Search Results (97)

Background: Several blood biomarkers have shown a major role in predicting major adverse complications (MACs) in patients who have undergone cardiac surgery. Here, we aimed to investigate the possible role of the blood urea nitrogen (BUN) to serum albumin ratio (BAR) and the inflammatory prognostic index (IPI) in predicting major adverse complication after surgical aorta valve replacement (SAVR). Methods: The clinical, echocardiographic, and clinical-chemistry laboratory data of 195 patients who underwent SAVR were evaluated. The post-surgical MACs (death, surgical re-exploration, myocardial infarction and cerebral ischemia) during the hospitalization were recorded. Univariate and multivariate logistic regression analyses were studied by comparing the basic clinical features, echocardiographic parameters, and patients’ hematological indices between patients with or without MACs. Results: The mean age was 66.1 years, and 62.5% were males. Logistic regression analysis showed that the left atrium volume (LAV), BAR, and IPI as either continuous or categorical variables were independently associated with MACs. Moreover, we found a combined effect of higher LAV with a higher value of BAR or IPI. Combined higher levels of LAV and BAR increased the risk of developing MACs by 9.8 (CI 95% = 2.8–34.3, p = 0.0003), while higher values of LAV and IPI increased the risk of developing MACs by 4.5. Conclusions: Higher levels of BAR and IPI, alone or in combination with higher LAVs, showed an independent predictive value of MACs after SAVR. These findings strongly support the importance of evaluating easily available biomarkers of the pre-operative status of patients in order to predict adverse outcomes. Full article

This article presents a unique approach to Arabic dialect identification using a pre-trained speech classification model. The system categorizes Arabic audio clips into their respective dialects by employing 1D and 2D convolutional neural network technologies built from diverse dialects from the Arab region using deep learning models. Its objective is to enhance traditional linguistic handling and speech technology by accurately classifying Arabic audio clips into their corresponding dialects. The techniques involved include record gathering, preprocessing, feature extraction, prototypical architecture, and assessment metrics. The algorithm distinguishes various Arabic dialects, such as A (Arab nation authorized dialectal), EGY (Egyptian Arabic), GLF (Gulf Arabic), LAV and LF (Levantine Arabic, spoken in Syria, Lebanon, and Jordan), MSA (Modern Standard Arabic), NOR (North African Arabic), and SA (Saudi Arabic). Experimental results demonstrate the efficiency of the proposed approach in accurately determining diverse Arabic dialects, achieving a testing accuracy of 94.28% and a validation accuracy of 95.55%, surpassing traditional machine learning models such as Random Forest and SVM and advanced erudition models such as CNN and CNN2D. Full article

Sorghum (Sorghum bicolor L.) is the fifth largest cereal crop in the world and widely used in the fields of food, feed, brewing, and fuel, while knowledge is mostly limited for sorghum grain development, including starch biosynthesis. B3 family transcription factors (TFs) play a crucial role in plant development, including grain development, dormancy, and storage of nutrients. In the present study, a comprehensive analysis of sorghum B3 genes was performed, and a total of 76 related genes were identified to be distributed on 10 chromosomes across the whole sorghum genome. According to the sequence features, the sorghum B3 family members were divided into four sub-families of ARF, RAV, LAV, and REM. Multiple elements, i.e., light-responsive elements, phytohormone-responsive elements, growth and development-related elements, and stress-responsive elements, were discovered to be located within the 2000 bp upstream of the translation start site. Results of expression analysis across multiple tissues suggested significantly different expression patterns of sorghum B3 genes. Further assays confirmed that SbLAV1, which belonged to the LAV subfamily of B3, co-expressed with 15 key starch biosynthesis-related genes (SBRGs), and the corresponding product of SbLAV1 could activate the promoter activities of multiple key SBRGs. Collectively, the integrative results of the present study indicate that B3 family members, including SbLAV1, might play critical roles in starch biosynthesis and grain development in sorghum. Full article

