Search Results (1,936)

Bovine Respiratory Disease (BRD) is a leading cause of economic losses in the global cattle industry, with Mannheimia haemolytica and Pasteurella multocida as the primary bacterial pathogens. This review provides a comprehensive overview of vaccine research progress against these two pathogens, covering inactivated vaccines, live attenuated vaccines, subunit vaccines, DNA vaccines, recombinant vector vaccines, and outer membrane vesicle vaccines. Their immune mechanisms, protective efficacy, adjuvant applications, and field performance are discussed. Key challenges include maternal antibody interference, the increasing prevalence of M. haemolytica serotype A6 that evades current commercial vaccines, and the serotype diversity of P. multocida. Future vaccine development should focus on overcoming maternal antibody interference, enhancing cross-serotype protection, optimizing mucosal adjuvants and delivery systems, and developing multivalent vaccines covering major epidemic serotypes. Integrating reverse vaccinology, multi-epitope vaccine design, and nanotechnology holds promise for safer, more effective, and broader-spectrum next-generation vaccines. Full article

Alternaria alternata, a major postharvest pathogen of grapes and goji berries, causes black spot disease and produces Alternaria toxins that threaten food safety and human health. Carbon quantum dots (CQDs) are emerging promising nanophotosensitizers for photodynamic antimicrobial therapy (PDT), yet their efficacy against A. alternata remains unclear. This study systematically investigated the antifungal effect of CDs-PDT against A. alternata and revealed the possible mechanisms at cellular and physiological-biochemical levels. The inhibitory effect of CDs-PDT against A. alternata exhibited a clear concentration-dependent characteristic, achieving a 100% inhibition rate at 48 h; meanwhile, mycelial dry and fresh weights were reduced by 98.4% and 94.7%, respectively. The possible inhibitory mechanism of CDs-PDT against A. alternata was revealed that it damages cell wall and membrane integrity, evidenced by scanning electron microscope (SEM) observation, propidium iodide (PI) staining, increased malondialdehyde (MDA) content, and altered lactate dehydrogenase (LDH) and alkaline phosphatase (AKP) activities. Intracellular reactive oxygen species (ROS) accumulation was confirmed via 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), 3,3′-diaminobenzidine (DAB), and nitroblue tetrazolium (NBT) staining, accompanied by initial upregulation followed by collapse of antioxidant defenses, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glutathione (GSH). CDs-PDT further impaired energy metabolism, reflected by decreased adenosine triphosphate (ATP) and acetyl-CoA content. Additionally, CDs-PDT can also increase A. alternata’s sensitivity to exogenous stress. These results indicate that CDs-PDT is an effective strategy for controlling A. alternata diseases and provide mechanistic insights into future nanophotosensitizer-based antifungal research in postharvest grape and goji berries management. Full article

T helper cells (Th) are central to mucosal IgA induction and key targets for modulation by vaccine adjuvants. To improve understanding of cellular mechanisms underlying mucosal vaccine-induced immunity, we analyzed antigen-specific peripheral blood Th responses elicited by the oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, administered with or without the double mutant heat-labile toxin (dmLT) adjuvant. ETVAX, consisting of inactivated E. coli overexpressing colonization factors CFA/I, CS3, CS5, and CS6 with a heat-labile toxin B-subunit toxoid, was given orally in two doses to adult volunteers, either alone or with 10 or 25 µg dmLT. Antigen-specific Th-associated cytokine responses were assessed in stimulated peripheral blood mononuclear cells isolated from 15 to 18 individuals/group using ELISA and electrochemiluminescence assays. ETVAX predominantly induced Th1 (IFN-γ) and Th17 (IL-17A) responses, with minimal Th2-associated cytokines. Responses were markedly reduced after CD4+ T-cell depletion, supporting a Th cell origin. The strongest responses targeted LTB and CS3, with IFN-γ responses detected in 60–80% and IL-17A in 40–60% across all vaccinees. Responses to CFA/I, CS5 and CS6 were generally weaker. Exploratory comparisons suggested broader IFN-γ responses and more consistent IFN-γ and IL-17A responses to lower-dose antigens, particularly CS6, in recipients receiving vaccine plus 10 µg dmLT. These trends paralleled IgA antibody-secreting cell response patterns, with significantly enhanced IgA responses to CS6 in the vaccine plus 10 µg dmLT group. In conclusion, ETVAX induces antigen-specific Th1- and Th17-type responses in peripheral blood, supporting a role for cellular immunity in mucosal responses to oral ETEC vaccines. Full article

