Search

Abstract Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Abstract Extracellular vesicles (EVs) constitute a vital component of intercellular communication, exerting significant influence on metastasis formation and drug resistance mechanisms. Malignant melanoma (MM) is one of the deadliest forms of skin cancers, because of its high metastatic potential and often acquired resistance to oncotherapies. The prevalence of BRAF mutations in MM underscores the importance of BRAF-targeted therapies, such as vemurafenib and dabrafenib, alone or in combination with the MEK inhibitor, trametinib. This study aimed to elucidate the involvement of EVs in MM progression and ascertain whether EV-mediated metastasis promotion persists during single agent BRAF (vemurafenib, dabrafenib), or MEK (trametinib) and combined BRAF/MEK (dabrafenib/trametinib) inhibition. Using five pairs of syngeneic melanoma cell lines, we assessed the impact of EVs – isolated from their respective supernatants – on melanoma cell proliferation and migration. Cell viability and spheroid growth assays were employed to evaluate proliferation, while migration was analyzed through mean squared displacement (MSD) and total traveled distance (TTD) measurements derived from video microscopy and single-cell tracking. Our results indicate that while EV treatments had remarkable promoting effect on cell migration, they exerted only a modest effect on cell proliferation and spheroid growth. Notably, EVs demonstrated the ability to mitigate the inhibitory effects of BRAF inhibitors, albeit they were ineffective against a MEK inhibitor and the combination of BRAF/MEK inhibitors. In summary, our findings contribute to the understanding of the intricate role played by EVs in tumor progression, metastasis, and drug resistance in MM.

Abstract Most of the review research papers previously published were mostly focused on solar dryer design, development, performance evaluation, modification, technologies of solar dryers, etc. There were no works of literature reviews that specifically concerned how much solar dryers can carry. So, the review gives some clues about the carrying capacity of solar dryers. Measuring or knowing solar capacity has critical importance in the drying industry. It helps to produce quality dried products, design efficient solar dryers, and provide valuable insights for researchers, engineers and policymakers involved in solar drying technologies. The current review systematically examines the relevant scientific literature published between 2000 and 2023. The exclusion and inclusion criteria were used to identify the documents. A total of 1230 studies were selected for analysis, encompassing a wide range of geographical regions, crop types, and solar drying technologies. Based on the review conducted; solar dryers (direct, indirect, mixed, and hybrid) can vary between 1 and 250 kg in capacity applied for agricultural products drying purposes. According to the reviewed articles, the minimum loading capacities designed and recorded in the first, second, third, and fourth quinquennial periods were 1 kg, 1 kg, 4.75 kg.m−2, and 5.4 kg.m−2, respectively. In the same order as the minimum, the maximum loading capacities observed in the stated quinquennial periods were 250 kg/per day, 250 kg, 70 kg, and 45 kg, respectively.

Cél: A kiválasztott rendőri intézkedések szabályozása változásainak vizsgálata, bemutatása. Módszertan: A cikk szerzője felkutatja és összefoglalja, hogy az elmúlt 140 évben milyen szabályok alapján intézkedtek a magyar rendészeti szervek közegei. Megállapítások: A kutatás során és a publikációban bemutatásra kerül, hogy nem tekinthető elavultnak a korábbi normaszöveg, illetve nem jelent minden esetben fejlődést a későbbi reguláció. Érték: A publikáció megmutatja, hogy a korábbi évek szabályozása útmutató lehet a jelen jogalkotói számára.

IntroductionOrganizational digitalization is a phenomenon that is becoming more widespread and holistic; that is responsible for more employees being affected by digital work and working from home. While introducing remote work offers numerous economic benefits for organizations, this transition must be aligned with employees' needs rather than in an authoritarian manner. Our research aimed to investigate how sub-factors of technostress, directly and indirectly, influence the satisfaction and desire to work from home.MethodsWe conducted a cross-sectional survey with a sample of 361 office workers with at least two years of experience who have spent some time working from home. We checked our hypotheses with a path model.ResultsOur research found that techno-insecurity and techno-complexity have a minimal direct influence on the desire to work from home. However, the desire to work from home significantly decreases through various mediation pathways via the status sub-factor (which can be seen as one of the latent benefits of remote work) and through satisfaction with working from home. Our model explains 33.7% of the variance in the desire to work from home.DiscussionThis suggests that leaders have a task of great significance: to decrease the technostress employees are exposed to and to draw the attention of researchers to the fact that technostress has more complex indirect effects than previously assumed.

