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ABSTRACTThe RNA molecule plays a pivotal role in many biological processes by relaying genetic information, regulating gene expression, and serving as molecular machines and catalyzers. This inherent versatility of RNA has fueled significant advancements in the field of RNA nanotechnology, driving the engineering of complex nanoscale architectures toward biomedical applications, including targeted drug delivery and bioimaging. RNA polymers, serving as building blocks, offer programmability and predictability of Watson-Crick base pairing, as well as non-canonical base pairing, for the construction of nanostructures with high precision and stoichiometry. Leveraging the ease of chemical modifications to protect the RNA from degradation, researchers have developed highly functional and biocompatible RNA architectures and integrated them into preclinical studies for the delivery of payloads and imaging agents. This review offers an educational introduction to the use of RNA as a biopolymer in the design of multifunctional nanostructures applied to targeted delivery in vivo, summarizing physical and biological barriers along with strategies to overcome them. Furthermore, we highlight the most recent progress in the development of both small and larger RNA nanostructures, with a particular focus on imaging reagents and targeted cancer therapeutics in pre-clinical models and provide insights into the prospects of this rapidly evolving field.

Abstract Usutu virus (USUV), an arbovirus from the Flaviviridae family, genus Flavivirus, has recently gained increasing attention because of its potential for emergence. After his discovery in South Africa, USUV spread to other African countries, then emerged in Europe where it was responsible for epizootics. The virus has recently been found in Asia. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. However, a few cases of neurological complications such as encephalitis or meningo-encephalitis have been reported in both immunocompromised and immunocompetent patients. USUV natural life cycle involves Culex mosquitoes as its main vector, and multiple bird species as natural viral reservoirs or amplifying hosts, humans and horses can be incidental hosts. Phylogenetic studies carried out showed eight lineages, showing an increasing genetic diversity for USUV. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to Usutu virus. This study was carried out on different strains from Senegal and Italy. The new approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for Usutu virus genomic surveillance to better understand the dynamics of evolution and transmission of the virus.

In cancer molecular imaging, selecting binders with high specificity and affinity for biomarkers is paramount for achieving high-contrast imaging within clinical time frames. Nanobodies have emerged as potent candidates, surpassing antibodies in pre-clinical imaging due to their convenient production, rapid renal clearance, and deeper tissue penetration. Multimerization of nanobodies is a popular strategy to enhance their affinity and pharmacokinetics; however, traditional methods are laborious and may yield heterogeneous products. In this study, we employ a Holliday junction (HJ)-like nucleic acid-based scaffold to create homogeneous nanostructures with precise multivalent and multiparatopic nanobody displays. The plug-and-play assembly allowed the screening of several nanobody multimer configurations for the detection of the breast cancer biomarker, human epidermal growth factor receptor 2 (HER2). In vitro studies demonstrated significant improvements in binding avidity, particularly with the biparatopic construct exhibiting high sensitivity, surpassing that of traditional antibody-based cell binding. Furthermore, our HJ platform allowed for adaptation from fluorescence-based to nuclear imaging, as demonstrated in xenografted mice, thereby allowing for future in vivo applications. This work highlights the potential of nucleic acid-mediated multimerization to markedly enhance nanobody binding, by exploring synergistic combinations and offering versatility for both in vitro diagnostics and cancer molecular imaging with prospects for future theranostic applications.

AbstractResearch on entrepreneurial intention has gained notable ground in the field of entrepreneurship, especially among university students, who represent the potential to become future entrepreneurs. In recent years, a special approach has emerged that has captured the attention of re-searchers: the comparison of entrepreneurial intentions between men and women, highlighting the existing entrepreneurial gap. This study was carried out with the objective of analyzing the factors that determine the entrepreneurial intention of entrepreneurial students, both female and male, from a comparative perspective in Peru. To achieve this, a quantitative analysis was carried out based on the Partial Least Squares Structural Equation Model (PLS-SEM), which integrated the Theory of Planned Behavior (TPB) and the Business Event Model (SEE) with a survey of 1006 students. university students. The results revealed that men have a higher entrepreneurial intention compared to women, being more influenced by factors such as current behavior control, personal attitude, and social support. On the other hand, women showed a greater influence of factors related to control and personal attitude towards entrepreneurship.

Abstract It is unclear whether West Nile virus (WNV) circulates between Africa and Europe, despite numerous studies supporting an African origin and high transmission in Europe. We integrated genomic data with geographic observations and phylogenetic and phylogeographic inferences to uncover the spatial and temporal viral dynamics of WNV between these two continents. We focused our analysis towards WNV lineages 1 (L1) and 2 (L2), the most spatially widespread and pathogenic WNV lineages. Our study shows a Northern-Western African origin of L1, with back-and-forth exchanges between West Africa and Southern-Western Europe; and a Southern African origin of L2, with one main introduction from South Africa to Europe, and no back introductions observed. We also noticed a potential overlap between L1 and L2 Eastern and Western phylogeography and two Afro-Palearctic bird migratory flyways. Future studies linking avian and mosquito species susceptibility, migratory connectivity patterns, and phylogeographic inference are suggested to elucidate the dynamics of emerging viruses.

