CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation.

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip (Stub1) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.

Prevention of postoperative nausea and vomiting after orthognathic surgery: a scoping review.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

An in vitro study using confocal laser scanning microscopy to evaluate the marginal misfits of different implant-supported frameworks.

PURPOSE: This study aimed to develop and evaluate a simple, non-destructive method for assessing the misfit and passivity of implant-retained prostheses frameworks. MATERIALS AND METHODS: To simulate the rehabilitation of a mandible posterior partially edentulous area using 3-unit screw-retained frameworks supported by two implants were fabricated and divided into the following five groups (n = 10 in each group): OP = one-piece framework cast in Co-Cr with the conventional method (control-group); Co-Cr frameworks sectioned and welded by laser (=LAS) or tungsten inert gas (=TIG); Co-Cr CAD-CAM = milled Co-Cr framework; Zir CAD-CAM = milled zirconia framework. The horizontal |X| and vertical |Y| misfits were measured using confocal laser scanning microscopy with one or both screws tightened. Data were analyzed by a two-way ANOVA with repeated measures and Bonferroni correction (α = 0.05). RESULTS: The greatest |X| misfit was observed in the OP group with both screws tightened (290 µm) and one screw tightened (388 and 340 µm). The conventional casting groups sectioned and welded by laser or TIG had lower mean values (235.35 µm, both screws tightened; and 275 µm, one screw tightened) than the OP framework. However, these values still exceeded those of the milled Co-Cr and zirconia frameworks (190 and 216 µm with both screws tightened). Across all reading conditions, every framework subjected to testing consistently maintained vertical |Y| misfit levels below the threshold of 53 µm; however, the milled frameworks exhibited higher vertical misfits than the frameworks obtained by the conventional cast method. CONCLUSIONS: The frameworks, whether cast and sectioned with laser welding or milled from Co-Cr, exhibit improved marginal misfit and enhanced passive fit when compared to other fabrication methods. Additionally, the use of confocal laser scanning microscopy is highly effective for passivity and misfit analysis.

A WWP2-PTEN-KLF5 signaling axis regulates odontoblast differentiation and dentinogenesis in mice.

WW domain-containing E3 Ubiquitin-protein ligase 2 (WWP2) has been found to positively regulate odontoblastic differentiation by monoubiquitinating the transcription factor Kruppel-like factor 5 (KLF5) in a cell culture system. However, the in vivo role of WWP2 in mouse teeth remains unknown. To explore this, here we generated Wwp2 knockout (Wwp2 KO) mice. We found that molars in Wwp2 KO mice exhibited thinner dentin, widened predentin, and reduced numbers of dentinal tubules. In addition, expression of the odontoblast differentiation markers Dspp and Dmp1 was decreased in the odontoblast layers of Wwp2 KO mice. These findings demonstrate that WWP2 may facilitate odontoblast differentiation and dentinogenesis. Furthermore, we show for the first time that phosphatase and tensin homolog (PTEN), a tumor suppressor, is expressed in dental papilla cells and odontoblasts of mouse molars and acts as a negative regulator of odontoblastic differentiation. Further investigation indicated that PTEN is targeted by WWP2 for degradation during odontoblastic differentiation. We demonstrate PTEN physically interacts with and inhibits the transcriptional activity of KLF5 on Dspp and Dmp1. Finally, we found WWP2 was able to suppress the interaction between PTEN and KLF5, which diminished the inhibition effect of PTEN on KLF5. Taken together, this study confirms the essential role of WWP2 and the WWP2-PTEN-KLF5 signaling axis in odontoblast differentiation and dentinogenesis in vivo.

Overexpression of PDE4D in mouse liver is sufficient to trigger NAFLD and hypertension in a CD36-TGF-ß1 pathway: therapeutic role of roflumilast.

Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD) may be both a consequence and a cause of hypertension. Recent studies have demonstrated that phosphodiesterase 4 (PDE4)-cAMP signaling represents a pathway relevant to the pathophysiology of metabolic disorders. This study aims to investigate the impact and the underlying mechanism of PDE4 in the pathogenesis of NAFLD and its associated hypertension. Here we demonstrated that high-fat-diet (HFD) fed mice developed NAFLD and hypertension, with an associated increase in hepatic PDE4D expression, which can be prevented and even reversed by PDE4 inhibitor roflumilast. Furthermore, we demonstrated that hepatic overexpression of PDE4D drove significant hepatic steatosis and elevation of blood pressure. Mechanistically, PDE4D activated fatty acid translocase CD36 signaling which facilitates hepatic lipid deposition, resulting in TGF-ß1 production by hepatocytes and excessive TGF-ß1 signaling in vessels and consequent hypertension. Specific silencing of TGF-ß1 in hepatocytes by siRNA using poly (ß-amino ester) nanoparticles significantly normalized hepatic PDE4D overexpression-activated TGF-ß1 signaling in vessels and hypertension. Together, the conclusions indicated that PDE4D plays an important role in the pathogenesis of NAFLD and associated hypertension via activation of CD36-TGF-ß1 signaling in the liver. PDE4 inhibitor such as roflumilast, which is clinically approved for chronic obstructive pulmonary disease (COPD) treatment, has the potential to be used as a preventive or therapeutic drug against NAFLD and associated hypertension in the future.

Effects of concentration of sodium hypochlorite as an endodontic irrigant on the mechanical and structural properties of root dentine: A laboratory study.

AIM: The use of high-concentration sodium hypochlorite (NaOCl) as an endodontic irrigant remains controversial because of its potential impact on the fracture strength of endodontically treated teeth. This study evaluated the effects of using different NaOCl concentrations, with 2-min-ethylenediaminetetraacetic acid (EDTA) as the final active irrigant, on the biomechanical and structural properties of root dentine. METHODOLOGY: A new test method, which is more clinically relevant, was utilized to calculate the fracture strength of root dentine. Bovine incisors were used to obtain root dentine discs. The root canals were enlarged to mean diameter of 2.90 mm with a taper of 0.06. The resulting discs were divided into five groups (n = 20) and treated with different concentrations of NaOCl (5.25%, 2.5%, and 1.3%) for 30 min plus 17% EDTA for 2 min. The discs were then loaded to fracture by a steel rod with the same taper through the central hole. The fractured specimens were examined by scanning electron microscopy to evaluate changes in the dimensions of the remaining intertubular dentine and the tubular radius. Micro-hardness was also measured with a Knoop diamond indenter along a radius to determine the depth of dentine eroded by the irrigation. Results were analysed by one-way anova and the Tukey test. The level of significance was set at α = 0.05. RESULTS: The damage by NaOCl increased with its concentration. 5.25% NaOCl greatly reduced the fracture strength of root dentine from 172.10 ± 30.13 MPa to 114.58 ± 26.74 MPa. The corresponding reduction in micro-hardness at the root canal wall was 34.1%. The damages reached a depth of up to 400 µm (p < .05). Structural changes involved the degradation of the intratubular wall leading to enlarged dentinal tubules and the loss of intertubular dentine. Changes in the microstructural parameters showed positive linear relationships with the fracture strength. CONCLUSIONS: With the adjunctive use of EDTA, NaOCl caused destruction to the intratubular surface near the root canal and, consequently, reduced the root dentine's mechanical strength. The higher the concentration of NaOCl, the greater the effect. Therefore, endodontists should avoid using overly high concentration of NaOCl for irrigation to prevent potential root fracture in endodontically treated teeth.

Adaptive Laboratory Evolution of Halomonas bluephagenesis Enhances Acetate Tolerance and Utilization to Produce Poly(3-hydroxybutyrate).

