Search Results (13,040)

A commercially available nitric oxide (NO)-releasing solution (NORS) has demonstrated in vitro efficacy for dermatophytosis, but a NO-releasing gel (NORG) may be more suitable for patient self-application. We present a preliminary investigation of NORS for tinea pedis and an in vitro investigation of NORG for dermatophyte infection, to complement the existing published data and expand support for a possible role of NO formulations in superficial dermatophyte infection. In vitro usage of NORS and NORG is reviewed. The antifungal efficacy of NORG was assessed via time-kill assays, zone of inhibition tests with synthetic dermal membrane permeation, and scanning electron microscopy. A randomized, controlled pilot study of NORS for tinea pedis investigated the safety and efficacy of treatment over three consecutive days, with a day-31 follow-up. The NORG demonstrated rapid fungicidal activity against T. rubrum and T. mentagrophytes and effective dermal membrane penetration while retaining antifungal action. Significant morphological damage to fungal cells was noted, indicating possible fungicidal activity. The clinical NORS treatment reduced the clinical symptom severity score by 67% on average, with no significant safety findings. These findings, in addition to existing publications, support NO-releasing formulations as potential therapies that warrant further clinical investigation for superficial fungal infection. Full article

Background: Parents of school-age children with neurodevelopmental and conduct difficulties face elevated stress, reduced self-efficacy and relational strain, yet evidence for scalable, school-embedded support remains limited. Drawing on mentalization theory—which emphasises parents’ capacity to understand behaviour in terms of underlying mental states—this mixed-methods study evaluated a weekly parent learning group integrating psychoeducation, mentalization-based practice and peer support, delivered within an alternative provision school. Methods: A group of twelve parents who attended at least six sessions completed retrospective pretest–posttest questionnaires assessing parental reflective functioning (PRFQ) and parenting self-efficacy (PSOC). Semi-structured interviews explored parents’ subjective experiences and perceived changes in parent–child interactions and parent–school relationships. Quantitative outcomes were analysed using paired t-tests and effect sizes; qualitative data underwent reflexive thematic analysis. Results: Quantitative analyses revealed statistically significant improvements in parental reflective functioning and self-efficacy. Pre-mentalizing scores decreased substantially (d = 1.34), indicating reductions in non-mentalizing, while interest and curiosity about children’s mental states increased markedly (d = 1.83). Parenting self-efficacy improved significantly (d = 1.61). Although a reduction in excessive certainty about mental states approached significance (d = 0.63, p = 0.053), trends suggested greater epistemic balance. Qualitative analysis identified six themes elucidating mechanisms of change, including enhanced mentalizing capacity, reduced parental stress, transformed parent–child interactions and facilitation style as a critical active ingredient. Integration of findings suggests that psychoeducational content provided conceptual grounding for understanding behaviour, facilitator modelling scaffolded reflective practice, and relational safety within the group enabled authentic engagement with challenging experiences. Conclusions: These preliminary findings indicate that a school-based parent learning group combining psychoeducation, mentalization-based practice and peer support is feasible and associated with meaningful improvements in parental reflective functioning and self-efficacy. Parent narratives of transformed relational practices and shifts from reactive to reflective engagement echo broader literature demonstrating that group-delivered mentalization-oriented programmes can enhance reflective capacities and caregiving quality in diverse family contexts. The school setting may extend the reach of such interventions to families not engaged with clinical services and support collaborative parent–school partnerships. Future research should employ larger, controlled designs, incorporate observational and child outcome measures, and explore scalability across educational contexts. Full article

