We present the detailed calculations of social distancing requirement. A comparative study of the growth pattern and death tolls in different communities indicates that the growth pattern of infected patients and death rate follow the similar distribution with different parametrizations. Every distribution follows an exponential growth pattern curve, like other microbes, then reaches the saturation point an d eventually decay s However, the argument for the exponential function depends on several parameters unbeknownst, as of yet. However, the slope varies different ial ly for various epicenter s and seems to have a relationship with parameters such as accessibi lity to healthcare facilities, pre existing medical conditions socio economic conditions and lifestyle. The mismatch of the growth pattern is also linked with the impact of various other factors and a premature interpretation of limit ed data. Novel behavi or of the virus brought many surprises, opened up new venues for medical research, and the need for the more detailed study of pathogens in the light of the interaction of RNA and DNA The adaptability to diverse ecological condition s and the relevant modification in the structure is also worth investigation The genetic modification can be studied using quantum mechanical probabilistic approach.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Poikilodermatous plaque-like hemangioma (PPH) is a recently described clinical and pathological entity, with only 18 cases reported in the literature. Although uncommon, this benign condition presents consistent clinical and histological findings. We present a new case of PPH in an 81-year-old male and review the existing literature. The persistence over time and the need to distinguish PPH from more significant lesions underscore the importance of its clinical and pathological recognition.

The present study aimed to develop a feeding strategy for pregnant sows which involved the prenatal administration of a mixture of pancreatic-like fungal enzymes, such as lipase, amylase, and protease, at (1) 1–115 days of gestation (group D1) and (2) 80–115 days of gestation (group D2) and to carry out a comparison with groups of sows that were not receiving such supplementation (negative control [NC] and positive control [PC]). It was found that the administration of the enzyme supplement resulted in a significant shortening of gestation (P ≤ 0.01). The pancreatic enzymes administered to sows had a significant effect on the number of liveborn piglets and weaned piglets, which was higher compared to the control groups that did not receive supplementation respectively: D1-12.1±1.1 and 11.12±1.1; D2- 12.8±1.3 and 11.75±0.07 vs. control groups KN-10.7±1.0 and 9.62±0,95 and KP 10.9±1.2 and 10.15±1.0 (P<0.006). Significant changes in piglet growth were observed after weaning up to 70 days of age. During this period, the most favorable growth parameters were found in groups D2 (420±91g) and PC (407±103g), in which piglets were given a mixture of pancreatic enzymes (lipase, amylase, and protease) at 3 weeks of age, and significantly higher weight gain and feed intake were observed compared to groups NC (378±114g) and D1 (381±96g) (P ≤ 0.007). In contrast, insulin levels were significantly lower in groups D1 and D2, respectively 6,8 IU/ml and 6,7 IU/ml compared to groups NC (14,6 IU/ml) and PC (16,6 IU/ml) ( (P ≤ 0.01). Piglets in group D2 had a significantly better feed conversion ratio (FCR) 1.604±0.10 compared to the other dietary groups: KN– 1.986±0.14; KP– 1.704±0.11; D1 – 1.932±0.15 (P ≤ 0.03). Histological imaging confirmed significantly thicker intestinal epithelium and intestinal mesenteron in animals from groups D2 and PC (P ≤ 0.03). Animals from the groups KP, D1 and D2 receiving enzymes showed a highly significant increase in the surface area of pancreatic follicles and pancreatic surface area compared to the group without KN supplementation (P<0.01). Furthermore, significantly higher activity of the brush border enzyme lactase was observed in groups D1; D2 and PC compared, respectively 32.90±3.99; 30.00±6.83 and 29.60±29.60 to group NC – 21.80± 3.27 (P ≤ 0.01).

Recent researches indicated that metal nanoparticles which have the unique optical properties can be used to enhance the spectral response of the photovoltaic modules. Since most of the nanoparticles have enhancement effects in a specific wavelength range, improving the spectral response of the photovoltaic modules in a broadband range is crucial for their applications in imaging, energy harvesting, and optical communication. In this study, flower-like silver particles are applied to achieve the enhancement effects in a broadband range. The optical absorption of photovoltaic modules is improved in a broad wavelength range of 400~2000 nm by immobilizing flower-like silver particles onto an amorphous Si p-i-n structure, and the peak responsivity of the spectral response is enhanced by about 10 times. Theoretical investigation further elaborates that the enhancement originates from the near-field effects of silver particles due to the interaction of different parts of the flower-like silver particles. Through these studies, we demonstrate that, utilizing the subwavelength silver particles with roughness surface can achieve the spectral response of the photovoltaic modules enhanced in broadband range, which can improve the utilization efficiency of optical energy for the applications of sensing, imaging, optical communication, and energy harvesting.

Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in &gt; 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged &lt;13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations; G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n=37, 67.2%) and comprised three G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 lineage). Both two G3 lineages have been recently detected in several countries. Our study is the first to document African children infection with G3 lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

Globin-like superfamily constitutes a superfamily of both extracellular and intracellular proteins that are found in 3 kingdoms of life. Globins are respiratory proteins that usually bind an oxygen molecule .Earlier, phylogenetic study of globin like superfamily was based on morphological character, however, molecular basis of their functional diversity is not completely understood. The present study focuses on the phylogenetic analysis of globin at molecular level. Firstly, proteins of SCOP families of globin like superfamily were retrieved from NCBI and then similar proteins are retrieved from PSI BLAST results and then pfam was used to predict the domains and two domains: Globin and Phycobilisome were analysed. Other analysis predicted the localization in cytoplasm of most of the proteins. The nucleotide sequences of same species for protein analysis were retrieved from NCBI, and phylogenetic analysis of aligned fasta files of proteins and nucleotides by using MEGA at molecular level was performed and analysis shows the difference on taxonomic tree and phylogenetic tree.

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

The induction of acoustic-mechanical oscillations to virus particles by illuminating them with microwave signals is analyzed theoretically. Assuming the virus particle being of spherical shape, its capsid consisting primarily of glycoproteins, a viscous fluid model is adopted while the outside medium of the sphere is taken to be ideal fluid. The electrical charge distribution of virus particle is assumed to be spherically symmetric with a variation along the radius. The generated acoustic-mechanical oscillations are computed by solving a boundary value problem analytically, making use of the Green’s function approach. Resonance conditions to achieve maximum energy transfer from microwave radiation to acoustic oscillation to the particle is investigated. Estimation of the feasibility of the technique to compete virus epidemics either for sterilization of spaces and/or use for future therapeutic applications is examined briefly.

