Search Results (3,434)

Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been the principal agent for RSV immunoprophylaxis, reducing hospitalization in defined high-risk groups through monthly intramuscular dosing. The recent approval of two second-generation long-acting mAbs, nirsevimab and clesrovimab, and maternal preF vaccine has fundamentally changed the RSV prevention landscape. In contrast to palivizumab, the long-acting mAbs offer single-dose seasonal protection across a broader infant population, enabling universal immunization programmes for the first time. In this review, we conjointly examine nirsevimab and clesrovimab across their mechanisms of action, pharmacokinetics, efficacy, safety and cost-effectiveness, using palivizumab as the reference standard. Cross-trial efficacy comparisons are complicated by differences in study populations and endpoint definitions; however, when these factors are considered, the available evidence suggests that all three agents offer broadly comparable protection against severe RSV disease. All three agents also demonstrate favourable and comparable tolerability profiles. Nirsevimab is now supported by a substantial body of real-world evidence confirming effectiveness in routine immunization programmes that closely align with registrational studies. Clesrovimab, as the newest agent, currently lacks real-world effectiveness, and both long-acting monoclonals require further confirmatory evidence in high-risk groups. Overall, existing data support that both monoclonals have equivalent efficacy and safety profiles as palivizumab, and choice should be based on cost-effectiveness and local availability, with consideration given to optimal integration of infant immunoprophylaxis alongside maternal RSV vaccination programmes. Full article

This study investigates the decay-like degradation mechanisms of the matrix material in composite insulators, focusing on the pronounced influence of humid environments on partial discharge (PD) characteristics and degradation pathways. A sealed chamber discharge platform was established, integrating PD signal monitoring, surface characterization, and gas chromatography-mass spectrometry (GC-MS) with molecular network analysis to examine the synergistic effects of thermal influences from PD and active atmospheric particles at humidity levels of 0% RH, 50% RH, and 100% RH. Results show that dry conditions favor high-energy, low-repetition-rate discharges, promoting cleavage and recombination of high-bond-energy bonds (e.g., benzene rings and (α)C–O), yielding primarily long-chain carboxylic acids (C9 and above). In contrast, humid conditions shift to low-energy, high-repetition-rate discharges, with water vapor decomposition generating highly oxidizing hydroxyl radicals (·OH). These facilitate selective scission of lower-bond-energy (β)C–O bonds and deep oxidation, significantly increasing short-chain dicarboxylic acids—especially oxalic acid—whose acidity and water solubility are nearly an order of magnitude higher than in dry environments, becoming the dominant acidic products. The work demonstrates that many PD-generated organic acids act as intrinsic corrosive agents in insulating systems, independent of ambient nitric acid. This elucidates, at the reaction pathway level, how high humidity modulates PD to enhance corrosive acid production, providing a microchemical basis for understanding regional decay-like failure patterns in composite insulators. Full article

Antimicrobial resistance represents a major global health challenge, highlighting the urgent need for alternative bioactive compounds from natural sources. This study investigated the phytochemical composition and antimicrobial potential of saponin-enriched extracts from the trunk bark of Argania spinosa (L.) Skeels, collected from two contrasting Algerian regions: the coastal area of Stidia (ES) and the Saharan region of Tindouf (ET). Extraction yields were comparable (approximately 12.6%). UHPLC-MS analysis revealed distinct phytochemical profiles, with ES enriched in oleanane-type saponins and flavonoids, whereas ET showed a higher abundance of bayogenin-type derivatives. Key compounds included arganine C, E, and J, as well as catechin and quercetin. Antimicrobial activity was evaluated using agar well diffusion and broth microdilution assays against clinically relevant microorganisms, including the reference strains Staphylococcus aureus and Listeria innocua, together with Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, and Candida albicans. Both extracts exhibited broad-spectrum antimicrobial activity, although ES consistently showed lower Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal, Fungicidal Concentration (MBC)/(MFC) values than ET. MIC values ranged from 25 to 50 mg/mL for ES and from 50 to 100 mg/mL for ET. Synergistic interactions were observed between ES and gentamicin against S. aureus and between both extracts and kanamycin against K. pneumoniae. Membrane permeability assays demonstrated that both extracts increased bacterial membrane permeability, with ET producing a stronger permeabilizing effect. Atomic force microscopy of ES-treated cells revealed marked alterations in bacterial surface morphology, while molecular docking supported strong interactions of mi-saponin B and arganine derivatives with key bacterial targets. Collectively, these findings highlight the potential of A. spinosa bark saponins as natural antimicrobial agents and promising antibiotic adjuvants against multidrug-resistant pathogens. Full article