Background: The global rise in antimicrobial resistance (AMR) has created an urgent need for innovative antibacterial strategies and localized delivery systems. This study aimed to develop and characterize electrospun poly (vinyl alcohol) (PVA) nanofibers co-loaded with atorvastatin (ATR) and zinc oxide (ZnO) nanoparticles for use as a multifunctional topical platform for wound healing and infection control. Methods: ZnO nanoparticles were prepared via ball milling and characterized for size and zeta potential. Four PVA-based nanofiber formulations were fabricated using electrospinning: blank (F1), ZnO-loaded (F2), ATR-loaded (F3), and ATR/ZnO co-loaded (F4). The nanofibers were evaluated for morphology, thermal properties, crystallinity, and drug release. Antibacterial efficacy was tested against S. aureus, S. epidermidis, MRSA, and P. aeruginosa using broth microdilution and checkerboard assays. Biocompatibility and wound healing potential were assessed via MTT and fibroblast scratch assays on human foreskin fibroblasts (hFFs). Results: SEM imaging confirmed the production of uniform, bead-free nanofibers. ATR and ZnO nanoparticles were successfully incorporated in the nanofiber. The co-loaded formulation (F4) demonstrated a sustained release profile, releasing approximately 78.7% of ATR over 24 h. While all treatments showed limited activity against P. aeruginosa, the ATR/ZnO co-loaded nanofibers exhibited significantly enhanced antibacterial activity against Gram-positive strains, achieving the lowest MIC values (1.5–2.0 mg/mL). Synergy analysis confirmed an enhanced effect with ATR and ZnO against MRSA. Furthermore, F4 achieved the highest wound closure rate of 92.41% in 24 h while maintaining acceptable cytocompatibility. Conclusions: The integration of ATR and ZnO into PVA nanofibers provides an enhanced antibacterial effect consistent with the synergistic potential observed between free agents targeting Gram-positive wound pathogens. The platform’s ability to simultaneously inhibit bacterial growth and promote rapid fibroblast migration positions it as a promising localized therapeutic for managing infected wounds. Full article

With the rapid development in new media and social platforms on the internet, some social hotspots or sensitive events can easily ferment and spread in the online space, attracting the attention or concentrated discussion of young students. Network cluster behavior is a collective behavior in which a large number of netizens collectively express and gather opinions around social hot issues of common concern, creating online public opinion. The study explored the influence of group psychology on the process of college students participating in online cluster behavior. A survey was conducted involving 2137 college students from over 10 universities in Zhejiang Province, Jiangsu Province, and other regions. The data were analyzed using correlation analysis and moderated mediation model testing. This study found that group psychological factors, such as emotional infection, depersonalization, the spiral of silence, relative deprivation, group polarization, and action mobilization, positively predicted network cluster behavior. The action mobilization of opinion leaders mediated the relationship between emotional infection and network cluster behavior. Group polarization mediated the relationship between the spiral of silence and network cluster behavior. Additionally, group efficacy moderated the latter part of the mediation process between group polarization and network cluster behavior. Full article

According to the World Health Organization, antibiotic research remains insufficient, emphasizing the urgent need for new active molecules, particularly against resistant bacteria. Based on known antibacterial scaffolds, new fluoroquinolone derivatives have been synthesized by our research group, including compound 7a, a difluoroboranyl-fluoroquinolone that previously demonstrated activity against sensitive strains. Methods: The minimum inhibitory (MIC) and bactericidal (MBC) concentrations of compound 7a were determined against Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. The selective development of ciprofloxacin-resistant S. aureus was induced by reseeding the isolate on seven consecutive days with an antibiotic concentration that was not capable of inhibiting its development. Pharmacokinetic and toxicological properties were predicted using SwissADME, Way2Drug, and molecular docking (AutoDock Vina). In vivo toxicity was evaluated in BALB/c mice through histopathological liver and kidney analysis and serum biochemical markers. The antibacterial efficacy of 7a (80 mg/kg/day) was assessed in a murine pneumonia model induced by ciprofloxacin-resistant S. aureus. DNA gyrase inhibition was confirmed through plasmid electrophoresis assays in E. coli DH5-α cells. Results: Compound 7a exhibited both MIC and MBC values of 0.25 μg/mL, while ciprofloxacin-resistant S. aureus strains did not exhibit a detectable MIC within the concentration range tested (up to 1024 μg/mL). In silico predictions revealed favorable ADME profiles, low toxicity, and strong interaction with DNA gyrase. In vivo, 7a showed no signs of hepatotoxicity or nephrotoxicity and effectively reduced pneumonic tissue to 1.99% in infected mice. Electrophoretic assays confirmed DNA gyrase inhibition consistent with the mechanism of fluoroquinolones. Conclusions: Compound 7a evidenced activity against ciprofloxacin-resistant S. aureus in vitro and reduced infection progression in vivo. It also displays favorable drug-like properties, low predicted toxicity, and DNA gyrase inhibition. Full article

