Search Results (9,047)

Extracellular vesicles (EVs) from Candida albicans can elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulent C. albicans cell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEV (91%) and ecm33 YEV immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs, which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs; and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEV-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties of C. albicans EVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs. Full article

Peptide-based nanomaterials can be easily functionalized due to their functional groups, as well as being biocompatible, stable under physiological conditions, and nontoxic. Here, diphenylalanineamide-based nanomaterials (FFANMs) were synthesized, decorated with Ca²⁺ ions to set the surface charge, and characterized for possible use in gene delivery and drug release studies. FFANMs were characterized by SEM, TEM, dynamic light scattering (DLS), and LC-MS/MS. Corona formation and biocompatible studies were also carried out. Some of the data obtained are as follows: FFANMs have a diameter of approximately 87.93 nm. While the zeta potentials of FFANMs and Ca²⁺@FFANMs were −20.1 mV and +9.3 mV, respectively, after corona formation with HSA and IgG proteins, they were shifted to −7.6 mV and −3.7 mV, respectively. For gene delivery studies, zeta potentials of Ca²⁺@FFANMs and DNA interactions were also studied and found to shift to −9.7 mV. Cytotoxicity and biocompatibility studies of NMs were also studied on HeLa and HT29 cell lines, and decreases of about 5% and 10% in viability at the end of 24 h and 72 h incubation times were found. We think that the results obtained from this study will assist the groups working in the relevant field. Full article

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated food allergy, usually presenting as bloody stools in breastfed, well-appearing, and regularly growing infants. The aim of our study was to describe the clinical features of Italian infants affected by FPIAP and their management and natural history in a real-life setting. Methods: A retrospective, observational study was performed at two tertiary pediatric hospitals (Florence and Trieste), including FPIAP-diagnosed infants between 2012 and 2022. Results: Most of the 100 enrolled patients were breastfed (68.0%), and the majority of those who underwent diagnostic tests (n = 51) showed normal hemoglobin and total IgE levels. A maternal elimination diet was performed in 69.0%, mostly for milk only, but 40.6% underwent multiple elimination diets. The remission rate was high both in breastfed infants (76.8%) and in those who received extensively hydrolyzed formula (81.8%). Nine subjects were left on a free diet, but six were lost at follow-up. The median time of complete remission was 30 days (IQR 14–60). Culprit food reintroduction was tolerated at a median age of 8 months (IQR 6–11), in ladder modality (for hen’s egg and cow’s milk) in 61.7%. Nine patients relapsed (14.3%) upon reintroduction with no associated variables identified at the regression analysis. The relapse rate was slightly higher when trigger food reintroduction was attempted > 12 months (16.7%) versus <12 months (13.0%). Conclusions: In our population, FPIAP had, as expected, a benign evolution. The early reintroduction of the suspect food in a gradual manner for cow’s milk and hen’s egg leads to good tolerance within the first year in most patients, avoiding unnecessary elimination diets. Full article

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article

Background/Objective: The utilization of maternal health services at the primary healthcare level is still considered an effective approach despite the critical role in improving maternal health outcomes. The study aimed to assess the influence of sociodemographic characteristics and interpersonal support on the use of maternal health services in three regions of the Province of Jambi, Indonesia. Methods: Using a mixed-methods sequential explanatory design, a quantitative survey of 432 women and qualitative focus group discussions with nine families were conducted. Quantitative data were analyzed using bivariate analysis, while the qualitative data were examined through conventional content analysis. Results: The research results show no significant association between sociodemographic factors (education, employment, residence) and the use of maternal health services for antenatal care and delivery. Direct support, such as accompaniment by spouses, and indirect support, including emotional encouragement and shared knowledge, were pivotal in influencing women’s decisions to seek care. Conclusions: Targeted interventions focusing on improving social support, addressing service accessibility barriers, and raising awareness about the benefits of community health centers are essential to enhancing maternal health outcomes. Policymakers and healthcare providers should integrate family-centered strategies to ensure women receive adequate maternal healthcare. Full article

