Search Results (14,867)

Background: While host immune responses to SARS-CoV-2 vaccination are routinely assessed through IgG measurements, less is known about the temporal dynamics of vaccine-induced cellular immunity, particularly in individuals who fail to develop detectable IgG antibodies after COVID-19 vaccination. Objective: To investigate the development and timing of T-cell immunity following SARS-CoV-2 vaccination in antibody-non-responders to COVID-19 vaccination. Methods: A cross-sectional analysis was conducted on COVID-19-naive individuals who had received full SARS-CoV-2 vaccination, categorized by SARS-CoV-2 IgG serostatus. T-cell response was evaluated using the IGRA methodology T-SPOT^®.COVID (Oxford Immunotec, Abingdon, Oxfordshire, UK). T-cell response rates and levels were compared between SARS-CoV-2 seropositive and seronegative groups, and a temporal cutoff analysis was applied to examine trends in T-cell response over time. Results: Within the seronegative group, IgG levels showed a strong negative correlation with time since vaccination (Spearman ρ = −0.65, p < 0.001), while T-cell response levels exhibited a weak positive time-dependent trend (ρ = 0.15, p = 0.019). Temporal cutoff analysis identified a critical time-point beginning at 80 days post-vaccination, after which both T-cell response rates and levels were significantly higher. Specifically, individuals tested after 80 days showed increased median T-cell response levels (U = 4205, p < 0.001) and higher positive T-cell response rate (67% vs. 38%, Χ² = 17.06, p < 0.001). Conclusions: Cellular immunity response against SARS-CoV-2 may emerge later than expected in antibody-non-responders to COVID-19 vaccination, with the 80-day post-vaccination mark emerging as a critical time point. Our results support the inclusion of cellular assays in post-vaccination monitoring and emphasize the need to reconsider the timing and criteria for evaluating vaccine response. Full article

As an emerging concept, steganography without embedding (SWE) hides a secret message without directly embedding it into a cover. Thus, SWE has the unique advantage of being immune to typical steganalysis methods and can better protect the secret message from being exposed. However, existing SWE methods are generally criticized for their poor payload capacity and low fidelity of recovered secret messages. In this paper, we propose a novel steganography-without-embedding technique, named DF-SWE, which addresses the aforementioned drawbacks and produces diverse and natural stego images. Specifically, DF-SWE employs a reversible circulation of double flow to build a reversible bijective transformation between the secret image and the generated stego image. Hence, it provides a way to directly generate stego images from secret images without a cover image. Besides leveraging the invertible property, DF-SWE can invert a secret image from a generated stego image in a nearly lossless manner and increase the fidelity of extracted secret images. To the best of our knowledge, DF-SWE is the first SWE method that can hide multiple images into one image with the same size, significantly enhancing the payload capacity. According to the experimental results, the payload capacity of DF-SWE achieves 24–72 BPP, which is 8000∼16,000 times more compared to its competitors while producing diverse images to minimize the exposure risk. Importantly, DF-SWE can be applied in the steganography of secret images in various domains without requiring training data from the corresponding domains. This domain-agnostic property suggests that DF-SWE can (1) be applied to hiding private data and (2) be deployed in resource-limited systems. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have transformed treatment paradigms, but assessing response remains challenging due to atypical patterns such as pseudoprogression, hyperprogression and dissociated response. Conventional evaluation criteria, such as RECIST 1.1, may not fully capture these patterns, leading to potential misclassification and premature therapy discontinuation. This review explores the role of 18F-FDG PET/CT in assessing immunotherapy response and highlights novel imaging criteria to enhance clinical decision-making. Methods: A systematic literature review was conducted across PubMed, Web of Science, Scopus, and Cochrane Library, selecting relevant studies published between 2013 and 2024. The review focuses on the strengths and limitations of PET-based imaging in monitoring NSCLC immunotherapy outcomes. Specific attention was given to evolving evaluation frameworks, including iRECIST, PERCIST, imPERCIST, and iPERCIST, as well as metabolic biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Results: Compared with anatomical-based assessment, metabolic imaging using 18F-FDG PET/CT may offer deeper insights into tumor behavior during immunotherapy. PET-derived parameters seem to improve the detection of immune-related response patterns, providing a more refined approach to differentiate true progression from pseudoprogression. Emerging evidence indicates that metabolic biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) could serve as useful predictors of therapeutic efficacy and support treatment adaptation. Nevertheless, current findings are mainly based on small, heterogeneous, and predominantly retrospective studies, with variable PET timing and threshold definitions that limit the generalizability of these results. Conclusion: 18F-FDG PET/CT represents a promising complementary tool for assessing immunotherapy response in NSCLC. Its integration with advanced imaging criteria and metabolic tumor biomarkers may enhance response evaluation and assist clinical decision-making. Nonetheless, the current evidence remains preliminary, and further standardization and large prospective validation studies are required before its routine implementation in clinical practice. Full article

