Search Results (6,859)

Creating a dependable approach for identifying both the mass of a shuttle car and how material is distributed in it removes the need for equipment operators to manually engage the flight chain. The quantification of environmental and installation conditions and the extent of influence considering their combined contribution towards inaccurate or exclusive measurements are to that degree limited. This experimental study investigated how two different strain transducers—installed in a force-shunt configuration—respond to thermo-mechanical loads when used to determine load distribution and position. Initial observations indicated that thermal effects at the installation site contributed to measurement inaccuracies or exclusive readings. The investigation quantified the impact of environmental and installation variables on measurement accuracy and found this influence to be indirectly linked to the mechanical properties of the substrate to which the strain transducers were mounted. Mounting bolt torque was determined to exert a negligible effect on strain measurement accuracy for the custom-built strain transducers. Nonetheless, both transducers failed to consistently return to the selected baseline at the start of experiments since thermal dependence persisted at the balanced state following the first cycle of loading. The research indicated that the custom-built force-shunt strain transducers are an effective means for mapping the profile and location of coal in shuttle cars, provided that the systems are subjected to continuous and cyclic rebalancing to maintain accuracy. Full article

Oral biofilms are complex polymicrobial communities involved in the development of dental caries and periodontal diseases. Chemical antiseptics are commonly used as adjuncts to mechanical plaque control; however, their antimicrobial efficacy varies depending on composition and mechanism of action. The aim of this study was to comparatively evaluate the antimicrobial and antibiofilm activities of four commercially available dental products (Corsodyl, Ozosan, HybenX, and Elugel) against a broad spectrum of oral microorganisms. This in vitro study included Gram-positive and Gram-negative bacterial strains, comprising both reference strains and clinical isolates, as well as Candida albicans. Antimicrobial activity was assessed using the disc diffusion assay, while antibiofilm activity was evaluated using a crystal violet microplate assay. All experiments were performed in triplicate. Statistical analysis was conducted using two-way ANOVA followed by Tukey’s post hoc test (p < 0.05). All tested products exhibited antimicrobial activity. Inhibition zones ranged from 9 to 56 mm for Gram-positive bacteria, 12 to 38 mm for Gram-negative bacteria, and 13 to 43 mm for Candida albicans. Two-way ANOVA revealed a significant effect of the dental product (p < 0.001), while incubation time was not significant (p > 0.05). HybenX showed the highest antimicrobial efficacy, while chlorhexidine-based products demonstrated consistent activity. Antibiofilm inhibition exceeded 80% for several strains. Dental antiseptics exhibit significantly different antimicrobial and antibiofilm profiles, highlighting the importance of appropriate product selection in oral biofilm control. Full article

Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic environmental exposure—remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin–eosin staining. Statistical analyses were performed using R software, with p ≤ 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity. Full article

Foodborne diseases represent a major public health concern, particularly those associated with dairy products contaminated with Staphylococcus aureus, a pathogen capable of producing heat-stable enterotoxins. This study evaluated the potential of native lactic acid bacteria (LAB) isolated from artisanal kefir grains as natural biocontrol agents in fermented dairy foods. Kefir grains obtained from three artisanal producers were microbiologically characterized, revealing LAB as the dominant group and the absence of Enterobacteriaceae. Strains belonging mainly to the genera Lactobacillus sensu lato, Leuconostoc, and Pediococcus were isolated and exhibited differentiated metabolic profiles. Safety assessment showed no hemolytic activity and an overall susceptibility to clinically relevant antibiotics, although genus-dependent intrinsic resistance patterns were observed. Several strains displayed enzymatic activities related to carbohydrate digestion and high tolerance to simulated gastrointestinal conditions, with survival rates exceeding 90% during both gastric and intestinal phases. Neutralized cell-free supernatant (CFS) demonstrated differential inhibitory activity, with significant antagonism of S. aureus and E. coli, comparable to those of commercial reference strains. In a yogurt model system stored at 4 °C, selected Lactobacillus and Pediococcus strains induced a progressive and significant reduction in S. aureus populations, achieving complete elimination to undetectable levels in shorter times than commercial probiotic strains. Overall, these results demonstrate that native LAB from artisanal kefir grains exhibit an adequate safety and functional profile, together with strong antagonistic activity, supporting their potential application as natural protective cultures to improve the food hygiene of fermented dairy products. Full article

Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4⁺ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group. Full article

