male, age 46) had upper limb necrotising fasciitis complicated by a subsequent cellulitis at the exact location. GAS emm1.3 (M1UK) was isolated in both patients, but patient A´s isolates carried a type-IV secretion system (T4SS), and this patient had a more severe course of infection. Patient C (male, age 66) had two episodes of bacteremia caused by GAS emm89.0 carrying T4SS and GAS emm12.37 with a frameshift in the rocA gene. Patient D (female, age 69) had upper limb cellulitis with bacteremia during the initial iGAS and upper limb cellulitis with septic gonitis as two concurrent manifestations of rGAS. All three isolates were identical, belonging to emm12.0 and carrying a 79 amino acid deletion in the SclA. Patients B and C had a reduced function of the complement lectin pathway and CD19+ lymphocyte deficiency. A combination of strain virulence factors and host immune deficiencies may predispose patients with iGAS to recurrence.

• Keywords
• CD19+ deficiency, Streptococcus pyogenes, cellulitis, lectin pathway complement deficiency, necrotizing fasciitis, sepsis,
• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Bacteremia microbiology   MeSH
• Adult MeSH
• Fasciitis, Necrotizing microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Recurrence MeSH
• Type IV Secretion Systems genetics   MeSH
• Whole Genome Sequencing MeSH
• Aged MeSH
• Streptococcus pyogenes * pathogenicity   genetics   immunology   MeSH
• Streptococcal Infections * immunology   microbiology   MeSH
• Virulence MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Type IV Secretion Systems MeSH

Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus that invades the central nervous system, leading to severe neurological manifestations. In this study, we developed a reporter virus comprising TurboGFP-expressing TBEV (tGFP-TBEV) as a versatile tool for advancing TBEV research. The tGFP-TBEV facilitates quantitative measurement of viral replication, enables precise tracking of individual infected cells, and supports high-throughput screening of potential antiviral compounds and virus-neutralization assays. Furthermore, tGFP-TBEV proved effective as a model for studying TBEV infection in rat organotypic cerebellar slices cultured ex vivo and for visualizing TBEV infection in the mouse brain. Using tissue-clearing protocols and light-sheet fluorescence microscopy, we achieved high-resolution, three-dimensional mapping of the TBEV distribution in the mouse brain. This analysis uncovered distinct patterns of TBEV tropism, with infections concentrated in regions associated with neurogenesis, olfactory processing, and specific neuroanatomical pathways. The ability to visualize infection at both the cellular and whole-organ level provides a new tool for detailed investigations into viral tropism, replication, and interactions with host tissues, paving the way for deeper insights into TBEV biology and the pathogenesis of tick-borne encephalitis.

• Keywords
• TBEV, light-sheet microscopy, neurotropism, organotypic cerebellar slices, reporter viruses, tissue clearing,
• MeSH
• Encephalitis, Tick-Borne * virology   MeSH
• Rats MeSH
• Humans MeSH
• Luminescent Proteins genetics   metabolism   MeSH
• Brain * virology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Virus Replication MeSH
• Genes, Reporter MeSH
• Viral Tropism MeSH
• Encephalitis Viruses, Tick-Borne * genetics   physiology   MeSH
• Imaging, Three-Dimensional MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Luminescent Proteins MeSH

