Protease-Loaded CuS Nanoparticles with Synergistic Photothermal/Dynamic Therapy against F. nucleatum-Induced Periodontitis.

Periodontitis is a chronic inflammatory disease induced by a plaque biofilm, which can lead to the destruction of the periodontal support tissue and even teeth loss. The common strategies of periodontitis treatment are to eliminate bacterial/biofilm-related inflammation and subsequently inhibit alveolar bone resorption, for which antibiotic therapy is the most traditional one. However, impenetrable polymeric substances on bacterial biofilms make it difficult for traditional antimicrobial agents to take effect. In this study, a novel nanoparticle protease-loaded CuS NPs was developed, combining the advances of photodynamic and photothermal therapy from CuS and enzymatic degradation of the biofilm by a protease. The photothermal activity and the reactive oxygen generation capacity of the designed nanoparticles were verified by the experimental results, constituting the basis of antibacterial function. Next, the high antimicrobial activity of CuS@A NPs onFusobacterium nucleatumand its biofilm was demonstrated. The proper hemo/cytocompatibility of CuS-based NPs was demonstrated by in vitro assays. Last, effective treatment against periodontitis was achieved in a rat periodontitis model through the significant efficacy of inhibiting bone resorption and alleviating inflammation. Thus, the developed CuS@A NPs prove a promising material for the management of periodontitis.

Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing.

Probiotics are beneficial bacteria located in the oral cavity which exhibit antimicrobial properties and contribute to the regulation of immune function and the modulation of tissue repair. Fucoidan (FD), a marine prebiotic, may further enhance the ability of probiotics to promote ulcer healing. However, neither FD nor probiotics are attached to the oral cavity and neither are well-suited for oral ulcer healing owing to the wet and highly dynamic environment. In this study, probiotic-loaded calcium alginate/fucoidan composite hydrogels were developed for use as bioactive oral ulcer patches. The well-shaped hydrogels exhibited remarkable wet-tissue adhesion, suitable swelling and mechanical properties, sustained probiotic release, and excellent storage durability. Moreover, in vitro biological assays demonstrated that the composite hydrogel exhibited excellent cyto/hemocompatibility and antimicrobial effects. Importantly, compared to commercial oral ulcer patches, bioactive hydrogels show superior therapeutic capability for promoting ulcer healing in vivo by enhancing cell migration, inducing epithelial formation and orderly collagen fiber deposition, as well as facilitating neovascularization. These results demonstrate that this novel composite hydrogel patch demonstrates great potential for the treatment of oral ulcerations.

Human gingival mesenchymal stem cell-derived exosomes cross-regulate the Wnt/ß-catenin and NF-κB signalling pathways in the periodontal inflammation microenvironment.

AIM: To examine the immunomodulatory effect of exosomes originating from gingival mesenchymal stem cells (GMSC-Exo) on periodontal bone regeneration and its role in the regulation of the nuclear-factor kappaB (NF-κB) and Wnt/ß-catenin pathways in the periodontal inflammatory microenvironment. MATERIALS AND METHODS: First, periodontal ligament stem cells (PDLSCs) were treated with GMSC-Exo or Porphyromonas gingivalis-derived lipopolysaccharide (P.g-LPS) in vitro. Quantitative real-time PCR (qRT-PCR) and western blot were carried out to detect the expressions of osteogenic differentiation-related factors in cells. Further, PDLSCs were treated with P.g-LPS or inhibitors. The expression of NF-κB pathway-related factors as well as of Wnt/ß-catenin pathway-related factors were detected by qRT-PCR and western blot. RESULTS: GMSC-Exo treatment promoted the expression of osteogenic differentiation-related factors within PDLSCs in both normal and inflammatory environments. Further investigations showed that GMSC-Exo could also inhibit the P.g-LPS-induced activation of the NF-κB pathway, leading to the up-regulation of the Wnt/ß-catenin pathway. When the Wnt/ß-catenin signalling was blocked, the inhibitory effect of GMSC-Exo on the NF-κB pathway was abolished. CONCLUSIONS: GMSC-Exo could promote the osteogenic differentiation of PDLSCs. There could be mutually exclusive regulatory roles between the NF-κB and Wnt/ß-catenin signalling pathways in a periodontal inflammatory environment. GMSC-Exo exhibited an effective cross-regulation ability for both pathways.

Verification of the detachment-transport coupling relationship of rill erosion using colluvium material in steep nonerodible slopes.

