Search Results (89)

Despite aesthetic trends, metal–ceramic restorations continue to be widely accepted due to their durability, and variations in surface preparation process can significantly influence bond strength outcomes. The purpose of this study was to determine whether there are differences in the bond strength depending on three surface treatment protocols for veneering ceramics on Ni-Cr alloys. The following surface treatments were used: (1) control (C) (no treatment), (2) airborne-particle abrasion (APA) with 50 µm Al₂O₃ (G1-APA), (3) APA followed by oxidation (G2-APA-O), and (4) APA-O, with a second APA (G3-APA-O-APA). Subsequently surface roughness (R_a and R_z) was evaluated using profilometry, hardness was measured through Leeb’s hardness dynamic test (HLD), morphology was investigated through scanning electron microscopy (SEM), and the chemical composition of the alloy surface was evaluated using energy-dispersive spectroscopy (EDS). After surface treatments, veneering ceramic was applied, the debonding crack initiation strength (DCIS) was investigated through the three-point bending test, failure mode was classified using a stereoscopic microscope, and chemical characterization of the fractured surfaces was performed using Raman spectroscopy (RS). For DCIS, G2-APA-O demonstrated the highest value 63.97 ± 44.40 (MPa) (p < 0.05). The results of this study indicate that oxidation treatment has a positive effect on the bonding strength between veneering ceramic and Ni-Cr alloys. Full article

The sarcopenic obesity-related phenotype (SOP) is defined by the coexistence of sarcopenia and obesity, leading to heightened disability, morbidity, and mortality. Its multifactorial pathogenesis involves chronic inflammation and metabolic alterations. In this cross-sectional study, 562 women were classified into four groups: control, sarcopenic, obese, and SOP. Body composition measurements, including fat mass, skeletal muscle mass, and extracellular water (ECW), were assessed using the bioimpedance method. Several inflammatory biomarkers were measured in plasma samples by ELISA. Discriminant function analysis identified age, ECW, chemerin, the systemic immune-inflammation index (SII), and the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) as significant discriminators among groups, clearly distinguishing SOP from control. Multivariable logistic regression analysis revealed that these variables were independently associated with SOP status (SOP vs. control), regardless of age, with odds ratios (ORs) ranging from 1.87 (95% confidence interval [CI]: 1.23–2.85) for SII to 7.77 (95% CI: 3.67–16.44) for ECW. A generalized estimating equation (GEE) analysis further demonstrated that SOP significantly increased the odds (OR: 3.04; 95% CI: 1.39–6.67) of multimorbidity (hypertension (HTN) + hyperlipidemia (HLD) + type 2 diabetes (D2T)). These findings suggest SOP is a clinically relevant phenotype linked to cardiometabolic comorbidities and systemic inflammation. Identifying SOP using accessible body composition and biomarker assessments may support early risk stratification and guide personalized preventive strategies in clinical care. Full article

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm-forming ability underscore the limitations of current antibiotics. In this study, a new compound named tripterhyponoid A was found to effectively combat MRSA, with an MIC of 2.0 μg/mL. It inhibited biofilm formation by downregulating genes related to the quorum sensing (QS) pathway (sarA, agrA, agrB, agrC, agrD, and hld) and eradicated mature biofilms. Furthermore, it induced DNA damage by binding to bacterial DNA, enhancing its efficiency against MRSA. Therefore, its anti-MRSA properties with multiple mechanisms of action make it less prone to developing resistance over 20 days. In addition, it reduced the bacterial load and regulated the levels of inflammatory cytokines IL-6 and IL-10 at the wound site in a mouse skin infection model. This paper provides the first in-depth investigation of the mechanisms of triterpenoids against MRSA by inhibiting the expression of QS system genes and binding to DNA. Full article

Staphylococcus aureus (S. aureus) colonizes the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Treatment-resistant S. aureus biofilms and intracellular persistence are common in CRS patients, requiring the expression of specific virulence factor genes to transition into these forms. We hypothesized that S. aureus isolates from non-diseased controls, CRSsNP patients, and CRSwNP patients would exhibit distinct virulence factor patterns contributing to persistence and intracellular survival in CRS patients. Nasal swabs from seventy-seven individuals yielded S. aureus cultures in eight non-diseased controls, eight CRSsNP patients, and five CRSwNP patients. Whole-genome sequencing analyzed stress, antimicrobial resistance, and virulence genes, including plasmids and prophages. Four virulence factor gene patterns emerged: a core set (hlgA, icaC, hlgB, hlgC, hld, and aur) present in all isolates, and accessory sets, including the enterotoxin gene cluster (seo, sem, seu, sei, and sen) and a partial/complete invasive virulence factor set (splE, splA, splB, lukE, and lukD) (p = 0.001). CRSwNP isolates exhibited incomplete carriage of the core set, with frequent loss of scn, icaC, and hlgA (p < 0.05). These findings suggest that S. aureus has clusters of virulence factors that may act in concert to support the survival and persistence of the bacteria, resulting in enhanced pathogenicity. This may manifest clinically with resistant disease and refractoriness to antibiotics. Full article

