Ticks infesting terrestrial small mammals in a rural settlement in the Amazonas state, Brazil.

There is limited knowledge about tick diversity in the Amazon region. Here, we survey small terrestrial mammals for tick infestation at the Rio Pardo settlement, Amazonas State, Brazil. Sampling included rainy and dry seasons and four ecotones (primary forest, forest in regeneration, field crops and households). Each animal was inspected for ticks, which, if present, were placed in 70% alcohol and identified. Parasitological indexes were calculated and the presence/absence of ticks on hosts was tested for possible associations with independent variables (ecotone, host sex, host order, host family, host age and season). A total of 208 small mammals were captured, 47 individuals (10 species) in the primary forest, 124 (15 species) in the forest in regeneration, 11 (7 species) in the field crops, and 26 (4 species) in the households. A total of 14 small mammals were infested by ticks (overall prevalence: 6.7%; 95% CI: 3.72 - 11.04%), which consisted of 51 specimens that were identified into four species, as follows: Amblyomma humerale (32 nymphs); Ixodes luciae (6 females); Amblyomma coelebs (1 nymph); and Ornithodoros mimon (1 larva). In addition, 11 larvae were retained as Amblyomma spp. Only host order showed association (P = 0.002) with tick infestation, with marsupials 5.5 times more infested than rodents. Our record of O. mimon on D. marsupialis is the first on this host species, and the first record of a Argasidae tick in the Brazilian state of Amazonas. To the best of our knowledge, this is the first study that actively screened free-living terrestrial small mammals and provided data on prevalence, mean intensity and mean abundance of tick infestations in the Brazilian Amazonas state.

Safety assessment of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt' for use in food contact materials.

The EFSA Panel on Food Contact Materials (FCM) assessed the safety of the substances 'wax, rice bran, oxidised' and 'wax, rice bran, oxidised, calcium salt', used as additives up to 0.3% in polyethylene terephthalate (PET), polyamide (PA), thermoplastic polyurethane (TPU), polylactic acid (PLA) and poly(vinyl chloride) (PVC) in contact with all food types for long-term storage at room temperature and below, after hot-fill and/or heating. The substances consist of the chemical classes wax esters, carboxylic acids, alcohols and calcium salts of acids, along with an unidentified organic fraction up to ■■■■■ w/w. Migration into 10% ethanol and 4% acetic acid was below 0.012 mg/kg for each chemical class, and about 0.001 mg/kg for the unidentified fraction. In isooctane, migration was up to 0.297 mg/kg food for wax esters, below 0.01 mg/kg food for the other chemical classes and about 0.02 mg/kg food for the unidentified fraction. The contact with dry food and food simulated by 20% ethanol were considered covered by the migration tests with aqueous simulants. Based on genotoxicity assays and compositional analyses, the constituents of the chemical classes did not raise a concern for genotoxicity. The potential migration of individual constituents or groups of chemically-related compounds of the unidentified fraction would result in exposures below (for aqueous food) and above (for fatty food) the threshold of toxicological concern for genotoxic carcinogens. Therefore, the FCM Panel concluded that the substances are not of safety concern for the consumer, if used as additives up to 0.3% w/w in PET, PLA and rigid PVC materials and articles intended for contact with all food types except for fatty foods, for long-term storage at room temperature and below, including hot-fill and/or heating up to 100°C for up to 2 h.

Anti-Leishmania amazonensis Activity of Morolic Acid, a Pentacyclic Triterpene with Effects on Innate Immune Response during Macrophage Infection.

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

Mapping of SINEs in the genome of Proechimys (Mammalia: Rodentia).

This study aimed to analyze the distribution of short interspersed elements (SINEs) in the chromosomes of five species of rodents of the genus Proechimys and in a variant karyotype of P. guyannensis. Molecular cytogenetic techniques were used to characterize the sequences of the B1, B4, MAR and THER SINEs, which were used as probes for hybridization in metaphase chromosomes. A wide distribution of SINEs was observed in the chromosomes of the Proechimys species examined, thus indicating differentiation of these retroelements. The signal of the B4 SINE was more evident than that of the B1 SINE, especially in P. echinothrix, P. longicaudatus, and P. cuvieri. Although the signal of the MAR SINE was more explosive than that of the THER SINE, in the species P. echinothrix, P. guyannensis (2n = 46) and P. longicaudatus, its distribution in the karyotypes was similar. The signals of these retroelements occurred at specific heterochromatic sites and were centromeric/pericentromeric and at the terminal regions in most chromosomes. This appears to be a typical distribution pattern of the SINEs and may indicate involvement with rearrangements during karyotypic diversification in Proechimys. The variation of the SINEs in the genome of Proechimys species demonstrates that these elements are distributed in a specific way in this genus and the preference for some sites, considered hotspots for chromosomal breakage, allows us to propose that these elements are related to the karyotypic evolution of Proechimys.

