Search Results (23)

Background/Objectives: African swine fever virus (ASFV) is a devastating disease affecting domestic and wild suids and causing significant economic losses in the global pig industry. Attenuated modified live virus (MLV) vaccines are the most promising approaches for vaccine development. This study aimed to evaluate the safety and efficacy of four recombinant ASFV genotype II strains, derived from the non-hemadsorbing (non-HAD) attenuated isolate Lv17/WB/Rie1, through the single or simultaneous deletion of virulence-associated genes. Methods: Recombinant viruses were engineered by deleting the UK, EP402R, and EP153R genes, either individually or in combination. Four recombinant strains were evaluated for safety and efficacy in domestic pigs vaccinated intramuscularly with 10² TCID₅₀. Clinical signs, viremia, virus shedding, and antibody responses were monitored. Protection efficacy was assessed by challenging vaccinated pigs with the virulent genotype II Armenia07 strain. Additionally, a reversion-to-virulence study involving an overdose of the vaccine candidate was conducted to evaluate its stability through serial immunizations. Results: Deletion of the UK gene alone increased virulence, whereas the double deletion of EP402R and EP153R (Lv17/WB/Rie1-ΔCD) significantly enhanced safety while maintaining full protective efficacy. Vaccinated pigs exhibited reduced viremia, no virus shedding, and robust virus-specific antibody responses, achieving complete protection against Armenia07. The reversion-to-virulence study revealed potential but limited pathogenicity after multiple passages, indicating areas for improvement in vaccine stability. Conclusions: The Lv17/WB/Rie1-ΔCD strain demonstrates excellent safety and efficacy, along with potential DIVA (differentiating infected from vaccinated animals) compatibility, positioning it as a strong candidate for an ASFV MLV vaccine. Further research is needed to refine the vaccine and address the potential risks of reversion to virulence. Full article

This article reviewed the urban vehicle access control policies derived from disparate spatiotemporal dimensions that aim to eliminate the negative externalities of traffic caused by urbanization. Urban access regulations are important tools often required to achieve the sustainable mobility vision of cities. Employing a systematic literature review methodology, this review summarized and analyzed various urban access control policies to enlighten policymakers and future scientific research. The results indicate that combinations of multiple-dimensional restriction policies (including inter-policy and intra-policy) have more significant effects than implementing a single policy. Classified according to their objectives, control policies were discussed in terms of their benefits and limitations. The authors are inspired to propose and describe five paradoxes of urban access control policies. Full article

Steroids are often considered valuable molecular tools for the development of anticancer agents with improved pharmacological properties. Conjugation of metal chelating moieties with a lipophilic sterane backbone is a viable option to obtain novel anticancer compounds. In this work, two estradiol-based hybrid molecules (PMA-E2 and DMA-E2) with an (N,N,O) binding motif and their Cu(II) complexes were developed. The lipophilicity, solubility, and acid-base properties of the novel ligands were determined by the combined use of UV-visible spectrophotometry, pH-potentiometry, and ¹H NMR spectroscopy. The solution speciation and redox activity of the Cu(II) complexes were also investigated by means of UV-visible and electron paramagnetic resonance spectroscopy. Two structurally analogous ligands (PMAP and DMAP) were also included in the studies for better interpretation of the solution chemical data obtained. Three pK_a values were determined for all ligands, revealing the order of the deprotonation steps: pyridinium-NH⁺ or NH(CH₃)₂⁺, secondary NH₂⁺, and OH. The dimethylamine derivatives (DMA-E2, DMAP) are found in their H₂L⁺ forms in solution at pH 7.4, whereas the fraction of the neutral HL species is significant (34–37%) in the case of the pyridine nitrogen-containing derivatives (PMA-E2, PMAP). Both estradiol derivatives were moderately cytotoxic in human breast (MCF-7) and colon adenocarcinoma (Colo-205) cells (IC₅₀ = 30–63 μM). They form highly stable complexes with Cu(II) ions capable of oxidizing ascorbate and glutathione. These Cu(II) complexes are somewhat more cytotoxic (IC₅₀ = 15–45 μM) than their corresponding ligands and show a better selectivity profile. Full article

