Characteristics and clinical significance of tertiary lymphoid structures in OSCC.

OBJECTIVES: This study aimed to investigate the characteristics of tertiary lymphoid structures (TLSs) in oral squamous cell carcinoma (OSCC) and their association with clinical and pathological features. MATERIALS AND METHODS: 12 TLS-related chemokines in TCGA database were analyzed to investigate the TLSs in OSCC. The density, maturity, and location of TLSs in a large cohort of 189 OSCC patients (114 of which had clinical and prognostic information) were assessed. And the significance between TLSs and clinicopathologic characteristics was analyzed. RESULTS: Bioinformatics and analysis showed that TLSs were associated with better clinical outcomes in OSCC. Histological staining and analysis showed that the overall survival rate of the high-density group (71/112, 63.4%) was significantly higher (p < 0.0001) than that of the low-density group (41/112, 36.6%), and the high-density group had fewer lymph node metastases (50.0%/68.3%, p = 0.021). And TLSs were divided into 4 types according to the maturity and location. Different types of TLSs are associated with prognosis (OS, p < 0.0001), clinical features (T stage, p = 0.028; degree of differentiation, p = 0.043), and precancerous lesion types (OSF, p = 0.049) of OSCC patients. CONCLUSION: TLSs were closely associated with better OSCC prognosis, and a more systematic classification may better guide the formulation of further treatment options.

Fluorescence detection of valence speciation of Cr(III) based on the catechol oxidase mimic enzyme activity of CuSeNP nanozymes.

Copper selenide nanoparticles (CuSeNP) were synthesized using histidine, ethylenediamine, and sodium selenate as precursors by one-step microwave digestion methods. The as-prepared CuSeNPs exhibit excellent catechol oxidase mimic enzyme and catalase (CAT)-like activities. Dopamine (DA) can be oxidized to aminochrome with H2O2 by CuSeNPs, and the intermediate product aminochrome can further react with α-naphthol to yield a highly fluorescent derivative. It was confirmed that Cr(III) could adsorb on the surface of CuSeNPs and inhibit the production of semiquinone radicals in the reaction system, and the catalytic activity of CuSeNPs was inhibited. The detection mechanisms, kinetics, and catalytic properties of CuSeNPs were systematically investigated. As a result, a novel fluorescence method for the assay of Cr(III) was established. The feasibility of CuSeNP nanozyme in detecting speciation Cr(III) in food samples was explored with satisfactory results. It showed the obvious potential for developing effective and dependable fluorescent detection method for protecting food safety.

Fluorescence detection of dopamine based on the peroxidase-like activity of Fe3O4-MWCNTs@Hemin.

A novel Fe3O4-MWCNTs@Hemin nanocomposite was synthesized using hemin and Fe3O4 with multi-walled carbon nanotubes (MWCNTs) by one-step hydrothermal methods. The as-prepared Fe3O4-MWCNTs@Hemin nanocomposites exhibited excellent peroxidase-like activities in the activation of H2O2. The mechanisms, kinetics, and catalytic performances of Fe3O4-MWCNTs@Hemin were systematically studied. Fe3O4-MWCNTs@Hemin can oxidize dopamine (DA) to dopaquinone in the presence of H2O2, and the intermediate products dopaquinone can further react with ß-naphthol to generate a highly fluorescent derivative at 415 nm excitation wavelength. Therefore, an innovative fluorescence platform for the detection of DA was developed. The fluorescence intensity increased linearly with DA concentration in the range 0.33 to 107 µM, with a low detection limit of 0.14 µM. Due to the excellent activity, substrate universality, fast response, high selectivity, and sensitivity of Fe3O4-MWCNTs@Hemin, the proposed fluorescence method was used to analyze complex biological blood samples with a satisfactory result. It demonstrated the significant potential for developing effective and dependable fluorescent analytical platforms for preserving human health.

Simulated Enzyme Activity and Efficient Antibacterial Activity of Copper-Doped Single-Atom Nanozymes.