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage. Full article

Background: The skin microbiome plays a crucial role in maintaining barrier function and preventing inflammaging. Heat-treated probiotics offer stability advantages for topical formulations while potentially maintaining bioactive properties. Objective: To evaluate the safety, molecular mechanisms, and clinical efficacy of heat-treated Lactiplantibacillus plantarum Skinbac™ SB01 and Bifidobacterium animalis spp. lactis Skinbac™ SB05 in reducing visible signs of skin aging. Methods: In vitro studies assessed cytotoxicity (MTT/LDH assays), Aquaporin-3 (AQP3) expression, and reactive oxygen species (ROS) production in Normal Human Epidermal Keratinocytes (NHEK). A 30-day open-label clinical study (n = 20 females, 18–70 years) evaluated three formulations (face cream, serum, and eye contour) using instrumental measurements of hydration, elasticity, density, and roughness parameters. Results: In vitro testing showed a significant increase in AQP3 expression (+22% ± 3%, p = 0.03) and a non-significant reduction in ROS levels (−33% ± 9%, p = 0.06) at 10⁷ TFU/well, with no cytotoxicity observed. Clinical evaluation demonstrated statistically significant improvements: eye contour formulation achieved +10.5% deep skin hydration (p < 0.0001) and −11% average roughness (p < 0.0001); serum showed +28.7% immediate hydration (p < 0.0001); and face cream improved gross skin elasticity by +6.3% (p < 0.01). No adverse events were reported. An independent and methodologically distinct placebo-controlled study was included for contextual support and was not directly compared with the present trial; this study evaluated a related 1% postbiotic formulation and reported statistically significant improvements over placebo in roughness, wrinkle depth, hydration, and biomechanical parameters. Conclusions: This pilot study provides preliminary evidence that heat-treated L. plantarum SB01 and B. animalis spp. lactis SB05 formulations could safely improve skin hydration and reduce roughness parameters. While in vitro results show a significant increase in AQP3 expression and an exploratory (non-significant) reduction in ROS levels, larger controlled trials are warranted to confirm clinical efficacy. Full article

Shigellosis remains a significant global cause of infectious colitis, increasingly complicated by multidrug-resistant strains and the microbiota-disrupting effects of broad-spectrum antibiotics. Although conventional antimicrobial therapy can reduce symptom duration and bacterial shedding, it also contributes to gut dysbiosis, loss of colonization resistance, and further selection for antimicrobial resistance. These challenges have renewed interest in precision antimicrobial strategies, particularly bacteriophage therapy, which provides strain-level specificity and preserves the gut microbiota. This narrative review evaluates the biological rationale, preclinical and early clinical evidence, safety considerations, and translational challenges associated with bacteriophage therapy targeting Shigella spp. The historical development and mechanistic basis of phage therapy are summarized, with emphasis on the advantages of obligately lytic phages, receptor-specific targeting, self-amplification at infection sites, and activity against both planktonic and biofilm-associated bacteria. Recent microbiota research indicates that shigellosis is closely associated with early and persistent disruption of gut ecology, including depletion of short-chain fatty acids-producing taxa and reduced microbial resilience. Phage-based approaches may reduce pathogen burden while preserving beneficial microbial communities. Evidence from in vitro systems, animal models, human intestinal organoids, and a Phase 1 clinical trial demonstrates targeted efficacy and favorable safety profiles for Shigella-specific phages and phage cocktails. Major barriers to clinical adoption include immune interactions, phage resistance dynamics, genomic safety screening, regulatory classification, and the need for standardized susceptibility testing. Future directions emphasize the development of personalized phage therapy platforms that integrate rapid diagnostics, phage libraries, metagenomics, and artificial intelligence-assisted matching to enable scalable, precision treatment. Full article