Understanding the genetic changes that allow avian influenza A viruses (IAVs) to switch their natural hosts and establish productive infection in humans is important for pandemic risk assessment. Adaptations in the IAV polymerase are required to overcome species-specific restrictions imposed by host ANP32 proteins. Notably, avian virus polymerase is generally only poorly supported by human ANP32 proteins due to species-specific differences. Consequently, efficient polymerase adaptation to the binding interface of human ANP32 requires distinct amino acid changes, such as PB2 E627K. A separate adaptation, PB2 M631L, has recently been reported in mammalian-adapted IAV; however, its functional role across divergent viral lineages and its relationship to host ANP32-dependent adaptation remain incompletely defined. Here, we examine PB2 M631L in the polymerases of a 1918 pandemic strain, a recombinant contemporary H1N1pdm09, and a recent clade 2.3.4.4b H5N1 virus. Using polymerase activity and protein-interaction assays, we show that PB2 M631L enhances polymerase activity and ANP32 binding in human—but not avian—contexts, and that this effect is conserved across multiple viral backgrounds. In H1N1pdm09, PB2 M631L also increased virus replication in mammalian cells. These findings indicate that PB2 M631L contributes to enhanced polymerase compatibility with human ANP32 proteins and are consistent with a role in adaptation across multiple influenza virus lineages. Our results highlight how analysis of historical pandemic strains can inform risk assessment for future emerging viruses. Full article

Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft^®; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAV_PR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness. Full article

Seasonal human coronaviruses (HCoVs) continue to undergo adaptive evolution under structural and immune-mediated constraints. We investigated the molecular epidemiology and spike (S) protein structural variation of circulating coronaviruses in Riyadh, Saudi Arabia, during the 2025–2026 winter season, with particular emphasis on genotype persistence and glycosylation architecture in HCoV-OC43. Among 293 nasopharyngeal aspirates (NPAs) collected from hospitalized patients with acute respiratory illness, HCoV-OC43 was detected in 26 cases (8.87%), whereas other seasonal coronaviruses were not identified. Partial sequencing of the S gene revealed 97.84–98.23% nucleotide identity relative to the prototype strain VR-759, with amino acid substitutions distributed at discrete positions rather than within extended variable domains, indicating structural conservation. Phylogenetic reconstruction demonstrated that all Riyadh isolates clustered within genotype C, together with previously circulating local strains, supporting sustained endemic persistence and in situ evolution. In silico analysis of the S protein glycosylation landscape identified four invariant N-linked glycosylation motifs (N-X-S/T) at residues 46, 121, 134, and 190, reflecting strong structural constraints on glycan-dependent folding and antigenic configuration. A genotype-associated K68N substitution generated an additional N-glycosylation motif (68NGTD) in multiple Riyadh isolates, potentially modifying local glycan shielding without disrupting the overall glycosylation framework. The preservation of core glycosylation sites alongside selective motif acquisition suggests evolutionary fine-tuning of S surface topology rather than large-scale structural remodeling. Collectively, these findings indicate that genotype C persistence in Riyadh is accompanied by conserved S architecture and subtle glycosylation adjustments that may modulate immune recognition while maintaining structural integrity. Continued high-resolution molecular surveillance will be critical for defining the functional consequences of S microevolution in endemic HCoVs. Full article

Cultivated lettuce (Lactuca sativa L.) is a major leafy crop and an emerging model for functional genomics within the Asteraceae family, supported by high-quality reference genomes and efficient transformation systems. Although CRISPR/Cas technology offers powerful opportunities for crop improvement, editing efficiency depends on optimized construct architecture and reliable guide RNA (gRNA) validation. However, a rapid platform for evaluating CRISPR reagents in lettuce is still lacking. Here, we developed an efficient hairyroot-based system to accelerate CRISPR/Cas genome editing optimization in L. sativa. Four Agrobacterium rhizogenes strains were compared for hairy root induction in two cultivars, ‘Saladin’ and ‘Osiride’, identifying strain ATCC15834 as the most effective based on transformation frequency and root production. Using this platform, we evaluated multiple CRISPR construct configurations, including alternative promoters for nuclease and gRNA expression. A plant-derived promoter combined with At-pU6-26 variant significantly improved editing efficiency. As a proof of concept, we targeted LsHB2, the putative ortholog of Arabidopsis thaliana ATHB2, a key regulator of the shade avoidance response using SpCas9, SaCas9, and LbCas12a nucleases. The system enabled rapid genotyping and quantitative indel profiling. Overall, this workflow provides a robust framework for efficient guide selection and construct optimization in lettuce genome editing. Full article