The detachment-transport coupling equation by Foster and Meyer is a classical equation that describes the relationship between detachment and transport. The equation quantifies the relationship between sediment loads and soil detachment rates, deepens the understanding of soil erosion and provides a reliable basis for the establishment of an erosion model. However, the applicability of this equation to slopes with gradients greater than 47% is limited. In this work, the detachment-transport coupling relationship is investigated using the colluvium material of Benggang. A nonerodible rill flume 4 m long and 0.12 m wide was adopted. The slope gradient ranged from 27% to 70%, the unit flow discharge ranged from 0.56 × 10-3 to 3.33 × 10-3 m2 s-1, and the sediment transport capacity (Tc ) was measured under each slope and discharge combination. The sediment was inputted into the flume according to the predetermined sediment addition rate (from 0% to 100% of Tc ), and the detachment rate (Dr ) under each combination of the slope and discharge was measured. Dr linearly decreased with increasing sediment loads, which is consistent with the detachment-transport coupling equation by Foster and Meyer. The linear equations can predict the detachment capacity (Dc ) and Tc well (Nash-Sutcliffe efficiency coefficient (NSE) = 0.98 for Dc , and NSE = 0.99 for Tc ). The detachment-transport coupling equation can adequately predict the Dr (NSE = 0.89). However, its applicability to slopes of <47% (NSE: 0.92-0.96) was greater than that to slopes of ≥47% (NSE: 0.81-0.89), and the predicted Dr under Tc levels of 20% and 40% were higher than the measured values, while the predicted value under a Tc level of 80% was lower than the measured value. In summary, the detachment-transport coupling equation by Foster and Meyer can accurately reflect the negative feedback relationship between detachments and transports along steep-slope fixed beds and is suitable for colluvial deposit research. The results provide a basis for the construction of steep-slope colluvial deposit erosion models. In the future, the study of the hydrodynamic characteristics of sediment transport processes should be strengthened to clarify the detachment-transport effect of flows through hydrodynamics.

Effects of Coupled-/soluble-Copper, Generating from Copper-doped Titanium Dioxide Nanotubes on Cell Response.

BACKGROUND: Endothelialization in vitro is a very common method for surface modification of cardiovascular materials. However, mature endothelial cells are not suitable because of the difficulty in obtaining and immunogenicity. METHODS: In this patent work, we determined the appropriate amount of copper by constructing a copper- loaded titanium dioxide nanotube array that can catalyze the release of nitric oxide, compared the effects of coupled-/soluble-copper on stem cells, and then induced stem cells to differentiate into endothelial cells. RESULTS: The results showed that it had a strong promotion effect on the differentiation of stem cells into endothelial cells, which might be used for endothelialization in vitro. CONCLUSION: SEM and EDS results prove that a high content of copper ions are indeed doped onto the surface of nanotubes with small amounts of Cu release. The release of NO confirms that the release of several samples within a period of time is within the physiological concentration.

Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats.

Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.

Enhanced Eradication of Enterococcus faecalis Biofilms by Quaternized Chitosan-Coated Upconversion Nanoparticles for Photodynamic Therapy in Persistent Endodontic Infections.

Due to the persistent presence of Enterococcus faecalis biofilms in apical root canals, persistent endodontic infections (PEIs) have always been an intractable disease to solve. The conventional root canal disinfectants (e.g., calcium hydroxide, chlorhexidine) are arduous to scavenge the stubborn infection. With the progress of nanomedicine in the biomedical field, antimicrobial photodynamic therapy (aPDT) is emerging as a prospective anti-infective therapy for PEIs. Herein, quaternized chitosan (QCh) modified upconversion nanoparticles (UCNP)@SiO2/methylene blue (MB) are developed with enhanced antibacterial/biofilm performance for aPDT in PEIs. QCh is coated on the UCNP@SiO2/MB by testing the changes in diameter, chemical functional group, and charge. Interestingly, QCh also increases the conversion efficiency of UCNP to generate more reactive oxygen species (ROS). Furthermore, the prepared UCNP@SiO2/MB@QCh exhibits highly effective antibacterial activity against free E. faecalis and related biofilm in vitro and extracted teeth. Importantly, the additional QCh with positive charges enhance UCNP@SiO2/MB@QCh contact with E. faecalis (negative charges) through electrostatic interaction. Then, UCNP@SiO2/MB@QCh could stick close to the E. faecalis and generate ROS under the irradiation by a 980 nm laser. The in vitro cellular test shows that UCNP@SiO2/MB@QCh has acceptable cytocompatibility. Thus, UCNP@SiO2/MB@QCh could offer a novel strategy for the potential aPDT clinical applications in the treatment of PEIs.

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells.