Evolution remains an incessant process in viruses, allowing them to elude host immune response and induce severe diseases, impacting the diagnostic and vaccine effectiveness. Predicting emerging viral genomes is crucial, particularly in diseases like dengue, where viruses disrupt host cells, leading to fatal outcomes. Deep learning has been applied to predict dengue fever cases; there has been relatively less emphasis on its significance in forecasting emerging Dengue Virus (DENV) serotype. While Recurrent Neural Networks (RNN) were originally designed for modeling temporal sequences, our proposed DL-DVE generative and classification model, trained on complete genome data of DENV, transcends traditional approaches by learning semantic relationships between nucleotides in a continuous vector space instead of representing contextual meaning of nucleotide characters. Leveraging 2000 publicly available DENV complete genome sequences, our Long Short-Term Memory (LSTM) based generative and Feedforward Neural Network (FNN) based classification DL-DVE model showcases proficiency in learning intricate patterns and generating sequences for emerging serotype of DENV. The generative model showed accuracy of 93% and the classification model provided insight into the specific serotype label, corroborated by BLAST search verification. Evaluation metrics such as ROC-AUC value 0.818, accuracy, precision, recall and F1 score all to be around 99.00%, demonstrated the classification model’s reliability.  Our model classified the generated sequences as DENV-4, exhibiting 65.99% similarity to DENV-4 and around 63-65% similarity with other serotypes, indicating notable distinction from other serotypes. Moreover, the intra-serotype divergence of sequences with a minimum 90% similarity underscored their uniqueness. We analyzed the conserved motifs in the genome through MEME Suite (version 5.5.5). Our research strives to contribute to the ongoing fight against the Dengue virus by offering predictive insights into its genomic evolution. Looking ahead, proactive predictive modeling before mutations occur holds potential for guiding vaccine design and diagnostic kit development.

Medicinal plants are being tested as options to prevent infectious diseases in many countries. Baccharis crispa Spreng. (Asteraceae), is a native medicinal species widely used throughout South America. Our objective was to evaluate the antiviral activity of four wild populations of B. crispa from the province of Córdoba (Argentina) and determine if there is variability between them. The cytotoxicity of the extracts (chlorofom, ethanol and aquose) was evaluated by the neutral red uptake method. Using the plaque-forming unit reduction assay, virucidal and antiviral activity against Herpes Simplex type 1 and Chikungunya viruses were tested. Phytochemical screening of each extract was also performed. Puesto Pedernera (PP) population showed the best antiviral and virucidal effect, standing out the ethanolic extract as the least toxic and with the best inhibitory activity against both viral models. Villa del Parque (VP) population was inactive, regardless of the extract and the virus tested. The results revealed that extracts bioactivities vary significantly depending on the geographic area of collection, with PP and VP populations showing the most significant variability, not only in activity but also in chemical composition. These findings support the potential use of extracts as a source of therapeutic agents against different viruses.

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be infected more frequently with flaviviruses due to their arboreal and diurnal habits, their genetic similarity to humans and their relative closeness to humans. However, the only known flavivirus in America that is maintained by sylvatic cycles involving NPs is Yellow Fever virus (YFV), and the NPs role as potential hosts of flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 free range and captive NPs of Costa Rica to evaluate their involvement in flavivirus transmission cycles and their potential as flavivirus hosts. We used a highly-specific micro plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, Dengue virus 1-4 (DENV), Zika virus, West Nile Virus (WNV) and Saint Louis Encephalitis virus (SLEV). We found evidence of seropositive NPs to DENV-1 8.2% (homotypic –3/86, heterotypic – 4/86), SLEV 15.1% (homotypic – 10/86, heterotypic – 2/86), WNV 2.3% (homotypic – 2/86) and 8.1% (7/86) undetermined Flavivirus species. No antibodies against YFV or ZIKV were found. This work provides compelling serological evidence of exposure in NPs of flaviviruses associated with urban cycles, i.e. DENV, and confirms decades of circulation of SLEV in the same environments. Also, the range of years of sampling and the socioeconomic region was statistically significant for the presence of Dengue and Flavivirus undetermined seropositive individuals, respectively. Both the years and socioeconomic regions with greater seroprevalence coincide with the years and socioeconomic regions with high numbers of Dengue human cases for the country. Our work suggests bidirectional? circulation of different flaviviruses between humans and wildlife with public health importance and underscores the necessity of further surveillance for flaviviruses in the humans/wildlife interface in Central America.

The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.

Glypicans are a family of heparan sulfate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glypicans are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs) and Bone Morphogenetic Proteins (BMPs), among others. In the Hh signalling pathway, glypicans have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix and for its unimpaired reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how glypicans may contribute to it. In this review, we describe the structure, biochemistry and metabolism of glypicans and their interactions with different components of the Hh signalling pathway that are important for the release, transport and reception of Hh.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSC remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). Orai3 expression was increased in a stepwise manner during the progression of OSCC. In addition, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of endogenous Orai3 in OSCC cells suppressed CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 were highly expressed in CSCs compared to non-CSCs, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

Glioblastoma (GBM) still presents as one of the most aggressive tumors in the brain, which despite enormous research efforts remains incurable until today. As many theories evolve around the persistent recurrence of this malignancy the assumption of a small population of cells with a stem-like phenotype remains as a key driver of its infiltrative nature. In this article we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of Bone Morphogenic Protein 4 (BMP4), which induces GSC differentiation and hence reduces tumorigenicity. We therefore employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell based assays (MTT, limiting dilution and sphere formation assays), western blots, irradiation procedures and quantitative real-time PCR that depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1-expression might also serve as a marker protein to determine BMP4-susceptibility.

Purpose: The study aimed to investigate if there were any links between liver function biomarkers and immunoglobulins levels in serum, and Toll-like receptors (TLRs) and neuropilin-1 (NRP1) in COVID-19 patients. The study also aimed to assess the accuracy—sensitivity, specificity, and area under the curve (AUC) by the receiver operator curve (ROC) analysis for immunoglobulins levels and TLRs expressions. Patients and Methods: This study included 150 patients (100 patients with confirmed COVID-19 and 50 healthy volunteers as a control group). Patients with COVID-19 were subdivided into two groups according to the severity of symptoms (moderate and severe, with 50 patients each). Serum C-reactive protein (CRP), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), albumin, lactate dehydrogenase (LDH), immunoglobulin (Ig) G, and IgM levels were estimated. TLRs (TLR2 and TLR4) and NRP1 gene expression in blood samples were investigated using quantitative real-time polymerase chain reaction (qRT-PCR). ROC analysis was also applied to determine the accuracy of various detected parameters in predicting the possibility of COVID-19 infection. Results: In COVID-19 patients, serum parameters related to liver function, except serum albumin, CRP, IgG, IgM, and TLR2, TLR4, and NRP1 mRNA expression levels, significantly elevated compared to controls. Severe COVID-19 patients exhibited significantly higher liver enzymes (ALT, AST and LDH), CRP, and TLR2 mRNA expression levels and lower albumin levels than the moderate group. In the moderate and severe groups, ALT, CRP, TLR2, and TLR4 had a significant positive correlation with IgM levels. ALT, AST, LDH, CRP, TLR2, and TLR4 showed a significant positive correlation with IgG levels in both groups. In both the moderate and severe groups, NRP1 expression was found to be significantly correlated with CRP, IgG, IgM, TLR2, and TLR4. In contrast, serum albumin levels exhibited a significant negative correlation with IgG and IgM levels only in the severe group, but they showed a significant negative correlation with TLR2, TLR4, and NRP1 expression in both moderate and severe groups. Serum ALT and AST activities were positively correlated with NRP1 expression in the moderate group but not in the severe group and as well as TLR2 and TLR4 expression in both the moderate and severe groups. ROC analysis indicated that AUC was higher than 0.800 for serum IgM level and TLR4 gene expression in moderate COVID-19 group. Conclusions: The increased liver function biomarkers in serum and NRP1 expression are closely correlated with sustained activations in humoral and innate immune responses during COVID-19 infection. As a result, TLR2, TLR4, and NRP1 could be targets for limiting COVID-19 infection and impairment effects on liver function. Moreover, detection of IgM level in serum and TLR4 expression in blood have a good accuracy in predicting the possibility of infection with COVID-19 in moderate cases.