Quantum beams-including X-rays, synchrotron radiation, electrons, neutrons, ions, and ultrafast photon sources-are indispensable tools for probing the structure, dynamics, and electronic properties of matter. The excitation time scale ${\tau }_{exc}$ is defined operationally as the characteristic temporal interval governing externally imposed energy deposition events within the interaction volume, such as pulse duration, bunch spacing, or beam dwell time. Interpretation of beam–matter interactions has traditionally relied on steady-state or quasi-equilibrium assumptions, implicitly presuming that intrinsic material relaxation processes can accommodate externally imposed excitation. Recent advances in high-brightness synchrotron sources, X-ray free-electron lasers (XFELs), and pulsed electron beams increasingly operate in regimes where this assumption is strained, and systematic nonequilibrium effects, radiation damage, and irreversible transformations are reported even under routine experimental conditions. This work examines the role of time-scale mismatch between beam-driven energy deposition and intrinsic material relaxation as a governing constraint in beam–matter interactions. Analyzing the hierarchy of excitation, electronic relaxation, phonon coupling, and thermal diffusion time scales, the analysis introduces a dimensionless mismatch parameter $\mathsf{\Lambda }={\displaystyle \frac{{\tau }_{rel}}{{\tau }_{exc}}}$, which quantifies the competition between externally imposed excitation and intrinsic relaxation processes in beam–matter interactions. The resulting framework provides a unified physical interpretation of beam-induced damage, signal distortion, dose dependence, and nonlinear response across quantum beam modalities, framing these effects as consequences of forced nonequilibrium dynamics rather than technique-specific artifacts. Full article

Intervertebral disc degeneration is the most recognized cause of low back pain, characterized by the decline in tissue structure and mechanics. Image-based mechanical parameters (e.g., strain, stiffness) may provide an ideal assessment of disc function that is lost with degeneration, but unfortunately, these remain underdeveloped. Moreover, it is unknown whether strain or stiffness of the disc may be predicted by MRI relaxometry (e.g., T₁ or T₂), an increasingly accepted quantitative measure of disc structure. In this study, we quantified T₁ and T₂ relaxation times and compared to in-plane strains measured with displacement-encoded MRI within human cadaveric discs under physiological levels of compression and bending. Using a novel inverse approach, we then estimated shear modulus in orthogonal image planes and regionally compared these values to relaxation times and 2D strains. Intratissue strain depended on the loading mode, and shear modulus in the nucleus pulposus was typically an order of magnitude lower than the annulus fibrosus. Relative shear moduli estimated from strain data derived under compression generally did not correspond with those from bending experiments. Only one anatomical region showed a significant correlation between relative shear modulus and relaxometry (T₁ vs. µ_rel, coronal plane under bending). Together, these results suggest that future inverse analyses may be improved by incorporating multiple loading conditions into the same model and that image-based elastography and relaxometry should be viewed as complementary measures of disc structure and function to assess degeneration in future studies. Full article

Fungal extracts have garnered considerable attention in recent years due to their diverse pharmaceutical potential. The present study investigates the secondary metabolite profile and biological activities of Alternaria citri, a fungal strain associated with citrus fruits. Metabolites were extracted from A. citri grown in Potato Dextrose Broth (PDB) using ethyl acetate and subsequently evaluated for antimicrobial, antioxidant, and cytotoxic activities, alongside gas chromatography–mass spectrometry (GC–MS) profiling. GC–MS analysis identified 14 bioactive compounds in the fungal extract. The extract exhibited antimicrobial activity against Aspergillus flavus, Trichoderma hamatum, Staphylococcus aureus, and Escherichia coli. Moderate total phenolic and flavonoid contents were observed, which correlated with concentration-dependent antioxidant activity as determined by the DPPH assay. Cytotoxic evaluation using NIH/3T3 cells demonstrated potential anticancer activity, with an IC₅₀ value of 126.63 µg/mL. A. citri is an interesting source of bioactive metabolites with potential therapeutic applications. These findings further strengthen the evidence that Alternaria species can serve as promising sources of natural antioxidants and antimicrobials, thereby supporting their potential applications in pharmaceutical and biomedical formulations. This study expands current knowledge of fungal metabolite diversity and establishes A. citri as a potential source of novel therapeutic agents. Full article