Efficient and financially sustainable social protection systems are essential under conditions of economic instability and increasing social demand. However, traditional administrative models are often characterized by high operational costs, procedural complexity, and delayed benefit delivery. This study examines the role of digitalization, process automation, and AI-driven administrative solutions in reducing administrative expenses while enhancing the sustainability and resilience of social protection systems. An integrated Automation Index is developed using standardized proxy indicators that reflect reductions in operational and transaction costs associated with digital and automated technologies. To assess future trajectories of administrative expenses, scenario-based modelling is applied under three digital transformation paths—baseline, moderate, and intensive. Administrative efficiency is estimated using a translog Stochastic Frontier Analysis (SFA) framework. The results indicate that digitalization and automation significantly reduce administrative costs only when supported by favorable institutional conditions, including decentralized governance, effective inter-agency coordination, and clearly regulated administrative procedures. Under the intensive digital transformation scenario, administrative expenses decline substantially relative to the baseline, while system responsiveness and beneficiary coverage improve. In contrast, weak institutional environments limit the efficiency gains of technological solutions. The study concludes that AI agents and automated systems should be viewed not as substitutes for human decision-making but as tools for optimizing administrative architectures. This transition from resource-intensive to technology-intensive models is particularly important for developing countries seeking sustainable social protection under constrained fiscal conditions. Full article

The increasing resistance of agricultural pests and disease-vectoring arthropods to synthetic pesticides underscores the urgent need for novel and sustainable biocidal agents. This study evaluates, for the first time, the insect antifeedant and ixodicidal activities of essential oils derived from ten Amazonian Piper species and their major constituents. Antifeedant effects were assessed against Spodoptera littoralis, Myzus persicae, and Rhopalosiphum padi, whereas ixodicidal activity was tested on Hyalomma lusitanicum. Additionally, the effects of these oils on the plant-parasitic nematode Meloidogyne javanica were investigated. Essential oils from Piper mituense (51.6% apiol) and P. sancti-felicis (76.1% apiol) exhibited the highest bioactivity, achieving more than 75% feeding inhibition across all insect species and 100% tick mortality. P. mituense consistently demonstrated greater potency, suggesting possible synergistic interactions among its minor constituents. Principal component analysis linked apiol-rich chemotypes with broad-spectrum activity. In contrast, oils rich in oxygenated caryophyllene derivatives, particularly those from P. casapiense, showed strong selective antifeedant effects against R. padi. Pure apiol displayed activity across all assays, whereas no nematicidal effects were observed. Molecular docking analyses supported these findings, indicating that apiol can interact with acetylcholinesterase in addition to its known effect on cytochrome P450 targets. Overall, these results identify complementary Piper chemotypes with promising potential as dual-purpose biopesticides for integrated pest management strategies. Full article

This study investigates the influence of PLA flowability and talc content on the performance of compostable thermoplastic starch/poly(butylene succinate) (TPS/PBS)-based systems for rigid applications. Different PLA grades with varying melt flow index (PLA23, PLA8 and PLA70) and talc contents (0, 5 and 10 wt%) were incorporated. Twelve formulations were compounded by twin-screw extrusion and processed by injection moulding. FTIR confirmed the coexistence of TPS, PBS and PLA phases without evidence of chemical interactions. Morphological analysis showed that PLA flowability plays a key role in phase distribution, with higher-flow PLA promoting improved dispersion and interfacial adhesion, while talc addition (5 and 10 wt%) increased structural heterogeneity; at higher loadings, particularly, DSC analysis revealed that talc acted as a nucleating agent for the PBS phase, increasing crystallisation temperatures from approximately 73 °C to 81 °C depending on formulation. Mechanical results showed that Young’s modulus increased from approximately 1.4 GPa to 2.7 GPa with decreasing PLA flowability and increasing talc content. Formulations containing low-flow PLA reached tensile strengths close to 32 MPa, although elongation at break decreased to values near 2%. In contrast, high-flow PLA formulations exhibited a more balanced mechanical response, with elongation values up to approximately 8%, associated with improved phase dispersion. Hybrid PLA systems showed intermediate behaviour, reaching elongations up to 22% while maintaining modulus values around 1.8 GPa. Talc provided additional reinforcement but reduced deformation capacity. HDT values remained relatively constant, indicating limited improvement in thermomechanical resistance despite increased stiffness. These results demonstrate that the combined control of PLA molecular characteristics and talc content enables tuning of the mechanical and thermomechanical performance of TPS/PBS/PLA/talc systems for rigid packaging applications. Full article