Zenith tropospheric delay (ZTD) is a significant atmospheric error that impacts the Global Navigation Satellite System (GNSS). Developing a high-precision, long-term forecasting model for ZTD can provide valuable insights into the overall trends of predicted ZTD, which is essential for improving GNSS positioning and analyzing changes in regional climate and water vapor. To address the challenges of incomplete information extraction and gradient explosion in a single neural network when forecasting ZTD long-term, this study introduces an Informer–LSTM Hybrid Prediction Model. This model employs a parallel ensemble learning strategy that combines the strengths of both the Informer and LSTM networks to extract features from ZTD data. The Informer model is effective at capturing the periodicity and long-term trends within the ZTD data, while the LSTM model excels at understanding short-term dependencies and dynamic changes. By merging the features extracted by both models, the prediction capabilities of each can complement one another, allowing for a more comprehensive analysis of the characteristics present in ZTD data. In our research, we utilized ERA5-derived ZTD data from 11 International GNSS Service (IGS) stations in Europe to interpolate the missing portions of GNSS-derived ZTD. We then employed this interpolated data from 2016 to 2020, along with an Informer–LSTM Hybrid Prediction Model, to develop a long-term prediction model for ZTD with a prediction duration of one year. Our numerical results demonstrate that the proposed model outperforms several comparative models, including the LSTM–Informer based on a serial ensemble learning model, as well as the Informer, Transformer, LSTM, and GPT3 empirical ZTD models. The performance metrics indicate a root mean square error (RMSE) of 1.91 cm, a mean absolute error (MAE) of 1.45 cm, a mean absolute percentage error (MAPE) of 0.60, and a correlation coefficient (R) of 0.916. Spatial distribution analysis of the accuracy metrics showed that predictive accuracy was higher in high-latitude regions compared to low-latitude areas, with inland regions demonstrating better performance than those near the ocean. This study introduced a novel methodology for high-precision ZTD modeling, which is significant for improving accurate GNSS positioning and detecting water vapor content. Full article

To explore the effect of density on large yellow croaker (Larimichthys crocea) under intensive aquaculture conditions and determine the appropriate culturing density, this study investigate the effects of different stocking densities on the nutritional composition, stress, and immune levels of large yellow croaker. Through a long-term aquaculture experiment, conducted under flow-through conditions of intensive aquaculture, three initial density groups were set: a low density group [LD], 4.92 kg/m³; a medium density group [MD], 7.56 kg/m³; and a high density group [HD], 10.08 kg/m³, for a 150-day rearing trial. Large yellow croaker were fed to satiation twice daily (6:00, 17:00). At the end of this trial, the final densities were 10.38 ± 0.50, 14.41 ± 1.06, and 18.71 ± 0.99 kg/m³ in the LD, MD, and HD groups, respectively. The results showed that the growth performances were adversely influenced by a high stocking density. Levels of cortisol in serum, superoxide dismutase (SOD) and catalase (CAT) in liver, Na⁺-K⁺ ATPase and Na⁺-K⁺ ATPase gene in gills, and heat shock protein (HSP70/90) genes and glutathione S-transferase (GST) genes in the liver significantly increased under HD treatment. Results of immune response analyses showed that there was a clear decrease in immunoglobulin M (IgM), complement component 4 (C4), and lysozyme (LZM) in serum, lysozyme (LZM) genes, tumor necrosis factor-alpha (TNF-α) genes and interleukin-1β (IL-1β) genes in the head kidney of large yellow croakers reared in the HD group. An obvious increase in free amino acids and fatty acids in the muscle of large yellow croakers reared in HD group was also observed. Overall, this study showed that the optimal final culturing density of large yellow croaker under flow-through systems should be between 14.41 kg/m³ and 18.71 kg/m³ to improve aquaculture efficiency and product quality. Full article