Lv17/WB/Rie1-Δ24 was produced via illegitimate recombination mediated by low-dilution serial passage in the Cos7 cell line and isolated on PAM cell culture. The virus contains a huge ~26.4 Kb deletion in the left end of its genome. Lv17/WB/Rie1-ΔCD-ΔGL was generated via homologous recombination, crossing two ASFV strains (Lv17/WB/Rie1-ΔCD and Lv17/WB/Rie1-ΔGL containing eGFP and mCherry markers) during PAM co-infection. The presence of unique parental markers in the Lv17/WB/Rie1-ΔCD-ΔGL genome indicates at least two recombination events during the crossing, suggesting that homologous recombination is a relatively frequent event in the ASFV genome during replication in PAM. Pigs infected with Lv17/WB/Rie1-Δ24 and Lv17/WB/Rie1/ΔCD-ΔGL strains have shown mild clinical signs despite that ASFV could not be detected in their sera until a challenge infection with the Armenia/07 ASFV strain. The two viruses were not able to induce protective immunity in pigs against a virulent Armenia/07 challenge. Full article

African swine fever virus (ASFV) is the etiological agent of a haemorrhagic disease that threatens the global pig industry. There is an urgency to develop a safe and efficient vaccine, but the knowledge of the immune–pathogenetic mechanisms behind ASFV infection is still very limited. In this paper, we evaluated the haematological and immunological parameters of domestic pigs vaccinated with the ASFV Lv17/WB/Rie1 strain or its derived mutant Lv17/WB/Rie1/d110-11L and then challenged with virulent Armenia/07 ASFV. Circulating levels of C-reactive protein (CRP), 13 key cytokines and 11 haematological parameters were evaluated throughout the study. Lv17/WB/Rie1 triggered an inflammatory response, with increased levels of CRP and pro-inflammatory cytokines, and induced lymphopenia, thrombocytopenia and a decline in red blood cell (RBC) parameters, although this was transitory. Lv17/WB/Rie1/d110-11L triggered only transitory thrombocytopenia and a mild inflammatory reaction, with no increase in serum levels of pro-inflammatory cytokines, but it raised IL-1Ra levels. Both strains counteracted several adverse reactions elicited by virulent challenge, like thrombocytopenia, a decline in RBC parameters, and inflammation. Within this paper, we provided a deep portrayal of the impact of diverse ASFV strains on the domestic pig’s immune system. A better understanding of these immune–pathological mechanisms would help to design suitable vaccines against this disease. Full article

Freight transportation performs a critical role in the supply networks of the global economy and is heavily influenced by the activities of the industrial and manufacturing sectors, contributing significantly to their global carbon footprint (CFP). This research evaluates the lifecycle-based CFP emissions of freight transport activities in seven selected countries (China, Japan, the United States, Canada, Brazil, Great Britain, and Germany) over fifteen years, considering international trade linkages with the rest of the world. In the literature, most researchers have investigated the CFP of the transportation sector in general or analyzed the CFP of two or three countries, such as the USA and China. However, this research is novel in that it examines the CFP of the freight transport sectors of the seven biggest industrial countries. In addition, a positive relationship was found between the CFP and the gross domestic product (GDP), population, level of urbanization, and area of these countries. Therefore, this study investigates the relationship between global CFP, GDP, population, level of urbanization, and country area. A total of 15 stochastic model-based multi-regional input–output lifecycle assessments were built for each country, comprising 35 key industries. Statistical modeling tools were used to assess carbon emissions. The results show that China is the largest contributor to the freight-related CFP, while the U.S. is the second largest. The manufacture of coke and refined petroleum products represents the dominant sector. In contrast, warehousing and support activities have the most significant contributions in Germany and Great Britain. Land transport and transport via pipelines contribute the most to Canada’s CFP. The results of the regression analysis show that there is a positive relationship between the investigated variables. Full article

African swine fever (ASF) is a highly lethal hemorrhagic viral disease that causes extensive economic and animal welfare losses in the Eurasian pig (Sus scrofa) population. To date, no effective and safe vaccines have been marketed against ASF. A starting point for vaccine development is using naturally occurring attenuated strains as a vaccine base. Here, we aimed to remove the multigene family (MGF) 110 gene of unknown function from the Lv17/WB/Rie1 genome to improve the usability of the virus as a live-attenuated vaccine, reducing unwanted side effects. The MGF 110-11L gene was deleted using the CRISPR/Cas9 method, and the safety and efficacy of the virus were tested in pigs after isolation. The vaccine candidates administered at high doses showed reduced pathogenicity compared to the parental strain and induced immunity in vaccinated animals, although several mild clinical signs were observed. Although Lv17/WB/Rie1/d110-11L cannot be used as a vaccine in its current form, it was encouraging that the undesirable side effects of Lv17/WB/Rie1 at high doses can be reduced by additional mutations without a significant reduction in its protective capacity. Full article