Background/Objectives: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination using live attenuated vaccines (LAVs). Most of these LAVs do not allow for the differentiation of vaccinated animals from infected animals (DIVA) based on their serological response. FlagT4G vaccine is a novel candidate that confers robust protective immunity early after vaccination and shows DIVA capabilities. Methods: This report presents the characterization of FlagT4G virus in terms of the stability of its genomic and attenuated phenotypes assessed by a reversion to virulence protocol, as well as its protective efficacy by determining the minimal protective dose. Results: Results presented here demonstrate that after five consecutive passages in groups of 5-week-old susceptible domestic pigs, FlagT4G virus remains genetically stable, and its attenuated phenotype remains unaltered. In terms of efficacy, FlagT4G virus induced solid protection against the intranasal challenge with 10⁵ tissue culture infectious dose (TCID₅₀) of virulent field isolate Brescia virus, even with a vaccine dose as low as 10² TCID50. Conclusions: Results presented here indicate that the FlagT4G vaccine may be a useful tool for CSFV control. Full article

Background/Objectives: Cardiac resynchronization therapy (CRT) with fusion pacing (“LV only”), also known as fusion-CRT (f-CRT), represents a feasible alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP), not only in cases of BiVP failure, but also as a primary therapy option due to its potential benefits over traditional CRT. Fusion pacing may be particularly beneficial in selected patients and understanding the structural and functional differences between responders could guide future optimization strategies. This study provides a descriptive comparison between super-responders (SRs) and non-super-responders (NSRs) undergoing fusion-CRT. Methods: Patients with RA/LV-only pacing systems or biventricular CRT systems operating predominantly in LV-only pacing mode due to intrinsic RV conduction were included. A follow-up protocol was conducted for all patients at 6 months and then annually. Data from the most recent follow-up were used for statistical analysis. Super-responders (SRs) were those with substantial reverse remodeling, quantified by a ≥30% reduction in LVESV and a stable LVEF of ≥45% at follow-up. Although SRs were defined based on these reverse remodeling criteria, separate analyses of additional echocardiographic parameters (e.g., left atrial dimensions) were performed to independently assess the broader impact of fusion-CRT on cardiac structure and function. Results: Among 71 patients, 55 were non-super-responders (NSRs) and 16 were super-responders (SRs), with a mean follow-up of 43.2 months. SRs were predominantly female and had smaller left ventricular (LV) dimensions: LVEDd (6.30 cm vs. 6.80 cm, p = 0.02), LVEDV (185 mL vs. 240 mL, p = 0.03), LVESV (132.5 mL vs. 175 mL, p = 0.03), and a higher LVEF (p = 0.03). The follow-up LVEF was positively correlated with changes in LVESV (ρ = 0.557, p < 0.001), but not with NYHA class changes (ρ = 0.184, p = 0.125). Larger baseline LV and left atrial (LA) volumes were associated with a reduced follow-up LVEF (LVESV: ρ = −0.426, p < 0.001; LVEDV: ρ = −0.394, p < 0.001; LAv: ρ = −0.374, p = 0.001). Both groups showed improvement in the NYHA class (p < 0.001, p = 0.007). MR improved significantly in SRs (p = 0.02) and worsened slightly in NSRs (p = 0.13), while TR worsened significantly in the NSRs group (p = 0.03). Conclusions: Our findings highlight key differences in clinical and echocardiographic parameters between SRs and NSRs following fusion-CRT. These observations may contribute to a better understanding of response patterns and inform future prospective studies aiming to optimize patient selection and timing of therapy. Full article