Respiratory and muscular effort during pre-slaughter stress affect Nile tilapia fillet quality.

Nile Tilapia (Oreochromis niloticus) management procedures are directly linked to the final quality of the product. The aim of this study was to evaluate the effect of pre-slaughter density and different stunning methods on biochemical, respiratory and muscle injury parameters associated with quality and sensory characteristics of Nile tilapia fillets. Fish with an average weight of 762±105 g were used, first collected called the control group. The experiment was conducted in a 2 × 2 factorial scheme, with two densities (50 and 300 kg of live weight m-3) and two stunning methods thus totaling four treatments, with 15 repetitions per treatment totaling 75 fish sampled. Blood gas analysis, evaluation of biochemical parameters, analysis of meat quality and sensory analysis were carried out. For blood gas, biochemical and enzymatic parameters, the highest values were obtained for the density of 300 kg m-3 and asphyxia method: partial pressures of CO2; glucose and lactate, the highest values presented were 268.98 and 11.33 mg dL-1 respectively. As well as enzymatic activities, Creatinine kinase (CPK); Creatinine kinase isoenzyme (CKMB) showed higher values (768.93 and 1078.98 mg dL-1 respectively) in the higher density and asphyxia method. Conversely, when evaluating the quality parameters, the highest values were observed for lower density and thermonarcosis. High depuration density (300 kg m-3), combined with the asphyxiation stunning method, promotes changes in respiratory dynamics and provides greater stress, less firm fillet texture and greater weight loss due to cooking, as well as changes in creatine kinase (CK) and its CK-MB isoenzyme, demonstrating greater muscle damage. On the other hand, the density of 50 kg m-3 during pre-slaughter, combined with the method of stunning by thermonarcosis, provide a longer period of permanence in pre rigor mortis, which will result in fillets with a better sensory profile.

Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Three New Polyprenylated Benzophenone Derivatives Isolated from Clusia burle-marxii.

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.

Educational technology to promote self-efficacy in newborn care: a validation study.

Objective: To build and validate an educational technology consisting of a flipchart to promote self-efficacy in newborn care. Methods: A methodological study was carried out in two stages: (i) creation of the flipchart and (ii) validation by 25 experts and 50 people who could be the target audience (pregnant women, mothers or family members of newborns). Clarity, language, practical relevance and theoretical relevance were reviewed using the Suitability Assessment of Materials (SAM) instrument. The Content Validity Index and the Flesch Readability Index were calculated. Results: The serial album "Can you take care of your baby" consists of 30 pages. The overall Content Validity Index was 0.93 among experts and 1.0 among the target audience. The flipchart was considered superior quality material, reaching an agreement percentage of 94.9, indicating that it is suitable as an educational technology. Participants suggested adjustments, incorporated into the material for printed production. Conclusion: The flipchart developed and with content validated by experts is suitable for use in health education activities that aim to promote self-efficacy in caring for newborns.

Gastrointestinal nematodes in Cuniculus paca (Linnaeus, 1766) from hunting fauna in the Western Amazonian region.

Cuniculus paca, commonly known as the paca, is a rodent of the Cuniculidae family that is widely distributed throughout the Americas, including all Brazilian territories, and is abundant in the Amazon region. It is one of the most hunted species and faces significant predation in the extreme western Amazon region of Brazil because it constitutes a staple in the diet of local communities, for subsistence and commercial purposes. Understanding the helminthic fauna of these animals is of paramount importance, given that some nematodes have zoonotic potential and may pose risks to consumer health. This study aimed to contribute to the records of the nemtodes of this highly consumed species in the Amazon region, highlighting the occurrence of gastrointestinal parasites in free-living pacas intended for human subsistence consumption. The study was conducted in the Paranã da Floresta community, located in the municipality of Guajará, Amazonas from 2022 to 2023. The community members hunted this rodent for consumption and voluntarily provided the viscera for analysis. Nematodes were extracted from each organ. The organs were opened, and the contents were processed using a sieve (0.15 mm) and subsequently evaluated separately. In total, 10,157 nematodes were found in the 14 pacas. Based on morphological analyses, the nematodes were identified as Heligmostrongylus sedecimradiatus (n = 10,068), Trichuris sp. (n = 85), and Physaloptera sp. (n = 4). This study provides insights into the nematodes diversity of free-living pacas in the extreme Western Amazon region, emphasizing the importance of sanitary surveillance and public awareness of the risks associated with bushmeat consumption.