Introduction Alterations in motor activity are an extremely important characteristic and one of the leading symptoms of major functional psychiatric disorders. These pattern disturbances can be observed in schizophrenia. Actigraphy is a non-invasive method that can be used to monitor these changes, and recent studies emphasize its significance in the early identification of disorders like schizophrenia. Objectives This study uniquely focuses on distinguishing latent liabilities for schizotypy from manifested schizophrenia using specific actigraphy features. Methods Actigraphy data were collected using specialized devices from the University of Szeged and Haukeland University Hospital datasets (Berle et al., 2010). At Haukeland University Hospital patients with chronic schizophrenia (N=23) (so-called: manifested group) were collected, separately, at the University of Szeged, healthy university students were recruited and screened for latent tendencies towards shizotypic pathological development. In the latter study, two main groups were formed based on their scores: a positive schizotypy factor group (so-called: latent group) (N=22) and a control group (N=25), with actigraphy data. Utilizing the pyActigraphy library (Hammad et al., 2021) and wavelet analysis, features such as activity mean, interdaily stability and sleep movement characteristics were derived. Feature selection employed machine learning algorithms, notably Logistic Regression, Random Forest, ANN, and AHFS aided by Shapley values and Click Forming Feature Selection for insight into the most influential features. Results The three models exhibited similar performance with a 60% accuracy threshold. In the latent group, sleep-related movements have a substantial impact, while in the manifested group, in addition to sleep characteristics, features like RA, IV, ADAT, M10, the mean activity level (all of which decreased), and the ratio of zero values also play a significant role. In the latent group, features related to the length of small amplitude movements were dominant, particularly the increased values, along with a decrease in the density of large movements. Conclusions Our study indicates that in the latent phase of schizophrenia, actigraphy features related to sleep are most significant, but as the disease progresses, both sleep and daytime activity patterns are crucial. Sleep disturbances may signal early susceptibility, with nighttime movements offering clearer insights. These variations might be influenced by medication effects in the manifested group, reflecting the broader challenges in schizophrenia research where the drug-free study of patients remains elusive. Further studies should explore these features in the Clinical High Risk and prodromal groups to refine our understanding of the development of the disorder. Disclosure of Interest None Declared

Abstract Background The action of mesenchymal stem cells (MSCs) is the subject of intense research in the field of regenerative medicine, including their potential use in companion animals, such as dogs. To ensure the safety of canine MSC batches for their application in regenerative medicine, a quality control test must be conducted in accordance with Good Manufacturing Practices (GMP). Based on guidance provided by the European Medicines Agency, this study aimed to develop and validate a highly sensitive and robust, nucleic acid-based test panel for the detection of various canine pathogens. Analytical sensitivity, specificity, amplification efficiency, and linearity were evaluated to ensure robust assessment. Additionally, viable spike-in controls were used to control for optimal nucleic acid extraction. The conventional PCR-based and real-time PCR-based pathogen assays were evaluated in a real-life setting, by direct testing MSC batches. Results The established nucleic acid-based assays displayed remarkable sensitivity, detecting 100–1 copies/reaction of template DNA. They also exhibited high specificity and efficiency. Moreover, highly effective nucleic acid isolation was confirmed by the sensitive detection of spike-in controls. The detection capacity of our optimized and validated methods was determined by direct pathogen testing of nine MSC batches that displayed unusual phenotypes, such as reduced cell division or other deviating characteristics. Among these MCS batches of uncertain purity, only one tested negative for all pathogens. The direct testing of these samples yielded positive results for important canine pathogens, including tick-borne disease-associated species and viral members of the canine infectious respiratory disease complex (CIRDC). Notably, samples positive for the etiological agents responsible for enteritis (CPV), leptospirosis (Leptospira interrogans), and neosporosis (Neospora caninum) were also identified. Furthermore, we conducted biosafety evaluation of 12 MSC batches intended for therapeutic application. Eleven MSC batches were found to be free of extraneous agents, and only one tested positive for a specific pathogen, namely, canine parvovirus. Conclusion In this study, we established and validated reliable, highly sensitive, and accurate nucleic acid-based testing methods for a broad spectrum of canine pathogens.

Abstract The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. “European Registry on H. pylori Management (Hp-EuReg)” data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18–59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p

Abstract Background Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear. Results Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits. Conclusions Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions.

