Search Results (20,086)

Magnetic hysteresis strongly influences energy dissipation and efficiency in power magnetic components under time-varying excitation. This work proposes a compact dynamic hysteresis model using a Hammerstein structure, consisting of a closed-form arctangent static operator followed by a first-order relaxation dynamic stage. The formulation enables direct datasheet-based parameterization and avoids iterative differential solvers or distributed hysteron representations, resulting in low calibration effort and computational cost. The static hysteresis behavior is characterized using four static parameters directly identified from manufacturer B-H datasheets, while dynamic effects are captured using two global calibration parameters derived from datasheet loss curves. This formulation enables accurate reconstruction of major and minor hysteresis loops, while introducing frequency-dependent phase lag and dynamic loop opening. Model performance is evaluated under diverse excitations, including sinusoidal, amplitude-modulated, FORC and chirp signals, showing waveform deviations below 7.2% peak-to-peak NRMSE relative to classical hysteresis models. Energy-loss predictions are validated against manufacturer datasheet curves for ferrite material 3C90 across multiple frequencies, yielding a root-mean-square relative error of 8.3% with 89% of operating points within ±20% deviation. The proposed model provides a datasheet-driven framework for hysteresis and energy-loss prediction in power magnetic components. Full article

Background: Continuous positive airway pressure (CPAP) is the most effective treatment for obstructive sleep apnoea (OSA). However, CPAP adherence in randomized controlled trials (RCTs) is frequently inadequate, potentially leading to an underestimation of the therapy’s true effect on relevant outcomes. The aim was to identify patient and study characteristics that predict adherence to CPAP therapy in RCTs. Methods: PubMed and the existing meta-analyses were searched (1984 to 31 December 2024). A study-level meta-analysis of RCTs comparing CPAP with inactive control in patients with OSA was conducted. Meta-regressions and subgroup analyses (<4 h vs. ≥5 h usage) were undertaken to identify the predictors of CPAP adherence. Risk-of-bias was assessed using the Cochrane RoB-2 tool. Results: In 136 RCTs reporting on CPAP use, including 8827 patients with OSA (55 [49.5–59.8] years, 77.4 [61.2–89.2]% male, BMI 31 [28.9–33.2] kg/m², Epworth Sleepiness Scale (ESS) 10.0 ± 2.8, apnoea–hypopnoea-index (AHI) 35.7 ± 13.4/h), mean nocturnal CPAP use was 4.5 ± 1 h. CPAP use of ≥4 h, ≥5 h, and ≥6 h per night was observed in 71.3%, 34.1%, and 7.8% of RCTs, respectively. Higher baseline AHI was the strongest predictor of longer CPAP use in meta-regressions (p < 0.001, β = 0.02, 95% CI 0.01–0.04). Baseline AHI was also significantly higher (40.3 ± 12.8 vs. 29.9 ± 12.6) in the ≥5 h vs. <4 h subgroup (p < 0.01, large effect size d = 0.84). A higher nightly CPAP usage was more likely in smaller (p < 0.05, d = 0.45) and single-centre trials (p < 0.05, h = 0.52). Sex distribution, age, BMI, ESS, and follow-up had no significant effect on nightly CPAP use. Conclusions: Higher baseline AHI independently predicted longer CPAP use in RCTs, while sleepiness and demographics did not. This study was registered at PROSPERO (CRD420250653394) and received no external funding. Full article

Bietti crystalline dystrophy (BCD) is a hereditary retinal disease caused by loss-of-function mutations in the CYP4V2 gene. Gene replacement therapy using rAAV-hCYP4V2 represents a promising therapeutic strategy, requiring robust bioassays for product quality control. This study developed and validated a sensitive LC-MS/MS method for quantifying CYP4V2 enzyme activity. Lysates from HeLa-AAVR cells transduced with rAAV-hCYP4V2 (MOI = 3 × 10⁵) were used, with lauric acid as substrate supplemented with cytochrome P450 reductase, cytochrome b5, and NADPH. The ω-hydroxylated product (12-hydroxy lauric acid) was quantified using tolbutamide as an internal standard. Method validation followed ICH guidelines. Results demonstrated excellent specificity with negligible background in negative controls. Linearity was achieved over 0.5–100 ng/mL (R² > 0.99), with an average recovery of 100.6%. Intra-batch and inter-batch precision RSDs were <47.8% and <28.4%, respectively. Product stability was maintained for ≥4 weeks at −80°C. The method was successfully applied to three AAV serotypes (AAV2, AAV8, and AAV2/8), with all RSDs < 23.9%. This validated LC-MS/MS bioassay provides a crucial quality control tool for potency assessment, process development, batch release, and stability studies of rAAV-hCYP4V2 gene therapy products. Full article