Acute toxicity and genotoxicity of Schinus molle L. aqueous extract/ethanol-soluble fraction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. is a medicinal species belonging to the Anacardiaceae family. It is commonly referred to as "aroeira" and its leaves and roots are utilized for treating different pathological conditions. However, despite its widespread use in traditional medicine, there is a lack of in-depth toxicological studies. AIM: To evaluate the acute toxicity and genotoxicity of S. molle aqueous extract/ethanol-soluble fraction in rats. MATERIAL AND METHODS: First, a purified aqueous extract was obtained from the leaves of S. mole through infusion (referred to as EESM) and its compounds were identified using LC-DAD-MS data. Female rats were then subjected to acute oral toxicity tests using doses of 5, 50, 300, and 2000 mg/kg of ESSM. Studies on genetic material, including the micronucleus test and comet assay, were conducted on male and female Wistar rats using the same doses as in the acute toxicity test. For both assays, ESSM was administered orally. RESULTS: The main metabolites annotated from ESSM were dimeric proanthocyanidins, phenylpropanoids acids, flavan-3-ols, simple organic acids (C6-C1), a flavonol di-O-glycosylated (rutin), and O-glycosylated megastigmane. The ESSM did not exhibit any acute toxic effects, such as changes in biochemical, hematologic, or histopathological analysis. Furthermore, no changes were observed in comet assay or micronucleus tests when rats were given doses of 5, 50, 300, or 2000 mg/kg of ESSM. CONCLUSION: The results showed that the ESSM does not induce acute toxicity or exhibit genotoxicity up to a dose of 2000 mg/kg.

The use of electronic cigarettes and other tobacco products among university students and their potential relationship with oral health: A cross-sectional study.

BACKGROUND: The aim of this study was to evaluate oral alterations among university students and explore possible associations with tobacco consumption in its various forms. METHODS: A cross-sectional study was conducted in 2 phases: the first phase involved administering an electronic questionnaire to participants determine the prevalence of tobacco use and the second phase involved a physical examination of the participants. The participants were grouped on the basis of their reported habits and compared using statistical analysis (P < .05). RESULTS: Of the 620 participants, 57.1% reported using tobacco in some form, with 47.4% reporting electronic cigarette (e-cigarette) use. In the clinical phase, comparing the presence of oral changes in tobacco users vs nonusers, e-cigarette users had a higher proportion of white-spot caries lesions (P = .041) and gingivitis (P = .012). When e-cigarette use was combined with other forms of tobacco use, additional oral changes were more prevalent, including coated tongue and nicotinic stomatitis (P < .05). CONCLUSIONS: The use of alternative forms of tobacco consumption is common among university students, with e-cigarette use being the most prevalent form, and may lead to detrimental effects on the oral cavity, such as caries and gingivitis, particularly when used in conjunction with other tobacco products. PRACTICAL IMPLICATIONS: The use of tobacco in alternative forms, such as e-cigarettes, can affect oral health directly or indirectly. Dentists should be familiar with the characteristics of this population and the potential oral repercussions associated with tobacco use to address the impact on health and raise awareness of the associated risks.

Influences on COVID-19 Vaccine Adherence among Pregnant Women: The Role of Internet Access and Pre-Vaccination Emotions.

