Search Results (731)

Activation of macrophages plays a key role in both inflammation and oxidative stress, key features of many chronic diseases. Pro-inflammatory M1-like macrophages, in particular, contribute to pro-oxidative environments and are a frequent focus of immunological research. This research examined the effects of kiwifruit allergen Act d 1, in comparison to LPS, on THP-1 macrophages in vitro differentiated under optimized conditions, both in the presence and in the absence of selected vanilloids. THP-1 monocyte differentiation was optimized by varying PMA exposure and resting time. Act d 1 induced M1-like phenotypic changes comparable to LPS, including upregulation of CD80, IL-1β and IL-6 secretion, gene expression of iNOS and NF-κB activation, in addition to increased reactive oxygen species (ROS) and catalase activity. Treatment with specific vanilloids mitigated these responses, primarily through reduced oxidative stress and NF-κB activation. Notably, vanillin (VN) was the most effective, also reducing CD80 expression and IL-1β levels. These results suggest that vanilloids can affect pro-inflammatory signaling and oxidative stress in THP-1 macrophages and highlight their potential to alter inflammatory conditions characterized by similar immune responses. Full article

Zwitterionic hydrogels have emerged as eco-friendly anti-fouling materials owing to their superior hydration-mediated resistance to biofouling. Nevertheless, their practical utility remains constrained by intrinsically poor mechanical robustness. Herein, this study proposes a novel strategy to develop novel tough zwitterionic hydrogels by freezing the gels’ polymer network. As a proof of concept, a zwitterionic hydrogel was synthesized via copolymerization of hydrophobic monomer phenyl methacrylate (PMA) and hydrophilic cationic monomer N-(3-dimethylaminopropyl) methacrylamide (DMAPMA), followed by post-oxidation to yield a zwitterionic structure. At service temperature, the rigid and hydrophobic PMA segments remain frozen, while the hydrophilic zwitterionic units maintain substantial water content by osmotic pressure. Synergistically, the zwitterionic hydrogel achieves robust toughness and adhesiveness, with high rigidity (66 MPa), strength (4.78 MPa), and toughness (2.53 MJ/m³). Moreover, the hydrogel exhibits a distinct temperature-dependent behavior by manifesting softer and more stretchable behavior after heating, since the thawing of the gel network at high temperatures increases segmental mobility. Therefore, it achieved satisfactory adhesiveness to substrates (80 kPa). Additionally, the hydrogel demonstrated remarkable anti-fouling performance, effectively suppressing biofilm formation and larval attachment. In summary, this work opens up promising prospects for the development of zwitterionic hydrogels with high application potential. Full article

Background/Objectives: Breastmilk offers numerous benefits for the health and development of preterm infants, while prolonged hospitalization may impair neurodevelopment. At our institution, the implementation of enhanced family-centered care (FCC) has enabled earlier discharge of preterm infants. This study aimed to assess the impact of early discharge on breastfeeding and breastmilk provision. Methods: This analysis is based on data from a prospective single-center longitudinal cohort study conducted from October 2020 to November 2023, involving six consecutive cohorts (one baseline and five intervention cohorts; n = 184). FCC was progressively enhanced across cohorts. The primary outcome of the main study was postmenstrual age (PMA) at discharge. In this secondary analysis, breastfeeding and breastmilk provision were assessed at four time points: 4 weeks postnatal age, at discharge, 4 weeks post-discharge, and at 3 months PMA. Results: From baseline to intervention cohort 5, the PMA at discharge declined significantly from 37.8 ± 2.1 to 35.7 ± 0.91 weeks (p = 0.03), while the percentage of infants necessitating home nasogastric tube feeding increased from 6.3% to 66.7% (p < 0.01). The proportion of breastmilk of daily feeding volume remained unchanged at 4 weeks postnatal age (0.66 ± 0.42 vs. 0.9 ± 0.28) and at discharge (0.6 ± 0.45 vs. 0.79 ± 0.36). At 4 weeks post-discharge, 65.8% vs. 62.5% of the infants were on partial or exclusive breastmilk (p = 0.91) feeding. Similarly, the percentage of exclusively breastfed infants at 4 weeks post-discharge (23.7% vs. 19.8%) and at 3 months PMA (20% vs. 28.6%) did not differ significantly between baseline and intervention cohort 5. Conclusions: Early discharge did not reduce breastmilk supply or exclusive breastfeeding. However, the persistently low rate of exclusive breastfeeding post-discharge highlights the need for additional support strategies during and after hospitalization. Full article