Background/Aim: Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma, including its subtypes, is the most common uterine tumor. The subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, this intravenous leiomyomatosis’ oncological features resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. Materials and Methods: We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. Result: CD44-positive mesenchymal tumor stem-like cells were detected in both intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological nature of intravenous leiomyomatosis was found to be similar to the oncological properties of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, Cyclin E and Ki-67-positive cells were rare, and no pathological findings suspected to be malignant were observed. Conclusion: It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

Bufadienolides-like chemicals, which mostly composed the active ingredient of Chansu, had been widely discovered to possess anti-inflammatory, tumor-suppressing and antipain activity, but the mechanisms of action were not clearly illuminated. In this research, in order to explore the potential mechanism of bufadienolides-like chemicals on breast cancer, a serious of bioinformatics analysis, included (1) differentially expressed genes identification combined with gene set variation analysis, (2) tissue specific co-expression network construction, (3) differentially regulated sub-networks detection with disease phenome, (4) hub gene selection and it’s relation to survival probability, and (5) similar small molecule detection were performed with gene expression profiles of bufadienolides-like chemicals. Results indicated bufadienolides-like chemicals had the most same target with valproic, estradiol and etc, could disturbed the pathways in RNA splicing, apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway and unfolded protein response, and had the potential ability to be used as anticancer, hormones and vasoprotectives agents.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Background and Aim. Since virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, post-hepatitis C virus (HCV) infection would be a cause for liver cirrhosis that would progress to HCC. Cytotoxic T cells (Tc) are known to be involved in post-HCV complications and HCC pathogenesis. The inhibitory checkpoint Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) is expressed on Tc. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression post-HCV and moreover, to evaluate LAIR-1 expression as a non-invasive biomarker for HCC progression in the context of liver cirrhosis post-HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. We studied LAIR-1 expression on Tc related to the progression of liver cirrhosis in a case-controlled study enrolled 64 patients with post-HCV G4-HCC and 37 patients with post-HCV G4-liver cirrhosis. Methods: LAIR-1 expression was analyzed by flow cytometry. Results: LAIR-1 expression on Tc and the percentage of Tc positive for LAIR-1 (LAIR-1+Tc %) were significantly higher in the post-HCV G4-HCC group compared to the post-HCV G4-liver cirrhosis

This paper describes new horizons in the diversity and taxonomy of negev-like viruses encoding the membrane-embedded SP24 protein. First, our data extend the known host range of SP24-encoding negev-like viruses to include brown algae, fungi, green plants, the phylum Entoprocta, the phylum Mollusca, and vertebrates. Second, our phylogenetic analysis suggests that the evolution of the SP24 gene family may have involved frequent events of inter-order virus genome shuffling. Third, the identification of 2-3 copies of SP24 protein genes in some virus RNAs shows that virus genomes may have acquired additional SP24 genes during the evolutionary process due to duplications or new acquisition steps. Forth, the broad host specificity of some SP24-encoded viruses may be related to an important adaptive role of SP24. Fifth, insect and nematode genomes may acquire viral SP24 genes by putative horizontal transfer from negev-like viruses known to infect species of both taxa.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Background: Every year, millions of people are hospitalized, and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection, and thus contribute to morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds of medicines commonly prescribed in Central Norway. Then we constructed a drug-target interaction network and identified potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on viability, transcription and metabolism of mock- and A/WSN/33(H1N1)-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that many drugs, such as acetylsalicylic acid, atorvastatin, candesartan, and hydroxocobalam, could target and modulate FLUAV-host cell interaction. In vitro experiments showed that these and other compounds at non-cytotoxic concentrations differently affected transcription and metabolism of mock- and FLUAV-infected cells. Conclusion: Many commonly prescribed drugs modulate FLUAV-host cell interactions in vitro and therefore could affect their interplay in vivo, thus, contributing to morbidity and mortality of patients with influenza virus infections.

It remains poorly understood how the life history strategies and transmission ecologies of viruses of plants, arthropods, and vertebrates are interrelated. The present analysis hinges on the virus transmission success. Virus transmission reflects where in the host-body viruses are retained or replicating. Plants, arthropods, and vertebrates share a protective outer-layer, a circulatory system, and reproductive organs. The latter enables vertical virus transmission and associates with virus-host mutualism. Two broadly opposing virus life history strategies are considered. Acute viruses tend to be replicative and are swiftly transmitted to the next host. Instead, persistent viruses keep virus replicating costs and host damage to a minimum. The intertwined life histories and transmission ecologies are accordingly pieced together, based on the virus mono- or instead dual-host tropism, the location of virus retention or replication on or in the host-body, the presence of cyclical or mechanical transmission by arthropods, and of horizontal and vertical host-to-host transmission modes. It is shown that in the arthropod and in the vertebrate animal host, virus circulation in the hemocoel or blood circulation goes hand-in-hand with vertical transmission. Instead, plant phloem viruses do not transmit via seed. The latter is the rule for the plant-only viruses. The risk management implications are discussed in brief.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Invasive weeds cause significant crop yield and economic losses in agriculture. The highest in-direct impact may be attributed to the role of invasive weeds as virus reservoirs especially within the commercial growing areas. The new tobamovirus tomato brown rugose fruit virus (ToBRFV), recently identified in the Middle-East, overcomes the Tm-22 resistance allele in the cultivated tomato varieties grown in greenhouses. In this study, we determined the role of invasive weed species as potential hosts for ToBRFV and pepino mosaic virus (PepMV). Out of all tested weed species, the invasive species So-lanum elaeagnifolium and S. rostratum, mechanically inoculated with ToBRFV, were positive for To-BRFV in both enzyme linked immunosorbent assay (ELISA) and RT-PCR tests. S. rostratum was also positive for PepMV. No conspicuous phenotype was observed on ToBRFV infected S. elaeagnifolium plants suggesting a hostplant associated defense response. S. rostratum plants inoculated with either ToBRFV alone or a mixture of ToBRFV and PepMV-IL, contained high ToBRFV levels. In addition, when inoculated with ToBRFV or PepMV-IL disease symptom manifestations were observed in S. rostratum plants and the symptoms were exacerbated upon mixed infections with both viruses. The distribution and abundance of both Solanaceae species increase the risks of virus transmission between species.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Canine distemper virus (CDV) is a serious contagious disease of canines, cats and sometimes ra-coons. The study included seven raccoons from Timisoara Zoo. The detection of CDV in all raccoons was accomplished using qRT-PCR, but several other exams were also conducted. Clinically, severe digestive disorders were observed, characterized by diarrhea and repeated hematemesis. Pseudomembranous gastroenteritis, congestion and pulmonary edema were found during the ne-cropsy of two racoons. Immunohistochemically, the brown color was highlighted in the examined sectionsand it was present in the cytoplasm of the cells from the germinal centers of the medullary area. Histopathological examination revealed lymphocyte depletion and intranuclear and intracy-toplasmic inclusions in the intestine. Based on the qRT-PCR assay, laboratory tests and lesions ob-served, it was established that the raccoons got infected with CDV, and two of them died as a result. The necropsy, histological lesions and immunohistochemical results are comparable between dogs and racoons. Through the results obtained, it was concluded that the interspecific infection is possible and the epidemiological risk of infection transmitted by racoons to domestic animals, such as dogs and cats, needs to be examined in the future.