Background: Fertility preservation aims to maintain reproductive potential in patients undergoing potentially gonadotoxic treatments, increasingly relying on centralized cryobanks requiring ovarian tissue transport. Ovarian tissue cryopreservation is a widely implemented, evidence-based procedure for young women (age 18–35) with a regular ovarian reserve. The ovaries of patients are typically transported overnight to a centralized cryobank for freezing and storage, using a certified hypothermic organ preservation solution such as histidine-tryptophan-ketoglutarate (HTK) at 4–8 °C. The molecular effects of transport on ovarian tissue remain unclear. Methods: In this prospective study of 36 breast cancer patients, we compared whole-transcriptome RNA (RNA-seq) expression in 18 frozen–thawed ovarian biopsies after overnight hypothermic transport followed by slow-freezing versus 18 direct slow-freezing within ≤2 h under FertiPROTEKT-standard conditions. Results: The RNA-seq analysis identified 6 significantly upregulated genes (Bonferroni < 0.05, fold change > 1.5), including histone H2B and mitochondrial NADH dehydrogenase subunit 6 (MT-ND6). The small number of differentially expressed genes suggests only limited transcriptional changes between the two transport conditions. H2B upregulation was confirmed by qPCR, while MT-ND6 showed only moderate levels in RNA-seq but remained stable in qPCR. Immunohistochemical analysis confirmed protein presence and localization in formalin-fixed tissue from four samples, constituting, to our knowledge, the first report of MT-ND6 protein expression in human ovarian tissue. Conclusions: Overall, these results are consistent with subtle changes in chromatin organization and mitochondrial energy metabolism. Since RNA-seq revealed only modest differences in gene expression, with no appreciable up- or downregulation of apoptosis- or damage-related genes after ≤24 h, this indicates tissue stability under the studied combined conditions (transport + cryopreservation). These findings are consistent with the feasibility of the workflow under the studied conditions of centralized ovarian tissue cryobanking combined with overnight transportation and hypothermic HTK solution. Full article

Background: Most patients with hepatocellular carcinoma (HCC) present with advanced disease and have limited systemic treatment options. Oxaliplatin shows clinical activity in HCC but its effectiveness is frequently curtailed by intrinsic and acquired resistance. We sought to systematically identify genetic vulnerabilities that increase oxaliplatin sensitivity in HCC. Methods: Genome-scale negative-selection CRISPR–Cas9 screens were conducted in two genetically distinct HCC cell lines (Hep3B and MHCC-97H) under low-dose oxaliplatin to discover conserved determinants of sensitivity. Selected DNA damage response (DDR) hits were validated. An oxaliplatin-resistant MHCC-97H subline was generated for transcriptomic profiling to characterize resistance-associated programs. Screen results were integrated with TCGA-LIHC expression and survival data to evaluate clinical relevance. Additionally, we analyzed bulk RNA-seq data from biopsy specimens collected from 36 HCC patients prior to initiation of hepatic arterial infusion chemotherapy (HAIC), comparing expression levels of the DDR genes between patients with objective response and non-responders. Results: Screens in both cell lines converged on DDR pathways, particularly nucleotide excision repair (NER) and the Fanconi anemia/interstrand crosslink repair network; shared sensitizers included ERCC4 (XPF), FANCE and SLX4. Validation experiments showed that disruption of representative DDR factors (POLH and XPA) synergistically increased oxaliplatin efficacy at concentrations as low as 0.5 μM. Transcriptomic analysis of the resistant MHCC-97H subline revealed coordinated upregulation of DNA repair programs, G2/M checkpoint and E2F target signatures, and epithelial–mesenchymal transition features. Integration with TCGA-LIHC data demonstrated frequent overexpression of many screen-identified DDR genes in primary HCC and an association between higher expression of selected factors and poorer patient survival. In the HAIC cohort, several DDR genes, including ATR, BRCA2, CDK7, MUS81, MUTYH, PARG, POLH, POLK and XPA, were significantly lower in the objective response group. Conclusions: DDR components represent candidate biomarkers and therapeutic targets whose inhibition may enhance oxaliplatin efficacy in HCC. Full article

