INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- Klíčová slova
- Angiogenic factors, Preeclampsia, Term pregnancy, Uterine Doppler,
- MeSH
- dospělí MeSH
- lidé MeSH
- placentární oběh fyziologie MeSH
- placentární růstový faktor * krev MeSH
- plocha pod křivkou MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * krev diagnostické zobrazování MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- reologie * metody statistika a číselné údaje MeSH
- reprodukovatelnost výsledků MeSH
- rychlost toku krve fyziologie MeSH
- těhotenství MeSH
- třetí trimestr těhotenství * krev fyziologie MeSH
- ultrasonografie dopplerovská metody statistika a číselné údaje MeSH
- ultrasonografie prenatální * metody statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- FLT1 protein, human MeSH Prohlížeč
- placentární růstový faktor * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * MeSH
A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.
- Klíčová slova
- BSA oxidation, Cytotoxic activity, Cytotoxicity of O-Mesylates, DFT calculations, Oxidation of triterpenoids, SeO(2) oxidation, α-phenylseleno-ketone,
- MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- oxidace-redukce MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- screeningové testy protinádorových léčiv MeSH
- selen * chemie MeSH
- teorie funkcionálu hustoty MeSH
- triterpeny * chemie farmakologie chemická syntéza 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
- lupane MeSH Prohlížeč
- pentacyklické triterpeny MeSH
- protinádorové látky * MeSH
- selen * MeSH
- triterpeny * MeSH
Single-structure scoring functions have been considered inferior to expensive ensemble free energy methods in predicting protein-ligand affinities. We are revisiting this dogma with the recently developed semiempirical quantum-mechanical (SQM)-based scoring function, SQM2.20, comparing its performance to the standard scoring functions on one hand and state-of-the-art molecular dynamics (MD)-based free-energy methods on the other hand. The comparison is conducted on a well-established Wang data set comprising eight protein targets with 200 ligands. The initial low correlation of SQM2.20 scores with the experimental binding affinities of R2 = 0.21 was improved to R2 = 0.47 by a systematic refinement of the input structures and omission of the ligand deformation energy. Consequently, SQM2.20 representing accurate single-structure scoring functions, exhibited an average performance comparable to that of MD-based methods (R2 = 0.52) and surpassed the performance of standard scoring functions (R2 = 0.26). The per-target analysis highlighted the pivotal role of high-quality input structures on the outcomes of single-structure methods. In the instances where such structures are available, SQM2.20 scoring has been shown to rival or even exceed MD-based methods in predicting protein-ligand binding affinities, while exhibiting significantly reduced computation time.
Micro- and nanoplastic pollution is pervasive worldwide, infiltrating drinking water and food chains, accumulating in the human body, and posing serious threats to public health and ecosystems. Despite these urgent challenges, effective strategies to curb the widespread presence of micro- and nanoplastics have not yet been sufficiently developed. Here, we present magnetically driven living bacterial microrobots that exhibit a nature-inspired three-dimensional (3D) swarming motion, allowing the dynamic capture and retrieval of aquatic micro- and nanoplastics originating from various commercial products. By combining autonomous propulsion with magnetically guided navigation, we enabled the multimodal swarming manipulation of magnetotactic bacteria-based living microrobots (MTB biobots). The actuation of a rotating magnetic field induces a fish schooling-like 3D swarming navigation, allowing the active capture of micro- and nanoplastics, which are then retrieved from the contaminated water by magnetic separation. Our results show that the 3D magnetic swarming of MTB biobots synergistically enhances the removal efficiencies of both model and real-world microplastics, demonstrating their practical potential in water treatment technologies. Overall, plastic-seeking living bacterial microrobots and their swarm manipulation offer a straightforward and environmentally friendly approach to micro- and nanoplastic treatment, providing a biomachinery-based solution to mitigate the pressing microplastic pollution crisis.
