Search Results (12,078)

The safety of titanium dioxide (TiO₂), widely used in foods and personal care products, has been of on-going concern. Adverse effects of TiO₂ have been reported, suggesting risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO₂ product, to which humans could be exposed, on microRNA (miRNA) expression (a primary epigenetic mechanism) was investigated using human cell lines (Caco-2, HCT116 (colorectal) and HepG2, SNU387 (liver)) relevant to human exposure. The effect of TiO₂ nanomaterial exposure on expression levels of miRNA was determined using the TaqMan Array Human microRNA A+B Card Set v3.0 platform. Differentially expressed miRNAs were identified (SNU387 (n = 112), HepG2 (n = 97), Caco-2 (n = 94), and HCT116 (n = 53)). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis of target genes provided insights into the roles of modulating pathways, which can be associated with diseases. Top 10 KEGG pathways in each cell line included MAPK signaling pathway, Axon guidance, cell cycle, Hippo signaling pathway, and Endocytosis. Findings from the study clearly demonstrate the impact of TiO₂ exposure on miRNA expression, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are important for the complete assessment of the potential risk from exposure. Full article

Severe southern soybean crinkle leaf disease (SSCLD) reduces soybean seed yield by approximately 40%. Identifying the genes that control SSCLD is crucial for breeding resistant varieties and elucidating the molecular mechanisms underlying SSCLD infection. In this study, recombinant inbred lines (RILs, n = 236) derived from a cross between Nannong1138-2 (NN1138-2) and Zhengxiaodou (ZXD) were used as experimental materials. A field trial employing a randomized block design was conducted in four environments across two locations, Nanning (2019–2021) and Du’an (2020) in Guangxi, to identify the disease severity grades of SSCLD in the field. QTLs controlling SSCLD were detected via a genetic map constructed using 3255 SLAF (specific locus amplified fragment) markers from the recombinant inbred lines. RT‒qPCR was used to analyze candidate gene expression at major effect loci. The results revealed that eight SSCLD-associated QTLs were identified on chromosomes 3, 6, 12, and 17. Notably, the qw12-1 locus on chromosome 12 was detected across three developmental stages in three of the four environments, explaining 10.18–58.20% of the phenotypic variation. RT‒qPCR analysis of 12 disease resistance-related genes within the qw12-1 interval revealed that GLYMA_12G233000 and GLYMA_12G239200 presented significantly higher expression in crinkled leaf lines than in normal leaf lines during the V5 (fifth trifoliolate stage), R2 (full bloom stage), and R6 (full seed stage) stages. These genes were prioritized as potential prime candidates for SSCLD resistance genes. This research provides foundational data for the fine mapping of qw12-1 and cloning SSCLD-related genes, advancing our understanding of the molecular mechanisms underlying SSCLD. Full article

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

Background: Large language models (LLMs) are being used by surgeons for education and reference yet concerns about hallucinations and reliability limit safe adoption. Retrieval-augmented generation (RAG) can offer a potential solution by grounding responses in a high-quality external database (e.g., medical textbooks) to enhance accuracy. However, performance tradeoffs across different RAG configurations—many of which exponentially increase computational cost—remain poorly characterized. Methods: In total, 120 lightweight, open-source RAG configurations were evaluated across 40 plastic surgery-focused question-answering tasks (20 single-hop, 20 multi-hop), spanning multiple subspecialties (4800 total evaluations). Configurations varied by base LLM (Phi-3-mini-128k-instruct vs. BioMistral-7B), embedding model, database size, chunk size, and query hop type. Performance was assessed using semantic similarity (Ragas) to physician-validated reference answers. Performance was analyzed using linear mixed-effects regression with query as a random effect and fixed and interaction effects selected via likelihood testing and AIC. Results: High performance was achievable using lightweight, open-source models. While BioMistral-7B had high mean sematic similarity under specific configurations (mean semantic similarity up to 0.786), Phi-3-mini-128k-instruct demonstrated more consistent performance across query complexity. Larger database sizes significantly improved semantic similarity, with the largest gain at intermediate sizes (e.g., size 5: +0.043, p = 0.001). Embedding choice had a strong effect, with bge-large-en-v1.5 improving performance (p = 0.0016) and Bio_ClinicalBERT markedly reducing it (p < 0.001). Multi-hop queries substantially reduced performance (p < 0.001), though this effect was attenuated for Phi-3-mini-128k-instruct via a strong model × hop-type interaction (p < 0.001). Conclusions: RAG systems for plastic surgery do not require large proprietary models, as performance depends on configuration choices and interaction effects rather than isolated components. With advancements, predictive modeling may enable resource-efficient, safe deployment of clinical RAG systems. Full article