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections. Full article

Background: The extracellular domain of the M2 protein (M2e) and the conserved region of the second subunit of the hemagglutinin (HA2, 76–130 а.а.) of the influenza A virus, could be used to develop broad-spectrum influenza vaccines. However, these antigens have low immunogenicity and require the use of special carriers to enhance it. Virus-like particles (VLPs) formed from viral capsid proteins are among the most effective carriers. Methods: In this work, we obtained and characterized VLPs based on capsid proteins (CPs) of single-stranded RNA bacteriophages Beihai32 and PQ465, simultaneously displaying M2e and HA2 peptides. Results: Fusion proteins expressed in Escherichia coli formed spherical VLPs of about 30 nm in size. Subcutaneous immunization of mice with chimeric VLPs elicited a robust humoral immune response against M2e and the whole influenza A virus, and promoted the formation of cytokine-secreting antigen-specific CD4⁺ and CD8⁺ effector memory T cells. Conclusions: VLPs based on CPs of phages Beihai32 and PQ465 carrying conserved peptides M2e and HA2 of the influenza A virus can be used for the development of universal influenza vaccines. Full article

Besides genomic and proteomic analyses of bulk and individual cancer cells, cancer research focuses on the mechanical analysis of cancers, such as cancer cells. Throughout the oncogenic evolution of cancer, mechanical inputs are stored as epigenetic memory, which ensures versatile coding of malignant characteristics and a quicker response to external environmental influences in comparison to solely mutation-based clonal evolutionary mechanisms. Cancer’s mechanical memory is a proposed mechanism for how complex details such as metastatic phenotypes, treatment resistance, and the interaction of cancers with their environment could be stored at multiple levels. The mechanism appears to be similar to the formation of memories in the brain and immune system like epigenetic alterations in individual cells and scattered state changes in groups of cells. Carcinogenesis could therefore be the outcome of physiological multistage feedback mechanisms triggered by specific heritable oncogenic alterations, resulting in a tumor-specific disruption of the integration of the target site/tissue into the overall organism. This review highlights and discusses the impact of the ECM on cancer cells’ mechanical memory during their metastatic spread. Additionally, it demonstrates how the emergence of a mechanical memory of cancer can give rise to new degrees of individuality within the host organism, and a connection to the cancer entity is established by discussing a connection to the metastasis cascade. The aim is to identify common mechanical memory mechanisms of different types of cancer. Finally, it is emphasized that efforts to identify the malignant potency of tumors should go way beyond sequencing approaches and include a functional diagnosis of cancer physiology and a dynamic mechanical assessment of cancer cells. Full article

Multiple Sclerosis (MS) is an autoimmune and neurodegenerative disorder of the central nervous system (CNS), characterized by demyelination, neuronal loss and physical disability. To date, the exact causes of MS remain unknown. Lifestyle factors, in particular diet, have received growing attention due to their impact on human health, their role in modulating disease pathogenesis, and their influence on gut microbiota composition and activity. As a result, numerous studies have been conducted to examine how specific nutrients, and thereby distinct dietary patterns, may affect the onset and progression of MS. In this narrative review, we aim to explore the most recent and updated evidence concerning the role of fatty acids, carbohydrates, proteins and fibers macronutrients in MS development and progression by evaluating the most relevant literature findings from preclinical models, and clinical trials on people with MS. Dietary macronutrients influence MS pathology through immune and gut–brain axis modulation. Diets rich in saturated fats and refined carbohydrates exacerbate neuroinflammation, promote Th1/Th17 polarization, and worsen disease severity. Conversely, monounsaturated and omega-3 polyunsaturated fatty acids, dietary fibers, and adequate tryptophan metabolism exert anti-inflammatory effects, enhance regulatory T cell (Treg) activity, and improve clinical outcomes. Fiber-derived short-chain fatty acids (SCFAs) and omega-3 metabolites also support gut barrier integrity and suppress astrocyte activation. Evidence on dairy, meat and gluten remains inconclusive, though certain milk proteins and certain components of red/processed meat and of wheat may promote inflammation. Overall, anti-inflammatory and fiber-rich diets, such as those emphasizing unsaturated fats and low sugar intake, appear to confer protective effects in MS. The clarification of the role of dietary components in relation to the disease could help to guide patients toward a healthy and balanced diet, with positive effects on their overall health. Full article

