Search Results (10,539)

An outbreak characterized by clinical signs of diarrhea and paralysis, occasionally progressing to fatal outcomes, occurred at an ostrich breeding facility. Conventional antibiotic treatments proved ineffective. To investigate the etiology of the disease, brain and liver specimens were collected for diagnostic analysis. An Escherichia coli (E. coli) isolate, designated strain HZDC01, was obtained from cerebral tissues, and whole-genome sequencing was performed for genomic characterization. Genomic analysis revealed that the chromosomal DNA harbors numerous resistance genes, conferring multidrug resistance through complex mechanisms. Furthermore, a p0111-type plasmid carrying the bla_CTX-M-55 gene and an IncX1-type plasmid harboring rmtB, sul1, APH(6)-Id, tet(A), AAC(3)-IIc, aadA2, bla_TEM-1B, and floR genes were identified. These plasmids carry numerous mobile genetic elements that can disseminate via horizontal gene transfer, thereby amplifying the risk of resistance-gene spread within bacterial populations. Additionally, the ibeB and ibeC genes, which encode proteins involved in the invasion of brain microvascular endothelial cells, were identified. These genes may facilitate E. coli penetration of the blood–brain barrier, potentially leading to meningitis and posing a life-threatening risk to the host. This is the first report of the isolation and characterization of extended-spectrum beta-lactamase E. coli from the brain of an ostrich with paralysis. The findings provide valuable genomic insights into the antimicrobial resistance profiles and pathogenic mechanisms of ostrich-derived E. coli isolates. Full article

Background/Objectives. Multi-drug-resistant (MDR) microorganisms pose a significant challenge in healthcare settings, particularly with beta-lactam-resistant Gram-negative bacteria and glycopeptide-resistant enterococci. Culture represents the most reliable technique in determining their presence within surveillance swabs. However, it requires a long time-to-result (TTR) and shows low sensitivity. Molecular techniques integrate diagnostic procedures, allowing TTR reduction and precise identification of genes. Methods. During our usual surveillance campaign, we had the opportunity to evaluate the Allplex Entero-DR assay (Seegene Inc., Seoul, Republic of Korea) and the Entero-DR Plus assay (Arrow Diagnostics srl, Genova, Italy) molecular kits for the detection of extended-β-lactamases (ESBL), carbapenem- and vancomycin-resistant genes, as well as Acinetobacter spp. and Pseudomonas aeruginosa spp. identification directly from rectal swabs. A comparison between these tests and the culture-based routine completed the study. Results. The analysis included 300 rectal swabs from the University Hospital Policlinico (Catania, Italy). One hundred and eighty-eight samples (62.6%) resulted as positive for at least one Allplex™ target, reaching optimal sensitivity and negative predictive value (100%). Our results underlined the ubiquitous blaCTX-M and van genes presence and demonstrated the diffusion of double-carbapenemases genes and metallo-β-lactamases-producing strains. In our epidemiological setting, few data were collected about carbapenem-resistant P. aeruginosa and Acinetobacter spp., which require further evaluations on simultaneous respiratory colonization and higher sample numbers. Conclusions. Our analysis highlighted the importance of combining conventional and advanced diagnostic methods in investigating MDR pathogens. The right approach should be based on the prevalence and variability of resistance mechanisms within a specific epidemiological area. Remarkably, molecular screenings may exclude negative samples within high-risk areas due to a significant negative predictive value. Full article

Pseudorabies virus (PRV), a highly pathogenic alphaherpesvirus, poses a potential threat to public health and safety due to its broad host range and risk of cross-species transmission. Viruses have evolved multiple strategies to exploit host factors for entry into and survival in host cells. Drebrin is an actin-binding protein that restricts rotavirus entry by inhibiting dynamin-mediated endocytosis. However, its role and mechanism in DNA virus infection, particularly in herpesviruses, remain unexplored. In this study, we investigated the role of Drebrin in PRV infection using pharmacological inhibition (BTP−2) and CRISPR-Cas9-mediated gene knockout. Both the Drebrin inhibitor BTP−2 and gene knockout significantly suppressed PRV replication. Intriguingly, Drebrin exhibited stage-specific effects on the viral life cycle: its inhibition enhanced viral internalization during early infection but impaired viral replication at later stages, suggesting that Drebrin plays a complex role in the regulation of PRV infection. PRV infection partially disrupted actin stress fibers and caused an increase in cell size. Drebrin knockout also altered the host-cell morphology, reduced the cell surface area, and induced actin cytoskeleton rearrangement, which was further modulated in PRV-infected cells. In summary, our data demonstrate that Drebrin functions as a critical host factor governing the entire PRV life cycle by regulating actin cytoskeleton reorganization. Full article