Acetate is a promising economical and sustainable carbon source for bioproduction, but it is also a known cell-growth inhibitor. In this study, adaptive laboratory evolution (ALE) with acetate as selective pressure was applied to Halomonas bluephagenesis TD1.0, a fast-growing and contamination-resistant halophilic bacterium that naturally accumulates poly(3-hydroxybutyrate) (PHB). After 71 transfers, the evolved strain, B71, was isolated, which not only showed better fitness (in terms of tolerance and utilization rate) to high concentrations of acetate but also produced a higher PHB titer compared with the parental strain TD1.0. Subsequently, overexpression of acetyl-CoA synthetase (ACS) in B71 resulted in a further increase in acetate utilization but a decrease in PHB production. Through whole-genome resequencing, it was speculated that genetic mutations (single-nucleotide variation (SNV) in phaB, mdh, and the upstream of OmpA, and insertion of TolA) in B71 might contribute to its improved acetate adaptability and PHB production. Finally, in a 5 L bioreactor with intermittent feeding of acetic acid, B71 was able to produce 49.79 g/L PHB and 70.01 g/L dry cell mass, which were 147.2% and 82.32% higher than those of TD1.0, respectively. These results highlight that ALE provides a reliable method to harness H. bluephagenesis to metabolize acetate for the production of PHB or other high-value chemicals more efficiently.

Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4.

Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.

In vitro hypoglycemic effects of hot water extract from Auricularia polytricha (wood ear mushroom).

Viscous dietary fibers were shown to alleviate postprandial blood glucose. Auricularia polytricha (wood ear mushroom, WEM) contains rich amount fibers and water extract WEM was highly viscous. This study aimed to investigate whether WEM extract exhibited hypoglycemic effect in vitro. The effects of WEM extract on glucose adsorption, glucose diffusion, starch digestion and α-amylase activity were examined and compared to those of two high soluble fibers, psyllium and oat fiber and one insoluble fiber, cellulose. Our results showed that WEM extract and psyllium possessed similar ability to adsorb glucose which may thus decrease the level of dialysis glucose. The decrease of dialysis rate is dose-dependent. WEM extract can also suppress the activity of α-amylase which may thus inhibit the digestion of polysaccharides. Since WEM extract exhibited the ability to adsorb glucose and to suppress the activity of α-amylase; it might contribute a beneficial effect on postprandial levels of blood sugar.

Characterization of a low shrinkage dental composite containing bismethylene spiroorthocarbonate expanding monomer.

In this study, a novel dental composite based on the unsaturated bismethylene spiroorthocarbonate expanding monomer 3,9-dimethylene-1,3,5,7-tetraoxa-spiro[5,5]undecane (BMSOC) and bisphenol-S-bis(3-meth acrylate-2-hydroxypropyl)ether (BisS-GMA) was prepared. CQ (camphorquinone) of 1 wt % and DMAEMA (2-(dimethylamino)ethyl methacrylate) of 2 wt % were used in a photoinitiation system to initiate the copolymerization of the matrix resins. Distilled water contact angle measurements were performed for the wettability measurement. Degree of conversion, volumetric shrinkage, contraction stress and compressive strength were measured using Fourier Transformation Infrared-FTIR spectroscopy, the AccuVol and a universal testing machine, respectively. Within the limitations of this study, it can be concluded that the resin composites modified by bismethylene spiroorthocarbonate and BisS-GMA showed a low volumetric shrinkage at 1.25% and a higher contact angle. The lower contraction stress, higher degree of conversion and compressive strength of the novel dental composites were also observed.

[Effects of different surface conditioning agents on the bond strength of resin-opaque porcelain composite].

