Search Results (536)

Introduction. Larvae of the insect Hermetia illucens can represent an alternative source for low-molecular-weight chitosan (CS) production compared with CS from crustaceans (CS_crustac), making it appealing in terms of pharmaceutical applications. Hence, the performances of CS_larvae and CS_crustac were compared herein by investigating the in vitro features of nanoparticles (NPs) made from each polysaccharide and administered with the antioxidant quercetin (QUE). Methods. X-ray diffraction and FT-IR spectroscopy enabled the identification of each type of CS. Following the ionic gelation technique and using sulfobutylether-β-cyclodextrin as a cross-linking agent, NPs were easily obtained. Results. Physicochemical data, release studies in PBS, and the evaluation of antioxidant effects via the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test were studied for both CS_larvae and CS_crustac. QUE-loaded NP sizes ranged from 180 to 547 nm, and zeta potential values were between +7.5 and +39.3 mV. In vitro QUE release in PBS was faster from QUE-CS_larvae NPs than from CS_crustac, and high antioxidant activity—according to the DPPH test—was observed for all tested NP formulations. Discussion. The agar diffusion assay, referring to Escherichia coli and Micrococcus flavus, as well as the microdilution assay, showed the best performance as antimicrobial formulations in the case of QUE-CS_larvae NPs. QUE-CS_larvae NPs can represent a promising vehicle for QUE, releasing it in a sustained manner, and, relevantly, the synergism noticed between QUE and CS_larvae resulted in a final antimicrobial product. Conclusions. New perspectives for low-molecular-weight CS are disclosed by adopting renewable sources from insects instead of the commercial CS_crustac. Full article

Polymicrobial biofilms involving fungal and bacterial species are increasingly recognized as contributors to persistent infections, particularly in the oral cavity. Candida albicans and Aggregatibacter actinomycetemcomitans are two commensals that can turn into opportunistic pathogens and are able to form robust biofilms. Objectives: This study aimed to assess the interaction dynamics between these two microorganisms and to evaluate their susceptibility to fluconazole and azithromycin in single- and mixed-species forms. Methods: Biofilm biomass was quantified using crystal violet assays, while biofilm cell viability was assessed through CFU enumeration (biofilm viability assay). To assess the resistance properties of single versus mixed-species coincubations, we applied the antimicrobial susceptibility test (AST) to each drug, and analysed spatial organization with confocal laser scanning microscopy, using PNA-FISH. Results: The results indicated that both species can coexist without significant mutual inhibition. However, a non-reciprocal synergism was also observed, whereby mixed-species biofilm conditions promoted the growth of A. actinomycetemcomitans, while C. albicans growth remained stable. As expected, antimicrobial tolerance was elevated in mixed cultures, likely due to enhanced extracellular matrix production and potential quorum-sensing interactions, contributing to increased resistance against azithromycin and fluconazole. Conclusions: This study provides novel insights into previously rarely explored interactions between C. albicans and A. actinomycetemcomitans. These findings underscore the importance of investigating interspecies interactions within polymicrobial biofilms, as understanding their mechanisms, such as quorum-sensing molecules and metabolic cooperation, can contribute to improved diagnostics and more effective targeted therapeutic strategies against polymicrobial infections. Full article

Modern microgrids face critical challenges in maintaining stability and efficiency due to renewable energy intermittency and dynamic load demands. This paper proposes a novel real-time energy management framework that synergizes a bio-inspired T-Cell optimization algorithm with decentralized voltage-based droop control to address these challenges. A JADE-based multi-agent system (MAS) orchestrates coordination between the T-Cell optimizer and edge-level controllers, enabling scalable and fault-tolerant decision-making. The T-Cell algorithm, inspired by adaptive immune system dynamics, optimizes global power distribution through the MAS platform, while droop control ensures local voltage stability via autonomous adjustments by distributed energy resources (DERs). The framework is rigorously validated through Hardware-in-the-Loop (HIL) testing using OPAL-RT, which interfaces MATLAB/Simulink models with Raspberry Pi for real-time communication (MQTT/Modbus protocols). Experimental results demonstrate a 91% reduction in grid dependency, 70% mitigation of voltage fluctuations, and a 93% self-consumption rate, significantly enhancing power quality and resilience. By integrating centralized optimization with decentralized control through MAS coordination, the hybrid approach achieves scalable, self-organizing microgrid operation under variable generation and load conditions. This work advances the practical deployment of adaptive energy management systems, offering a robust solution for sustainable and resilient microgrids. Full article