Small interfering RNAs (siRNAs) are short, double-stranded RNA molecules that play a crucial role in the regulation of gene expression, particularly through a natural process called RNA interference (RNAi). Their discovery, about 25 years ago, paved the way for a whole series of research leading to synthetic molecules. The gene silencing potential of these siRNAs was initially oriented towards diseases resulting from genetic dysfunctions. This led to the development of the first synthetic siRNAs approved for human use in hereditary transthyretin amyloidosis. Subsequently, the field of application expanded beyond the confines of genetic diseases. The refinement of pharmacological techniques has led to the synthesis of a variety of siRNAs capable of blocking the production of individual proteins responsible for various disease conditions, thus expanding their field of therapeutic application. The kidney has also been affected by this new therapeutic tool, largely indirectly but also, with some difficulty, directly. The structural complexity of the kidney has made the search for siRNAs targeting its individual components very challenging. Nevertheless, the first results of the application of this new therapeutic technology to the kidney are beginning to be seen in experimental animals and in humans. siRNAs have been approved for the treatment of amyloidosis with patisiran and oxalosis with lumasiran and nedosiran. Studies are ongoing for the use of siRNAs as anti-complement drugs in IgA nephropathy, as angiotensinogen inhibitors in hypertension, or against some mediators of acute kidney injury. In this review, the biological mechanisms underlying the use of siRNAs are briefly exposed. The results of the therapeutic application of RNA interference to the kidney and its diseases are also analyzed and discussed. Full article

Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed. Additionally, immunoglobulin (Ig) levels post-tumor induction were tracked via enzyme-linked immunosorbent assays (ELISA). Following tumor induction, GCs, as well as increasing numbers of GL7⁺CD95⁺ GC B cells in the spleen and tumor tissues, were detected. In parallel, we observed CD39⁺CD73⁺ B cells in tumors and spleens of tumor-bearing mice. Notably, CD39⁺CD73⁺ expression was primarily detected on MZ B cells and to a lesser extent on follicular (FO) and non-follicular, newly formed (NF) B cells, supposing an immunosuppressive function of MZ B cells in the TME. Parallel to increased MZ B cell numbers in secondary lymphoid organs (SLOs) as well as in the tumor tissue, IgM antibody (Ab) levels rose continuously. In contrast, IgG1, IgG2, and IgG3 levels increased at later time points. Understanding the complex interactions between B cell subsets and the TME could lead to new strategies for enhancing the treatment and prognosis of HNSCC patients. Full article

This study investigated the effects of dietary capsaicin supplementation on antioxidant capacity, immune function, and gut microbiota in periparturient dairy cows. Twenty Holstein cows with an average parity of 2.5 ± 0.76, milk production of 31.30 ± 2.39 kg, and 36.10 ± 2.38 days to calving were randomly assigned to either a control group fed a basal diet or a treatment group supplemented with 1.2 g/head/day of capsaicin. The supplementation was administered during an evaluation period spanning from 28 days before delivery to 21 days after delivery using a randomized block experimental design. Results showed that capsaicin significantly reduced milk somatic cell count and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while enhancing serum antioxidant enzymes (SOD, GSH-Px, and CAT) and immunoglobulin levels (IgG, IgA, and IgM). Moreover, capsaicin altered gut microbiota composition, increasing the relative abundance of beneficial genera. These findings suggest that dietary capsaicin supplementation during the transition period improves lactation performance and supports immune function, as well as alleviates oxidative stress. This study highlights the potential of capsaicin as a practical dietary strategy for enhancing productivity in dairy farming. Full article

Crimean–Congo hemorrhagic fever (CCHF) is a serious tick-borne disease with a wide geographical distribution. Classified as a level 4 biosecurity risk pathogen, CCHF can be transmitted cross-species due to its aerosol infectivity and ability to cause severe hemorrhagic fever outbreaks with high morbidity and mortality. However, current methods for detecting anti-CCHFV antibodies are limited. This study aimed to develop a novel luciferase immunosorbent assay (LISA) for the detection of CCHFV-specific IgG antibodies. We designed specific antigenic fragments of the nucleoprotein and evaluated their sensitivity and specificity in detecting IgG in serum samples from mice and horses. In addition, we compared the efficacy of our LISA to a commercial enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that the optimal antigen for detecting anti-CCHFV IgG was located within the stalk cut-off domain of the nucleoprotein. The LISA exhibited high specificity for serum samples from indicated species and significantly higher sensitivity (at least 128 times) compared with the commercial ELISA. The proposed CCHFV-LISA has the potential to facilitate serological diagnosis and epidemiological investigation of CCHFV in natural foci, providing valuable technical support for surveillance and early warning of this disease. Full article