Diesel engines remain the foundation for obtaining mechanical energy in sectors where autonomy and reliability are required; however, predictive diagnostics under real-world conditions remain challenging. The purpose of this scoping review is the investigation and systematization of published scientific data on the application of vibration methods for monitoring the technical condition of diesel engines in industrial or controlled laboratory conditions. Based on numerous results of publication analysis, sensor configurations, diagnosed components, signal analysis methods, and their application for assessing engine technical condition are considered. As methods for determining vibration parameters, time-domain and frequency-domain analysis, adaptive decompositions, and machine and deep learning algorithms predominate; high accuracy is more often achieved under controlled conditions, while confirmations of robustness on industrial installations are still insufficient. Key limitations for the application of vibration monitoring methods include the multicomponent and non-stationary nature of signals, a high level of noise, requirements for sensor placement, communication channel limitations, and the need for on-site processing; meanwhile, the assessment of torsional vibrations remains technically challenging. It is concluded that field validations of vibroacoustic data, the use of multimodal sensor platforms, noise-immune algorithms, and model adaptation to the specific environment are necessary, taking into account fuel quality, transient conditions, and climatic factors. Full article

Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, which may affect, e.g., gene mRNA stability and also VDR gene expression. There are four main polymorphic sites within the gene, BsmI, ApaI, FokI and TaqI, and two polymorphisms related to the gene promoter: GATA and Cdx2. One of the functions of vitamin D is to modulate the immune system. It affects T lymphocytes, B lymphocytes and dendritic cells. Currently, vitamin D deficiency is a common global problem that is associated with an increased risk of autoimmune diseases, including Hashimoto’s thyroiditis. Numerous studies have demonstrated an association between low vitamin D levels and elevated thyroid-stimulating hormone (TSH) levels, and have also proven the existence of a negative correlation between vitamin D levels andanti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody titers. Review objectives and a concise summary of the methodology: The review aims to analyze studies examining the relationship between specific VDR polymorphisms, vitamin D levels, and the development of various diseases, with a particular emphasis on Hashimoto’s thyroiditis. This review is based on original and review articles written in English published between March 2018–November 2024 searched primarily in the PubMed, and additionally in Google Scholar databases. A narrative review of the literature was conducted. Conclusions: The presence of specific VDR polymorphisms influences the effectiveness of vitamin D supplementation, but the role of supplementation in the prevention of autoimmune diseases has not been definitively confirmed. To date, studies have primarily involved relatively small groups of patients with significant population heterogeneity, with case–control investigations being the most common. Therefore, further research on larger, more homogeneous groups is recommended to achieve more standardized results. Additionally, the influence of epigenetic factors modulating VDR activity and its interactions with the environmental factors is also important. Full article

Furin, a calcium-dependent serine endoprotease of the proprotein convertase family, plays a pivotal role in both physiological homeostasis and viral pathogenesis. By cleaving polybasic motifs within viral glycoproteins, furin enables the maturation of structural proteins essential for viral entry, fusion, and replication. This mechanism has been documented across a broad spectrum of human pathogens, including SARS-CoV-2, influenza virus, human immunodeficiency virus, human papilloma virus, hepatitis B virus, flaviviruses, herpesviruses, and paramyxoviruses, highlighting furin as a conserved molecular hub in host–virus interactions. Genetic variability within the FURIN gene further modulates infection outcomes. Several single-nucleotide polymorphisms (SNPs), such as rs6226 and rs1981458, are associated with altered COVID-19 severity, whereas variants like rs17514846 confer protection against human papilloma virus infection. Conversely, mutations predicted to reduce enzymatic activity have been linked to attenuated SARS-CoV-2 pathogenesis in certain populations. These findings underscore the importance of considering population genetics when evaluating viral susceptibility and disease progression. Despite advances, unresolved questions remain regarding furin’s non-canonical roles in viral life cycles, tissue-specific regulation, and interactions with other host proteases and immune modulators. Targeted inhibition of furin and related convertases represents a promising avenue for broad-spectrum antiviral interventions. Collectively, current evidence positions furin as a central node at the intersection of viral pathogenesis, host genetic variability, and translational therapeutic potential. Full article

