Effect of margin designs and loading conditions on the stress distribution of endocrowns: a finite element analysis.

BACKGROUND: Margin designs and loading conditions can impact the mechanical characteristics and survival of endocrowns. Analyzing the stress distribution of endocrowns with various margin designs and loading conditions can provide evidence for their clinical application. METHODS: Three finite element analysis models were established based on the margin designs: endocrown with a butt-joint type margin (E0), endocrown with a 90° shoulder (E90), and endocrown with a 135° shoulder (E135). The E0 group involved lowering the occlusal surface and preparing the pulp chamber. The E90 group created a 90° shoulder on the margin of model E0, measuring 1.5 mm high and 1 mm wide. The E135 group featured a 135° shoulder. The solids of the models were in fixed contact with each other, and the materials of tooth tissue and restoration were uniform, continuous, isotropic linear elasticity. Nine static loads were applied, with a total load of 225 N, and the maximum von Mises stresses and stress distribution were calculated for teeth and endocrowns with different margin designs. RESULTS: Compared the stresses of different models under the same loading condition. In endocrowns, when the loading points were concentrated on the buccal side, the maximum von Mises stresses were E0 = E90 = E135, and when there was a lingual loading, they were E0 < E90 = E135. In enamel, the maximum von Mises stresses under all loading conditions were E0 > E90 > E135. In dentin, the maximum von Mises stresses of the three models were basically similar except for load2, load5 and load9. Compare the stresses of the same model under different loading conditions. In endocrowns, stresses were higher when lingual loading was present. In enamel and dentin, stresses were higher when loaded obliquely or unevenly. The stresses in the endocrowns were concentrated in the loading area. In enamel, stress concentration occurred at the cementoenamel junction. In particular, E90 and E135 also experienced stress concentration at the shoulder. In dentin, the stresses were mainly concentrated in the upper section of the tooth root. CONCLUSION: Stress distribution is similar among the three margin designs of endocrowns, but the shoulder-type designs, especially the 135° shoulder, exhibit reduced stress concentration.

Photothermal modulation of gingival fibroblasts via polydopamine-coated zirconia: A novel approach for promoting peri-implant soft tissue integration.

Achieving robust soft tissue integration around dental implants is crucial for long-term clinical success, as it forms a protective biological seal against bacterial invasion. However, the soft tissue attachment to implants is relatively deficient compared to natural teeth, particularly in the connective tissue region lacking sufficient gingival fibroblasts and collagen fiber alignment. This study proposed an innovative strategy to enhance peri­implant soft tissue integration by modulating gingival fibroblast behavior via photothermal conversion. Zirconia surfaces were coated with polydopamine (PDA), a melanin-like polymer exhibiting near-infrared (NIR) absorption for photothermal conversion. Under NIR irradiation, the PDA coating enabled mild hyperthermia (42-43 °C) on the zirconia surface. Remarkably, this mild photothermal stimulation significantly promoted human gingival fibroblast proliferation, adhesion, and collagen production compared to unmodified zirconia in vitro. By utilizing the photothermal properties of PDA coatings to modulate cellular behaviors beneficial for connective tissue formation, this approach provides a promising avenue to achieve improved soft tissue integration and long-term stability of dental implants. The findings highlight the innovative potential of combining biomaterial surface engineering with photothermal therapy for applications in implant dentistry.

Influence of clinical zirconia surface treatments on microscopic characteristics and adhesion-proliferation behavior of human gingival fibroblasts.

Zirconia is favored in dental implant applications due to its biocompatibility, mechanical properties, and esthetic appeal, particularly in its interaction with soft oral tissues such as the gingiva. To optimize zirconia for clinical use, surface treatments like sanding and polishing are essential. The aim of this study was to investigate the effects of clinical surface treatments on the microscopic characteristics of zirconia and the adhesion and proliferation of human gingival fibroblasts (HGFs). Scanning electron microscopy (SEM) and fluorescence microscopy were utilized to examine the microscopic morphology and roughness resulting from various clinical surface treatment procedures on zirconia and to assess their impact on the microscopic appearance and behavior of HGFs. The results showed that the application of surface treatment procedures, particularly polishing treatments, resulted in the formation of a regular shallow groove morphology and a significant reduction in roughness in zirconia. This was accompanied by improved cell proliferation, cell adhesion, and the expression of integrin ß1 in HGFs. The results suggest that smoother zirconia surfaces promote better cell-material interactions, potentially improving the clinical success of dental implants. This research contributes to our understanding of the optimal surface roughness for soft tissue adhesion and the effect of different micro-morphologies on HGF attachment.