Vaccine responses differ substantially among individuals and across populations. Although factors such as age, genetics, and vaccine type are recognized contributors, they do not fully explain this heterogeneity. Emerging evidence suggests that the human microbiota, particularly the gut microbiota, may modulate immune responses to vaccination and represents a potentially modifiable component of immunity. This review integrates data from human studies, microbiota-targeted clinical trials, and experiments using germ-free and humanized models to clarify the mechanisms underlying microbiota–immune system interactions during vaccination. Identified mechanisms include pattern-recognition receptor signaling, modulation of innate immune activation, regulation of germinal-center responses, maintenance of mucosal barrier integrity, and the influence of microbial metabolites on T and B lymphocytes. The relevance of these pathways varies by age, developmental stage, and vaccine platform, including live-attenuated, inactivated, subunit, viral-vector, and mRNA vaccines. Additional factors such as diet, antibiotic exposure, infections, medications, and environmental or social determinants also affect both the microbiota and vaccine outcomes. Current research explores approaches to improve vaccine potency through microbiota modulation using probiotics, prebiotics, synbiotics, postbiotics, and engineered microbes, though clinical results remain inconsistent. A greater understanding of microbiota–vaccine interactions may enable personalized immunization strategies; however, further research is required to establish causality and identify actionable microbial targets. Longitudinal studies using multi-omics, advanced cellular analyses, robust clinical trials, and in silico modeling are essential to determine whether microbiome-based interventions can improve vaccine efficacy and durability. Full article

Background/Objectives: Toxoplasma gondii is a globally distributed parasite responsible for significant morbidity in both humans and animals. VXN-Toxo, is an intranasal vaccine based on maltodextrin nanoparticles formulated with inactivated T. gondii parasites. A vaccination campaign conducted worldwide in zoological parks demonstrated high efficacy across multiple species and geographical regions. These findings suggest that VXN-Toxo may induce broad cross-reactive immunity against T. gondii strains circulating in various regions. Methods: To further characterize the immune mechanisms, we evaluated the cellular immune response induced by VXN-Toxo in C57BL/6 mice. Following vaccination, splenocytes were stimulated with antigens derived from multiple T. gondii strains, representing the major haplogroups (types I, II, III, and atypical strains). Results: ELISPOT analysis demonstrated that VXN-Toxo induced strong antigen-specific T cell responses, characterized by robust IFN-γ and IL-17 production upon stimulation with both homologous and heterologous antigens. Flow cytometry analysis further revealed the activation of both CD4⁺ and CD8⁺ T cells, with the notable presence of IFN-γ–producing CD8⁺ central and effector memory cells and CD4⁺ effector memory T cells. Conclusions: Altogether, these results indicate that VXN-Toxo induces a broad, T cell–mediated immune response with cross-reactive properties and highlight its potential as a promising vaccine candidate for both human and veterinary applications. Full article

Pre-treatment before drying is a crucial phase in food processing. This review highlights key traditional and innovative pre-treatment methods, focusing on their mechanisms of action at the cellular and tissue levels. This discourse examines innovative technologies with significant promise across various applications, as well as widely recognised methodologies. These include cold plasma, ultrasonication, pulsed electric fields, high-pressure processing, UV-C light, pulsed light, and coating techniques. It addresses biological components that act as barriers to mass transfer, thereby significantly influencing the efficiency of moisture evaporation. Understanding these interactions is crucial for optimising drying processes and enhancing the quality of dried food. Key pre-treatment parameters that affect outcomes are analysed and must be tailored to the specific characteristics of biological materials, which often require individualised adjustments. Each method is evaluated against goals like accelerated drying, microbiological purity, enzyme inactivation, and preservation of active components, emphasising the need for a targeted optimisation approach. The classification of biological materials into distinct categories has been proposed based on their structural and integumentary characteristics. The research outlines effective methodologies for each material type and pre-treatment purpose. This analysis also incorporates an economic perspective, considering the initial investment and operational costs of implementing the proposed methods. Full article

