A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

The effects of post-treatment temperature-based methods on 1D single PLA filaments after FFF have been studied. This lets to decouple the variables related to the 3D structure (layer height, raster angle, infill density, and others) from the variables solely related to the material (molecular weight, molecular orientation, crystallinity, and others). PLA 1D filaments have been aged at 20, 39, 42, 51, 65, 75 and 80 ºC in a water-bath-inspired process in which the hydrolytic degradation of the PLA has been minimised for the ageing temperatures of interest. The evolution of the thermal and mechanical properties of the PLA filaments at different temperatures was recorded. Differential scanning calorimetry (DSC) was used to evaluate thermal and physical properties, in which the glass transition, enthalpic relaxation, crystallisation and melting reactions were analysed. Tensile tests were performed to evaluate the tensile strength and elastic modulus. The flow-induced molecular orientation, the degradation, the logistic fitting and the so-called summer effect –stabilisation of properties at higher temperatures– are discussed for assessing the safeness of accelerating ageing.

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.

Abstract:Global ship demolition is mostly concentrated in south Asian countries, namely Bangladesh, India, Pakistan and China, since 1990’s, having competitive advantage for their high natural tide, and low environmental and social costs. Due to high social and environmental externalities, stakeholders increase monitoring of the externalities and continue to prescribe improvement towards sustainability, which put pressures on profitability and competitiveness. As a consequence, also seen in the past, a leakage effect may emerge, leading to shift of this activity to a region, with relatively less monitored and less stricter on social and environmental impacts. Unfortunately, the leakage effect is never predicted in shipbreaking in order to understand the level of push compatible in the given socio-economic contexts. In this study, we have attempted to predict the future ship demolition landscape, applying machine learning technique to 34,531 in-service vessels worldwide, larger than 500 gross tonnage (GT), which is run against a learning model based on 3500 demolished vessels from 2014. This study shows that redistribution may occur among the top recycling nations: India may emerge out to be a dominant player in shipbreaking, surpassing Bangladesh by a margin of two-fold, while Pakistan and China are in decreasing trend. In addition, the leakage effect is observed, in that Vietnam is predicted to be the fourth largest ship demolition country, while China and Pakistan recede from the third and fourth place to 6th and 8th. Turkey is predicted to advance from fifth position to third position by vessel count but stays same in term of total GT dismantled. Although it is not clear if any leakage is to be observed in the near future, this study may be a model for future predictive analytics and help stakeholders take evidence-based business decisions.

In this study, a novel absorbable hemostatic agent was developed using carrageenan (CRG) as a natural polymer and cerium oxide nanoparticles (CeO2 NPs).  CRG-CeO2-0.5 and CRG-CeO2-1 composites were prepared by compositing CRG and CeO2 at a weight ratio of 200:1 and 100:1, respectively. Physio-chemical and structural properties of these compounds were studied and compared with pristine CRG. Upon incorporation of CeO2 nanoparticles into the CRG matrix, significant reductions in hydrogel degradation were observed. In addition, it was noted that CRG-CeO2 exhibited better antibacterial and hemostatic properties than CRG hydrogel without CeO2.The biocompatibility of the materials was tested using the NIH 3T3 cell line and all samples were found to be nontoxic. Particularly, CRG-CeO2-1 demonstrated superior hemostatic effects, biocompatibility, and a lower degradation rate since more CeO2 Nps were present in the CRG matrix. Therefore, CRG-CeO2-1 has the potential to be used as a hemostatic agent and wound dressing.

Abstract: The study focuses on how socio-economic and demographic indicators affect fertilization sustainability (excessive amount of fertilization). Principally we aim to examine the significance magnitude of the effects of three socio-demographic variables such as traditional way of fertilization, rental land farming, and farmers’ younger age on over-fertilization in Bangladesh and other developing countries. In 1960s, Bangladesh state authority launched a campaign ‘Grow more Food’ to feed huge numbers of population and thus the farmers are provided chemical fertilizers and pesticides at a subsidized low price. Farmers began to use huge amount of fertilizers for gaining high yields and continued it to present causing environmental woes a lot. We interview (face-to-face, focus group discussion, and phone interview) 210 Bangladesh farmers in 2016 by semi-structured questionnaire. Data has been analyzed using General Linear Model (GLM) in Univariate Analysis of Variance. The study found the effect of traditional way of fertilization on excessive amount of fertilization is strongly significant at 1% level. Apart from, rental land farming and farmers’ younger age have a significant influence on over- fertilization; though their significance level (5% and 10% respectively) is quasi-strong. Policy makers can be able to formulate fertilizer policy on the basis of these findings.

Abstract Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerizes and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes lead to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research, However, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia

This paper reports aligned activities to promote energy and resource-efficient construction practice in Vietnam. First, the governance framework is introduced, including government decrees and technical standards. Then, a laboratory with building physics measurement technology is designed and partly set up at the local partner Vietnam Institute for Building Materials (VIBM), which can be used to determine the essential characteristic values required for the implementation of energy standards. The basis for the prioritization of the characteristic values are the requirements of the National technical regulation on energy efficient buildings of Vietnam – QCVN09:2017/BXD. Furthermore, basic characteristic values from international standards are described, which can also be used for calculations to optimize the energy consumption of buildings. In order to be able to carry out transient hygrothermal computer simulations, special characteristic values were also included. These are particularly useful for the research and development of new building materials and the evaluation of entire buildings in terms of thermal and moisture protection In order to communicate the material properties to the market and enable informed decision making by the stakeholders, a labeling system has been developed. Thereby, the practical means for implementing governance instruments are provided, and the related technical applications are supported.

Optical properties of the cornea are responsible for correct vision, ultrastructure allows optical transparency and biomechanical properties governs the shape, elasticity or stiffness of the cor-nea affecting ocular integrity and intraocular pressure. Therefore, optical aberrations, corneal transparency, structure and biomechanics play a fundamental role in the optical quality of hu-man vision, ocular health and refractive surgery outcomes. However, the convergence of those properties is not yet reported at macroscopic scale within the hierarchical structure of the cornea. This work explores the relationships between biomechanics, structure and optical properties (corneal aberrations and optical density) at macrostructural level of the cornea through dual Placido-Scheimpflug imaging and air-puff tonometry systems in a healthy young adult popula-tion. Results showed convergence between optical transparency, corneal macrostructure and biomechanics.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

The utilization of fermented foods has been a longstanding practice in human civilization worldwide for example sauerkraut from the Roman Empire, Jiangshui, and PaoCai, which are popular traditional foods in China. In Korea, Russia, and Mongolia, Kimchi and Kefir are widely used. Similarly, Japan, Indonesia, and Pakistan have their traditional fermented foods such as Miso, Natto, Tempeh, and sourdough, respectively. In America and Europe, fermented alcoholic beverages made from sorghum and maize are among the most common. Nevertheless, the full potential of fermented foods to enhance the bioavailability of bioactive compounds and restore probiotic communities has yet to be thoroughly explored. In this review, we focus on the bioactive compounds and probiotic stability in food fermented with probiotic bacterial strains. Probiotic fermented food improves the bioactive compound contents and has been gaining interest in basic and clinical research. Bioactive compounds, including phenolic, alkaloids, terpenoids, flavonoids, stilbenes, coumarins, tannins, anthocyanidins, flavones, isoflavonoids, and polyphenols, along with beneficial bacteria such as Lactobacilli, Bifidobacteria, Pediococcus, and Weissella demonstrate increased levels and restoration in probiotic fermented foods. These bioactive compounds, combined with a thriving microbiota, play a role in preventing viral infections by targeting influenza, noroviruses (NoVs), Murine norovirus-1 (MNV-1), and COVID-19, while also stimulating the host's immune function. Clinical and pre-clinical investigations are warranted to explore the dose-response and duration efficacy of probiotic fermented foods against viral infections.

Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, and many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes, including proteins, metabolites, nucleic acids, and lipids. Consequently, it is argued that exosomes may serve as unconventional secretory vesicles, playing a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses both qualitatively and quantitatively. Thus, the analysis of EVs from multiple biofluids, due to its ease of implementation, has become a booming tool for monitoring various pathologies, particularly cancer, as we shall outline further on. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Indeed, during a viral infection, the production of EVs and circulating exosomes is often enhanced to signal danger, stimulate immunity, and possibly serve as pathological biomarkers. Conversely, viruses can disrupt or hijack the exosome content and production. In this review, we discuss the particular and ambiguous functions of exosomes in infectious contexts. Furthermore, we explore the vectoring capacity of exosomes in light of the extensive literature examining their function in mounting adaptive immune responses. Exosomes provide an interesting platform for antigen presentation and could therefore serve as novel therapeutic targets or be used in vaccine strategies.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to its inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The previous COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances when vaccination is not accessible or in individuals with compromised immune systems, drugs can give additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds including anti-viral. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Epigenetic modifications in the genome can affect gene expression without altering DNA sequence. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses have recruited cellular epi transcriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we are exploring the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing modulation processes and anti-viral effects on DNA and RNA viruses, and addressing future research objectives in this rapidly emerging field.

Alphaviruses are positive-sense RNA arboviruses that are capable of causing severe disease in otherwise healthy individuals. There are many aspects of viral infection that determine pathogenesis and major efforts regarding the identification and characterization of virulence determinants have largely focused on the roles of the nonstructural and structural proteins. Nonetheless, the viral RNAs of the alphaviruses themselves play important roles in regard to virulence and pathogenesis. In particular, many sequences and secondary structures within the viral RNAs play an important part in the development of disease and may be considered important determinants of virulence. In this review article, we summarize the known RNA-based virulence traits and host:RNA interactions that influence alphaviral pathogenesis for each of the viral RNA species produced during infection. Overall, the viral RNAs produced during infection are important contributors to alphaviral pathogenesis and more research is needed to fully understand how each RNA species impacts the host response to infection as well as the development of disease.

The work is devoted to the investigation of virus quasispecies evolution and diversification due to mutations, competition for host cells, and cross-reactive immune responses. The model consists of a nonlocal reaction-diffusion equation for the virus density depending on the genotype considered as a continuous variable and on time. This equation contains two integral terms corresponding to the nonlocal effects of virus interaction with host cells and with immune cells. In the model, a virus strain is represented by a localized solution concentrated around some given genotype. Emergence of new strains corresponds to a periodic wave propagating in the space of genotypes. The conditions of appearance of such waves and their dynamics are described.

Viruses are the most abundant biological entities in aquatic ecosystems and harbor an enormous genetic diversity. While their great influence on the marine ecosystems is widely acknowledged, current information about their diversity remains scarce. A viral metagenomic analysis of three water samples was conducted from sites on the South Scotia Ridge (SSR) near the Antarctic Peninsula, during the austral summer 2016. The taxonomic composition and diversity of the viral communities were investigated and a functional assessment of the sequences was determined. Phylotypic analysis showed that most viruses belonging to the order Caudovirales, especially the family Podoviridae (41.92-48.7%), similar to the viromes from the Pacific Ocean. Functional analysis revealed a relatively high frequency of phage-associated and metabolism genes. Phylogenetic analyses of phage TerL and Capsid_NCLDV (nucleocytoplasmic large DNA viruses) marker genes indicated that many sequences associated with Caudovirales and NCLDV were novel and distinct from known phage genomes. High Phaeocystis globosa virus virophage (Pgvv) signatures were found in SSR area and complete and partial Pgvv-like were obtained which may have an influence on host-virus interactions. Our study expands the existing knowledge of viral communities and their diversities from the Antarctic region and provides basic data for further exploring polar microbiomes.

RNAi is considered a major antiviral defense mechanism in insects but its relative importance compared to other antiviral pathways has not been evaluated comprehensively. Here, it is attempted to give an overview of the antiviral defense mechanisms in Drosophila that involve both RNAi and non-RNAi to acquire a sense of their relative importance. While RNAi is considered important in most viral infections, many other pathways can exist that confer antiviral resistance. It is noted that very few direct recognition mechanisms of virus infections have been identified in Drosophila and that the activation of immune pathways may be accomplished indirectly through cell damage incurred by viral replication. In several cases, protection against viral infection can be obtained in RNAi mutants by non-RNAi mechanisms, confirming the variability of the RNAi defense mechanism according to the type of infection and the physiological status of the host. This analysis invites to investigate more systematically the relative contribution of RNAi in the antiviral response and more specifically to ask whether RNAi efficiency is affected when other defense mechanisms predominate. While Drosophila can function as a useful model, this issue may be more critical for economically important insects that are either controlled (agricultural pests and vectors of diseases) or protected from parasite infection (beneficial insects as bees) by RNAi products.

Background: To compare the clinical efficacy of Japas osteotomy of the middle foot and first metatarsal sequence osteotomy in treating children with cavovarus foot deformity. Methods: A retrospective analysis was performed on the clinical effect of cavovarus foot surgery from January 2012 to January 2019. Thirty light and medium cavovarus foot cases underwent osteotomy based on soft tissue release. Among them, 16 cases of 22 feet underwent first metatarsal sequence osteotomy, and 14 cases of 21 feet underwent middle foot Japas osteotomy. Ankle-posterior foot (Wicart) scoring system was used to evaluate the good and good rates of the two surgical methods. X-ray films were taken before and after the last follow-up in a standing weight-bearing position, and Meary Angle, Hibb Angle, and Pitch Angle were measured to compare the clinical efficacy of the two surgical methods in correcting the light and medium-cavovarus foot deformity.Results: (1) All patients were followed up for an average of 30 months. There was no significant difference in Meary, Hibb, and Pitch Angle between first metatarsal osteotomy and middle foot Japas osteotomy before surgery, indicating that the severity of malformation was similar between the two groups. (2) The Meary, Hibb, and Pitch Angle of the last follow-up were compared between the two groups (P>0.05), which showed no statistical significance, indicating that the two surgical methods had similar effects on cavovarus deformity correction. (3) At the most recent follow-up, there was no statistically significant difference between the two groups regarding the percentage of patients who achieved an excellent or good Wicart score; for the first metatarsal osteotomy group, the rate was 87%, and for the Japas osteotomy group was 90%; the Fisher test p>0.05 indicates that the postoperative excellent and good rates of the two treatments are comparable.II (4) Comparison of operation time and intraoperative blood loss between the two groups, P<0.05, showed statistically significant differences, indicating that the first metatarsal osteotomy had obvious advantages over Japas osteotomy operation time and intraoperative blood loss. Conclusions: There is no significant difference in postoperative efficacy between first metatarsal osteotomy and Japas osteotomy for light and medium-cavovarus with the apex of the deformity located at the medial cuneus or navicular cuneiform joint. However, the intraoperative blood loss and operative time of first metatarsal osteotomy are superior to Japas osteotomy of the middle foot, and the trauma to children is less. Therefore, the first metatarsal osteotomy can be considered a surgical procedure.

Live attenuated vaccines have through history proved themselves as safe and efficient. Pasteur has developed a vaccine against rabies, through a long process of passage of the virus wild type through rabbits. The result was one of the most efficient attenuated live-virus vaccines. This paper suggests a method based on calculations of biothermodynamic properties of potential tissues for vaccine application, predilected host tissue and virus wild type. Gibbs energy of biosynthesis represents the thermodynamic driving force for virus multiplication. The attenuated strain of the virus should possess Gibbs energy of biosynthesis, which is less negative than the predilected target tissue, but more negative than the vaccine portal tissue. In that way, the attenuated virus strain should be able to multiply in the vaccine portal of entry tissue and cause an immune response, making it efficient. On the other hand, the attenuated strain cannot multiply in the predilected host tissue, making it safe. The attenuation is achieved by adding a gene to the virus, which encodes a ballast protein. Production of the ballast protein would make virus multiplication less favorable, since it would require energy, but be useless to the virus.

Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.

A reduced-dimension (RD) method based on the proper orthogonal decomposition (POD) technology and the linearized Crank-Nicolson mixed finite element (CNMFE) scheme for solving the 2D nonlinear Extended Fisher-Kolmogorov (EFK) equation is proposed. The method reduces CPU runtime and error accumulation by reducing the dimension of the unknown CNMFE solution coefficient vectors. For this purpose, The CNMFE scheme of the EFK equation is established and the uniqueness, stability and convergence of the CNMFE solutions are discussed. Subsequently, the matrix-based RDCNMFE scheme is derived by applying the POD method. Furthermore, the uniqueness, stability and error estimates of the linearized RDCNMFE solution are proved. Finally, numerical experiments are carried out to validate the theoretical findings. In addition, we contrast the RDCNMFE method with the CNMFE method, highlighting the advantages of the dimensionality reduction method.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

Psychiatric disorders, characterized by complex and fluctuating patterns of thoughts, emotions, and behaviors, can be effectively modeled and visualized using mathematical wave equations. This study explores the representation of three major psychiatric conditions— Psychosis, Bipolar Disorder and Obsessive Compulsive Disorder (OCD)—through the application of differential equations, damping factors, and noise perturbations. Psychosis is modeled using Lissajous figures with high-frequency components, damping, and noise, symbolizing the irregular and erratic thought patterns characteristic of this condition. The inclusion of random perturbations and varying frequencies illustrates the chaotic and unpredictable nature of psychotic episodes, while damping effects reflect the temporary reductions in symptom intensity. For bipolar disorder, a system of partial differential equations simulates the cyclical nature of manic and depressive episodes. The model captures high-energy manic phases with periodic disturbances and the subsequent transition to lower-energy depressive states through damping effects. This representation highlights the oscillatory behavior and recurring episodes inherent to bipolar disorder. OCD is represented with Circumferential Complex Equations in Mult directions. The resulting graphical representations provide intuitive visual insights into the dynamics of these psychiatric disorders. By leveraging wave equations and mathematical modeling, this approach offers a novel perspective on understanding and analyzing the complex behaviors associated with OCD, bipolar disorder and psychosis. This method not only aids in the conceptualization of psychiatric phenomena but also underscores the potential of mathematical tools in the study of mental health conditions.

Assessing the genetic diversity of metabolic resistance genes such as cytochrome P450s helps to understand the dynamics and evolution of resistance in the field. Here, we analysed the polymor-phisms of CYP6M2 and CYP6P4 associated with pyrethroid resistance in Anopheles coluzzii and An. gambiae, to detect potential resistance markers. Field-caught resistant mosquitoes and susceptible lab-strains were crossed and F4 was exposed to permethrin for 15min and 90min to discriminate highly susceptible (HS) and highly resistant (HR) mosquitoes respectively. Significant permethrin mortality reduction was observed after pre-exposure to PBO, suggesting P450s genes involvement. QPCR analysis revealed significant over-expression of CYP6M2 (FC=19.57 [95%CI 13.96-25.18] for An. coluzzii; 10.16 [7.86-12.46] for An. gambiae) and CYP6P4 (FC=6.73 [6.15-7.30] An. coluzzii; 23.62 [26.48-20.76] An. gambiae). Full-gene and ≈1kb upstream were sequenced. For CYP6M2, upstream region shows low diversity in HR and HS (overall Hd=0.49, π=0.018), whereas the full-gene shows allelic-variation but without evidence of ongoing selection. CYP6P4 upstream region showed a lower diversity in HR (Hd=0.48) than HS (Hd=0.86) of An. gambiae. These results highlighted that CYP6P4-associated resistance is potentially driven by modification in upstream region. However further work is needed to determine the real causative variants which will help design rapid detec-tion tools.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

The energy transition is a challenge that affects all sectors, from transport to civil structures and industry. In the industrial sector, the greatest need is the decarbonisation of energy-intensive in-dustries, such as producers of iron and steel, aluminum, cement, petrochemicals, paper, and more. The steel industry, in particular, is a hard-to-abate high-emissivity industry that, due to chemical processes and high thermal demands (often above 500 °C), contributed to 7.4% of global CO2 emissions in 2021. This paper explores the potential applications of hydrogen in these hard-to-abate sectors, highlighting its versatility and significance in decarbonization efforts, especially as a me-dium to facilitate the transition to green electric energy uses. It provides an overview of hydrogen production methods, emphasizing the importance of sustainable and green hydrogen production. It reviews hydrogen production methods, storage, and potential in blended combustion. In the final part of the article, some considerations are introduced on the possible role of hydrogen in the steel sector (both as a supplementary fuel and as a reducing agent in innovative processes), showing that while there is potential for its inclusion as an element for decarbonization, it is necessary to carefully evaluate the energy balances of the various processes and the methods of hydrogen production, in order to avoid achieving only marginal effects.

Background: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Objectives: To investigate the efficacy of manual therapy (MT) program combined with Capacitive and Resistive Electric Transfer (TECAR) therapy in individuals with CNSLBP. Method: Sixty adults with CNSLBP were randomly equally divided into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet and the third group (Control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 hours with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), Pressure Pain Threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both in the second week as well as in the one-month follow-up (p < .001). Between-groups differences were also noticed between the two intervention groups in the second week (p < .05). Differences in the RMDQ score in the second week and on the one-month follow-up were detected between the intervention groups and the control group (p < .001), while differences between the two intervention groups were only detected in the one-month follow-up (p < .001). Regarding the PPT values, differences were found mainly between the MT + TECAR and the control group and between the MT + TECAR and the MT group (p < .05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant in the one-month follow-up (p < .05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region in both time points compared to the control group without, however, statistically significant differences between them (p> .05). Conclusion: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.

Abstract: The contribution of breakfast to diet quality (DQ) can inform future dietary guidelines. This study examined breakfasts that were associated with highest-quality diets. Dietary data came from the first reported day of the National Health and Examination Survey (NHANES) 2011-2014 (n=14,488). DQ measures were the Nutrient Rich Foods Index (NRF9.3) and the USDA Healthy Eating Index 2015 (HEI 2015). Analyses of breakfast intakes were conducted by NRF9.3 tertiles and by age and socioeconomic groups. Four out of 5 NHANES participants ate breakfast. Breakfast provided 19-22% of dietary energy depending on age. Breakfast intakes of complex carbohydrates and total sugars were higher and intakes of protein and fats were lower relative to energy intakes. Breakfast provided more that 20% of daily intakes of B vitamins, vitamins A and D, folate, calcium, iron, potassium and magnesium. Eating breakfast was associated with higher NRF9.3d scores. Breakfasts associated with top tertile of NRF9.3d had more carbohydrates and less added sugars and fats. Such breakfasts had more fruit and juices, more whole grains, more milk and yogurt and less meat and eggs. Breakfast patterns that favored fruit, whole grains, and dairy were associated with healthiest diets.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

Hashimoto’s thyroiditis (HT) is a common autoimmune disease, with its prevalence rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed features of HT through bioinformatics analysis so as to identify markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed Gene Set Enrichment Analysis (GSEA) using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. GSEA results revealed activation of autoimmune disease-related pathways and several viral infection pathways. Autoimmune disease and viral infection pathways were highly interconnected by common genes, while the HLA genes which are shared by both were significantly upregulated. CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor, which responds to viral activity, might serve as potential marker of HT.

The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination deeply reduced the viral load throughout the experiment and allowed cellular recovery, thus representing a potential innovation, to be considered as an additional weapon for therapy of COVID-19 and even other infectious diseases.

There is a relatively high risk of virus transmission in dental procedures and oropharyngeal examinations. We investigated the effects of mouthwashes on covid-19 viral load reduction during dental practices and oro-pharyngeal assessments. We performed a systematic search in PubMed, EMBASE, Scopus, Web of Science, Cochrane library for relevant studies up to February 2021. Papers evaluating patients with covid-19 infection (patients) who rinse mouthwashes (intervention) compared to patients who don’t rinse them (comparison) for reducing covid-19 viral load or reducing cross-infection of covid-19 (outcome) in the randomized and non-randomized clinical trial and quasi-experimental studies (study) were included due to PICOS question. Three independent authors conducted literature screening and data extraction. We extracted the most relevant data and we evaluated the risk of bias from the included studies. Out of 344 potentially eligible articles, six studies were included in this systematic review. Regarding viral load and negative cycle threshold (ct) values, 1% PVP_I and Listerine mouthwash were effective. 0.12% CHX mouthwash was effective 0-2 hours post rinsing, but it was not effective after 2 hours. A mixture solution of 0.2% Chlorhexidine gluconate and 6% Hydrogen peroxide was effective on day 5 of intervention. Gargling 1% hydrogen peroxide, 0.075% Cetylpiridinum Chloride (CPC), 0.5%PVP-I and 0.2% CHX mouthwashes was not effective on SARS-COV-2. It cannot be guaranteed that rinsing a specific kind of mouthwash prevents cross-infection of covid-19; however, the viral load of SARS-COV-2 in saliva will be decreased after rinsing mouthwashes containing 1%PVP-I and Listerine.

This review seeks to explain four features of viral respiratory illnesses that have perplexed many generations of microbiologists: (1) the seasonal occurrence of viral respiratory illness; (2) the occurrence of respiratory illness year-round in the Tropics; (3) the rapid response of illness to temperature drops in temperate regions; (4) the explosive arrival and rapid termination of epidemics caused by influenza and other respiratory viruses. I discuss the inadequacy of the popular explanations of seasonality, and propose a simple hypothesis, called Temperature Dependent Viral Tropism (TD-VT), that is compatible with the above and other features of respiratory illness. TD-VT notes that viruses can often transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining the mobility of their hosts) and suggests that most endemic respiratory viruses accomplish this by developing thermal sensitivity, in the sense that they normally replicate rapidly only at temperatures below normal body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. I review biochemical and tissue-culture studies that found that “wild” respiratory viruses often show natural thermal sensitivity within a range that supports organ-specific tropism within the human body, and I discuss the evident tendency for viral strains to adapt their thermal sensitivity to their local climate and season. I also explore the possible misinterpretation of early experiments where volunteers were inoculated nasally with viral samples and then chilled. Next, I discuss the practical implications of the TD-VT hypothesis for preventing and treating respiratory illness. Finally, I note that the hypothesis is very testable and make suggestions for the most important experiments to increase our understanding of the seasonality and pathogenicity of viral respiratory illness.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Corporate governance has received increasing attention from practitioners and politicians after the collapse of large companies due to accounting errors and failure to disclose information that reflects the true financial condition of companies. Voluntary risk disclosure includes several aspects, including financial risks, including risks of interest rate, exchange rate, liquidity as well as risks of operations. In Jordan, the most common type of business is family businesses, where boards of directors usually serve the interests of the family that owns the majority stake in the company.This study identifies the moderate effect of family in the link joining the audit committee with the voluntary risk disclosure of financial institutions in Jordan. It's population is the Jordanian commercial banks registered and operating in Jordan during the period extending from 2017 to 2023.Significantly, it concluded with revealing that the characteristics of the audit committee; namely, independence, experience, and committee size, obviously impact disclosure of voluntary risk in the selected banks. However, the results made it obvious that the number of audit committee meetings did not affect the degree of voluntary risk disclosure. In addition, the results view family ownership as moderately affecting the relationship joining some audit committee characteristics with voluntary risk disclosure.

Enterprise risk management (ERM) was introduced in the 1990s and has become an expectation by boards of directors and regulators as a sign of good management and good corporate governance. However, many organizations struggle to implement ERM, and still seek practical ad-vice on ERM implementation. This article explains many of the reasons why organizations are unsuccessful in their efforts at implementation and provides practical solutions by an experienced risk manager and consultant, an ex-Chief Risk Officer, and an academic, all who has writ-ten extensively in the subject. This article should be of interest to practitioners involved in implementing ERM, to consultants in ERM, and to academics teaching courses on ERM, risk management, and related topics. This article also provides a base against which further future re-search can be done as ERM best practices continue to evolve.

Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary palliative care

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing (TaqManTM Array Cards). More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were co-detected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.

The technique of using drugs to target latent virus reservoirs has been introduced to reawaken dormant viruses so that the immune system can attack them. However, further tests have shown this method to fail in laboratory tests. In this work, the author tries to mathematically analyze whether drugs can be used to reawaken dormant virus reservoirs and proposed the use of viral proteins to activate the sleeping virus. The results show that the amino acid sequences ARG of gag proteins of HTLV1, HTLV2, STLV1 and STLV2 match with their primer binding site GGGGGCTCG in the 3'-to-5' direction, and the amino acid sequences SPR of gag proteins of HIV1, HIV2, SIV and FIV match with their primer binding site GGCGCCCGA in the 3'-to-5' direction. The gag proteins are promising for reawakening dormant retrovirus infection. The author hence believes that the latency-reversing drugs were involved in the process of transcription of cancer genes, and the virus genome they reawaken were just happened to contain the same NF-κB binding sites, so the drugs were indirectly reawakened dormant retrovirus infection. On the other hand, it is more reliable to use viral proteins to directly reawaken retrovirus, just as androgen receptor activates the IGF1R gene.

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and a several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in-vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.

Alphaviruses are arboviruses that cause arthritis and encephalitis in humans. Eastern Equine Encephalitis Virus (EEEV) is a mosquito transmitted alphavirus that is implicated in severe encephalitis in humans with high mortality. However, limited insights are available into its fundamental biology of EEEV and residue-level details of its interactions with host proteins. In recent years, outbreaks of EEEV have been reported mainly in the United States, raising concerns about public safety. This review article summarizes recent advances in the structural biology of EEEV based mainly on recent single particle cryogenic electron microscopy (cryoEM) structures. Together with functional analyses of EEEV and related alphaviruses, these structural investigations provide clues to how EEEV interacts with host proteins, which may open avenues for the development of therapeutics.

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

Poliovirus 2A protease (PV2Apro) plays a vital role in viral replication and down-regulation of host cell protein synthesis. In order to understand more concerning PV2Apro, the protein was over-expressed in bacteria following amplification using sense and antisense primers and cloning in pET15b. Several expression hosts were tested and BL21 (DE3) pLysS cells gave the best expression of PV2Apro with minimal unwanted protein expression following IPTG induction. The 2Apro protein was purified to homogeneity using column chromatography, its solubility determined and its molecular weight and composition determined by MALDI-TOF mass spectrometry. The protease was found in the insoluble fraction and the purified protein had a slightly lower molecular weight than predicted. Moreover, three dimensional structure was modelled using template 1z8r with 58% identity and validated using ramachandran plot. Results revealed that most of the residues lie in favoured and allowed regions. These findings could help in a better understanding of PV2Apro structure and inhibition thus, highlighting potential targets for antiviral drug development.

