Search Results (45)

The use of agricultural by-products as feed is essential for sustainable animal husbandry. This study assessed the effects of substituting whole-plant corn silage with a mixed silage of cotton stalks and grape pomace on growth, serum biochemistry, and jejunal metabolomics in Suffolk rams. In this experiment, 135 rams (6-mo, 30.55 kg BW) were allocated to 0%, 50%, or 100% replacement (CG, EG50, EG100) and fed for 120 d after a 15-d adaptation. Compared with the CG, average daily gain improved by 27.3% and 17.5%, and feed conversion improved by 30.8% and 15.4% in EG50 and EG100 (p < 0.01). Compared with CG, the levels of BUN, TNF-α and IL-1β in serum of EG50 and EG100 were significantly decreased. The levels of IgG, IgM, IL-4, antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.05). Subsequently, the slaughter performance and jejunal content metabolome of CG and EG50 were further detected and analyzed. The results indicated that the live weight, eye area and muscle crude protein content of EG50 were extremely significantly higher than those of CG (p < 0.01). In jejunal contents, 31 differential metabolites (EG50 vs. CG) were enriched in ABC transporters, branched-chain amino acid biosynthesis, mineral absorption, purine and biotin metabolism, and glucagon signaling. In conclusion, substituting corn silage with the mixed silage promotes growth, improves antioxidant and immune status, reduces serum urea nitrogen, enhances muscle protein deposition (EG50), modulates intestinal nitrogen, purine, lipid, and carbohydrate metabolism (EG50), and supports sustainable meat sheep production. Full article

Background: Immune-mediated hypophysitis comprises a heterogeneous group of inflammatory pituitary disorders, including primary lymphocytic hypophysitis, immune checkpoint inhibitor (ICI)-induced hypophysitis, IgG4-related hypophysitis, and paraneoplastic autoimmune hypophysitis. Although these entities share immune-mediated mechanisms, they differ substantially in clinical presentation, imaging features, and therapeutic implications. Methods: This narrative review synthesizes current evidence on the pathophysiology, clinical manifestations, radiological characteristics, diagnostic approach, and management of immune-mediated hypophysitis, with particular emphasis on etiological heterogeneity. Results: Hypopituitarism—particularly ACTH deficiency—is the most frequent and clinically relevant manifestation, as secondary adrenal insufficiency may be life-threatening if not promptly recognized and treated. It is often accompanied by headache, arginine vasopressin deficiency, or mass effect depending on the subtype. Magnetic resonance imaging typically shows symmetrical pituitary enlargement and stalk thickening in inflammatory forms, although findings vary according to etiology and may be minimal in certain subtypes such as PD-1/PD-L1 inhibitor-associated hypophysitis. Distinct clinical phenotypes are observed across subtypes, particularly in ICI-induced hypophysitis and IgG4-related disease. Diagnosis relies on the integration of endocrine, radiological, and clinical features, supported by clinicoradiological scoring systems in selected cases. Management is primarily based on prompt hormone replacement, with selective use of glucocorticoids or immunosuppressive therapies depending on disease severity and underlying etiology. Conclusions: Immune-mediated hypophysitis represents a clinically relevant and increasingly recognized spectrum of disorders requiring a multidisciplinary and etiology-specific approach. Early recognition is essential to prevent life-threatening endocrine complications. Advances in the understanding of immunopathogenic mechanisms and the identification of reliable biomarkers may enable earlier diagnosis and more personalized therapeutic strategies. Full article

