Search Results (12,031)

Background/Objectives: Multidrug-resistant (MDR) strains of Streptococcus suis are increasingly prevalent and present significant challenges in clinical management. Given that the development of new antibiotics is a resource-intensive process and time-consuming, there is an urgent need for alternative therapeutic strategies to address resistance in the short term. One promising approach is the use of combination therapy, which involves pairing potent antibiotics with agents that may be less effective on their own, to enhance therapeutic efficacy and potentially overcome resistance mechanisms. This study aimed to investigate the in vitro antibacterial activity of combining two classes of antibiotics with distinct mechanisms of action—cell wall synthesis inhibitors and protein synthesis inhibitors—against MDR S. suis strains isolated from diseased pigs. Methods: A total of 36 MDR S. suis strains were tested using a microbroth dilution checkerboard assay to determine the minimum inhibitory concentration (MIC) of four cell wall synthesis inhibitors —amoxicillin/clavulanic acid (AMC), ampicillin (AMP), penicillin G (PEN), and vancomycin (VAN)— in combination with four protein synthesis inhibitors —gentamicin (GEN), neomycin (NEO), tilmicosin (TMS), and tylosin (TYL). Time–kill curve assays were conducted to evaluate the in vitro bactericidal activity of synergistic antibiotic combinations (PEN–GEN and AMP–NEO) against Beta-lactam-resistant and Beta-lactam-susceptible MDR S. suis strains. Results: Checkerboard analysis revealed that penicillin-gentamicin combination exhibited the most effective synergistic activity against the MDR S. suis strains (10/19, 52.6%), with ∑FIC values of 0.25–1.06 and MIC reductions from resistant to susceptible levels. Time-kill assays further confirmed the synergistic bactericidal effect of the combination, demonstrating complete bacterial clearance within 6–9 h, markedly rapid bacterial killing compared to monotherapy. Conclusions: This study demonstrates that antibiotic combinations, particularly Beta-lactams combined with aminoglycosides, show synergistic activity against pig-isolated S. suis MDR strains. The PEN-GEN combination exhibited strong synergistic and bactericidal effects, supporting combination therapy as a potential strategy to address antimicrobial resistance. Further evaluation in diverse strain backgrounds and prudent antibiotic use are essential to confirm efficacy and limit the emergence of antibiotic resistance. Full article

Natural products have emerged as promising multi-target agents for addressing the complex biology of gastric cancer, a malignancy characterized by marked molecular heterogeneity, late clinical presentation, and frequent resistance to systemic therapies. This narrative synthesis integrates primarily preclinical evidence, with emerging clinical data, on how naturally derived compounds modulate three central molecular processes that drive gastric tumor progression and therapeutic failure: evasion of programmed cell death, persistent tumor-promoting inflammation, and chemoresistance. Compounds such as curcumin, resveratrol, berberine, ginsenosides, quercetin, and epigallocatechin gallate restore apoptotic competence by shifting the balance between pro-survival and pro-death proteins, destabilizing mitochondrial membranes, promoting cytochrome c release, and activating caspase-dependent pathways. These agents also exert potent anti-inflammatory effects by inhibiting nuclear factor kappa B and signal transducer and activator of transcription signaling, suppressing pro-inflammatory cytokine production, reducing cyclooxygenase activity, and modulating the tumor microenvironment through changes in immune cell behavior. In parallel, multiple natural compounds function as chemo-sensitizers by inhibiting drug efflux transporters, reversing epithelial–mesenchymal transition, attenuating cancer stem cell-associated traits, and suppressing pro-survival signaling pathways that sustain resistance. Collectively, these mechanistic actions highlight the capacity of natural products to simultaneously target interconnected hallmarks of gastric cancer biology. Ongoing advances in formulation strategies may help overcome pharmacokinetic limitations; however, rigorous biomarker-guided studies and well-designed clinical trials remain essential to define the translational relevance of these compounds. Full article

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici, threatens global wheat production, with climate change intensifying its spread. This meta-analysis, following PRISMA protocol, evaluated chemical and biological control methods through a systematic review of literature (2005–2025), identifying 12 peer-reviewed studies with 156 experimental comparisons under various conditions. Random effects models assessed treatment impacts on disease severity and grain productivity using standardized mean differences (SMDs). Chemical control significantly reduced stripe rust severity (SMD = −1.04) and improved productivity (SMD = 1.30), with low to moderate variability and consistent yield responses. Effectiveness varied by active ingredients and wheat types, with the greatest benefits in highly susceptible varieties. Biological control agents, particularly Bacillus, Pseudomonas, and Trichoderma species, also reduced disease severity (SMD = −2.19) and increased yield (SMD = 2.39), though with greater heterogeneity reflecting strain-specific and environmental effects. Chemical fungicides provided more predictable disease control, while biological agents offered significant yield increases with agroecological benefits. This meta-analysis demonstrates complementary roles for both approaches, strongly supporting integrated disease management combining plant resistance, optimal fungicide use, and strategic biological control to enhance resilience and sustainability of global cereal production systems. Full article

Background: Candida auris has emerged as a multidrug-resistant fungal pathogen, presenting significant clinical challenges worldwide. Although considerable progress has been made in antifungal research, the specific mechanisms underlying drug resistance in C. auris remain incompletely understood. To overcome this problem, natural compounds can be used as valuable alternatives. The present study aimed to evaluate the antifungal activity of NEO against C. auris and to understand the functional mechanisms underlying its antifungal activity. Methods: The antifungal activity of NEO against C. auris strain CBS10913T was examined using broth microdilution and spot assays to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Mechanistic investigations were performed using phenotypic-, biochemical-, and fluorescence-based assays to evaluate its effects on cell wall integrity, membrane permeability, efflux pump activity, oxidative stress, lipid peroxidation, biofilm formation, and host cell adherence. Hemolytic assays were performed to evaluate preliminary biocompatibility. Results: During our study, we found that NEO showed strong fungicidal activity against C. auris, with an MIC of 500 µg/mL and an MFC of 650 µg/mL, and disrupted fungal cell wall integrity, significantly reduced ergosterol content, and inhibited efflux pump activity, leading to increased accumulation of fluorescent substrates. NEO induced increased intracellular reactive oxygen species, leading to oxidative-mediated lipid peroxidation and DNA damage. Moreover, NEO also suppressed stress biofilm formation, reduced metabolic activity, and decreased adherence to buccal epithelial cells, and it showed negligible hemolytic activity up to 2× MIC, indicating preliminary biocompatibility. Conclusions: This study demonstrates that NEO utilizes broad antifungal activity through multiple functional and phenotypic mechanisms, including disruption of membrane integrity, inhibition of efflux pump, induction of oxidative stress, and suppression of biofilm formation. Although the direct effects on pathogenicity-related genes or proteins were not studied, the findings still show NEO as a promising natural antifungal agent. Full article

Kaolin is an abundant, low-cost filler for elastomeric compounds. The kaolin used here is primarily kaolinite, chemically clean, and contains a fine particle population. Although agglomeration is evident, it can be mitigated by appropriate physical processing and, when desired, by chemical coupling. This study evaluates kaolin in natural rubber (NR) and examines how adding bis(triethoxysilylpropyl) tetrasulfide (TESPT) during mixing affects filler–matrix compatibility, viscoelastic response, cure stability, and mechanical performance. Kaolin was structurally and morphologically characterized, and the compounds were prepared in a closed mixer coupled to a torque rheometer under controlled dispersion conditions. Part 1 assessed NR with kaolin without a coupling agent, and Part 2 assessed the NR–kaolin with TESPT added during mixing (0.5 and 5 phr). Small-amplitude oscillatory shear (SAOS) was used to probe viscoelastic behavior, while oscillating disk rheometry (ODR) and tensile tests quantified cure and mechanical properties. In Part 1, kaolin increased NR stiffness in SAOS and raised the 100% and 300% moduli by about 40% and 50%, respectively, relative to the unfilled NR compound, while reducing cure reversion from 30% to 10% at 150 °C. In Part 2, TESPT produced a threshold-like response: 0.5 phr caused only minor changes, whereas 5 phr led to pronounced stiffening and cure stabilization. At 5 phr, a low-frequency plateau in G′ below 0.1 Hz with no G′–G″ crossover was observed, accompanied by higher M_H and ΔM in ODR and reversion suppressed to 1% after 30 min. These trends indicate the formation of a more connected filler-rubber network, promoted by TESPT-assisted interfacial coupling/adhesion, while also reflecting the ability of TESPT (tetrasulfide) to contribute sulfur and modify the curing chemistry. Mechanically, kaolin produced marked stiffness increases, with the 100% and 300% moduli increasing by an additional 9% and 36%, respectively, at 5 phr TESPT. At the same time, ultimate tensile strength remained lower than that of neat NR, and elongation at break decreased slightly. Overall, adding TESPT during mixing enhances interfacial coupling and network connectivity and, at higher loading, also influences cure chemistry, yielding higher modulus and strongly improved reversion resistance without increasing ultimate tensile strength relative to neat NR. Full article

The increasing resistance of agricultural pests to conventional pesticides necessitates the development of alternative biological control strategies. This study evaluated the acaricidal potential of two Photorhabdus luminescens strains (0805-P2R and the newly isolated 2103-RUVI) against the spider mite Tetranychus truncatus. Culture conditions were optimized using a Taguchi L9(3⁴) design to maximize growth, protease activity, and acaricidal efficacy. The optimized medium for strain 2103-RUVI achieved 90% mortality against T. truncatus at 72 h, compared to 83% for strain 0805-P2R under equivalent conditions. Genomic analysis identified putative phosphoporin PhoE genes exclusively in 2103-RUVI, which may contribute to its enhanced virulence, although this association remains correlative and requires functional validation. Histopathological observations confirmed severe tissue disruption in treated mites. Comparative analysis demonstrated complex, strain-specific relationships among bacterial growth, enzyme activity, and acaricidal effects. These results highlight the potential of the P. luminescens strain 2103-RUVI as an effective biocontrol agent, providing insights for its application in sustainable integrated pest management programs. Full article

Background: Chemotherapy is a cornerstone of cancer treatment; however, resistance to first-line chemotherapeutic agents remains a major challenge. ROS1, one of fifty-eight receptor tyrosine kinases, has been implicated in various cancer subtypes, including glioblastoma, non-small-cell lung cancer, and cholangiocarcinoma. Notably, the Gly2032Arg mutation in the ROS1 protein has been linked to resistance against the kinase inhibitor crizotinib. Objectives: Given the challenge, we conducted a comprehensive in silico study to identify new drug candidates. Methods: The study starts with modeling the Gly2032Arg-mutated ROS1 protein, followed by structure-based screening of the PubChem database. Results: Out of 1760 molecules screened, we selected the top 4 molecules (PubChem CID: 67463531, 72544946, 139431449, and 139431487) with structural features similar to crizotinib, a high docking score, and drug likeness. To further validate the effectiveness of the identified compounds, we assessed their binding affinity using the Molecular Mechanics with Generalized Born Surface Area (MM-GBSA) scoring method. To underpin the behavior and stability of protein–ligand complexes, 500 ns molecular dynamics (MD) simulations were conducted, and parameters including RMSD, RMSF, and H-bond dynamics were studied and compared. Density functional theory (DFT) at the B3LYP/6-31G* level was performed to elucidate molecular features of the identified compounds. Conclusions: Overall, this study sheds light on a new series of compounds effective against mutated targets, thereby offering a new horizon in this area. Full article