The B3 transcription factor superfamily, crucial for plant growth and stress adaptation, remains poorly characterized in cucumber (Cucumis sativus), a globally important vegetable crop. Here, we conducted the first genome-wide identification of 52 B3 superfamily genes in cucumber, classifying them into LAV, ARF, RAV, and REM subfamilies through integrated phylogenetic and structural analyses. These genes exhibited conserved B3 domains with lineage-specific motif architectures and diverse exon–intron organizations, particularly within the structurally divergent REM subfamily. Collinearity analysis revealed segmental duplication as a key driver of family expansion, notably between syntenic REM clusters on chromosomes 2 (CsREM5-7) and 6 (CsREM18-20). Promoter cis-element profiling identified enrichment in hormone-responsive and stress adaptation motifs, suggesting functional diversification in signaling pathways. Furthermore, tissue-specific expression divergence was observed across 10 organs, with ARF members displaying broad regulatory roles and REM genes showing apical meristem enrichment. Strikingly, CsRAV8 exhibited glandular trichome-specific expression, a novel finding, given Arabidopsis RAVs’ lack of trichome-related functions. Spatial validation via in situ hybridization localized CsRAV8 transcripts to trichome glandular head cells. Functional investigation using virus-induced gene silencing (VIGS) demonstrated that CsRAV8 suppression caused significant glandular trichome shriveling, implicating its role in maintaining glandular cavity integrity. This study provides the first comprehensive genomic inventory of B3 transcription factors in cucumber, providing evolutionary insights and functional frameworks for future functional genomics studies. Full article

As an essential type of vaccine, live attenuated vaccines (LAVs) play a crucial role in animal disease prevention and control. Nevertheless, developing LAVs faces the challenge of balancing safety and efficacy. Understanding the mechanisms animal viruses use to antagonize host antiviral innate immunity may help to precisely regulate vaccine strains and maintain strong immunogenicity while reducing their pathogenicity. It may improve the safety and efficacy of LAVs, as well as provide a more reliable means for the prevention and control of infectious livestock diseases. Therefore, exploring viral antagonistic mechanisms is a significant clue for developing LAVs, which helps to explore more viral virulence factors (as new vaccine targets) and provides a vital theoretical basis and technical support for vaccine development. Among animal viruses, ASFV, PRRSV, PRV, CSFV, FMDV, PCV, PPV, and AIV are some typical representatives. It is crucial to conduct in-depth research and summarize the antagonistic strategies of these typical animal viruses. Studies have indicated that animal viruses may antagonize the antiviral innate immunity by directly or indirectly blocking the antiviral signaling pathways. In addition, viruses also do this by antagonizing host restriction factors targeting the viral replication cycle. Beyond that, viruses may antagonize via regulating apoptosis, metabolic pathways, and stress granule formation. A summary of viral antagonistic mechanisms might provide a new theoretical basis for understanding the pathogenic mechanism of animal viruses and developing LAVs based on antagonistic mechanisms and viral virulence factors. Full article

Background/Objectives: Lavender has been utilized for its medicinal properties since ancient times, with numerous health benefits reported. This study aimed to valorize solid waste from lavender essential oil production by developing a novel lavender extract from solid lavender residues. The extract’s preclinical safety and efficacy were evaluated with emphasis on plasma lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue metabolic activity. Methods: Male C57BL/6 mice were divided into four groups of five mice each and fed for 30 days with lavender extract encapsulated in 10% maltodextrin, mixed with a standard chow diet. The first group (Lav 1×) received 21.1 mg/kg/day, the second group (Lav 10×) received 211 mg/kg/day, and the third group (Lav 100×) received 2110 mg/kg/day. A placebo group consumed the standard diet without lavender extract. Key outcomes included plasma lipid and lipoprotein profiles, transaminase levels, HDL antioxidant and anti-inflammatory potential, glucose tolerance, and mitochondrial activity in white (WAT) and brown (BAT) adipose tissues. Results: The novel lavender extract induced dose-dependent improvements in lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue activity. The 2110 mg/kg dose (100×) demonstrated the most significant beneficial effects, although it was associated with a slight elevation in hepatic transaminase levels, indicating potential mild hepatic stress. Conclusions: Overall, the novel lavender extract exhibits promising health benefits with no major safety concerns at the tested doses, supporting its potential for therapeutic applications. Full article