Nanozymes with good biocompatibility are novel antibacterial agents because they mimic the structure and properties of enzymes and destroy bacterial structures by generating reactive oxygen species in large quantities. Herein, we synthesized a Cu single-atom nanozyme (Cu-N-C) with intrinsic peroxidase- and oxidase-like activities. Cu-N-C can generate ·OH and O2·- during oxidase-catalyzed reactions, which have good antibacterial effects. Meanwhile, the antimicrobial performance can be further enhanced by light emitting diode light incubation due to photocatalysis. Lethal disruption of the membrane structure was confirmed by biofilm staining and scanning electron microscopy analysis. Notably, the antibacterial effect of Cu-N-C (MIC = 16 µg/mL) was significantly better than that of vancomycin (MIC = 1500 µg/mL), a commonly used drug for methicillin-resistant Staphylococcus aureus, and Cu-N-C outperformed the positive control cephalexin and gentamicin in terms of resistance development (27.3% less production of drug-resistant bacteria). Good biocompatibility was also verified using the MTT method, hemolysis analysis, and routine blood measurements in mice. The results of this work suggest that Cu-N-C has great potential for clinical applications as an efficient metal antimicrobial agent.

Survival Rates of Splinted and Nonsplinted Prostheses Supported by Short Dental Implants (≤8.5 mm): A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate and compare the implant survival rates, marginal bone loss, and mechanical complications of prostheses supported by splinted and nonsplinted short implants (≤8.5 mm). MATERIAL AND METHODS: Electronic database (MEDLINE, CENTRAL, Web of Science, and EMBASE) and manual searches up to May 2021 were conducted to identify studies comparing splinted and nonsplinted short implants (≤8.5 mm). The primary outcome was implant survival rate. Secondary outcomes were marginal bone loss and mechanical complications. The quality of included studies and risk-of-bias were assessed according to the Newcastle-Ottawa Scale. A random-effects model was used to analyze the data. RESULTS: Twelve studies fulfilled the inclusion criteria and featured 1506 short implants (596 nonsplinted and 910 splinted) with a follow-up time ranging from 1 to 16 years. Quantitative analysis found no statistically significant differences between splinted and nonsplinted short implants (≤8.5 mm) for survival rate (RR = 0.98; 95% CI 0.96, 1.01; p = 0.26)) and marginal bone loss (SMD = -0.08; 95% CI - 0.23, 0.07; p = 0.28). Veneer chipping, abutment screw breakage, screw loosening, and loss of retention were reported in the selected studies as common complications. However, no statistically significant difference was found between splinted and nonsplinted short implants (RR = 0.56; 95% CI 0.20, 1.54; p = 0.26). CONCLUSIONS: Within the limitations of the present meta-analysis, it might be concluded that splinted short implants (≤8.5 mm) do not present superior performance in survival rate, marginal bone maintenance and prevention of mechanical complications compared with single-unit prostheses.

A multifunctional nanozyme-based enhanced system for tert-butyl hydroquinone assay by surface-enhanced Raman scattering.

An Au-based nanozyme composite (AuNPs/Cu,I) was constructed by using Cu,I-doped carbon dots (Cu,I-CDs) as the reducing agent as well as the nanozyme. Notably, AuNPs/Cu,I nanozyme not only possessed the intrinsic activity of mimicking enzymes of superoxide dismutase, peroxidase, and catalase at different conditions but was also employed as surface-enhanced Raman spectroscopy (SERS) enhancer. The combination of Cu,I-CDs and AuNPs promoted the electron transferability, leading to increased peroxidase-like activity and superoxide-like activity. Compared to the individual Cu,I-CDs and AuNPs nanozyme, the AuNPs/Cu,I composite demonstrated promising peroxidase-like activity by transferring electrons instead of generating OH. Interestingly, the multienzyme-like activity of AuNPs/Cu,I nanozyme could be finely tuned by changing the composition of Cu0/Cu+ and Au. The tert-butyl hydroquinone (TBHQ) as the substrate could be catalyzed with AuNPs/Cu,I nanozyme to produce red substances, resulting in a significant Raman enhancement effect at the same time, showing good linear range from 0.11 to 10 mg L-1. Overall, the current investigation provides a flexible and controllable way to design multifunctional nanozymes along with the Raman enhancement strategy based on the catalysis of nanozyme.

