Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Polystyrene nanoplastics exposure triggers spermatogenic cell senescence via the Sirt1/ROS axis.

Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-ß-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.

Two effective clinical prediction models to screen for obstructive sleep apnoea based on body mass index and other parameters.

BACKGROUND AND OBJECTIVE: The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography which is time-consuming and expensive. We therefore aimed to develop two simple, non-invasive models to screen adults for OSA. METHODS: The effectiveness of using body mass index (BMI) and a new visual prediction model to screen for OSA was evaluated using a development set (1769 participants) and confirmed using an independent validation set (642 participants). RESULTS: Based on the development set, the best BMI cut-off value for diagnosing OSA was 26.45 kg/m2, with an area under the curve (AUC) of 0.7213 (95% confidence interval (CI), 0.6861-0.7566), a sensitivity of 57% and a specificity of 78%. Through forward conditional logistic regression analysis using a stepwise selection model developed from observed data, seven clinical variables were evaluated as independent predictors of OSA: age, BMI, sex, Epworth Sleepiness Scale score, witnessed apnoeas, dry mouth and arrhythmias. With this new model, the AUC was 0.7991 (95% CI, 0.7668-0.8314) for diagnosing OSA (sensitivity, 75%; specificity, 71%). The results were confirmed using the validation set. A nomogram for predicting OSA was generated based on this new model using statistical software. CONCLUSIONS: BMI can be used as an indicator to screen for OSA in the community. We created an internally validated, highly distinguishable, visual and parsimonious prediction model comprising BMI and other parameters that can be used to identify patients with OSA among outpatients. Use of this prediction model may help to improve clinical decision-making.

Comparison of stress distribution between zirconia/alloy endocrown and CAD/CAM multi-piece zirconia post-crown: three-dimensional finite element analysis.

OBJECTIVES: This study aimed to evaluate a digital multi-piece zirconia post-crown to restore a mandibular second molar with extensive coronal loss and limited restoration space, and to compare the stress distribution between endocrowns made of zirconia or alloy and CAD/CAM multi-piece zirconia post-crowns. MATERIAL AND METHODS: Four three-dimensional finite element analysis models of a mandibular second molar with extensive coronal loss and limited restoration space were created as follows: (A) intact molar; (B) zirconia endocrown restored molar; (C) multi-piece post-crown restored-molar with tapered nail; (D) multi-piece post-crown restored molar with T-shaped nail. Models C and D were divided into two subgroups according to the material type: C1/D1, zirconia; C2/D2, NiCr alloy. The maximum modified von Mises failure criterion (mvM) stresses were calculated, and the stress distribution was recorded to analyze the effects of the restoration and material types on the biomechanical properties of dentin and prosthesis. RESULTS: The maximum mvM stress of dentin in model B (33.80 MPa) was lower compared with models C (C1, 37.81 MPa; C2, 36.36 MPa) and D (D1, 36.34 MPa; D2, 34.97 MPa) under vertical load, but the opposite was observed under oblique load. The highest mvM stress was concentrated in the nail region located in the root canal, and the T-shaped nail values were greater than the tapered nail, whereas model D with T-shaped nail showed a lower mvM stress level in dentin compared with Model C with tapered nail. CONCLUSIONS: The digital multi-piece zirconia post-crown is a potential approach to restore mandibular second molars with extensive coronal loss and limited restoration space. CLINICAL RELEVANCE: The digital multi-piece zirconia post-crown has potential to restore mandibular second molars with extensive coronal loss and limited restoration space using an innovative approach.

Evaluation of intraoral optical scanning accuracy for fine structure reconstruction and occlusal records of inlay/onlay preparations.