INTRODUCTION: The onset of the COVID-19 pandemic brought about global uncertainties and fears, escalating the dissemination of fake news. This study aims to analyze the impact of fake news on COVID-19 vaccine adherence among pregnant women, providing crucial insights for effective communication strategies during the pandemic. METHODS: A cross-sectional, exploratory study was conducted with 113 pregnant women under care at a Women's Health Reference Center. Data analysis included relative frequency and odds ratio to assess the relationship between sociodemographic and behavioral variables regarding vaccination. RESULTS: In the behavioral context of vaccination, internet access shows a significant association with decision-making, influencing vaccine refusal due to online information. Nuances in the odds ratios results highlight the complexity of vaccine hesitancy, emphasizing the importance of information quality. Pre-vaccination sentiments include stress (87.61%), fear (50.44%), and anxiety (40.7%), indicating the need for sensitive communication strategies. DISCUSSION: Results revealed that pregnant women with higher education tend to adhere more to vaccination. Exposure to news about vaccine inefficacy had a subtle association with hesitancy, while finding secure sources was negatively associated with hesitancy. The behavioral complexity in the relationship between online information access and vaccination decision underscores the need for effective communication strategies. CONCLUSIONS: In the face of this challenging scenario, proactive strategies, such as developing specific campaigns for pregnant women, are essential. These should provide clear information, debunk myths, and address doubts. A user-centered approach, understanding their needs, is crucial. Furthermore, ensuring information quality and promoting secure sources are fundamental measures to strengthen trust in vaccination and enhance long-term public health.

Assessment of toxicity of pyriproxyfen, Bacillus thuringiensis, and malathion and their mixtures used for mosquito control on embryo-larval development and behavior of zebrafish.

Pyriproxyfen (PPF), Bacillus thuringiensis israelensis (BTI), and malathion (MLT) are widely used worldwide to control the population of mosquitos that transmit arboviruses. The current work aimed to evaluate the toxicity of these single pesticides and their binary mixtures of PPF + BTI, PPF + MLT, and MLT + BTI on the embryo-larval stage of zebrafish (Danio rerio) as an animal model. Epiboly, mortality, apical endpoints, affected animals, heart rate, morphometric, thigmotaxis, touch sensitivity, and optomotor response tests were evaluated. PPF and MLT and all mixtures reduced the epiboly percentage. Mortality increased significantly in all exposed groups, except BTI, with MLT being the most toxic. The observed apical endpoints were pericardial and yolk sac edemas, and tail and spine deformation. Exposure to MLT showed a higher percentage of affected animals. A reduction in heart rate was also observed in MLT- and PPF + MLT-exposed groups. The PPF + MLT mixture decreased head measurements. Behavioral alterations were observed, with a decrease in thigmotaxis and touch sensitivity responses in PPF + MLT and MLT + BTI groups. Finally, optomotor responses were affected in all groups. The above data obtained suggest that the MLT + PFF mixture has the greatest toxicity effects. This mixture affected embryo-larval development and behavior and is close to the reality in several cities that use both pesticides for mosquito control rather than single pesticides, leading to a reevaluation of the strategy for mosquito control.

Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network.

BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING: Janssen and Leukemia & Lymphoma Society.

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development.

Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis.

This study investigates the short and long-term effects of IFNT and PAG on the transcriptome of endometrium and blood leukocytes. Holstein heifers received intrauterine infusions of one of the following treatments: 20 mL of a 200 µg/mL bovine serum albumin solution (BSA; vehicle) from day 14 to 16 of the estrous cycle (BSA), vehicle + 10 µg/mL of IFNT from day 14 to 16 (IFNT3), vehicle + 10 µg/mL of IFNT from day 14 to 19 (IFNT6), and vehicle + 10 µg/mL of IFNT from day 14 to 16 followed by vehicle + 10 µg/mL of IFNT + 5 µg/mL of PAG from day 17 to 19 (IFNT+PAG). RNA-seq analysis was performed in endometrial biopsies and blood leukocytes collected after treatments. Acute IFNT signaling in the endometrium (IFNT3 vs BSA), induced differentially expressed genes (DEG) associated with interferon activation, immune response, inflammation, cell death, and inhibited vesicle transport and extracellular matrix remodeling. Prolonged IFNT signaling (IFNT6 vs IFNT3) altered gene expression related to cell invasion, retinoic acid signaling, and embryo implantation. In contrast, PAG induced numerous DEG in blood leukocytes but only 4 DEG in the endometrium. In blood leukocytes, PAG stimulated genes involved in development and TGFB signaling while inhibiting interferon signaling and cell migration. Overall, IFNT is a primary regulator of endometrial gene expression, while PAG predominantly affected the transcriptome of circulating immune cells during early pregnancy. Further research is essential to fully grasp the roles of identified DEG in both the endometrium and blood leukocytes.

Magnesium whitlockite nanoparticles: Hydrothermal synthesis, anti-inflammatory and anti-cancer potential.

This study revealed the potential of magnesium whitlockite [WH: Ca18Mg2(HPO4)2(PO4)12] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments.