Search Results (34,888)

Background: An accurate, sensitive, and robust potency assay is essential for the quality control of mRNA drug substances, which are characterized by complex manufacturing processes, intricate molecular structures, and high susceptibility to degradation. Currently, mRNA vaccine manufacturers use a variety of biological potency assays, often without systematic method development or rigorous evaluation. As a result, these assays may lack sufficient accuracy and robustness, making it difficult to reliably distinguish mRNA drug substance samples with different potency levels. Therefore, there is a need for a standardized, robust, and reliable potency assay for the evaluation of mRNA drug substance samples across a range of potencies. Methods: In this study, we developed a cell-based relative potency assay for a respiratory syncytial virus (RSV) mRNA drug substance encoding an engineered prefusion (PreF) form of the RSV type A (RSV-A) F protein, a recognized target for RSV vaccine development. The RSV mRNA drug substance was complexed with transfection reagents and introduced into cells in vitro to enable expression of the RSV-A PreF protein, which was then quantified using a double-antibody sandwich ELISA. Results: Systematic optimization showed that cell line, cell density, transfection reagent, mRNA-to-transfection reagent ratios, and transfection duration all influenced assay performance. Under optimized conditions, the assay demonstrated acceptable accuracy and precision, with relative bias values ranging from −25% to 13% across the potency range of 44~156%, measured-to-expected ratios within 0.8~1.2, and relative standard deviations of 18% and 16% for intra- and inter-assay precision, respectively. Furthermore, the optimized potency assay effectively distinguished mRNA drug substance samples with varying potency levels. Conclusions: This study provides a useful functional complement to physicochemical characterization and supports quality control and batch-to-batch consistency of RSV mRNA drug substances. In addition, the development strategy may also serve as a useful reference for the establishment of in vitro potency assays for other mRNA drug substances. Full article

Background/Objectives: Multidrug-resistant (MDR) Escherichia coli resistant to third-generation cephalosporins are a growing One Health concern, but data on extraintestinal pathogenic E. coli (ExPEC) from wildlife in North Africa remain scarce. We aimed to characterize ESBL/AmpC-producing ExPEC from captive wild mammals in Tunisia and to situate these isolates in a global genomic context. Methods: In 2018, 30 fecal samples from 14 captive wild mammals in a private farm were screened on cefotaxime agar. Four cefotaxime-resistant E. coli isolates were recovered from a llama, lion, hyena, and tiger. Antimicrobial susceptibility testing and Illumina whole-genome sequencing were combined with in silico typing, resistome and virulome profiling, plasmid and mobile element analysis, human pathogenicity prediction and core-genome MLST-based minimum-spanning trees. Results: All isolates were MDR but remained susceptible to carbapenems, colistin and tigecycline. Two ST162/B1 isolates from the llama and tiger carried bla_CMY-2, whereas two ST69/D isolates from the lion and hyena harbored bla_CTX-M-15 and qnrS1. Genomes encoded 61–68 antimicrobial resistance genes and 114–131 virulence-associated genes, together with IncF-, IncI1- and IncY-type plasmids and IS26-rich insertion sequence profiles. Mating-out assays yielded cefotaxime-resistant transconjugants, supporting plasmid transferability of bla_CMY-2 or bla_CTX-M-15. PathogenFinder predicted a ≥0.93 probability of human pathogenicity for all isolates. cgMLST-based trees showed that Tunisian ST69 and ST162 clustered within internationally disseminated lineages containing human, animal and food isolates, rather than forming wildlife-restricted branches. Conclusions: Captive wild mammals in Tunisia can harbor high-risk ExPEC lineages combining ESBL/AmpC production, multidrug resistance and extensive virulence and mobility gene repertoires. These findings highlight captive wildlife as potential reservoirs and sentinels of clinically relevant E. coli and underscore the need for integrated WGS-based One Health surveillance at the human–animal–environment interface in North Africa. Full article

A comparative investigation of the corrosion behavior evolution of 15%SiCp/Al-Cu-Mg aluminum matrix composites (AMC) subjected to different heat treatments in a salt spray environment containing 5wt% NaCl was performed. Metallographic microscopy was used to observe the surface morphology of the corroded materials. Field-emission transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used for microstructural evaluation and elemental analysis of the samples. Polarization curves and electrochemical impedance spectroscopy (EIS) were also employed to investigate the corrosion performance of the particle-reinforced aluminum matrix composites under different heat treatments. The test results indicate that, in addition to the influence of various grain boundary precipitates and electrochemical inhomogeneities between the precipitate-free zone (PFZ) and the aluminum matrix, differences in electrochemical properties between the SiC reinforcement particles and the aluminum alloy matrix are also a primary factor contributing to the corrosion of the aluminum-based composites in a 5wt% NaCl salt spray environment. Microstructural observations and electrochemical testing of AMC specimens at different corrosion stages indicate that under-aged samples exhibit relatively higher intergranular corrosion susceptibility. Under prolonged exposure to a salt spray environment, the over-aged specimen exhibited more pronounced galvanic corrosion phenomena, specifically, a significant decrease in Charge transfer resistance (R_ct) values and an increase in CPE values. R_ct results indicate that naturally aged AMC exhibits higher corrosion resistance than artificially aged AMC. With increased salt spray corrosion time, varying degrees of crevice corrosion occurred at the Al–SiC interface in all heat-treated samples. Full article

This study investigated the epidemiology, antimicrobial resistance, and transmission risks of β-lactamase, cefotaxime-hydrolyzing, Munich (bla_CTX-M)-positive Escherichia coli (CTX-M-EC) in large-scale pig farms in Jiangxi Province (China). In total, 278 samples (manure, wastewater, drinking water, and flies) were collected. CTX-M-EC strains were isolated and analyzed using antimicrobial susceptibility testing, resistance gene profiling, multilocus sequence typing, and genetic environment analysis with gene transfer assessed by transduction experiments. Twenty-seven CTX-M-EC strains (9.71%) were isolated, all exhibiting multi-drug resistance with 100% resistance to cefotaxime, ciprofloxacin, and tetracycline, and >90% resistance to ceftazidime, florfenicol, and trimethoprim-sulfamethoxazole. Four bla_CTX-M subtypes were identified. bla_CTX-M-55 was the predominant subtype (70.37%) and was distributed across diverse sequence types and serotypes. Each strain harbored multiple antibiotic resistance genes, plasmids, and virulence genes. Mobile elements such as ISEcp1 and IS26 were detected surrounding the bla_CTX-M gene, and 96.29% of strains successfully transferred the bla_CTX-M gene via transduction. Clones highly homologous to pig manure strains were detected in flies and sewage, suggesting that this resistance gene can spread between animals, the environment, and vectors. These findings highlight the high transmission risk of bla_CTX-M and underscore the need for rational antibiotic use, waste management, and vector control within a One Health framework. Full article

The search for harmless alternative solutions to protect crops has become urgent and has recently attracted widespread attention from researchers around the world focusing on natural polyphenols, which represent a treasure chest of molecules with potent activities. Due to the low water solubility of polyphenols, microemulsions were selected as nanovectors. Curcumin and mangiferin solubility in different excipients was evaluated by HPLC. Microemulsion was developed using pseudo-ternary phase diagrams. Sizes and polydispersity of microemulsion globules were evaluated by dynamic light scattering. Activity against Fusarium verticillioides was evaluated by a microdilution method. Vitamin E acetate was selected as the oily phase, Transcutol P as cosurfactant and Tween 80 as surfactant. S_mix was composed of Transcutol P and Tween 80 in a 1:2 gravimetric ratio and combined with oil-phase vitamin E acetate at a weight ratio of 3:1. Microemulsions were loaded with 5 mg/mL of each polyphenol and recovery results were 99.5% and 99.3% for curcumin and mangiferin, respectively. Sizes of the lipid phase were 121.7 ± 29.2 nm and 172.6 ± 19.3 nm, respectively, for mangiferin and curcumin microemulsions. F. verticillioides was very susceptible to both microemulsions with a very high activity at a dose of 0.9 mg/mL (log-4 reduction), evidencing a possible use of these nanoformulations to protect crops from F. verticillioides. Full article

Carbon fiber-reinforced polymer (CFRP) laminates are susceptible to barely visible impact damage (BVID) under low-energy bird-strike-like conditions. However, in previous studies, most damage evaluations for BVID were limited to a single scale. In this work, a multiscale characterization and evaluation method integrating the analytic hierarchy process (AHP) and the CRITIC weighting method was proposed to investigate the damage evolution of CFRP laminates under low-energy impacts (approximately 12–33 J). Delamination area (S_Da), indentation depth (P_D), surface crack aspect ratio (R_A), energy dissipation, and compression-after-impact (CAI) strength were analyzed based on phased-array ultrasonic C-scanning, 3D optical profilometry, and scanning electron microscopy. The results showed that P_D, S_Da, and energy dissipation increased from 108.73 μm to 213.93 μm, from 228.6 mm² to 695.8 mm², and from 5.96 J to 21.40 J, respectively, with increasing impact energy. Meanwhile, CAI strength decreased from 202.2 MPa to 118.9 MPa, with a maximum degradation rate of 41.16%. A critical transition was observed in the medium-to-high energy range, where delamination growth gradually plateaued, while intralaminar cracking and fiber fracture became increasingly dominant. The proposed framework enables quantitative grading of BVID severity and provides a practical basis for assessing residual damage in impacted CFRP laminates. Full article