AIM: The present study aimed to determine the impact of different degrees of salivary contamination and variations in occlusal force during intraoral scanning of inlay/onlay cavities on the accuracy of fine structure reconstruction and occlusal records. MATERIALS AND METHODS: Digital data of inlay/onlay models, collected using an intraoral scanner, were divided into 40 groups according to the restoration type (onlay or inlay), salivary contamination level (none, completely dry; mild, moist but not visually completely apparent; moderate, half-filled cavity; severe, filled-up cavity), and simulated occlusal force (0, 2, 4, 6 or 8 kg). The acquired 120 datasets were used to measure the average interocclusal space and cavity buccolingual internal angle. RESULTS: Salivary contamination and occlusal force did affect the occlusal contact (P < 0.001), but restoration type did not (P > 0.05). An interaction was found between inlay type and salivary contamination (P < 0.001), but not between occlusal force and salivary contamination (P > 0.05). Salivary contamination also affected the accuracy of fine structure reconstruction (P < 0.001), but restoration type did not (P > 0.05), and no interaction was found between the two factors (P > 0.05). The difference in the measured internal angle increased with the increase in salivary contamination. CONCLUSIONS: Intraoral optical scanning of inlay/onlay preparations was reliable for recording occlusal contact but showed uncertainty in cavity fine structure reconstruction when moderate or severe salivary contamination was present in the cavity. Nevertheless, a moist cavity surface with no visually apparent salivary contamination is acceptable. (Int J Comput Dent 2022;25(3):257-265; doi: 10.3290/j.ijcd.b2599691).

Novel Bio-Based Materials and Applications in Antimicrobial Food Packaging: Recent Advances and Future Trends.

Food microbial contamination not only poses the problems of food insecurity and economic loss, but also contributes to food waste, which is another global environmental problem. Therefore, effective packaging is a compelling obstacle for shielding food items from outside contaminants and maintaining its quality. Traditionally, food is packaged with plastic that is rarely recyclable, negatively impacting the environment. Bio-based materials have attracted widespread attention for food packaging applications since they are biodegradable, renewable, and have a low carbon footprint. They provide a great opportunity to reduce the extensive use of fossil fuels and develop food packaging materials with good properties, addressing environmental problems and contributing significantly to sustainable development. Presently, the developments in food chemistry, technology, and biotechnology have allowed us to fine-tune new methodologies useful for addressing major safety and environmental concerns regarding packaging materials. This review presents a comprehensive overview of the development and potential for application of new bio-based materials from different sources in antimicrobial food packaging, including carbohydrate (polysaccharide)-based materials, protein-based materials, lipid-based materials, antibacterial agents, and bio-based composites, which can solve the issues of both environmental impact and prevent foodborne pathogens and spoilage microorganisms. In addition, future trends are discussed, as well as the antimicrobial compounds incorporated in packaging materials such as nanoparticles (NPs), nanofillers (NFs), and bio-nanocomposites.

Curcumin Inhibits Polyethylene-Induced Osteolysis via Repressing NF-κB Signaling Pathway Activation.

BACKGROUND/AIMS: Aseptic loosening is a common reason for failed artificial hip replacement after total hip arthroplasty. Aseptic loosening is mostly the result of wear debris that causes osteolysis and weakens the structures that support the prosthesis. Wear debris plays a crucial role in osteolysis during the loosening process, and polyethylene (PE) particles are found as wear debris more frequently than any other type of particle. In the absence of effective therapeutic agents, osteolysis has been hard to treat. Previous studies have demonstrated that curcumin influences signalosome-associated kinases and the proteasome-ubiquitin system during osteoclastogenesis. The aims of this study were to explore the anti-osteolysis effect of curcumin and if possible to identify the signaling pathway involved in a model of PE-induced osteolysis. METHODS: Differentiation of osteoclasts was induced in vitro by PE particles in RAW264.7 (monocyte/macrophage) cells and in vivo by calvarial and air pouch models of osteolysis established by PE stimulation in mice. We performed a set of TRAP staining, realtime polymerase chain reaction (PCR), and Western blot experiments to evaluate the anti-osteolytic effect of curcumin by comparing specimens that were exposed and not exposed to curcumin. RESULTS: Curcumin had a promising inhibitory effect on osteolysis induced by wear debris and suppressed the RANK/c-Fos/NFATc1 signaling pathway. CONCLUSION: Curcumin can prevent PE-induced osteolysis and bone loss. An inhibitory effect on the RANK/c-Fos/NFATc1 signaling pathway may explain the anti-osteolysis activity of curcumin.