Background/Objectives: Chimpanzee adenoviral-vectored vaccines have proven to be both safe and effective, with a manufacturing and distribution pipeline capable of rapid global supply, as demonstrated during the COVID-19 pandemic. Yellow fever is a mosquito-borne viral hemorrhagic disease endemic in parts of Africa and Latin America, and although an effective live attenuated vaccine exists, its use is limited by safety and eligibility restrictions. Moreover, large outbreaks continue to expose critical challenges, such as an insufficient vaccine supply, reliance on fractional dosing, and slow and difficult-to-scale manufacturing processes. Here, we report the design, development and in vivo immunogenicity of multiple yellow fever virus (YFV) antigen constructs based on the pre-membrane (prM) and envelope (E) proteins—with or without the transmembrane domain (TM or ΔTM)—delivered using the ChAdOx1 adenoviral vector. Methods: Four ChAdOx1 YF vaccines were developed, and immunogenicity was evaluated. The efficacy of the full-length YF envelope vaccine was also tested in Balb/c mice. Results/Conclusions: In contrast to previously described orthoflavivirus vaccines on the same platform, the full-length antigen elicited superior immunogenicity and conferred protection against intracranial challenge with the YF17D virus in mice. Notably, this protection was comparable to that induced by the licensed YF17D vaccine, highlighting the promise of this platform as a next-generation yellow fever vaccine candidate. Full article

In the drift mining of sharp, inclined, narrow veins, the efficacy of cutting blasting directly governs the efficiency of blasting operations. However, the mechanisms of rock mass damage and fracturing induced by cutting blasting in sharp inclined narrow vein mines remain inadequately understood. This study employs a 3D numerical model of cutting blasting calibrated with field test data to analyze the damage and fracture processes of rock mass under cutting blasting in sharp inclined narrow vein mines. A parametric study further examines the effects of vein thickness and in situ stress on blast-induced damage and fracturing of a rock mass. The results show that cutting blasting produces a significantly asymmetric damage distribution in sharp, inclined, narrow vein mines. Under conditions of small vein thickness, the propagation of damage along the vein–rock interface increases, and the clamping effect on the rock in the cutting blasting zone intensifies. Additionally, high bidirectional equal in situ stress substantially suppresses blast-induced damage development, with the suppression intensity showing a positive correlation to in situ stress magnitude. The findings provide a theoretical basis for cutting blasting design in the drift mining of sharp inclined narrow veins. Full article

Although previous studies have examined factors influencing organizational appeal, how AI-adoption signals influence prospective applicants remains unclear. Building on signaling theory, this study explores whether, when, and how organizations’ AI-adoption signals enhance their attractiveness to potential applicants. Two experiments were conducted to test the hypothesized model. Study 1 (N = 145) employed a scenario-based design to compare organizational attractiveness between AI-adoption signal and no-signal conditions, confirming that AI-adoption signals are significantly positively associated with organizational attractiveness. Study 2 (N = 240) recruited active job seekers and validated a moderated mediation model: perceived innovation ability mediates the positive association between AI-adoption signals and organizational attractiveness, especially among job seekers with high AI self-efficacy. By conceptualizing AI adoption as an organizational signal, this research extends signaling theory to the context of technology-infused recruitment and offers practical insights for designing more effective recruitment strategies in the digital era. Full article

Background/Objectives: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is linked to poorer overall survival and a higher risk of brain metastases compared to HER2-negative breast cancer. Current preclinical studies lack robust HER2+ metastatic syngeneic mouse models for investigating targeted and immunomodulatory therapies. This study aims to develop effective HER2+ mouse models to investigate response dynamics to HER2-targeted therapy and immunotherapy. Methods: The human HER2 gene (WT or mutant p.A775_G776insYVMA, GFP-tagged at the C-terminus) was introduced into triple-negative breast cancer (TNBC) mouse mammary carcinoma cells with known metastatic potential (4T1 and EO771) via lentiviral transduction. HER2 expression and phosphorylation were analyzed using Western blotting and immunohistochemistry. Tumors were treated with HER2-targeted therapy (trastuzumab and tucatinib), immune checkpoint blockade (anti-PD-1 and anti-CTLA-4), and anti-HER2 antibody–drug conjugate (ADC) to evaluate treatment efficacy. Metastatic potential was assessed with brain fluorescence imaging. Statistical analysis included ANOVA and Kaplan–Meier tests. Results: Newly established lines demonstrated expression of HER2+, with HER2^YVMA lines showing higher phosphorylation than HER2^WT lines. Cells were tumorigenic, demonstrating in vivo tumor take rates at 100% for 4T1-HER2 and 15–30% for EO771-HER2. HER2 overexpression led to a 30% increase in spontaneous brain metastasis in the 4T1-HER2 models. Trastuzumab alone did not reduce primary tumor size but significantly reduced brain GFP signal by 17% ± 8% and 26% ± 7% in the 4T1-HER2^WT and 4T1-HER2^YVMA models, respectively. Combinational therapies with anti-HER2 therapy and immune checkpoint blockade effectively suppressed primary tumor growth and prolonged survival in EO771-HER2^YVMA model. T-Dxd, but not T-DM1, demonstrated partial treatment response in the EO771-HER2^WT model. Conclusions: HER2+ syngeneic tumor models were developed that spontaneously metastasize to the brain and demonstrate variable responses to immunotherapies and ADCs. These models are valuable for advancing molecular imaging modalities for HER2+ brain metastasis, studying blood–brain barrier penetration of HER2-targeted drugs, and exploring the combination of therapies, including immunotherapy. Full article