Plastic microbeads, widely incorporated into personal care and cleansing products, have emerged as a pervasive contaminant in freshwater systems, including in North America. Historical estimates indicate that North American consumers alone contributed trillions of microbeads daily to municipal wastewater, with global usage reaching quadrillions per day. Regulatory actions in 2017 in Canada and the USA to ban microbeads in personal care products appear to have greatly reduced microbead contamination levels, including a decrease in microbead proportion from 2 to 5% to 0.003%, and an 86% reduction in PE microbead discharge from wastewater treatment plants. Yet these particles still persist in the environment due to their resistance to degradation and continued release from unregulated sources, including industrial abrasives and certain cleaning agents. Studies across the Great Lakes, one of the world’s largest freshwater systems, have documented widespread microbead contamination in surface waters, sediments, and shorelines, highlighting their persistence and accumulation. This review synthesizes findings from key studies conducted between 2013 and 2017 to establish a pre-ban baseline of microbead distribution in the Great Lakes, and presents new data collected from 2018 to 2021 as a post-ban contamination assessment. The review emphasizes the unique challenges posed by microbeads within the broader context of microplastic pollution. We also hope that this paper underscores the critical role of polymer chemists and engineers in developing innovative materials and removal strategies to mitigate future contamination. Full article

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, a burden further exacerbated by HIV co-infection and the increasing prevalence of drug-resistant strains. Although a wide range of laboratory diagnostic methods are currently available, their applicability, implementation, and clinical impact vary substantially across healthcare settings with different levels of complexity and resources. This review provides a comprehensive overview of the main laboratory diagnostic methods for active and latent TB, emphasizing their clinical applicability, implementation challenges, and role within integrated diagnostic strategies. Conventional approaches, such as smear microscopy and culture, are discussed alongside modern diagnostic technologies, including automated nucleic acid amplification tests (NAATs), loop-mediated isothermal amplification (LAMP), line probe assays (LPAs), next-generation sequencing (NGS), and lateral flow assays, highlighting their strengths and limitations in distinct epidemiological and operational contexts. Unlike existing WHO guidelines and prior reviews that predominantly focus on test performance and recommendation status, this review adopts an implementation-oriented perspective, critically examining diagnostic methods in light of real-world constraints, regional disparities, and evidence gaps. Particular attention is given to limitations related to laboratory infrastructure, biosafety, workforce capacity, and sustainability, as well as to under-addressed areas such as latent TB, metagenomic approaches, and the investigation of co-pathogens. By integrating WHO guidance with contextual and operational considerations, this review aims to support rational test selection and the development of flexible, integrated diagnostic workflows tailored to local health system capacity, patient populations, and clinical scenarios, thereby strengthening the effectiveness and equity of TB diagnostic strategies. Full article

Background/Objectives: Reverse total shoulder arthroplasty (RTSA), a commonly performed procedure in elderly patients with osteoarthritis, is frequently complicated by postoperative infections—primarily caused by Cutibacterium acnes and coagulase-negative staphylococci (CoNS)—which remain a major clinical challenge. While standard antiseptic skin protocols can reduce the bacterial load at the surgical site, they often fail to achieve complete eradication, particularly with C. acnes, a resident species of the shoulder microbiome. Recent evidence indicates that intraoperative povidone–iodine irrigation is effective in significantly decreasing microbial burden; however, a thorough characterization of the virulence factors of the isolated strains remains essential. Methods: A total of 187 clinical strains isolated immediately after RTSA were characterized with respect to their antibiotic resistance profiles and biofilm-forming capacity, and the impact of intraoperative povidone–iodine irrigation on the reduction in bacteria that express these virulence traits was evaluated. Results: Of the 120 C. acnes isolates, 97.67% were susceptible to the tested antimicrobial agents, while only 3.33% exhibited resistance, specifically to clindamycin. In contrast, 53% of CoNS isolates were classified as susceptible, whereas the remaining 47% demonstrated multidrug resistance. Biofilm production was detected in 24% (29/120) of C. acnes and 39% (25/64) of CoNS isolates, with a statistically significant reduction observed after irrigation only for C. acnes. No association was found between biofilm formation and clindamycin resistance in C. acnes, likely due to the low number of resistant isolates. Conversely, among CoNS, a correlation was observed, with the 17.2% of biofilm-producing strains also exhibiting resistance to antimicrobial agents. Conclusions: Notwithstanding the presence of these virulence factors, povidone–iodine irrigation proved effective in substantially reducing the number of bacterial isolates recovered at the surgical site without selecting for strains with enhanced pathogenicity. Notably, the majority of resistant bacteria were detected prior to intraoperative irrigation. This intraoperative procedure may be a key approach to reducing prosthetic joint infections frequently caused by more virulent pathogens, which are unlikely to be selected following this disinfection strategy. Full article