Background/Objectives: Atopic dermatitis (AD) is associated with gut dysbiosis linked to early-life antibiotic use and Staphylococcus aureus colonization. Gum Arabic (GA), a prebiotic, may modulate this dysbiosis and influence AD-related microbial balance. This study evaluated whether GA could support AD-associated probiotics-Lactobacillus casei, Bifidobacterium bifidum, and Bifidobacterium infantis-under amoxicillin- or azithromycin-containing conditions, examined the response of S. aureus under the same screening conditions, and developed GA-phospholipid-based semisolid carriers for topical application. Methods: Probiotic strains were cultured with 1–5% GA in the presence and absence of antibiotics, and viable cell counts were assessed. Sixteen topical formulations containing propylene glycol or isopropyl myristate in a hydrogenated phosphatidylcholine base were prepared and screened for rheological properties and galactose release using in vitro release testing (IVRT) and HPLC-UV. Results: GA at 1–2% concentrations promoted probiotic growth in antibiotic-free conditions. GA preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, numerical CFU differences were observed between antibiotic-only and GA-containing conditions; however, the present screening design was not intended to determine antibiotic interaction outcomes. Formulations F14 (2% GA + 7% IPM) and F15 (3% GA + 7% IPM) exhibited optimal spreadability. IVRT showed that 6 h cumulative galactose release varied by formulation (F6 > F10 > F14 > F15). Conclusions: GA demonstrated dose-dependent prebiotic activity and preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, the observed CFU differences between antibiotic-only and GA-containing conditions should be considered exploratory only and do not allow for conclusions regarding interference with antibiotic efficacy. Optimized GA-HPC systems with suitable rheological and release characteristics represent promising candidates for further preclinical investigation. Full article

Members of the genus Brucella are bacterial pathogens of global importance, and their increasing detection in marine mammals has raised concerns for wildlife conservation and public health. In this study, we evaluated the biological and pathogenic characteristics of two Brucella sp. sequence type 27 (ST27) isolates obtained from a dwarf sperm whale (Kogia sima). We compared them with terrestrial and marine Brucella reference strains. We assessed resistance to polymyxin B and human serum complement, intracellular infection dynamics in HeLa epithelial cells, persistence in a murine model, and associated hematological and histopathological changes, and analyzed lipopolysaccharide (LPS) profiles. The Kogia isolates exhibited resistance to polymyxin B and serum complement, comparable to that of B. abortus 2308W and marine mammal Brucella strains. In HeLa cells, the isolates displayed distinct, strain-specific intracellular infection dynamics. In the murine model, both isolates persisted in the spleen and induced granulomatous lesions. However, splenic bacterial loads and histopathological scores were generally lower than those observed with B. abortus 2308W, which exhibited the highest virulence among the strains evaluated. Hematological alterations associated with Kogia isolates were also less pronounced than those induced by B. abortus 2308W, indicating an intermediate and strain-dependent virulence phenotype without evidence of enhanced virulence relative to the terrestrial reference strain. Western blot analyses showed that Brucella sp. ST27 isolates were not recognized by anti-B. abortus or anti-O-antigen monoclonal antibodies, while exhibiting a distinct recognition pattern with anti-B. canis serum, indicating differences in surface antigen composition. Comparative whole-genome analysis identified a limited number of isolate-specific variants affecting coding and intergenic regions. Collectively, these findings highlight phenotypic and genetic features of Brucella sp. ST27 from Kogia sima, which distinguishes it from other marine and terrestrial Brucella strains and supports further investigation into its biological behavior and potential public health relevance. Full article

Sanghuangporus vaninii (Ljub.) is an edible and medicinal macrofungus that has become the main strain for artificial cultivation of Sanghuang. In this study, twenty-six compounds (1–26), including five previously undescribed ergosterols, named sanghusterols A–E (1–5), were isolated from the fruiting bodies of S. vaninii. Their structures were elucidated by spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 1, 15, 17, 21 and 25 exhibited potent inhibitory activity against NO production with the IC₅₀ value of 8.3–14.8 μM and dose-dependently decreased iNOS and COX-2 protein expression in RAW264.7 cells. Molecular docking studies confirmed the capacity of compounds 1, 15, 17, 21 and 25 to interact with iNOS and COX-2 proteins. These findings may provide a solid phytochemical and pharmacological basis for developing the mushroom as potential anti-inflammatory agents. Full article