- Klíčová slova
- biohybrid microrobots, magnetically driven, magnetotactic bacteria, microplastics, nanoplastics, swarming behavior, water purification,
- MeSH
- chemické látky znečišťující vodu * izolace a purifikace chemie MeSH
- čištění vody * metody MeSH
- magnetické pole MeSH
- mikroplasty * izolace a purifikace chemie MeSH
- robotika * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chemické látky znečišťující vodu * MeSH
- mikroplasty * MeSH
BACKGROUND: Socially assistive robots (SARs) hold promise for supporting older adults (OAs) in hospital settings by promoting social engagement, reducing loneliness, and enhancing emotional well-being. They may also assist health care professionals by delivering information, managing routines, and alleviating workload. However, their acceptability and usability remain major challenges, particularly in dynamic real-world care environments. OBJECTIVE: This study aimed to evaluate the acceptability and usability of a SAR in a geriatric day care hospital (DCH) and to identify key factors influencing its adoption by OAs and their informal caregivers. METHODS: Over the course of 1 year, 97 participants (n=65, 67%, OA patients and n=32, 33%, informal caregivers) took part in a mixed methods evaluation of ARI, a socially assistive humanoid robot developed by PAL Robotics. ARI was deployed in the waiting area of a geriatric day care robot in Paris (France), where it interacted with users through voice-based dialogue. After each session, participants completed 2 standardized assessments, the Acceptability E-scale (AES) and the System Usability Scale (SUS), administered orally to ensure accessibility. Open-ended qualitative feedback was also collected to capture subjective experiences and contextual perceptions. RESULTS: Acceptability scores significantly increased across waves (wave 1: mean 15.4/30, SD 5.81; wave 2: mean 20.9/30, SD 5.25; wave 3: mean 22.5/30, SD 4.23; P<.001). Usability scores also improved (wave 1: mean 47.9/100, SD 24.18; wave 2: mean 57.4/100, SD 22.46; wave 3: mean 69.3/100, SD 16.03; P<.001). A strong positive correlation was observed between acceptability and usability scores (r=0.664, P<.001). Qualitative findings indicated improved ease of use, clarity, and user satisfaction over time, particularly following the integration of a large language model (LLM) in wave 2, leading to more coherent, natural, and context-aware interactions. CONCLUSIONS: Successive system enhancements, most notably the integration of an LLM, led to measurable gains in usability and acceptability among patients and informal caregivers. These findings underscore the importance of iterative, user-centered design in deploying SARs in geriatric care environments. TRIAL REGISTRATION: Approved by the French national ethics committee (CPP Ouest II, IRB: 2021/20) as it did not involve randomization or clinical intervention.
- Klíčová slova
- acceptability, gerontology, hospital environment, human-robot interaction, informal caregivers, large language model, older adults, socially assistive robot, usability,
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- pomůcky pro sebeobsluhu * MeSH
- robotika * přístrojové vybavení MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- velké jazykové modely MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Francie MeSH
BACKGROUND AND OBJECTIVE: Digital Holographic Microscopy provides a new kind of quantitative image data about live cells' in vitro activities. Apart from non-invasive and staining-free imaging, it offers topological weighting of cell mass. This led us to develop a particular tool for assessing cell mass dynamics. METHODS: Programming language Python and a training set of time-lapse images of adherent HT-1080 cells derived from human fibrosarcoma taken with dry objective 40x/0.95 at 30-second intervals were used to create the Analytical Image Differencing (AID) method. RESULTS: The AID makes the best of these new data by evaluating the difference between the chosen two quantitative phase images from the time-lapse series. The contribution of the method is demonstrated on hiQPI (Holographic Incoherent-light-source Quantitative Phase Imaging) image data taken with a Q-phase microscope. The analysis outputs are graphical and complemented with numerical data. To underscore the significance of the Analytical Image Differencing (AID) method, an initial pilot experiment was conducted to show the available analyses of sequential overlapping images capturing the movement of cancer cells. Notably, besides defining changes in areas used by the cell (newly or steadily occupied or better abandoned) it is an introduction to the zero-line concept, which denotes spots of tranquility among continuously moving surroundings. CONCLUSIONS: The measurement of zero-line length has emerged as a novel biomarker for characterizing cell mass transfer. The sensitivity of phase change measurements is demonstrated. The noise quality of input images obtained with incoherent (hiQPI) and coherent (QPI) methods is compared. The resulting effect on the AID method output is also shown. The findings of this study introduce a novel approach to evaluating cellular behavior in vitro. The concept emerged as a particularly noteworthy outcome. Collectively, these results highlight the substantial potential of AID in advancing the field of cancer cells biology, particularly.
- Klíčová slova
- Biophysics, Cancer cell migration, Digital holographic microscopy, Image processing, Live cell imaging, Non-invasive, Quantitative phase imaging, Staining-free imaging,
- MeSH
- algoritmy MeSH
- časosběrné zobrazování MeSH
- fibrosarkom patologie MeSH
- holografie metody MeSH
- lidé MeSH
- mikroskopie MeSH
- nádorové buněčné linie MeSH
- počítačové zpracování obrazu MeSH
- pohyb buněk * MeSH
- programovací jazyk MeSH
- software MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Inspired by Richard Feynman's 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to scaling up production, commercialization, and regulatory frameworks that are crucial for transitioning from research to practical applications. We also emphasize the need for interdisciplinary collaboration to address both technical and nontechnical challenges, such as sustainability, ethics, and business considerations. Finally, we propose a roadmap for future research to accelerate the development of micro/nanorobots, positioning them as essential tools for addressing grand challenges and enhancing the quality of life.
