An explainable predictive model of direct pulp capping in carious mature permanent teeth.

OBJECTIVE: To introduce a novel approach for predicting the personalized probability of success of DPC treatment in carious mature permanent teeth using explainable machine learning (ML) models. METHODS: Clinical data were obtained from our previous single-center retrospective study, comprising 393 carious mature permanent teeth from 372 patients who underwent DPC and attended 1-year follow-up between January 2015 and February 2021. Six ML models were derived based on 80 % cases of the cohort, with the remaining 20 % cases used for validation. Shapley additive explanation (SHAP) values were utilized to assess feature importance and the clinical relevance of prediction models. RESULTS: Within the cohort, 9.67 % (38 out of 393) of teeth experienced failure at the 1-year follow-up after DPC treatment. Among the six evaluated ML models, the XGBoost model exhibited the highest discriminative ability. By prioritizing features based on their importance, streamlined and interpretable XGBoost model with 11 features were developed for 1-year prognostication post-DPC. The model demonstrated predictive accuracy with area under the curve (AUC) scores of 0.86 for the 1-year prediction. The final model has been translated into a web application to facilitate clinical decision-making. CONCLUSION: By incorporating demographic and clinical examination data, the XGBoost model offered a user-friendly tool for dentists to predict personalized probability of success, thereby improving personalized dental care and patient counseling. The utilization of SHAP for model interpretation provided transparent insights into the decision-making process.

Polydopamine-coated bioactive glass for immunomodulation and odontogenesis in pulpitis.

Preserving vital pulp in cases of dental pulpitis is desired but remains challenging. Previous research has shown that bioactive glass (BG) possesses notable capabilities for odontogenic differentiation. However, the immunoregulatory potential of BG for inflamed pulp is still controversial, which is essential for preserving vital pulp in the context of pulpitis. This study introduces a novel approach utilizing polydopamine-coated BG (BG-PDA) which demonstrates the ability to alleviate inflammation and promote odontogenesis for vital pulp therapy. In vitro, BG-PDA has the potential to induce M2 polarization of macrophages, resulting in decreased intracellular reactive oxygen species levels, inhibition of pro-inflammatory factor, and enhancement of anti-inflammatory factor expression. Furthermore, BG-PDA can strengthen the mitochondrial function in macrophages and facilitate odontogenic differentiation of human dental pulp cells. In a rat model of pulpitis, BG-PDA exhibits the capacity to promote M2 polarization of macrophages, alleviate inflammation, and facilitate dentin bridge formation. This study highlights the notable immunomodulatory and odontogenesis-inducing properties of BG-PDA for treating dental pulpitis, as evidenced by both in vitro and in vivo experiments. These results imply that BG-PDA could serve as a promising biomaterial for vital pulp therapy.

In vitro evaluation of the impact of a bioceramic root canal sealer on the mechanical properties of tooth roots.

Bacground/purpose: Endodontically treated teeth are more prone to vertical root fracture with the mechanical property changes to some extent during root canal treatment. This study aimed to investigate the effects of a bioceramic sealer on the mechanical properties of tooth roots. Materials and methods: Dentin discs were dried by two different methods (ethanol drying and paper points drying) and then filled with a BC sealer named iRoot SP. SEM and EDS were used to analyze the newly formed minerals in dentin tubules. Elastic modulus and hardness of the secondary dentin in areas proximal to the primary dentin (PD-SD) and areas proximal to canal or iRoot SP (SD-C/SD-iRoot SP) were measured using nanoindentation technique. The compressive strength of roots filled with iRoot SP were tested by compressive loading test. Results: (1) Penetration and mineralization: Paper points drying was more conducive to iRoot SP adhesion, spreading and penetration into the dentin tubules than 95% ethanol drying. (2) Micromechanical properties: After filling root canal with iRoot SP, the elastic modulus and hardness of SD-iRoot SP were higher than those of PD-SD (P = 0.001 and P = 0.000). (3) Fracture resistance: The compressive strength of the roots filled with iRoot SP was not significantly different from that of the roots unprepared and unfilled (P = 0.957), but was higher than that of the roots prepared and unfilled (P = 0.009). Conclusion: Excessive drying (95% ethanol drying method) is not conducive to the penetration and mineralization of the BC sealer iRoot SP into dentin tubules. The good bioactivity of iRoot SP was responsible for increasing the elastic modulus and hardness of dentin, which strengthened the prepared roots.