This study explored the electronic and structural tunability of fullerene (C₆₀) derivatives via functionalization with heteroatoms (O, S, Se) in mono-, di-, and tri-bridged configurations, including covalently modeled dimers. Calculations were performed using density functional theory (DFT) at the B3LYP/6-31G(d,p) level. Electronic descriptors such as total dipole moments (TDMs), HOMO–LUMO energy gaps (ΔE), global reactivity descriptors, total density of states (TDOS), molecular electrostatic potential (MESP) and non-covalent interactions (NCIs) were analyzed to elucidate how functionalization alters reactivity and stability. Key findings indicate that TDM increases and ΔE decreases in all functionalized C₆₀; for example, the TDM increased from 0 Debye for C₆₀ to 2.156 Debye for C₆₀–O–S–Se, and ΔE decreased from 2.762 eV (C₆₀) to 2.532 eV (C₆₀–Se), indicating enhanced reactivity. This aligns with global reactivity descriptors such as reduced ionization energy and hardness. Mapped MESP surfaces showed activation around heteroatom sites. Quantum theory of atoms in molecules (QTAIM) and NCI analyses revealed that while mono-bridged structures retain covalent linkages, dimeric systems such as C₆₀–O–C₆₀ and C₆₀–S–C₆₀ relax into weak, van der Waals-type interactions. OPDOS (overlap population density of states) highlighted antibonding character between the fragments in the conduction region. These results demonstrate that heteroatom functionalization enhances the electronic properties of C₆₀, making it a promising candidate for optoelectronic, organic photovoltaic, and sensor applications. Full article

Background/Objectives: Lifestyle behaviors such as smoking, vaping, and physical activity can induce epigenetic modifications that influence health trajectories and may provide forensic value. DNA methylation signatures linked to these behaviors offer potential for behavioral inference, personalized health assessment, and improved investigative practices. This study aimed to characterize methylation patterns associated with nicotine exposure and exercise using buccal cell DNA profiling, and to evaluate the extent to which these patterns differentiate harmful and protective lifestyle habits. Methods: Buccal epithelial DNA was analyzed using the Illumina Infinium MethylationEPIC v2 BeadChip to assess genome-wide methylation. Participants were categorized by smoking status, vaping behavior, and exercise activity. Differentially methylated regions (DMRs) and CpG sites were identified through pairwise comparisons among smokers, vapers, non-smokers/non-vapers, athletes, and sedentary individuals. A threshold of p < 1 × 10⁻⁴ was applied for significant differentially methylated CpG sites. Results: Distinct epigenetic profiles were associated with smoking/vaping and physical activity. Five DMRs differentiated smokers from non-smokers/non vapers, while 11 DMRs distinguished vapers from the same reference group. Twenty-eight DMRs displayed divergent methylation patterns between smokers and vapers. Exercise also showed measurable epigenetic influence: control athletes exhibited 26 significantly differentially methylated CpG sites relative to non-athletes, and smoker athletes demonstrated 126 suggestive differential sites compared to sedentary smokers. Additionally, 63 sites differentiated smoker athletes from non-smoker/non-vaper non-athletes, indicating interactions between risk-associated and health-promoting behaviors. Conclusions: Buccal cell DNA methylation profiling effectively captured signatures associated with smoking, vaping, and physical activity. These findings underscore the potential of epigenetic markers for lifestyle assessment in both personalized medicine and forensic investigations. Full article