Background/Objectives: Lichen simplex chronicus (LSC) of the vulva is a chronic dermatologic disorder characterized by persistent pruritus, compulsive scratching, and progressive thickening of the vulvar skin. Currently, LSC diagnosis primarily relies on clinical presentation, with histopathological examination performed when the diagnosis is unclear. However, the precise pathogenic mechanisms driving the disease remain poorly understood. This study aimed to investigate the pathogenesis of LSC and evaluate the feasibility of tape stripping as a non-invasive diagnostic technique. Methods: Skin specimens were obtained using both traditional biopsy and tape stripping methods, and the metabolites and oxidized lipids in these samples were analyzed using advanced mass spectrometry techniques. Results: Our findings suggest that 20-hydroxyeicosatetraenoic acid (20-HETE), an oxidized derivative of arachidonic acid (AA), activates the TRPV1 receptor, thereby exacerbating the itch–scratch cycle. This activation upregulates energy metabolism and promotes epidermal hyperplasia, providing new insights into the disease’s pathophysiology. Conclusions: Our study suggests that tape stripping could serve as a viable non-invasive diagnostic tool for LSC, with linoleic acid (LA) and AA potentially acting as biomarkers for the disease. Full article

Background/Objectives: The global increase in multidrug-resistant (MDR) bacterial infections underscores the urgent need for effective and sustainable antimicrobial alternatives. This study investigates the antimicrobial activity of exometabolite-based formulations (ExAFs), derived from the cell-free supernatants (CFS) of native lactic acid bacteria (LAB) applied individually or in combination thereof, against MDR-Escherichia coli strain L1PEag1. Methods: Fourteen ExAFs were screened for inhibitory activity using time–kill assays, and structural damage to bacterial cells was assessed via scanning and transmission electron microscopy (SEM/TEM). The most potent formulation was further characterized by liquid chromatography–tandem mass spectrometry (LC–MS/MS) employing a Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH) approach for untargeted metabolite profiling. Results: Among the tested formulations, E10, comprising CFS from Weissella cibaria UTNGt21O, exhibited the strongest inhibitory activity (zone of inhibition: 17.12 ± 0.22 mm), followed by E1 (CFS from Lactiplantibacillus plantarum Gt28L and Lactiplantibacillus plantarum Gt2, 3:1 v/v) and E2 (Gt28L CFS + EPS from Gt2, 3:1 v/v). Time–kill assays demonstrated rapid, dose-dependent bactericidal activity: E1 and E10 achieved >98% reduction in viable counts within 2–3 h, at 1× MIC, while E2 sustained 98.24% inhibition over 18 h, at 0.25× MIC. SEM and TEM revealed pronounced ultrastructural damage, including membrane disruption, cytoplasmic condensation, and intracellular disintegration, consistent with a membrane-targeting mode of action. Metabolomic profiling of E10 identified 22 bioactive metabolites, including lincomycin, the proline-rich peptide Val–Leu–Pro–Val–Pro–Gln, multiple flavonoids, and loperamide. Several compounds shared structural similarity with ribosomally synthesized and post-translationally modified peptides (RiPPs), including lanthipeptides and lassopeptides, suggesting a multifaceted antimicrobial mechanism. Conclusions: These findings position ExAFs, particularly E10, as promising, peptide-rich, bio-based antimicrobial candidates for food safety or therapeutic applications. The co-occurrence of RiPP analogs and secondary metabolites in the formulation suggests the potential for complementary or multi-modal bactericidal effects, positioning these compounds as promising eco-friendly alternatives for combating MDR pathogens. Full article

Postharvest losses due to fungal decay pose a significant challenge to global fruit and vegetable production, especially in regions where rot pathogens are prevalent. Traditional control methods rely heavily on synthetic fungicides, which are increasingly criticized for their environmental risks, human health concerns, and their role in fostering pathogen resistance. These issues underscore the urgent need for sustainable, residue-free alternatives that not only manage postharvest diseases but also enhance produce quality. Light-emitting diode [LED] technology has emerged as a promising, eco-friendly solution capable of modulating plant physiological responses through specific light wavelengths. However, the exact defense mechanisms activated by LED exposure in postharvest decay control and nutritional enhancement remain underexplored. This review provides a comprehensive synthesis of recent findings on LED-induced control of fungal decay, focusing on how LED treatments modulate pathogen–fruit interactions, activate innate defense pathways, regulate gene networks linked to defense and nutritional traits, and contribute to improved fruit and vegetable quality and health benefits. Full article