Surface-modified Ti3C2 MXene nanosheets for mesenchymal stem cell osteogenic differentiation via photothermal conversion.

In the field of bone tissue engineering, the practical application of growth factors is limited by various factors such as systemic toxicity, instability, and the potential to induce inflammation. To circumvent these limitations, the use of physical signals, such as thermal stimulation, to regulate stem cells has been proposed as a promising alternative. The present study aims to investigate the potential of the two-dimensional nanomaterial Ti3C2 MXene, which exhibits unique photothermal properties, to induce osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via photothermal conversion. Surface modification of Ti3C2 MXene nanosheets with PVP (Ti3C2-PVP) was employed to enhance their colloidal stability in physiological solutions. Characterization and cellular experiments showed that Ti3C2-PVP nanosheets have favorable photothermal properties and biocompatibility. Our study demonstrated that the induction of photothermal stimulation by co-culturing Ti3C2-PVP nanosheets with BMSCs and subsequent irradiation with 808 nm NIR significantly promoted cell proliferation, adhesion and osteogenic differentiation of BMSCs. In conclusion, the results of this study suggest that Ti3C2-PVP is a promising material for bone tissue engineering applications as it can modulate the cellular functions of BMSCs through photothermal conversion.

Significantly Suppressed Dielectric Loss and Enhanced Breakdown Strength in Core@Shell Structured Ni@TiO2/PVDF Composites.

An insulating shell on the surface of conductive particles is vital for restraining the dielectric loss and leakage current of polymer composites. So as to inhibit the enormous loss and conductivity of pristine nickel (Ni)/poly(vinylidene fluoride)(PVDF) composites but still harvest a high dielectric permittivity (εr) when filler loading approaches or exceeds the percolation threshold (fc), pristine Ni particles were covered by a layer of titanium dioxide (TiO2) shell via a sol-gel approach, and then they were composited with PVDF. The impacts of the TiO2 coating on the dielectric performances of the Ni/PVDF composites were explored as a function of the filler concentration, the shell thickness and frequency. In addition, the dielectric performances were fitted using the Havriliak-Negami (H-N) equation in order to further understand the TiO2 shell's effect on polarization mechanism in the composites. The Ni@TiO2/PVDF composites exhibit high εr and enhanced breakdown strength (Eb) but remarkably suppressed loss and conductivity when compared with pristine Ni/PVDF because the TiO2 shell can efficiently stop the direct contact between Ni particles thereby suppressing the long-range electron transportation. Further, the dielectric performances can be effectively tuned through finely adjusting the TiO2 shell' thickness. The resulting Ni@TiO2/PVDF composites with high εr and Eb but low loss show appealing applications in microelectronics and electrical fields.

Current treatment of chronic hepatitis B: Clinical aspects and future directions.

Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients' health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective.

Biological activity of titania coating prepared with zirconium oxychloride and titania on zirconia surface.

Zirconia is recognized as a promising dental implant material because of its good biocompatibility, sufficient mechanical strength, minimal ion release and aesthetic effects similar to natural teeth. However, the limitations of inert surface of zirconia affect the long-term efficacy of zirconia implants. To enhance the osseointegration of zirconia implants, titania (TiO2) coating is prepared on the zirconia surface by immersion in a mixed zirconium oxychloride (ZrOCl2) and TiO2 suspension in a water bath. The surface and longitudinal section morphology are observed by scanning electron microscopy (SEM). The chemical composition is evaluated through energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The roughness and hydrophilicity of zirconia surface are also examined. A three-point bending test is conducted on the samples to explore the effect of this surface treatment on the mechanical strength of zirconia. Vickers hardness measurements are performed to evaluate the gradient change of the longitudinal section of the zirconia substrate. The MC3T3-E1 cells are seeded on zirconia discs, and a LIVE/DEAD double-staining test is conducted to detect the cytotoxicity of the TiO2 coating. The cell morphology is studied through fluorescence microscope. The degrees of cell proliferation, mineralization and alkaline phosphatase (ALP) activity are calculated and compared. Detection of the mRNA expression of osteogenic differentiation-related markers is performed by RT-PCR. A TiO2 coating is generated on the zirconia surface and significantly improves the surface roughness and hydrophilicity while not adversely affecting the mechanical strength of zirconia. The hardness of the zirconia substrate shows a gradient change. The TiO2 coating can promote proliferation, spreading and osteogenic differentiation of MC3T3-E1 cells. These findings suggest that modifying the surface of zirconia with a TiO2 coating may have a favourable osteogenic effect.

2D titanium carbide(MXene) nanosheets and 1D hydroxyapatite nanowires into free standing nanocomposite membrane: in vitro and in vivo evaluations for bone regeneration.