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article

Thailand is facing a rapidly aging society, raising concerns about how retiring workers will maintain their quality of life. Insured persons in the social security system—especially voluntary members under Section 40 of the Social Security Act B.E. 2533 (1990), who are often informal workers—frequently lack formal retirement plans, underscoring the need for interventions that address financial security and subjective well-being (SWB) in later life. This study aimed to develop and evaluate a retirement planning program designed to enhance subjective well-being and improve the quality of life for pre-retirees in Songkhla Province. A Research and Development (R&D) design was employed in four phases. Phase 1 (R1) involved a needs assessment: survey data from 500 insured individuals (ages 40–60) were collected to identify gaps between current and desired retirement preparedness. Phase 2 (D1) utilized the needs assessment results and theoretical frameworks to design a Subjective Well-being Retirement Planning Program, encompassing financial, health, and psychosocial components. Content-relevance experts validated the draft program. Phase 3 (R2) involved implementing the program with 15 volunteer participants over four weekly workshops (each 3 h long) and evaluating its short-term pilot outcomes using pretest-posttest measures of subjective well-being. Phase 4 (D2) refined the program based on evaluation findings and expert feedback. Results indicated that following participation in the program, participants’ overall subjective well-being and all sub-dimensions (life satisfaction, positive and negative affect balance, sense of meaning, social connectedness, security, and health) were significantly higher than before (p < 0.001). Additionally, the proportion of participants classified as inadequately prepared for retirement (high-risk due to low planning) decreased markedly, suggesting increased readiness within the pilot group. Expert evaluations of the program design reflected a high content validity index and strong agreement on the program’s accuracy, appropriateness, and usefulness for the target group. In conclusion, the developed retirement planning program was associated with short-term improvements in subjective well-being and quality-of-life indicators among insured pre-retirees. This theory-informed program, developed through an R&D process, offers a model for supporting aging workers in the social security system, with implications for policymakers and practitioners seeking to promote healthy, happy, and secure retirements in an aging society. Full article

Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8⁺ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic modulator via protein lactylation. Nevertheless, the role of lactate in vitiligo pathogenesis has not been explored. Here, we report that serum lactate levels are significantly elevated in vitiligo patients and correlate positively with disease activity. In a mouse model, lactate administration accelerated vitiligo progression, accompanied by increased CD8⁺ T cell infiltration and melanocyte destruction in lesional skin. In vitro, lactate enhanced CD8⁺ T cell effector molecule expression (granzyme B, perforin, IFN-γ, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8⁺ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibility and transcriptional activation of effector genes, as revealed by RNA sequencing and CUT&Tag analyses. Pharmacological inhibition of lactate production or lactylation abrogated these effects. Collectively, our findings identify lactate as a critical driver of CD8⁺ T cell pathogenicity in vitiligo through H3K9la-mediated epigenetic reprogramming, highlighting lactate metabolism and lactylation as potential therapeutic targets. Full article

Human parainfluenza virus type 4 (hPIV4) remains poorly characterized compared with other hPIV serotypes and information on its genomic diversity is particularly limited for Russia and Eastern Europe. In this study, we report the first complete genome sequences of hPIV4 isolates from Russia and place them in the context of global hPIV4 genetic diversity. Eight hPIV4 viruses were isolated in cell culture from respiratory samples collected from hospitalized children in Saint Petersburg between 2017/2018 and 2023/2024. Complete viral genomes were recovered using a metagenomic whole-genome amplification approach based on SMART-9N technology. Phylogenetic analysis of 178 complete hPIV4 genomes showed clear separation into hPIV4a (n = 132) and hPIV4b (n = 46) subtypes. Based on genetic distance approach, hPIV4a formed two major clusters, with the dominant cluster B subdivided into four subclusters (B1–B4); and subcluster B4 further resolved into four genetic lineages. All Russian isolates belonged to the subcluster B4 and were distributed among multiple co-circulating lineages. In contrast, hPIV4b genomes segregated into three distinct clusters, reflecting structured genetic diversity within the subtype. Collectively, this study provides, to the best of our knowledge, the first p-distance-based framework for hPIV4 whole-genome classification and contributes new complete genome sequences for an underrepresented region. Full article

