Search Results (2,341)

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Nanotechnology offers innovative methodologies for enhancing the diagnosis and treatment of ovarian cancer by utilizing specialized nanoparticles. The utilization of nanoparticles offers distinct advantages, specifically that these entities enhance the bioavailability of therapeutic agents and facilitate the targeted delivery of pharmacological agents to neoplastic cells. A diverse array of nanoparticles, including but not limited to liposomes, dendrimers, and gold nanoparticles, function as proficient carriers for drug delivery. Nevertheless, notwithstanding the auspicious potential of these applications, challenges pertaining to toxicity, biocompatibility, and the necessity for comprehensive clinical evaluations pose considerable barriers to the widespread implementation of these technologies. The incorporation of nanotechnology into clinical practice holds the promise of significantly transforming the management of ovarian cancer, offering novel diagnostic tools and therapeutic strategies that enhance patient outcomes and prognoses. In summary, the deployment of nanotechnology in the context of ovarian cancer epitomizes a revolutionary paradigm in medical science, amalgamating sophisticated materials and methodologies to enhance both diagnostic and therapeutic outcomes. Continued research and development endeavors are essential to fully realize the extensive potential of these innovative solutions and address the existing challenges associated with their application in clinical settings. Full article

In this paper, a novel 4H-SiC LDMOS structure with a trench heterojunction in the source (referred as to THD-LDMOS) is proposed and investigated for the first time, to enhance the reverse recovery performance of its parasitic diode. Compared with 4H-SiC, silicon has a smaller band energy, which results in a lower built-in potential for the junction formed by P+ polysilicon and a 4N-SiC N-drift region. A trench P+ polysilicon is introduced in the source side, forming a heterojunction with the N-drift region, and this heterojunction is unipolar and connected in parallel with the body PiN diode. When the LDMOS operates as a freewheeling diode, the trench heterojunction conducts first, preventing the parasitic PiN from turning on and thereby significantly reducing the number of carriers in the N-drift region. Consequently, THD-LDMOS exhibits superior reverse recovery characteristics. The simulation results indicate that the reverse recovery peak current and reverse recovery charge of THD-LDMOS are reduced by 55.5% and 77.6%, respectively, while the other basic electrical characteristics remains unaffected. Full article

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article

The cement sheath is critical for ensuring the long-term safety and operational efficiency of oil and gas wells. However, complex geological conditions and operational stresses during production can induce cement sheath deterioration and cracking, leading to reduced zonal isolation, diminished hydrocarbon recovery, and elevated operational expenditures. This study investigates the development of a novel microbial self-healing well cement slurry system, employing fly ash as microbial carriers and sustained-release microcapsules encapsulating calcium sources and nutrients. Systematic evaluations were conducted, encompassing microbial viability, cement slurry rheology, fluid loss control, anti-channeling capability, and the mechanical strength, permeability, and microstructural characteristics of set cement stones. Results demonstrated that fly ash outperformed blast furnace slag and nano-silica as a carrier, exhibiting superior microbial loading capacity and viability. Optimal performance was observed with additions of 3% microorganisms and 3% microcapsules to the cement slurry. Microscopic analysis further revealed effective calcium carbonate precipitation within and around micro-pores, indicating a self-healing mechanism. These findings highlight the significant potential of the proposed system to enhance cement sheath integrity through localized self-healing, offering valuable insights for the development of advanced, durable well-cementing materials tailored for challenging downhole environments. Full article

CdTe nanocrystals (NCs) have emerged as a promising active layer for efficient thin-film solar cells due to their outstanding optical properties and simple processing techniques. However, the low hole concentration and high resistance in the CdTe NC active layer lead to high carrier recombination in the back contact. Herein, we developed a novel 2-iodothiophene as a wet etching solution to treat the surface of CdTe NC. We found that surface treatment using 2-iodothiophene leads to reduced interface defects and improves carrier mobility simultaneously. The surface properties of CdTe NC thin films after iodide salt treatment are revealed through surface element analysis, space charge limited current (SCLC) studies, and energy level investigations. The CdTe NC solar cells with 2-iodothiophene treatment achieved power conversion efficiency (PCE) of 4.31% coupled with a higher voltage than in controlled devices (with NH₄I-treated ones, 3.08% PCE). Full article