Role of the arecoline/YAP1/BMP4 pathway in promoting endothelial-mesenchymal transition in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a potentially malignant lesion characterized by epithelial-mesenchymal transition (EMT). Bone morphogenetic protein 4 (BMP4) promotes EMT in fibrotic diseases, but the underlying mechanisms and its potential role in OSF are unclear. This study investigates whether BMP4 plays a role in the pathogenesis of OSF and explores the underlying mechanisms. METHODS: The expression of BMP4 and the EMT proteins E-cadherin and vimentin was investigated in OSF specimens by immunohistochemical staining. Pearson's correlation analysis was conducted to explore the correlation between BMP4 and the EMT markers. Western blotting and RT-PCR assays were used to analyze the effect of arecoline (a known EMT-promoting pathogenic factor in OSF) on BMP4 and identify the transcription factor involved. Confocal microscopy was used to observe the intracellular sublocalization of the identified transcription factor, Yes-associated protein 1 (YAP1). Finally, siRNA silencing of BMP4 was used to determine its effect on YAP1 activation and arecoline-induced EMT. RESULTS: BMP4 is overexpressed in OSF and plays a role in EMT, as its expression correlates with the expression of E-cadherin and vimentin. Arecoline induces BMP4 expression via the activation of YAP1 (through its nuclear translocation). Furthermore, the YAP1/BMP4 mechanism is the main molecular event in arecoline-induced EMT, as knockdown of BMP4 expression affects expression of the EMT markers and inhibits extracellular matrix accumulation. CONCLUSIONS: Arecoline induces EMT in OSF via the YAP1/BMP4 pathway. Thus, BMP4 could be considered as a potential therapeutic target for the treatment of OSF.

Efficacy of locally-delivered statins adjunct to non-surgical periodontal therapy for chronic periodontitis: a Bayesian network analysis.

BACKGROUND: Studies indicate locally-delivered statins offer additional benefits to scaling and root planning (SRP), however, it is still hard to say which type of statins is better. This network meta-analysis aimed to assess the effect of locally-delivered statins and rank the most efficacious statin for treating chronic periodontitis (CP) in combination with SRP. METHODS: We screened four literature databases (Pubmed, Embase, Cochrane Library, and Web of Science) for randomized controlled clinical trials (RCTs) published up to June 2018 that compared different statins in the treatment of chronic periodontitis. The outcomes analyzed were changes in intrabony defect depth (IBD), pocket depth (PD), and clinical attachment level (CAL). We carried out Bayesian network meta-analysis of CP without systemic diseases. Traditional and Bayesian network meta-analyses were conducted using random-effects models. RESULTS: Greater filling of IBD, reduction in PD, and gain in CAL were observed for SRP treated in combination with statins when compared to SRP alone for treating CP without systemic diseases. Specifically, SRP+ Atorvastatin (ATV) (mean difference [MD]: 1.5 mm, 1.4 mm, 1.8 mm, respectively), SRP + Rosuvastatin (RSV) (MD: 1.8 mm, 2.0 mm, 2.1 mm, respectively), and SRP + Simvastatin (SMV) (MD: 1.1 mm, 2.2 mm, 2.1 mm, respectively) were identified. However, no difference was found among the statins tested. In CP patients with type 2 diabetic (T2DM) or in smokers, additional benefits were observed from locally delivered statins. CONCLUSION: Local statin use adjunctive to SRP confers additional benefits in treating CP by SRP, even in T2DM and smokers. RSV may be the best one to fill in IBD. However, considering the limitations of this study, clinicians must use cautious when applying the results and further studies are required to explore the efficacy of statins in CP with or without the risk factors (T2DM comorbidity or smoking history).

Effect of non-surgical periodontal therapy on glycemic control of type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice. METHODS: We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias. RESULTS: Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI - 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11). CONCLUSION: The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.

Colorimetric-SERS dual-mode sensing of Pb(II) ions in traditional Chinese medicine samples based on carbon dots-capped gold nanoparticles as nanozyme.