Although there are extensive literature reports on the use of gold nanoparticle (AuNP) based homogeneous assays for detection of biomolecules, very few experimental description and procedures involving their preparation are described. In this study, AuNPs conjugated to Bovine Serum Albumin or Envelope protein from Dengue II were developed as a homogeneous immunoassay for antibody detection. We report here optimization of key parameters to prepare an immunoassay like conjugation protein concentration, centrifugation time, electrolyte addition and assay temperature. We determined that saturating protein concentrations improved AuNPs surface coverage and uniformity of the assay and addition of sodium chloride improved sensitivity of the antibody detection method and assay stability. Furthermore, we showed that dynamic light scattering can be used to monitor changes in gold nanoparticles in the preparation and detection steps. Additionally, numerical simulations of the plasmonic optical response of AuNPs were carried out to scan for size-dependent response of the AuNPs. The AuNPs homogeneous immunoassay developed was further used in the detection of antibodies in vitro to detect Dengue virus infection.

Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis Hand, foot, and mouth disease (HFMD) in children worldwide especially in the Asia‐Pacific region. EV71 and coxsackievirus A16 are two viruses responsible for HFMD which are members of group A enterovirus. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the EV71 genome that determine virulence remain unclear. Although an EV71 vaccine has been currently approved, there is no effective therapy for treating EV71 infected patients. Therefore, understanding the host-pathogen interaction could provide the knowledge in viral pathogenesis and further benefit in the anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands to the host receptor as well as the activation of immune related signalling pathways for the activation of innate immunity and involvement of different cytokines and chemokines in the host pathogen interaction of EV71 along with interaction of viral proteins, mainly 2A and 3C protease, and Interferons production/signaling pathway and their inhibitory effects.

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group), and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota, with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days, and examined 16.71% weight loss at 300 days after treatment. In the whole subjects, 60.4%, 21.3% and 6.3% achieved weight reductions exceeding 5%, 10% and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p=0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In vivo, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

In crystal structure prediction, Newton's second law can always be applied to particles (atoms or ions) in a cell to determine their positions. However the values of the period vectors (crystal cell edge vectors) should be determined as well. Here we applied the dynamical equations of period vectors derived recently based on Newton's laws (doi:/10.1139/cjp-2014-0518) for that purpose, where the period vectors are driven by the imbalance between the internal and external pressures/stresses. For equilibrium states, they became equations of state, which essentially turn out the equilibrium conditions of crystals from mechanical point of view. For external pressure, by ignoring some effects, they reduced to the Mie-Gruneisen equation. Since the internal stress has both a full kinetic energy term and a full interaction term, the influences of both external temperature and stress/pressure on crystal structures can be calculated, then thermodynamical properties and processes were presented. Contrary to usual ideas, the equations show that pure harmonic vibrating phonons can result in thermal expansion in crystals when the external temperature is changed. Finally, crystal system collapse due to temperature and/or stress/pressure change was discussed.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Viral hepatitis is currently acknowledged as a significant public health issue that necessitates a prompt and immediate response. Hepatitis is a significant worldwide health problem that causes the death of approximately 1.5 million individuals annually. The objective of this study was to ascertain the occurrence rate of hepatitis A, E, B, and C infections in the Hajjah governorate of Yemen from 2020 to 2023.A retrospective study was conducted in the Hajjah Governorate of Yemen for four years, 2020– 2023. About 41162 cases were collected from the clinical records of epidemiological surveillance in the Public Health Office of the Hajjah Governorate. All cases were diagnosed in different laboratories based on direct observation of viral hepatitis in the blood sample. The required data were obtained by using the designed questionnaire. The findings of the present investigation were summarized as follows: The current findings indicate that the prevalence rate of Hepatitis A and E was 761 (1.85%), while the prevalence rate of Hepatitis B and C was 971 (2.36%) among the participants of the study. The current findings indicate that the incidence of Hepatitis A and E was greater in 2022 (2.3%), while Hepatitis B and C had a higher rate in 2020 (2.9%). The study revealed a higher prevalence of hepatitis A and E among individuals originating from Al Miftah district 116, with a rate of 7.5%. Furthermore, the prevalence of hepatitis B and C in Hajjah city was significantly higher, reaching 579 cases (22.9%). The month with the highest incidence of hepatitis A and E viruses was September, with a rate of 85 cases (2.6%), while the lowest incidence was observed in April, with a rate of 1.3%. The prevalence of hepatitis B and C viruses was highest in October 1997, with a rate of 2.8%, followed by November 1997 with the same rate. The lowest observed incidence of 1.6% was recorded in April. In Autumn, a significant prevalence of hepatitis A and B viruses, as well as hepatitis B and C viruses, was identified at rates of 2.2% and 2.6%, respectively.The study findings indicate that the occurrence of HAV, HEV, HBV, and HCV in the study area is consistent with global trends. Although the study found a low prevalence of hepatitis viruses, these types of viruses will continue to pose a significant risk to public health. Based on this study, it is imperative for authorities to actively enhance public awareness in order to enable prompt planning and essential arrangements for an effective response to outbreaks or epidemics. This will ultimately lead to a reduction in illness, death, and economic burden.

Extracellular vesicle-derived microRNAs (EV-miRNAs) are promising circulating biomarkers for chronic liver disease. In this study, we explored the potential significance of plasma EV-miRNAs in non-hepatitis B-, non-hepatitis C-related HCC (NBNC-HCC). We compared plasma EV-miRNA profiles between NBNC-HCC and control groups including non-alcoholic fatty liver disease (NAFLD) and healthy controls using NanoString method. The differentially expressed EV-miRNAs were validated in another set of plasma samples by qRT-PCR. A total of 66 significantly differentially expressed EV-miRNAs between the HCC and control groups were identified in the discovery set. In the validation cohort including plasma samples of 70 NBNC-HCC, 70 NAFLD and 35 healthy controls, 5 plasma EV-miRNAs were significantly elevated in HCC, which included miR-19-3p, miR-16-5p, miR-223-3p, miR-30d-5p, and miR-451a. These miRNAs were found to participate in several cancer-related signaling pathways based on bioinformatic analysis. Among them, EV-miR-19-3p exhibited the best diagnostic performance and displayed a high sensitivity for detecting AFP-negative HCC and early-stage HCC. In multivariate analysis, high EV-miR-19-3p level was demonstrated as an independently unfavorable predictor of overall survival in patients with NBNC-HCC. In conclusion, our data have indicated for the first time that EV-miR-19-3p could serve as a novel circulating biomarker for the diagnosis and prognosis of NBNC-HCC.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

The outbreak of coronavirus disease-19 (COVID-19) has infected more than 11 million people and has claimed more than 530.000 deaths world-wide. In July 2020, still, there is no specific treatment for disease caused by the novel coronavirus. In the search to curb the global pandemic COVID-19, some eastern and developing countries have approved various treatment with controversial efficacy, among that the use of the antimalarial Hydroxychloroquine (HCQ), so far with inconclusive clinical evidence of effectiveness. On the other hand, computer-based screening suggest that HCQs analog are promising molecules, to impair viral replication in vitro[1]. Therefore, what is emerging from this complex background, is the need to understand molecular mechanism beyond drugs that can be helpful against viral infection for this and future pandemic. The intent of this Brief Report is to highlight: i) the involvement of the Mitogen Activated Protein Kinase (MAPK) cascade in viral infection and ii) the urgent need to have molecular data on the effectiveness of the combination of MAPK inhibitors together with HCQ and HCQs analogs in curbing viral infection. We are convinced that a better understanding of the patterns of elicited molecular mechanisms will be critical for new molecular approaches to this severe disease

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

The proposal of novel drugs and approaches for effective treatment of the novel coronavirus is a necessity after the quick outbreak of the disease. Since the commencement of the coronavirus spread, enormous efforts have been made to protect, alleviate and cure the disease, though no specific treatment has been approved. While there have been convincing results in the use of chemical drugs and interferon therapy, such therapeutic approaches have various drawbacks and lack the required performance for the treatment of the new coronavirus. Medicinal plant species can provide a solution as a source of natural antiviral compounds by the accumulation of secondary metabolites and lectins as well as acting as a platform to express the viral immunogenic proteins. This study reviews the advantages and the results of previous research for the treatment of the novel coronavirus disease and previous generations of similar coronaviruses. Several plant-derived anti coronavirus compounds have been nominated that could be targeted for further research due to the similarity of the coronavirus disease in 2003 and the current coronavirus. This review regards plant species such as Scutellaria baicalensis (Baikal skullcap), and Utrica dioica (Stinging nettle) as suitable candidates for the new coronavirus antiviral research. Furthermore, the use of plants such as Nicotiana tabacum (Tobacco) for the expression of the coronavirus viral antigens can be a target for the future vaccinal research of the new coronavirus due to the efficiency of expression and intrinsic antiviral properties.