The influence of conducted electromagnetic disturbances on the energy measurement error of electricity meters remains insufficiently explored in electromagnetic compatibility (EMC) studies, particularly in the frequency range above the classical harmonic domain. The aim of this study was to investigate the susceptibility of electricity meters with different input configurations to conducted disturbances in the frequency range 1 kHz–150 kHz, including the 2 kHz–150 kHz band covered by IEC 61000-4-19. The novelty of this work lies in the comparative analysis of meters employing a shunt resistor, current transformer, Rogowski coil, Hall-effect sensor, and a digital system based on a Merging Unit and Sampled Values. The tests were performed as a preliminary screening stage of the study, using a test procedure based on IEC 61000-4-19, in which the energy measurement error was determined from the difference between the energy measured by the meter under test and that measured by a reference meter while disturbances were injected into the current circuit. The results showed that, for most of the tested electronic meters, the influence of the disturbances at the applied 1 A level was limited. For the tested Class B meters, the observed maximum error deviations remained below 1%, while the largest deviation under continuous-wave disturbance was observed for the Merging Unit + SV system. The highest immunity to amplitude-modulated disturbances was found for the shunt-based meter and the Rogowski coil-based meter. In none of the investigated cases were large error deviations on the order of several percent or several tens of percent observed. The obtained results indicate that, under the applied test conditions, conducted disturbances in the investigated frequency range did not cause significant deterioration of the metrological performance of most of the analyzed electronic meters. However, the results should be interpreted as a comparative assessment under modified IEC-based test conditions, rather than as a full compliance evaluation at the normative disturbance levels for directly connected meters. Full article

Horizontal wells in bottom-water reservoirs are highly susceptible to water coning during production. Consequently, accurately evaluating the water-control performance of inflow control valves (ICVs) is critical for optimizing completion strategies. Conventional semi-analytical models often struggle to capture the transient dynamics of multiphase flow, while standard numerical reservoir simulators fail to explicitly resolve the complex geometries of completion hardware. To address these limitations, this study proposes a multiscale composite modeling framework tailored for bottom-water reservoirs. At the near-well scale, a semi-analytical model is developed to characterize wellbore hydraulics and the pressure drops induced by ICV completions. At the reservoir scale, a numerical model is employed to simulate multiphase fluid transport, with the two scales coupled via cross-scale pressure field mapping. Validation against NETool software under steady-state conditions confirms the physical consistency of the near-well model in determining zonal flow allocation. Comparisons with conventional equivalent well numerical models demonstrate that the proposed composite model offers superior resolution of ICV-induced flow redistribution, yielding distinct production performance profiles. Furthermore, the integration of a Particle Swarm Optimization (PSO) algorithm enables the dynamic optimization of ICV settings. Results indicate that this composite framework provides a robust theoretical and computational basis for designing and evaluating intelligent water-control completions in bottom-water reservoirs. Full article

The rectal mucosa houses a large number of viruses with important roles in shaping the local microbial communities and modulating immune responses, which could influence host susceptibility to infection and other diseases. Unique composition of the gut microbiome, including the predominance of clinically significant eukaryotic viruses like herpesviruses, cytomegalovirus, and human papillomavirus, has been described in both people with HIV (PWH) and men who have sex with men (MSM) vulnerable to HIV. Despite these insights, the rectal virome and the clinical implications of virome–bacteriome–immune interactions in the rectal mucosa remain poorly understood. In this review, we synthesize existing data on the composition of the rectal virome, its interactions with the bacteriome and the immune system, and implications on clinical outcomes in people living with or vulnerable to HIV. We also highlight the gaps and research needed to further explore and unravel these relationships. Full article