Peroxidase (POD)-mimicking nanozymes have got great progress in the sensing field, but most nanozyme assaying systems are built with a single-signal output mode, which is vulnerable to the effect of different factors. Thus, establishment of a dual-signal output mode is necessary for acquiring dependable and durable performance. This work described an Fe doped noradrenaline-based carbon dots and Prussian blue (Fe,NA-CDs/PB) nanocomposite as a POD-like nanozyme and modified gold nanoparticles (AuNPs) for the colorimetric and surface-enhanced Raman scattering (SERS) dual-mode sensor of Pb(II) in traditional Chinese medicine samples. With 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB) as the substrates, it was found that the addition of Pb(II) inhibited the POD-like activity of Fe,NA-CDs/PB and AuNPs, so it was used for colorimetric and SERS dual-mode assays. The POD-like activity was shown to be a "ping-pong" catalytic mechanism, whereas the addition of Pb(II) produced noncompetitive inhibition with modulatory effects on Fe,NA-CDs/PB. The linear response range for colorimetric and SERS sensor detection of Pb(II) was 0.01-1.00 mg/L with the detection limit of 5 µg/L and 8 µg/L, respectively. This dual-mode detection system shows excellent selectivity. More importantly, the Pb(II) in traditional Chinese medicine samples have successfully assayed with good recovery from 90.4 to 108.9 %.

A colorimetric platform for sensitive sensing of Hg2+ and S2- based on Se-AuNPs with Hg2+-activated peroxidase-like activity.

Herein, the selenium (Se) modified gold nanoparticles (Se-AuNPs) was synthesized using cerium doped carbon dots (Ce-CDs) as a reducing agent and template. As desired, Se-AuNPs displays enhanced peroxidase (POD)-like activity in the presence of Hg2+. The mechanism for the enhanced activity was attributed to the increased affinity between Se-AuNPs-Hg2+ and the substrate, in which Se and Au elements have a strong binding capacity to Hg2+, forming Hg-Se bonds and Au-Hg amalgam to generate more ·OH. This POD-like activity of Se-AuNPs-Hg2+ correlates with the colorimetric reaction by the catalytic reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The oxidation of TMB was completely inhibited by the introduction of the reductive S2-. Based on the above findings, a strategy for the colorimetric detection of Hg2+ and S2- by Se-AuNPs was established with linear ranges of 0.33-66 µg/L and 0.625-75 µg/L, and low detection limits of 0.17 µg/L and 0.12 µg/L (3.3 δ/k), respectively. When the colorimetric probes for detection of Hg2+ and S2- was applied in environmental water samples, the recoveries were in the range of 90.3-108.0 %. This method will provide a new idea for the colorimetric detection strategy of Hg2+ due to the strong interaction between Hg and Se.

Colorimetric detection for raloxifene based on Cu-PTs nanozyme with peroxidase-like activity.

The amorphous Cu-containing phosphomolybdate (Cu-PTs) composite with high peroxidase (POD)-like activity at neutral conditions was explored as biosensors for raloxifene (RAF) detection. The strong attraction between negatively charged Cu-PTs and positively charged substrates 3,3',5,5'-tetramethylbenzidine (TMB), as well as the acceleration of the conversion of active Cu+/Cu2+ by the Cu/W bimetallic redox couples were demonstrated to play significant roles in POD-like activity in physiological environment. When RAF is presence, it can bind to the surface of Cu-PTs and changes the chemical signal on the material surface, leading to the decreased POD-like activity. Based on this, a colorimetric method was established for the sensitive assay of RAF with a lower limit of detection (LOD) of 0.025 mg/L and good recovery from 90.13% to 108.9%. This work paves a new way to design a POD-like colorimetric protocol for tracing RAF in pharmaceutical products and environmental samples.

Ultrasound and defect engineering-enhanced nanozyme with high laccase-like activity for oxidation and detection of phenolic compounds and adrenaline.