Reversible Thermoresponsive Plasmonic Core-Satellite Nanostructures That Exhibit Both Expansion and Contraction (UCST and LCST).

The assembly of sophisticated gold nanoparticle constructs where thermoresponsive core-satellite nanostructures are created and the satellites are close enough to the core for strong surface plasmon resonance coupling to occur, has begun to be developed. The linker between the core and the satellites being a thermoresponsive polymer means that a dispersion of these nanostructures will show temperature-dependent optical properties as the distance between the core and the satellites changes. Unlike previous related thermoresponsive core-satellite systems that undergo a single thermoresponsive transition, herein a polymer system with dual thermoresponsive transitions (block copolymer with both lower critical solution temperature and upper critical solution temperature) is employed as a linker that modulates the gap distance between the "core" and "satellites" in response to the temperature. In this way, optical properties of dispersions can be dynamically tuned. The system permits wide and reversible control of the optical properties, which may render them excellent candidates for reversible nanosensors.

Layer-by-layer self-assembled multilayers on PEEK implants improve osseointegration in an osteoporosis rabbit model.

This study aims to fabricate and deposit nanoscale multilayers on polyetheretherketone (PEEK) to improve cell adhesion and osseointegration. Bio-activated PEEK constructs were designed with prepared surface of different layers of polystyrene sulfonate (PSS) and polyallylamine hydrochloride (PAH) multilayers. Irregular morphology was found on the 5 and 10-layer PEEK surfaces, while "island-like" clusters were observed for 20-layer (20 L) multilayers. Besides, the 20 L PEEK showed more hydrophilic feature than native PEEK, and the surface contact angle reduced from 39.7° to 21.7° as layers increased from 5 to 20. In vitro, modified PEEK allowed excellent adhesion and proliferation of bone marrow stromal cells, and induced higher cell growth rate and alkaline phosphatase level. In vivo, this bio-active PEEK exhibited significantly enhanced integration with bone tissue in an osteoporosis rabbit model. This work highlights layer-by-layer self-assembly as a practical method to construct bio-active PEEK implants for enhanced osseointegration.

Hominin teeth from the Middle Pleistocene site of Yiyuan, Eastern China.

In 1981-1982, some hominin fossils, including a relatively complete skull and seven isolated teeth, were recovered from the Middle Pleistocene site of Yiyuan in Eastern China. In the present study we provide a detailed metric and morphological comparison of the Yiyuan dental sample in order to characterize better the variability of the human populations that inhabited China during the Middle Pleistocene. Aside from taxonomic and phylogenetic questions, the lack of understanding and/or knowledge about the morphological variability of these populations have caused concern about the human versus non-human nature of some of the hominin dental remains found in East Asia during the Early and the Middle Pleistocene. Thus, our study aims to present a detailed description and comparison of the Yiyuan isolated teeth to 1) discuss and support their human nature and 2) to explore their taxonomic affinities with regard to other penecontemporaneous populations from Asia. Our results clearly differentiate the Yiyuan sample from Pongo specimens and support a human attribution for the Yiyuan material. Our analyses also suggest that the Yiyuan teeth form a morphologically coherent group together with samples from Zhoukoudian, Chaoxian and Hexian. They are different from the more derived specimens from Panxian Dadong, suggesting a pattern of biogeographic isolation and different evolutionary trends between northern and southern China during the Middle Pleistocene. In addition, and despite sharing a common morphological bauplan with Homo erectus sensu stricto (s.s.), the Yiyuan, Zhoukoudian and Hexian teeth are also different from the Indonesian Early Pleistocene samples. In particular, the expression of a highly crenulated or dendritic enamel-dentine surface could be unique to these groups. Our study supports the notion that the taxonomy of the Pleistocene hominins from Asia may have been oversimplified. Future studies should explore the variability of the Asian specimens and reconsider whether all the samples can be attributed to H. erectus s.s.