Background/Objectives: The spread of African swine fever virus (ASFV) has led to major economic losses to pork worldwide. In Russia, there are no developed or registered vaccines against ASFV genotype II, which is associated with numerous ASFV outbreaks in populations of domestic pigs and wild boars in the country. Methods: We introduced deletions of the six MGF360 and MGF505 genes of the ASFV virulent Stavropol_01/08 strain, isolated in Russia in 2008. Results: We show here that this deletion did lead to full attenuation of the ASFV virulent Stavropol_01/08 strain. Animals intramuscularly inoculated with 10⁴ HAD₅₀ of ΔMGF360/505_Stav developed a strong immune response and short period of viremia (at 3–7 days post-inoculation). Recombinant ΔMGF360/505_Stav strain provides complete protection of pigs against the ASFV parental Stavropol_01/08 strain (10³ HAD₅₀). Therefore, in our experiment, we did not detect the genome of both the virulent and the recombinant strains in the blood and organs post-challenge with the Stavropol_01/08. In contrast, we found only partial protection (40%) of the ΔMGF360/505_Stav-immunized pigs against challenge with the ASFV heterologous Rhodesia strain. Additionally, the surviving animals had a prolonged fever, and their condition was depressed for most of the experiment. Conclusions: Thus, the ASFV recombinant ΔMGF360/505_Stav strain is the first live attenuated vaccine (LAV) in Russia that induces complete protection in pigs challenged with the highly virulent, epidemiologically relevant strains genotype II and serotype 8. However, this ASF LAV is not able to provide a high level of protection against other variants of serotype 8. Full article

Plague, caused by Yersinia pestis, poses a public health threat not only due to sporadic outbreaks across the globe but also due to its potential as a biothreat agent. Ironically, among the seven deadliest pandemics in global history, three were caused by Y. pestis. Pneumonic plague, the more contagious and severe form of the disease, is difficult to contain, requiring either prophylactic antibiotic treatment or vaccination. However, no vaccine (live attenuated or subunit) is currently approved by the Food and Drug Administration, requiring rigorous preclinical studies in different animal models, thus forming the basis of this study. Objectives: The aim of this study was to evaluate the efficacy and immune responses of two live attenuated vaccines (LAVs), LMA and LMP, either alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV), in IL-17A-depleted and IgG control mice by using an anti-IL-17A monoclonal antibody (mAb) or its matched isotype IgG, respectively. Methods: IL-17A mAb or IgG isotype control was administered to mice twice per week to their respective groups during the course of immunization. Serum, spleens, and broncho-alveolar lavage fluid (BALF) were collected for assessing immunological responses, and another cohort of mice was intranasally challenged with a lethal dose of parental Y. pestis CO92. Results: Robust humoral and cellular immune responses followed by complete protection were observed in all vaccinated animals against highly lethal intranasal challenge doses of parental Y. pestis CO92. Serum IgG titers to YscF and overall mucosal IgA titers to all three antigens of the Ad5-YFV vaccine were significantly lower, with slightly reduced serum LcrV-neutralizing antibodies when IL-17A was depleted compared to IgG control animals during the course of immunization. A remarkable reduction in Th1 (IFNγ or IL-2) and Th17 cell populations was observed in IL-17A-depleted mice compared to IgG controls in response to vaccination. On the other hand, B cell activities in germinal centers, overall activated antigen-specific T cells, and memory B and T cells remained at comparable levels in both vaccinated IL-17A-depleted and IgG control mice. Conclusions: These data demonstrated the effectiveness of our vaccines even under the reduced levels of both Th1 and Th17 responses and thus should be suitable for those individuals associated with certain immune deficiencies. Full article