This research introduces an innovative passive vibration control methodology employing acoustic black hole (ABH) structures to mitigate vibration transmission in electric automotive steering machines—a prevalent issue adversely affecting driving comfort and vehicle safety. Leveraging the inherent bending wave manipulation properties of ABH configurations, we conceive an integrated vibration suppression framework synergizing advanced computational modeling with intelligent optimization algorithms. A high-fidelity finite element (FEM) model integrating ABH-attached steering machine system was developed and subjected to experimental validation via rigorous modal testing. To address computational challenges in design optimization, a hybrid modeling strategy integrating parametric design (using Latin Hypercube Sampling, LHS) with Kriging surrogate modeling is proposed. Systematic parameterization of ABH geometry and damping layer dimensions generated 40 training datasets and 12 validation datasets. Surrogate model verification confirms the model’s precise mapping of vibration characteristics across the design space. Subsequent multi-objective genetic algorithm optimization targeting RMS velocity suppression achieved substantial vibration attenuation (29.2%) compared to baseline parameters. The developed methodology provides automotive researchers and engineers with an efficient suitable design tool for vibration-sensitive automotive component design. Full article

The underwater environment severely degrades image quality by absorbing and scattering light. This causes significant challenges, including non-uniform illumination, low contrast, color distortion, and blurring. These degradations compromise the performance of critical underwater applications, including water quality monitoring, object detection, and identification. To address these issues, this study proposes a detail-oriented hybrid framework for underwater image enhancement that synergizes the strengths of traditional image processing with the powerful feature extraction capabilities of unsupervised deep learning. Our framework introduces a novel multi-scale detail enhancement unit to accentuate structural information, followed by a Latent Low-Rank Representation (LatLRR)-based simplification step. This unique combination effectively suppresses common artifacts like oversharpening, spurious edges, and noise by decomposing the image into meaningful subspaces. The principal structural features are then optimally combined with a gamma-corrected luminance channel using an unsupervised MU-Fusion network, achieving a balanced optimization of both global contrast and local details. The experimental results on the challenging Test-C60 and OceanDark datasets demonstrate that our method consistently outperforms state-of-the-art fusion-based approaches, achieving average improvements of 7.5% in UIQM, 6% in IL-NIQE, and 3% in AG. Wilcoxon signed-rank tests confirm that these performance gains are statistically significant (p < 0.01). Consequently, the proposed method significantly mitigates prevalent issues such as color aberration, detail loss, and artificial haze, which are frequently encountered in existing techniques. Full article

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

Mechanistic relationships between heat shock protein 90 (HSP90) and human epidermal growth factor receptor 2 (HER2) are complex and clinical correlations in breast cancer remain inconsistent. We investigated the role of HSP90 expression in the response of breast cancer cells to HER2-targeted treatments, by measuring cell viability/proliferation and protein expression after genetic and pharmacologic HER2/HSP90 modulation. HSP90 expression was also assessed by immunohistochemistry in a series of 72 metastatic, HER2+ breast cancer patients. In HER2+ breast cancer models (AU565, BT474, MCF7-HER2), HER2 downregulation induced HSP90 upregulation and growth inhibitory synergism between trastuzumab and docetaxel. HSP90 downregulation blunted the response to trastuzumab and docetaxel and their synergistic interactions. The addition of pertuzumab caused little additional growth inhibition, but HSP90 silencing unmasked a synergistic growth inhibitory effect with the triple combination. Conversely, HSP90 downregulation blunted the therapeutic response to trastuzumab/pertuzumab/tamoxifen or trastuzumab–emtansine. In HER2+ breast cancer patients, high HSP90 expression was associated with significant progression-free survival benefit with the triple combination, as compared with trastuzumab and chemotherapy, although the interaction test was not statistically significant. Overall, our results highlight a mechanistic role for HSP90 in determining the response of breast cancer cells to HER2-targeted agents and suggest that trastuzumab/pertuzumab combinations may be particularly advantageous in HSP90-high, HER2+ breast cancer. Full article