Background and Objectives: Oral isotretinoin has revolutionized the treatment of severe acne vulgaris. Isotretinoin is associated with multiple adverse effects, one of which is dyslipidemia (DLP). Materials and Methods: This single-center prospective study recruited 498 patients who were eligible for isotretinoin for severe acne. Risk factors for hyperlipidemia and serum lipids were assessed at baseline. Patients received daily doses ranging from 0.25 to 1 mg/kg of their body weight, and their fasting serum lipids were checked regularly until they reached a cumulative dose of 120–150 mg/kg. Our primary objective is to investigate dyslipidemia incidence and predictors, while the secondary objective is to assess the impact of dose reduction on lipid panels. Results: Our sample was primarily female (n = 380, 76.3%), with a normal Body Mass Index (23.2 ± 4.0) and a mean age of 20.7 (±4.1) years. About 72.5% had a family history of acne, 17.1% a family history of dyslipidemia. Around 17.3% reported tobacco use. A total of 57 (11.4%) patients on isotretinoin developed DLP. Smoking was independently associated with a higher risk of dyslipidemia (OR 1.97, 95% CI [1.01, 3.82], p = 0.046). The mean onset of DLP was at 3.23 (±2.13) months. A total of 52 patients out of the 57 had a dose reduction of 10 mg (n = 5) or 20 mg (n = 47). A dose reduction of 50% was found to significantly improve triglyceride levels. Conclusions: More than 1 out of 10 patients on isotretinoin developed DLP. Tobacco use was significantly associated with developing DLP. Dose reduction significantly impacted a decrease in triglyceride levels. Full article

Using microemulsions (µEs) as preservation media for cells was pursued in the 1990s; however, the difficulty in formulating biocompatible µEs and keeping unacclimatized cells alive for more than three days hindered developments in this area. This work explores the use of fully dilutable self-microemulsifying delivery systems (SMEDS) formulated with lecithin (Le) and polyglycerol-10-caprylate (PG10C) at a ratio of 2/5. This surfactant blend was mixed with ethyl oleate (EOL) at a ratio of 60 surfactant/40 EOL to produce a D60 dilution line. This D60 SMEDS was diluted with 0.9% w/v NaCl solution to produce lecithin-linker µEs (LLMs). The properties of the resulting LLMs were predicted using the hydrophilic–lipophilic-difference (HLD) and net-average curvature (NAC) model, indicating that LLMs with aqueous content from 5% to 60% are bicontinuous, confirmed via viscosity and conductivity. The largest yeast activity and viability obtained with LLMs were achieved with 30% aqueous content, resulting from the balance between having enough water for the effective transport of metabolites, enough SMEDS to contribute nutrients and lipids, and a low enough water to limit the partition of PG10C that, when present in the aqueous phase, inhibited yeast activity. For SMEDS, its low water activity ensured that the yeast remained dormant, keeping them alive for at least 10 weeks. Full article

This work provides a comprehensive review of experimental methods used to measure rheological properties of interfacial layers stabilized by surfactants, asphaltenes, and proteins that are relevant to systems with large interfacial areas, such as emulsions and foams. Among the shear methods presented, the deep channel viscometer, bicone rheometer, and double-wall ring rheometers are the most utilized. On the other hand, the main dilational rheology techniques discussed are surface waves, capillary pressure, oscillating Langmuir trough, oscillating pendant drop, and oscillating spinning drop. Recent developments—including machine learning and artificial intelligence (AI) models, such as artificial neural networks (ANN) and convolutional neural networks (CNN)—to calculate interfacial tension from drop shape analysis in shorter times and with higher precision are critically analyzed. Additionally, configurations involving an Atomic Force Microscopy (AFM) cantilever contacting bubble, a microtensiometer platform, rectangular and radial Langmuir troughs, and high-frequency oscillation drop setups are presented. The significance of Gibbs–Marangoni effects and interfacial rheological parameters on the (de)stabilization of emulsions is also discussed. Finally, a critical review of the recent literature on the measurement of interfacial rheology is presented. Full article