Correlation of Circadian Rhythms and Improvement of Depressive Symptoms in Acute Ischemic Stroke Patients

OBJECTIVES: To investigate the correlation between evening melatonin timing secretion, dim light melatonin onset (DLMO), and post-stroke depression (PSD) in acute ischemic stroke patients and their influence on the improvement of depressive symptoms. MATERIALS AND METHODS: 120 patients with a recent magnetic resonance imaging confirmed stroke were included. Salivary melatonin samples were collected at 5 time points within 1 week after hospitalization (7 p.m.-11 p.m., 1 sample per hour). The circadian phase was defined by calculating DLMO secretion. Post-stroke depressive symptoms were evaluated by the 17-item Hamilton Rating Scale for Depression (HRSD) both on day 7 of hospitalization and 3 months after stroke. Patients were divided into PSD and non-PSD groups based on whether the acute phase HRSD score was ≥8. Similarly, patients were divided into the improved depressive symptoms (IDS) and no improvement in depressive symptoms (non-IDS) groups based on whether the HRSD score at 3 months was lower than at baseline. Neurological recovery at 3 months was assessed using the modified Rankin Scale (mRS). RESULTS: The difference in DLMO between PSD and non-PSD patients was not statistically significant (p =0.173). In the non-IDS group, there was a significant decrease in melatonin secretion at 10 p.m. (p =0.012), and DLMO was significantly later than in the IDS group (p =0.017). Logistic regression analysis showed that DLMO (OR 1.91, 95%CI:1.13-3.23, p = 0.016) was an independent risk factor for persistent no improvement in depressive symptoms, which was associated with a markedly worse prognosis (p <.001). CONCLUSION: Our findings suggest possible interventions for the very early identification of non-IDS patients.

[Poorly differentiated neuroendocrine carcinoma of the tongue base: a case report].

Neuroendocrine carcinoma(NEC) is a malignant tumor derived from neuroendocrine cells, with distinct clinical, morphological and immunohistochemical characteristics. Neuroendocrine carcinoma of the head and neck is very rare in clinic. Larynx is the most common affected site, and the root of the tongue is extremely rare. The clinical manifestations are mainly eating pain, cauliflower like mass in the mouth, and ulcerative lesions that have not healed for a long time. Maxillofacial MRI and contrastenhanced CT are the most commonly used examination tools for such diseases, which can detect the spaceoccupying lesions of tumors. Neuroendocrine granules found in the cytoplasm under pathological light microscope can be diagnosed as neuroendocrine carcinoma. However, for most cases, it is difficult to make a diagnosis only under light microscope, and it is often necessary to make a diagnosis by means of immunohistochemistry and other technical means. This paper reports a case of neuroendocrine carcinoma of the root of the tongue, introduces its characteristics, diagnosis and treatment, and reviews the relevant literature of this case.

Polyphenols Can Improve Resin-Dentin Bond Durability by Promoting Amorphous Calcium Phosphate Nanoparticles to Backfill the Dentin Matrix.