To clarify the genetic classification, diagnostic strategies, and precision treatment pathways of steroid-resistant nephrotic syndrome (SRNS), this review systematically reviews the genetic stratification system of SRNS by integrating recent advances in genetic testing technologies and pathogenesis research. It contains the pathogenic mechanisms, diagnostic protocols, and therapeutic correlations of different genetic subtypes, while summarizing current progress and clinical challenges in gene therapy. Results indicate SRNS can be categorized into genetic (38–58%) and non-genetic/immune-mediated (40–60%). A stepwise diagnostic system comprising core proteinuria gene panel testing, whole-genome sequencing (WGS), whole-exome sequencing (WES), and supplementary multi-omics/long-range sequencing is proposed, suited for populations with “typical phenotypes and moderate genetic risk”, “atypical phenotypes and high genetic suspicion”, and “complex structural/non-coding region variants” respectively. Pathogenic mechanisms directly determine therapeutic strategies: COQ2/PDSS2 mutations respond to coenzyme Q10 suplementation, while NPHS1 mutations necessitate early renal transplantation. Adeno-associated virus (AAV)-mediated gene therapy and CRISPR-Cas editing show preclinical promise but face challenges including incomplete detection coverage and clinical translation difficulties. Genetic technologies are driving SRNS management transformation from “empirical treatment” to “mechanism-oriented precision diagnosis and therapy”. Future efforts should focus on overcoming genetic testing limitations and gene therapy translation bottlenecks to enhance diagnostic and therapeutic efficacy. Full article

Background: The control of fleas and ticks in companion animals is a persistent challenge with animal welfare and public health implications. The increasing resistance to antiparasitic treatments, coupled with concerns over the environmental impact and non-target effects of synthetic acaricides, has driven interest in sustainable alternatives. Essential oils (EOs) have emerged as potential candidates due to their complex chemistry and modes of action. Methods: This review critically analyzes the scientific literature on essential oils for ectoparasite control in companion animals. Specifically, it examines their chemical composition, multi-target mechanisms of action, laboratory and field efficacy, role in resistance mitigation, and integration into IPM strategies. Results: Several EOs, particularly those rich in phenolic compounds (thymol, carvacrol, eugenol, and cinnamaldehyde), demonstrate promising in vitro insecticidal and acaricidal activity. Their multi-target mechanisms, affecting neuronal, respiratory, and cuticular functions, not only provide efficacy but also represent a significant barrier to rapid resistance development. However, their translation to reliable field performance is hampered by high volatility, formulation instability, and innate variability. Conclusions: EOs represent a valuable source of bioactive compounds for reducing reliance on conventional acaricides and can play a key role within IPM strategies. To realize their full potential in mitigating resistance, focused advancements are needed in standardized testing, formulation science to enhance stability and residual activity, and rigorous field studies to confirm safety and efficacy. Full article

In today’s AI-driven world, nurturing students’ capacity for independent, self-reflective learning is vital. They must build lifelong learning skills and develop personalized strategies through ongoing self-regulation. In this study, we employed a learning journal template to support self-regulated physics learning, highlighting the role of homework assignments designed to target different levels of cognitive domains. Our learning journal-supported approach aims to facilitate students’ preparation for lessons at home. Guided questions help students review the content covered in previous classes and reflect on the effectiveness of the instructional methods applied. The intervention focused specifically on the physics topic of dynamics, examining how students’ conceptual understanding and performance developed within this domain. The efficacy of this approach was tested among 7th- and 9th-grade students. Results indicate that the learning journal-based method, combined with structured homework, had a positive impact on students’ performance within the topic of dynamics. Full article