Coal preparation tailings from the K18 seam of the Abayskaya mine were evaluated as a potential secondary source of critical rare earth elements (REEs). The study showed that REEs are predominantly associated with the mineral fraction of coal; therefore, during beneficiation, approximately 70% of their total content is transferred to flotation tailings. The concentrations of valuable elements in the tailings are as follows (g/t): Li—65; Sc—16; Y—17; Yb—2.5; V—135; and Ti—2293. These values significantly exceed the Clarke values and are comparable to those of some low-grade primary ores, indicating the potential of coal preparation wastes as a technogenic raw material for critical elements. To extract REEs from the resistant aluminosilicate matrix, a fluorine–ammonium sulfate thermochemical activation method was proposed. Using a probabilistic–deterministic experimental design approach, a mathematical model of the process was developed and optimal parameters were determined (400 °C, 120 min, (NH₄)₂SO₄ consumption—140% relative to Al, NH₄HF₂ consumption—110% relative to Si), providing a feed liberation degree (by Al extraction) of up to 94%. Under optimal conditions, high leaching efficiencies of key elements were achieved: Sc (95%), Y (100%), Yb (100%), and Li (100%). The results demonstrate the significant potential of coal preparation tailings as a secondary resource of rare earth elements and confirm the efficiency of fluorine–ammonium sulfate technology for processing this type of technogenic waste. Full article

Multiport DC–AC converters are widely used in photovoltaic-energy storage–charging systems, but traditional two-stage schemes face challenges in circuit cost and efficiency improvements. To address this issue, a novel three-port single-stage DC–AC converter is proposed for grid-connected applications. The proposed converter integrates two DC ports and one AC port through circuit multiplexing, eliminating the high-voltage DC bus and reducing system complexity. An unfolding bridge is employed at the AC port, and full bridge circuits are used at DC ports, reducing the number of high-frequency switches. The proposed single-stage topology inherently achieves galvanic isolation and bidirectional power conversion. To achieve accurate grid current regulation and wide-range zero-voltage-switching, a multiple-phase-shift modulation method is developed to ensure a sinusoidal current waveform. The effectiveness of the proposed converter and modulation method is verified through simulation results, demonstrating a peak efficiency of 97% and a total harmonic distortion of 2.91%. Full article

Pancreatic ductal adenocarcinoma (PDAC) has limited effective therapeutic strategies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and may affect tumor cell fitness via the mevalonate pathway, mitochondrial function, and redox homeostasis. We systematically compared seven statins in patient-derived PDAC cell lines and related viability effects to mitochondrial, redox, cell-cycle, apoptotic, and metabolic responses. Statins were tested in three PDAC cell lines (PDAC-1/2/3) using MTT assays (5–20 µM; 24–120 h). Based on MTT responses, mechanistic profiling was performed after 72 h at 20 µM concentration using lipophilic statins, including apoptosis (Annexin V/7-AAD), cell-cycle distribution, mitochondrial membrane potential (Δψm), intracellular ROS, and ¹H-NMR quantification of intracellular and extracellular metabolites. Statins reduced viability in a concentration- and time-dependent manner, with lipophilic statins more active than hydrophilic. PDAC-1 was highly sensitive, PDAC-3 intermediate, and PDAC-2 comparatively resistant. PDAC-1 and PDAC-3 showed G0/G1 accumulation, Δψm depolarization, reactive oxygen species (ROS) elevation, and Annexin V–positive apoptosis, whereas PDAC-2 (high basal ROS) showed ROS reduction and limited apoptosis despite Δψm loss. Metabolomics indicated reduced glucose and amino-acid utilization and lactate secretion while preserving line-specific metabolic fingerprints. PDAC cell lines display marked inter-tumoral heterogeneity in statin responses, supporting evaluation of statins as chemosensitizing adjuvants in functionally guided PDAC treatment strategies. Full article

In this work, a high-performance mid-wave infrared (MWIR) photodetector (PD) utilizing an InAs/GaSb Type-II superlattice absorber and a quaternary AlGaAsSb barrier is designed and analyzed based on numerical simulations aimed at determining an optimized detector structure. Through these simulations, the composition of the AlGaAsSb barrier is carefully designed to achieve lattice matching, high conduction band offset and zero valence band offset. By optimizing the barrier thickness and doping concentration, the depletion region is effectively shifted from the narrow-bandgap absorber to the wide-bandgap barrier; additionally, at 150 K and a reversed bias of 0.05 V, the dark current density in the PD with the barrier (pBn) is reduced to 1.83 × 10⁻⁵ A/cm², about two orders of magnitude lower than that of the PD without the barrier. Furthermore, the effect of the barrier on the generation–recombination (G-R) and the trap-assisted tunneling (TAT) currents are analyzed and compared in detail, and it is found that the barrier structure is much more effective in suppressing the TAT current at low reversed bias when the electric field is low in the absorber layer. These results demonstrate the efficacy of the proposed AlGaAsSb barrier design for realizing high-operating-temperature MWIR PDs. It also provides an insight into the physical mechanism that leads to the performance enhancement of InAs/GaSb PDs. Full article