The increasing global demand for animal-source protein underscores the importance of sustainable livestock systems, including commercial rabbit production. Rabbits are valued for their short production cycle, high prolificacy, efficient feed utilization, and favorable meat quality. In parallel, agro-industrial by-products are being explored as functional feed ingredients to improve efficiency and reduce environmental impact. Grape by-products (GBPs), including pomace, seeds, stalks, and derived extracts, are rich in polyphenols, dietary fiber, and lipid bioactives with potential physiological benefits. This scoping review synthesizes current evidence regarding the effects of GBPs on rabbit health, growth performance, nutrient digestibility, reproductive function, and meat quality. Available studies indicate that moderate dietary inclusion can enhance antioxidant status, support immune function, modulate gut fermentation, and improve meat oxidative stability without consistently compromising growth performance when appropriately formulated. Benefits appear particularly evident under environmental stress conditions. However, outcomes vary according to inclusion level, processing method, and physiological stage, and excessive inclusion may impair nutrient utilization due to fiber and tannin content. Overall, this synthesis identifies functional mechanisms, practical feeding considerations, and key knowledge gaps to inform evidence-based application of GBPs in sustainable rabbit nutrition. 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

This study investigates the efficacy of fermented corn straw as a viable corn substitute in rabbit diets, evaluating its impact on growth performance, intestinal health, cecal microbiota, and metabolite profiles to determine its potential for addressing corn shortages in animal husbandry. Over 35 days, 120 New Zealand rabbits were assigned to four treatments: (i) 12% corn (C100), (ii) 6% corn + 6% fermented straw (FS50), (iii) 12% fermented straw (FS100), and (iv) 6% corn + 6% dry straw (DS50). Fermented straw enhanced the rabbits’ average daily feed intake (ADI) and average daily gain (ADG) and elevated cecal cellulase activity. It also downregulated TLR4 in the jejunum mucosa, upregulated MUC2 in the ileum mucosa, strengthened the intestinal barrier, and reduced the diarrhea index and incidence in weaned rabbits. Specific microbial families influenced amino acid and phospholipid concentrations, altering the cecal metabolic environment. In summary, replacing corn with fermented corn straw in rabbit diets significantly boosts ADG and ADI, potentially lowers the feed-to-gain ratio, and enhances cecal microbiota and metabolite profiles without compromising growth performance. Full article

This study explored the impact of licorice stem and leaf forage in the diet of meat sheep on their growth performance, physiological parameters, immunity, and gut microbiota. Conducted in the Hotan region of Xinjiang, the experiment involved 40 healthy local Hotan sheep (5–6 months old) that were randomly assigned to four groups, with both corn stalks and corn grain partially substituted at varying levels (30%, 40%, and 50%) by licorice stems and leaves for 80 days. Daily feed intake and refusal were recorded to assess feeding behavior and efficiency, while body weight was measured every 20 days to monitor growth performance. On day 80, blood samples were collected via venipuncture for biochemical and immune function analysis, followed by slaughter to obtain meat samples for quality assessment. Results showed that dietary licorice supplementation significantly improved growth performance. Sheep in the 40% replacement group had the highest final body weight and average daily gain (p < 0.05), indicating better feed efficiency. These findings suggest that replacing corn stalks and grain with licorice stems and leaves at a 40% ratio can significantly improve growth performance. Biochemical results showed improved protein metabolism and lipid profiles, with increased TP and ALB and decreased TC and TG levels. Immune indicators, including IgG, IgM, IgA, and IL-6, were also elevated in licorice-fed groups. In summary, licorice stems and leaves demonstrated clear nutritional and immunological benefits, especially at the 40% inclusion level. Gut microbiota analysis showed that licorice stems and leaves increased the relative abundance of Firmicutes while reducing Bacteroidota. At the genus level, UCG_005 and Bacteroides increased with higher licorice concentrations, whereas Treponema decreased. Pearson correlation analysis indicated that UCG_005 was positively correlated with TP, ALB, IgM, and IL-6 and negatively correlated with TG and TNF-α. These findings suggest that using licorice stems and leaves as a replacement for both corn stalks and corn grain modulates gut microbiota composition and is closely associated with immune and biochemical responses in sheep. Full article

Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part of pandemic preparedness efforts necessary. Although NiV is a zoonotic pathogen with high case fatality, there is still no licensed vaccine. Methods: Herein, NiV attachment glycoprotein G (NiV-G), which is crucial to host cell receptor binding, was used to develop Nipah epitope-based peptide vaccines. A total of 39 B- and T-cell epitopes of NiV-G were shortlisted for peptide synthesis and evaluation using in silico analysis. Results: The in vitro antigenicity evaluation of the peptide candidates showed eight synthesized peptides (G7, stalk-domain epitopes) with relatively high binding to NiV-G antibody-positive serum (A_450nm: 1.39–3.78). Moreover, nine-mer (9-mer) peptides were found to be less reactive than their longer peptide counterparts (15–30 aa, G7-1, and G7-4), but 9-mer activity was enhanced with cyclization (NPLPFREYK, A_450nm: 2.66) and C-terminal amidation modification (NPLPFREYK-NH2, A_450nm: 1.39). Subsequently, in vivo validation in immunized mice revealed the immunogenicity potential of the G7-1 peptide vaccine (30 aa, NENVNEKCKFTLPPLKIHECNISCPNPLPF) to elicit a strong antigen-specific antibody response against their homologous peptide antigen (I.V., A_450nm: 1.48 ± 0.78; I.M., A_450nm: 1.66 ± 0.66). However, antibody binding to recombinant NiV-G protein remained low, suggesting limited recognition to the native antigen. Conclusions: This study focused on the preliminary screening and validation of peptide vaccines using single formulations with minimal modifications in the peptide candidates. Our findings collectively show the immunogenic potential of the NiV-G stalk-based epitope peptide vaccine as a novel therapeutic for NiV and underscores the need for strategic design, delivery, and formulation optimization to enhance its protective efficacy and translational application. Full article

Fusarium verticillioides can systematically infect maize through seeds, triggering stalk rot and ear rot at a later stage, thus resulting in yield loss and quality decline. Seeds carrying F. verticillioides are unsuitable for storage and pose a serious threat to human and animal health due to the toxins released by the fungus. Previously, the candidate gene ZmC2GnT was identified, using linkage and association analysis, as potentially implicated in maize seed resistance to F. verticillioides; however, its disease resistance mechanism remained unknown. Our current study revealed that ZmC2GnT codes an N-acetylglucosaminyltransferase, using sequence structure and evolutionary analysis. The candidate gene association analysis revealed multiple SNPs located in the UTRs and introns of ZmC2GnT. Cloning and comparing ZmC2GnT showed variations in the promoter and CDS of resistant and susceptible materials. The promoter of ZmC2GnT in the resistant parent contains one extra cis-element ABRE associated with the ABA signal, compared to the susceptible parent. Moreover, the amino acid sequence of ZmC2GnT in the resistant parent matches that of B73, but the susceptible parent contains ten amino acid alterations. The resistant material BT-1 and the susceptible material N6 were used as parents to observe the expression level of the ZmC2GnT. The results revealed that the expression of ZmC2GnT in disease-resistant maize seeds was significantly up-regulated after infection with F. verticillioides. After treatment with F. verticillioides or ABA, the expression activity of the ZmC2GnT promoter increased significantly in the resistant material, but no discernible difference was detected in the susceptible material. When ZmC2GnT from resistant and susceptible materials was overexpressed in Arabidopsis thaliana, the seeds’ resistance to F. verticillioides increased, although there was no significant difference between the two types of overexpressed plants. Our study revealed that ZmC2GnT could participate in the immune process of plants against pathogenic fungus. ZmC2GnT plays a significant role in regulating the disease-resistance process of maize seeds, laying the foundation for future research into the regulatory mechanism and the development of new disease-resistant maize varieties. Full article