Freshwater ecosystems are increasingly threatened by eutrophication and other anthropogenic and climate-driven pressures that undermine ecological functioning and biodiversity. This study evaluates the transferability of a GIS-based multi-criteria decision analysis (GIS–MCDA) framework with Fuzzy Analytic Hierarchy Process (F-AHP), originally developed for a shallow coastal lake, to a morphologically distinct deep upland lake (Lough Tay, Ireland). Monthly in situ measurements at a single monitoring point in 2024 were analysed together with meteorological variables using Spearman rank correlations. Because spatial interpolation of in-lake water quality parameters was not feasible, eutrophication susceptibility was mapped using four external spatial drivers: distance from water resources (River Cloghoge inflows), land-based nitrogen export potential, distance from environmental pollutants represented by the transportation network, and a wind exposure index derived from a DEM and wind-rose analysis. Criteria were standardized with fuzzy membership functions, weighted using F-AHP (consistency index 0.056), and aggregated using weighted linear combination at 25 m resolution. The resulting Eutrophication Susceptibility Index (ESI) ranged from 0.18 to 0.81, indicating generally moderate to good conditions, with higher ESI values concentrated in the northern lake sector near inflow zones. The results demonstrate that GIS–MCDA can be adapted to lakes with limited monitoring by relying on external drivers, providing a spatial proxy for susceptibility rather than measured trophic status. Full article

Gray mold caused by Botrytis cinerea poses a severe threat to tomato production. In this study, physiological, biochemical, transcriptomic, and proteomic analyses were integrated to characterize the dynamic responses of tomato ‘Ailsa Craig’ to B. cinerea infection. During B. cinerea infection, peroxidase (POD) activity showed a progressive increase, while catalase (CAT) activity was significantly upregulated at 24 hpi and remained stable through 48 hpi. Malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) contents showed a delayed response, increasing significantly only at 48 hpi, whereas SOD activity exhibited a biphasic pattern. Transcriptome and proteome profiling identified 5824 differentially expressed genes and 124 differentially expressed proteins. Functional enrichment analysis highlighted defense-related pathways, including plant–pathogen interaction, flavonoid biosynthesis, and inositol phosphate metabolism. Notably, the chlorophyll a/b-binding protein SlLhcb13 exhibited post-transcriptional upregulation despite transcriptional suppression. Functional validation demonstrated that overexpression of SlLhcb13 enhanced resistance, whereas silencing increased susceptibility. These findings identify SlLhcb13 as a positive regulator linking photosynthesis to immunity and provide new insights into the defense mechanisms of tomato. Full article

Otitis externa in dogs is primarily caused by Malassezia pachydermatis. Treatment involves antifungal and antiseptic agents; however, resistance among causative organisms has been noted. Pomelo (Citrus maxima) is a source of bioactive compounds with antimicrobial activity. Its extract mainly includes essential oils, which are mostly applied for alternative treatment for M. pachydermatis. The study aimed to investigate the anti-M. pachydermatis effects of pomelo peel extracts and their potential use in topical solutions for canine infections. M. pachydermatis was isolated from dogs and confirmed with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS). Antifungal susceptibility of M. pachydermatis to itraconazole was evaluated. Phytochemicals of essential oil and crude extract from C. maxima peel were determined using Gas Chromatograph–Mass Spectrometry (GC-MS/MS). In addition, the antifungal activity of the extracts was assessed using an agar plate dilution assay. The essential oil was formulated into a prototypic topical solution, and its effects on M. pachydermatis were observed in vitro. The prevalence of M. pachydermatis was 42%, with 53% having yeast on both ear sides. The minimum inhibitory concentrations (MIC) of itraconazole, essential oil, and crude extract to M. pachydermatis were 0.03–0.25 µg/mL, 1.0% v/v, and >200 mg/mL, respectively. The prominent phytochemicals in peel extracts were meranzin hydrate and D-limonene, identified in the crude extract and essential oil, respectively. Moreover, a topical solution containing essential oils inhibited M. pachydermatis growth and showed destructive effects on the yeast cell wall at higher concentrations. The essential oil exhibits antifungal activity against M. pachydermatis, primarily due to the high concentration of D-limonene. The growth was inhibited completely at MIC, observed over a 5-day period. Furthermore, the prototypic topical solution demonstrated an anti-M. pachydermatis effect. These findings suggest potential veterinary applications for pomelo peel extract, though further studies are necessary to assess stability, mechanism of action, and industrial suitability. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a global threat to human, animal, and environmental health. Among bacteria, E. coli is frequently used as a key indicator of AMR. Despite their genetic proximity to humans, studies on AMR in Non-Human Primates (NHPs) remain limited, particularly in semi-anthropized environments. This study aims to characterize the antibiotic resistance profiles and phylo-groups of E. coli isolated from NHPs and humans at a primatology center. Methods: A total of 143 stool samples were collected, including 125 from NHPs and 18 from humans. Isolates were cultured on Eosin Methylene Blue agar and then identified by MALDI-TOF mass spectrometry. Antibiotic susceptibility was assessed using the Kirby–Bauer disk diffusion method, with 30 antibiotics following CASFM-EUCAST recommendations. E. coli phylo-groups were characterized by quadruplex PCR according to the Clermont method, targeting the genes. Results: A total of 122 E. coli isolates (85.31%) were recovered, with comparable prevalence observed across NHPs and human staff. More than half of the isolates (55.74%) were resistant to at least one antibiotic tested, and 12.3% were classified as multi-drug resistant (MDR). Resistance rates of isolates in Mandrillus sphinx, Pan troglodytes, and humans were 50.6%, 57.7%, and 80.0%, respectively, with no significant statistical difference (p = 0.11). A single Extended-Spectrum Beta-Lactamase (ESBL) producing isolate was identified in the mandrill. Phylo-group analysis revealed the dominance of group A (50%), followed by groups B1, D, and C. Conclusions: Resistance profiles and phylo-group distribution among NHPs could suggest bacterial exchange and potential for cross-transmission of AMR within the shared environment. Full article

