Search Results (408)

Advances in additive manufacturing have accelerated the development of 3D-printed dental resin composites. These materials contain a higher proportion of organic matrix and less filler than light-cured representatives, which may affect their behavior in the oral environment. This study aimed to evaluate the biological and chemical properties of 3D-printed dental resin composites before and after artificial aging, and to compare them with the light-cured representative. Specimens from a light-cured composite (Omnichroma—OMCR) and two 3D-printed composites (GT Temp PRINT—GTPR; SprintRay CROWN—SPRY) were subjected to aging treatments: unaged (T0) or thermocycled for 5000 (T1) and 10,000 cycles (T2). Biological evaluation was performed using MTT assay and Live/Dead cell fluorescence microscopy using human gingival fibroblasts, whereas Raman spectroscopy analysed materials’ structural changes. Materials exhibited good biocompatibility (>70% cell viability), with OMCR displaying greater variability. OMCR was more susceptible to chemical degradation under thermal stresses than both 3D-printed materials. Tested 3D-printed composites can provide comparable or even superior biological and chemical properties compared to light-cured representative, likely due to optimized resin formulations and post-curing protocols that improve polymer network organization and reduce residual monomer release. These findings support the potential of tested 3D-printed composites for manufacturing dental restorations. Full article

Background/Objectives: Approximately 20% of familial ALS (fALS) cases are linked to mutations in Cu/Zn superoxide dismutase (SOD1). Through a gain function, SOD1 misfolding exerts a toxic effect on motor neurons, leading to their degradation and ALS symptomology in both fALS cases and sporadic ALS (sALS) cases with no known genetic cause. To further our understanding of SOD1-ALS etiology, identifying motor neuron-specific SOD1 post-translational modifications (PTMs) and studying their structural influence is necessary. To this end, we have conducted a study on the influence of the deamidation of Asn53, a PTM proximal to key stabilizing motifs in SOD1, which has scarcely been addressed in the literature to date. Methods: Deamidation to N53 was identified by tandem mass spectrometry of SOD1 immunoprecipitated from motor neuron (MN) cultures derived from wild-type (WT) human induced pluripotent stem cells (iPSCs). WT SOD1 and N53D SOD1, a mutant mimicking the deamidation, were expressed in Escherichia coli and purified for in vitro analyses. Differences between species were measured by experiments probing metal cofactors, relative monomer populations, and aggregation propensity. Furthermore, molecular dynamics experiments were conducted to model and determine the influence of the PTM on SOD1 structure. Results: In contrast to WT, N53D SOD1 showed non-native incorporation of metal cofactors, coordinating more Zn²⁺ cofactors than total Zn-binding sites, and more readily adopted monomeric forms, unfolded, and aggregated with heating, possibly while releasing coordinated metals. Conclusions: Deamidation to N53 in SOD1 encourages the adoption of non-native conformers, and its detection in WT MN cultures suggests relevance to sALS pathophysiology. Full article

Aggregates of misfolded α-synuclein proteins are key markers of Parkinson’s disease. The protein α-synuclein (aSyn) is an intrinsically disordered protein (IDP) and therefore lacks a single stable 3D structure, instead sampling multiple conformations in solution. It is primarily located in presynaptic terminals and is thought to help regulate synaptic vesicle trafficking and neurotransmitter release. ASyn proteins have three domains: an N-terminal domain, a hydrophobic non-amyloid-β component (NAC) core implicated in aggregation, and a proline-rich C-terminal domain. Asyn proteins with truncated C-terminal domains are known to be prone to aggregation and suggest that understanding domain–domain interactions in aSyn monomers could help elucidate the role of the flanking domains in modulating protein structure. To this end, we used Gaussian accelerated molecular dynamics (GAMD) to simulate wild-type (WT), N-terminal truncated (ΔN), C-terminal truncated (ΔC), and isolated NAC domain (isoNAC) aSyn protein variants. Using clustering and contact analysis, we found that removal of the N-terminal domain led to increased contacts between NAC and C-terminal domains and the formation of inter-domain β-sheets. Removal of either flanking domain also resulted in increased compactness of every domain. We also found that the contacts between flanking domains in the WT protein result in an electrostatic potential (ESP) that may lead to favorable interactions with anionic lipid membranes. Removal of the C-terminal domain disrupts the ESP in a way that could result in over-stabilized protein–membrane interactions. These results suggest that cooperation between the flanking domains may modulate the protein’s structure in a way that helps maintain elongation and creates an ESP that may aid favorable interactions with the membrane. Full article