Influenza has been a global health concern for the past century. Current seasonal influenza vaccines primarily elicit an antibody response that targets the immunodominant head domain of the viral glycoprotein hemagglutinin (HA), which consistently mutates due to selective pressure. To circumvent this problem, we introduce a “tethered antigenic suppression” strategy to shield the HA head domain and refocus the immune response towards the conserved but immunosubdominant stalk domain of HA. Specifically, we tethered an antibody fragment (Fab) that recognizes the Sb antigenic site in the HA head domain to the HA protein with a linker. We immunized separate groups of female mice with the Fab-tethered HA or regular HA and characterized the elicited antibody response. We demonstrate that shielding the HA head domain with a tethered Fab suppresses the antibody titers towards all five key antigenic sites in the HA head domain while eliciting a robust anti-stalk antibody response. Our work highlights the potential of tethered antigenic suppression as a strategy to refocus the antibody response towards conserved epitopes on protein antigens. Full article

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses. Glycan-free S2 peptides were synthesized and attached to SARS-CoV-2 virus-like particles (VLPs) lacking the S antigen. Humoral and cellular immune responses were analyzed after the second booster immunization in BALB/c mice. Enzyme-linked immunosorbent assay revealed the reactivity of sera against SARS-CoV-2 variants, and pseudovirus neutralization assay confirmed neutralizing activities. Among the S2 peptide-conjugated VLPs, the S2.3 (N1135-K1157) and S2.5 (A1174-L1193) peptide–VLP conjugates effectively induced S2-specific serum immunoglobulins. These antisera showed high reactivity against SARS-CoV-2 variant S proteins and effectively inhibited pseudoviral infections. S2 peptide-conjugated VLPs activated SARS-CoV-2 VLP-specific T-cells. The SARS-CoV-2 vaccine incorporating conserved S2 peptides and CoV-2 VLPs shows promise as a universal vaccine capable of generating neutralizing antibodies and T-cell responses against SARS-CoV-2 variants. Full article

Sugarcane white leaf (SCWL) disease, caused by Candidatus Phytoplasma sacchari, results in the most damage to sugarcane plantations. Some SCWL canes can grow unnoticed through the maturation phase, subsequently resulting in an overall low sugar yield, or they can be used accidentally as seed canes. In this work, 12-month-old SCWL and asymptomatic canes growing in the same field were investigated. An abundance of phytoplasma in SCWL canes affected growth and sugar content as well as alterations of transcriptomic profiles corresponding to several pathways that responded to the infection. Suppression of photosynthesis, porphyrin and chlorophyll metabolism, coupled with an increase in the expression of chlorophyllase, contributed to the reduction in chlorophyll levels and photosynthesis. Blockage of sucrose transport plausibly occurred due to the expression of sugar transporters in leaves but suppression in stalks, resulting in low sugar content in canes. Increased expression of genes associated with MAPK cascades, plant hormone signaling transduction, callose plug formation, the phenylpropanoid pathway, and calcium cascades positively promoted defense mechanisms against phytoplasma colonization by an accumulation of lignin and calcium in response to plant immunity. Significant downregulation of CPK plausibly results in a reduction in antioxidant enzymes and likely facilitates pathogen invasion, while expression of sesquiterpene biosynthesis possibly attracts the insect vectors for transmission, thereby enabling the spread of phytoplasma. Moreover, downregulation of flavonoid biosynthesis potentially intensifies the symptoms of SCWL upon challenge by phytoplasma. These SCWL sugarcane transcriptomic profiles describe the first comprehensive sugarcane–phytoplasma interaction during the harvesting stage. Understanding molecular mechanisms will allow for sustainable management and the prevention of SCWL disease—a crucial benefit to the sugar industry. Full article

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300–1000 μm from HL), and distal stalk region (1500–2000 μm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 μm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings. Full article