Aquaculture is expanding rapidly worldwide, but its sustainability is threatened by intensive production practices, environmental stressors and recurrent disease outbreaks. Natural feed additives are increasingly studied as alternatives to antibiotics and synthetic compounds. Among them, bee-derived products—pollen, bee bread, propolis, royal jelly, honey and fermented derivatives—represent a promising resource due to their richness in proteins, amino acids, fatty acids, vitamins, flavonoids and phenolic compounds with demonstrated antioxidant, antimicrobial and immunostimulant properties. Evidence from studies on species such as Nile tilapia, rainbow trout, European sea bass, meagre and African catfish indicates that dietary supplementation with bee products can improve growth performance, immune and antioxidant responses, stress tolerance and resistance to bacterial infections while, in some cases, enhancing the nutritional value and shelf-life of fish products. Prominent examples include ~45% higher growth in African catfish with 10–30 g kg⁻¹ bee pollen, up to 93% protection in Nile tilapia fed 25 g kg⁻¹ pollen against Aeromonas hydrophila, and increased trout fillet carotenoids with pollen-derived pigments (with overall growth unchanged and pigmentation lower than synthetic astaxanthin). Conversely, meagre fed 20–40 g kg⁻¹ raw pollen showed reduced growth and digestibility with elevated intestinal stress markers, underscoring species- and dose-specific responses. Nevertheless, the available data remain fragmented and heterogeneous, reflecting differences in product type, origin, dosage and experimental design. This review critically analyses the current knowledge on bee products in aquaculture nutrition, identifies the main gaps and limitations, and outlines future research directions. By linking fish physiology, nutritional strategies and product quality, bee-derived products emerge as innovative tools for promoting fish health and resilience in sustainable aquaculture. Full article

This study evaluated the effects of feeding juvenile southern catfish (Silurus meridionalis) with one of six isonitrogenous and isoenergetic diets where fish meal (FM) was replaced by black soldier fly larval meal (BSFLM) at 0%, 10%, 20%, 30%, 40%, and 50% levels on growth, muscle quality, antioxidant capacity, immune response, and gut microbiota of juvenile southern catfish (Silurus meridionalis). A total of 1620 fish (9.20 ± 0.15 g) were fed one of six experimental diets for 8 weeks. Results demonstrated that a 50% replacement (H50 group) significantly improved weight gain rate, specific growth rate, and protein efficiency ratio (p < 0.001). Antioxidant capacity (T-AOC) was enhanced in groups H30 and H50, while immune markers lysozyme (LZM) and alkaline phosphatase (AKP) showed mixed responses. Muscle texture properties such as chewiness and adhesiveness were significantly altered across treatments. Gut villi remained structurally intact in all groups, and liver histology appeared normal. No significant differences were found in muscle amino acid or fatty acid profiles. Gut microbiota analysis revealed shifts in microbial composition, with increased abundance of Clostridia and Escherichia and functional enrichment in metabolic pathways at higher substitution levels. Interspecies network analysis indicated potential cooperation among beneficial microbes through metabolite exchange. It is concluded that 50% BSFLM substitution optimizes growth performance, muscle quality, and antioxidant capacity, while modulating gut microbiota, indicating its promise as a sustainable FM alternative and functional ingredient in aquafeeds. Full article

Background/Objectives: Varicellovirus bovinealpha1 and Varicellovirus bovinealpha5 (BoAHV-1 and BoAHV-5), respectively, are widely distributed pathogens that cause distinct clinical conditions in cattle including infectious bovine rhinotracheitis, infectious pustular vulvovaginitis/balanoposthitis, and meningoencephalitis. Due to the establishment of viral latency, controlling these infections is challenging, and vaccination remains the most effective strategy. In this study, vaccine candidates targeting both BoAHV-1 and BoAHV-5 were developed. Methods: A synthetic gene encoding immunodominant epitopes from the gB and gD proteins and tegument phosphoprotein of BoAHV-1 and BoAHV-5 was designed to produce a multi-epitope recombinant antigen, expressed both in a prokaryotic system (RecBoAHV) and by a modified vaccinia Ankara (MVA-BoAHV) viral vector. The binding affinity of MHC-I to bovine leukocyte antigens (BoLA) was predicted using the NetMHCpan tool (version 4.1). The immunogenicity of the vaccine candidates was evaluated in rabbit and mouse models, using prime-boost immunization protocols. Sera from bovines naturally infected with BoAHV-1 and/or BoAHV-5 were used to evaluate the chimeric protein antigenicity. Immune responses were assessed by indirect ELISA and Western blot. Results: The recombinant multi-epitope protein was effectively recognized by IgG and IgM antibodies in sera from cattle naturally infected with BoAHV-1 or BoAHV-5, confirming the antigenic specificity. Both RecBoAHV and MVA-RecBoAHV induced strong and specific humoral immune responses in rabbits following a homologous prime-boost regimen. In mice, both homologous and heterologous prime-boost protocols revealed robust immunogenicity, particularly after the second booster dose. Conclusions: These findings highlight the immunogenic potential of the RecBoAHV multi-epitope vaccine candidates for controlling BoAHV-1 and BoAHV-5 infections. Further characterization of these vaccine formulations is currently underway in bovine, the target specie. Full article