The objective of this research is to evaluate the effects of different silane coupling agents on the bond strength between Ceramco3 opaque porcelain and indirect composite resin. Five groups of Co-Cr metal alloy substrates were fabricated according to manufacturer's instruction. The surface of metal alloy with a layer of dental opaque porcelain was heated by fire. After the surface of opaque porcelain was etched, five different surface treatments, i.e. RelyX Ceramic Primer (RCP), Porcelain Bond Activator and SE Bond Primer (mixed with a proportion of 1:1) (PBA), Shofu Porcelain Primer (SPP), SE bond primer (SEP), and no primer treatment (as a control group), were used to combine P60 and opaque porcelain along with resin cement. Shear bond strength of specimens was tested in a universal testing machine. The failure modes of specimens in all groups were observed and classified into four types. Selected specimens were subjected to scanning electron microscope and energy disperse spectroscopy to reveal the relief of the fracture surface and to confirm the failure mode of different types. The experimental results showed that the values of the tested items in all the tested groups were higher than that in the control group. Group PBA exhibited the highest value [(37.52 +/- 2.14) MPa] and this suggested a fact that all of the specimens in group PBA revealed combined failures (failure occurred in metal-porcelain combined surface and within opaque porcelain). Group SPP and RCP showed higher values than SEP (P < 0.05) and most specimens of SPP and RCP performed combined failures (failure occurred in bond surface and within opaque porcelain or composite resin) while all the specimens in group SEP and control group revealed adhesive failures. Conclusions could be drawn that silane coupling agents could reinforce the bond strength of dental composite resin to metal-opaque porcelain substrate. The bond strength between dental composite resin and dental opaque porcelain could meet the clinical requirements.

Metabolic profile changes of zebrafish larvae in the single- and co-exposures of microplastics and phenanthrene.

Microplastics (MPs) are ubiquitous in the environment, and can adsorb organic contaminants (OCs) and be taken by various microorganisms and organisms, which could eventually lead to risk to humans. In this study, the phenotypic changes and metabolic profile alternations of zebrafish in the single- and co-exposure of MPs and phenanthrene (Phe) were investigated. The results showed that significantly higher tail malformation rate and edema rate in zebrafish induced by MPs can be enhanced due to the co-existence of Phe. The metabolomic analysis revealed that both synergistic and antagonistic effects of MPs and Phe on the metabolic alternation of zebrafish larvae exist, since unique perturbations of metabolites or pathways were found in all of the three exposure scenarios. Based on Partial least squares-discriminant analysis, porphine, ribose, and L-glutamic acid were the most important metabolites resulting in the difference between the treated and control groups in the MP exposure, Phe exposure and co-exposure, respectively. Two dysregulated pathways namely d-glutamine and D-glutamate metabolism, and alanine, aspartate and glutamate metabolism were significantly affected in the co-exposure while not in either of the single exposure. These findings provide new insights into the toxic effects of MPs on aquatic organisms, and further studies on combined effects of MPs and OCs are suggested to be conducted.

Oroxylin A inhibits inflammatory cytokines in periodontitis via HO­1.

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti­inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase­1 (HO­1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription­quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)­2, TNF­α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ­2, TNF­α, RANKL and OPG. Following HO­1 knockdown, the same treatment was performed. The expression of COX­2 in rat gingival tissue was observed by immunohistochemistry. One­way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. With increase of Oroxylin A dose, the expression of HO­1 was gradually upregulated. When HO­1 was knocked down, Oroxylin A did not downregulate the expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. Immunohistochemical results showed that expression of COX­2 was downregulated by Oroxylin A, and the expression of TNF­α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS­induced RGFs and had a good inhibitory effect on periodontitis in rats.

Characterization of dental light-curing resin composites incorporating multiple modified low-shrink monomers.