The long-term success of composite restorations largely depends on the performance of dental adhesives at the adhesive–tooth interface. Despite ongoing improvements, secondary caries remains the leading cause of restoration failure, primarily due to the adhesive layer’s susceptibility to hydrolytic degradation, bacterial invasion, and limited biological functionality. This review provides a comprehensive overview of recent advances in bioactive dental adhesives for preventing recurrent caries, focusing on their mechanisms of action, material performance, therapeutic functions, and clinical potential. Bioactive adhesives combine durable bonding with biofunctional benefits, including remineralization, antimicrobial activity, enzymatic inhibition, and support for tissue regeneration. By integrating these properties, they enhance both the durability of the adhesive interface and oral health. Recent strategies include the incorporation of ion-releasing fillers such as calcium phosphate and bioactive glass, antimicrobial monomers such as MDPB and quaternary ammonium methacrylates, enzymatic inhibitors, and hydrolytically stable resin matrices. Together, these components strengthen the adhesive interface and provide biologically active effects to prevent recurrent caries. Although in vitro findings are promising, challenges remain, including limited long-term clinical data, the absence of standardized evaluation protocols, and barriers to clinical translation. Addressing these gaps is essential to ensure predictable clinical outcomes. Bioactive dental adhesives represent a paradigm shift in restorative dentistry, evolving from passive bonding agents to multifunctional therapeutic materials. By combining structural durability with biological protection, they hold significant potential to prevent recurrent caries and improve the long-term success of composite restorations. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disease. The pathogenesis of AD remains incompletely understood. It is characterized by a variety of neuropathological changes, including neuroinflammation, neuronal loss and synaptic damage. Multiple pathological changes make achieving good therapeutic effects with a single drug treatment difficult, and using multiple drugs for combination therapy is currently the most effective method. Currently, the mainstay drugs used for AD treatment are hydrophobic drugs, such as curcumin, donepezil, and resveratrol. Because hydrophobic drugs cannot dissolve in bodily fluids and often aggregate or precipitate, their efficacy is greatly reduced. Therefore, there is an urgent need for a drug carrier that can effectively load and continuously release drugs. However, currently, there are few drug carriers that can achieve efficient co-loading of multiple hydrophobic drugs. Therefore, three of two-dimensional imine covalent organic frameworks (COFs) with different monomers were synthesized through rational design and screening. These three synthesized COFs are simultaneously loaded with curcumin (CUR) and benzofurazan (BZ) to achieve combined therapy. The results indicate that among this series of synthesized COFs, the COF synthesized from 4,4′,4″-(1,3,5-Triazine-2,4,6-triyl) trianiline and benzene-1,3,5-tricarboxaldehyde (COF-TB) exhibits optimal hydrophobic drug-loading capacity, enabling effective co-loading of CUR and BZ (BC@COF-TB). After treatment with BC@COF-TB, the cognitive function of 5×FAD mice was significantly improved. The COF platform provides a new way to deliver hydrophobic drugs for AD treatment. Full article

Cyanoacrylate-based adhesives are commonly used for wound closure due to their short synthesis time, aesthetic outcomes, and minimal discomfort. However, reported adverse effects include the release of cytotoxic metabolites, inflammation, and foreign body reactions. This study evaluated and compared the effectiveness of three cyanoacrylate-based adhesives for skin incision closure in Rattus norvegicus. The subjects were divided into three groups based on the type of monomer: G1 (n-2-ethyl-cyanoacrylate), G2 (n-2-butyl-cyanoacrylate), and G3 (n-2-octyl-cyanoacrylate). Each animal received two 2 cm paramedian incisions, which were closed using either a topical over dermal (OD) or a topical transdermal (TD) application, resulting in two subgroups per group. Wounds were evaluated on postoperative days 3, 7, 14, and 21 to compare the different monomers and application techniques. Assessment of the inflammatory infiltrate revealed differences in polynuclear cells between the TD and OD on days 3 and 7, while TD demonstrated improved results in mononuclear cells at all time points. Sustained inflammatory processes and foreign body reactions were observed. Quantification of tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) indicated that TD maintained stability throughout the assessment periods, though it exhibited higher values than OD from days 7 to 21. These higher values were associated with a foreign body reaction and increased oxidative stress. Regarding tissue formation, OD produced more aligned wound edges, supporting the production of types I and III collagen and improving scar resolution compared to TD. Our findings indicate that the patch application technique has a greater impact on healing than the size of the cyanoacrylate monomer. Full article

