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Abstract A significant hurdle in untargeted lipid/metabolomics research lies in the absence of reliable, cross-validated spectral libraries, leading to a considerable portion of LC-MS features being labeled as unknowns. Despite continuous advancement in annotation tools and libraries, it is important to safeguard, publish and share acquired data through public repositories. Embracing this trend of data sharing not only promotes efficient resource utilization but also paves the way for future repurposing and in-depth analysis; ultimately advancing our comprehension of Covid-19 and other diseases. In this work, we generated an extensive MS-dataset of 39 Covid-19 infected patients versus age- and gender-matched 39 healthy controls. We implemented state of the art acquisition techniques including IDA and SWATH-DIA to ensure a thorough insight in the lipidome and metabolome, ensuring a repurposable dataset.

Joanna Cymerys,1,* Michalina Bartak,1,* Anna Słońska,1 Agata Lange,2 Sławomir Jaworski,2 Marcin Chodkowski,3 Agnieszka Ostrowska,2 Mateusz Wierzbicki,2 Ewa Sawosz,2 Marcin W Bańbura1 1Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland; 2Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland; 3Military Institute of Hygiene and Epidemiology, Warsaw, Poland*These authors contributed equally to this workCorrespondence: Joanna Cymerys, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-786, Warsaw, Poland, Email joanna_cymerys@sggw.edu.plBackground: The high infectivity of coronaviruses has led to increased interest in developing new strategies to prevent virus spread. Silver nanoparticles (AgNPs) and graphene oxide (GO) have attracted much attention in the antiviral field. We investigated the potential antiviral activity of GO and AgNPs combined in the nanocomposite GO-Ag against murine betacoronavirus MHV using an in vitro model.Methods: GO, AgNPs, and GO-Ag characterization (size distribution, zeta potential, TEM visualization, FT-IR, and EDX analysis) and XTT assay were performed. The antiviral activity of GO-Ag nanocomposites was evaluated by RT-qPCR and TCID50 assays. The results were compared with free AgNPs and pure GO. Cell growth and morphology of MHV-infected hepatocytes treated with GO-Ag composites were analyzed by JuLI™Br. Immunofluorescence was used to visualize the cell receptor used by MHV. Ultrastructural SEM analysis was performed to examine cell morphology after MHV infection and GO-Ag composite treatment.Results: A significant reduction in virus titer was observed for all nanocomposites tested, ranging from 3.2 to 7.3 log10 TCID50. The highest titer reduction was obtained for GO 5 μg/mL - Ag 25 μg/mL in the post-treatment method. These results were confirmed by RT-qPCR analysis. The results indicate that GO-Ag nanocomposites exhibited better antiviral activity compared to AgNPs and GO. Moreover, the attachment of AgNPs to the GO flake platform reduced their cytotoxicity. In addition, the GO-Ag composite modulates the distribution of the Ceacam1 cell receptor and can modulate cell morphology.Conclusion: Graphene oxide sheets act as a stabilizing agent, inhibiting the accumulation of AgNPs and reducing their cellular toxicity. The GO-Ag composite can physically bind and inhibit murine betacoronavirus from entering cells. Furthermore, the constant presence of GO-Ag can inhibit MHV replication and significantly limit its extracellular release. In conclusion, GO-Ag shows promise as an antiviral coating on solid surfaces to minimize virus transmission and spread. Keywords: graphene oxide, silver nanoparticles, GO-Ag composite, antiviral, coronavirus, MHV

The global pandemic of COVID-19 caused by SARS-CoV-2 has had a devastating impact. Although many survived the acute effects of the pandemic, a significant number of survivors, including those with only mild symptoms, are now experiencing a prolonged and debilitating post-viral syndrome known as LC/PASC (long COVID/post-acute sequelae of SARS-CoV-2). Typical symptoms of LC/PASC include fatigue, breathlessness, chest pain, impaired cognition, difficulty sleeping, fever and gastrointestinal symptoms. Anxiety and depression can also last for weeks to months and range from mild to disabling. The association between neuropsychiatric symptoms and SARS-CoV-2 infection raises questions about the possible routes of SARS-CoV-2 entry to the central nervous system (CNS) and long-term effects of the virus on the CNS, their molecular basis, and the potential risk of neuronal damage associated with the subsequent development of neurodegenerative diseases.