Health care workers (HCWs), specifically dentists, are at the front line for acquiring blood-borne virus infections. The highest proportion of occupational transmission is through percutaneous injuries via hollow-bore needles. Several studies around the world have reported that hepatitis viruses and human immunodeficiency virus are the main pathogens for most cases of occupationally acquired blood-borne infection. We aim to investigate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and human immunodeficiency virus (HIV) among Mexican dentists. Methods. We included 159 dentists who attended the annual meeting at the Medica Sur Clinic & Foundation held in Mexico City in May 2016. A survey was applied in order to obtain data of occupational exposure to blood-borne viruses (BBV). Serum samples were screened serologically using enzyme-linked immunosorbent assays. Results. Two dentists (1.2%) were positive for antibodies against HCV antigen, one (0.6%) was positive for antibodies against HBV antigen and three (1.8%) were positive for the detection of IgG antibodies against HEV. Two cases (1.2%) were positive for antibodies against HIV. Conclusions. The infection by HEV was the most prevalent among dentists. However, the prevalence of BBV in dentists was similar to that in the general population.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

Plants have developed unique mechanisms to cope with the harsh environmental conditions to compensate for their lack of mobility. A key part of their coping mechanisms is the synthesis of secondary metabolites. In addition to their role in plants’ defense against pathogens, they also possess therapeutic properties against diseases, and their use by humans predates written history. Viruses are a unique class of submicroscopic agents, incapable of independent existence outside a living host. Pathogenic viruses continue to pose a significant threat on global health, leading to unprecedented fatalities on a yearly basis. The use of medicinal plants as a natural source for an-tiviral agents has been widely reported in literature in the past decades. Metabolomics is a powerful research tool for the identification of plant metabolites with antiviral potentials and can be used to isolate compounds with antiviral activities in plants and study the biosynthetic pathways involved in viral disease progression. This review discusses the use of medicinal plants as antiviral agents, with a special focus on the metabolomics evidence supporting their efficacy. Additionally, suggestions are made for the optimization of various metabolomics methods for characterizing the bio-active compounds in plants and subsequent understanding of the mechanism of their operation.

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

The prediction of tertiary RNA structures is significant to the field of medicine (e.g. mRNA vaccines, genome editing), and the exploration of viral transcripts. Though many RNA folding software exist, few studies have condensed their locus of attention solely to viral pseudoknotted RNA. These regulatory pseudoknots play a role in genome replication, gene expression, and protein synthesis. This study explores five RNA folding engines that compute either the minimum free energy (MFE) or the maximum expected accuracy (MEA). These folding engines were tested against 26 experimentally derived short pseudoknotted sequences (20-150nt) using metrics that are commonly applied to software prediction accuracy (e.g. F1 scoring, PPV). This paper reports higher accuracy RNA prediction engines (pKiss) when compared to previous iterations of the software, and when compared to older folding engines. They show that MEA folding software does not always outperform MFE folding software in prediction accuracy when assessed with metrics such as percent error, sensitivity, PPV, and F1 scoring when applied to viral pseudoknotted RNA. Moreover, the results suggest that thermodynamic model parameters will not ensure accuracy if auxiliary parameters such as Mg2+ binding, dangling end options, and H-type penalties are not applied. The observations reported in this paper highlight the quality between different ab initio prediction methods while enforcing the idea that a better understanding of intracellular thermodynamics is necessary for a more efficacious screening of RNAs.

Cellular Integrated Stress Response (ISR), the mitochondrial Unfolded Protein Response (UP-Rmt) and the IFN signaling are associated with viral infections. The Activating transcription fac-tor 4 (ATF4) plays a pivotal role in these pathways and controls the expression of many genes involved in redox processes, amino acid metabolism, protein misfolding, autophagy and apop-tosis. The precise role of ATF4 during viral infection is unclear and depends on cell hosts, viral agents and models. Furthermore, ATF4 signaling can be hijacked by pathogens to favor viral in-fection and replication. In this review, we summarize the ATF4-mediated signaling pathways in response to viral infections, focusing on human immunodeficiency virus (HIV). We examine the consequences of ATF4 activation for HIV replication and reactivation. The role of ATF4 in au-tophagy and apoptosis is explored as in the context of HIV infection programmed cell deaths contribute to the depletion of CD4 T cells. Furthermore, ATF4 can also participate in the estab-lishment of innate and adaptive immunity that are essential for the host to control viral infec-tions. We finally discuss the putative role of the ATF4 paralogue, named ATF5, in HIV infection. This review underlines the role of ATF4 at the crossroads of multiple processes reflecting host-pathogen interactions.

The generation of different types of defective viral genomes (DVG) is an unavoidable consequence of the error-prone replication of RNA viruses. In recent years, a particular class of DVGs, those containing long deletions or genome rearrangements, has gain interest due to their potential therapeutic and biotechnological applications. Identifying such DVGs in high-throughput sequencing data has become an interesting computational problem. Up to nowadays, several algorithms have been proposed, though all incur in false positives, a problem of practical interest if such DVGs have to be synthetized and tested in the laboratory. Here we develop a novel software, DVGfinder, that wraps the two most commonly used algorithms into a pipeline that predicts DVGs. Using a gradient boosting classifier machine learning algorithm, we evaluate the performance of DVGfinder compared to previous algorithms and found that it outcompetes their precision and sensitivity in simulated datasets. DVGfinder generates user-friendly output files in HTML format that can assist users to identify DVGs based on their associated probability of being true positives.

Over the past decade, Knowledge bases (KB) have been increasingly utilized to complete and enrich the representation of queries and documents in order to improve the document retrieval task. Although many approaches have used KB for such purpose, understanding how effectively lev-erage entity-based representation still needs to be resolved. This paper proposes a Purely Enti-ty-based Semantic Search Approach for Information Retrieval (PESS4IR) as a novel solution. The approach includes (i) its own entity linking method, (ii) an inverted indexing method, and for document retrieval and ranking, (iii) an appropriate ranking method is designed to take advantage of all the strengths of the approach. We report the findings on the performance of our approach tested by queries annotated by two known entity linking tools, REL and DBpedia-Spotlight. The experiments are performed on the standard TREC 2004 Robust and MSMARCO collections. By using the REL method, for queries whose all terms are annotated and whose average annotation scores are greater than or equal to 0.75, our approach achieves the maximum nDCG@5 score (1.000). Thus, using our approach with any other document retrieval method would be an added value, unless that method achieves the maximum nDCG@5 score for those highly annotated queries.