Objective: To investigate the effects of proanthocyanidins (PA), myricetin, resveratrol, and kaempferol on the modification of dentin collagen and the inhibition of matrix metalloproteinase (MMP) activity, and to evaluate their contributions to the biomimetic remineralization and resin-dentin bonding performance. Methods: Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and in situ zymography were applied to verify the collagen modification and MMP activity inhibition induced by these four polyphenols. Scanning electron microscopy/energy dispersive spectrometer (SEM/EDS) analysis, X-ray diffraction (XRD), ATR-FTIR, Vickers hardness numbers (VHN), and micro-computed tomography (micro-CT) were performed to characterize the remineralized dentin. Microtensile bond strength (µTBS) and nanoleakage were investigated to evaluate the effects of the four polyphenols on resin-dentin bonding durability. Results: ATR-FTIR and in situ zymography confirmed that these four polyphenols could modify dentin collagen and inhibit MMP activity, respectively. Chemoanalytic characterization exhibited the efficacies of the four polyphenols in promoting dentin biomimetic remineralization. The surface hardness of PA-pretreated dentin was the greatest. Micro-CT results demonstrated that the PAs group possessed the highest amount of dentin surface minerals and the lowest amount of deep-layer minerals. The surface and deep-layer mineral contents of the Myr group were higher than Res and Kae groups. Treatment with these four polyphenols significantly increased the initial µTBS compared with the control group without primer conditioning. µTBS decreased significantly during aging, and the decrease was more severe in the PAs and Kae groups than in the Myr and Res groups. With or without aging, the polyphenol groups exhibited relatively less fluorescence. However, the Myr and Res groups showed less serious nanoleakage after aging. Conclusion: PA, myricetin, resveratrol, and kaempferol can modify dentin collagen, inhibit MMP activity, promote biomimetic remineralization, and improve resin-dentin bond durability. Compared with PA and kaempferol, myricetin and resveratrol are more effective in improving resin-dentin bonding.

Microplastics cause reproductive toxicity in male mice through inducing apoptosis of spermatogenic cells via p53 signaling.

BACKGROUND: Studies on male reproductive toxicity of microplastics are still scarce and the precise mechanism is not distinct. METHODS: C57BL/6 male mice were given oral gavage treatments treated with 5 µm (MPs) and 80 nm (NPs) polystyrene microplastics every day for 60 consecutive days in a row at dosages of 0, 10 and 40 mg/kg/d. The major damage of MPs and NPs were assessed by the assays in vivo and in vitro. Transcriptome sequencing was applied to screen the key involved pathways. RESULTS: In the 10 mg/kg/d NPs group, there was an increase in testicular organ coefficient, and in the 40 mg/kg/d MPs group, an increase in epididymal weight was observed. Vacuolization of spermatogenic cell layer, interstitial congestion, and germ cell apoptosis were found in the testes of MPs and NPs treatment mice at different dose groups. Higher apoptosis rate was observed in GC-2 cells after MPs and NPs treatment at different concentrations. Transcriptome analysis suggested that p53 pathway might be the key signal pathway of the cell apoptosis, and the expressions of p53 and other markers of cell apoptosis were indeed altered after exposure to MPs and NPs. CONCLUSIONS: MPs and NPs can cause reproductive toxicity in male mice through inducing apoptosis of spermatogenic cells via p53 signaling pathway, indicating MPs and NPs exposure be an unnegligible risk factor for reproductive health in male mice.

Improved bond performances of self-etch adhesives to enamel through increased MDP-Ca salt formation via phosphoric acid pre-etching.