Insects lack adaptive immunity and rely exclusively on innate immune system for pathogen defense. However, the specific role of BmToll9-2, a key Toll receptor in the silkworm (Bombyx mori), in mediating immune responses, particularly against bacterial challenges in the larval fat body, remains incompletely understood. To address this gap, this study employed a combination of molecular approaches, including RNA interference (RNAi) targeting BmToll9-2, bacterial challenges with heat-inactivated Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), and quantitative real-time PCR (qPCR) to assess the transcriptional changes of BmToll9-2 and immune-related genes in the fat body, a key immune tissue. Quantitative analysis showed that after BmToll9-2 RNAi, bacterial challenges significantly upregulated BmToll9-2 expression in the fat body at 12 h post-challenge, whereas BmToll9-2 silencing alone notably downregulated most downstream signaling genes of the Toll pathway by 53.07–83.14%, as well as 11 immune effector genes, including antimicrobial peptide genes, by 64.48–93.40%. Importantly, feeding bacteria post-RNAi reversed these downregulations: E. coli induced a stronger upregulation of both signaling and effector genes compared to S. aureus. This study provides transcriptional evidence that BmToll9-2 may act as a positive regulator of the Toll pathway signaling and antimicrobial peptides in silkworm larval fat body, facilitating robust and rapid immune signaling. This study deepens our understanding of Lepidopteran innate immunity by elucidating key molecular mechanisms, thereby providing a solid foundation for refining RNAi-based pest control strategies. Full article

The performance of coatings, corrosion barriers, photocatalysts, and tribological materials is greatly influenced by in situ surface properties, requiring highly sensitive and reproducible operando surface characterization methods. We previously developed a temperature-programmed photoelectron emission (TPPE) method to clarify electron transfer behavior on light-irradiated metal surfaces. TPPE is sensitive to surface temperature and prior chemical exposure, which affect the total photoemitted electron count (N_T), the photothreshold, and the activation energy derived from Arrhenius plots of N_T obtained during heating–cooling cycles. This study examines the reproducibility of TPPE data and the TPPE mechanisms for Cu₂O/Cu surfaces subjected to mechanical abrasion, cleaning, plasma treatment, and subsequent immersion in organic liquids. The resulting Arrhenius plots reveal both positive and negative activation energies, depending on the treatment conditions. Negative activation energies during cooling are associated with photoredox-mediated emission. TPPE is attributed to oxygen vacancies within the Cu₂O surface layer, which is interfaced with metallic Cu, serving as a direct probe of these vacancy-related states. The TPPE characteristics (N_T intensity and activation energy) following exposure to various polar and nonpolar organic molecules (e.g., acetone, toluene, hexane, and ethanol) correlate with the electronic properties of these vacancies, consistent with previous observations for ambient air, alcohol, and water vapor exposure. Under illumination, Cu₂O vacancy states enhance photocarrier extraction (electrons and holes) and accelerate surface redox reactions within adsorbed thin films, thereby improving photocatalytic performance. Notably, the solvent’s reciprocal dielectric constant significantly influences TPPE, indicative of electrostatic surface–solvent interactions. Finally, the TPPE mechanism is discussed in the context of antiviral inactivation at the metallic copper–environment interface. Full article

Alternariol (AOH) is a mycotoxin produced mainly by Alternaria alternata on fruits including tomatoes and strawberries as well as cereal grains including wheat and soybeans. In this study, we isolated Rhodotorula taiwanensis (R. taiwanensis) P1 from a pear and investigated the effects of incubation time and temperature on AOH reduction rates and the mechanism involved in AOH detoxification by the yeast strain. The yeast strain showed a 76.10% AOH reduction rate from the initial level (1 μg/mL) at 30 °C after 48 h of incubation. The yeast cell-free filtrate from the yeast culture did not increase the AOH reduction rate relative to the control without cell-free filtrate after 48 h. In addition, the AOH reduction rate by heat-inactivated yeast cells (74.57%) was similar to that by viable yeast cells (76.33%). The AOH detoxification test using the yeast cell wall fraction showed that AOH binds to its cell walls and that approximately 1/3 of the AOH bound onto the cell walls was extracted from them. These data strongly suggest that the AOH detoxification by the yeast strain was not due to degradation by either intracellular enzymes or extracellular enzymes of the yeast culture but was due to binding to yeast cell walls. The use of spheroplasts, in which cell walls are deficient, confirmed that AOH detoxification occurred by binding onto the cell walls of R. taiwanensis. Our data demonstrated that R. taiwanensis P1 was able to remove AOH by adsorption onto its cell walls. These results could help in the development of potential strategies to effectively mitigate AOH contamination of food. Full article

Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively map the neutralization escape landscape of the Omicron variant JN.1 and its descendant lineage XEC, under immune pressure from individuals who experienced Omicron breakthrough infections following three doses of inactivated vaccines. A neutralization escape map for the single amino acid substitutions in the RBD of JN.1 or XEC was generated, and the escape efficiency of each mutation was determined. The results show that RBD escape mutations are hierarchically organized: low-intensity signals are widespread, whereas high-intensity escape is confined to a few key sites. These escape mutations are not confined solely to the receptor-binding motif (RBM) but are broadly distributed across the entire RBD. Many escape sites could accommodate multiple amino acid substitutions. Integration of DMS data with genomic surveillance of circulating variants from 2024 to 2025 revealed significant overlap between experimentally identified escape sites and mutations observed in natural isolates. This overlap increased substantially in 2025, with site concordance rising from 27.17% and 26.81% to 45.09% and 47.10% for JN.1 and XEC, respectively. The natural prevalence of these escape mutations is further shaped by factors such as receptor-binding affinity, protein stability, and epistatic interactions. Overall, our findings suggest that SARS-CoV-2 antigenic evolution follows the pattern of multiple pathways within a constrained space, providing new insights into the adaptive mechanisms of Omicron-derived variants under hybrid immune pressure. Full article

Enzymatic browning, primarily catalyzed by polyphenol oxidase (PPO), is a major cause of postharvest losses and quality degradation in fresh-cut fruit and vegetable processing. To control this browning, conventional methods such as sulfite treatment and thermal inactivation have been widely used, yet they increasingly face safety, sensory, and regulatory concerns. Because of this, more attention has been directed toward natural PPO inhibitors from agro-industrial by-products as safer, value-added alternatives. However, current knowledge of PPO inhibition mechanisms and rational inhibitor discovery remains fragmented across the literature, limiting the development of effective and sustainable anti-browning approaches. To address this gap, this review presents an integrated framework that covers (i) the structural and kinetic basis of PPO catalysis at the binuclear copper active site; (ii) the mechanistic classification of reversible and irreversible inhibitors, together with kinetic characterization using IC₅₀, K_i, and nonlinear regression approaches; (iii) computational screening strategies, including molecular docking and molecular dynamics simulations as modern tools for predicting enzyme–inhibitor interactions and prioritizing candidate inhibitors; and (iv) the potential of agro-industrial by-products as renewable sources of natural PPO inhibitors for extending the shelf life of fresh-cut produce. Through this framework, this review provides an integrated perspective to support the rational evaluation and future development of effective, sustainable PPO inhibitors for food processing. Full article

The combination of ultraviolet (UV) and periodate (PI) is a promising advanced oxidation process. We investigated the inactivation of a typical harmful algae species, Heterosigma akashiwo by UV/PI treatment and explored the inactivation mechanism at the cellular and molecular levels. The inactivation efficacy of H. akashiwo by UV/PI and UV treatment alone was 9.21-ln and 1.23-ln within 37.5 min, respectively. Hydroxyl radicals (•OH) and singlet oxygen (¹O₂) contributed to H. akashiwo inactivation in the UV/PI system. Obvious destruction of the cell structure observed by transmission electron microscopy and the increases in extracellular DNA levels indicated membrane damage by the reactive species. The activity changes in the antioxidant enzymes and the decreases in ATP contents of H. akashiwo after UV/PI treatment were both more severe than that after UV treatment. The results indicated that the antioxidant defense system and the mitochondria of H. akashiwo cells were disrupted. The photosynthesis was also affected as both of the chlorophyll-a content and the maximum dark-adapted photochemical efficiency (Fv/Fm) of H. akashiwo decreased obviously. The transcriptomics analysis proved that UV/PI treatment caused abnormal energy metabolism and cell function. Moreover, the down regulation of gene expression enriched in the phagocytic pathway indicated that the cell was severely damaged and inactivated under oxidative stress. Full article