This study proposes improving the process of the vertical diffusion of temperature in numerical models to enhance the accuracy of sea surface temperature (SST) simulation. SST tends to be underestimated in the coastal and tidal flat regions, such as the Yellow Sea around Korea. In particular, SST in coastal areas is highly sensitive to wet/dry treatment, implying that the sensitivity of SST increases with the slope of coastal bathymetry. Therefore, during the calculation of vertical temperature diffusion terms, the numerical model’s surface boundary condition (SBC) was modified to limit excessive temperature differences below a certain depth in the coastal regions. Under wet or dry conditions defined by the wet/dry treatment, SBC and bottom boundary condition (BBC) adjustments are stabilized within a predefined depth limit. While horizontal diffusion also plays a role in the model, SST is significantly influenced by the balance of heat advection and shortwave radiation. To demonstrate this, Heat Limit Depth (HLD) was added as an input parameter into the vertical diffusion algorithm in the model to enhance sensitivity to the SBC. If the total water depth in the tidal flat is below the HLD and less than 1.0 m, the model is changed to estimate surface sediment temperature instead of SST. The improvement in the vertical diffusion term for SST was effective primarily in tidal flat areas. In contrast, the impact was less pronounced in coastal areas with average depths exceeding 5 m. The rationale for separating SBC and BBC in the improved air–sea interaction process is twofold: SBC adjustments are suitable for reducing heat flux effects, specifically in shallow depths or tidal flats, without significantly affecting the entire model domain, while combined SBC and BBC adjustments are more appropriate for inducing coastal SST changes across the domain. Full article

Introduction: In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system. Methodology: We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation. Results: Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation. Conclusions: These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment. Full article

Staphylococcus aureus is well known to be the primary causal agent of clinical or subclinical mastitis in dairy sheep. The production of virulence factors allows S. aureus strains to cause mastitis. In the present study, 96 strains isolated from dairy sheep farms used for the production of autologous vaccines were tested for enterotoxin and hemolysin genes by PCR. In addition, 14 strains isolated from half udders of ewes with subclinical mastitis belonging to a single farm were also tested for the same genes. The phylogenetic trees were constructed, and spatial analysis was performed. Overall, 20 gene patterns were identified, but 43.64% of the tested strains showed the same profile (sec+, sel+, hla+, hld+, hlgAC+). Considering only the enterotoxin genes, four profiles were identified while the evaluation of the hemolysin genes revealed the presence of 12 gene patterns. In the farm with subclinical mastitis, six gene profiles were found. Spatial analysis of the isolated strains and their virulence genes did not show a specific pattern. The present study highlights the importance of identifying and analyzing virulence genes of S. aureus strains involved in dairy sheep mastitis, and the presence of different strains in the same farm. Full article

Introduction: Adult-onset Still’s disease (AOSD) is a rare chronic autoinflammatory condition characterized by a spiking fever, arthritis, a rash, hepatosplenomegaly, lymphadenopathy, leucocytosis, and hyperferritinemia. It is sometimes accompanied by life-threatening complications like macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH). Treatment options for AOSD include glucocorticoids (GCs), immunosuppressive drugs, biological medications, and Janus kinase (JAK) inhibitors. The features that differentiate MAS/HLH from AOSD are: in MAS/HLH, a different type of fever, which is persistent, a sharp decrease in the number of leukocytes and thrombocytes, a further increase in the level of transaminases and ferritin, significant hepatosplenomegaly, lymphadenopathy, symptoms of the central nervous system (CNS), disseminated intravascular coagulation (DIC) and hemophagocytosis in the bone marrow. This study aimed to evaluate the course of AOSD, which results in MAS/HLD. Patients and methods: Nine AOSD patients, four of whom developed MAS/HLH, were treated at the Rheumatology Clinic in the Central Clinical Hospital of the Ministry of Interior Affairs from 1 January 2015 to 15 March 2020 and at the Rheumatology Clinic in the National Institute of Geriatric, Rheumatology and Rehabilitation from 1 September 2021 to 1 March 2024. Medical history, clinical data, demographic data, laboratory data, imaging data, Hscore, and treatment data were collected. Results: All the patients with MAS and an Hscore above 150 recovered. Discussion: MAS/HLH requires rapid diagnosis as well as treatment with methylprednisolone pulses, cyclosporine A, and etoposide. When comparing patients who developed MAS/HLH with those who did not, possible risk factors were identified: the presence of pregnancy (two cases) and an aggressive course of AOSD. The Hscore is a useful tool for identifying patients with MAS/HLH. Full article