Background: Drug therapy remains the principal management strategy for malaria but is increasingly challenged by the emergence of drug-resistant malaria parasites. The need for new antimalarial drugs is urgent, yet drug discovery and development are hindered by high costs, long durations, and safety concerns that prevent approval. The current study aimed to determine antiplasmodial activities of approved drugs in combination with artemether (ART) and lumefantrine (LU). Methods: Using the SYBR Green I assay test, this study investigated the efficacy of epirubicin (EPI) and pelitinib (PEL) combined with ART and LU at fixed drug–drug ratios (4:1, 3:1, 1:1, 1:2, 1:3 and 1:4) and volume/volume. These combinations, as well as single drug treatments, were tested against cultured strains of Plasmodium falciparum (W2, DD2, D6, 3D7 and F32-ART) and fresh and cultured clinical isolates. The fifty percent inhibition concentration (IC₅₀) and a mean sum of fifty percent fractional inhibition concentration (FIC₅₀) were determined. Results: Synergism was observed when EPI was combined with both ART and LU across all fixed ratios with a mean of mean FIC₅₀ values of <0.6. The combination of LU and EPI against the 3D7 strain demonstrated the highest efficacy with a synergism FIC₅₀ value of 0.18. Most combinations of PEL with ART and LU showed antagonism (FIC₅₀ > 1) when tested against strains of P. falciparum and clinical isolates. Conclusions: This study underscores the utility of alternative drug discovery and development strategies to bypass cost, time, and safety barriers, thereby enriching the antimalarial drug pipeline and accelerating the transition from lab to market. Full article

Since ancient times, Royal Jelly (RJ) has been known for its remarkable properties in traditional medicine, and it is still widely recommended for mental and physical well-being. RJ consists of a unique and complex mixture of multiple constituents in different concentrations, and some of its biological activities are directly associated with specific components not found elsewhere in nature, such as (E)-10-hydroxy-2-decenoic acid (10-HDA) and its precursor 10-hydroxydecanoic acid (10-HDAA), two medium-chain fatty acids. Together, 10-HAD and 10-HDAA represent the major constituents of the total lipid fraction in RJ, but despite their structural similarity, the former has been extensively investigated over the years, while the latter has been only marginally reported. This review focuses on the promising effects of 10-HDAA that have emerged in a series of recent in vitro, in vivo, and docking simulation studies. Important bioactivities were observed for 10-HDAA, tested both as an individual compound, especially for immunoregulatory, estrogenic, and anti-inflammatory activities, and in synergic combination with other molecules. Specific anti-infective effects against endemic diseases, as well as the structural modification to synthesize biocompatible and biodegradable 10-HDAA-based amphiphiles, are also reported. Full article