In the absence of commercialized vaccines for most arboviruses, including dengue, chikungunya, and Zika, which are transmitted by Aedes aegypti, the management of vector populations to prevent disease transmission remains the cornerstone of arbovirus control strategies. Larviciding targets the early stages of the mosquito life cycle and subsequently reduces the capacity of adult population to transmit pathogens. Here, we report the susceptibility profile of Ae. aegypti larval populations from two West Africa cities, namely Niamey and Ouagadougou, to organophosphates larvicides. In Niamey, sampling was carried out using ovitraps at two sites, whereas in Ouagadougou, larvae were collected from three different types of larval containers at a single site. Temephos and fenitrothion were tested at six different concentrations each. Mosquito populations from Niamey and Ouagadougou were found susceptible to temephos and fenitrothion, with LD₅₀ < 0.015 mg/L and RR₅₀ < 5. However, Ae. aegypti populations from Ouagadougou showed reduced susceptibility to temephos compared to baseline data from 2016, as indicated by RR₅₀ values. This observation highlights the need for regular surveillance of larval susceptibility, as it may signal the emergence of temephos resistance in Ouagadougou. The acetylcholinesterase (AChE) mutation and the expression levels of metabolic genes Carboxy-/Cholinesterase (CCE) should be characterized to understand the molecular mechanisms underlying the observed phenotype response. Our results provide up-to-date data that could inform the potential deployment of these larvicides for the prevention and control of dengue and chikungunya outbreaks in Ouagadougou and Niamey. Full article

Streptomycetes are vital microbial resources used in agriculture and biotechnology and are diverse secondary metabolites. The Streptomyces olivoreticuli YNK-FS0020 strain was isolated from the rhizosphere soil in Yunnan’s Wuliangshan Forest; its functions were explored via a series of experiments and genomic analysis. Indoor assays showed that this strain inhibits seven plant pathogens (including Fusarium oxysporum f. sp. cubense Tropical Race 4) and exhibits phosphorus solubilization, siderophore production, and plant-growth promotion. Genomic analysis revealed 47 secondary metabolite biosynthetic gene clusters: 12 shared over 60% similarity with known clusters (4 exhibited 100% similarity, involving antimycin and ectoine), while 19 showed low similarity or unknown functions, indicating the strain’s potential in the development of novel compounds. Genes related to tryptophan-IAA synthesis, phosphate metabolism, and siderophore systems were annotated, while metabolomics detected indole-3-acetic acid and kitasamycin, revealing mechanisms like hormonal regulation and antimicrobial secretion. In summary, YNK-FS0020 has potential for use in plant-growth promotion and disease control, aiding agricultural microbial resource utilization. Full article

Background/Objectives: Tick-borne diseases (TBDs) are increasingly recognized as causes of both systemic and neurologic illness. While their impact on vascular health is established, their role in cerebrovascular disease remains underexplored. This review aims to synthesize clinical evidence linking TBDs with cerebrovascular events, focusing on mechanisms of injury, pathogen-specific associations, and treatment outcomes. Methods: A narrative review was conducted using Boolean keyword searches across PubMed, Scopus, EMBASE, and Web of Science. Relevant literature on ischemic and hemorrhagic stroke, cerebral vasculitis, and stroke mimics associated with TBDs was examined. The review included case reports, observational studies, and mechanistic research. Pathogen-specific data and disease characteristics were extracted and summarized. Results: Several tick-borne pathogens were associated with cerebrovascular complications. Borrelia burgdorferi was most commonly implicated and typically presented with large-vessel vasculitis. Rickettsia, Ehrlichia, and Anaplasma species caused endothelial injury through immune-mediated inflammation. Powassan virus and Crimean–Congo hemorrhagic fever virus exhibited central nervous system involvement and hemorrhagic potential. Babesia species contributed to vascular injury through thrombocytopenia and embolic complications. Neuroimaging frequently demonstrated multifocal stenoses and vessel wall inflammation. Antimicrobial treatment, particularly with doxycycline or ceftriaxone, was often effective, especially when administered early. Supportive care for stroke symptoms varied by presentation and underlying pathogen. Conclusions: Cerebrovascular disease caused by tick-borne pathogens is an underrecognized but potentially reversible condition. Despite diverse etiologies, most pathogens share a final common pathway of endothelial dysfunction. Early recognition and targeted antimicrobial therapy, combined with supportive stroke care, are essential to improving patient outcomes. Full article