The African swine fever virus (ASFV) causes fatal disease in pigs and is currently spreading globally. Commercially safe vaccines are urgently required. Aiming to generate a novel live attenuated vaccine (LAV), a recombinant ASFV was generated by deleting the viral O174L (PolX) gene. However, during in vitro generation, an additional spontaneous deletion of genes belonging to the multigene families (MGF) occurred, creating a mixture of two viruses, namely, Arm-ΔPolX and Arm-ΔPolX-ΔMGF. This mixture was used to inoculate pigs in a low and high dose to assess the viral dynamics of both populations in vivo. Although the Arm-ΔPolX population was a much lower proportion of the inoculum, in the high-dose immunized animals, it was the only resulting viral population, while Arm-ΔPolX-ΔMGF only appeared in low-dose immunized animals, revealing the role of deleted MGFs in ASFV fitness in vivo. Furthermore, animals in the low-dose group survived inoculation, whereas animals in the high-dose group died, suggesting that the lack of MGF and PolX genes, and not the PolX gene alone, led to attenuation. The two recombinant viruses were individually isolated and inoculated into piglets, confirming this hypothesis. However, immunization with the Arm-ΔPolX-ΔMGF virus did not induce protection against challenge with the virulent parental ASFV strain. This study demonstrates that deletion of the PolX gene alone neither leads to attenuation nor induces an increased mutation rate in vivo. Full article

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (10³, 10⁴, and 10⁵ TCID₅₀). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14–17 days post-infection, even at the highest dose (10⁵ TCID₅₀). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (10³, 10⁴, and 10⁵ TCID₅₀). Furthermore, a single vaccination (10⁴ TCID₅₀) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV. Full article

Background: Chronic obstructive pulmonary disease has extrapulmonary manifestations, such as cardiovascular diseases and osteoporosis. The purpose of this research was to determine the relationship between the type and extent of emphysema with thoracic aorta calcification (TAC) and bone mineral density (BMD) at Th4, Th8, and L1 vertebrae. Methods: Emphysema was described by computed tomography parameters (both Fleischner classification and low attenuation value percentage, LAV%) and the clinical FEV₁/FVC ratio (Tiffeneau–Pinelli index, TI, TI < 0.7; TI > 0.7). Results: Of 200 included patients (median age 64, 33% women), signs of clinical obstruction (TI) were observed in 104 patients, which had significantly lower BMD and more heavy TAC. BMD correlated negatively with LAV%, Rho = −0.16 to −0.23, while a positive correlation of aortic calcification with LAV% was observed, Rho = 0.30 to 0.33. Multiple linear regression showed that age and TI < 0.7 were independent predictors of BMD, β = −0.20 to −0.40, and β = −0.21 to −0.25; age and hypercholesterolemia were independent predictors of TCA, β = 0.61 and β = 0.19. Conclusions: Clinical TI and morphological LAV% parameters correlated with BMD and TAC, in contrast to Fleischer-graded emphysema, which showed no correlation. However, only TI was an independent predictor of BMD, while the morphologically described type and extent of emphysema could not independently predict any extrapulmonary manifestation. Full article

Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution. Full article

Porcine epidemic diarrhea virus (PEDV) is the etiology of porcine epidemic diarrhea (PED), a highly contagious digestive disease in pigs and especially in neonatal piglets, in which a mortality rate of up to 100% will be induced. Immunizing pregnant sows remains the most promising and effective strategy for protecting their neonatal offspring from PEDV. Although half a century has passed since its first report in Europe and several prophylactic vaccines (inactivated or live attenuated) have been developed, PED still poses a significant economic concern to the swine industry worldwide. Hence, there is an urgent need for novel vaccines in clinical practice, especially live attenuated vaccines (LAVs) that can induce a strong protective lactogenic immune response in pregnant sows. Reverse genetic techniques provide a robust tool for virological research from the function of viral proteins to the generation of rationally designed vaccines. In this review, after systematically summarizing the research progress on virulence-related viral proteins, we reviewed reverse genetics techniques for PEDV and their application in the development of PED LAVs. Then, we probed into the potential methods for generating safe, effective, and genetically stable PED LAV candidates, aiming to provide new ideas for the rational design of PED LAVs. Full article