IntroductionThe development of costs-effective and sensitive screening solutions to prevent amblyopia and identify its risk factors (strabismus, refractive problems or mixed) is a significant priority of pediatric ophthalmology. The main objective of our study was to compare the classification performance of various vision screening tests, including classic, stereoacuity-based tests (Lang II, TNO, Stereo Fly, and Frisby), and non-stereoacuity-based, low-density static, dynamic, and noisy anaglyphic random dot stereograms. We determined whether the combination of non-stereoacuity-based tests integrated in the simplest artificial intelligence (AI) model could be an alternative method for vision screening.MethodsOur study, conducted in Spain and Hungary, is a non-experimental, cross-sectional diagnostic test assessment focused on pediatric eye conditions. Using convenience sampling, we enrolled 423 children aged 3.6–14 years, diagnosed with amblyopia, strabismus, or refractive errors, and compared them to age-matched emmetropic controls. Comprehensive pediatric ophthalmologic examinations ascertained diagnoses. Participants used filter glasses for stereovision tests and red-green goggles for an AI-based test over their prescribed glasses. Sensitivity, specificity, and the area under the ROC curve (AUC) were our metrics, with sensitivity being the primary endpoint. AUCs were analyzed using DeLong’s method, and binary classifications (pathologic vs. normal) were evaluated using McNemar’s matched pair and Fisher’s nonparametric tests.ResultsFour non-overlapping groups were studied: (1) amblyopia (n = 46), (2) amblyogenic (n = 55), (3) non-amblyogenic (n = 128), and (4) emmetropic (n = 194), and a fifth group that was a combination of the amblyopia and amblyogenic groups. Based on AUCs, the AI combination of non-stereoacuity-based tests showed significantly better performance 0.908, 95% CI: (0.829–0.958) for detecting amblyopia and its risk factors than most classical tests: Lang II: 0.704, (0.648–0.755), Stereo Fly: 0.780, (0.714–0.837), Frisby: 0.754 (0.688–0.812), p

Abstract In the past decade, extracellular vesicles (EVs) have attracted substantial interest in biomedicine. With progress in the field, we have an increasing understanding of cellular responses to EVs. In this Technical Report, we describe the direct nanoinjection of EVs into the cytoplasm of single cells of different cell lines. By using robotic fluidic force microscopy (robotic FluidFM), nanoinjection of GFP positive EVs and EV‐like particles into single live HeLa, H9c2, MDA‐MB‐231 and LCLC‐103H cells proved to be feasible. This injection platform offered the advantage of high cell selectivity and efficiency. The nanoinjected EVs were initially localized in concentrated spot‐like regions within the cytoplasm. Later, they were transported towards the periphery of the cells. Based on our proof‐of‐principle data, robotic FluidFM is suitable for targeting single living cells by EVs and may lead to information about intracellular EV cargo delivery at a single‐cell level.

The aim of the present study was to determine the antioxidant capacity and total polyphenol content of raw milk, dairy products (ricotta and cottage cheese), and by-products (sweet and acid whey) from different animal breeds (cow, goat).Overall, the total polyphenol content of raw milk ranged from 420.34 to 490.72 mg GAE/100 mL, while the total antioxidant content changed between 8.95 and 28.72 mg AAE/100 mL. These values in the case of cottage cheeses were 32.29–124.29 mg GAE/100 mL for polyphenols and 14.12–16.38 mg AAE/100 g for antioxidants. Significant differences were observed between the total polyphenol content and antioxidant properties of sweet- (10.85–197.55 mg AAE/100 g antioxidant; 32.29–124.29 mg GAE/100 g polyphenol) and acid whey (13.28–158.69 mg AAE/100 g antioxidant; 43.50–98.03 mg GAE/100 g polyphenol). In addition, slight differences in total polyphenol content (10.55–19.01 mg GAE/100 g) and antioxidant capacity (10.84–15.93 mg AAE/100 g) were observed for ricotta cheeses made from milk of different animal breeds. The results show that milk and dairy products are excellent sources of antioxidants and polyphenols.