Cancer continues to pose a major global health burden, with conventional therapeutic modalities such as surgical resection, chemotherapy, radiotherapy, and immunotherapy often hindered by limited tumor specificity, substantial systemic toxicity, and the emergence of multidrug resistance. The rapid advancement of nanotechnology has introduced functionalized nanomaterials as innovative tools in the realm of precision oncology. These nanoplatforms possess desirable physicochemical properties, including tunable particle size, favorable biocompatibility, and programmable surface chemistry, which collectively enable enhanced tumor targeting and reduced off-target effects. This review systematically examines recent developments in the application of nanomaterials for cancer therapy, with a focus on several representative nanocarrier systems. These include lipid-based formulations, synthetic polymeric nanoparticles, inorganic nanostructures composed of metallic or non-metallic elements, and carbon-based nanomaterials. In addition, the article outlines key strategies for functionalization, such as ligand-mediated targeting, stimulus-responsive drug release mechanisms, and biomimetic surface engineering to improve in vivo stability and immune evasion. These multifunctional nanocarriers have demonstrated significant potential across a range of therapeutic applications, including targeted drug delivery, photothermal therapy, photodynamic therapy, and cancer immunotherapy. When integrated into combinatorial treatment regimens, they have exhibited synergistic therapeutic effects, contributing to improved efficacy by overcoming tumor heterogeneity and resistance mechanisms. A growing body of preclinical evidence supports their ability to suppress tumor progression, minimize systemic toxicity, and enhance antitumor immune responses. This review further explores the design principles of multifunctional nanoplatforms and their comprehensive application in combination therapies, highlighting their preclinical efficacy. In addition, it critically examines major challenges impeding the clinical translation of nanomedicine. By identifying these obstacles, the review provides a valuable roadmap to guide future research and development. Overall, this work serves as an important reference for researchers, clinicians, and regulatory bodies aiming to advance the safe, effective, and personalized application of nanotechnology in cancer treatment. Full article

Background: The AFFINITY trial (NCT05890872) is a prospective, non-randomized, open-label, single-arm study evaluating the safety, immunological impact, and preliminary efficacy of Aliya pulsed electric field ablation in patients with solid tumors. Thirty-one patients were enrolled; thirty received lung lesion ablation prior to continuation on standard-of-care treatment. This manuscript reports six-month local control outcomes and immunological response characteristics. Radiological outcomes were assessed using a modified RECIST 1.1, and immunological impact was evaluated via changes in peripheral blood immunocyte populations and detection of immunoglobulins (Ig) to tumor-associated antigens in serum post-ablation. Methods: Twenty-eight patients underwent radiological assessment of ablated lesions at approximately 1-, 3-, and 6-month post-ablation to evaluate local control. Peripheral blood was collected for immune monitoring using flow cytometry and to detect IgG responses to biopsy-specific and tumor-associated antigens. Results: At 6 months, two cohorts emerged: 12 received ablation only, and 16 received ablation plus systemic and/or focal therapies (radiotherapy or second ablation). In the ablation-only group, imaging showed local control in all ablated lesions (8/12 SD, 4/12 PR), suggesting local efficacy without systemic therapy in those patients. Immunophenotyping showed dynamic changes in circulating immune cells, including T and B cell activation. A subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response. Conclusions: This analysis provides preliminary evidence that this form of ablation may promote local tumor control and modulate systemic immune function. These findings support the immunogenic potential of this specialized energy and warrant further investigation. Extended 12-month data for the full cohort will be reported in a future manuscript. Full article