The efficacy of coated fertilizers in enhancing nutrient use efficiency and reducing environmental impacts depends on their coating properties. This study developed three biodegradable, waterborne polyacrylate latexes (A, B, and C) as eco-friendly coatings for controlled-release fertilizers (CRFs) using the Wurster fluidized bed process. The latexes were synthesized with varying hard-to-soft monomer ratios and cross-linked with 2 wt% aziridine to investigate how monomer composition affects coating properties and nutrient release. The results showed that coating B, which had an intermediate hard-to-soft monomer ratio, demonstrated optimal properties. It exhibited the lowest swelling capacity (2.54% at 60 °C), a suitable glass transition temperature (15.34 °C), and the slowest nutrient release, with cumulative nitrogen release remaining below 60% after 11 days in water at 40 °C. In field trials, the fertilizer coated with material B produced the highest rice yield among tested domestic CRF brands. It also achieved a significant 19.1% yield increase compared to a single basal application of conventional compound fertilizer. These findings confirm that this modified latex provides an effective and environmentally friendly solvent-free coating strategy for high-performance CRFs. Full article

Previous studies suggest that multiple inflammatory chemokines (e.g., CCL5, CXCL12) bind to the allosteric site of integrins (site 2) and induce allosteric integrin activation and inflammatory signals. PF4 is abundantly present in platelet granules, but PF4 levels are very low in plasma. PF4 is released from damaged platelets and is markedly increased in plasma (>1000×) in pathological conditions. PF4 (tetramer) is an inhibitory chemokine, and the specifics of PF4 signaling are unclear. Docking simulation predicted that PF4 monomer binds to site 2, but PF4 by itself did not induce allosteric integrin activation. Anti-PF4 mAbs KKO and RTO generate complexes with PF4 tetramer and monomer, respectively. We discovered that the PF4/RTO complex induced potent integrin activation, but the PF4/KKO complex did not. We hypothesize that inactive PF4 tetramer is converted by RTO to active monomer. A PF4 mutant (4E), in which four basic amino acid residues in the predicted site 2 binding site were mutated to Glu, did not induce integrin activation and acted as a dominant-negative antagonist, suggesting that the RTO/PF4 complex is required to bind to site 2 for integrin activation. Notably, RTO-like autoantibody was detected in plasma of healthy people. We propose that autoanti-PF4 in healthy controls may not be a problem since plasma PF4 levels are very low. When plasma PF4 tetramer is increased, active PF4 monomer is generated by autoanti-PF4 and plays a role in disease pathogenesis. Notably, anti-inflammatory cytokine neuregulin-1 and anti-inflammatory ivermectin bind to site 2 and suppress integrin activation induced by RTO/PF4 complex, suggesting that neuregulin-1 and ivermectin are potentially useful to suppress PF4/anti-PF4-mediated inflammatory signals. Full article

This study evaluated post-processing protocols for 3D-printed implant surgical guides, aiming to determine the ideal timing after printing and post-curing durations that do not compromise residual monomer release and leachable components or mechanical properties. Specimens made of a surgical guide resin were 3D-printed (Formlabs Form 2) into bars (14 × 1 × 1 mm; n = 10) and square-shaped samples (10 × 10 × 1 mm; n = 1). They were grouped based on the time elapsed after printing (immediate, 24 h, and 72 h) and underwent washing in 99% isopropyl alcohol. Post-curing was performed for 5, 10, 20, or 30 min using a UV-light curing unit (NextDent LC-3DPrint Box). Residual monomer and components levels were assessed through solvent dissolution tests (n = 5), while mechanical properties were evaluated via flexural strength (n = 10) and hardness (n = 10). Statistical analysis with one-way ANOVA and Tukey’s post hoc test showed no significant differences in flexural strength across curing times or storage periods (p > 0.05), with values ranging from 42.93 MPa to 59.43 MPa. Monomers and leachable components were significantly higher immediately after printing (0.84 ± 0.36 mm³) compared to other groups (p < 0.05). For Vickers hardness, a 10 min curing protocol produced values comparable to longer durations (20.26 HV at 20 min/24 h), while the lowest hardness was 14.59 HV in the 5 min groups (p < 0.001). These findings suggest that delaying post-processing up to 72 h and reducing curing time to 10 min do not compromise mechanical properties, released monomers, and leachable components. Full article