Saline–alkali stress severely limits crop production worldwide. Soybean [Glycine max (L.) Merr.] is particularly sensitive during seed germination, a stage critical for stand establishment. This complex stress environment encompasses two distinct yet equally critical dimensions: neutral salt stress and alkaline salt stress, each eliciting specialized physiological and metabolic responses. Here, a comparative assessment of four genotypes (tolerant: CN16, CN17; sensitive: Williams 82, K18) under 100 mmol/L Na⁺ revealed that alkaline salt stress exerts a significantly more potent inhibitory effect than neutral salt stress. Tolerant cultivars maintained 75–80% germination under alkaline conditions, whereas sensitive ones dropped below 15%, a divergence primarily driven by superior oxidative mitigation capacity. Integrated multi-omics analysis of the tolerant variety CN16 identified stage-specific regulatory shifts: early alkaline salt stress (60 h) triggers extensive transcriptional reprogramming focused on physical barrier reinforcement, including cell walls and lipid remodeling. By 96 h, regulatory modes between the two stress types diverged: neutral salt elicited a transcriptional surge, while alkaline salt transitioned to a metabolically dominant regulation, shifting flux from growth-related isoflavonoids to defense-related anthocyanins. Crucially, this study uncovers the distinct bioenergetic trade-offs governing these responses: whereas adaptation to neutral salt relies on low-energy galactose metabolism, tolerance to alkaline salt demands energy-intensive processes, specifically the active vacuolar compartmentalization of organic acids and anthocyanins for intracellular buffering. This obligatory energy expenditure restricts biomass accumulation, explaining the severe growth penalties observed in complex saline-alkali environments. Finally, the identification of a core regulatory module driven by key genes, including GmPHOT2b, GmLOG, and GmSHMT08, enriches the metabolic regulatory network under saline-alkali stress, providing core targets and a theoretical framework for precisely balancing metabolic expenditure with biomass accumulation in breeding practice. Full article

Doxorubicin is an effective chemotherapeutic agent, but it causes gastrointestinal toxicity that impairs treatment efficacy and quality of life. This study investigated the effects of liraglutide, a GLP-1 analog, on acute doxorubicin-induced gut toxicity in rats. Sixty male Wistar rats were assigned to four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). Groups L and DL received liraglutide (0.6 mg/kg, s.c.) for two weeks. D and DL were given a single dose of doxorubicin (20 mg/kg, i.p). After 48 h, the distal colon, feces, and blood were collected. Results: Doxorubicin caused crypt disruption, goblet cell loss, apoptosis, and reduced fecal short-chain fatty acids. Levels of TNF-α, NF-κB, Bcl-2, TLR4, and antioxidant enzymes were unchanged among groups. Microbiota analysis showed similar α-diversity but altered β-diversity. Doxorubicin reduced Bacteroidetes and increased Proteobacteria, with higher Arcanobacterium and Clavibacter genera abundance. Liraglutide alone decreased Bacteroidetes and increased Corynebacterium and Actinobaculum genera. Combined treatment showed no significant effects. We conclude that acute doxorubicin administration induces intestinal structural damage, reduces short-chain fatty acids, and changes microbiota composition. Although liraglutide alters microbial profiles, it does not attenuate doxorubicin-induced gut toxicity. Full article

Boron neutron capture therapy (BNCT) is a binary targeted radiotherapy that uses boron agents to treat refractory malignancies. This study developed a novel boronophenylalanine (BPA)-loaded liposome doped with o-carborane (CB) for BNCT. We applied response surface methodology (RSM) to identify factors affecting BPA loading and optimized encapsulation efficiency (EE) to minimize BPA loss. In in vitro experiments, these liposomes demonstrated promising characteristics for BNCT. The nanoparticle properties of CB-BPA-Lips remain stable for at least 48 h, and CB-BPA-Lips can effectively reduce the release of the agents loaded within them. Both cell viability assays and apoptosis assays have shown that CB-BPA-Lips have good biocompatibility and a lower inhibitory effect on cell viability than BPA. Cellular boron uptake peaked at 47.3642 ng B/10⁶ cells in A549 lung cancer cells and peaked at 38.8875 ng B/10⁶ cells in Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) human normal bronchial epithelial cells at 24 h post-treatment, with both exceeding uptake in the BPA control group. Overall, this work presents an optimized liposomal formulation that enhances boron delivery to cancer cells and provides a potential candidate boron agent for BNCT pending in-depth in vivo studies. Full article