Perusing metal-based redox nanozyme offers new opportunity for pollutant removal and biosensor, but ultrasound (US)-driven laccase-like nanozyme remains a significant challenge, especially in combination with defect engineering strategy. Herein, the Cu2Ov@Ce-TCPP was synthesized by doping Ce3+ on the surface of Cu2O nanocube and then coating with the porphyrin sonosensitizer. The Ce-doped porphyrin metal-structure in nanozyme was demonstrated to generate oxygen vacancy defects, which could obviously promote the laccase-like activity of Cu2Ov@Ce-TCPP nanozyme under US. XPS characterization and density functional theory (DFT) theoretical calculation revealed that the ultrasonic stimulation is beneficial to accelerate the electron transfer rate and O2 adsorption to improve catalytic activity, and Cu2Ov@Ce-TCPP nanozyme exhibits low adsorption energy and activation energy due to the presence of oxygen defect site, resulting in high laccase-like activity. The interaction between Ce atom and porphyrin structure also improved the sonocatalytic ability of the nanozyme. Meanwhile, Cu2Ov@Ce-TCPP nanozyme has been used for detecting and degrading a series of phenolic compounds. The detection adrenaline method has a linear range of 3.3-1000 µM and a detection limit as low as 0.96 µM with good reproducibility. The developed US-enhancing and recyclable laccase-like nanozyme system provides a promising strategy for the oxidation and detection of phenolic compounds.

Enhancing diabetic wound healing with a pH-responsive nanozyme hydrogel featuring multi-enzyme-like activities and oxygen self-supply.

Diabetic wound treating remains a challenging due to bacterial infections, oxidative stress, tissue hypoxia, and high glucose levels. Herein, a multi-enzyme-like activities nanocomposite (Mo,Fe/Cu,I-Ag@GOx) was designed and anchored to a multifunctional fluorescence hydrogel. The nanozyme gel, loaded with glucose-oxidase (GOx), exhibits intrinsic GOx, peroxidase (POD)-, oxidase (OXD)-, catalase (CAT)- and superoxide dismutase (SOD)-like activities with pH-switchable glucose-initiated cascade reaction for diabetic wound healing. In the first cascade-reaction, initiated by GOx, the nanozyme gel catalyzes glucose and O2 into gluconic acid and H2O2 to further generate superoxide anion radical (O2·-) and hydroxyl radicals (·OH) to eradicate bacteria. In the second cascade-reaction, as the wound pH changes alkalescent microenvironment, the nanozyme gel simulates SOD to transform O2·- into O2 and H2O2, and then decomposes endogenous and exogenous H2O2 into O2 via CAT-like activity to reduce oxidative stress and alleviate hypoxia. The gel by calcium ion (Ca2+) cross-linked sodium alginate (SA) and chitosan (CS) containing nanozyme was constructed with injectability, adhesion and fluorescence properties, as well as beneficial biocompatible. Importantly, the water/alcohol solubility of the nanozyme gel allows it to be used as a dressing without causing secondary injury to the wound. The multifunctional fluorescence hydrogel exhibits efficiently promote pro-angiogenesis and bacteria-infected wound healing.

Novel insights into causal effects of maternal nonalcoholic fatty liver disease on adverse pregnancy outcomes: evidence from Human Genetics and Mendelian Randomization Study.

BACKGROUND: Observational studies have associated nonalcoholic fatty liver disease (NAFLD) with adverse pregnancy events, but findings show heterogeneity, leaving the causal direction and mediating pathways unclear. We aimed to investigate the causal relation between NAFLD and various pregnancy events, and to elucidate the underlying mediating pathways while determining the proportion of this correlation that is mediated through these pathways. METHODS: A genome-wide association study involving over 6 million participants employing Mendelian randomization (MR) and mediation analysis was performed. The study used genetically predicted NAFLD as exposures and cardiometabolic traits as mediators, with various adverse pregnancy events as outcomes. The main analysis was performed using the inverse variance weighted (IVW) approach, while sensitivity analyses included the weighted median, weighted mode, MR-Egger, and MR-PRESSO methods. Mediation analyses were performed using a two-step MR framework. RESULTS: In this MR cohort study, NAFLD was found to be strongly associated with elevated risks of GDM (P = 0.019 for the discovery dataset, P < 0.001 for the discovery dataset) and HDPs, including any HDP (P < 0.001 for the both datasets), gestational hypertension (P = 0.007 for the discovery dataset, P < 0.001 for the discovery dataset), and pre-eclampsia or eclampsia (P = 0.040 for the discovery dataset, P < 0.001 for the discovery dataset). However, no significant associations were found with hemorrhage in early pregnancy, postpartum hemorrhage, preterm birth, or offspring birthweight for both datasets. Cardiometabolic traits played a significant mediating role in these associations, rather than solely acting as confounding factors. CONCLUSIONS: This study provided evidence supporting a correlation between NAFLD and a higher risk of adverse pregnancy events and introduces some new insights. These findings may inform preventions and interventions for remediating adverse pregnancy outcomes attributable to NAFLD.