Background/Objectives: The increasing occurrence of carbapenem resistance A. baumannii (CRAB) has forced clinicians to seek out alternative options with activity against CRAB. CRAB with inactivated PBP7/8 has been shown to result in an increased outer membrane permeability and could serve as a potential new adjuvant target. Methods: Two isogenic clinical isolates of A. baumannii HUMC1 were utilized (WT and HUMC1 ΔPBP7/8). Static concentration time-kill assays were performed against both isolates with escalating exposures to antibiotics. The resulting data were modeled using the Monolix software suite to capture parameters related to bacterial killing and PBP7/8 synergism. The model results were used to prospectively simulate clinically relevant antibiotic dosing of three antibiotics under physiological conditions and were validated using a hollow-fiber infection model (HFIM). Results: Treatment with monotherapy or combination therapy resulted in concentration-dependent killing for both isolates. Bacterial killing was greater with HUMC1 ΔPBP7/8 for all tested antibiotic concentrations. The mean bacterial population reduction was 4.38 log₁₀ CFU/mL for HUMC1 and 5.38 log₁₀ CFU/mL for HUMC1ΔPBP7/8 knockout isolate. The final mechanism-based model demonstrated improved antibacterial activity with PBP7/8 inhibition through a decline in KC₅₀ values of 59.7% across the beta-lactams in the PBP7/8 knockout. HFIM observations that were retrospectively compared to the simulated model-predicted bacterial concentration time course showed our final model was able to appropriately capture changes in bacterial population within a dynamic HFIM scenario. Conclusions: The quantification of KC₅₀ decline and increase in effectiveness of previously sidelined antimicrobial therapies with PBP7/8 inhibition suggests PBP7/8 is a promising potential target for an antibacterial adjuvant. This lends further support to advance to next-stage studies for identifying compounds that specifically inhibit PBP7/8 activity. Full article

To tackle the challenges of unknown image distortion and catastrophic forgetting in incremental inverse synthetic aperture radar (ISAR) target classification, this article introduces a deformation-robust non-exemplar incremental ISAR target classification method based on the Mix-Mamba feature adjustment network (MMFAN). The Mix-Mamba backbone employs channel-wise spatial transformations across multi-scale feature maps to inherently resist deformation distortions while generating compact global embedding through Mamba vision blocks. Then, the feature adjustment network facilitates knowledge transfer between base and incremental classes by dynamically maintaining a prototype for each target class. Finally, the loss bar synergizes supervised classification, unsupervised adaptation, and prototype consistency enforcement, enabling stable incremental training. Extensive experiments on ISAR datasets demonstrate the performance improvements of incremental learning and classification robustness under scaled, rotated, and mixed deformation test scenarios. Full article

In this study different strategies have been adopted to promote the shelf-life prolongation of fresh chicken nuggets. Two different by-products, grape pomace powder (GPP) and pomegranate peel extract (PE), alone and in combination with lactic acid, were suggested as meat preservatives. The antioxidant properties measured by different assays confirmed the presence of bioactive compounds in both by-products. To test their effects on meat samples, a control nugget without any compounds and a nugget with sole lactic acid were also used for comparison. During a refrigerated storage of about 2 weeks, microbiological stability and changes in sensory properties were monitored to assess the product shelf life. Results demonstrated that GPP promoted a good preservation of meat, and its combination with other compounds further increased the effectiveness. The control without any active agent remained acceptable for less than 1 day, the control with lactic acid for less than 2 days (p > 0.05). The other active samples lasted longer depending on the combinations of active compounds. When the sole GPP was used, about 3 days of shelf life were recorded (p < 0.05). While the combination of GPP with PE promoted only a slight increase of shelf life by 1 day (2.9 vs. 3.9 days), the combination of GPP with LA prolonged the shelf life to more than 6 days (2.9 vs. 6.58 days) (p < 0.05). The best results were found when both LA and PE were combined with GPP because the nuggets lasted about 10 days (p < 0.05). To better highlight the single and combined effects of the tested active agents, a proper index $\left(∆\%\right),$ comprising the normalized percent difference between the shelf life of the sample with the most antimicrobials and that of the sample with the least antimicrobials, was calculated, thus comparing the various samples and demonstrating the potential synergic effects among them. Full article