This study aimed to explore the effects of exosomes derived from human gingival mesenchymal stem cells (GMSC-Exo) on the inflammatory response of periodontal ligament stem cells (PDLSCs) in an inflammatory microenvironment in order to restore the regenerative potential of PDLSCs, which promotes periodontal tissue regeneration in patients with periodontitis. Periodontitis is a chronic infectious disease characterized by periodontal tissue inflammation and alveolar bone destruction. PDLSCs are regarded as promising seed cells for restoring periodontal tissue defects because of their ability to regenerate cementum/PDL-like tissue and alveolar bone. However, PDLSCs in the inflammatory environment show significantly attenuated regenerative potential. GMSC-Exo have been reported to have anti-inflammatory and immunosuppressive properties. In this study, we investigated the effects of GMSC-Exo on the inflammatory response of PDLSCs induced by lipopolysaccharides (LPS). LPS was used to simulate the inflammatory microenvironment of periodontitis in vitro. GMSC-Exo were extracted from the culture supernatant of GMSCs by ultracentrifugation. We found that GMSC-Exo attenuated the inflammatory response of PDLSCs induced by LPS. Furthermore, compared to treatment with LPS, treatment with GMSC-Exo attenuated the expression of NF-κB signaling and Wnt5a in LPS-induced PDLSCs. In conclusion, we confirmed that GMSC-Exo could suppress the inflammatory response of PDLSCs by regulating the expression of NF-κB signaling and Wnt5a, which paves the way for the establishment of a therapeutic approach for periodontitis.

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform.

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Influence of hyperocclusion on the remodeling of gingival tissues.

OBJECTIVE: The purpose of this study was to observe the effect of hyperocclusion on the remodeling of gingival tissues and detect the related signaling pathways. DESIGN: Hyperocclusion models were established by tooth extraction in mice. The mice were sacrificed at 3, 7, 14, 28, or 56 days after the surgery, and the left mandibular first molars with gingival tissues were isolated and examinations were focused on the gingival tissues. Apoptotic cells were examined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technology. Proliferating cells, p65, inflammatory cytokines, and ß-catenin were detected using immunohistochemical methods. RESULTS: A series of apoptosis and proliferation responses were triggered in stressed gingival tissues. It was observed that the levels of p65, proinflammatory factors including interleukin-1ß and tumor necrosis factor-α in extraction group were higher compared with those from mice with intact dentition, and peaked on days 14, 14 and 7 respectively. The expression of ß-catenin was increased under hyperocclusion situations, peaked on day 14, and declined to the initial levels over time. CONCLUSIONS: The results of this study suggest that hyperocclusion causes remodeling of the gingival tissues by activating a series of adaptive responses. Both nuclear factor kappa B and Wnt/ß-catenin signaling pathways may be responsible for those adaptive responses though the exact mechanism is not clear.

Projection from the basolateral amygdala to the anterior cingulate cortex facilitates the consolidation of long-term withdrawal memory.

The process through which early memories are transferred to the cerebral cortex to form long-term memories is referred to as memory consolidation, and the basolateral amygdala (BLA) is an important brain region involved in this process. Although functional connections between the BLA and multiple brain regions are critical for the consolidation of withdrawal memory, whether the projection from the BLA to the anterior cingulate cortex (ACC) is involved in the formation or consolidation of withdrawal memory remains unclear. In this paper, we used a chemical genetic method to specifically label the BLA-ACC projection in a combined morphine withdrawal and conditioned place aversion (CPA) animal model. We found that (1) the inhibition of the BLA-ACC projection during conditioning had no effects on the formation of early withdrawal memory; (2) the inhibition of the BLA-ACC projection had no effects on the retrieval of either early or long-term withdrawal memory; and (3) the persistent inhibition of the BLA-ACC projection after early withdrawal memory formation could inhibit the formation of long-term withdrawal memory and decrease Arc protein expression in the ACC. These results suggested that the persistent activation of the BLA-ACC projection after the formation of early withdrawal memory facilitates the formation of long-term withdrawal memory by increasing the plasticity of ACC neurons.

Size-controllable carbon spheres doped Ni (II) for enhancing the catalytic oxidation of methanol.

Ni(II)/CSs were prepared using a simple two-step hydrothermal method. The morphology and composition of the catalysts were studied with scanning electron microscope, transmission electron microscope, and X-ray diffraction. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy showed that the surface of the prepared carbon spheres was rich in hydroxyl groups, which was beneficial to remove CO intermediates, and therefore, improving the catalytic efficiency and the antipoisoning ability of the catalysts. The results of cyclic voltammetry and chronoamperometry showed that the electrocatalytic activity and stability of Ni(II)/CSs were higher than that of unloaded NiAc under alkaline environment. When the nickel content was 5 wt.%, the peak oxidation current density of methanol on Ni(II)/CSs electrocatalyst reached the maximum of 34.54 mA/cm2, which was about 1.8 times that of unloaded NiAc. These results indicate that Ni(II)/CSs has potential applications in the electrocatalytic oxidation of methanol.