OBJECTIVES: The chemical affinity between 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and hydroxyapatite (HAp) is an important factor in the enamel bonding provided by MDP-based self-etch (SE) adhesives, besides microinterlocking mechanisms. This study aimed to investigate how phosphoric acid pre-etching affects MDP-Ca salt formation in the application of MDP-based SE adhesives. METHODS: Single Bond Universal (SBU), All Bond Universal (ABU), Clearfil Universal Bond Quick (CBQ), and a MDP-based all-in-one adhesive (EXP) were used in both SE and etch-and-rinse (ER) modes, along with Clearfil SE Bond and untreated enamel (UE) as controls. The MDP-Ca salts produced with or without etching were examined by nuclear magnetic resonance, Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy. Zeta potential, contact angle, and scanning electron microscopy measurements were employed to elucidate the mechanism behind the changes in MDP/HAp chemical affinity upon pre-etching. RESULTS: The percentage of MDP-Ca salt in EXP_ER (73.13%) was higher than that in EXP_SE (43.27%). Characteristic CH2 (1130, 1441, 2853, and 2909 cm-1), CC (1641 cm-1), and CO (1718 cm-1) bands were observed in the Raman spectra of EXP_ER. Pre-etching increased the negative zeta potential of the enamel surface compared to that of UE (P < 0.001). The contact angles of MDP-based adhesives applied to pre-etched enamel were significantly lower than those of the self-etched surface (P < 0.05). SIGNIFICANCE: The increased MDP-Ca salt formation is a significant advantage of phosphoric acid pre-etching, improving the MDP/HAp chemical affinity in addition to increasing surface wettability.

Influence of Acidic Environment on Hydrolytic Stability of MDP-Ca Salts with Nanolayered and Amorphous Structures.

Purpose: This study aimed to investigate the hydrolytic stability of 10-methacryloyloxydecyl dihydrogen phosphate calcium (MDP-Ca) salts with nanolayered and amorphous structures in different pH environments. Methods: The MDP-Ca salts were synthesized from MDP and calcium chloride and characterized by X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to quantify the release of calcium from the synthesized MDP-Ca salt, MDP-treated hydroxyapatite (MDP-HAp), and untreated HAp after soaking in acidic and neutral solutions for 1, 7, and 30 days. To study the hydrolytic process, we carried out molecular dynamics (MD) simulations of the nanolayered MCS-MD (monocalcium salt of the MDP dimer) and DCS-MD (dicalcium salt of the MDP dimer) structures, as well as of the amorphous-phase MCS-MM (monocalcium salt of the MDP monomer). Results: The TEM images showed that the nanolayered structures were partially degraded by acid attack. Based on the ICP-MS results, the hydrolysis rate of the MDP-Ca salt in acidic and neutral environments followed the order HAp > MDP-HAp > MDP-Ca salt. The MD simulations showed that, in acidic environments, clusters of MDP remained aggregated and all Ca2+ ions separated from the MDP monomer to interact with water molecules in aqueous solution. In neutral environments, Ca2+ ions always interacted with phosphate groups, OH- ions, and water molecules to form clusters centered on Ca2+ ions. Conclusion: MDP-Ca presented higher hydrolysis rates in acidic than neutral environments. Nanolayered MCS-MD possessed the highest resistance to acidic hydrolysis, followed by amorphous MCS-MM and DCS-MD.

The roles of 10-methacryloyloxydecyl dihydrogen phosphate and its calcium salt in preserving the adhesive-dentin hybrid layer.

OBJECTIVES: 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) has been regarded as the most effective dentin-bonding monomer for more than 20 years. Although the dentin-bonding promoting effect of MDP has been well demonstrated, the mechanisms by which it benefits the stably of collagen within the adhesive-dentin hybrid layer are not currently fully understood. The objective of this study was to investigate the roles of MDP and its calcium salt in preserving the adhesive-dentin hybrid layer. METHODS: MDP-conditioned collagen was investigated by Fourier-transform infrared spectroscopy, Ultraviolet-visible spectroscopy, and molecular docking. The structural changes to the dentin surface upon acid-etching and MDP-conditioning were observed by SEM. X-ray diffraction and nuclear magnetic resonance were used to investigate the chemical interactions between MDP and HAp. The collagen-protecting effects of MDP and its Ca salt were investigated using in-situ zymography, rhMMP-9 colorimetric assay, hydroxyproline assay, and molecular docking. RESULTS: MDP forms a stable collagen-phosphate complex through hydrogen bonding with the collagen in dentin. Furthermore, it generates MDP-Ca salts that are deposited on the dentin collagen scaffold, protecting it from degradation. Moreover, both free MDP and the MDP-Ca salt inhibit matrix metallopeptidase and exogenous proteases, with the inhibitory effect of the calcium salt being significantly stronger than that of the free form. SIGNIFICANCE: MDP-based adhesives preserve the collagen within the hybrid layer by simultaneously improving collagen's resistance to exogenous enzymes and inhibiting MMP activity, both of which contribute to the longevity of dentin-resin bonding.