Evaluating cancer gene mutations is critical for effective therapeutic selection. Although massive parallel sequencing can efficiently detect gene mutations, most are variants of uncertain significance (VUS). Saturation genome editing (SGE) can facilitate VUS analysis by leveraging CRISPR-Cas9 and homology-directed repair to simultaneously introduce abundant gene mutations. Chronic myelogenous leukemia-derived HAP1 cells are widely used in SGE because of their clear genotype–phenotype relationship; however, the sole use of haploid cells limits SGE applicability in cancer research. Therefore, we developed an SGE-based system for evaluating KRAS mutations in diploid HCT 116 colon carcinoma cells. Single-nucleotide variants (SNVs) in KRAS codons A11–V14 were generated using Cas9-based SGE. Massive parallel sequencing revealed increased abundance of KRAS ^G12 and KRAS ^G13 SNVs and decreased abundance of the KRAS ^G12C SNV after KRAS ^G12C inhibitor treatment in SGE pooled cells. These results indicate that SGE is applicable to diploid HCT 116 cells and useful for evaluating SNV population changes and drug sensitivity. Thus, although haploid HAP1 cells are the primary models for SGE, the successful application of SGE to diploid HCT 116 colon carcinoma cells provides a practical framework for implementing SGE in KRAS-dependent carcinoma cells. Full article

Ionic polymer–metal composites consist of an ion-conducting polymer–gel membrane sandwiched between two flexible electrodes, representing a class of soft electroactive materials capable of large deformation under low voltage. The gel membrane, swollen with solvent, facilitates ion migration under an electric field, enabling actuation. Tailoring the interfacial architecture between the electrode and the polymer–gel membrane is pivotal for advancing high-performance IPMC actuators. This study presents a comparative investigation of three core–shell nanocomposite electrodes, fabricated via in situ polymerization, for IPMC applications. Among these, the polyaniline-coated multi-walled carbon nanotube composite exhibits a deliberately designed hierarchical structure, with a specific surface area of 32.345 m²·g⁻¹ and a conductive doped polyaniline shell, as confirmed through XPS analysis. This optimized interface enables superior charge storage and transport, endowing the corresponding electrode with a specific capacitance of 40.28 mF·cm⁻² at 100 mV·s⁻¹—3.2 times greater than that of conventional silver-based electrodes—along with a reduced sheet resistance. When integrated with a Nafion ion–gel membrane, the PANI@MWCNT electrode achieves a 67% increase in force density and a larger displacement output compared to standard devices, directly correlated with its enhanced electrical and electrochemical properties. This work highlights the critical role of core–shell interfacial engineering in governing electromechanical performance at the electrode–gel interface and offers a practical design strategy for developing high-performance, cost-effective IPMC actuators for soft robotics, flexible electronics, and related applications. Full article

Cotton, a globally vital cash crop, is severely constrained by V. dahliae. Lignin, a core structural component of plant cell walls, plays a crucial role in physical defense, with its biosynthesis regulated by hydroxycinnamoyltransferase (HCT)—a key enzyme in the phenylpropanoid pathway. However, the HCT gene family in upland cotton (Gossypium hirsutum) and its role in resistance to V. dahliae remain poorly understood. In this study, we performed a genome-wide identification of the HCT gene family in G. hirsutum, identifying 74 GhHCT genes that were classified into five evolutionary subfamilies. Bioinformatics analysis revealed that GhHCT proteins exhibit conserved functional domains but diverse gene structures, with promoter regions enriched in hormone-responsive and stress-responsive cis-acting elements. Expression profiling revealed that multiple GhHCT genes were significantly induced in response to V. dahliae infection. Three genes, GhHCT2, GhHCT35, and GhHCT47, showed significantly higher expression levels in resistant cultivars than in susceptible cultivars during early infection stages, suggesting pivotal roles in defense. These three candidate genes, which contain MeJA/SA-responsive elements in their promoters, may enhance resistance by regulating lignin synthesis to strengthen the cell wall barrier. In summary, this study provides the first comprehensive characterization of the HCT gene family in upland cotton. It identifies key candidates for improving resistance to V. dahliae, offering valuable genetic resources for molecular breeding. Full article