This paper proposes an energy-efficient current control strategy for drive modules of permanent magnetic actuators (PMAs) to reduce the cost and volume of DC-link capacitors. The drive module of the PMA does not receive the input power from an external power source during operation. Instead, the externally charged DC-link capacitors are used as internal backup power sources to guarantee the reliable operation even in the case of an emergency. Therefore, it is important to use the charged energy efficiently within the limited DC-link capacitors. However, conventional control strategies using a voltage open loop have trouble reducing the energy waste. This is because the drive module with the voltage open loop uses unnecessary energy even after the PMA mover has finished its movement. To figure it out, the proposed control strategy adopts a current control loop to save energy even if the displacement of the PMA mover is unknown. In addition, the proposed strategy can ensure the successful operation of the PMA by using the driving force analysis. The efficacy of the proposed strategy is verified through the experimental test. It would be expected that the proposed strategy can reduce the cost and volume of the PMA drive system. Full article

Pasteurella multocida (Pm) is a zoonotic pathogen that poses a significant threat to animal health and causes substantial economic losses, further aggravated by rising tetracycline resistance. To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity of doxycycline combined with metformin, an FDA-approved antidiabetic agent. Among several non-antibiotic adjuvant candidates, metformin exhibited the most potent in vitro synergy with doxycycline, especially against capsular serogroup A strain (PmA). The combination demonstrated minimal cytotoxicity and hemolysis in both mammalian and avian cells and effectively inhibited resistance development under doxycycline pressure. At 50 mg/kg each, the combination of metformin and doxycycline significantly reduced mortality in mice and ducks acutely infected with PmA (from 100% to 60%), decreased pulmonary bacterial burdens, and alleviated tissue inflammation and damage. Mechanistic validation confirmed that metformin enhances membrane permeability in Pm without compromising membrane integrity, dissipates membrane potential, increases intracellular doxycycline accumulation, and downregulates the transcription of the tetracycline efflux gene tet(B). Morphological analyses further revealed pronounced membrane deformation and possible leakage of intracellular contents. These findings highlight metformin as a potent, low-toxicity tetracycline adjuvant with cross-species efficacy, offering a promising therapeutic approach for managing tetracycline-resistant Pm infections. Full article

Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the periodontal supporting tissues, including alveolar bone, potentially resulting in tooth loss. Etiopathogenesis involves a dysbiotic shift in the subgingival microbiota where the presence of pathogenic species such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola has been documented. This disbalance is combined with an inadequate host immune response, often exacerbated by other systemic comorbidities including diabetes mellitus and cardiovascular diseases. Conventional therapy typically comprises mechanical debridement and adjunctive local or systemic antimicrobials, but emerging antibiotic resistance highlights a need for alternative adjuvant therapeutic strategies. The present descriptive analysis of microbiome and clinical trends study evaluated the adjuvant effects of a clinoptilolite-based zeolite material, namely PMA-zeolite, with professional prophylaxis on clinical and microbiological parameters in patients with chronic periodontitis over a 10-week period. Clinical assessment revealed significant reductions in bleeding on probing (BoP) and periodontal pocket depth (PD), indicating improved inflammatory status. Microbiome profiling demonstrated a marked decrease in key periodontal pathogens, suggesting that PMA-zeolite can help rebalance the oral microbiome. These findings suggest that the combined therapy exhibits promising anti-inflammatory and antimicrobial properties, indicating its role in promoting microbial homeostasis and reducing periodontal inflammation. However, further investigation through larger, controlled clinical trials is needed to validate the efficacy of the therapy. Full article

Background: The COVID-19 pandemic has had a profound impact on pediatric mental health, contributing to a global surge in psychiatric emergencies among children and adolescents. This study aimed to evaluate trends in pediatric emergency department (PED) visits for three key psychiatric conditions—anxiety disorders (ADs), self-injury behaviors (SIBs), and psychomotor agitation (PMA)—before and after the onset of the COVID-19 pandemic. Methods: We conducted a retrospective observational study at a tertiary pediatric hospital in Italy, analyzing all psychiatric presentations to the PED from 1 January 2018 to 31 December 2024. The data were divided into pre-COVID and post-COVID periods and included patient demographics, recurrence of visits, clinical features, hospital admissions, and pharmacological management. Diagnoses were confirmed by chart review. Results: Of 233,867 total PED visits, 1082 were due to primary psychiatric concerns. A marked increase in visits was observed postCOVID: SIB incidence rose from 3.6 to 15.1 per 10,000 visits (p < 0.0001), PMA from 9.4 to 17.8 (p < 0.0001), and AD from 17.7 to 21.6 (p = 0.018). SIB cases showed increased recurrence (from 3.4% to 27.4%, p = 0.004) and greater pharmacological intervention, whereas PMA was associated with a rise in heteroaggression (from 14.3% to 39.8%, p < 0.0001). Pharmacological treatment remained largely consistent, with benzodiazepines and neuroleptics most frequently used. The emerging use of intranasal ketamine was noted in select cases. Conclusions: This study highlights the increasing burden of pediatric psychiatric emergencies in the wake of the COVID-19 pandemic. The findings underscore the urgent need to implement standardized emergency care protocols, strengthen outpatient mental health services, and develop pediatric-specific pharmacological guidelines to improve outcomes in this vulnerable population. Full article

Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To improve the clinical relevance of TTV quantification, in this study, we investigated the use of PMAxx™, a virion viability dye that selectively blocks the amplification of compromised virions. Serum samples from 10 Hepatitis C Virus-positive (HCV+) individuals, 81 liver transplant recipients (LTRs), and 40 people with HIV (PWH) were treated with PMAxx™ and analyzed for TTV DNA loads by digital droplet PCR (ddPCR). Furthermore, anti-SARS-CoV-2 IgG levels and neutralizing antibody (nAbs) titers were measured post-COVID-19 vaccination. Using ddPCR, the PMAxx™ treatment significantly reduced the TTV DNA levels in all the groups (mean reduction: 0.66 Log copies/mL), indicating the abundant presence of non-intact, circulating viral genomes. However, correlations between TTV DNA and SARS-CoV-2 IgG or nAbs were weak or absent in both PMAxx™-treated and untreated samples. These findings suggest that while PMAxx™ enhanced the specificity of TTV quantification, it did not improve the predictive value of TTV viremia at assessing vaccine-induced humoral responses. Full article

Background/Objectives: Verbena officinalis L. (common vervain) is a medicinal plant traditionally used and investigated in phytotherapy for its neuroprotective, antioxidant, and anti-inflammatory properties. This study aims to investigate the phytochemical diversity and biological activity of V. officinalis extracts prepared with different ratios of butanol and ethanol. Methods: Aerial parts of V. officinalis were extracted using four solvent systems: 100% butanol (B1), 75:25 (BE7.5), 50:50 (BE5), and 25:75 (BE2.5) butanol:ethanol mixtures. Metabolite profiling was conducted using liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS). Antioxidant activities were evaluated through six assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric ion-reducing antioxidant capacity (CUPRAC), ferric-reducing antioxidant power (FRAP), metal-chelating ability (MCA), and the phosphomolybdenum assay (PMA). Enzyme inhibition assays targeted acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, and α-amylase. Antibacterial activity against Pseudomonas aeruginosa was tested via microdilution, while dominant phytochemicals were evaluated for binding affinity through molecular docking. Results: Seventy-five compounds, including phenolic acids, flavonoids, iridoids, phenylethanoids, and xanthones, were identified. BE5 extract exhibited the highest total phenolic content and strongest antioxidant capacity, while BE2.5 demonstrated the greatest antibacterial and metal-chelating effects. All extracts showed comparable AChE inhibition, with BE5 achieving the strongest tyrosinase and α-amylase inhibition. Docking studies confirmed high binding affinities of luteolin glucuronides to human and bacterial target enzymes. Conclusions: Solvent composition markedly influenced the chemical and biological profiles of V. officinalis extracts. BE5 and BE2.5 emerged as promising systems for obtaining bioactive fractions with therapeutic potential. Full article

Several of the integrin family of cell adhesion receptors have been popular targets for the development of anticancer agents, but with little clinical success to date. Cancer cells usually express multiple redundant integrins; one hypothesis for the lack of efficacy of current antagonists is their high selectivity for a single integrin. To address this, we developed a functional dual-β3-expressing cell model to investigate the effects of combined αIIbβ3/αvβ3 antagonism. We established that treating K562 chronic myeloid leukemia cells with 0.04 μM phorbol 12-myristate 13-acetate (PMA) for 40 h significantly upregulates functional αIIbβ3 and αvβ3 integrins. This optimized method provides a reliable platform for adhesion and detachment assays, enabling the characterization of dual integrin targeting strategies. Using this model, we demonstrate that combining αIIbβ3 and αvβ3 antagonists (GR144053 and cRGDfV) synergistically enhances inhibition of cell adhesion and promotes cell detachment compared to single-agent treatments. Our findings establish a reproducible approach for studying dual β3 integrin targeting, which can be used to investigate potential strategies for overcoming integrin redundancy in cancer therapeutics. Full article