Interactions of two phosphate ester monomers with hydroxyapatite and collagen fibers and their contributions to dentine bond performance.

OBJECTIVES: To evaluate the interactions of two phosphate ester monomers [10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and dipentaerythritol penta-acrylate phosphate (PENTA)] with hydroxyapatite and collagen and understand their influence on dentine bonding. METHODS: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, nuclear magnetic resonance, ultraviolet-visible, and molecular docking were applied for separately evaluating the interactions of two monomers with hydroxyapatite and collagen. Hydrophilicity tests and morphological observation were employed to characterize pretreated dentine. Microtensile bond strength (µTBS) and nanoleakage were investigated to evaluate the bonding performance. Hydroxyproline assay, in situ zymography, and matrix metalloproteinase-9 (MMP-9) activity assay were used to confirm the MMP inhibition. RESULTS: Chemoanalytic characterization confirmed the interactions of 10-MDP and PENTA with hydroxyapatite and collagen. The interactions of PENTA were weaker than 10-MDP. PENTA possessed better dentine tubule sealing after etching than 10-MDP. Dentine treated with PENTA was more hydrophilic than 10-MDP. 10-MDP and PENTA treating significantly increased the initial µTBS than the control group without primer conditioning. µTBS decreased significantly during aging, and the decrease was more severe in the PENTA group than 10-MDP. The 10-MDP and PENTA groups exhibited relatively less fluorescence than the control. The relative inhibition percentages of MMP-9 decreased in the order of 10-MDP-Ca salt, 10-MDP and PENTA. The 10-MDP, PENTA, and 10-MDP-Ca salt groups showed significantly lower hydroxyproline contents than the control. CONCLUSIONS: Although PENTA adsorbed on hydroxyapatite, it did not form a stable calcium salt. The interactions of 10-MDP with hydroxyapatite and collagen are different than those of PENTA. CLINICAL SIGNIFICANCE: The sealing of dentinal tubules by PENTA and the inhibition of MMP by 10-MDP and its calcium salts contribute to improving the dentine bonding durability.

Cells-Micropatterning Biomaterials for Immune Activation and Bone Regeneration.

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/ß-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.

Bamboo-Based Biomaterials for Cell Transportation and Bone Integration.

The construction of hierarchical porous structure in biomaterials is of great significance for improving nutrient transport and biological performance. However, it is still challenging to design porous bone substitutes with high strength and biological properties, which limits their clinical applications in load-bearing bone regeneration. Herein, based on hierarchical porous structure of renewable bamboo, the mineralized calcium phosphate/bamboo composite scaffolds with high strength and excellent transport performance are successfully prepared in combination of biotemplated approach and biomimetic mineralization. The mineralized biomaterials have simultaneously achieved high mechanical strength and low modulus, similar to those of cortical bone. Furthermore, the mineralized biomaterials exhibit good liquid transport capacity and can transport cells along anti-gravity direction. Based on density functional theory (DFT) calculations, the mineralized calcium phosphate reveals the optimal H2 O adsorption energy (-0.651 eV) and low diffusion energy barrier (0.743 eV), which is conducive to enhance hydrophilicity and liquid transport performance. Moreover, owing to the synergistic effect of the porous structure of biotemplate and bioactive mineralized components, the mineralized biomaterials possess enhanced bone integration and osteoconduction properties. The present study shed light on deeper understanding of mineralized biosourced materials, offering a strategy of combining green chemistry with tissue engineering to prepare eco-friendly biomaterials.