Abstract Introduction Over the past few years, anti-CD20 therapies like rituximab, ocrelizumab or ofatumumab have seen an increase in interest in the treatment of neurological autoimmune disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), or resistant forms of generalized myasthenia gravis (MG). They are generally well-tolerated, but recent reports have highlighted severe dental disorders in patients undergoing anti-CD20 therapies. The aim was to describe a series of cases and to compare with the available scientific literature. Methods We reviewed 6 patient cases with dental disorders during anti-CD20 therapy that were reported to the pharmacovigilance center. A disproportionality analysis was also conducted on Vigibase® for each anti-CD20 and each adverse effect described in the cases. Results Six cases of dental and gingival conditions in relatively young patients were reported (median age: 40.5 years old [min: 34; max: 79]). Oral conditions were developed in four patients with MS treated with ocrelizumab and in two patients receiving rituximab (one patient with MG and one with NMOSD). The onset of oral conditions ranged from 10 days to 2 years after treatment initiation. Notably, all patients treated with ocrelizumab experienced gingival recession. Various dental pathologies were observed, including tooth loss, dental pain, caries, brittle teeth, dental fractures, dental abscesses, and periodontitis. Analysis of Vigibase® revealed 284 worldwide cases of dental and gingival conditions under ocrelizumab, 386 cases under rituximab, and 80 under ofatumumab. Significant associations were found between these therapies and dental pathologies, particularly tooth abscesses and infections. Conclusion To our knowledge, this is the first case series reporting dental conditions developed in patients long-term treated with anti-CD20 treatments. This issue, literature data, and Vigilyze® analysis might be considered a safety signal that necessitates being confirmed with more robust data, such as a retrospective study with a control group. Meanwhile, proactive measures are essential like frequent dental checkups and dental hygienic measures to prevent oral health problems associated with anti-CD20 therapies.

Quality of Life (QoL) is a multifaceted concept encompassing economic, social, environmental, psychological, and physical dimensions of an individual’s life, including personal living conditions, happiness, well-being, and life satisfaction. As a vital criterion for sustainable development and active social policy in countries, QoL has been significantly influenced by the dynamic technological evolution of social media. However, the comprehensive impact of social media, including its role in disseminating disinformation – a major social and socio-economic concern – on QoL remains underexplored. This research aims to develop a novel fuzzy model to assess the level of disinformation on digital platforms and its correlation with the population’s QoL. Employing a mathematical approach rooted in expert evaluation, this study leverages intellectual knowledge analysis and fuzzy set theory. Grounded in data from real respondents and knowledge-based models, this study pioneers an information model to evaluate inhabitants’ QoL, incorporating factors such as financial concerns, perception of disinformation, and its influence on digital platforms. The fuzzy estimation model, verified with data from 3,036 respondents, quantitatively assesses citizens’ QoL. An illustrative application of the model demonstrates its effectiveness. The findings are particularly valuable for policymakers, experts in economic and innovative development, aiding the creation of regulatory and monitoring mechanisms to foster sustainable economic growth and devise effective development strategies.