"Medusaviridae" is a proposed family of large DNA viruses so far represented by a sole virus isolated from a hot spring. In the present study, we report the isolation and genome sequencing of a new member of this family, medusavirus stheno, discovered from a freshwater sample with Acanthamoeba castellanii coculture.

BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

The recently discovered Jingmenvirus group includes viruses with a segmented genome, RNA of a positive polarity, and several proteins with distant homology to the proteins of the members of the genus Flavivirus. Some Jingmenvirus group members, namely Alongshan virus (ALSV) and Jingmen tick virus, are reported to be tick-borne human pathogens, causing a wide variety of symptoms. ALSV is widely distributed in Eurasia, yet there is no reliable assay for its detection. Here, we describe a qPCR system for the detection of ALSV. Our data show that this system can detect as low as 10⁴ copies of ALSV in the probe. It shows no amplification with common tick-borne viruses circulating in Eurasia, Yanggou tick virus—another member of the Jingmenvirus group—or some known members of the genus Flavivirus. The qPCR system was tested have no non-specific signal for Ixodes ricinus, I. persulcatus, Dermacentor reticulatus, D. marginatus, Haemaphysalis concinna, and H. japonica ticks. Overall, the qPCR system described here can be used for reliable and quantitative ALSV detection.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The development of compartmentalized neuron culture systems has been invaluable in the study of neuroinvasive viruses, including the alpha herpesviruses Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PRV). This chapter provides updated protocols for assembling and culturing rodent embryonic superior cervical ganglion (SCG) and dorsal root ganglion (DRG) neurons in Campenot trichamber cultures. In addition, we provide several illustrative examples of the types of experiments that are enabled by Campenot cultures: 1. Using fluorescence microscopy to investigate axonal outgrowth/extension through the chambers, and alpha herpesvirus infection, intracellular trafficking, and cell-cell spread via axons. 2. Using correlative fluorescence microscopy and cryo electron tomography to investigate the ultrastructure of virus particles trafficking in axons.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

The red fox, found on all continents except Antarctica, occupies diverse habitats. In Croatia it is an indigenous wild species with a population density of 0.7 animals per square kilometer. While tumors in wild animals from the Canidae family are scarce, the true prevalence and diversity of tumors are likely underestimated due to limited research. So far, a limited number of tumors were observed among the red fox population, either in their natural habitat or in captivity. As part of the National rabies control program, we examined 1,890 red fox carcasses over a four-year period. Our focus was on identifying abnormalities on the skin and internal organs that suggest potential neoplastic proliferation. Five red foxes, three males and two females, were found to have growths resembling potential tumors. Their age distribution spanned from 2 to 7 years. Microscopic investigation revealed two collagenous hamartomas, two Meibomian gland adenomas and one intra-abdominal teratoma within a cryptorchid testis. This retrospective study aims to provide a comprehensive description of tumor and tumor-like lesions observed in free-range red foxes from Croatia, marking the first research of its kind in Croatia.

The effect of ferromagnetic CaMnO3 (CMO) addition on structural, magnetic, dielectric, and ferroelec-tric properties of BiFeO3 are presented. X ray diffraction and Raman investigation allowed the identifi-cation of single pseudo cubic perovskite structure. The magnetic measurement showed that the pre-pared films exhibit a ferromagnetic behavior at low temperature with both coercive field and remnant magnetization increased with increasing CMO content. However, a deterioration of magnetization was observed at room temperature. Ferroelectric study revealed an antiferroelectric like behavior with a pinched P-E hysteresis loop for 5%CMO doping BFO resulting in low remnant polarization and double hysteresis loops. Whereas, high remnant polarization and coercive field with a likely square hysteresis loop are obtained for 10 % CMO addition. Furthermore, a bipolar resistive switching behavior with a threshold voltage of about 1.8V is observed for high doped film that can be linked to the ferroelectric polarization switching.

The Burkholderia cepacia complex (Bcc) are a group of increasingly multi-drug resistant opportunistic bacteria that can cause severe pulmonary infections. This resistance is driven through a combination of intrinsic factors and the carriage of a broad range of conjugative plasmids harbouring virulence determinants. Therefore, novel treatments are required to not only treat Bcc infection but also to prevent further spread of these virulence determinants. In the search for phages infective for two clinical Bcc isolates, CSP1 phage, a PRD1-like phage was isolated. CSP1 phage was found to require pilus machinery commonly encoded on conjugative plasmids to facilitate infection of multiple Gram-negative bacteria genera including Escherichia and Pseudomonas. Whole genome sequencing and characterisation of one of the clinical Burkholderia isolates revealed it to be Burkholderia contaminans. B. contaminans 5080 was found to contain a genome of over 8 Mbp encoding multiple intrinsic resistance factors, such as efflux pump systems, but more interestingly, carried three novel plasmids encoding multiple putative virulence factors for increased host fitness, including antimicrobial resistance. Even though PRD1-like phages are broad host range, their use in novel antimicrobial treatments shouldn’t be dismissed, as the dissemination potential of conjugative plasmids is extensive. Continued survey of clinical bacterial strains is

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

A half-harmonic oscillator, which gets its name because the coordinate is strictly positive, has been quantized and determined that it was a physically correct quantization. This positive result was found using affine quantization (AQ). The main purpose of this paper is to compare results of this new quantization procedure with those of canonical quantization (CQ). Using Ashtekar-like classical variables and CQ, we quantize the same toy model. While these two quantizations lead to different results, they both would reduce to the same classical Hamiltonian if $\hbar\rightarrow0$. Since these two quantizations have differing results, only one of the quantizations can be physically correct. Two brief sections illustrate how AQ can correctly help quantum gravity and the quantization of most field theory problems.

The measurements of the proton electromagnetic form factors in the time-like region using the initial state radiation technique are reviewed. Recent experimental studies have shown that initial state radiation processes at high luminosity electron-positron colliders can be effectively used to probe the electromagnetic structure of hadrons. The BABAR experiment at the B-factory PEP-II in Stanford and the BESIII experiment at the $\tau$-charm factory BEPC-II in Beijing have measured the time-like form factors of the proton using the initial state radiation process $e^{+}e^{-}\to pbar{p}\gamma$. The two kinematical regions where the photon is emitted from the initial state at small and large polar angles have been investigated. In the first case the photon is in the region not covered by the detector acceptance and is not detected. The Born cross section and the proton effective form factor have been measured over a wide and continuous range of the the momentum transfer squared $q^2$ from threshold up to ~42 (GeV/c)$^2$. The ratio of electric and magnetic form factors of the proton has been also determined. In this report, the theoretical aspect and the experimental studies of the initial state radiation process $e^{+}e^{-}\to p\bar{p}\gamma$ are described. The measurements of the Born cross section and the proton form factors obtained in these analyses near the threshold region and in the relatively large $q^2$ region are examined. The experimental results are compared to the predictions from theory and models. Their impact on our understanding of the nucleon structure is discussed.

There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic pa-tients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma that later developed SS led us to review previous tumors of patients with SS. The aim of the study is to see if granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of which had a previous tumor. We were able to review 29 cases 12 of which showed tumor associated granulomas (TAGs)(41.4%). This ratio is much higher than that of the normal population. We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we have observed TAGs in patients who later develop SS. In our series, the ratio of TAGs in patients with SS was significantly greater than in the normal population. To prove our findings, we suggest reviewing the history of patients with SS in search of previous tumors. The histology of such tumors should be reviewed in an attempt to identify granulomas.