To promote sustainable urban mobility and reduce environmental pollution, transportation policies worldwide aim to decrease reliance on fossil fuels. This requires reducing private car use through policy instruments such as urban vehicle access regulations (UVARs) and promoting alternative sustainable transport technologies such as electromobility. Considering that the deployment of such regulations and the market penetration of battery electric vehicles (BEVs) is still low in Hungary, this study aimed to examine the willingness of urban dwellers in Budapest, Hungary, to adopt battery electric vehicles (BEVs) upon implementation of an UVAR measure. The study analysed the BEV adoption intention of 409 urban residents who participated in an UVAR study in 2022. The results show that age is a significant factor, with individuals aged 35–44 most likely to adopt BEVs. However, other socio-demographic characteristics did not significantly affect willingness to adopt BEVs. Additionally, pro-environmental behaviour or attitude did not significantly predict BEV adoption. Based on these findings, this study highlights the importance of considering multiple interrelated factors and provides policy insights for promoting sustainable transportation technology adoption. Full article

The application of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the treatment of the rare cholesterol and lipid storage disorder Niemann–Pick disease type C opened new perspectives in the development of an efficient therapy. Even if the systemic administration of HPBCD was found to be effective, its low permeability across the blood–brain barrier (BBB) limited the positive neurological effects. Nevertheless, the cellular interactions of HPBCD with brain capillary endothelial cells have not been investigated in detail. In this study, the cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated. HPBCD shows no cytotoxicity on endothelial cells up to 100 µM, measured by impedance kinetics. Using a fluorescent derivative of HPBCD (FITC-HPBCD) the permeability measurements reveal that on an in vitro triple co-culture BBB model, FITC-HPBCD has low permeability, 0.50 × 10⁻⁶ cm/s, while on hCMEC/D3 cell layers, the permeability is higher, 1.86 × 10⁻⁵ cm/s. FITC-HPBCD enters brain capillary endothelial cells, is detected in cytoplasmic vesicles and rarely localized in lysosomes. The cellular internalization of HPBCD at the BBB can help to develop new strategies for improved HPBCD effects after systemic administration. Full article

Driverless vehicles (i.e., autonomous and shared autonomous vehicles) are associated with many advantages for the transportation market. However, they may also increase the traveled miles on roads due to improved accessibility, thus aggravating congestion. Road pricing (RP) is a possible solution for mitigating traffic-related problems like congestion. Despite its benefits, RP is usually resented by the public, which may hinder its introduction. This study investigates the factors that may influence RP acceptability in the era of driverless vehicles and driverless vehicle adoption in the presence of RP. For this purpose, a survey was distributed in Hungary, Jordan, Ukraine, and Brazil. The study applied factor analysis, multiple linear regression, and multinomial logit modeling to examine RP acceptability and driverless vehicle adoption. All examined factors have a significant impact on mode choice. For instance, respondents willing to share their trips with others due to the application of RP, opted for shared autonomous vehicles, while those who enjoy driving were less likely to choose autonomous vehicles. In terms of RP acceptability, the respondents who were environmentally conscious in their trip planning showed more acceptance of RP. This study shows the significant impacts of the investigated factors on RP acceptability and driverless vehicle adoption. Full article

The introduction of autonomous vehicles (AVs) and shared autonomous vehicles (SAVs) is projected to enhance network performance and accessibility. The future share distribution of AV and SAV is not yet apparent, nor is which of these two future transport modes will become dominant. Therefore, this research deploys a simulation-based dynamic traffic assignment using Visum software to investigate the impact of varying the share distribution of AVs and SAVs on Budapest’s network performance and consumer surplus in three projected future traffic scenarios for the years 2030 and 2050 compared to the Base scenario for 2020. The three future scenarios are presented and characterized by different penetration rates of AVs and SAVs to reflect the uncertainty in the market share of these future cars as follows: Mix-Traffic scenario for 2030, and AV-Focused and SAV-Focused scenarios for 2050. The results revealed that the emergence of AVs and SAVs would improve the overall network performance, and better performance was observed with increasing the share distribution of SAVs. Similarly, the consumer surplus increased in all future scenarios, especially with increasing the share distribution of AVs. Consequently, the advent of AVs and SAVs will improve traffic performance and increase consumer surplus, benefiting road users and authorities. Full article