Growing concerns over the toxicity and sustainability of dental materials have driven the search for alternatives to bisphenol A-glycidyl methacrylate (Bis-GMA), a widely used dental resin monomer associated with health risks. This study highlights the potential of less health-hazardous dental formulations by incorporating high-value materials derived from the glycolysis of poly(ethylene terephthalate) (PET). Dimethacrylated oligoesters (PET-GLY-DM), synthesized through the methacrylation of PET glycolysis products, were blended with Bis-GMA and triethylene glycol dimethacrylate (TEGDMA), toward the gradual replacement of Bis-GMA content. The innovative PET-GLY-DM-based resins exhibited a higher degree of conversion compared to traditional Bis-GMA/TEGDMA formulations, as measured by FTIR spectroscopy, accompanied by an increase in polymerization shrinkage, evaluated via a linear variable displacement transducer system. While the incorporation of PET-GLY-DM slightly reduced flexural strength and elastic modulus, it significantly decreased water sorption, resulting in a smaller reduction in mechanical properties after water immersion for 7 days at 37 °C and improved long-term performance. Furthermore, PET-GLY-DM resins exhibited low bisphenol-A (BPA) release measured with HPLC. It was thus confirmed that PET-GLY-DM resins derived from the glycolysis of PET wastes represent a promising alternative to conventional light-cured dental resins, offering reduced BPA release and improved water resistance. Full article

A novel quinoline-containing benzoxazine resin, 8HQ-fa, has been successfully synthesized at room temperature using sustainable raw materials, such as 8-hydroxyquinoline and furfurylamine as the phenol and amine source, respectively. The chemical structure of the hereinafter referred to as quinolinoxazine is fully characterized by Fourier transform infrared spectroscopy (FT-IR), ¹H and ¹³C nuclear magnetic resonance spectroscopy (NMR), as well as by 2D ¹H–¹H nuclear Overhauser effect spectroscopy (NOESY) and ¹H–¹³C heteronuclear multiple quantum correlation (HMQC) NMR. Thermal properties and polymerization behavior of the monomer are studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The resulting polymer is also characterized in terms of its thermal and fire-related properties by DSC, TGA, and microscale combustion calorimetry (MCC). The resulting thermoset, poly(8HQ-fa), presents good thermal stability as evidenced by its T_g (201 °C), T_d5 and T_d10 (307 and 351 °C, respectively), and char yield (42%), and low flammability as determined by the LOI, heat release capacity, and total heat released values (34.3, 143 J/gK, and 10.8 kJ/g, respectively), making it a self-extinguishing thermoset. The combination of properties and advantages in the synthesis of 8HQ-fa, accompanied by a low polymerization temperature, suggests its great potential in the field of high-performance polymers. Full article

Condensed tannins from grape seed residues show high antioxidant activity but low oral bioavailability because of their high degree of polymerization and covalent interactions with proteins. This study aimed to improve their bioaccessibility through depolymerization and encapsulation. Depolymerization was carried out using microwave-assisted SN1 reactions with gallic acid as a nucleophile under food-grade conditions, mainly producing epicatechin monomers with 99.8% polymer degradation efficiency. Importantly, the inhibition of ABTS●+ and DPPH● radicals remained unaffected (p > 0.05), indicating that depolymerization preserved the antioxidants’ redox function, maintaining about 90% of their inhibition activity. The products were encapsulated in phosphatidylcholine liposomes, which had nanometric sizes and high encapsulation efficiency (83.11%), and remained stable for up to 60 days. In vitro release of nanoliposomal epicatechin in a D1 simulant was less than 10% after 48 h, fitting a Weibull model (β = 0.07), suggesting sub-diffusive transport and demonstrating high bioactive retention capacity in aqueous systems. During in vitro digestion, bioaccessibility of gallic acid and epicatechin reached 95.61 ± 0.58% and 98.56 ± 0.81%, respectively, with a 2333% increase in the bioaccessible mass of flavan-3-ols in native liposomal condensed tannins, which otherwise showed no detectable bioaccessibility. These findings highlight the potential of polyphenols from agro-industrial waste with enhanced bioaccessibility for applications in nutraceuticals and functional foods. Full article