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.

Semiconductor materials have been shown to have better photocatalytic behavior and can be utilized for the photodegradation of organic pollutants. In this work, three-dimensional flower-like SnS₂ were synthesized by a facile hydrothermal method. Core-shell structured SiO₂@α-Fe₂O₃ nanocomposites were then deposited on the top of the SnS₂ flowers. The as-synthesized nanocomposites were characterized by X-ray diffraction (XRD), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) and photoluminescence spectroscopy (PL). The photocatalytic behavior of the SnS₂-SiO₂@α-Fe₂O₃ nanocomposites was observed by observing the degradation of methylene blue (MB). The results show an effective enhancement of photocatalytic activity for the degradation of MB especially for the 15 wt. % SiO₂@α-Fe₂O₃ nanocomposites on SnS₂ flowers.

Background: Benveniste’s biology experiments suggested the existence of molecular-like effects without molecules (“memory of water”). In this article, it is proposed that these disputed experiments could have been the consequence of a previously unnoticed and non-conventional experimenter effect. Methods: A probabilistic modelling is built in order to describe an elementary laboratory experiment. A biological system is modelled with two possible states (“resting” and “activated”) and exposed to two experimental conditions labelled “control” and “test”, but both biologically inactive. The modelling takes into account not only the biological system, but also the experimenters. In addition, an outsider standpoint is adopted to describe the experimental situation. Results: A classical approach suggests that, after experiment completion, the “control” and “test” labels of biologically-inactive conditions should be both associated with “resting” state (i.e. no significant relationship between labels and system states). However, if the fluctuations of the biological system are also considered, a quantum-like relationship emerges and connects labels and system states (analogous to a biological “effect” without molecules). Conclusions: No hypotheses about water properties or other exotic explanations are needed to describe Benveniste’s experiments, including their unusual features. This modelling could be extended to other experimental situations in biology, medicine and psychology.

SARS-CoV-2, influenza A/B virus (IAV/IBV) and respiratory syncytial virus (RSV) are among the common viruses causing acute respiratory infections. Clinical diagnosis to differentiate these viruses is challenging due to similar clinical presentations, thus laboratory-based real-time RT PCR is the gold standard for diagnosis. The study aimed to evaluate the diagnostic performance of STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor Inc, Seoul, Korea). This retrospective study was conducted with archived respiratory samples positive and negative for SARS-CoV-2, IAV, IBV or RSV. The evaluation study involved a total of 322 respiratory samples comprising 215 positive samples (49 SARS-CoV-2, 48 IAV, 53 IBV, 65 RSV) and 107 negative samples. All samples were tested with both STANDARD M10 and either Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV (Cepheid, USA). The sensitivity, specificity, positive predictive value and negative predictive value rates of STANDARD M10 were very similar to Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV ranges for each virus (98-100%). The overall agreement was 99.4% with 99.1% agreement for positive samples and 100% agreement for negative samples. In conclusion, the STANDARD M10 point-of-care test is suitable for rapid simultaneous detection of SARS-CoV-2, IAV, IBV and RSV.

Hepatitis B virus (HBV) remains a dominant cause of hepatocellular carcinoma (HCC). Recently it was shown that HBV and woodchuck hepatitis virus (WHV) integrate into hepatocyte genome minutes after invasion. Retrotransposons and transposable sequences were frequent sites of the initial insertions suggesting a mechanism for spontaneous HBV DNA disperse throughout hepatocyte genome. Several somatic genes were also identified as early insertional targets in infected hepatocytes and woodchuck livers. Head-to-tail joints (HTJs) dominated amongst fusions indicating their creation by non-homologous-end-joining (NHEJ). Their formation coincided with robust oxidative damage of hepatocyte DNA. This was associated with activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated dsDNA repair as reflected by augmented transcription of PARP1 and XRCC1, the PARP1 binding partner, OGG1, a responder to oxidative DNA damage, and by increased activity of NAD+, a marker of PARP1 activation, and HO1, an indicator of cell oxidative stress. The engagement of the PARP1-mediated NHEJ repair pathway explains HTJ format of the initial merges. The findings showed that HBV and WHV are immediate inducers of oxidative DNA damage, hijack dsDNA repair to integrate into hepatocyte genome and by this may initiate pro-oncogenic process. Tracking initial integrations may uncover early markers of HCC and help to explain HBV-associated oncogenesis.

Background and Aim: Spontaneous bacterial peritonitis is a common infection in liver cirrhosis. This systematic review and meta-analysis provides detailed information on the prevalence of SBP among HBV and HCV-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV, and HCV related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1,713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7 – 21.0%; I2= 96.13%; p < 0.001)], followed by SBP in HCV associated liver cirrhosis [4.0% (95% CI, 1.3% – 11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1 – 66.3%), the USA (50.0%, CI: 34.6 – 65.4%), and Holland (31.1%, CI: 21.6 – 42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV+HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P<0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed an increase in the incidence of SBP in viral hepatitis over the last decade, the latter could be due to the global increase in Bacterial resistance. This indicates a possible future rise in the global prevalence of SBP among HBV, and HCV-related liver cirrhosis.

The irregular timing and spatial variation in zoonotic arbovirus spillover from vertebrate hosts to humans and livestock present challenges to predicting their occurrence from year to year and within their broader geographic range, compromising effective prevention and control strategies. The objective of this study was to quantify effects of landscape composition and configuration and dynamic temperature and precipitation values on the 2018 spatiotemporal distribution of eastern equine encephalitis virus (EEEV) (Togaviridae, Alphavirus) and West Nile virus (WNV) (Flaviviridae, Flavivirus) sentinel chicken seroconversion in northeastern Florida using Earth Observation (EO) data and a modeling framework that incorporated joint spatial and temporal effects. We investigated environmental effects using Bernoulli generalized linear mixed effects models (GLMMs) including a site level random effect, and then added spatial random effects and spatiotemporal random effects in subsequent runs. Models were executed using integrated nested Laplace approximation (INLA) and a stochastic partial differential equation (SPDE) approach in R-INLA. GLMMs that included a spatiotemporal random effect performed better relative to models that included only spatial random effects and better than non-spatial models. Results indicated strong spatiotemporal structure in seroconversion for both viruses, but EEEV exhibited more punctuated and compact structure at the beginning of the sampling season, while WNV exhibited more gradual and diffuse structure across the study area toward the end of the sampling season. Percentage of cypress/tupelo wetland land cover within 3500 m of coop sites and edge density of forest land cover within 500 m had a strong positive effect on EEEV seroconversion, while the best fitting model for WNV was the intercept only model with spatiotemporal random effects. Lagged temperature and precipitation variables included in our study did not have a strong effect on seroconversion for either virus when accounting for temporal autocorrelation, demonstrating the utility of capturing this structure to avoid Type I errors. Predictive accuracy on out-of-sample data for EEEV seroconversion demonstrates the potential to develop a temporally dynamic framework to predict arbovirus transmission.