Abstract Background High fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations in the liver tissue have not been studied before. The aim of the current study was to investigate the effect of HFD on hepatic triglyceride (TG), diglyceride (DG) and ceramide (CER) levels and on the expression of four key genes involved in lipid homeostasis (Pcsk9, Ldlr, Cd36 and Anxa2) in the liver. In addition, the potential role of PCSK9 in the observed changes was further investigated by using PCSK9 deficient mice. Methods We used two in vivo models: mice kept on HFD for 20 weeks and PCSK9−/− mice. The amount of the major TGs, DGs and CERs was measured by using HPLC–MS/MS analysis. The expression profiles of four lipid related genes, namely Pcsk9, Ldlr, Cd36 and Anxa2 were assessed. Co-localization studies were performed by confocal microscopy. Results In HFD mice, hepatic PCSK9 expression was decreased and ANXA2 expression was increased both on mRNA and protein levels, and the amount of LDLR and CD36 receptor proteins was increased. While LDLR protein level was also elevated in the livers of PCSK9−/− mice, there was no significant change in the expression of ANXA2 and CD36 in these animals. HFD induced a significant elevation in the hepatic levels of all measured TG and DG but not of CER types, and increased the proportion of monounsaturated vs. saturated TGs and DGs. Similar changes were detected in the hepatic lipid profiles of HFD and PCSK9−/− mice. Co-localization of PCSK9 with LDLR, CD36 and ANXA2 was verified in HepG2 cells. Conclusions Our results show that obesogenic HFD downregulates PCSK9 expression in the liver and causes alterations in the hepatic lipid accumulation, which resemble those observed in PCSK9 deficiency. These findings suggest that PCSK9-mediated modulation of LDLR and CD36 expression might contribute to the HFD-induced changes in lipid homeostasis.

Abstract Background According to the European Society of Gastrointestinal Endoscopy guidelines, self-expandable metal stents (SEMSs) are preferable to plastic stents (PSs) in the management of pancreatic cancer, regardless of cancer stage. The aim of this study was to compare the therapeutic efficacy and treatment costs of SEMS and PS in the management of malignant biliary obstruction. Methods One hundred and thirty-five patients who underwent endoscopic stent placement were retrospectively enrolled and divided into PS (41 patients), primary SEMS (39 patients) and secondary SEMS (55 patients) groups. We determined the technical and functional success rate, stent patency, and cumulative treatment cost. Results A total of 111 SEMSs and 153 PSs were placed with similar technical (100% vs. 98.69%) and functional success rate (90.10% vs. 86.27%) but with different stent patency (10.28 vs. 22.16 weeks; p

The comprehensive examination of bile acids is of paramount importance across various fields of health sciences, influencing physiology, microbiology, internal medicine, and pharmacology. While enzymatic reaction-based photometric methods remain fundamental for total BA measurements, there is a burgeoning demand for more sophisticated techniques such as liquid chromatography–tandem mass spectrometry (LC-MS/MS) for comprehensive BA profiling. This evolution reflects a need for nuanced diagnostic assessments in clinical practice. In canines, a BA assessment involves considering factors, such as food composition, transit times, and breed-specific variations. Multiple matrices, including blood, feces, urine, liver tissue, and gallbladder bile, offer insights into BA profiles, yet interpretations remain complex, particularly in fecal analysis due to sampling challenges and breed-specific differences. Despite ongoing efforts, a consensus regarding optimal matrices and diagnostic thresholds remains elusive, highlighting the need for further research. Emphasizing the scarcity of systematic animal studies and underscoring the importance of ap-propriate sampling methodologies, our review advocates for targeted investigations into BA alterations in canine pathology, promising insights into pathomechanisms, early disease detection, and therapeutic avenues.

Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives.

After a long device enhancement phase, scientific operation resumed in 2022. The main new device components are the water cooling of all plasma facing components and the new water-cooled high heat flux divertor units. Water cooling allowed for the first long-pulse operation campaign. A maximum discharge length of 8 min was achieved with a total heating energy of 1.3 GJ. Safe divertor operation was demonstrated in attached and detached mode. Stable detachment is readily achieved in some magnetic configurations but requires impurity seeding in configurations with small magnetic pitch angle within the edge islands. Progress was made in the characterization of transport mechanisms across edge magnetic islands: Measurement of the potential distribution and flow pattern reveals that the islands are associated with a strong poloidal drift, which leads to rapid convection of energy and particles from the last closed flux surface into the scrape-off layer. Using the upgraded plasma heating systems, advanced heating scenarios were developed, which provide improved energy confinement comparable to the scenario, in which the record triple product for stellarators was achieved in the previous operation campaign. However, a magnetic configuration-dependent critical heating power limit of the electron cyclotron resonance heating was observed. Exceeding the respective power limit leads to a degradation of the confinement.

Filaments are studied by examining fast camera images on the Wendelstein 7-X stellarator. Fast cameras offer a unique perspective, revealing the complex 3D structure of filaments in the entire poloidal cross-section of the plasma. By correlating individual pixels, their location, shape, and movement are analyzed in standard and high- ι configurations. The presence of filaments is not uniform poloidally around. The number of active areas matches the number of magnetic islands in both configurations. Filaments are found to extend to multiple toroidal turns in standard configuration. No time delay is observed between the different toroidal sections. Such behavior is not seen in high- ι configuration. Filaments are observed within and without the edge shear layer, indicated by the direction of their poloidal rotation. Inside the shear layer, their velocity scatters around 1.25 km s ^−1 , accompanied by a lifetime between 80 and 120 µ s. Outside, their velocity shows greater absolute values and variance, but still in a few km s ^−1 range. The similarities and differences between the two configurations are discussed and compared to previous results.