Petrochemical fires pose severe threats to public safety and environmental sustainability, necessitating urgent advancements in efficient and eco-friendly fire suppression technologies. This study systematically investigated the influence of gas–liquid ratio (GLR) on the foam properties and fire suppression efficacy of a novel short-chain fluorocarbon (PFH-BZ) foam fire extinguishing agent. Through comprehensive experimental analysis, the underlying mechanism governing foam performance was elucidated, and the burn-back resistance of optimized formulation was evaluated. The results indicate that GLR significantly impacts PFH-BZ foam performance. Foaming capacity and structural stability exhibit a positive correlation with increasing GLR until reaching a plateau. Low GLRs result in insufficient foam formation and thermal stability, while inducing detrimental combustion intensification. Conversely, excessively high GLRs impair foam spreading capacity, hindering rapid extinguishment. The optimal fire extinguishing performance is achieved at a GLR of 12, where PFH-BZ foam attains an excellent balance among drainage characteristics, spreading capacity, and structural stability. This optimized formulation achieves complete extinguishment within 26.16 s and maintains burn-back resistance of 662.37 s while effectively mitigating the vapor explosion phenomenon. These findings provide critical guidance for the application of a PFH-BZ-based foam extinguishing agent and deepen understanding of the influence of system parameters on suppression performance. Full article

Air quality management in greenhouses is critical to safeguarding plant health and occupational safety, yet conventional filtration methods often fall short in performance and sustainability. These enclosed environments are prone to the accumulation of bioaerosols, including fungi, bacteria, pollen, and dust particles, which can compromise crop productivity and pose health risks to workers. This review explores recent advancements in air filtration technologies for controlled environments such as greenhouses, where airborne particulate matter, bioaerosols, and volatile organic compounds (VOCs) present ongoing challenges. Special focus is given to the development of filtration media based on electrospun nanofibers, which offer high surface area, tunable porosity, and low airflow resistance. The use of biodegradable polymers in these systems to support environmental sustainability is examined, along with electrospinning techniques that enable precise control over fiber morphology and functionalization. Antimicrobial enhancements are discussed, including inorganic agents such as metal nanoparticles and bio-based options like essential oils. Essential oils, known for their broad-spectrum antimicrobial properties, are assessed for their potential in long-term, controlled-release applications through nanofiber encapsulation. Overall, this paper highlights the potential of integrating sustainable materials, innovative fiber fabrication techniques, and nature-derived antimicrobials to advance air filtration performance while meeting ecological and health-related standards. Full article

In recent years, silver nanoparticles have emerged as potent antimicrobial agents capable of combating extensively drug-resistant pathogenic bacteria that pose serious health risks. The primary aim of our research was to explore the green synthesis of AgNPs using Candida glabrata as an antibacterial agent. A single clinical isolate of Candida glabrata was re-examined via traditional yeast identification methods. Biosynthesis of AgNPs was accomplished by incubating Candida glabrata cell-free supernatant with silver nitrate. AgNP formation was verified by UV-Vis spectroscopy, and the XRD technique assessed the physical properties of the lyophilized AgNPs. EDX and SEM provided insights into the AgNPs’ composition, shape, and size. The antibacterial efficacy was evaluated against pathogenic bacteria through the Agar Well Diffusion method. The formation of AgNPs was evidenced by a shift in color to dark brown. The formation of AgNPs at an absorbance wavelength of 430 nm revealed a polycrystalline structure with an average crystal size of 21.91 nm. The silver constituted 29.50% of the composition and indicated a spherical shape with sizes ranging from 74.96 to 100.40 nm. Significant antimicrobial activity was obtained against pathogenic bacteria. Hence, the proposed research highlights a single-step, cost-effective, and environmentally friendly AgNP synthesis approach that exhibits considerable antibacterial properties. Full article