Xylazole is a sedative and analgesic agent widely used in Chinese veterinary practice, valued for its convenient administration and effectiveness. This study aimed to clarify its mechanism of action by investigating the effects on cAMP and monoamine neurotransmitters using both in vitro and in vivo rat models. In rat cortical neurons, Xylazole increased cAMP levels in a concentration- and time-dependent manner, transiently increased extracellular DA levels, which subsequently declined, consistently reduced extracellular NE levels, and enhanced extracellular 5-HT along with its metabolite 5-HIAA. In contrast, in vivo administration in adult rats reduced cAMP, DA, and NE levels across multiple brain regions, including the cerebrum, hippocampus, and brainstem, while increasing 5-HT and 5-HIAA. Notably, in the cerebellum group, cAMP was elevated after drug washout, a pattern not observed in the other brain regions. These findings reveal a striking divergence: in P7 cortical neurons, Xylazole triggers an α₂-adrenoceptor-dependent cAMP elevation, whereas in adult brain regions, a high concentration of locally delivered Xylazole leads to predominantly inhibitory cAMP changes, with a notable delayed increase in the cerebellum. Because of the non-physiological concentration used in reverse microdialysis, the in vivo neurochemical patterns should be regarded as exploratory regional responses, not as evidence of specific receptor-mediated mechanisms. Full article

Zinc deficiency is increasingly recognized as a risk factor for neurodegenerative diseases, yet the underlying molecular mechanisms remain incompletely understood. In this study, we investigated the impact of intracellular zinc depletion on oxidative stress and inflammasome activation in microglial (SIM-A9) and neuronal (SH-SY5Y) cell models, and evaluated the protective effects of polyphenolic compounds. Intracellular zinc chelation with the membrane-permeable chelator TPEN markedly increased reactive oxygen species (ROS) production, reduced cell viability, and upregulated the mRNA expression of NLRP3 inflammasome-related genes and pro-inflammatory cytokines. In contrast, extracellular zinc chelation had no effect, highlighting the critical role of intracellular zinc homeostasis in maintaining redox balance. Zinc supplementation significantly attenuated these responses. Among 32 polyphenols screened by DPPH radical scavenging assay, caffeic acid derivatives—chicoric acid (ChA), rosmarinic acid (RA), and caffeic acid phenethyl ester (CAPE)—exhibited the most potent antioxidant activity, surpassing that of edaravone. These compounds suppressed ROS production and differentially protected against zinc deficiency-induced cellular damage. ChA showed the strongest ROS inhibitory activity (IC50: 1.9 µM in SIM-A9), RA provided robust cytoprotection even at low concentrations, and CAPE most effectively suppressed inflammasome-related gene expression and inhibited aggregation of both Aβ1–42 and the highly neurotoxic pyroglutamate-modified variant pEAβ3–42. These findings demonstrate that intracellular zinc deficiency drives ROS-dependent upregulation of NLRP3 inflammasome-related genes, and suggest that caffeic acid derivative polyphenols may serve as complementary agents for mitigating neuroinflammatory and amyloidogenic processes relevant to Alzheimer’s disease. Full article

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. The hallmark pathophysiological alteration consists of involuntary, action-induced adductor spasms of the laryngeal muscles during respiration, particularly during inspiration. LABD must be distinguished from inducible laryngeal obstruction (ILO), a broader, heterogeneous condition encompassing episodic, stimulus-triggered supraglottic or glottic closure, associated with asthma, reflux, or psychological triggers, that is generally not task-specific and lacks the neurological substrate characteristic of dystonia. In contrast, LABD is a persistent, effort-dependent, neurologically driven dystonia, demonstrable by paradoxical adductor spasms on fibreoptic laryngoscopy during normal inspiration and confirmed electromyographically by paradoxical thyroarytenoid muscle activation instead of the expected inspiratory relaxation. Traditional treatments, including respiratory retraining, speech therapy, biofeedback, psychotherapy, benzodiazepines, dopamine-blocking agents, and anticholinergic drugs, have proved largely ineffective. Tracheostomy may be required in cases of severe respiratory compromise. Botulinum toxin type A (BoNT/A) injections have been reported to successfully reduce inspiratory stridor in selected patients. Here, we present three cases of LABD displaying distinct phenotypes, in which typical features were associated with involvement of extra-laryngeal cranial districts, further expanding the known phenotypic spectrum of this condition. Full article

