Cardiovascular diseases, including thrombotic events such as ischemic stroke, pulmonary embolism, and myocardial infarction, are among the leading causes of morbidity and disability worldwide. The application of clot-dissolving thrombolytic enzymes is a cost-effective therapeutic intervention for these life-threatening conditions. However, the effectiveness and safety profiles of current drugs are suboptimal, necessitating the discovery of new medicines or the engineering and enhancement of the existing ones. Here, we present a set of optimized biochemical protocols that allow robust screening and the therapeutic potential assessment of thrombolytic biomolecules. The assays provide information on multiple characteristics such as enzymatic activity, fibrinolysis rate, fibrin and fibrinogen stimulation, fibrin selectivity, clot binding affinity, and inhibition resistance. Such detailed characterization enables a rapid and reliable evaluation of candidate effectiveness and provides an indication of biological half-life, associated bleeding complications, and other side effects. We demonstrate the credibility of the methodology by applying it to the two most widely used thrombolytic drugs: alteplase (Activase®/Actilyse®) and tenecteplase (Metalyse®/TNKase®). Consistent with previous studies, tenecteplase exhibited increased fibrin selectivity and inhibition resistance, which explains its extended half-life. Our findings reinforce the growing consensus that tenecteplase may be a superior alternative to alteplase for thrombolytic treatment.
- Klíčová slova
- PAI‐1 inhibition resistance, alteplase, fibrinolysis, plasminogen activator, staphylokinase, tenecteplase,
- Publikační typ
- časopisecké články MeSH
Cyanines comprise a diverse group of small-molecule polymethine dyes combining tunable optical properties with high molar absorptivity and fluorescence emission quantum yield, enabling various applications in bioimaging, diagnostics, molecular electronics, photonics, and nonlinear optics. These applications can be facilitated by adjusting the length of their polymethine chain and their functionalization through their end groups or the polymethine chain. Yet, the latter approach remains largely unexplored, with limited information scattered throughout literature. This review focuses on cyanines substituted on their chain, covering their synthesis, properties, and applications and providing an overview of how substituents on their polymethine chain influences their spectroscopic properties, akin to other factors, such as polymethine length and end groups. Lastly, this review illustrates how substituents on the polymethine chain facilitate the application of cyanine dyes in promising research areas.
- Klíčová slova
- applications, cyanines, dyes, polymethines, spectroscopy, structure–property relationships, substituents,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Marginalized Roma communities (MRCs) in Slovakia experience longstanding exclusion from essential services, including healthcare. Roma women, in particular, face compounded vulnerabilities that contribute to unequal access and poorer health outcomes. Despite increasing attention to these issues, a deeper understanding of the lived experiences that shape healthcare access in MRCs remains necessary. METHODS: A qualitative study was conducted using semi-structured interviews with 13 Roma mothers living in MRCs and 13 professionals working in healthcare, public health, or policy, including six of Roma origin. Data were analyzed using consensual qualitative research and thematic analysis to identify significant access barriers. RESULTS: Roma women face multiple, often interconnected barriers to accessing healthcare, many of which are rooted in longstanding structural inequalities. These include distrust of the health system stemming from prior discrimination, difficulties in understanding health-related information and navigating the system, and financial hardship. On the side of healthcare providers, barriers involve shortages in the healthcare workforce, poor care coordination, and discriminatory attitudes. CONCLUSIONS: Improving access to healthcare for Roma women requires a comprehensive, multi-level strategy. Efforts should focus on building trust, improving communication, addressing financial and systemic obstacles, and investing in culturally sensitive primary care. Health promotion assistants play a crucial role in bridging the gaps between communities and healthcare providers. Culturally sensitive healthcare interventions and inclusive policies are essential to reducing health disparities and promoting equitable access. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-025-13482-2.
Following rapid climate change, tundra plant communities are experiencing extensive compositional shifts. A conservation concern is the potential encroachment of boreal species into the tundra ('borealisation'). Tundra borealisation has been sporadically reported, but not systematically quantified. Here, we synthesised data from across 32 study areas, spanning 1137 plots and 287 vascular plant species, resurveyed between 1981 and 2023. We (i) quantified tundra borealisation as the colonisation and increase in abundance of Boreal and Boreal-Tundra species, (ii) assessed biogeographical, climatic and local borealisation drivers and (iii) identified species contributing to borealisation and their associated traits. Half of the plots experienced borealisation, although borealisation rates were not different to random expectation. Borealisation was greater in Eurasia, closer to the treeline, at higher elevations, in warmer and wetter regions, where climate change was limited, and where initial boreal abundance was lower. Boreal coloniser species were generally short-statured, and more often shrubs and graminoids. Boreal species colonised around three times less frequently than Boreal-Tundra species. Hence, our findings indicate that tundra borealisation is mainly driven by the spread of already established boreal-low Arctic tundra species. These plant community composition changes could have cascading impacts on land-atmosphere interactions, trophic dynamics and Indigenous and local livelihoods.