Bovine respiratory disease (BRD) remains one of the most consequential health and economic challenges in U.S. beef production, particularly within integrated systems where microbial, environmental, and management factors intersect. This review synthesizes contemporary epidemiological insights, emphasizing BRD’s multifactorial pathogenesis driven by dynamic host–pathogen–environment interactions involving agents such as Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma bovis, alongside stressors from transportation, weaning, and commingling. BRD imposes annual losses exceeding two billion dollars through diminished feed efficiency, reduced carcass yield, increased treatment costs, and mortality. Despite progress in vaccination, biosecurity, and therapeutic interventions, BRD persists due to diagnostic subjectivity and limitations of traditional control measures. The review underscores emerging innovations, including precision livestock technologies, AI-enabled surveillance, and metabolomic biomarkers as transformative tools for early detection and targeted mitigation, while noting barriers related to cost, data harmonization, and scalability. The rising threat of antimicrobial resistance further highlights the need for stewardship frameworks that balance therapeutic effectiveness and public health priorities. Additionally, the paper analyzes policy and economic considerations, arguing for coordinated efforts among producers, veterinarians, researchers, and regulators. BRD is reframed as a systems-level challenge requiring integrated scientific, operational, and regulatory strategies to enhance resilience and sustainability across U.S. beef production. Full article

Background/Objectives: Simple urinary tract infections (sUTIs) are common in women and increasingly affected by multidrug-resistant (MDR) Escherichia coli. Extended-spectrum β-lactamase (ESBL) and AmpC producers restrict oral treatment options and promote carbapenem use. This study aimed to (i) describe the etiology and antimicrobial susceptibility of sUTIs in women of reproductive age in Oman, (ii) determine the prevalence of ESBL/AmpC-producing E. coli, (iii) evaluate nitroxoline, fosfomycin, mecillinam, and temocillin against ESBL and non-ESBL E. coli, and (iv) characterize circulating clones and resistance/virulence determinants using whole-genome sequencing (WGS). Methods: In this multicentric study (September 2022–August 2023), 795 uropathogens from 762 women (15–50 years) with sUTI were collected from four Omani hospitals. Identification and susceptibility testing of E. coli (n = 489) and Klebsiella pneumoniae (n = 140) using BD Phoenix and MALDI-TOF MS was performed (CLSI 2022). Thirty ESBL-producing and 82 non-ESBL E. coli underwent phenotypic ESBL/AmpC testing and evaluation of mecillinam, temocillin, nitroxoline, and fosfomycin. WGS was performed on 26 isolates (23 ESBL, 3 wild type) and analyzed for MLST, and SNP phylogeny using ResFinder, CARD, PlasmidFinder, VirulenceFinder. Statistical significance was set at p < 0.05. Results: E. coli (62%) and K. pneumoniae (18%) were the predominant pathogens. E. coli showed high susceptibility to nitrofurantoin (~97%), carbapenems, aminoglycosides, and piperacillin–tazobactam, but reduced susceptibility to cephalosporins, fluoroquinolones, cotrimoxazole, and ampicillin. ESBL prevalence ranged from 38–51%; AmpC producers were rare (4.6%). Mecillinam, nitroxoline, and fosfomycin exhibited 100% activity against both ESBL and non-ESBL isolates; temocillin showed 89.3% activity in ESBL strains. WGS identified 15 sequence types dominated by ST-131, ST-1193, ST-73, and ST-174, with blaCTX-M-15 as the major ESBL genotype. Conclusions: sUTIs in Oman show a high burden of ESBL-producing E. coli. Nitrofurantoin, mecillinam, fosfomycin, temocillin, and nitroxoline would be effective carbapenem-sparing oral options. Continuous phenotypic and genomic surveillance are crucial to guide antimicrobial therapy and stewardship. Full article