A new series of piperazine derivatives were synthesized and studied with the aim of obtaining dual inhibitors of P-glycoprotein (P-gp) and carbonic anhydrase XII (hCA XII) to synergistically overcome the P-gp-mediated multidrug resistance (MDR) in cancer cells expressing the two proteins, P-gp and hCA XII. Indeed, these hybrid compounds contain both P-gp and hCA XII binding groups on the two nitrogen atoms of the heterocyclic ring. All compounds showed good inhibitory activity on each protein (P-gp and hCA XII) studied individually, and many of them showed a synergistic effect in the resistant HT29/DOX and A549/DOX cell lines which overexpress both the target proteins. In particular, compound 33 displayed the best activity by enhancing the cytotoxicity and intracellular accumulation of doxorubicin in HT29/DOX and A549/DOX cells, thus resulting as promising P-gp-mediated MDR reverser with a synergistic mechanism. Furthermore, compounds 13, 27 and 32 induced collateral sensitivity (CS) in MDR cells, as they were more cytotoxic in resistant cells than in the sensitive ones; their CS mechanisms were extensively investigated.

Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose, and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin.

The piperazine moiety is often found in drugs or in bioactive molecules. This widespread presence is due to different possible roles depending on the position in the molecule and on the therapeutic class, but it also depends on the chemical reactivity of piperazine-based synthons, which facilitate its insertion into the molecule. In this paper, we take into consideration the piperazine-containing drugs approved by the Food and Drug Administration between January 2011 and June 2023, and the synthetic methodologies used to prepare the compounds in the discovery and process chemistry are reviewed.

West Nile virus (WNV) is a globally significant mosquito-borne Flavivirus that causes West Nile disease (WND). In Libya, evidence of WNV circulation has been reported in humans but never in animals. The aim of this study was to determine the seroprevalence of WNV infection in horses and dogs in Libya. In total, 574 and 63 serum samples were collected from apparently healthy, unvaccinated horses and dogs, respectively, between 2016 and 2019. A commercially available competitive enzyme-linked immunosorbent assay (c-ELISA) kit was initially used to test the collected samples for the presence of WNV Ig-G antibodies. Positive and doubtful sera were also tested using a more specific virus neutralisation assay to confirm whether the ELISA-positive results were due to WNV or other Flavivirus antibodies. The seroprevalence of WNV IgG antibodies according to ELISA was 13.2% out of 574 of total horses’ samples and 30.2% out of 63 of total dogs’ samples. The virus neutralisation test (VNT) confirmed that 10.8% (62/574) and 27% (17/63) were positive for WNV-neutralising titres ranging from 1:10 to 1:640. Univariable analysis using chi-square tests was conducted to measure the statistical significance of the association between the hypothesized risk factors including city, sex, breed, and age group and were then analyzed using the subsequent multivariable logistic regression model for horse samples. Age group was found to be the only significant risk factor in this study. The results of the present study provide new evidence about WNV circulation in Libya.

Abstract Background Bluetongue (BT), a vector‐borne disease of wild and domestic ruminants, is responsible for severe economic losses in flocks. To reduce this impact, a surveillance and control plan was implemented in Tunisia. However, the epidemiological situation of BT remains incompletely understood, especially for the circulating serotypes. Objective The aim of this survey was to determine the seroprevalence, to identify the circulating serotypes and to identify the associated risk factors for bluetongue virus (BTV) circulation in Tunisia using risk‐based sampling (RBS). Methods A total of 3314 blood samples were randomly collected from 67 sectors using risk‐based sampling and screened by competitive enzyme‐linked immunosorbent assays (c‐ELISAs). Out of the 1330 positive samples, 200 samples were analysed by serum neutralization test (SNT) to identify circulating BTV serotypes. Results Of 3314 sera, 1330 were c‐ELISA‐positive (40.1%) for antibodies against the BTV structural protein VP7. The result of SNT showed the presence of BTV‐1, BTV‐2, BTV‐3, BTV‐4 and, for the first time in Tunisia, BTV‐26. The logistic regression model revealed that older animals had nearly two times the odds of being infected with BTV compared to younger animals. Flocks with a history of BT were almost 1.5 times more likely to be at risk for contracting BTV infection. The flock size, housing indoors and intensive production system were significant protective factors. Conclusions High seroprevalence of BTV among sheep was highlighted in Tunisia. The neutralization test showed the presence of the following BTV serotypes: BTV‐1, BTV‐2, BTV‐3, BTV‐4 and, for the first time in Tunisia, BTV‐26. Age, production system and flock size were important variables associated with BTV infection in sheep. This finding is crucial, as it will allow the adjustment of the BT control programme in Tunisia.

Las universidades en Perú han enfrentado reformas a lo largo de los años, estas reformas han ido modificando la concepción que se tiene sobre las mismas. Lo que se pretende a través de este artículo es examinar las normativas que han abarcado estas reformas en Perú hasta el año 2019, de manera que puedan ser usadas de base para futuras investigaciones. Metodológicamente se realizó una revisión de las normativas que se encontraban vigentes a la fecha para resumir los elementos que involucran. Se realiza un resumen al respecto de las leyes que antecedieron la ley actual para presentar los elementos más relevantes de las mismas. Al final del documento se recomiendan documentos actuales que tratan sobre la temática en cuestión.

The development of technologies has made digital accessibility relevant to many everyday processes. Multiple resources have been designed to meet the special needs of a wide variety of people, such as Deaf sign language users, who require inclusive technologies to facilitate their communication in work, educational, and social environments. The objective of this study is to identify assistive technologies that favor and improve communication between Deaf and hearing people. To this end, a systematic review was carried out following the PRISMA checklist and using the Scopus, Web of Science, and PubMed databases. A total of 492 documents were identified and subjected to inclusion and exclusion criteria, of which 27 were included in the quantitative synthesis. As a result, technologies based on gesture recognition for the translation of sign language into speech and vice versa, technologies for sign language teaching, technologies for automatic caption generation, technologies based on online content, and technologies based on text and illumination networks were found in the studies. The findings suggest that there is a need for further research into the motivations for developing sign language technologies, as a contribution to the inclusion of Deaf communities in society without linguistic impositions.