Vaccine hesitancy remains a significant public health challenge, particularly during pandemics when high immunization rates are crucial. While individual psychological antecedents of vaccine hesitancy have been extensively studied, limited empirical evidence exists on how contextual determinants, such as socioeconomic status, political trust, and digital literacy, collectively shape vaccine-related behaviors, particularly in Central European populations. This study explores the key determinants of COVID-19 vaccine hesitancy among Czech adults. A cross-sectional study was conducted using data from the 48th wave of the Czech national panel survey Život během pandemie [Life During Pandemic], carried out in March 2023. The data were obtained via an online questionnaire administered to a nationally representative sample of Czech adults (n = 1,708). Sociodemographic, socioeconomic, and anamnestic variables were examined alongside political attitudes. Psychological antecedents of vaccination were assessed using the 5C model (confidence, complacency, constraints, risk calculation, and collective responsibility), and digital vaccine literacy was measured using seven items covering trust in official sources, trust in social media, and the ability to evaluate and apply vaccine information. Statistical analyses included bivariate tests and multivariable regression models to identify vaccine uptake and intent determinants. Higher trust in constitutional institutions, including the president (OR = 1.55; 95/ CI: 1.38-1.74), government (1.60; 1.38-1.85), Chamber of Deputies (1.73; 1.48-2.02), and Senate (1.47; 1.29-1.69), was significantly associated with higher vaccine uptake. Similarly, positive attitudes toward the integration of Ukrainian refugees into Czech society - across domains such as work (1.63; 1.39-1.90), housing (1.59; 1.36-1.86), school (1.64; 1.41-1.92), language (1.57; 1.34-1.84), and culture (1.74; 1.50-2.03) - were positively associated with uptake. Greater confidence in vaccine safety and effectiveness was also a significant predictor (1.51; 1.44-1.58). In contrast, lower education (0.64; 0.56-0.73), lower income (0.91; 0.86-0.95), female sex (0.60; 0.47-0.76), and higher complacency (0.76; 0.73-0.80) were associated with reduced uptake. Respondents with better digital vaccine literacy, particularly those more adept at identifying misinformation, showed significantly greater vaccine confidence (mean score: 3.62 vs. 3.30, p < .001). Beyond psychological antecedents, institutional trust, political orientation, and digital vaccine literacy significantly shape COVID-19 vaccination behaviors. These findings underscore the importance of targeted interventions that address political and digital influences on vaccine hesitancy, and they highlight the need for future research to examine the causal pathways and longitudinal dynamics underlying these associations, particularly within Central and Eastern European contexts.

• Keywords
• COVID-19, Czech Republic, refugees, social determinants of health, vaccination hesitancy,
• MeSH
• COVID-19 * prevention & control   psychology   MeSH
• Adult MeSH
• Trust * psychology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Vaccination Hesitancy * psychology   statistics & numerical data   MeSH
• Politics MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Social Media MeSH
• Socioeconomic Factors MeSH
• Vaccination * psychology   MeSH
• COVID-19 Vaccines * administration & dosage   MeSH
• Health Literacy * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• COVID-19 Vaccines * MeSH

From tumorigenesis to the establishment of local or metastatic high-grade tumours, an integral part of the cellular lifespan relies on various signalling pathways. Particular pathways that allow cells to proliferate by creating a network of new blood vessels have been documented, whereas other pathways are primarily involved with a migration to distant body parts, partially through the process of epithelial-mesenchymal transition (EMT). This review will discuss the different signalling pathways, such as TGF-β, Cripto-1, Wnt pathways, Hedgehog, Notch and NF-κB pathways, and how they promote tumour initiation and progression by influencing diverse cellular processes and EMT in general and in benign and malignant prostate tumours. This review will discuss only the critical pathways. Therefore, many other types of signalling pathways which are related to prostate cancer will not be discussed. Possibilities for further investigation will be mentioned, as many underlying mechanisms involved in these pathways have potential as targets in future tumour therapy. This review will also introduce some novel clinical trials relating to the inhibition of signalling pathways and their clinical outcomes.

• Keywords
• EMT, Hedgehog, NF-κB, Notch, Prostate cancer, TGF, WNT/β-catenin, castration resistance, signalling pathways, therapeutic target, β,
• MeSH
• Epithelial-Mesenchymal Transition physiology   MeSH
• Humans MeSH
• Prostatic Neoplasms * pathology   metabolism   therapy   drug therapy   MeSH
• NF-kappa B metabolism   MeSH
• Hedgehog Proteins metabolism   MeSH
• Signal Transduction * physiology   MeSH
• Transforming Growth Factor beta metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• NF-kappa B MeSH
• Hedgehog Proteins MeSH
• Transforming Growth Factor beta MeSH

Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with Salmonella Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after Salmonella infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited Salmonella colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates Salmonella colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against Salmonella and possibly other pathogens.

• Keywords
• Salmonella, carrier-state, chicken, excretion, immune response, microbiota, super-shedder, virulence,
• MeSH
• Bacteria * immunology   classification   genetics   MeSH
• Chickens immunology   microbiology   MeSH
• Poultry Diseases * microbiology   immunology   prevention & control   MeSH
• Salmonella enteritidis * immunology   growth & development   physiology   MeSH
• Salmonella Infections, Animal * immunology   microbiology   prevention & control   MeSH
• Gastrointestinal Microbiome * immunology   MeSH
• Symbiosis MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