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes. Full article

Photocatalytic antibacterial coatings have emerged as a promising antibiotic-free strategy for combating healthcare-associated infections, biofilm formation, marine biofouling, and environmental microbial contamination. Unlike conventional antimicrobial approaches, photocatalytic systems continuously generate reactive oxygen species (ROS) under light irradiation, enabling broad-spectrum antimicrobial activity while minimizing the risk of antimicrobial resistance. This review systematically summarizes the fundamental mechanisms underlying photocatalytic antibacterial activity, including photogenerated charge-carrier dynamics, ROS generation pathways, and microbial inactivation processes. We further highlight recent advances in photocatalyst design, spanning conventional semiconductor photocatalysts, heterojunction engineering, cocatalyst modification, and two-dimensional material-assisted strategies for enhanced photocatalytic performance. Crucially, particular emphasis is placed on coating architectures and interfacial regulation, including encompassing fabrication methodologies, coating–substrate adhesion, internal heterointerface design, and coating–microorganism interactions, which dictate long-term durability and antibacterial efficacy. Finally, we explore the diverse applications of these coatings in medical devices, environmental remediation, and marine antifouling, while identifying current bottlenecks and future research trajectories toward developing durable, highly efficient, and clinically translatable antimicrobial surface technologies. Full article

The treatment of gastric ulcers based on antisecretory drugs is often associated with side effects and high recurrence rates, reinforcing the need for new therapeutic alternatives. Medicinal chemistry guided by natural prototypes represents a productive strategy in this context. The antiulcer potential of 2-phenylquinoline (2-PQ), an alkaloid from Conchocarpus longifolius (A.St.-Hil.) Kallunki & Pirani (syn. Galipea longiflora Krause), has been previously reported by our research group. In the present work, four 2-PQ derivatives were synthesized—2,4-diphenylquinoline (1), 2-(4-methoxyphenyl) quinoline (2), 2-phenylquinolin-4-ol (3), and 4-methoxy-2-phenylquinoline (4)—and evaluated for gastroprotective activity in the HCl/ethanol-induced gastric ulcer model in mice. The quinoline derivatives were prepared mainly by trifluoroacetic acid-catalyzed condensations of aminated benzaldehyde or benzophenone precursors with the corresponding ketones under reflux at 100 °C, affording yields of 68–94%. Compound 3 was synthesized via a two-step sequence involving the acylation of 2-aminobenzophenone followed by base-induced cyclization, providing an 85% yield. Compound 4 was obtained by O-methylation of compound 3 using iodomethane (MeI) and potassium carbonate (K₂CO₃) in dimethylformamide (DMF), affording a 95% yield. So, this study provides the first comparative analysis linking structural modifications to gastroprotective activity in synthetic quinoline derivatives inspired by 2-phenylquinoline, a natural alkaloid previously shown to exert gastroprotective effects. Carbenoxolone (200 mg/kg, p.o., positive control) inhibited gastric lesion formation by 94.1%. The synthetic quinoline derivatives also showed significant gastroprotective activity after oral administration (30 mg/kg), reducing ulcer area by 72.4% (compound 1), 76.1% (compound 2), 49.1% (compound 3), and 66.1% (compound 4). Compounds 2, 3, and 4 further retained efficacy following intraperitoneal administration (3 mg/kg), whereas compound 1 was inactivated by this route. Overall, compound 4 exhibited the greatest efficacy, significantly reducing the gastric lesion area, decreasing lipid hydroperoxide (LOOH) and tumor necrosis factor-alpha (TNF-α) levels, and increasing glutathione (GSH) content in ulcerated gastric tissue. These findings suggest that its gastroprotective effects are mediated by antioxidant and anti-inflammatory mechanisms, identifying compound 4 as the most promising candidate for the prevention and treatment of peptic ulcers. Its promising pharmacological profile warrants further investigation to elucidate its molecular mechanisms of action, assess its safety and efficacy in additional preclinical studies, and explore its potential for future therapeutic development. Full article