Aptamer-functionalized Fe3O4/MWCNTs@Mo-CDs nanozyme for rapid colorimetric detection toward Escherichia coli.

The pathogenic bacteria induced foodborne disease has been detrimental to public health worldwide. Herein, the peroxidase (POD)-like Fe3O4/MWCNTs@Mo-CDs (FMMC) nanozyme was applied for the detection of Escherichia coli (E. coli). The E. coli aptamer was conjugated with the surface of the FMMC, which effectively enhanced the POD-like activity attributing to the higher affinity to the substrate, and then specific capture of E. coli in food matrices, leading to the reduction of POD-like activity. Therefore, a robust and facile colorimetric aptasensor was developed for detecting E. coli with a wide linear range of 101-106 CFU/mL, low LOQ of 101 CFU/mL and LOD of 0.978 CFU/mL. The aptasensor demonstrated the satisfied selectivity for E. coli compared to the other strains. This method possessed the potential application for fast in situ screening of foodborne pathogens in food products.

Cu,Zn,I-Doped Carbon Dots with Boosted Triple Antioxidant Nanozyme Activity for Treatment of DSS-Induced Colitis.

Nanozyme-mediated antioxidative therapy is a promising star for treating a myriad of important diseases through eliminating excessive reactive oxygen species (ROS) such as O2·- and H2O2, a critical mechanism for inflammatory bowel disease (IBD). This work provides a high biocompatibility iodine-copper-zinc covalent doped carbon dots (Cu,Zn,I-CDs) with the catalase (CAT)-, superoxide dismutase (SOD)- and glutathione peroxidase (GPx)-like catalytic activities for treating ulcerative colitis (UC) by scavenging overproduced ROS. We found that I dopant aids in counteracting the positive charge at Cu,Zn dopants brought on by low pH, enabling Cu,Zn,I-CDs to process strong triple antioxidant nanozyme activities rather than Cu,Zn-CDs. Vitro experiments displayed that the Cu,Zn,I-CDs could scavenge the excessive ROS to protect cellular against oxidative stress and reduce the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. In sodium dextran sulfate (DSS)-induced colitis mice models, Cu,Zn,I-CDs with excellent biocompatibility could effectively relieve the inflammation of the colon, containing the reduction of the colon length, the damaged epithelium, the infiltration of inflammatory cells, and upregulation of antioxidant genes. Therefore, the therapy of Cu,Zn,I-CD antioxidant nanozymes is an effective approach and provides a novel strategy for UC treatment.

Silk fibroin microgrooved zirconia surfaces improve connective tissue sealing through mediating glycolysis of fibroblasts.

The use of zirconia has significantly enhanced the aesthetic outcomes of implant restorations. However, peri-implantitis remains a challenge to long-term functionality of implants. Unlike the perpendicularly arranged collagen fibers in periodontal tissue, those in peri-implant tissue lie parallel to the abutment surface and contain fewer fibroblasts, making them more prone to inflammation. Studies have shown that microgroove structures on implant abutments could improve surrounding soft tissue structure. However, creating precise microgrooves on zirconia without compromising its mechanical integrity is technically challenging. In this study, we applied inkjet printing, an additive manufacturing technique, to create stable silk fibroin microgroove (SFMG) coatings of various dimensions on zirconia substrates. SFMG significantly improved the hydrophilicity of zirconia and showed good physical and chemical stability. The SFMG with 90 µm interval and 10 µm depth was optimal in promoting the proliferation, alignment, and extracellular matrix production of human gingival fibroblasts (HGFs). Moreover, the in vitro results revealed that SFMG stimulated key glycolytic enzyme gene expression in HGFs via the PI3K-AKT-mTOR pathway. Additionally, the in vivo results of histological staining of peri-abutments soft tissue showed that SFMG promoted the vertical alignment of collagen fibers relative to the abutment surface, improving connective tissue sealing around the zirconia abutment. Our results indicated that SFMG on zirconia can enhance HGF proliferation, migration and collagen synthesis by regulating glycolysis though PI3K-AKT-mTor pathway, thereby improving connective tissue sealing.