Background: The increasing antimicrobial resistance has led to a greater demand for alternative treatment options, which in turn has increased interest in naturally occurring biomolecules such as pyocyanin. Methods: In this study, a three-factor Box–Behnken Design (BBD)-based response surface methodology (RSM) was employed to optimize the effects of glycerol, peptone, and pH on pyocyanin production by Pseudomonas aeruginosa OG1. The antimicrobial efficacy of the optimized pyocyanin was subsequently evaluated in vitro against three Candida species and four clinically important bacterial pathogens using the disk diffusion method, with gentamicin and fluconazole used as positive controls. Results: The second-order polynomial model demonstrated excellent fit (F = 176.3, p < 0.0001) with a non-significant lack of fit, indicating adequate representation of the experimental data. The optimal conditions were determined to be glycerol at 1.11% (w/v), peptone at 17.86 g/L, and a pH of 7.27, yielding a predicted pyocyanin concentration of 25.92 mg/L. Antimicrobial testing revealed broad-spectrum, dose-dependent activity against all tested microorganisms. The highest efficacy was observed against Bacillus cereus (26.4 ± 1.3 mm at 40 µg/mL), followed by Candida glabrata (21.5 ± 1.6 mm), Klebsiella pneumoniae (17.6 ± 1.4 mm), Candida albicans (15.4 ± 1.8 mm), Candida parapsilosis (13.2 ± 1.9 mm), Proteus mirabilis (12.5 ± 1.3 mm), and MRSA Staphylococcus aureus (9.2 ± 1.1 mm). Conclusions: These findings demonstrate that BBD-based RSM is a robust approach for optimizing pyocyanin production and that pyocyanin represents a promising dose-dependent antimicrobial agent against susceptible pathogens. Full article

Background: Selective immunoglobulin A deficiency (sIgAD), the most common primary immunodeficiency, is associated with recurrent respiratory infections. Despite the established role of IgA in mucosal immunity, population-based data evaluating COVID-19 susceptibility and severity among individuals with sIgAD are scarce. Objectives: This study aimed to evaluate the association between selective IgA deficiency and the risk of SARS-CoV-2 infection, recurrent infection, COVID-19-related hospitalization, and vaccination uptake. Design and Setting: We conducted a retrospective population-based cohort study using the Clalit Health Services electronic health record database in Israel. Methods: Adults aged ≥18 years with documented serum IgA measurements between 2020 and 2022 were included. Selective IgA deficiency was defined as serum IgA < 7 mg/dL with normal IgG and IgM levels. Individuals with sIgAD were matched 1:4 with controls with normal IgA levels by age and sex. Outcomes included documented SARS-CoV-2 infection, recurrent infection (>2 episodes), COVID-19-related hospitalization, and vaccination status. Multivariable logistic regression models were adjusted for demographic characteristics, comorbidities, and vaccination status. Results: The matched cohort included 61,150 individuals (12,230 with sIgAD and 48,920 controls). The risk of primary SARS-CoV-2 infection did not differ significantly between groups (13.0% vs. 14.0%; adjusted OR 1.03, 95% CI 0.95–1.12). However, individuals with sIgAD had increased odds of recurrent infection (adjusted OR 1.15, 95% CI 1.09–1.22) and COVID-19-related hospitalization (adjusted OR 1.40, 95% CI 1.22–1.60). Booster vaccination uptake was slightly higher among individuals with sIgAD. Conclusions: Selective IgA deficiency was not associated with increased susceptibility to primary SARS-CoV-2 infection but was independently associated with recurrent infection and increased risk of hospitalization. These findings underscore the importance of mucosal immunity in post-infection viral control and suggest that individuals with sIgAD may benefit from closer monitoring after COVID-19 infection. Full article