Background: The prevalence of BARD1 mutations in breast and ovarian cancers varies across different ethnic groups. Evaluating the cancer risk and clinical significance of BARD1 mutations in the local Chinese patients with breast cancer, ovarian cancer, or both is clinically important for designing an appropriate surveillance scheme. Methods: This study used a 30 gene panel to identify BARD1 germline mutations in 2658 breast and ovarian cancer patients. Results: Among this cohort, the BARD1 mutation prevalence was 0.45% for breast cancer and 0.29% for ovarian cancer. In our 12 mutation carriers, we identified eight types of mutation variants, including three novel mutations. BARD1 mutation carriers were more likely to have a family history of liver, prostate, and cervical cancers (p-values = 0.004, 0.018, and 0.037, respectively) than patients who tested negative for mutations. Among the BARD1 mutants, the majority of the breast tumors were invasive ductal carcinoma (NOS type) (10/11, 90.9%) of high-grade disease (9/9, 100%) and half of them were triple-negative breast cancer (5/10, 50%). Conclusions: Although the prevalence of BARD1 mutations is low and the penetrance is incomplete, we recommend including BARD1 in the test panel for breast cancer patients. Our data suggest that more comprehensive surveillance management may be considered in mutation carriers due to the familial aggregation of a relatively wide spectrum of cancers. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

The vast majority of photocatalysts find it difficult to consistently and stably exhibit high performance due to the variability of sunlight intensity within a day, as well as the high energy consumption of artificial light sources. In this study, mechanoluminescent Sr₂MgSi₂O₇:Eu,Dy phosphors is combined with NiS@g-C₃N₄ composite to construct a ternary heterogeneous photocatalytic system, denoted as NCS. In addition to the enhanced separation efficiency of photogenerated charge carriers by the formation of a heterojunction, the introduction of Sr₂MgSi₂O₇:Eu,Dy provides an ultra-driving force for the photocatalytic reactions owing to its mechanoluminescence-induced excitation. Results show that the degradation rate of RhB increased significantly in comparison with pristine g-C₃N₄ and NiS@g-C₃N₄, indicating the obvious advantages of the ternary system for charge separation and migration. Moreover, the additional photocatalytic activity of NCS under ultrasound stimulation makes it a promising all-weather photocatalyst even in dark environments. This novel strategy opens up new horizons for the synergistic combination of light-driven and ultrasound-driven heterogeneous photocatalytic systems, and it also has important reference significance for the design and application of high-performance photocatalysts. Full article

Traditional wound and burn treatments often fall short in balancing antimicrobial efficacy, patient comfort, and ease of application. This study introduces a novel, transparent, thermoresponsive sol–gel formulation incorporating polyhexamethylene biguanide (PHMB) for advanced topical therapy. Utilizing Poloxamer 407 as a biocompatible carrier, the formulation remains a sprayable liquid at room temperature and instantly gels upon contact with body temperature, enabling painless, pressure-free application on sensitive, injured skin. Comprehensive in vitro and in vivo evaluations confirmed the formulation’s broad-spectrum antimicrobial efficacy (≥5 log₁₀ reduction in 30 s), high biocompatibility (viability > 70% in fibroblasts), non-irritancy (OECD 425-compliant), and physical stability across three months. Importantly, the formulation maintained fibroblast migration capacity—crucial for wound regeneration—while exhibiting rapid sol-to-gel transition at ~34 °C. These findings highlight the system’s potential as a next-generation wound dressing with enhanced user compliance, transparent monitoring capability, and rapid healing support, particularly in disaster or emergency scenarios. Full article