Alkali-extracted proteins from the tooth dentin matrix as a mixture of bioactive molecules for cartilage repair and regeneration.

Introduction: Dentin matrix extracted protein (DMEP) is a mixture of proteins extracted from the organic matrix of a natural demineralized dentin matrix that is rich in a variety of growth factors. However, the effect of DMEP on cartilage regeneration is unclear. The aim of this study was to investigate the efficacy of DMEP extracted via a novel alkali conditioning method in promoting cartilage regeneration. Methods: Alkali-extracted DMEP (a-DMEP) was obtained from human dentin fragments using pH 10 bicarbonate buffer. The concentration of chondrogenesis-related growth factors in a-DMEP was measured via enzyme-linked immunosorbent assay (ELISA). Human bone marrow mesenchymal stem cells (hBMMSCs) in pellet form were induced with a-DMEP. Alcian blue and Safranin O staining were performed to detect cartilage matrix formation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess chondrogenic-related gene expression in the pellets. Rabbit articular osteochondral defects were implanted with collagen and a-DMEP. Cartilage regeneration was assessed with histological staining 4 weeks after surgery. Results: Compared with traditional neutral-extracted DMEP, a-DMEP significantly increased the levels of transforming growth factor beta 1(TGF-ß1), insulin-like growth factor-1(IGF-1) and basic fibroblast growth factor (bFGF). After coculture with hBMMSC pellets, a-DMEP significantly promoted the expression of the collagen type II alpha 1(COL2A1) and aggrecan (ACAN) genes and the formation of cartilage extracellular matrix in cell pellets. Moreover, compared with equivalent amounts of exogenous human recombinant TGF-ß1, a-DMEP had a stronger chondrogenic ability. In vivo, a-DMEP induced osteochondral regeneration with hyaline cartilage-like structures. Conclusions: Our results showed that a-DMEP, a compound of various proteins derived from natural tissues, is a promising material for cartilage repair and regeneration.

Hazards of toxic metal(loid)s: Exploring the ecological and health risk in soil-crops systems with long-term sewage sludge application.

Sewage sludge (SS) is commonly used as agricultural fertilizer worldwide. However, the toxic metal(loid)s in SS raises concerns about soil contamination and the potential risks to human health. This study, conducted since 2007 on the North China Plain, examines the impact of SS use on crops. An experiment was designed with five treatments: conventional fertilization (CK) and four levels of SS application (W1, W2, W3, and W4: 4.5, 9.0, 18.0, and 36.0 t ha-1, respectively). Soil concentrations of eight toxic metal(loid)s (Zn, Cu, Cr, Cd, Ni, Pb, As, and Hg) were analyzed to assess pollution risk using various indices. Health risks associated with maize and wheat grains were also evaluated. Additionally, the impact of long-term SS application on crop yield, soil quality, and human health within a wheat-maize rotation system was examined. SS application increased wheat and maize yields by 5.37 to 19.08 % and 6.97 to 17.94 %, respectively, across treatments W2 to W4. Despite the toxic metal(loid)s in the grains remaining within safe limits, their concentrations showed an upward trend, especially under the W4 treatment. Moreover, SS application significantly increased the soil Zn, Cu, Cr, Cd, Pb, and Hg levels (P < 0.05) without exceeding the national standards. The geo-accumulation index values revealed rising pollution levels for Zn, Cu, Cd, and Hg, which shifted from no contamination to moderate contamination and then to moderate-to-high contamination, yet the overall pollution level remained safe. Soil ecological risks increased from moderate to serious, with Hg posing the greatest risk, particularly under the W4 treatment. Long-term crop intake from the area significantly exposed children and adults to As, contributing 42.12 % and 34.62 % to hazard index (HI), respectively. The HI values for toxic metal(loid)s in these grains surpassed one in both age groups, suggesting health risks from long-term SS cultivated crops.