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

Canine infectious respiratory disease complex (CIRDC) is caused by different viruses and bacteria. Viruses associated with CIRDC include canine adenovirus-2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine herpesvirus (CHV), canine coronavirus (CCoV) and canine parainfluenza virus (CPIV). Bacteria associated with CIRDC include Bordetella bronchiseptica, Streptococcus equi subspecies zooepidemicus, and Mycoplasma spp. The present study examined the prevalence of pathogens associated with CIRDC in specimens received by a Veterinary Diagnostic Laboratory in Georgia from 2018 to 2022. Out of 459 cases, viral agents were detected in 34% cases and bacterial agents were detected in 58% cases. A single pathogen was detected in 31% cases, while two or more pathogens were identified in 24% cases. The percentages of viral agents identified were CAV-2 (4%), CDV (3%), CPIV (16%), CCoV (7%), and CIV (2%). The percentages of bacterial agents were Bordetella bronchiseptica (10%), Mycoplasma canis (24%), Mycoplasma cynos (21%), and S treptococcus zooepidemicus (2%). Positive viral cases ranged from 2-4% for CAV-2, 1-7% for CDV, 1-4% for CHV, 9-22% for CPIV, 4-13% for CCoV, and 1-4% for CIV. Overall, the study showed that the most prevalent pathogens associated with CIRDC during the study period were CPIV, M. canis, and M. cynos.

The World Health Organization has estimated an annual occurrence of approximately 392 million Dengue virus (DENV) infections in more than 100 countries where the virus is endemic, and this represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus Flavivirus, in the family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid [C], pre-membrane [prM], and envelope [E]) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different times of infection. This study demonstrated that miRNAs-15/16 are overexpressed during infection of HepG2 and Huh 7.5 cells by DENV-4 and have a relationship with NS1 protein expression, viral load, and activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.

The Human Herpesviruses persist in the form of a latent infection in specialized cell types. During latency, the herpesvirus genomes associate with cellular histone proteins and the viral lytic genes assemble into transcriptionally repressive heterochromatin. Although there is divergence in the nature of heterochromatin on latent herpesvirus genomes, in general the genomes assemble into forms of heterochromatin that can convert to euchromatin to permit gene expression and therefore reactivation. This reversible form of heterochromatin is known as facultative heterochromatin and is most commonly characterized by polycomb silencing. Polycomb silencing is prevalent on the cellular genome and plays a role in developmentally regulated and imprinted genes, as well as X chromosome inactivation. As herpesviruses initially enter the cell in an un-chromatinized state, they provide an optimal system to study how de novo facultative heterochromatin is targeted to regions of DNA and how it contributes to silencing. Here, we describe how polycomb-mediated silencing potentially assembles onto herpesvirus genomes, synergizing what is known about herpesvirus latency with facultative heterochromatin targeting to the cellular genome. A greater understanding of polycomb silencing of herpesviruses will inform on the mechanism of persistence and reactivation of these pathogenic human viruses and provide clues regarding how de novo facultative heterochromatin forms on the cellular genome.

Novel Coronavirus infection mediated pandemic started in China in December 2019 and is still killing 1000s of people throughout the world. The second most populous country, India too is fighting against this infectious disease. The country is taking effective measures to curb the pandemic by exerting extensive campaigning on sanitation and strict social distancing measures to quell the explosion of the infection rate. The future of the COVID-19 infections in India still remain unpredictable, so precautionary methods need to be continued until the growth rate of new cases drop below one.

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non- canonical latency program of EBV with an activated PD-L1 pathway. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC₅₀ values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.

The Influenza A virus (IAV) is a highly infectious virus that poses a significant threat to global public health and food supplies. The current subtype of avian influenza virus (AIV), H5N1, is being closely monitored worldwide due to its unprecedented spread from Europe to North America and now to Central and South America. This review summarizes recent updates on the evolution of the different IAV subtypes in birds and mammals including humans, in Chile. The distribution and spread of AIV H5N1 in Chile indicated a complex interplay between ecological and human factors in that it was negatively correlated with distance to the closest urban center and precipitation and temperature seasonality. It is evident that highly pathogenic avian influenza (HPAI) H5N1 in Chile was introduced from North America via the Atlantic migratory flyways as opposed to local transmission from other countries in South America. The presence of these viruses in Chile underscores the need for increased biosecurity on poultry farms and continuous genomic surveillance approaches to understand and control AIVs in both wild and domestic bird populations in Chile.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

The production and quality of Phaseolus vulgaris (snap bean) have been negatively impacted by leaf crumple disease caused by two whitefly-transmitted begomoviruses; cucurbit leaf crumple virus (CuLCrV) and sida golden mosaic Florida virus (SiGMFV), which often appear as a mixed infection in Georgia. Host resistance is the most economical management strategy against whitefly-transmitted viruses. Currently, information is not available with respect to resistance to these two viruses in commercial cultivars. In two field seasons (2018 and 2019), we screened Phaseolus sp. genotypes (n = 84 in 2018; n = 80 in 2019; most of the genotypes were common in both years with a few exceptions) for resistance against CuLCrV and/or SiGMFV. Twenty genotypes with high- to moderate-levels of resistance (disease severity ranging from 5-50%) to CuLCrV and/or SiGMFV were identified. Twenty-one genotypes were found to be highly susceptible with a disease severity of ≥66%. Adult whitefly counts differed significantly among snap bean genotypes for both years. The whole genome of these Phaseolus sp. (n=82) genotypes was sequenced and genetic variability among them was identified. Over 900 giga-base (Gb) of filtered data were generated and >88% of the resulting data were mapped to the reference genome, and SNP and Indel variants in Phaseolus genotypes were obtained. A total of 645,729 SNPs and 68,713 Indels including 30,169 insertions and 38,543 deletions were identified, which were distributed in 11 chromosomes with chromosome 02 harboring the maximum number of variants. These phenotypic and genotypic information will be helpful in genome-wide association studies that will aid in identifying genetic basis of resistance to these begomoviruses in Phaseolus sp.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. Here we report that BeWo and HUVEC cells are permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication is cell line dependent. Embryoid bodies are also permissive to ZIKV and the presence of YFV antibodies collected 1 to 6 months post vaccination enhances ZIKV infection. Our data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

With ongoing colony losses driven in part by the Varroa mite and the associated exacerbation of virus load, there is an urgent need to protect honey bees (Apis mellifera) from fatal levels of virus infection and from nontarget effects of insecticides used in agricultural settings. A continuously replicating cell line derived from the honey bee would provide a valuable tool for study of molecular mechanisms of virus – host interaction, for screening of antiviral agents for potential use within the hive, and for assessment of the risk of current and candidate insecticides to the honey bee. However, the establishment of a continuously replicating, honey bee cell line has proved challenging. Here we provide an overview of attempts to establish primary and continuously replicating hymenopteran cell lines, methods (including recent results) for establishing honey bee cell lines, challenges associated with the presence of latent viruses (especially Deformed wing virus), in established cell lines and methods to establish virus-free cell lines. We also describe the potential use of honey bee cell lines in conjunction with infectious clones of honey bee viruses for examination of fundamental virology.

The recent outbreak of the new virus in Wuhan city, China from the sea food market has led to the identification of a new strain called the corona virus and named as novel corona virus (2019-nCoV) belonging to Coronaviridae family. This has created major havoc and concern due to the mortality of 250 persons and affecting more than 10,000 people. This virus causes sudden fever, pneumonia and also kidney failure. In this study a computational approach is proposed for drug and vaccine design. The spike protein sequences were collected from a protein database and analysed with various bioinformatics tools to identify suitable natural inhibitors for the N-terminal receptor binding domain of spike protein. Also, it is attempted to identify suitable vaccine candidates by identifying B-Cell and T-cell epitopes. In the drug design, the tanshinone Iia and methyl Tanshinonate were identified as natural inhibitors based on the docking score. In the vaccine design, B-cell epitope VLLPLVSSQCVNLTTRTQLPPAYTN was found to have the highest antigenicity. FVFLVLLPL of MHC class-I allele and FVFLVLLPL of MHC class-II allele were identified as best peptides based on a number of alleles and antigencity scores. The present study identifies natural inhibitors and putative antigenic epitopes which may be useful as effective drug and vaccine candidates for the eradication of novel corona virus.