Background/Objectives: An increasing number of studies have reported liver involvement in both children and adults with celiac disease (CD). This often manifests as isolated hypertransaminasemia or hepatic steatosis (HS). The aim of this study was to define the prevalence of hypertransaminasemia and HS in a pediatric population with CD before starting a gluten-free diet (GFD) and to analyze how the introduction of a GFD could modify this condition. We also conducted a state-of-the-art literature review of the association between hypertransaminasemia, metabolic dysfunction-associated steatotic liver disease (MASLD) and CD. Methods: We retrospectively reviewed the clinical charts of pediatric CD patients diagnosed in three different pediatric units of Sicily, analyzing clinical, laboratory, ultrasound, and histology data before and 12 months after the introduction of a GFD. Results: A total of 160 patients (65.0% females, median age 6.4 (0.8–13.2) years) were included; hypertransaminasemia and HS prevalences at diagnosis were 8.1% and 6.1%, respectively. Subjects with hypertransaminasemia were younger (p = 0.01) than those without and had higher frequencies of HS (p = 0.034) and anti-tissue transglutaminase (tTg) immunoglobulin (Ig)G positivity (p = 0.046). Subjects with HS were younger (p = 0.0001) and had a higher frequency of hypertransaminasemia (p = 0.029) compared to non-steatotic ones. After 12 months of a GFD, hypertransaminasemia and HS persisted in 53.8% and 50.0% of patients, respectively. Conclusions: The prevalences of hypertransaminasemia and HS in Sicilian pediatric CD patients seem to be lower than those reported in other geographical areas. A GFD can reverse the trend of liver involvement, although periods of longer than 12 months may be necessary. However, a GFD has been associated with an increased prevalence of HS, and so regular follow-up involving a nutritionist should be recommended to guide physicians in patient management. Full article

Informal green spaces (IGSs) are vital yet under-researched urban areas that enhance biodiversity, provide ecosystem services, and improve the well-being of urban residents. However, the lack of a consistent definition and comprehensive understanding of their multifunctional roles has hindered their effective integration into urban planning. The current literature review aimed to clarify the concept of IGSs, analyze research trends, and identify further research areas. Using a combined bibliometric and systematic analysis approach, 150 articles from the Web of Science database, published from 1996 to 2024, were analyzed. The systematic analysis identified 54 relevant documents on the effects of green areas, revealing a diverse and growing body of research on IGSs, including their types, distribution, and socioeconomic contexts. The findings indicated an increasing trend in collaborative studies, using “informal green space” as the official term. This review proposed a clear and comprehensive definition of IGS, emphasizing its visibility, lack of formal recognition, minimal management, spontaneous vegetation, and temporary nature and underscoring its substantial environmental and social benefits. Furthermore, this review highlighted the need for standardized definitions and interdisciplinary studies to fully harness the potential of IGSs, thereby emphasizing their essential contribution to urban biodiversity and the regulation of urban microclimates. Full article

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. Full article

Background: Atopic dermatitis (AD) is a chronic skin condition that weakens the skin barrier, leading to increased trans-epidermal water loss and reduced skin moisture. Understanding how these changes in the skin barrier relate to AD severity in Mongolian children may offer insights that could apply to other regions facing similar environmental challenges. Methods: A cross-sectional study was conducted at the National Dermatology Center of Mongolia, involving 103 children with AD. Severity was assessed using the SCORAD index, and skin barrier function was measured through TEWL, skin moisture, and pH. Linear regression analyses were conducted, adjusting for age, skin physiological parameters, AD severity characteristics, and total IgE levels. Results: Among the participants, 48.54% were classified as having moderate AD, while 34.95% had severe AD. The mean SCORAD index was 43.19 ± 17.11. In the final adjusted regression analysis, higher TEWL was significantly associated with greater AD severity (non-lesional: B = 0.328, p = 0.004; lesional: B = 0.272, p = 0.007), while skin moisture showed an inverse association (non-lesional: B = −0.771, p < 0.001; lesional: B = −0.218, p < 0.001). The total IgE level was significantly higher in the severe AD group (p = 0.013). Although skin pH initially correlated with AD severity, it did not remain significant in multivariate analysis. Conclusions: This study emphasizes the role of skin barrier function, particularly increased TEWL and reduced moisture, in AD severity among Mongolian children. Full article