Small drone-borne W-band synthetic aperture radar (SAR) systems are highly susceptible to motion errors that conventional navigation sensors and phase-based autofocus algorithms cannot effectively resolve due to phase wrapping. This paper presents a sensor-independent imaging framework to robustly suppress these errors. First, joint time-frequency analysis is employed to identify and discard motion-corrupted pulses. Subsequently, a compressed sensing-based backprojection algorithm reconstructs high-resolution images from the remaining sparse dataset. To alleviate the substantial memory burden of matrix-based compressed sensing, the reconstruction is reformulated iteratively. Experimental results confirm that the proposed method maintains structural integrity even when up to 60% of the received pulses are corrupted and demonstrates robust focusing down to an SNR of −25 dB. This approach provides a practical, memory-efficient, and cost-effective solution for SAR platforms. Full article

Cucurbit crops—including cucumber (Cucumis sativus), watermelon (Citrullus lanatus), and melon (Cucumis melo)—are of major economic and nutritional importance worldwide. Yet their productivity and quality are severely compromised by foliar fungal diseases, particularly powdery mildew (PM), downy mildew (DM), and target leaf spot (TLS). While PM and DM have been extensively studied, TLS has emerged as an increasingly prevalent and damaging disease in key production regions, yet it remains comparatively understudied—especially with respect to its molecular basis and comparative pathobiology relative to PM and DM. Current reliance on chemical fungicides is hampered by escalating pathogen resistance and concerns over residual toxicity, whereas conventional breeding approaches face inherent limitations in pyramiding durable, broad-spectrum resistance against multiple pathogens. In this context, cucumber has emerged as a pivotal model species for dissecting foliar disease resistance mechanisms in cucurbits, supported by a high-quality reference genome, extensive resequencing datasets, diverse germplasm collections, and an efficient Agrobacterium-mediated transformation system. Despite these advantages, existing reviews predominantly address PM or DM resistance in isolation; comprehensive syntheses integrating TLS resistance advances—and critically, cross-disease comparisons of genetic architecture, transcriptional reprogramming, and defense signaling—are notably scarce. Furthermore, the translational pipeline—from gene discovery and functional validation to deployment in marker-assisted or genome-edited breeding—lacks systematic evaluation. Here, we provide a focused, cucumber-centered review that (i) synthesizes recent progress in mapping QTLs and GWAS loci, and characterizing key resistance-associated gene families (such as NLRs, RLKs, PR genes) conferring resistance to PM, DM, and TLS; (ii) integrates transcriptomic, epigenomic, and proteomic evidence to delineate conserved versus pathogen-specific host responses; (iii) highlights breakthroughs and unresolved questions in TLS resistance research, including the roles of novel susceptibility factors and non-canonical immune regulators; and (iv) critically assesses bottlenecks in translating resistance genes into practical breeding outcomes—such as linkage drag, functional redundancy, and genotype-by-environment interactions—and proposes empirically grounded strategies for accelerating molecular design of multi-disease-resistant cultivars. Collectively, this review aims to bridge fundamental insights with applied breeding goals, offering a conceptual and strategic framework for integrated management of foliar fungal diseases and the development of durable, broad-spectrum resistance in cucurbits. Full article