Aedes aegypti (L.) is the primary vector of chikungunya, dengue, yellow fever and Zika viruses. The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in invertebrates and vertebrates, as well as plants. We focused on the AaeLRIM1 and AaeAPL1 gene expressions in response to Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection using a time course study, as well as the developmental expressions in the eggs, larvae, pupae, and adults. RNA-seq analysis data provided 60 leucine-rich repeat related transcriptions in Ae. aegypti in response to Zika virus (Accession number: GSE118858, https://www.ncbi.nlm.nih.gov/gds/?term=GSE118858). RNA-seq analysis data showed that AaeLRIM1 (AAEL012086-RA) and AaeAPL1 (AAEL009520-RA) were significantly upregulated 2.5 and 3-fold during infection by ZIKV 7-days post infection (dpi) of an Ae. aegypti Key West strain compared to an Orlando strain. The qPCR data showed that LRR-containing proteins AaeLRIM1, AaeAPL1 and five paralogues were expressed 100-fold lower than other nuclear genes, such as defensin, during all developmental stages examined. Together, these data provide insights into transcription profiles of LRR proteins of Ae. aegypti during its development and in response to infection with emergent arboviruses.

In 2015 in Brazil, Zika virus showed features of geographic expansion and potentially increased virulence. In 2016, New York State issued emergency regulations after the World Health Organization declared Zika virus a Public Health Emergency of International Concern. In this study, mosquito surveillance was conducted in Westchester County, New York, to identify Zika virus and other arboviruses. Twenty trap sites were used for surveillance of Aedes albopictus mosquitoes, the Zika virus vector. The Westchester County Department of Health performed testing for Zika, West Nile, Eastern equine encephalitis, and other flaviviruses on 369 batches comprising 8,891 mosquitoes. Aedes albopictus mosquitoes were identified in Nassau, Rockland, Suffolk, Westchester, and New York City. Despite the increased capacity for specimen analysis, Zika virus was not detected. This study provides the first evidence of appropriate Zika virus surveillance. However, the results do not allow determination of the potential mechanism of local vector-to-human transmission of Zika virus among Aedes albopictus mosquitoes. This study adds to the evidence regarding the distribution, emergence, and trapping capabilities of potential Zika virus vectors.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

In this study, we investigate the behavior of randomly moving particles with a defined average energy, focusing on their biased motion around a specific point. These particles' velocity magnitudes follow a Maxwell distribution with a specific scale parameter. Our analysis derives the stochastic rotation rules for these particles and introduces the Ito equation conditions for biased stochastic rotation at a given curl value. We also consider the special relativistic-like effects in this context. The findings are validated through a representative example.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

The study of mechanical properties of rock mass can be effectively carried out through rock-like material model test. The similarity of mechanical properties between rock-like material and protolith is dependent on the appropriate selection of composition and content of rock-like materials. In this research, X-Ray diffraction test was conducted to analyze the composition of deep rock, which confirmed silica, quartz, and dolomite as the primary components of deep sandstone. An orthogonal design test was used to execute the ratio test of rock-like material. River sand was used as an aggregate, cement as a binder, gypsum powder as a regulator, and polystyrene foam (EPS) as rock damage simulation material. The influencing factors considered in the orthogonal mechanical tests were the proportion of aggregate and binder, ratio of binder and regulator, quantity of damage simulation material, and size of damage simulation material. Three levels were set for each factor, and mechanical parameters such as compressive strength, tensile strength, elastic modulus, axial strain, and Poisson's ratio were tested for each group of samples. The changes of those parameters with the levels of the above four factors were studied. The study revealed that adjusting the size of polystyrene foam (EPS) can adjust the values of elastic modulus, tensile strength, and Poisson's ratio of rock-like material. Similarly, changing the ratio of binder and regulator can adjust the values of axial strain and compressive strength of rock-like material. The rock-like material developed in the study can simulate the mechanical properties of different rock masses such as granite, sandstone, shale, and limestone.

Existence of carcinogenic nitrite in food has attracted much attention, however, it is still a challenge to develop nitrite sensor with higher sensitivity and selectivity to enlarge its applications in daily life. Herein, one-dimensional honeycomb-like carbon nanofibers (HCNFs) were synthesized with an electrospun technology, and its specific structure enables the controlling growth and highly dispersed bismuth nanoparticles (Bi NPs) on its surface, which endows the obtained Bi/HCNFs with excellent electrocatalytic activity toward nitrite oxidation. By modifying Bi/HCNFs on screen-printed electrode, the constructed Bi/HCNFs electrode (Bi/HCNFs-SPE) can be used for nitrite detection in one drop of solution, and exhibits higher sensitivity (1269.9 μA mM-1 cm-2) in a wide range of 0.1~800 μM with lower detection limit (19 nM). Impressively, the Bi/HCNFs-SPE has been successfully used for nitrite detection in food and environment samples, the satisfactory property and recovery indicates its feasibility in further practical applications.

In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and of some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10-3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this critical review was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. The review will also put into perspective the exposure from diapers with that from breast milk whose benefits for child’s health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.

A typical white-light light-emitting diode (LED) can achieve a sunlight-like spectral profile in the visible spectrum by means of using an optical filter, with an inverted transmission profile to the white LED, fabricated using a deposition coating process. The unfiltered white LED generates white light by mixing light emitted by a blue LED (450 nm) with emission from the yellow phosphorescence excited by the blue light and differs significantly from the characteristics of the full-spectrum natural light. In this study, the spectral characteristics of the filtered LED light can be improved to reach a general color rendering index value (Ra) of 95.6 at the D65.

In the last decade, the objectives outlined by the needs of personal robotics have led to the rise of new biologically-inspired techniques for arm motion planning. This paper presents a literature review of the most recent research on the generation of human-like arm movements in humanoid and manipulation robotic systems. Search methods and inclusion criteria are described. The studies are analysed taking into consideration the sources of publication, the experimental settings, the type of movements, the technical approach, and the human motor principles that have been used to inspire and assess human-likeness. Results show that there is a strong focus on the generation of single-arm reaching movements and biomimetic-based methods. However, there has been poor attention to manipulation, obstacle-avoidance mechanisms, and dual-arm motion generation. For these reasons, human-like arm motion generation may not fully respect human behavioural and neurological key features and may result restricted to specific tasks of human-robot interaction. Limitations and challenges are discussed to provide meaningful directions for future investigations.