Coastal zones are dynamic interfaces where land, ocean, and atmosphere interact, making them sensitive indicators of environmental change. However, quantifying shoreline movement across long distances and over multi-year timescales remains challenging using traditional ground-based methods alone. We conducted an analysis of environmental factors and shoreline dynamics along a 58 km stretch of the arid Cabo Pulmo shoreline in Mexico from 2020 to 2026 using the CoastSat tool. The landscape is characterized by a diverse array of geographical features, including sandy beaches, granite cliffs, estuarine systems, and various anthropogenic structures. Results indicated a sea-level rise of 2 mm/year over the last 27 years, which is consistent with the reported range for the Pacific (1.8 to 3.8 mm/year). Notably, we observed an increasing trend of Category 4 and 5 hurricanes in the Mexican Pacific, with an average of 1 additional hurricane per decade (1950–2023). A total of 457 Sentinel-2 satellite images were used for automated analysis using the CoastSat platform, all of which were acquired under tidal conditions not exceeding 1 m. Our findings indicate that the granite cliffs show no detectable horizontal changes in the satellite images; however, their minimal vertical erosion contributes sediment to adjacent beaches. The most significant shoreline erosion was observed north of a marina breakwater, measuring −19.7 m, attributed to the disruption of littoral transport toward the southeast. In contrast, sandy beaches located in front of streams and estuaries—characterized by a lack of infrastructure (houses and breakwaters) and gentle slopes of 2° to 4°—demonstrated positive accretion of up to 5.9 m. According to the autoregressive distributed lag model, wave energy and hurricane-driven wind gusts are the primary agents of shoreline retreat, displacing sediment seaward to the continental shelf. Sea level rise exacerbates this retreat, while rainfall plays a minor but contributing role by transporting sediment during hurricanes in this arid region. This study highlights the effectiveness of CoastSat as a neural network-based tool for analyzing shoreline changes; however, we faced certain limitations, such as the absence of in situ beach profiles due to restricted access. Full article

Transmission electron microscopy (TEM) is a key tool for ultrastructural analysis, yet its performance critically depends on contrast agents, many of which are constrained by toxicity and regulatory concerns. In this study, Wells–Dawson (WD)-type polyoxometalates (POMs), including Parent WD-POM, Lacunary WD-POM, Zr-WD 1:2 POM, and Hf-WD 1:2 POM, were investigated as alternative contrast agents for TEM imaging of rat kidney tissue. Among the tested compounds, Hf-WD 1:2 POM provided the most consistent contrast enhancement, enabling clear visualization of subcellular structures with minimal background interference and no detectable aggregation. Its contrast performance depended on both concentration and incubation time, with higher concentration (0.01 mol/L) and prolonged incubation (24 h) yielding increased signal-to-noise ratio (SNR), although SNR alone did not fully reflect image quality. In comparison with conventional staining agents (uranyl acetate and Uranyless), Hf-WD 1:2 POM achieved significantly improved contrast effectiveness without inducing detectable tissue damage. These findings identify Hf-WD 1:2 POM as a promising non-radioactive alternative for TEM imaging and support the potential of POMs as versatile platforms for the development of advanced contrast agents. Full article

Urinary tract infections (UTIs), particularly catheter-associated UTIs (CAUTIs), represent a significant clinical problem due to the predominance of Gram-negative uropathogens, their ability to form biofilms, and the increasing prevalence of antimicrobial resistance, which together reduce the effectiveness of conventional antibiotic therapy. This study aimed to evaluate the antimicrobial activity of selected natural plant-derived compounds against clinical Gram-negative uropathogens isolated from CAUTIs. The antibacterial effects of gallic acid, quercetin-3-D-glucuronide, and apigenin were assessed against Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, including both ciprofloxacin-susceptible and -resistant strains. Antimicrobial activity was determined using the broth microdilution method, followed by quantitative assessment of bacterial viability based on colony-forming unit (CFU) enumeration. Gallic acid exhibited the strongest concentration-dependent inhibitory activity, reducing bacterial viability by up to 2–3 log₁₀ CFU across all tested species. Quercetin-3-D-glucuronide demonstrated moderate antibacterial effects with a predominantly bacteriostatic profile, resulting in a partial but consistent reduction in CFU counts. In contrast, apigenin showed only weak effects on bacterial viability under the applied experimental conditions. None of the tested compounds achieved complete bacterial eradication. These findings indicate that gallic acid and quercetin-3-D-glucuronide possess inhibitory activity against Gram-negative uropathogens, including antibiotic-resistant strains, supporting their potential use as adjunctive agents targeting bacterial persistence in UTIs rather than as standalone antimicrobials. In the present study, the viability of planktonic bacterial cells was assessed; however, future studies should focus on evaluating the direct impact of the tested compounds on biofilm structure and biofilm formation dynamics. Full article