Nature-based Solutions (NbS) have rapidly been gaining traction across the research, policy, and practice spheres, touted as transformative actions to jointly address biodiversity loss and climate change. However, there are multiple, alternative ways to imagine NbS in those three spheres. To inform the NbS discourses across these three spheres, we critically reflect on the prevailing framing of NbS and consider the potential of a different framing of NbS to support transformations towards regenerative relationships between humans and nature. Such reflection is urgently needed to ensure that research, policy, and practice delivers on the transformative ambitions of NbS. We propose a novel “core framing” of NbS, charting two pathways for how such a framing can support a human value-based transformation – first through influencing individual beliefs and values, and second through the communication and application of the NbS concept in research, policy, and practice. We argue that for NbS to support transformation, it must support a reframing of human-nature relationships, one where the interdependencies between people and nature are recognized as essential for social and environmental well-being. We elaborate on how such a framing is key to support inclusivity and collaboration between diverse research perspectives, policy objectives across scales, and implementation practices, to deliver successful NbS.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

The emergence of drug resistance inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A including H57R and S139P within the catalytic triad. We then modeled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e. cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A-ligand interaction, resulting in an unbalanced energy distribution within the binding site leading to drug resistance. cpd-217 was identified to interact with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. The study will pave the way for drug design and development of HCV G3 NS3/4A.

Since the discovery of the first reported case with Zinc-deficiency in Iran¹ by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response ^2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency⁴. In the western world, Zinc deficiency is more prevalent among the geriatric population³, vegans/vegetarians, and people with certain underlying conditions⁴such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders^4,5. Zinc and Zinc deficiency has been associated with several infectious diseases ^2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21^st century^6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.

Aim: This study aims to analyze the structure of the co-authorship network in viral hepatitis research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 60,720 publications related to viral hepatitis research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The findings reveal that the viral hepatitis research network is characterized by low network density, indicating sparse overall collaboration. However, the clustering coefficient is high, suggesting strong collaborations within small, cohesive groups. Over the years, researchers such as Stefan Zeuzem, Maria Buti, and Fabien Zoulim have played pivotal roles, serving as central figures in the network. A noticeable increase in network density and clustering from 2020-2023 suggests growing collaboration in recent years.Conclusion: This study underscores the importance of international collaboration in advancing viral hepatitis research. Key researchers have emerged as influential contributors, facilitating global research activities. Network analysis provides valuable insight into the structure of these collaborations and helps identify potential areas for future research and partnerships to combat viral hepatitis globally. The results of this study should be used to reduce global healthcare disparities, promote research collaboration, and address viral hepatitis as a global public health problem.

Protein 53 (P53) shows different functions either to support or to contrast malignant growth. P53 history tells that discoveries of molecular features have contributed to the emergence of P53 functions. Conversely, the shift of paradigms demonstrates that P53 functions coexist even if are in conflict with one another. Since 1979, five paradigms have been assembled then deconstructed by taking into account P53 functions of viral protein, oncogene, tumor suppressor gene, transcription factor, apoptotic factor. By summarizing the past five disassembled P53 paradigms, in this investigation the current paradigm involving P53 in the modulation of a composite bio-morphological entity namely, tumor immune microenvironment (TIME) is analyzed. The aims of this investigation were to provide an overview of solid and validated knowledge occurring in all P53 paradigms and to determine P53 abilities to modify TIME through manipulation of viruses. As a result, definitive P53 evidence concerns its genetic localization, amino acids composition, its isoforms and subcellular expression in organelles. P53 “mutome” assembles all mutations affecting this complex protein. Lastly, both categories of tumor promoting and non-oncogenic viruses related to P53 were scrutinized. In conclusion, paradigms teach that P53 is undruggable because its drugs inevitably target all P53 functions.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Historically, viral hepatitis is a considerable public health problem in Central Asian countries, which may have worsened after dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n=1075). Participants, children and adults, were recruited from an outpatient clinic. Data were collected during face-to-face interviews. A blood sample (6 ml) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D and E). Poststratification weighting was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval: 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg positive participants, five (15%) were anti-HDV positive. Our study confirms that Kyrgyzstan remains a high endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

Though there has been a decline in the number of new cases of viral hepatitis-induced acute liver failure in Europe and the United States of America, viral hepatitis still remains the leading cause of acute liver failure in Asia-Pacific and South America. However, the epidemiology of viral-hepatitis-induced acute liver failure in sub-Saharan Africa-the world epicenter of viral hepatitis-is unclear. The aim of this review was to collate data on the incidence, prevalence, specific etiologic agents, features/diagnosis, treatment and prognosis of viral-induced acute liver failure in sub-Saharan Africa. One hundred and forty-seven cases of viral-induced acute liver failure were recorded in 11 studies conducted in six countries between 1981-2020. Etiological agents were: Hepatitis viruses A, B, C, and E, as well as Adenovirus, Enterovirus, Parvovirus, Herpes Simplex Virus (HSV) and EBV. HAV was the most frequent in paediatric subjects: (11/16) 69% and (19/30) 63%. HBV was the only etiological agent in the study that only included adults. HEV (genotype 2 in one study) contracted amidst hepatitis E outbreaks was the most commonly reported cause of ALF in pregnant women. Treatment was mainly supportive, and liver transplantation reported only in South Africa. Where reported, case fatality rates were high. In conclusion, viral-hepatitis induced acute liver failure is largely understudied in sub-Saharan Africa. The few available data are consistent with literature from the other parts of the world regarding aetiologic agents. Liver transplantation is not available in most sub-Saharan African countries, and short-term case fatality rates of individuals with acute liver failure could outstrip current rates from the other world regions.

Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of monoclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerful therapeutic potential. Methods: Layers were immunized twice with 14-day interval using purified RBD of SARS-CoV-2. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgY to RBD was measured by indirect ELISA. Neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry strain using fluorescence and cell viability assay. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bind RBD of S protein of SARS-CoV-2 in situ, neutralize the virus in vitro, and lower viral RNA amplification without significant alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicated that chicken polyclonal IgYs can be attractive targets for pre-clinical and clinical development for rapid management of outbreaks of emerging and re-emerging viruses.

HIV-1 protease (PR) is a viral enzyme that cleaves viral polyprotein precursors to convert them into functional forms, a process essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. While PR typically has low levels of intracellular activity prior to viral budding, induction of premature PR activation to trigger CARD8-mediated cell killing may help eliminate latent reservoirs in people living with HIV. In this review, we discuss the viral and host substrates of HIV-1 protease and highlight potential applications and advantages of targeting CARD8 sensing of HIV-1 PR.

Among all economically important plant species in the world, grapevine (Vitis vinifera L.) is the most cultivated fruit plant. It has a significant impact on the economies of many countries through wine and fresh and dried fruit production. In recent years, the grape and wine industry has been facing outbreaks of known and emerging viral diseases across the world. Although high-throughput sequencing (HTS) has been used extensively in grapevine virology, the application and potential of third-generation sequencing have not been explored in understanding grapevine viruses and their impact on the grapevine. Nanopore sequencing, a third-generation technology, can be used for direct sequencing of both RNA and DNA with minimal infrastructure. Compared to other HTS methods, the MinION nanopore platform is faster and more cost-effective and allows for long-read sequencing. Due to the size of the MinION device, it can be easily carried for field viral disease surveillance. This review article discusses grapevine viruses and their diagnostic methods, the principle of nanopore sequencing technology and its application in grapevine virus detection, virus–plant interactions, as well as the characterization of viral RNA modifications.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin rings formation, and lowers osteoclastogenesis-related gene expression (cathepsin K, CTR, TRAF6, TRAP, MMP-9). It also impedes NFATc1, c-Fos, NF-κB, and MAPK signaling pathways, and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis, osteoblast differentiation and increases Runx2 and OCN expression. In vivo studies show its effectiveness in enhancing BMD in PMOP mice, re-straining osteoclast maturation, and increasing active osteoblast percentage in bone tissue. It modulates mRNA expressions (increasing EEF2 and decreasing HDAC1, thereby activating os-teoprotective epigenetic mechanisms) and alters various serum markers, including decrease of CTX-1, TRAcp5b, RANKL, M-CSF, TRAP, and increase of ALP and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic MMP-3, IL-6, TNF-α, and en-hances anti-osteoporotic IL-10 and TIMP3 expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