The self-organized differentiation from MSCs into SMCs with manipulated micro/Nano two-scale arrays on TiO2 surfaces for biomimetic construction of vascular endothelial substratum.

The endothelialization on biomaterial surface has been seen as an important strategy to solve the clinic problems with the cardiovascular implant device. However, the continuous and large surfaces such as artificial heart or artificial cardiac valve cannot maintain the structural and functional stability of the endothelium without the supply of substratum structures. Herein, we combined the micro/nano technology of material surface engineering and the tissue engineering technology to construct the biomimetic vascular endothelial substratum for high quality and complete endothelialization through inducing self-organized differentiation from MSCs to SMCs, controlling their self-aggregation structure and further manipulating micro-tissue on the surface. In the present work, the micro/nano two-scale features of surface were manipulated by preparing the micro arrays of TiO2 nanotubes on titanium surface. The responses of MSCs to these surfaces revealed that the MSCs could be highly regulated and then their self-organized differentiation to SMCs could be induced and improved based on anchoring of the adhesion complex protein and traction of F-actin adjusted by the micro/nano features of the surfaces. Besides, SMCs' self-aggregation structure could also be adjusted effectively by manipulating micro/nano features on two-scale surfaces, and three types of tissue-like structures could be achieved for the further use in formation and surface manipulation of micro-tissue and biomimetic construction of vascular endothelial substratum.

The co-deposition coating of collagen IV and laminin on hyaluronic acid pattern for better biocompatibility on cardiovascular biomaterials.

Construct a coating to repair the endothelium function is the ordinary and effective method to get out of the troubles which introduced by the cardiovascular implant devices. It indeed has plenty works on function construction which could inhibit the hyperplasia or accelerate the endothelialization with different functional proteins or molecules. However, a complete and healthy endothelium couldn't survive without the environment around. Thus, a logical biomimetic reconstruction with structure and function factors which using hyaluronic acid patterns to imitate the blood flow shear stress and co-depositing collagen type IV and laminin to achieve the biofunction of basement membrane had been proposed and realized in this work. After the tests of hemocompatibility, cytocompatibility and tissue compatibility, it had been indicated that this biomimetic coating could inhibit the adhesion of platelets, promote the proliferation and biofunction of endothelium cells, regulate smooth muscle cells with contractile phenotype and have much lower inflammatory response which might be a meaningful strategy on reconstruction and repairing of endothelium.

Research on the rapid and accurate positioning and orientation approach for land missile-launching vehicle.

Getting a land vehicle's accurate position, azimuth and attitude rapidly is significant for vehicle based weapons' combat effectiveness. In this paper, a new approach to acquire vehicle's accurate position and orientation is proposed. It uses biaxial optical detection platform (BODP) to aim at and lock in no less than three pre-set cooperative targets, whose accurate positions are measured beforehand. Then, it calculates the vehicle's accurate position, azimuth and attitudes by the rough position and orientation provided by vehicle based navigation systems and no less than three couples of azimuth and pitch angles measured by BODP. The proposed approach does not depend on Global Navigation Satellite System (GNSS), thus it is autonomous and difficult to interfere. Meanwhile, it only needs a rough position and orientation as algorithm's iterative initial value, consequently, it does not have high performance requirement for Inertial Navigation System (INS), odometer and other vehicle based navigation systems, even in high precise applications. This paper described the system's working procedure, presented theoretical deviation of the algorithm, and then verified its effectiveness through simulation and vehicle experiments. The simulation and experimental results indicate that the proposed approach can achieve positioning and orientation accuracy of 0.2 m and 20″ respectively in less than 3 min.

Research on Parameter Estimation Methods for Alpha Stable Noise in a Laser Gyroscope's Random Error.

Alpha stable noise, determined by four parameters, has been found in the random error of a laser gyroscope. Accurate estimation of the four parameters is the key process for analyzing the properties of alpha stable noise. Three widely used estimation methods-quantile, empirical characteristic function (ECF) and logarithmic moment method-are analyzed in contrast with Monte Carlo simulation in this paper. The estimation accuracy and the application conditions of all methods, as well as the causes of poor estimation accuracy, are illustrated. Finally, the highest precision method, ECF, is applied to 27 groups of experimental data to estimate the parameters of alpha stable noise in a laser gyroscope's random error. The cumulative probability density curve of the experimental data fitted by an alpha stable distribution is better than that by a Gaussian distribution, which verifies the existence of alpha stable noise in a laser gyroscope's random error.