Forward-directed genetic screens are extremely powerful in identifying novel genes involved in a specific biological process, including various chromatin regulatory pathways. However, the traditional ways of genetic mapping are time- and cost-demanding. Recently, the whole process was revolutionized by the development of mapping-by-sequencing (MBS) protocols. In MBS, the causal mutations and their positions within genes are identified directly by whole-genome sequencing and bioinformatics analysis of the bulk of mutant plants selected based on the mutant phenotype from a segregating population. MBS increases precision and economizes the mapping. Here, we describe a general protocol and provide practical tips on how to proceed with the mapping-by-sequencing on the example of Arabidopsis forward-directed genetic screen designed to identify mutants sensitive to a specific type of DNA damage. The described protocol is generally applicable to a wide range of genetic screens in various inbreeding species with a reference genome sequence.

• Keywords
• DNA damage repair, DNA-protein crosslinks, Forward genetics, Genetic mapping, High-throughput sequencing, Mapping-by-sequencing, SNP calling, Zebularine,
• MeSH
• Arabidopsis * genetics   MeSH
• Phenotype MeSH
• Genome, Plant MeSH
• Chromosome Mapping * methods   MeSH
• Mutation MeSH
• Whole Genome Sequencing methods   MeSH
• Computational Biology methods   MeSH
• High-Throughput Nucleotide Sequencing * methods   MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.

• Keywords
• Actinium-225, Bismuth-213, Nanoparticles, Targeted alpha therapy, TiO(2),
• MeSH
• Actinium * chemistry   MeSH
• Isotope Labeling MeSH
• Mice MeSH
• Nanoparticles * chemistry   MeSH
• Radioisotopes * chemistry   MeSH
• Titanium * chemistry   MeSH
• Tissue Distribution MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Actinium-225 MeSH Browser
• Actinium * MeSH
• Radioisotopes * MeSH
• Titanium * MeSH
• titanium dioxide MeSH Browser

A series of ruthenium(II) and osmium(II) half-sandwich complexes was synthesized and characterized for its potential as a new class of anticancer agents. The complexes feature polycyclic aromatic hydrocarbon (PAH)-substituted Schiff bases and were rationally designed to combine the redox-modulating MoA of half-sandwich Ru, Rh, Os and Ir complexes, connected with their ability to induce the formation of various reactive oxygen species (ROS), with the ability of PAH-substituents to target and disrupt DNA. The complexes [Ru(η6-pcym)Cl(L)]PF6 (1-4) and [Os(η6-pcym)Cl(L)]PF6 (5-8) were stable in aqueous environments, in contrast to the rapid degradation observed for the co-studied rhodium(III) (9-12) and iridium(III) (13-16) [M(η5-Cp∗)Cl(L)]PF6 complexes; L = ethane-1,2-diamine-based Schiff bases (L1-L4) bearing two terminal PAH substituents 2-naphtyl (for L1), 9-anthracenyl (for L2), 9-phenanthrenyl (L3) or 1-pyrenyl (L4); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), Cp∗ = pentamethylcyclopentadienyl. Biological testing demonstrated that 1-8 possess significant antiproliferative activity against various lung cancer cell lines, including those resistant to cisplatin, with Os(II) complex 5 showing the highest cytotoxicity. Treatment with these complexes led to the activation of stress-related gene pathways, including unconventional endoplasmic reticulum stress, apoptotic signalling, and mitochondrial membrane depolarization. Activation of p21/GADD45A pathway indicates DNA-damage response, as well. Notably, these complexes did not induce significant inflammatory responses, a notable advantage over cisplatin. The results highlight the potential of Ru and Os half-sandwich complexes as alternative metallodrugs, capable of overcoming platinum resistance and minimizing inflammatory side effects. This study suggests that these compounds could serve as a promising class of anticancer agents for future clinical development.

• Keywords
• Antiproliferative activity, Endoplasmic reticulum, Mitochondria, Osmium, Ruthenium, Stress gene expression,
• MeSH
• Coordination Complexes * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Mitochondria * drug effects   metabolism   MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Organometallic Compounds * pharmacology   chemistry   chemical synthesis   MeSH
• Osmium * chemistry   pharmacology   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Ruthenium * chemistry   pharmacology   MeSH
• Drug Screening Assays, Antitumor MeSH
• Endoplasmic Reticulum Stress * drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Coordination Complexes * MeSH
• Organometallic Compounds * MeSH
• Osmium * MeSH
• Antineoplastic Agents * MeSH
• Reactive Oxygen Species MeSH
• Ruthenium * MeSH