Acid phosphatase (ACPase) is an essential industrial enzyme, but its production via recombinant bacterial fermentation is often limited by insufficient dissolved oxygen control. This study optimized the aerobic fermentation of the ACPase-producing recombinant bacterium Bacillus subtilis 168/pMA5-Acp by refining the bioreactor’s aerodynamic structure using computational fluid dynamics (CFD) simulations. This was combined with fermentation kinetics modeling to achieve precise process control. First, the gas distributor structure of the 5 L bioreactor was optimized using CFD simulation results. Optimal mass transfer conditions were identified through comprehensive analysis of K_La in different reactor regions (aeration ratio: 1.142 VVm, K_La = 264.2 h⁻¹). The simulation results showed that the optimized oxygen transfer efficiency increased 2.49 fold compared to the prototype. Second, the process control issue was addressed by developing a BP (backpropagation) neural network model to predict K_La under alternative media conditions. The prediction error was less than 5%, and the model was combined with the logistic equation to construct the bacterial growth kinetic model (R² > 0.99). The experiments demonstrated that using the optimized reactor with a molasses–urea medium (molasses 7.5 g/L; urea 15 g/L; K₂HPO₄ 1.2 g/L; MgSO₄·7H₂O 0.25 g/L) reduced production costs while maintaining enzyme activity (215.99 U/mL) and biomass (OD₆₀₀ = 101.67) by 90.03%. This study provides an efficient and cost-effective process solution for the industrial production of ACPase and a theoretical foundation for bioreactor design and scale-up. Full article

Background and Objectives: Sarcopenia and lower urinary tract symptoms (LUTSs) are both prevalent among older adults and may share underlying pathophysiological mechanisms. However, their association has not been systematically quantified. This systematic review and meta-analysis aimed to evaluate the association between sarcopenia and LUTSs, including the pooled estimates of prevalence and odds ratios (ORs), and to explore the influence of diagnostic definitions and study-level factors. Materials and Methods: A comprehensive literature search was conducted using PubMed and Embase for studies published between 1 January 2000 and 26 April 2025. This study adhered to PRISMA and MOOSE guidelines and was registered in PROSPERO (CRD420251037459). Eligible observational studies reported LUTS prevalence or ORs in individuals with sarcopenia, low muscle strength (LMS), low lean mass (LLM), low gait speed (LGS), or sarcopenia risk identified by SARC-F (score ≥4). Pooled ORs and prevalence rates were calculated using a random-effects model. Subgroup analyses were performed based on sarcopenia definitions—Asian Working Group for Sarcopenia (AWGS) and European Working Group on Sarcopenia in Older People (EWGSOP)—as well as LUTS subtypes and diagnostic components. Univariate meta-regression assessed associations with age, BMI, sex distribution, WHO region, and risk of bias. Results: Twenty-five studies comprising 84,484 participants were included. Sarcopenia was significantly associated with LUTSs (pooled OR = 1.78; 95% CI: 1.29–2.45; p < 0.001), with a pooled LUTS prevalence of 43.2% (95% CI: 26.9–61.0%). Stronger associations were observed in studies using AWGS diagnostic criteria (OR = 2.24; 95% CI: 1.41–3.56; p = 0.001), in those evaluating severe sarcopenia (OR = 1.66; 95% CI: 1.03–2.68; p = 0.038), and in institutionalized populations (OR = 3.68; 95% CI: 2.18–6.24; p < 0.001) compared to community-dwelling populations (OR = 1.43; 95% CI: 1.06–1.92; p = 0.018). Sarcopenia risk identified by SARC-F (score ≥4) showed the strongest association with LUTSs (OR = 3.20; 95% CI: 1.92–5.33; p < 0.001). Significant associations were also found for LLM (OR = 1.52; 95% CI: 1.19–1.95; p = 0.001) and LGS (OR = 1.37; 95% CI: 1.06–1.76; p = 0.015), but not for LMS (OR = 0.94; 95% CI: 0.47–1.89; p = 0.871). Exploratory analyses comparing LLM diagnostic modalities—including standardized criteria (ASMI, ASM/BMI), imaging-based methods (SMI, PMA), and surrogate measures (calf circumference)—revealed no significant differences (all p > 0.05). Heterogeneity was high (I² > 90%). Egger’s test indicated no evidence of publication bias (p = 0.838), and trim-and-fill analysis did not affect the pooled estimates. Conclusions: Sarcopenia—particularly in its severe forms—is significantly associated with LUTSs. Additionally, individuals who screened positive for sarcopenia using the SARC-F tool demonstrated a heightened risk of LUTSs. Subgroup analyses revealed a stronger association in institutionalized populations, suggesting that care setting may modify risk. These findings underscore the importance of assessing muscle health in older adults with urinary symptoms. Standardization of diagnostic criteria and longitudinal studies are needed to clarify causality and guide targeted interventions. Full article