- Klíčová slova
- boreal forest, boreal‐tundra ecotone, climate change, plant borealisation, tundra, vascular plants,
- MeSH
- biodiverzita * MeSH
- klimatické změny * MeSH
- rostliny * klasifikace MeSH
- tundra * MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Arktida MeSH
Pesticides can have adverse effects on soil microorganisms, but they are underrepresented in the currently required OECD 216 test for environmental risk assessment of plant protection products (PPP). The guideline monitors soil microbial nitrogen transformation over 28 days, potentially missing long-term effects of persistent pesticides. Additionally, nitrate alone may be not sensitive enough to detect disruptions in microbial functions. We investigated whether functional gene analysis could provide a more sensitive bioindicator of pesticide impact. To compare this method with the standard test, we conducted a microcosm experiment following the OECD 216 experimental setup. To capture long-term effects beyond the typical test period, we extended the incubation duration to 56 days. Four different concentrations of the persistent fungicide boscalid were added based on predicted environmental concentration. We also assessed microbial responses to fungicide exposure by measuring classical soil microbial parameters. According to the standard test, boscalid had no harmful long-term effects on soil microbiota. In contrast, our analysis of functional genes found an overall reduction in the acid phosphatase-encoding phoN gene abundance on Day 56, and correspondingly, in acid phosphatase activity in the highest fungicide treatment. Simultaneously, we observed a tendency towards lower fungal abundance based on measured copy numbers of an ITS region of nuclear ribosomal DNA (rDNA) and increased cumulative CO2 production. These results indicate a fungicide-related response of the microbial community and impaired microbial phosphorus cycling. Extending the experimental period to 56 days revealed long-term effects that would have otherwise been undetected under the typical 28-day test duration.
- Klíčová slova
- Boscalid, Non-target soil microorganisms, OECD 216, Pesticide risk assessment, phoN,
- MeSH
- bifenylové sloučeniny MeSH
- hodnocení rizik metody MeSH
- houby genetika účinky léků MeSH
- látky znečišťující půdu * toxicita MeSH
- mikrobiota účinky léků MeSH
- monitorování životního prostředí * metody MeSH
- niacinamid analogy a deriváty MeSH
- pesticidy * toxicita MeSH
- průmyslové fungicidy * toxicita MeSH
- půdní mikrobiologie * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2-chloro-N-(4-chlorobiphenyl-2-yl)nicotinamide MeSH Prohlížeč
- bifenylové sloučeniny MeSH
- látky znečišťující půdu * MeSH
- niacinamid MeSH
- pesticidy * MeSH
- průmyslové fungicidy * MeSH
BACKGROUND: Chronic kidney disease (CKD) contributes to global morbidity and mortality. Early, targeted intervention can help mitigate its impact. CK273 is a urinary peptide classifier previously validated in a prospective clinical trial for the early detection of nephropathy. We hypothesized that drug-induced molecular changes in the urinary peptidome could be predicted in silico and guide selecting interventions for individual patients. METHODS: The efficacy of the urinary peptidomic classifier CKD273 in predicting major adverse kidney events (≥ 40% decline in estimated glomerular filtration rate or kidney failure -median follow-up: 1.50 (95%CI 0.35, 5.0) years), was confirmed in a retrospective cohort of 935 participants. In silico prediction of treatment effects from four drug-based interventions (Mineralocorticoid receptor antagonist, Sodium-glucose co-transporter 2 inhibitor, Glucagon-like peptide-1 receptor agonist, and Angiotensin receptor blocker), dietary intervention (olive oil), and exercise was performed based on: a) individual baseline urinary peptide profiles, and b) previously defined fold changes in peptide abundance after treatment in clinical trials. Following recalibration to align with outcomes of these trials, CKD273 scores were calculated for each patient after in silico treatment. For combination treatments, the effects of multiple interventions were combined. RESULTS: Simulated interventions demonstrated a significant reduction in median CKD273 scores, from 0.57 (IQR: 0.19-0.81) before to 0.039 (IQR: -0.192-0.363) after the most beneficial intervention (paired Wilcoxon test, P < 0.0001). The combination of all available treatments was not the most frequently predicted optimal intervention. Patients with higher baseline CKD273 scores required more complex intervention combinations to achieve the greatest score reduction. CONCLUSIONS: This study supports the feasibility of in silico predicting effects of therapeutic interventions on CKD progression. By identifying the most beneficial treatment combinations for individual patients, this approach paves the way for precision medicine trials in CKD. A prospective study is currently being planned to validate the in silico-guided intervention approach and determine its exact benefits on patient-relevant outcomes.