OBJECTIVE: Polymerization shrinkage poses a significant challenge in dental resin composites. The objective of this study is to introduce spiroorthocarbonate monomer 3,9-dimethylene-1,3,5,7-tetraoxa-spiro[5,5]undecane (BMSOC) and epoxy resin monomer 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexane carboxylate (ECHM-ECHC) into bisphenol-S-bis(3-methacrylato-2-hydroxy propyl)ether (BisS-GMA) based resin composites to develop composites with reduced shrinkage properties. METHODS: BMSOC and BisS-GMA were synthesized and thoroughly mixed with ECHM-ECHC, followed by inorganic fillers and photoinitiators. Based on the composition of the resin matrix, five groups of experimental composites were prepared, with traditional bisphenol A-dimethacrylate glycidyl ester (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) based composite serving as the control. The polymerization properties, including degree of conversion (DC) and polymerization shrinkage (PS), as well as marginal microleakage, wettability, flexural strength (FS), flexural modulus (FM), and biocompatibility were evaluated. RESULTS: The results demonstrated that compared with the control group, the PS of BisS-GMA based composites containing BMSOC and ECHM-ECHC were significantly reduced (P < 0.05), and the lowest PS (0.96 ± 0.08 %) was observed when the ratio of BisS-GMA: (Epoxy + BMSOC) was 4:6. Additionally, the experimental composites also exhibited improved DC, minimal microleakage, low hydrophilicity, enhanced mechanical properties, qualified in vivo biocompatibility, and slight/moderate in vitro biocompatibility. SIGNIFICANCE: The resin composites incorporating multiple modified low-shrink monomers are promising for dental applications to prevent various clinical problems caused by PS and extend restoration longevity.

Masticatory habits of the adult Neanderthal individual BD 1 from La Chaise-de-Vouthon (France).

OBJECTIVES: The analysis of dental wear provides a useful approach for dietary and cultural habit reconstructions of past human populations. The analysis of macrowear patterns can also be used to better understand the individual chewing behavior and to investigate the biomechanical responses during different biting scenarios. The aim of this study is to evaluate the diet and chewing performance of the adult Neanderthal Bourgeois-Delaunay 1 (BD 1) and to investigate the relationship between wear and cementum deposition under mechanical demands. MATERIALS AND METHODS: The macrowear pattern of BD 1 was analyzed using the occlusal fingerprint analysis method. We propose a new method for the bilateral measurement of the cementum volume along both buccal and lingual sides of the molar root. RESULTS: BD 1's anterior dentition is more affected by wear compared to the posterior one. The macrowear pattern suggest a normal chewing behavior and a mixed-diet coming from temperate environments. The teeth on the left side of the mandible display greater levels of wear, as well as the buccal side of the molar crowns. The cementum analysis shows higher buccal volume along the molar roots. DISCUSSION: BD1 could have been preferably chewing on the left side of the mandible. The exploitation of various food resources suggested by the macrowear analysis is compatible with the environmental reconstructions. Finally, the greater wear on the buccal side of the molar occlusal surface and the greater volume of cementum in that side of the molar roots offers a preliminary understanding about the potential correlation between dental wear and cementum deposition.

Synthesis of a novel monomer "DDTU-IDI" for the development of low-shrinkage dental resin composites.

OBJECTIVE: The current dental resin composites often suffer from polymerization shrinkage, which can lead to microleakage and potentially result in recurring tooth decay. This study presents the synthesis of a novel monomer, (3,9-diethyl-1,5,7,11-tetraoxaspiro[5,5]undecane-3,9-diyl)bis(methylene) bis((2-(3-(prop-1-en-2-yl)phenyl)propan-2-yl)carbamate) (DDTU-IDI), and evaluates its effect in the formulation of low-shrinkage dental resin composites. METHODS: DDTU-IDI was synthesized through a two-step reaction route, with the initial synthesis of the required raw material monomer 3,9-diethyl-3,9-dihydroxymethyl-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU). The structures were confirmed using Fourier-transform infrared (FT-IR) spectroscopy and hydrogen nuclear magnetic resonance (1HNMR) spectroscopy. Subsequently, DDTU-IDI was incorporated into Bis-GMA-based composites at varying weight percentages (5, 10, 15, and 20 wt%). The polymerization reaction, degree of conversion, polymerization shrinkage, mechanical properties, physicochemical properties and biocompatibility of the low-shrinkage composites were thoroughly evaluated. Furthermore, the mechanical properties were assessed after a thermal cycling test with 10,000 cycles to determine the stability. RESULTS: The addition of DDTU-IDI at 10, 15, and 20 wt% significantly reduced the polymerization volumetric shrinkage of the experimental resin composites, without compromising the degree of conversion, mechanical and physicochemical properties. Remarkably, at a monomer content of 20 wt%, the polymerization shrinkage was reduced to 1.83 ± 0.53%. Composites containing 10, 15, and 20 wt% DDTU-IDI exhibited lower water sorption and higher contact angle. Following thermal cycling, the composites exhibited no significant decrease in mechanical properties, except for the flexural properties. SIGNIFICANCE: DDTU-IDI has favorable potential as a component which could produce volume expansion and increase rigidity in the development of low-shrinkage dental resin composites. The development of low-shrinkage composites containing DDTU-IDI appears to be a promising strategy for reducing polymerization shrinkage, thereby potentially enhancing the longevity of dental restorations.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Three-dimensional nanocharacterization of porous hydrogel with ion and electron beams.