To address critical technical challenges in coalbed methane fracturing, including the uncontrollable release rate of conventional breaker agents and incomplete gel breaking, this study designs and fabricates an intelligent controlled-release breaker system based on paraffin-coated mesoporous silica nanoparticle carriers. Three types of mesoporous silica (MSN) carriers with distinct pore sizes are synthesized via the sol-gel method using CTAB, P123, and F127 as structure-directing agents, respectively. Following hydrophobic modification with octyltriethoxysilane, n-butanol breaker agents are loaded into the carriers, and a temperature-responsive controlled-release system is constructed via paraffin coating technology. The pore size distribution was analyzed by the BJH model, confirming that the average pore diameters of CTAB-MSNs, P123-MSNs, and F127-MSNs were 5.18 nm, 6.36 nm, and 6.40 nm, respectively. The BET specific surface areas were 686.08, 853.17, and 946.89 m²/g, exhibiting an increasing trend with the increase in pore size. Drug-loading performance studies reveal that at the optimal loading concentration of 30 mg/mL, the loading efficiencies of n-butanol on the three carriers reach 28.6%, 35.2%, and 38.9%, respectively. The release behavior study under simulated reservoir temperature conditions (85 °C) reveals that the paraffin-coated system exhibits a distinct three-stage release pattern: a lag phase (0–1 h) caused by paraffin encapsulation, a rapid release phase (1–8 h) induced by high-temperature concentration diffusion, and a sustained release phase (8–30 h) attributed to nano-mesoporous characteristics. This intelligent controlled-release breaker demonstrates excellent temporal compatibility with coalbed methane fracturing processes, providing a novel technical solution for the efficient and clean development of coalbed methane. Full article

In this work, we report a novel mechanochemical synthesis method for the synthesis of quinoxaline derivatives—a spiral gas–solid two-phase flow approach, which enables the efficient preparation of quinoxaline compounds. Compared to conventional synthetic methods, this approach eliminates the need for heating or solvents while significantly reducing reaction time. The structures of the synthesized compounds were characterized using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV–Vis) absorption spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and high-performance liquid chromatography (HPLC). Using the synthesis of 2,3-diphenylquinoxaline (1) as a model reaction, the synthetic process was investigated with UV–Vis spectroscopy. The results demonstrate that when the total feed amount was 2 g with a carrier gas pressure of 0.8 MPa, the reaction completed within 2 min, achieving a yield of 93%. Furthermore, kinetic analysis of the reaction mechanism was performed by monitoring the UV–Vis spectra of the products at different time intervals. The results indicate that the synthesis of 1 follows the A4 kinetic model, which describes a two-dimensional diffusion-controlled product growth process following decelerated nucleation. Full article

Doxorubicin-induced cardiotoxicity (DIC) significantly constrains the clinical efficacy of anthracycline chemotherapy, primarily through the induction of ferroptosis, an iron-dependent, regulated cell death driven by oxidative stress and lipid peroxidation. However, the upstream regulators of ferroptosis in DIC remain incompletely defined. Cold-inducible RNA-binding protein (CIRBP) exhibits cardioprotective effects in various pathological contexts, but its precise role in ferroptosis-related cardiotoxicity is unknown. This study investigated whether CIRBP mitigates DIC by modulating the ferroptosis pathway via the SLC7A11 (Solute carrier family 7 member 11)/GPX4 (Glutathione peroxidase 4) axis. We observed marked downregulation of CIRBP in cardiac tissues and cardiomyocytes following doxorubicin exposure. CIRBP knockout significantly exacerbated cardiac dysfunction, mitochondrial damage, oxidative stress, and lipid peroxidation, accompanied by increased mortality rates. Conversely, CIRBP overexpression alleviated these pathological changes. Molecular docking and dynamics simulations, supported by transcriptomic analyses, revealed direct binding of CIRBP to the 3′-UTR of Slc7a11 mRNA, enhancing its stability and promoting translation. Correspondingly, CIRBP deficiency markedly suppressed SLC7A11 and GPX4 expression, impairing cystine uptake, glutathione synthesis, and antioxidant defenses, thus amplifying ferroptosis. These ferroptotic alterations were partially reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, this study identifies CIRBP as a critical regulator of ferroptosis in DIC, elucidating a novel post-transcriptional mechanism involving Slc7a11 mRNA stabilization. These findings offer new insights into ferroptosis regulation and highlight CIRBP as a potential therapeutic target for preventing anthracycline-associated cardiac injury. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article