The influence of hygroscopic expansion of resin supporting dies on the fracture resistance of ceramic restorations during thermal cycling.

OBJECTIVES: To evaluate the hygroscopic expansion characterization of resin composite dies during thermal cycling, and their influence on the fracture resistance of dental ceramic materials as well as the effect of pre-immersion on these measurements. METHODS: Disc-shaped specimens (φ = 15.0 mm, h = 1.2 mm) and anatomical crown dies of four resin composites (epoxy, Z350, P60, G10) were fabricated. Disc-shaped samples were continuously soaked in distilled water and the volume expansion was measured at different time point by Archimedes method. Disc-shaped samples were pre-immersed for 0, 7, or 30 days, elastic modulus and hardness were measured using Nanoindentation test; thermal cycling (TC) test was performed (5 °C-55 °C, 104 cycles), and volume expansion during TC was measured. Four kinds of resin die with pre-immersion for 0, 7, or 30 days were cemented to 5Y-Z crown, or epoxy dies without pre-immersion were cemented to 5Y-Z, 3Y-Z and lithium disilicate glass (LDG) crowns, and load-to-failure testing was performed before and after TC. Finite element analysis (FEA) and fractography analysis were also conducted. RESULTS: The hygroscopic expansion was in the order: epoxy > Z350 > P60 > G10. Except for G10, the other three resin composites exhibited different degrees of hygroscopic expansion during TC. Only the elastic modulus and hardness of epoxy decreased after water storage. However, only the fracture loads of 5Y-Z and LDG crowns supported by epoxy dies were significantly decreased after TC. FEA showed a stress concentration at the cervical region of the crown after volume expansion of the die, leading to the increase of the peak stress at the crown during loading. SIGNIFICANCE: Only the hygroscopic expansion of epoxy dies caused by TC led to the decrease in the fracture resistance of the 5Y-Z and LDG crown, which may be related to the decrease in the elastic modulus of the epoxy die and the tensile stress caused by it.

Effect of low-temperature degradation on the fatigue performance of dental strength-gradient multilayered zirconia restorations.

OBJECTIVES: Fatigue and low-temperature degradation (LTD) are the main factors contributing to zirconia restoration failure. This study evaluated the effect of LTD on the fatigue performance of the novel "strength & shade-gradient" multilayered zirconia restorations. METHODS: Discs (15 mm × 1.2 mm) of each yttria content layer from a newly developed strength-gradient multilayered zirconia were fabricated and under accelerated aging in an autoclave at 134℃ for 0 h, 32 h, and 64 h. Then, the phase transformation, microstructure, and mechanical properties after LTD were assessed. In addition, the crown samples, including the multi-Zir, 3Y-Zir, and 5Y-Zir were fabricated, and their monotonic and fatigue load before and after LTD, percentage of fatigue degradation (Sd) and the fracture morphology were investigated. Statistical analyses were performed using paired samples t-test (α' = α/3 = 0.017), one-way ANOVA and Weibull analysis. RESULTS: After LTD, the phase transformation, surface roughness, depth of transformed zone, and residual stress were increased and inversely associated with the yttria content. The indentation elastic modulus and hardness after LTD decreased; however, there was no significant difference between the different yttria content layers. The monotonic and fatigue load of multi-Zir restorations decreased, but their Weibull modulus increased, and Sd decreased, similar to 3Y-Zir. The crack origin was associated with the cervical region. CONCLUSION: These results show that although LTD reduces the absolute fatigue strength of strength-gradient multilayered zirconia restorations, it also reduces the effect of cyclic fatigue itself on the strength of zirconia (relative to monotonic strength), which might be due to the increase of residual stress. CLINICAL SIGNIFICANCE: The novel "strength & shade-gradient" multilayered zirconia restorations show a promising performance during in vitro LTD and fatigue test and their reliability to some extent is comparable to 3Y-Zir. Yet, further in vivo longitudinal studies are warranted to confirm their precise performance.