Inflammatory diseases are strongly associated with global morbidity and mortality. Several mediators are involved in this process, including proinflammatory interleukins and cytokines produced by damaged tissues that, somehow, act as initiators of the autoreactive immune response. Bioactive compounds present in plant-based foods and byproducts have been largely considered active agents with the potential to treat or prevent inflammatory diseases, being a valuable alternative to traditional therapeutic agents used nowadays, which present several side effects. In this regard, the present research uncovers the anti-inflammatory activity of the bioaccessible fraction of broccoli stalks processed, by applying different conditions that render specific concentrations of bioactive sulforaphane (SFN). The raw materials’ extracts exhibited significantly different contents of total glucosinolates (GSLs) that ranged between 3993.29 and 12,296.48 mg/kg dry weight (dw), with glucoraphanin as the most abundant one, followed by GI and GE. The indolic GSLs were represented by hydroxy-glucobrassicin, glucobrassicin, methoxy-glucobrassicin, and neo-glucobrassicin, with the two latter as the most abundant. Additionally, SFN and indole-3-carbinol were found in lower concentrations than the corresponding GSL precursors in the raw materials. When exploring the bioaccessibility of these organosulfur compounds, the GSL of all matrices remained at levels lower than the limit of detection, while SFN was the only breakdown product that remained stable and at quantifiable concentrations. The highest concentration of bioaccessible SFN was provided by the high-ITC materials (~4.00 mg/kg dw). The results retrieved on the cytotoxicity of the referred extracts evidenced that the range of supplementation of growth media tested (0.002–430.400 µg of organosulfur compounds/mL) did not display cytotoxic effects on Caco-2 cells. The obtained extracts were assessed based on their capacity to reduce the production of key proinflammatory cytokines (interleukin 6 (IL-6), IL-8, and TNF-α) by the intestinal epithelium. Most of the tested processing conditions provided plant material with significant anti-inflammatory activity and the absence of cytotoxic effects. These data confirm that SFN from broccoli stalks, processed to optimize the bioaccessible concentration of SFN, may be potential therapeutic leads to treat or prevent human intestinal inflammation. Full article

One of the most destructive diseases, Gibberella stalk rot (GSR), caused by Fusarium graminearum, reduces maize yields significantly. An induced resistance response is a potent and cost-effective plant defense against pathogen attack. The functional counterpart of JAs, coronatine (COR), has attracted a lot of interest recently due to its ability to control plant growth and stimulate secondary metabolism. Although several studies have focused on COR as a plant immune elicitor to improve plant resistance to pathogens, the effectiveness and underlying mechanisms of the suppressive ability against COR to F. graminearum in maize have been limited. We investigated the potential physiological and molecular mechanisms of COR in modulating maize resistance to F. graminearum. COR treatment strongly enhanced disease resistance and promoted stomatal closure with H₂O₂ accumulation, and 10 μg/mL was confirmed as the best concentration. COR treatment increased defense-related enzyme activity and decreased the malondialdehyde content with enhanced antioxidant enzyme activity. To identify candidate resistance genes and gain insight into the molecular mechanism of GSR resistance associated with COR, we integrated transcriptomic and metabolomic data to systemically explore the defense mechanisms of COR, and multiple hub genes were pinpointed using weighted gene correlation network analysis (WGCNA). We discovered 6 significant modules containing 10 candidate genes: WRKY transcription factor (LOC100279570), calcium-binding protein (LOC100382070), NBR1-like protein (LOC100275089), amino acid permease (LOC100382244), glutathione S-transferase (LOC541830), HXXXD-type acyl-transferase (LOC100191608), prolin-rich extensin-like receptor protein kinase (LOC100501564), AP2-like ethylene-responsive transcription factor (LOC100384380), basic leucine zipper (LOC100275351), and glycosyltransferase (LOC606486), which are highly correlated with the jasmonic acid–ethylene signaling pathway and antioxidants. In addition, a core set of metabolites, including alpha-linolenic acid metabolism and flavonoids biosynthesis linked to the hub genes, were identified. Taken together, our research revealed differentially expressed key genes and metabolites, as well as co-expression networks, associated with COR treatment of maize stems after F. graminearum infection. In addition, COR-treated maize had higher JA (JA-Ile and Me-JA) levels. We postulated that COR plays a positive role in maize resistance to F. graminearum by regulating antioxidant levels and the JA signaling pathway, and the flavonoid biosynthesis pathway is also involved in the resistance response against GSR. Full article

Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model. Full article