This review explores the transformative impact of sensor technologies in early disease detection. It highlights recent advancements in nanotechnology-based sensors, particularly focusing on their applications in identifying disease biomarkers at early stages. The integration of these sensors with artificial intelligence for predictive analytics in healthcare is also discussed. Applications in cancer, infectious diseases, and chronic disease management underscore their diverse utility. Challenges in sensor technology adoption and future directions, including multiplexed sensors and wearable devices, are examined. This review underscores sensors' potential in enhancing disease management and patient outcomes.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis, and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

Energy demand has exponentially increased with the increase in the world population and ur-banization. Renewable energy is clean, renewable, and environmentally friendly. Hydrogen production through Proton Exchange Membrane (PEM) electrolyzer is an efficient way to produce renewable energy. The efficiency and energy consumption of the PEM electrolyzer depends on the feed water quality. In this report, we study the effect of pH, TDS, and conductivity on hydrogen production as well as energy consumption during the process. pH values (3, 7, 9), TDS values (300ppm, 600ppm, 900ppm), and conductivity values (30mS/cm, 70mS/cm, 100mS/cm) were studied to understand and optimize the hydrogen production using PEM electrolyzer. The in-vestigations showed that hydrogen production is significantly affected by pH, total dissolved solids, and conductivity, and the best levels of each variable were identified by extensive testing. The findings show both the scientific significance of proton exchange electrolysis in meeting the growing energy demands of society as well as the importance of knowing the influence that di-verse conditions have on the creation of hydrogen. Our research, in general, contributes to the expanding body of scientific knowledge on the topic of the effective production of hydrogen and offers useful insights for the continuation of investigation in this field.

The article is aimed at a brief comparison and analysis of the results of queries to IEEE Xplore and the leading abstract databases Scopus and Web of Science to identify research trends. Some errors in the Author Keywords in Web of Science have been revealed. Therefore, a more detailed analysis was conducted by comparing different types of key terms for IEEE Xplore and Scopus platforms only. I used IEEE Access journal metadata as indexed on both platforms. The sample match for IEEE Xplore and Scopus was achieved by comparing DOI. The IEEE Xplore metadata contains more types of key terms, which provides an advantage in analyzing research trends. Using NSPEC Controlled Terms from expert-compiled vocabulary provides a more stable data, which gives an advantage when considering the change of terms over time. Apriori, an algorithm for finding association rules, has been used to compare co-occurrence of terms for a more detailed description of sample subjects on both platforms. VOSviewer was used to analyze trends in scientific research based on IEEE Xplore data. The 2011-2021 ten-year period was divided into two sub-intervals for comparing the occurrence of Author Keywords, IEEE Terms, and NSPEC Controlled Terms. Using the IEEE conference proceedings bibliometric data, I illustrated the importance of context in estimating the rate of growth of publishing activity on a topic of interest.

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine-Laponite (BRI/LAP) can be monitored non-invasively using vitreous imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterization was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

Besides the increase in global energy demand, access to clean energy, reduction in greenhouse gas emissions caused by conventional power generation sources, energy security, and availability of electricity in remote villages in emerging nations are some of the factors that foster the use of renewable energy sources (RESs) in generating electricity. One of the aims of initiating microgrids (MGs) is to maximize the benefits of RES and alleviate the associated grid integration issues. Microgrids are made up of RES connected to electrical loads within clearly delineated electrical limits that operate as individual controllable units on the electrical network. It can operate in-dependently as well as in connection with the grid. The paper presents an overview of microgrids and investigates the system's performance when connected to and disconnected from the grid. Furthermore, in both modes of operation, the functioning and behavior of system components such as the bidirectional DC-DC converter and energy storage system (ESS) were evaluated. The architecture of the proposed microgrid consists of a small hydropower plant, a wind farm, and a battery energy storage system (BESS). The microgrid under investigation is modeled and simu-lated using MATLAB and Simulink.

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations, and DNA damage. With next-generation sequencing (NGS), we can now precisely identify viral and host genomic breakpoints and chimeric sequences, which are useful for integration site analysis. In this study, we evaluated a commercial hybrid-capture NGS panel specifically designed for detecting three key viruses: HPV, HBV, and HIV-1. We also tested workflows for Viral Hybrid Capture (VHC) and Viral Integration Site (VIS) analysis, leveraging customized viral databases in CLC Microbial Ge-nomics. By analyzing sequenced data from virally infected cancer cell lines (including SiHa, HeLa, CaSki, C-33A, DoTc2, 2A3, SCC154 for HPV; 3B2, SNU-182 for HBV; and ACH-2 for HIV-1), we precisely pinpointed viral integration sites. The workflow also highlighted disrupted and neigh-boring human genes that may play a crucial role in tumor development. Our results included in-formative virus-host read mappings, genomic breakpoints, and integration circular plots. These visual representations enhance our understanding of the integration process. In conclusion, our seamless end-to-end workflow bridges the gap in understanding viral contributions to cancer development, paving the way for improved diagnostics and treatment strategies.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

Recent advancements in experimental and computational methods for RNA secondary structure detection have revealed the crucial role of RNA structural elements in diverse molecular processes within living cells. It has been demonstrated that the secondary structure of the entire viral genome is often responsible for performing crucial functions in the viral life cycle and also influences virus evolution. To investigate the role of viral RNA secondary structure, alongside experimental techniques, the use of bioinformatics tools is important for analyzing various secondary structure patterns, including hairpin loops, internal loops, multifurcations, external loops, bulges, stems, and pseudoknots. Here, we have introduced a Python package for analyzing RNA secondary structure elements in viral genomes, which includes the recognition of common secondary structure patterns, the generation of descriptive statistics for these structural elements, and the provision of their basic properties. We applied the developed package to analyze the secondary structures of complete viral genomes collected from the literature, aiming to gain insights into viral function and evolution. Both the package and the collection of secondary structures of viral genomes are available at http://github.com/KazanovLab/RNAsselem.

Gal-3BP is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of IFN and pro-inflammatory cytokines, including interleukin-6, mainly interacting with galectin-3, targeting TRAF-6 and TRAF-3 complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. In Bolivia it is cultivated in different parts of the High Andes and in the Interandean Valleys. The species is affected by several fungal diseases which reduce production, but before 2016 hardly any mention had been made of virus disease in the region. The aims of the present work were: 1) to describe the symptomology of this apparent viral disease, and ii) determine its effects on the yield of different alfalfa cultivars available from the CIF-UMSS. In 2016, a plot was established at Tiquipaya (Dept. of Cochabamba) (altitude 2480 m) was planted with 12 alfalfa cultivars. Disease incidence values were estimated and the area under the disease progress curves (AUDPC) calculated. The disease progress curves themselves were analyzed using logit functions for polycyclic diseases, and yields were determined. Disease symptoms included deformation of the folioles, thickened veins, the presence of vein enations and papillae on the abaxial leaves, reduced plant size - all symptoms of infection apparently caused by Alfalfa Dwarf Virus. The different cultivars returned different incidence values. They also returned different apparent infection rates ranging from 0.072/day for Cóndor, to 0.113/day for Tamborada. The different cultivars returned different dry weight yields, with yields inversely related to the AUDPC. In conclusion, based on the foliar symptoms registered, the viral disease is associated with the Alfalfa Dwarf Virus. The twelve cultivars evaluated presented different incidence levels of the viral disease.

Background: The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. Methods: The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 hours; T2 12 hours – T3 24 hours) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. Results: SARS-CoV-2 viral RNA was still detectable in 70,3% of cases within 2 hours after death and in 66,6% of cases up to 24 hours after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 hours post-mortem (T3) in comparison to that evaluated 2 hours after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 hours after death) from 4 subjects who were negative at T1 (2 hours after death). Conclusion: The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.