Abstract Nowadays, the population is still struggling with a post-COVID19 syndrome known as long COVID, including a broad spectrum of neurological problems. There is an urgent need for a better understanding and exploration of the mechanisms of coronavirus neurotropism. For this purpose, the neurotropic strain of mouse hepatitis virus (MHV-JHM) originating from the beta-coronavirus genus, the same as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been used. The role of the cytoskeleton during virus replication in neurons in vitro was determined to understand the mechanisms of MHV-JHM neuroinfection. We have described for the first time the changes of actin filaments during MHV-JHM infection. We also observed productive replication of MHV-JHM in neurons during 168 h p.i. and syncytial cytopathic effect. We discovered that the MHV-JHM strain modulated neuronal cytoskeleton during infection, which were manifested by: (i) condensation of actin filaments in the cortical layer of the cytoplasm, (ii) formation of microtubule cisternae structures containing viral antigen targeting viral replication site (iii) formation of tunneling nanotubes used by MHV-JHM for intercellular transport. Additionally, we demonstrated that the use of cytoskeletal inhibitors have reduced virus replication in neurons, especially noscapine and nocodazole, the microtubule shortening factors.

COVID-19 infections are accompanied by adverse changes in inflammatory pathways that are also partly influenced by increased oxidative stress and might result in elevated DNA damage. The aim of this case-control study was to examine whether COVID-19 patients show differences in oxidative stress-related markers, unconjugated bilirubin (UCB), an inflammation panel and DNA damage compared to healthy, age-and sex-matched controls.The Comet assay with and without the treatment of formamidopyrimidine DNA glycosylase (FPG) and H2O2 challenge was used to detect DNA damage in whole blood. qPCR was applied for gene expression, UCB was analyzed via HPLC, targeted proteomics were applied using Olink® inflammation panel and various oxidative stress as well as clinical biochemistry markers were analyzed in plasma.Hospitalized COVID-19 patients (n = 48) demonstrated higher serum levels of 55 inflammatory proteins (p 0.05). Although various oxidative stress markers were not altered (e.g., FRAP, malondialdehyde, p > 0.05), a significant increased ratio of oxidized to reduced glutathione was detected in COVID-19 patients compared to healthy controls (p

Measures for consumer protection against food adulteration and misleading labelling are integrated into EU legislation, including methods for detecting misleading practices. Verification of the meat content is available for marine products, but not for salmonid fish due to the lack of standard nitrogen factors. This study aimed to establish nitrogen factors for rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis). The study analysed 340 fish from Czech fisheries obtained in the summer of 2018-2020. According to the established ISO methods, fillet samples with and without skin were analysed for their nitrogen content (protein), dry matter, ash, and fat. The recommended nitrogen factor for rainbow trout fillets with and without the skin is 3.07 ± 0.12 and 3.06 ± 0.14, respectively, and the nitrogen factor for fat-free rainbow trout fillets with and without the skin is 3.33 ± 0.15 and 3.29 ± 0.15, respectively. The recommended nitrogen factor for brook trout fillets with and without the skin is 3.16 ± 0.10 and 3.12 ± 0.09, respectively, and the nitrogen factor for fat-free brook trout fillets with and without the skin is 3.42 ± 0.13 and 3.36 ± 0.12, respectively. The established nitrogen factors will enable the analysis of the meat content to ensure that consumers purchase correctly described and labelled fish products.

The paper presents a new method to detect economic growth regimes based on time-series similarity analysis. The procedure builds upon a fuzzy concept-based model, the Jaccard Index, and a hierarchical clustering procedure. Having introduced the proposed method, we apply it to the time series of economic growth and its proximate factors. Further, we study the stability of the obtained results under different parameters. The proposed procedure allows us to detect groups of countries that share a common growth performance and akin growth mechanisms. Simultaneously, the method let us identify countries that escape any fixed classifications.