The spread of non-native freshwater turtles in urban, peri-urban, and natural environments poses increasing ecological and sanitary concerns, particularly due to their potential role as reservoirs of infectious agents. Among these, DNA viruses remain largely unexplored in both invasive and native chelonians. In this study, a molecular survey targeting selected viral pathogens was conducted on oral and cloacal swabs collected from non-native freshwater turtles from natural and confinement ponds in Northeastern Italy, with the aim of assessing the pathogen’s presence and their potential epidemiological relevance. One hundred sixty-four pond sliders (Trachemys scripta) were sampled from three sites: Herpesviruses and ranaviruses were not detected; in contrast, adenoviruses were frequently identified (72/163, 44.2%). Sequence analyses allowed their classification mostly as Testadenovirus trachemys, with only a single detection of a strain closely related to siadenoviruses and previously associated with mortality events in other tortoise species. Although the pathogenic significance of these viruses remains unclear, their detection highlights the potential role of non-native turtles as viral carriers and underlines the need for systematic virological surveillance in non-native species, particularly in ecosystems shared with susceptible native fauna. Full article

An anti-contamination agent (Zn/Al–ATMP–LDH) was synthesized by intercalation and used to correct the abnormal thickening and related operational risks caused by contact contamination between drilling fluids and cement slurries during high-temperature/high-pressure cementing. The experimental results show that the agent is chemically stable and exhibits good compatibility with conventional spacer fluid additives. When compared with the direct addition of amino tris(methylenephosphonic acid) (ATMP), confining ATMP within a layered double hydroxide (LDH) markedly mitigates the retarding effect. At a dosage exceeding 0.3 wt%, the compressive strength of cement stone increased from 0 to 32.84 MPa following curing at 90 °C for 1 day and continued to develop steadily after 7 days. Following conditioning at 187 °C and 145 MPa for 120 min, the spacer system formulated using the proposed agent as the core component served to enhance the rheology of the mixed slurry via synergistic adsorption–regulation–dispersion stabilization-controlled release. The mixed slurry maintained stable rheological properties before and after aging with no uncontrolled thickening. When mixing the cement slurry and drilling fluid at a 7:3 volume ratio, the slurry consistency exceeded 60 Bc within 1 h, failing to meet operational requirements. In contrast, the mixed slurry containing the anti-contamination spacer (cement slurry–drilling fluid–spacer = 7:2:1) exhibited a thickening time greater than 300 min and was successfully applied in field-cementing operations in a well in the Gaomo area. Full article

Surface modification of zinc oxide nanoparticles (ZnO NPs) with organosilane capping agents represents an effective strategy to control their physicochemical and biological properties. In this work, we report for the first time the use of halogenosilanes, namely (3-chloropropyl)trimethoxysilane (CPTMS), (3-bromopropyl)trimethoxysilane (BPTMS) and (3-iodopropyl)trimethoxysilane (IPTMS), for the surface functionalization of ZnO NPs obtained by chemical precipitation. Structural and morphological characterization (PXRD, TEM, SEM-EDX and FTIR) confirmed successful surface modification and revealed a significant particle size reduction from ~31 nm for unmodified ZnO to ~8 nm for BPTMS-modified ZnO (ZnO_b). The biological evaluation showed that halogenosilane-modified ZnO NPs exhibit enhanced cytotoxic activity against prostate cancer cell lines (PC3 and 22Rv1), with ZnO_b displaying the highest activity, likely associated with improved cellular uptake and increased reactive oxygen species (ROS) generation. In contrast, antimicrobial assays revealed only moderate bactericidal effects against Escherichia coli and Staphylococcus aureus at relatively high concentrations (≥1250 µg mL⁻¹), while no significant activity was observed against Pseudomonas aeruginosa, Burkholderia contaminans or Candida spp., within the tested range. These findings suggest that halogenosilane functionalization modulates the biological profile of ZnO nanoparticles by enhancing anticancer effects while also influencing microbiocidal activity, highlighting the role of surface chemistry in tuning biological selectivity. The present study supports the concept that rational surface engineering of ZnO-based nanoplatforms can be exploited to favor tumor-targeted activity over broad-spectrum antimicrobial effects, providing new perspectives for the design of application-oriented nanomaterials. Full article