The paper reports for the first time the heat and particle exhaust at the plasma boundary through various edge diagnostics for the high-performance plasma obtained after pellet injection on Wendelstein 7-X. The plasma density at the edge is found to be reduced by a factor of 2 in the high-performance phase, supporting the previously reported density peaking at the plasma centre. The plasma beta effect on the magnetic topology is reflected by the appearance of the second strike line, which is well understood with simulation. However, during the rapid decay phase of the enhanced confinement, a transient localized heat flow of up to 16 MW m ^−2 is observed at the leading edge of a poorly cooled divertor component, which has not been understood but raises concerns about machine safety.

A support laboratory has been set up to study pellet production, launch and shattering of cryogenic protium, deuterium, and neon pellets for the ITER disruption mitigation system, which plans to use 28.5 × 57 mm (diameter × length) protium, neon an mixture pellets in the Shattered Pellet Injectors. Such large protium pellets have not been produced and launched before, therefore the desublimation and launch process have been studied in detail in two steps. First 19 mm diameter pellets were produced, followed by the demonstration of the final pellet size. Pellet desublimation recipes were established for all pellet types, and it was found that, under certain conditions, even the large neon pellets can be launched with a propellant gas pulse, without requiring a mechanical punch device. This is attributed to cryogenic snow formation on the surface of the pellet. Conditions for the snow formation are studied and tendencies are understood using simple calculations.

Increased solar radiation during solar flare events can cause additional ionization and enhanced absorption of the electromagnetic (EM) waves in the ionosphere leading to partial or even total radio fade-outs. In this study, the ionospheric response to large solar flares has been investigated using the ionosonde data from Juliusruh (54.63° N, 13.37° E), Průhonice (49.98° N, 14.55° E) and San Vito (40.6° N, 17.8° E) Digisonde (DPS-4D) stations. We studied the effect of 13 intense (>C4.8) solar flares that occurred between 06:00 and 16:30 (UT, daytime LT = UT+1 h) from 04 to 10 September 2017 using three different methods. A novel method based on the amplitude data of the measured EM waves is used to calculate and investigate the relative absorption changes (compared to quiet period) occurring during the flares. The amplitude data are compared with the variation of the fmin parameter (fmin, the minimum measured frequency, it is considered as a qualitative proxy for the “non-deviative” radio wave absorption). Furthermore, the signal-to-noise ratio (SNR) measured by the Digisondes was used as well to quantify and characterize the fade-out events and the ionospheric absorption. In order to compare the three different methods, residuals have been defined for all parameters, which provide the percentage changes compared to the selected reference periods. Total and partial radio fade-outs, increased values (+0.4%–318%) of the fmin parameter, and +20%–1400% amplitude changes (measured at 2.5 and 4 MHz) were experienced during and after the investigated flares. Generally, the observed changes depended on the intensity, solar zenith angle and duration of the flare events. Although the three different methods have their own advantages/disadvantages and their limitations, the combination of them seems to be an efficient approach to monitor the ionospheric response to solar flares.

Abstract Extracellular vesicles (EVs) are cell-derived, membrane-enclosed particles with the potential for a wide range of future therapeutic applications. However, EVs have almost always been administered by direct injection, likely hindering their efficacy because of rapid clearance from the injection site. The present study aimed to incorporate medium-sized extracellular vesicles (mEVs) into fast-dissolving electrospun polyvinylpyrrolidone-based nanofibers to explore the storage-dependent structure–activity relationship of the resulting nanofibrous formulations. Aqueous polyvinylpyrrolidone-based precursor solutions were selected for the electrospinning process. The presence of EVs in the electrospun samples was confirmed by transmission electron microscopy, flow cytometry, and confocal laser scanning microscope. The results indicate that the fibrous structure of the samples was preserved until the end of the 12-week storage period. Furthermore, regardless of the storage temperature (4 °C or room temperature), nanofibers and nanofiber-associated EVs were present throughout the experimental period. Incorporating EVs into a stable solid polymeric delivery base could preserve their stability; meanwhile, according to the characteristics of the polymer, their targeted and controlled release can be achieved.