Background/Objectives: Biodegradable and pH-responsive nanocarriers using zwitterionic moieties represent a promising avenue for targeted delivery of chemotherapeutics. The present study addresses this by developing zwitterionic nanoparticles based on polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers grafted with SBMA, designed to combine acid-triggered drug release with stealth-like biocompatibility. Methods: A series of polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers with varying compositions (95/5, 90/10, and 75/25 w/w) were synthesized via ring-opening polymerization, followed by controlled radical grafting of the zwitterionic monomer [2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which was then successfully grafted upon their backbone. The resulting zwittenionic copolymers were thoroughly characterized for their structural and physicochemical properties, displaying tunable molecular weights of 3200–4900 g/mol, enhanced hydrophilicity and controlled degradation, with mass loss ranging from 8% to 83% over 30 days, depending on PEAd content and pH. Paclitaxel-loaded nanoparticles of spherical shape with sizes ranging from 220 to 565 nm were then fabricated. Drug release was pH-dependent with significantly higher release at pH 5.0 (up to ~79% for PLAPEAd7525-SBMA) compared to pH 7.4 (~18–35%). Hemolysis assays demonstrated excellent hemocompatibility, and cytotoxicity studies showed strong anticancer activity (>80% cell death in MDA-MB-231) with lower toxicity toward iMEFs, especially for PEAd-rich formulations. Conclusions: Our findings underline the potential of SBMA-functionalized PLA/PEAd nanoparticles as effective nano-carriers for tumor-targeted chemotherapy. Full article

Polyvinyl chloride (PVC) is the third most widely produced plastic on an industrial scale, due to its diverse applications and physicochemical properties. Its production through suspension polymerization presents significant safety challenges due to the handling of hazardous substances. To assess the impact of energy integration on process risks, the inherent safety analysis was implemented to determine the characteristic hazards of PVC suspension production. The methodology’s indicators were quantified by reviewing databases, literature, and safety data sheets, considering process steps such as vinyl chloride monomer recovery, PVC purification, and drying. The results revealed that the PVC production process under energy integration conditions is intrinsically unsafe, with a total inherent safety index (ISI) of 34. The chemical component would contribute 19 points, with VCM being the main chemical risk given its flammable and carcinogenic nature, contributing a value of 15, along with the heat released by the reactions. Process safety would contribute 15 points, associated with hazardous equipment such as furnaces, burners, and dryers, as well as risks related to inventories and similar plant accidents. To improve process safety, it is recommended to reduce VCM inventories, optimize operating conditions, and implement advanced control systems for possible accidental releases. Full article

This study investigates the influence of cellulose nanofibrils (CNFs) on the polymerization kinetics of methyl methacrylate (MMA) during in situ suspension polymerization at 70 °C (343.15 K). Four CNF concentrations were evaluated and compared to a reference system without CNFs. Polymerizations were carried out in a thermostatted flask immersed in an ethylene glycol bath and covered to ensure thermal stability. The temperature profiles of both the reaction medium and the surrounding bath were continuously recorded, allowing for the calculation of heat flow, polymerization rate (R_p), and monomer conversion. The incorporation of CNFs led to a significant increase in R_p and faster MMA conversion. This effect was attributed to the presence of nanocellulose within the polymerizing medium, which restricted diffusion and contributed to the onset of the phenomenon of autoacceleration. Additionally, CNFs promoted a higher total heat release, underscoring the need for thermal control during scale-up. The resulting material qualifies as a biocomposite, as biobased nanofibrils became integrated into the polymer matrix. These findings demonstrate that CNFs act as effective kinetic promoters in MMA polymerizations and may serve as functional additives to enhance both reaction performance and sustainability. However, safety considerations remain critical when transferring this approach to industrial processes. Full article