- Klíčová slova
- collective behavior, functionality, intelligence, micro/nanorobots, nanotechnology, propulsion, smart materials, technological translation,
- MeSH
- lidé MeSH
- nanotechnologie * metody MeSH
- robotika * přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Self-propelled nano- and micromachines have immense potential as autonomous seek-and-act devices in biomedical applications. In this study, we present microrobots constructed with inherently biocompatible materials and propulsion systems tailored to skin-related applications. Addressing the significant treatment challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) skin infections, we demonstrate that photocatalytic titanium dioxide microrobots decorated with silver or platinum can effectively and rapidly eradicate MRSA biofilms grown on skin-mimicking membranes and porcine skin tissues. These microrobots are powered by hydrogen peroxide or ultraviolet light─agents considered toxic in high concentrations but commonly used in controlled amounts for skin disinfection and naturally encountered by the skin. By examining the effects of different metal coatings on the propulsion abilities of the microrobots, we show that these chemically propelled devices can eliminate biofilms without causing significant damage to the surrounding skin tissues, as confirmed by histological analysis. This work paves the way for the use of microrobots in skin-related biomedical applications, particularly in cases where traditional antibiotics are ineffective.
- Klíčová slova
- Janus particles, biofilm, microrobots, skin infection, titanium dioxide,
- MeSH
- antibakteriální látky * farmakologie chemie MeSH
- biofilmy účinky léků MeSH
- kůže * mikrobiologie účinky léků MeSH
- methicilin rezistentní Staphylococcus aureus * účinky léků fyziologie MeSH
- peroxid vodíku chemie farmakologie MeSH
- platina chemie farmakologie MeSH
- prasata MeSH
- robotika * přístrojové vybavení MeSH
- stafylokokové infekce kůže * farmakoterapie mikrobiologie MeSH
- stříbro chemie farmakologie MeSH
- titan chemie farmakologie MeSH
- ultrafialové záření MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- peroxid vodíku MeSH
- platina MeSH
- stříbro MeSH
- titan MeSH
- titanium dioxide MeSH Prohlížeč
The Protein Data Bank (PDB) is the largest database of experimentally determined protein structures, containing more than 230 000 experimentally determined structures. The chemical reactivity of proteins is based on the electron density distribution, which is usually approximated by partial atomic charges. However, because of the size and high variability, there is not yet a universal and accurate tool for calculating the partial atomic charges of these structures. For this reason, we introduce the web application PDBCharges: a tool for quick calculation of partial atomic charges for protein structures from PDB. The charges are calculated using the recent semi-empirical quantum-mechanical method GFN1-xTB, which reproduces PBE0/TZVP/CM5 charges. The computed partial atomic charges can be downloaded in common data formats or visualized online via the powerful Mol* Viewer. The PDBCharges application is freely available at https://pdbcharges.biodata.ceitec.cz and has no login requirement.
- MeSH
- databáze proteinů * MeSH
- internet MeSH
- konformace proteinů MeSH
- kvantová teorie MeSH
- proteiny * chemie MeSH
- software * MeSH
- statická elektřina MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- proteiny * MeSH
The GPCR signalling cascade is a key pathway responsible for the signal transduction of a multitude of physical and chemical stimuli, including light, odorants, neurotransmitters and hormones. Understanding the structural and functional properties of the GPCR cascade requires direct observation of signalling processes in high spatial and temporal resolution, with minimal perturbation to endogenous systems. Optical microscopy and spectroscopy techniques are uniquely suited to this purpose because they excel at multiple spatial and temporal scales and can be used in living objects. Here, we review recent developments in microscopy and spectroscopy technologies which enable new insights into GPCR signalling. We focus on advanced techniques with high spatial and temporal resolution, single-molecule methods, labelling strategies and approaches suitable for endogenous systems and large living objects. This review aims to assist researchers in choosing appropriate microscopy and spectroscopy approaches for a variety of applications in the study of cellular signalling. LINKED ARTICLES: This article is part of a themed issue Complexity of GPCR Modulation and Signaling (ERNST). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.14/issuetoc.
- Klíčová slova
- G protein, G protein‐coupled receptor, biosensors, cell signalling, microscopy, spectroscopy, super‐resolution,
- MeSH
- lidé MeSH
- mikroskopie * metody MeSH
- receptory spřažené s G-proteiny * chemie metabolismus MeSH
- signální transdukce MeSH
- spektrální analýza * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- receptory spřažené s G-proteiny * MeSH