Bone loss or insufficiency remains a great challenge for implant integrated and subsequently functional loading, where developing biomaterials to augment bone quantity and regenerate alveolar bone defects at implant site is vitally necessary. Recently, MXene, as a large new family of 2D materials, exhibits a great prospect in biomedical applications owing to its ultrathin structure and morphology with a range of extraordinary properties such as chemical, electronic, optical and biological properties etc. Besides, hydroxyapatite is a favorable biomaterial with outstanding bioactivity and osteogenic capacity. In this study, we prepared free standing UHAPNWs/MXene nanocomposite membranes via introducing ultralong hydroxyapatite nanowires (UHAPNWs) with different weight ratios into MXene to explore their potential in bone regeneration. SEM, XPS, FTIR, XRD, tensile strength, Young's modulus and water contact angles were used to characterize the morphology, chemical composition, surface properties, mechanical properties and hydrophilicity of the materials. Subsequently, in vitro studies like cell adhesion, proliferation and osteogenic differentiation of MC3T3-E1 were evaluated. The incorporation of UHAPNWs improved mechanical properties and hydrophilicity with an enhancement in cell adhesion, proliferation, and osteogenic differentiation. More importantly, 10 wt% UHAPNWs/MXene exhibited the optimal mechanical properties while biological improvement was more pronounced along with the addition of UHAPNWs when the weight fraction of UHAPNWs was from 0 to 30 wt%. Furthermore, in vivo experiments the UHAPNWs/MXene nanocomposite membranes effectively enhanced bone tissue formation quantitatively and qualitatively in a rat calvarial bone defect. Therefore, an appropriate amount of UHAPNWs into MXene plays a positive and evident role in enhancing mechanical properties, biocompatibility and osteoinductivity, leading a novel inorganic composite material for regeneration of bone tissue.

Multilayered Titanium Carbide MXene Film for Guided Bone Regeneration.

PURPOSE: MXenes are two-dimensional (2D) materials that are increasingly being applied in biomedical fields. This is ascribed to their good physiochemical properties, unique structure and high biological compatibility. However, the osteogenic activity and suitability of these materials for bone tissue engineering are not clearly understood. Thus, the aim of this study is to evaluate the biocompatibility, osteoinductivity and guided bone regeneration ability of Ti3C2Tx MXene in vitro and in vivo. METHODS: Multilayered Ti3C2Tx MXene films were prepared and characterized by XRD and SEM. In vitro experiments were performed to evaluate the effect of MXene films on cell adhesion and morphology with SEM and fluorescence microscopy. The cytotoxicity of MXene films was detected with the Live/Dead double-staining tests. The EdU assay was employed to evaluate cell proliferation on MXene films and ALP activity was tested to determine the effect of the films on osteogenic differentiation in vitro. The mRNA expression of osteogenic differentiation-related markers was measured using qRT-PCR. In vivo animal studies were performed in which the MXene films were implanted subcutaneously in rats to evaluate biocompatibility and host tissue response in vivo. In addition, a rat calvarial defect model was established to examine the bone regeneration performance of the Ti3C2Tx MXene films. The specimens were analyzed with micro-CT evaluation and histological tests. RESULTS: The XRD and SEM analyses revealed that the Ti3C2Tx MXene film was successfully synthesized. The cellular experiments showed that MXene films were highly cytocompatible and enhanced osteogenic differentiation in vitro. When implanted into subcutaneous sites and calvarial defect sites in rats, MXene films showed good biocompatibility, osteoinductivity and bone regeneration activity in vivo. CONCLUSION: In summary, this study presents new applications of MXenes in bone tissue engineering and in guided bone regeneration therapy.

Expression of protein disulfide isomerase A3 precursor in colorectal cancer.

INTRODUCTION: Over 20% of colorectal cancer (CRC) patients seek medical attention for the first time when they are in the advanced stages of CRC. Thus, early and reliable detection of CRC is critical to early diagnosis of CRC. Protein disulfide isomerase A3 precursor (PDIA3) has been implicated in various types of cancers. However, little is known about PDIA3 in CRC. METHODS: In this study, we screened PDIA3 expression in CRC tissues and cell lines. Small interfering RNA (siRNA) was introduced into SW480 cells to knockdown PDIA3 expression. The effect of PDIA3 in cell growth was evaluated. RESULTS: Significant upregulation of PDIA3 expression was found in CRC tissues as compared with adjacent non-cancer tissues, and was found in established CRC cell lines (SW480, HCT116, CACO2, NCM460 and HT-29). In SW480 cells, knockdown of PDIA3 expression with siRNA resulted in subcellular morphological change, reduced cell proliferation and increased apoptosis. CONCLUSION: PDIA3 inhibition could suppress CRC, likely through inducing apoptosis. PDIA3 could be a potential therapeutic target for CRC.

Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site.

A series of aminochalcone derivatives have been synthesized, characterized by HRMS, 1H NMR and 13C NMR and evaluated for their antiproliferative activity against HepG2 and HCT116 human cancer cell lines. The most of new synthesized compounds displayed moderate to potent antiproliferative activity against test cancer cell lines. Among the derivatives, compound 4 displayed potent inhibitory activity with IC50 values ranged from 0.018 to 5.33 µM against all tested cancer cell lines including drug resistant HCT-8/T. Furthermore, this compound showed low cytotoxicity on normal human cell lines (LO2). The in vitro tubulin polymerization assay showed that compound 4 inhibited tubulin assembly in a concentration-dependent manner with IC50 value of 7.1 µM, when compared to standard colchicine (IC50 = 9.0 µM). Further biological evaluations revealed that compound 4 was able to arrest the cell cycle in G2/M phase. Molecular docking study demonstrated the interaction of compound 4 at the colchicine binding site of tubulin. All the results indicated that compound 4 is a promising inhibitor of tubulin polymerization for the treatment of cancer.

Visual and fluorescent assays for selective detection of beta-amyloid oligomers based on the inner filter effect of gold nanoparticles on the fluorescence of CdTe quantum dots.

Beta-amyloid (Aß) peptides are the major constituents of senile plaques in the brains of Alzheimer's disease (AD) patients. Aß monomers (AßMs) can coalesce to form small, soluble oligomers (AßOs), followed by reorganization and assembly into long, thread-like fibrils (AßFs). Recently, soluble AßOs have been regarded as reliable molecular biomarkers for the diagnosis of AD because of their high toxicity for neuronal synapse and high concentration levels in the brains of AD patients. In this work, we reported a label-free, sensitive and selective method for visual and fluorescent detection of AßOs based on the inner filter effect (IFE) of gold nanoparticles (AuNPs) on the fluorescence of CdTe quantum dots (QDs). Specifically, the fluorescence of CdTe QDs was quenched significantly by AuNPs through the IFE. PrP(95-110), an AßOs-specific binding peptide from cellular prion protein, triggered the aggregation and color change of AuNPs suspension; thus, the IFE of AuNPs on the fluorescence of CdTe QDs was weakened and the fluorescence intensity was recovered. However, in the presence of AßOs, the specific interaction of AßOs and PrP(95-110) prevented the absorption of PrP(95-110) onto the surface of AuNPs. As a result, the aggregation of AuNPs was inhibited and the fluorescence intensity of CdTe QDs was quenched again. This label-free method is specific for detection of AßOs but not for AßMs and AßFs. The detection limits were found to be 0.5nM for the visual assay and 0.2nM for the fluorescent detection. We believe that this work would be valuable for many investigations related to AD diagnosis and drug discovery.

[P53 gene mutation detection by bioluminometry assay].

AIM: To develop a simple, fast and inexpensive approach as well as an instrument for detection of gene mutation. METHODS: Pyrosequencing based on bioluminometry assay was employed to detect gene mutation. Pyrosequencing is a method of sequencing by synthesis step-by-step using four enzymes, DNA-polymerase, ATP sulfurylase, luciferase and apyrase. The signal was produced by detecting pyrophosphate released during a dNTP incorporation. For mutation detection, a DNA fragment was amplified by PCR at first, followed by a single-stranded DNA preparation. In the second step, a short primer was annealed to the position just before the mutation point. Finally, specific dNTPs were added in terms of the template sequence. The mutation species can be readily determined by the sequence. RESULTS: A new instrument was developed for gene mutation detection by pyrosequencing. To iteratively inject small amount of each dNTP for the sequencing reaction, capillaries were used to connect dNTP reservoirs and the reaction chamber. Each dNTP was delivered by adding a gas pressure on the top of a corresponding dNTP reservoir, by which 0.2 microL of dNTP can be exactly added each time. It was theoretically proved that undesired liquid seep through the capillary did not affect the sequencing reactions in pyrosequencing. In addition, the three possible variants (wildtype, mutant and heterozygote) of a mutant point Cys275Ser in P53 gene exon 8 were determined by pyrosequencing using the instrument. A simple method was also described for rapidly distinguishing the type of a variant. CONCLUSION: The developed method is very simple, and the corresponding instrument is inexpensive and easy to operate, which can be used to detect many types of mutation.