Helicobacter pylori (H. pylori) is a highly adaptable gastric pathogen with marked genomic plasticity. Whilst functional CRISPR-Cas systems provide adaptive immunity in many bacteria, they have not been identified in H. pylori, unlike CRISPR-like sequences. In this study, eight H. pylori genomes were analysed using the bioinformatics tools CRISPRCasFinder, CRISPRCasTyper, and CRISPRloci. A total of 25 CRISPR-like arrays were identified, showing high conservation (88%) both between and within strains, suggesting that these arrays are not random remnants but rather organised structures possibly involved in cellular processes. Notably, a structural association was observed between the CRISPR-like sequences and the cag pathogenicity island (CagA-PAI). Conversely, CagA-PAI instability in specific strains was observed in the presence of the TnpA and TnpB transposons. Furthermore, in strain 29CaP, CRISPR-like assemblies were located in genomic proximity to the prophage Helico 1961P, leading to the hypothesis of a compensatory or regulatory effect in the absence of CagA-PAI. Taken together, these findings indicate that CRISPR-like arrays in H. pylori characterise a genomic architecture within regions of high plasticity. This study provides a solid exploratory foundation for future functional research on the adaptive and pathogenic evolution of H. pylori. Full article

Anemia is a major global public health problem and is most commonly associated with iron deficiency; however, deficiencies in other micronutrients, including vitamin B₁₂, may also contribute to its development. Increasing evidence suggests that Helicobacter pylori infection may influence the occurrence of anemia through several mechanisms related to alterations in the gastric environment. Chronic gastric inflammation and increased gastric pH associated with H. pylori infection may impair the absorption of non-heme iron and reduce the concentration of vitamin C in gastric juice. Since vitamin C enhances iron bioavailability by reducing ferric iron (Fe³⁺) to the more absorbable ferrous form (Fe²⁺), decreased levels of this vitamin may further limit iron absorption. At the same time, the increase in gastric pH may hinder the release of vitamin B₁₂ from food proteins, potentially contributing to disturbances in its absorption. This review aimed to present an integrated overview of the relationships between H. pylori infection, alterations in the gastric environment, and mechanisms that may contribute to the development of anemia, including disturbances in vitamin B₁₂ absorption, with particular emphasis on the potential role of vitamin C. Full article

In recent years, bacteria-based self-healing has emerged as a promising bioengineering strategy to address the self-repair of cracks in cement-based materials, which represent one of the persistent durability challenges. This approach relies on microbiologically induced calcium carbonate (CaCO₃) precipitation (MICP), in which metabolically active bacteria promote CaCO₃ formation of crystals that can heal cracks and restore material integrity. This study compares the self-healing potential of a natural (N-) alkaline soil Bacillus licheniformis strain with a UV-strain (phenotypic mutant) generated through controlled UV exposure followed by adaptive evolution. Both strains were evaluated under conditions relevant to cementitious environments. The UV-strain exhibited enhanced ureolytic performance, reaching urease activity of 0.32 U/mg compared to 0.24 U/mg in the N-strain. This translated into improved biomineralization, with CaCO₃ precipitation reaching 2.37 mg versus 2.23 mg/100 mL in the N-strain. Additionally, the UV-strain showed increased cell hydrophobicity and aggregation, indicating improved nucleation potential and surface-mediated mineral deposition. Multivariate analysis confirmed strong correlations between ureolytic metabolism, alkalization, and mineral formation, while artificial neural network (ANN) modeling (MLP 6-10-14) successfully predicted biomineralization-related parameters with high accuracy (R² > 0.90 for urease activity, NH₄⁺, ΔpH, and CaCO₃). The results demonstrate that UV-induced phenotypic adaptation can enhance biomineralization efficiency with minor trade-offs in physiological robustness. For the first time, that controlled UV-induced phenotypic adaptation can be used as a targeted strategy to enhance biomineralization efficiency in B. licheniformis, while maintaining functional stability under cement-relevant conditions. These findings provide a novel framework for tailoring bacterial performance in self-healing systems for construction biotechnology. Full article