Porous hydrogels provide an excellent environment for cell growth and tissue regeneration, with high permeability for oxygen, nutrients, and other water-soluble metabolites through their high water-content matrix. The ability to image three-dimensional (3D) cell growth is crucial for understanding and studying various cellular activities in 3D context, particularly for designing new tissue engineering scaffold, but it is still challenging to study cell-biomaterial interfaces with high resolution imaging. We demonstrate using focused ion beam (FIB) milling, electron imaging, and associated microanalysis techniques that novel 3D characterizations can be performed effectively on cells growing inside 3D hydrogel scaffold. With FIB-tomography, the porous microstructures were revealed at nanometer resolution, and the cells grown inside. The results provide a unique 3D measurement of hydrogel porosity, as compared with those from porosimetry, and offer crucial insights into material factors affecting cell proliferation at specific regions within the scaffold. We also proved that high throughput correlative imaging of cell growth is viable through a silicon membrane based environment. The proposed approaches, together with the protocols developed, provide a unique platform for analysis of the microstructures of novel biomaterials, and for exploration of their interactions with the cells as well.

Altered plasma and brain disposition of isopropylidene shikimic acid liposome in rats and the brain protection in cerebral ischemia-reperfusion.

CONTEXT: Cerebral ischemia-reperfusion (I/R) injury is a secondary injury caused by oxidative stresses and inflammatory responses after recovery from cerebral ischemia. Brain protective drugs were used to reduce the injury. In order to improve the distribution in brain and enhance the brain-protective efficacy, some pharmaceutical technologies were used to achieve brain targeting delivery. OBJECTIVE: To investigate the physiological disposition of ISA liposome, and provide references for the further study about high-efficacy brain-protective preparations for I/R injury. MATERIALS AND METHODS: Comparative studies were carried out. The pharmacodynamics in t-MCAO model rats were studied first, and then the pharmacokinetics and brain distribution of the two preparations were determined. RESULTS: At the same dose, the efficacy of ISA liposome was better (P < 0.05). The efficacy was dose dependent, with significant difference of 20 mg/kg (P < 0.01) and indistinctive difference of 10 mg/kg (P = 0.22), compared with vehicle-treated rats. The parameters, T(1/2ß), MRT and AUC were different significantly between the two preparations. The enhancement of brain distribution for ISA in the liposome was obvious, with the maximum concentration 7.18 µg/g, while close to zero for the solution group. DISCUSSION AND CONCLUSION: ISA liposome could increase the distribution in brain and enhance the efficacy significantly. The results revealed that the liposomal DDS was potential as a novel strategy for the treatment of cerebral I/R injury. In addition, further targeted modification, such as PEG-modified liposomes, which possess a long circulating property in the bloodstream, would further improve the targeting delivery to the brain and lead to more significant efficacy.