Heparin-Functionalized Bioactive Glass to Harvest Endogenous Growth Factors for Pulp Regeneration.

Pulp and periapical diseases can lead to the cessation of tooth development, resulting in compromised tooth structure and functions. Despite numerous efforts to induce pulp regeneration, effective strategies are still lacking. Growth factors (GFs) hold considerable promise in pulp regeneration due to their diverse cellular regulatory properties. However, the limited half-lives and susceptibility to degradation of exogenous GFs necessitate the administration of supra-physiological doses, leading to undesirable side effects. In this research, a heparin-functionalized bioactive glass (CaO-P2O5-SiO2-Heparin, abbreviated as PSC-Heparin) with strong bioactivity and a stable neutral pH is developed as a promising candidate to addressing challenges in pulp regeneration. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis reveal the successful synthesis of PSC-Heparin. Scanning electron microscopy and X-ray diffraction show the hydroxyapatite formation can be observed on the surface of PSC-Heparin after soaking in simulated body fluid for 12 h. PSC-Heparin is capable of harvesting various endogenous GFs and sustainably releasing them over an extended duration by the enzyme-linked immunosorbent assay. Cytological experiments show that developed PSC-Heparin can facilitate the adhesion, migration, proliferation, and odontogenic differentiation of stem cells from apical papillae. Notably, the histological analysis of subcutaneous implantation in nude mice demonstrates PSC-Heparin is capable of promoting the odontoblast-like layers and pulp-dentin complex formation without the addition of exogenous GFs, which is vital for clinical applications. This work highlights an effective strategy of harvesting endogenous GFs and avoiding the involvement of exogenous GFs to achieve pulp-dentin complex regeneration, which may open a new horizon for regenerative endodontic therapy.

LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae.

Linalool and caryophyllene are the main monoterpene and sesquiterpene compounds in lavender; however, the genes regulating their biosynthesis still remain many unknowns. Here, we identified LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae. LaMYC7 was highly expressed in glandular trichomes, and LaMYC7 overexpression could significantly increase the linalool and caryophyllene contents and reduce susceptibility to P. syringae in Nicotiana. In addition, the linalool possessed antimicrobial activity against P. syringae growth and acted dose-dependently. Further analysis demonstrated that LaMYC7 directly bound to the promoter region of LaTPS76, which encodes the terpene synthase (TPS) for caryophyllene biosynthesis, and that LaTPS76 was highly expressed in glandular trichomes. Notably, the LaMYC7 promoter contained hormone and stress-responsive regulatory elements and responded to various treatments, including ultraviolet, low temperature, salt, drought, methyl jasmonate, and P. syringae infection treatments. Under these treatments, the changes in the linalool and caryophyllene contents were similar to those in LaMYC7 transcript abundance. Based on the results, LaMYC7 could respond to P. syringae infection in addition to being involved in linalool and caryophyllene biosynthesis. Thus, the MYC transcription factor gene LaMYC7 can be used in the breeding of high-yielding linalool and caryophyllene lavender varieties with pathogen resistance.

Promoting bond durability by a novel fabricated bioactive dentin adhesive.

OBJECTIVE: To prepare a bioactive dentin adhesive and investigate its effect on promoting bonding durability of dentin. METHODS: The mineralization of the bioactive glass with high phosphorus (10.8 mol% P2O5-54.2 mol% SiO2-35 mol% CaO, named PSC) and its ability to induce type I collagen mineralization were observed by SEM and TEM. The Control-Bond and the bioactive dentin adhesive containing 20 wt% PSC particles (PSC-Bond) were prepared, and their degree of conversion (DC), microtensile bond strength (µTBS), film thickness and mineralization performance were evaluated. To evaluate the bonding durability, dentin bonding samples were prepared by Control-Bond and PSC-Bond, and mineralizated in simulated body fluid for 24 h, 3 months, and 6 months. Then, the long-term bond strength and microleakage at the adhesive interface of dentin bonding samples were evaluated by microtensile testing and semiquantitative ELIASA respectively. RESULTS: The PSC showed superior mineralization at 24 h and induced type I collagen mineralization to some extent under weakly alkaline conditions. For PSC-Bond, DC was 62.65 ± 1.20%, µTBS was 39.25 ± 4.24 MPa and film thickness was 17.00 ± 2.61 µm. PSC-Bond also formed hydroxyapatite and maintained good mineralization at the bonding interface. At 24 h, no significant differences in µTBS and interface microleakage were observed between the Control-Bond and PSC-Bond groups. After 6 months of aging, the µTBS was significantly higher and the interface microleakage was significantly lower of PSC-Bond group than those of Control-Bond group. SIGNIFICANCE: PSC-Bond maintained bond strength stability and reduced interface microleakage to some extent, possibly reducing the occurrence of secondary caries, while maintaining long-term effectiveness of adhesive restorations.