- Klíčová slova
- Chronic kidney disease, Clinical proteomics, Drug response prediction, Optimizing intervention, Urine peptides,
- MeSH
- chronická renální insuficience * moč terapie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidy moč MeSH
- počítačová simulace * MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- peptidy MeSH
To obtain materials with desired properties, material compositions are primarily altered, whereas thin films offer additional unique avenues. By combining state-of-the-art first-principles calculations and experimental investigations of thin films of strontium titanate as an exemplary representative of a broad class of perovskite oxides and the extensive family of ferroelectrics, a novel approach is presented to achieving superior material responses to external stimuli. The findings reveal that substrate-imposed deformations, or strains, significantly alter the frequencies and magnitudes of atomic vibrations in thin films. Consequently, material-specific response-stimulus coefficients can become strain-dependent. The strain-dependent Curie constant, which characterizes the dielectric response to thermal stimuli, is theoretically justified and experimentally validated. Given that atomic vibrations fundamentally govern various response coefficients in a wide range of materials, and that thin films are typically deformed by substrates, it is anticipated that unprecedented responses can be generally attained through substrate-induced control of atomic vibrations in thin films.
- Klíčová slova
- computational methods, condensed matter physics, ferroelectrics, physics & engineering,
- Publikační typ
- časopisecké články MeSH
Open science is now established as an important paradigm for publicly funded research. The main principle being that to ensure best use of research data and integrity of the scientific process the information from experiments should be made widely and freely available. However, dedicated technical infrastructure to enable useful access to comprehensive experimental information in molecular biophysics is lacking, in particular in regard to repositories for raw measurement data. The Molecular Biophysics Database (MBDB) was created to fill this gap. The MBDB provides a common and extensible framework to store and access raw measurement data from a growing number of biophysical methods, currently including bio-layer interferometry, isothermal titration calorimetry, surface plasmon resonance, and microscale thermophoresis, with additional methods planned for the future. Alongside the raw measurement data from these methods, a rich set of metadata to enable data reuse is captured in accordance with the FAIR data management principles. An overview of the data models and technologies that were used to create the MBDB is presented here.
- Klíčová slova
- Database, FAIR principles, Metadata model, Molecular biophysics, Raw data, Repository,
- Publikační typ
- časopisecké články MeSH
The hippocampus is a key brain region for memory and cognitive functions, which consists of distinct subregions with different developmental trajectories throughout adolescence. However, trajectories of hippocampal subfield change in young adulthood remain uncharacterized, as is their potential relationship with cortical brain aging and cognitive ability during this time. We conducted two magnetic resonance imaging (MRI) follow-ups of a prenatal birth cohort in young adulthood and studied the effects of chronological age and cortical brain age on the volume of hippocampal subfields in the early 20s (n = 109; 51% men) and late 20s (n = 251; 53% men) and how these age-related volumetric changes might relate to full-scale IQ (FSIQ). We showed that CA1 and CA4DG subfields continue to grow in the third decade of life and that this growth can be observed both at the level of chronological age as well as estimated cortical brain age at both MRI timepoints. Moreover, in men, a larger size of these age-related subfields was associated with higher FSIQ, and the deviations between cortical brain age and chronological age mediated the relationships between right CA1 and FSIQ, as well as right CA4DG and FSIQ. These findings reveal that coordinated patterns of advanced cortical brain aging and hippocampal maturation may confer a cognitive advantage in young adulthood.
- Klíčová slova
- CA1, CA4DG, brain aging, full‐scale IQ, hippocampal subfields, young adulthood,
- MeSH
- dospělí MeSH
- hipokampus * růst a vývoj diagnostické zobrazování anatomie a histologie MeSH
- inteligence fyziologie MeSH
- kognice * fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- stárnutí * fyziologie MeSH
- velikost orgánu MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Motion Capture (MoCap) is rapidly growing in the sports, biomechanics, healthcare, and medicine segments, where accuracy is crucial. Current research studies are concurrently confirming that the accuracy can be determined only for the specific analyzed configuration and thus recommending performing your own accuracy verification on your specific setup. However, it is often hard to perform since it requires significant effort, time, knowledge of statistical data analysis and often equipment and tools that are not commonly available. This paper deals with this by creating a standardized setup with carefully evaluated accuracy, substituting the on-site validation process (in case of using such a setup) or providing the worst-case accuracy (when a more advanced setup is used). The setup is designed to be low-cost, easily reproducible and cover a wide range of applications - thus VICON setup with five VERO v1.3 cameras is used. The accuracy was evaluated using the robotic manipulator EPSON C3, determining that the absolute positioning accuracy of such a standardized setup is 0.65 mm on average (SD = 0.48, with maximal error of 2.47 mm) and rotation accuracy 0.40° (SD = 0.35, with maximal error of 2.0°), which is negligible considering the experimental diameter of 1.4 m and full angular span. The major source of error was specific to particular spatial and rotational positions; other systematic and other random errors were noticeably smaller. If the standardized setup is used and all its requirements are met, a similar accuracy as validated above can be expected without the need to explicitly validate the specific configuration, which is time-consuming and resource-intensive.
- Klíčová slova
- Accuracy assessment, Motion capture, Standardization, VICON, Validation,
- Publikační typ
- časopisecké články MeSH