Human adenovirus (HAdV) is a common pathogen, which can lead to various clinical symptoms and—in some cases—central nervous system (CNS) dysfunctions, such as encephalitis and meningitis. Although the initial events of virus entry have already been identified in various cell types, the mechanism of neuronal uptake of adenoviruses is relatively little understood. The aim of this study was to investigate early events during adenoviral infection, in particular to determine the connection between cellular coxsackievirus and adenovirus receptor (CAR), clathrin, caveolin, and early endosomal proteins (EEA1 and Rab5) with the entry of HAdVs into primary murine neurons in vitro. An immunofluorescence assay and confocal microscopy analysis were carried out to determine HAdV4, 5, and 7 correlation with CAR, clathrin, caveolin, and early endosomal proteins in neurons. The quantification of Pearson’s coefficient between CAR and HAdVs indicated that the HAdV4 and HAdV5 types correlated with CAR and that the correlation was more substantial for HAdV5. Inhibition of clathrin-mediated endocytosis using chlorpromazine limited the infection with HAdV, whereas inhibition of caveolin-mediated endocytosis did not affect virus entry. Thus, the entry of tested HAdV types into neurons was most likely associated with clathrin but not caveolin. It was also demonstrated that HAdVs correlate with the Rab proteins (EEA1, Rab5) present in early vesicles, and the observed differences in the manner of correlation depended on the serotype of the virus. With our research, we strove to expand knowledge regarding the mechanism of HAdV entry into neurons, which may be beneficial for developing potential therapeutics in the future.

Sialodacryoadenitis virus (SDAV) has been identified as the etiological agent responsible for the respiratory system and salivary gland infections in rats. The existing literature on SDAV infections is insufficient to address the topic adequately, particularly in relation to the central nervous system. In order to ascertain how SDAV gains access to neuronal cells and subsequently exits, our attention was focused on the small molecule valosin-containing protein (VCP), which is an ATPase. VCP is acknowledged for its function in the ubiquitin-mediated proteasomal degradation of proteins, including those of viral origin. To ascertain the potential influence of VCP on SDAV replication and egress, high-content screening was employed to determine the viral titer and protein content. Western blot analysis was employed to ascertain the relative expression of VCP. Real-time imaging of SDAV-infected cells and confocal imaging for qualitative morphological analysis were conducted. The Eeyarestatin I (EerI) inhibitor was employed to disrupt VCP involvement in the endoplasmic reticulum-associated protein degradation pathway (ERAD) in both pre- and post-incubation systems, with concentrations of 5 μM/mL and 25 μM/mL, respectively. We demonstrated for the first time that SDAV productively replicates in cultured primary neurons. VCP expression is markedly elevated during SDAV infection. The application of 5 μM/mL EerI in the post-treatment system yielded a statistically significant inhibition of the SDAV yield. It is likely that this modulates the efficacy of virion assembly by arresting viral proteins in the submembrane area. [ABSTRACT FROM AUTHOR]

The global pandemic of COVID-19 caused by SARS-CoV-2 has had a devastating impact. Although many survived the acute effects of the pandemic, a significant number of survivors, including those with only mild symptoms, are now experiencing a prolonged and debilitating post-viral syndrome known as LC/PASC (long COVID/post-acute sequelae of SARSCoV-2). Typical symptoms of LC/PASC include fatigue, breathlessness, chest pain, impaired cognition, difficulty sleeping, fever and gastrointestinal symptoms. Anxiety and depression can also last for weeks to months and range from mild to disabling. The association between neuropsychiatric symptoms and SARS-CoV-2 infection raises questions about the possible routes of SARS-CoV-2 entry to the central nervous system (CNS) and longterm effects of the virus on the CNS, their molecular basis, and the potential risk of neuronal damage associated with the subsequent development of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A significant hurdle in untargeted lipid/metabolomics research lies in the absence of reliable, cross-validated spectral libraries, leading to a considerable portion of LC-MS features being labeled as unknowns. Despite continuous advancement in annotation tools and libraries, it is important to safeguard, publish and share acquired data through public repositories. Embracing this trend of data sharing not only promotes efficient resource utilization but also paves the way for future repurposing and in-depth analysis; ultimately advancing our comprehension of Covid-19 and other diseases. In this work, we generated an extensive MS-dataset of 39 Covid-19 infected patients versus age- and gender-matched 39 healthy controls. We implemented state of the art acquisition techniques including IDA and SWATH-DIA to ensure a thorough insight in the lipidome and metabolome, ensuring a repurposable dataset. [ABSTRACT FROM AUTHOR]