Genome-wide identification and expression of BAHD acyltransferase gene family shed novel insights into the regulation of linalyl acetate and lavandulyl acetate in lavender.

The BAHD acyltransferase superfamily has a variety of biological functions, especially in catalyzing the synthesis of ester compounds and improving plant stress resistance. Linalyl acetate and lavandulyl acetate, the most important volatile esters in lavender, are generated by LaBAHDs. However, the systematic identification, expression characteristics of LaBAHD genes and their correlations with ester formation remain elusive. Here, 166 LaBAHD genes were identified from the lavender genome. Based on detailed phylogenetic analysis, the LaBAHD family genes were divided into five groups, among which the LaBAHDs involved in volatile ester biosynthesis belong to the IIIa and Va clades. Whole-genome duplications (WGDs) and tandem duplications (TDs) jointly drive the expansion of LaBAHD superfamily. The promoter regions of LaBAHDs contained a variety of stress- and hormone-related motifs, as well as binding sites with five types of transcription factors (TFs). Then, linalyl acetate- and lavandulyl acetate-regulated coexpression modules were established and some candidate TFs that may function in inducing ester formation were identified. Based on the correlation analysis between the ester contents and expression profiles of BAHD genes in different tissues, five candidate genes were screened for further examination. Drought, salt and MeJA treatments increased the accumulation of linalyl acetate and lavandulyl acetate, and induced the expression of LaBAHDs. Our results indicated that LaBAHD57, LaBAHD63, LaBAHD104, LaBAHD105 and LaBAHD119 are crucial candidate genes involved in linalyl acetate and lavandulyl acetate biosynthesis. Our findings offer a theoretical foundation for further studying the specific biological functions of LaBAHD family and improving the quality of lavender essential oil.

Chemical Compositions of Essential Oil Extracted from Eight Thyme Species and Potential Biological Functions.

Thymus is an herbaceous perennial or subshrub of the Lamiaceae family and is widely distributed worldwide. Essential oils extracted from thymus have attracted much attention, owing to their potential biological functions. Here, we evaluated the chemical compositions of eight thyme essential oils (TEOs) using gas chromatography mass spectrometry and assessed their antioxidant activity. The results showed that (1) the main components in eight TEOs were monoterpene hydrocarbons and oxygenated monoterpenes (84.26-92.84%), and the chemical compositions of the TEOs were affected by the specie factor; (2) eight TEOs could be divided into three groups (thymol-, geraniol-, and nerol acetate-types), and thymol was the main type; (3) eight TEOs had some common compounds, such as thymol and p-cymene, which were the main components in seven TEOs; (4) eight TEOs had antioxidant activity, and Thymus pulegioides, Thymus thracicus, and Thymus serpyllum EOs had stronger antioxidant activity than vitamin E (0.07-0.27 fold) at a concentration of 1 mg/mL, while Thymus quinquecostatus and Thymus longicaulis EOs had relatively weak antioxidant activity. In addition, three chemical type standards were used to evaluate potential roles in antibacterial and tumor therapy. The results showed that thymol had strong antibacterial activity against the growth of Escherichia coli and Staphylococcus aureus, and antimigratory activity for A549 cell. Overall, our results can provide a theoretical basis for further exploring the function of natural products from thyme essential oils.