Improving agricultural by-product utilization can alleviate tropical feed shortages. This study used corn stover (CS, Zea mays L.) at the maturity stage as the material, with four silage treatments: control, lactic acid bacteria (LAB, Lactiplantibacillus plantarum), cellulase (AC, Acremonium cellulolyticus), and LAB+AC. After 60 days fermentation in plastic drum silos, the silos were opened for sampling. PacBio single-molecule real-time sequencing technology was used to study bacterial community structure, symbiotic network functionality, and pathogenic risk to clarify CS fermentation regulatory mechanisms. The CS contained 59.9% neutral detergent fiber and 7.1% crude protein. Additive-treated silages showed better quality than the control: higher lactic acid (1.64–1.83% dry matter, DM), lower pH (3.62–3.82), and reduced ammonia nitrogen (0.54–0.81% DM). Before ensiling, the CS was dominated by Gram-negative Rhizobium larrymoorei (16.30% of the total bacterial community). Functional prediction indicated that the microbial metabolism activity in diverse environments was strong, and the proportion of potential pathogens was relatively high (14.69%). After ensiling, Lactiplantibacillus plantarum as Gram-positive bacteria were the dominant species in all the silages (58.39–84.34% of the total bacterial community). Microbial additives facilitated the establishment of a symbiotic microbial network, where Lactiplantibacillus occupied a dominant position (p < 0.01). In addition, functional predictions showed an increase in the activity of the starch and sucrose metabolism and a decrease in the proportion of potential pathogens (0.61–1.95%). Among them, the synergistic effect of LAB and AC inoculants optimized the silage effect of CS. This study confirmed that CS is a potential high-quality roughage resource, and the application of silage technology can provide a scientific basis for the efficient utilization of feed resources and the stable development of animal husbandry in the tropics. Full article

Monocytes/macrophages promote the repair of acutely injured muscle while contributing to dystrophic changes in chronically injured muscle in Duchenne muscular dystrophy (DMD) patients and animal models including mdx and mdx^5cv mice. To elucidate the molecular mechanisms underlying this functional difference, we compared the transcriptomes of intramuscular monocytes/macrophages from wild-typed (WT) uninjured muscles, WT acutely injured muscles, and mdx^5cv dystrophic muscles, using single cell-based RNA sequencing (scRNA-seq) analysis. Our study identified multiple transcriptomically diverse monocyte/macrophage subclusters, which appear to be induced by the intramuscular microenvironment. They expressed feature genes differentially involved in muscle inflammation, regeneration, and extracellular matrix (ECM) remodeling, but none of them conform to strict M1 or M2 activation. The Gpnmb⁺Spp1⁺ macrophage subcluster, an injury-associated subcluster that features the signature genes of reported scar-associated macrophages (SAMs) involved in ECM remodeling and fibrosis, is present transiently in acutely injured muscle and persistently in chronically injured dystrophic muscle, along with the persistence of monocytes. Our findings suggest that the persistent monocyte/macrophage infiltration and activation induced by continuous injury may underlie the pathogenic roles of macrophages in mdx^5cv muscles. Controlling muscle injury and subsequent macrophage infiltration and activation may be important to the treatment of DMD. Full article

Background: Viral–bacterial co-infections can amplify disease severity through complex biological mechanisms. Mathematical models are critical tools for understanding these threats, but it is unclear how well they capture the underlying biology. This systematic review addresses a central question: to what extent does the current generation of models mechanistically represent co-infections, or do the mathematical assumptions underlying these models adequately represent the known biological mechanisms? Methods: Following PRISMA guidelines, we systematically reviewed the literature on mechanistic models of human virus–bacteria co-infections. A systematic search of articles on the scientific literature repositories PubMed, Scopus, and Dimensions was conducted and data on study objectives, model structure, assumptions about biological interactions (e.g., susceptibility, mortality), control measures (if evaluated), and the empirical sources used for key parameters were extracted. Results: We identified 72 studies for inclusion in this analysis. The reviewed models are consistently built on the established premise that co-infection alters disease severity and host susceptibility. However, we found they incorporate these dynamics primarily through high-level mathematical shortcuts, such as applying static “multiplicative factors” to transmission or progression rates. Our quantitative analysis also revealed questionable approaches; for example, 79% (57) of these studies relied on non-empirical sources (assumed or borrowed values) for parameter values including interaction parameters (e.g., increased susceptibility to a secondary pathogen following primary infection, or elevated mortality rates in co-infected individuals). Conclusions: An apparently unjustified practice exists in co-infection modeling, where complex biological processes are simplified to fixed numerical assumptions, often without empirical support. This practice limits the predictive reliability of current models. We identify an urgent need for data-driven parameterization and interdisciplinary collaboration to bridge the gap between biological complexity and modeling practice, thereby enhancing the public health relevance of co-infection modeling. Full article