Trophoblasts are the first cell-type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription factor OVO-like 2 (OVOL2) fail to produce a functioning placenta, and die around embryonic day 10.5, suggesting that OVOL2 may be critical for trophoblast development. Therefore, our objective was to determine the role of OVOL2 in mouse TS cell fate. We found that OVOL2 was highly expressed in mouse placenta and differentiating TS cells. Placentas and TS cells lacking OVOL2 showed poor trophoblast differentiation potential, including increased expression of stem-state associated genes (Eomes, Esrrb, Id2) and decreased levels of differentiation-associated transcripts (Gcm1, Tpbpa, Prl3b1, Syna). Ectopic OVOL2 expression in TS cells elicited precocious differentiation. OVOL2 bound proximate to the gene encoding inhibitor of differentiation 2 (ID2), a dominant negative helix-loop-helix protein, and directly repressed its activity. Overexpression of ID2 was sufficient to reinforce the TS cell stem state. Our findings reveal a critical role of OVOL2 as a regulator of TS cell differentiation and placental development, in-part by coordinating repression of ID2.

Physical measurements might display range values extending towards infinite. The occurrence of infinity in physical equations, such as the black hole singularities, is a troublesome issue that causes many theories to break down when assessing extreme events. Different methods, such as re-normalization, have been proposed to avoid detrimental infinity. Here a novel technique is proposed, based on physical geometrical considerations and the Alexander Horned sphere, that permits to undermine infinity in physical equations. In this unconventional approach, a continuous monodimensional line becomes an assembly of countless bidimensional lines that superimpose in quantifiable knots and bifurcations.

Introduction. The “memory of water” experiments suggested the existence of molecular-like effects without molecules. Although no convincing evidence of modifications of water – specific of biologically-active molecules – has been reported, consistent changes of biological systems were nevertheless recorded. We propose an alternate explanation based on classical conditioning of the experimenter.Methods. Using a probabilistic modelling, we describe not only the biological system, but also the experimenter engaged in an elementary dose-response experiment. We assume that during conventional experiments involving genuine biologically-active molecules, the experimenter is involuntarily conditioned to expect a pattern, namely a relationship between the descriptions (or “labels”) of experimental conditions and the corresponding biological system states.Results. The modelling predicts that the conditioned observer could continue to record the learned pattern even in the absence of the initial cause, namely biologically-active molecules. The phenomenon is self-sustained since the observation of the expected pattern reinforces the initial conditioning. A necessary requirement is the use of a system submitted to random fluctuations with autocorrelated successive states (no forced return to the initial position). The relationship observed by the conditioned observer is however not causal and has a quantum-like structure. The modelling predicts also that blind experiments with an “outside” supervisor lead to a loss of correlations (i.e. system states randomly associated to “labels”). Conclusion. This psychophysical modelling allows explaining the results of “memory of water” experiments without referring to water or another local cause. It could be extended to other scientific fields in biology, medicine and psychology when an experimenter effect is suspected.

In this work, a mixture of Elzaki transform and projected differential transform method is applied to solve a nonlinear wave-like equations with variable coefficients. Nonlinear terms can be easily manipulated by using the projected differential transformation method. The method gives the results show that the proposed method is very efficient, simple and can be applied to other applications.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.

It is introduced and studied para-Ricci-like solitons with potential Reeb vector field on almost paracontact almost paracomplex Riemannian manifolds. The special cases of para-Einstein-like, para-Sasaki-like and having a torse-forming Reeb vector field have been considered. It is proved a necessary and sufficient condition the manifold to admit a para-Ricci-like soliton which is the structure to be para-Einstein-like. Explicit examples are provided in support of the proven statements.

Background: Humoral memory and specific antibodies levels depend on kind of the antigen and individual immunofactors., The presence of IgM antibodies or fourfold rise in specific IgG level, are generally accepted as diagnostic in serology of acute viral infection. This basic model is not adequate for herpesvirome especially after hematopoietic stem cell transplantation (HSCT) due to continuous, usually multifocal antigenic stimulation, various donor serostatus, immunosuppresion and individual immunoreconstitution. Methods: A  case-control study was conducted for identifying cases of Human herpesviruses (HHV) active infection (from 300 diagnosed immunocompromised patients) and evaluating historically associated humoral factors to look at outcomes. We enrolled only patients’ data with meticulous differential diagnosis to exclude other causes, thereby observe pathways and temporal relationships, not statistical ones, usually collected in cohorts. Despite the small number such data collection and analysis avoids a number of biases and indicates cause and effect.Results. In the observational study retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex (HSV) and varicella zoster virus(VZV) reactivation showed a number of biases. In two well differentiated cases (confirmed by Tzanck test) with various disease and conditioning evolution of immunoparameters showed interesting pathway. Exponential decrease of specific IgG after HSCT precedes virus replication with cytopathic effect (shingles, VZV-encephalitis and HSV-induced mucositis). Minima (smallest IgG levels) before herpes virus reactivation were 234,23 mIU/ml and 94 RU/ml for VZV and HSV, respectively. This coincides with low CD4 titer, but without other infectious process. Other immune response parameters such as Treg, cytotoxic T cells, complement and total IgG level were quite the same as before the transplant procedure. Interestingly, the second wave of immunoreconstitution with anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. Patient with lymphocyte depletion in conditioning showed earlier second wave of immunoreconstitution (6th vs 14th month) Conclusions: Typical for infancy kinetics of IgG level is unique after HSCT (the decline phase is first). Host-microbiome factors (i.e. HHV1-3 -serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help to predict the prognosis and improve the management. The lack of differentiation, assessor and confusing bias are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be first to build evidence of a pathway and association between immunoparameters and HHV disease.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

Rapid spread of African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries world-wide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemi-nation. Twelve out of 13 gilts aborted at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to im-planted embryos. These results underline the critical role that boar semen could play in ASFV transmission.

Quebec is the third-largest wine grape producing province in Canada, and the industry is constantly expanding. Traditionally, 90% of the grapevine cultivars grown in Quebec were rustic or semi-rustic and largely dominated by winter hardy interspecific hybrid Vitis sp. cultivars. Over the years, the winter protection techniques adopted by growers and climate changes have offered an opportunity to establish V. vinifera L. cultivars (e.g. Pinot Noir). We characterized the virome of leafroll-infected interspecific hybrid cultivar and compared it to the virome of V. vinifera cultivar to support and facilitate the transition of the industry. A dsRNA sequencing method was used to sequence symptomatic and asymptomatic grapevine leaves of different cultivars. The results suggested a complex virome in terms of composition, abundance, richness, and phylogenetic diversity. Three viruses, grapevine Rupestris stem pitting-associated virus, grapevine leafroll-associated virus (GLR) 3 and 2 and hop stunt viroid (HSVd) largely dominated the virome. However, their presence and abundance varied among grapevine cultivars. The symptomless grapevine cultivar Vidal was frequently infected by multiple virus and viroid species and different strains of the same virus, including GLR virus 3 and 2. Our data shows that viruses and viroids associated with the highest number of grapevines expressing symptoms included HSVd, GLR3 and GLR2, in gradient order. However, co-occurrence analysis revealed that the presence of GLR species was randomly associated with the development of virus-like symptoms. These findings and their implication for grapevine leafroll disease management were discussed.

A generalization of $\eta$-Ricci solitons is considered involving an additional metric and functions as soliton coefficients. The soliton potential is torse-forming and orthogonal to the contact distribution of the almost contact B-metric manifold. Then such a manifold can also be considered as an almost Einstein-like manifold, a generalization of an $\eta$-Einstein manifold with respect to both B-metrics and functions as coefficients. Necessary and sufficient conditions are found for a number of properties of the curvature tensor and its Ricci tensor of the studied manifolds. Finally, an explicit example of an arbitrary dimension is given and some of the results are illustrated.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.