Small GTP-binding proteins of the Rab family regulate intracellular vesicle trafficking across many aspects of the transport system. Among these, Rab9 is recognized for its role in controlling the transport system not only around the trans-Golgi network but also around the late endosome. However, the specific functions across different cell types and tissues remain unclear. Here, for the first time, we report that Rab9 negatively regulates morphological changes in the FBD-102b cell line, an oligodendroglial precursor cell line undergoing morphological differentiation. The knockdown of Rab9 led to an increase in cell shape alterations characterized by widespread membrane extensions. These changes were accompanied by increased expression levels of oligodendroglial cell differentiation and myelination marker proteins. Notably, the knockdown of Rab9 was capable of recovering defective cell morphological changes induced by tunicamycin, an inducer of endoplasmic reticulum (ER) stress, which is one of the major causes of oligodendroglial cell diseases such as Pelizaeus–Merzbacher disease (PMD, currently known as hypomyelinating leukodystrophy type 1 [HLD1]). In addition, Rab9 knockdown recovered levels of ER stress marker proteins and differentiation markers. Similar results were obtained in the cases of dithiothreitol (DTT), another chemical ER stress inducer, as well as HLD1-associated proteolipid protein 1 (PLP1) mutant protein. These results indicate a unique role for Rab9 in oligodendroglial cell morphological changes, suggesting its potential as a therapeutic target for mitigating diseases such as HLD1 at the molecular and cellular levels. Full article

Transmembrane protein 106B (TMEM106B), which is a type II transmembrane protein, is believed to be involved in intracellular dynamics and morphogenesis in the lysosome. TMEM106B is known to be a risk factor for frontotemporal lobar degeneration and has been recently identified as the receptor needed for the entry of SARS-CoV-2, independently of angiotensin-converting enzyme 2 (ACE2). A missense mutation, p.Asp252Asn, of TMEM106B is associated with hypomyelinating leukodystrophy 16 (HLD16), which is an oligodendroglial cell-related white matter disorder causing thin myelin sheaths or myelin deficiency in the central nervous system (CNS). However, it remains to be elucidated how the mutated TMEM106B affects oligodendroglial cells. Here, we show that the TMEM106B mutant protein fails to exhibit lysosome distribution in the FBD-102b cell line, an oligodendroglial precursor cell line undergoing differentiation. In contrast, wild-type TMEM106B was indeed localized in the lysosome. Cells harboring wild-type TMEM106B differentiated into ones with widespread membranes, whereas cells harboring mutated TMEM106B failed to differentiate. It is of note that the output of signaling through the lysosome-resident mechanistic target of rapamycin (mTOR) was greatly decreased in cells harboring mutated TMEM106B. Furthermore, treatment with hesperetin, a citrus flavonoid known as an activator of mTOR signaling, restored the molecular and cellular phenotypes induced by the TMEM106B mutant protein. These findings suggest the potential pathological mechanisms underlying HLD16 and their amelioration. Full article

Cell-based interception and precision medicine is a novel approach aimed at improving healthcare through the early detection and treatment of diseased cells. Here, we describe our recent progress towards developing cell-based interception and precision medicine to detect, understand, and advance the development of novel therapeutic approaches through a single-cell omics and drug screening platform, as part of a multi-laboratory collaborative effort, for a group of neurodegenerative disorders named leukodystrophies. Our strategy aims at the identification of diseased cells as early as possible to intercept progression of the disease prior to severe clinical impairment and irreversible tissue damage. Full article

SARS-CoV-2 infections, commonly referred to as COVID-19, remain a critical risk to both human life and global economies. Particularly, COVID-19 patients with weak immunity may suffer from different complications due to the bacterial co-infections/super-infections/secondary infections. Therefore, different variants of alternative antibacterial therapeutic agents are required to inhibit those infection-causing drug-resistant pathogenic bacteria. This study attempted to explore these bacterial pathogens and their inhibitors by using integrated statistical and bioinformatics approaches. By analyzing bacterial 16S rRNA sequence profiles, at first, we detected five bacterial genera and taxa (Bacteroides, Parabacteroides, Prevotella Clostridium, Atopobium, and Peptostreptococcus) based on differentially abundant bacteria between SARS-CoV-2 infection and control samples that are significantly enriched in 23 metabolic pathways. A total of 183 bacterial genes were found in the enriched pathways. Then, the top-ranked 10 bacterial genes (accB, ftsB, glyQ, hldD, lpxC, lptD, mlaA, ppsA, ppc, and tamB) were selected as the pathogenic bacterial key genes (bKGs) by their protein–protein interaction (PPI) network analysis. Then, we detected bKG-guided top-ranked eight drug molecules (Bemcentinib, Ledipasvir, Velpatasvir, Tirilazad, Acetyldigitoxin, Entreatinib, Digitoxin, and Elbasvir) by molecular docking. Finally, the binding stability of the top-ranked three drug molecules (Bemcentinib, Ledipasvir, and Velpatasvir) against three receptors (hldD, mlaA, and lptD) was investigated by computing their binding free energies with molecular dynamic (MD) simulation-based MM-PBSA techniques, respectively, and was found to be stable. Therefore, the findings of this study could be useful resources for developing a proper treatment plan against bacterial co-/super-/secondary-infection in SARS-CoV-2 infections. Full article