Background: Periodontal disease in non-human primates (NHPs) has gained relevance due to its similarities with human pathology and its potential to influence systemic health. The purpose of this study was to investigate the relationship between periodontal disease and the development of systemic conditions in NHPs, aiming to understand the mechanisms involved and their clinical significance. Methods: An integrative literature review was conducted using the PICO strategy, including observational studies, experimental research, and integrative reviews that examined periodontal disease in NHPs and its association with systemic diseases. Results: A total of eleven studies were analyzed, revealing consistent associations between periodontal disease and systemic conditions such as diabetes mellitus, cardiovascular diseases, osteoporosis, metabolic syndrome, and adverse pregnancy outcomes. The reviewed studies identified inflammatory pathways, including elevated cytokines, acute-phase proteins and immune responses, as key mediators linking periodontal disease to systemic dysfunction. Oral pathogens and chronic inflammation were shown to impact distant organs, suggesting a broader role of oral health in systemic disease. Conclusions: The findings support the hypothesis that periodontal disease in NHPs contributes to systemic disease progression and is not merely a localized condition. Full article

Glaesserella parasuis (GPS) is a Gram-negative, pathogenic bacterium that colonizes the upper respiratory tract of piglets and causes Glässer’s disease with peritonitis under stress conditions. The mechanism underlying GPS-induced peritonitis in piglets remains unclear. Baicalin is one of the main active ingredients of Huangqin (Scutellaria baicalensis), which has a significant anti-inflammatory effect on inflammatory diseases. Therefore, this study aimed to elucidate the molecular mechanism by which baicalin alleviates GPS-induced peritonitis in piglets, specifically focusing on the role of the ADAM17/EGFR signaling axis. We investigated the effects of baicalin in vitro using porcine peritoneal mesothelial cells (PPMCs) and in vivo in GPS-infected piglets. Our results showed that baicalin reduced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in PPMCs and the peritoneum of piglets after GPS infection. Concurrently, baicalin significantly reduced the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (p-EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK induced by GPS infection in PPMCs and the peritoneum of piglets. Crucially, in vitro mechanistic investigations revealed that baicalin can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by ADAM17 overexpression in PPMCs. Furthermore, ADAM17 small interfering RNA can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by GPS infection in PPMCs. These findings demonstrate that baicalin can inhibit the expression of inflammatory factors TNF-α, IL-1β, and IL-6 through the ADAM17/EGFR axis, and then alleviate the peritonitis caused by GPS in piglets. This provides a theoretical basis for developing novel non-antibiotic strategies, including phytochemical therapeutics and feed additives, for preventing and controlling GPS. Full article

Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such as sialylation, fucosylation, and sulfation underpins their functional specificity and regulatory capacity. This review provides a comprehensive overview of glycan biosynthesis, with a focus on N-glycans, O-glycans, glycosaminoglycans (GAGs), and glycolipids. It explores their essential roles in maintaining cellular homeostasis, development, and immune surveillance. In health, glycans mediate cell–cell communication, protein interactions, and immune responses. In disease, however, aberrant glycosylation is increasingly recognized as a hallmark of numerous pathological conditions, including cancer, neurodegenerative disorders, autoimmune diseases, and a wide range of infectious diseases. Glycomic alterations contribute to tumor progression, immune evasion, therapy resistance, neuroinflammation, and synaptic dysfunction. Tumor-associated carbohydrate antigens (TACAs) and disease-specific glycoforms present novel opportunities for biomarker discovery and therapeutic targeting. Moreover, glycan-mediated host–pathogen interactions are central to microbial adhesion, immune escape, and virulence. This review highlights current advances in glycomics technologies, including mass spectrometry, lectin microarrays, and glycoengineering, which have enabled the high-resolution profiling of the glycome. It also highlights the emerging potential of single-cell glycomics and multi-omics integration in precision medicine. Understanding glycome and its dynamic regulation is essential for uncovering the molecular mechanisms of disease and translating glycomic insights into innovative diagnostic and therapeutic strategies. Full article