Porcine Parvovirus (PPV) is one of the most important infectious agents causing severe reproductive failure in pigs. In the last two decades a particular, a novel genotype emerged in Europe and PPV-27a was named as the prototype of this genetic cluster. It was suggested that members of the PPV-27a cluster may adversely influence effective vaccination against PPV. For a reliable updated 27a definition, we aligned 93 databank-deposited partial or full nucleotide and protein sequences of the VP2 of different PPV isolates. We confirmed that the 27a cluster could indeed be distinguished from other members of the species, however, some divergences were identified compared to earlier defined genetic markers. Based on genetic differences, we developed a dual allele-specific polymerase chain reaction for the easy and quick discrimination of members of the 27a cluster from other PPV strains. The detection limit of dual PCR was found <1.66 × 10⁴ copies/reaction. To sensitize and make it more user friendly, the method was further developed for qPCR application with fluorescent probes. Regarding the detection limit of the two PCRs (<1.66 × 10⁴ copies/reaction of the dual PCR versus <2.40 × 10² copy/reaction of the dual qPCR), approximately two log improvement was achieved in the sensitivity of the method. Full article

Electric mobility has great potential to help achieve global climate change mitigation goals. Within the domain of electric vehicles (EVs), battery electric vehicles (BEVs) have the largest advantage over conventional internal combustion engine technology. However, their penetration depends on many factors. Several studies have investigated the different policy incentives supporting the EV market, but less analytical research has been conducted to evaluate the different incentives. This study investigates the wide range of incentives that were adopted across 15 countries between 2010 and 2018, and their effectiveness in the market amidst other factors, using a generalized linear model. The results of the statistical analysis identified the availability of local BEV production facility, income, accessibility to fast charging infrastructure, and value-added tax exemptions as positive and statistically significant factors to the market share of BEVs across the years, while positive significant correlations were not identified for the other factors and incentives investigated. This emphasizes the impact of economic performance, technological certainty, and the presence of charging infrastructure with fast charging solutions in BEV adoption decision making, and could be an indication to policymakers of the limited impact of other factors when considered over a length of time. Full article

Nanosized drug delivery systems targeting transporters of the blood-brain barrier (BBB) are promising carriers to enhance the penetration of therapeutics into the brain. The expression of solute carriers (SLC) is high and shows a specific pattern at the BBB. Here we show that targeting ligands ascorbic acid, leucine and glutathione on nanoparticles elevated the uptake of albumin cargo in cultured primary rat brain endothelial cells. Moreover, we demonstrated the ability of the triple-targeted nanovesicles to deliver their cargo into midbrain organoids after crossing the BBB model. The cellular uptake was temperature- and energy-dependent based on metabolic inhibition. The process was decreased by filipin and cytochalasin D, indicating that the cellular uptake of nanoparticles was partially mediated by endocytosis. The uptake of the cargo encapsulated in triple-targeted nanoparticles increased after modification of the negative zeta potential of endothelial cells by treatment with a cationic lipid or after cleaving the glycocalyx with an enzyme. We revealed that targeted nanoparticles elevated plasma membrane fluidity, indicating the fusion of nanovesicles with endothelial cell membranes. Our data indicate that labeling nanoparticles with three different ligands of multiple transporters of brain endothelial cells can promote the transfer and delivery of molecules across the BBB. Full article

Electric mobility is one of the key technologies that may contribute to tackling externalities especially in the fight against climate change, and consequently in achieving sustainable transportation. Among the different electric vehicle (EV) technologies, battery electric vehicles (BEVs) constitute a strong option for future transportation. Despite the large investments made in the EV industry and the large-scale promotion of electric mobility through several policy measures in the last decade, this market segment is still underrepresented in the total automotive market. The available evidence indicates that there is a remarkable gap between the expectations and experiences in applying the measures. This study investigates the available measures that, directly or indirectly, may contribute to the future success of the BEVs. The authors categorize the available measures (financial incentives, non-financial incentives, disincentives) and highlight the possible cross-effects between them through a descriptive analysis. The main finding of this study is that, as there are synergies between the different measures, decision makers need a complex approach to excavate the market mechanism and implement effective and efficient policy measures. Full article