The radiological finding of Dark White Matter (DWM)—characteristic diffuse subcortical white matter hypointensity on T2/FLAIR sequences—is underrecognized, but has important clinical implications. Recent systematic evidence shows that over 60% of previously published cases showed seizures in association with DWM findings—it is also particularly predictive of the underlying etiology, particularly non-ketotic hyperglycemic hyperosmolar state (NKH). Based on our previous work, we reinterpret the data, focusing only on patients with seizures and DWM, to summarize the most essential and distinguishing features of these patients. Both cortical and subcortical abnormalities in DWM are more frequently associated with anti-MOG encephalitis. DWM with or without cortical involvement is more commonly found in NKH among patients with seizures. This updated systematic review will describe the proposed pathophysiological mechanisms, clinical associations, and implications for DWM in patients with seizures, and highlight how early recognition of DWM may allow for targeted diagnostic strategies and treatment options. We expanded our previous search with details regarding seizure features, our results show that DWM is associated with repetitive seizures and Status Epilepticus (both convulsive and non), in line with other peri-ictal MRI abnormalities associated with prolonged seizure activity. DWM-associated seizures are mostly focal, rather than generalized. Moreover, the high percentage of clinical recovery at follow-up suggests that DWM may be predictive of a good outcome, especially in NKH cases, although this needs to be confirmed in future studies. Full article

Objectives: To elucidate the influence of eye selection criteria (ESC) on the reliability of biomarkers in diagnosis and prediction using pre-surgical parameters, assessments were undertaken as the subject of analysis. Methods: Pituitary macroadenoma (PMA) diagnosis and postsurgical visual function recovery biomarker analysis was used as the subject to illustrate the point. Six datasets (right, left, best, worst, random and both eyes), derived from a longitudinal study that involved 42 PMA patients and age-matched healthy volunteers, were generated. A comparison of the diagnostic efficacies of the amplitude of pattern visual evoked potentials (pVEP) and bi-nasal sector thickness in the ganglion cells complex plus the inner plexiform layer was performed using ESC. Afterwards, multivariate models for PMA diagnosis and the prediction of postsurgical visual function recovery, using Stable Sparse Biomarkers Detection methodology, were developed. A comprehensive evaluation was performed once for controls and in pre-surgical PMA patients at 3 and 12 months after transsphenoidal tumor removal. Results: The proposed biomarkers displayed specificity and sensibility ≥ 0.74 and AUC ≥ 0.87. The diagnostic values derived were ESC-dependent. All the prediction models had accuracies over 0.96, and the proposed biomarkers had stability ≥ 99% and the highest β values. Conclusions: Although the diagnostic values of the proposed biomarkers are affected by ESC, they exhibit equal accuracy for the same eye. Worse eye data represent the best choice for the analysis. Further studies are needed to validate the models for use in the prediction of the 12-month postsurgical restoration of parvocellular traffic. Full article

In this study, an axial flux double airgap permanent magnet-assisted synchronous reluctance motor (AF-Pma-SynRM) was designed for electric vehicles (EVs). The AF-Pma-SynRM model employs a forced liquid cooling method (cooling jacket) for a high current density. The model was tested using multi-objective optimization and multi-physics analysis. The AF-Pma-SynRM design has achieved 95.6 Nm of torque, 30 kW of power, and 93.8% efficiency at a 3000 rpm rated speed. The motor exhibits a maximum speed of 10,000 rpm, 253.1 Nm of torque, and 65 kW of output power. This study employs a novel barrier structure for axial motors characterized by fixed outer and inner dimensions, and is suitable for mass production. In the final stage, the motor was cooled using the cooling jacket method, and the average temperature of the winding was measured as 73.83 °C, and the average magnet temperature was 66.44 °C at a nominal power of 30 kW. Also to show variable speed performance, an efficiency map of the AF-Pma-SynRM is presented. Full article