Background: Endophthalmitis, associated with intraocular procedures, is an infection of the eye that can rapidly result in substantial irreversible loss of vision and may even lead to removal of the eye. Prevention strategies vary globally and often include antibiotic use—often consisting of a broad-spectrum mono-therapeutic agent. The purpose of this study is to test the efficacy and value of combinations of cefuroxime (cefu), cefazolin (cefa), azithromycin (azith), and/or tobramycin (tob) as alternatives to the use of moxifloxacin. We looked for synergism since these antimicrobials used different mechanisms of inhibition. Methods: Initially, we examined individual antimicrobials to determine the minimal bactericidal concentrations (MBC) of each individual treatment against Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, two clinical isolates of MRSA, and Staphylococcus epidermidis, by both the Zone of Inhibition (ZOI) and the Colony Forming Unit (CFU) assays. We then used these data in a combinatorial study. Results: We found combinations that were synergistic against all the bacteria tested, resulting in total eradication [8 logs] of all bacteria. We found that the ZOI assay provided less consistent results than the CFU assays. Conclusions: We have found combinations of these antimicrobials that were synergistic in the total eradication (8 logs) of all bacteria tested. These three combinations were: cefuroxime/azithromycin; azithromycin/tobramycin; and cefuroxime/tobramycin. Moxifloxacin (Vigamox) did not completely eradicate Staphylococcus epidermidis. These combinations can then be used as eye drops to serve as a prophylactic for endophthalmitis after eye injections and eye surgery. Full article

The precise extractions of tree components such as wood (i.e., trunk and branches) and leaves are fundamental prerequisites for obtaining the key attributes of trees, which will provide significant benefits for ecological and physiological studies and forest applications. Terrestrial laser scanning technology offers an efficient means for acquiring three-dimensional information on tree attributes, and has marked potential for extracting the detailed tree attributes of tree components. However, previous studies on wood–leaf separation exhibited limitations in unsupervised adaptability and robustness to complex tree architectures, while demonstrating inadequate performance in fine branch detection. This study proposes a novel unsupervised model (NE-PC) that synergizes geometric features with graph-based path analysis to achieve accurate wood–leaf classification without training samples or empirical parameter tuning. First, the boundary-preserved supervoxel segmentation (BPSS) algorithm was adapted to generate supervoxels for calculating geometric features and representative points for constructing the undirected graph. Second, a node expansion (NE) approach was proposed, with nodes with similar curvature and verticality expanded into wood nodes to avoid the omission of trunk points in path frequency detection. Third, a path concatenation (PC) approach was developed, which involves detecting salient features of nodes along the same path to improve the detection of tiny branches that are often deficient during path retracing. Tested on multi-station TLS point clouds from trees with complex leaf–branch architectures, the NE-PC model achieved a 94.1% mean accuracy and a 86.7% kappa coefficient, outperforming renowned TLSeparation and LeWos (ΔOA = 2.0–29.7%, Δkappa = 6.2–53.5%). Moreover, the NE-PC model was verified in two other study areas (Plot B, Plot C), which exhibited more complex and divergent branch structure types. It achieved classification accuracies exceeding 90% (Plot B: 92.8 ± 2.3%; Plot C: 94.4 ± 0.7%) along with average kappa coefficients above 80% (Plot B: 81.3 ± 4.2%; Plot C: 81.8 ± 3.2%), demonstrating robust performance across various tree structural complexities. Full article

Infections caused by multi-drug-resistant Acinetobacter baumannii are a global threat. The World Health Organization has recognized carbapenem-resistant A. baumannii as critical pathogens for which further research and development of effective drugs are needed. The aim of this study was to identify antibiotic combinations with possible potential for additive or synergistic action with colistin, and thus to find new therapeutic possibilities for the treatment of infections caused by multi-drug-resistant A. baumannii. The research involved the two multi-drug-resistant A. baumannii strains isolated from hospitalized patients. In this study, six antibiotics were chosen to combine with colistin: amikacin, gentamicin, ampicillin/sulbactam, tigecycline, imipenem, and meropenem. For both strains, the synergistic activity of colistin and ampicillin/sulbactam was demonstrated, and additive activity for ABA25, colistin, and meropenem or imipenem. The MICs of antibiotics that showed synergism with colistin were reduced by 8- to 128-fold. Additive interactions have been shown in colistin combination with carbapenems, aminoglycosides, and tigecycline. The results prove the synergistic effect of the tested antibiotics, which may be helpful in the selection of potentially effective multi-drug therapies and their application in clinical practice, which may involve reducing the doses of colistin in therapy and its toxicity. Full article