Systemic Type 2 Inflammation-Associated Atopic Dermatitis Exacerbates Periodontitis.

INTRODUCTION: Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis. METHODS: Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition. RESULTS: Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP+ osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix. CONCLUSIONS: These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

Hybrid Vibration and UV Fluorescence Technology for Rapid Imaging and Guidance for Manual Removal of Fish Bones from Fish Floss.

The objective of the proposed human-machine cooperation (HMC) workstation is to both rapidly detect calcium-based fish bones in masses of minced fish floss and visually guide operators in approaching and removing the detected fish bones by hand based on the detection of fingernails or plastic-based gloves. Because vibration is a separation mechanism that can prevent absorption or scattering in thick fish floss for UV fluorescence detection, the design of the HMC workstation included a vibration unit together with an optical box and display screens. The system was tested with commonly used fish (swordfish, salmon, tuna, and cod) representing various cooking conditions (raw meat, steam-cooked meat, and fish floss), their bones, and contaminating materials such as derived from gloves made of various types of plastic (polyvinylchloride, emulsion, and rubber) commonly used in the removal of fish bones. These aspects were each investigated using the spectrum analyzer and the optical box to obtain and analyze the fluorescence spectra and images. The filter was mounted on a charge-coupled device, and its transmission-wavelength window was based on the characteristic band for fish bones observed in the spectra. Gray-level AI algorithm was utilized to generate white marker rectangles. The vibration unit supports two mechanisms of air and downstream separation to improve the imaging screening of fish bones inside the considerable flow of fish floss. Notably, under 310 nm ultraviolet B (UVB) excitation, the fluorescence peaks of the raw fillets, steam-cooked meat, and fish floss were observed at for bands at longer wavelengths (500-600 nm), whereas those of the calcium and plastic materials occurred in shorter wavelength bands (400-500 nm). Perfect accuracy of 100% was achieved with the detection of 20 fish bones in 2 kg of fish floss, and the long test time of around 10-12 min results from the manual removal of these fish bones.

RICK regulates the odontogenic differentiation of dental pulp stem cells through activation of TNF-α via the ERK and not through NF-κB signaling pathway.

Dental pulp stem cells (DPSCs) are capable of both self-renewal and multilineage differentiation, which play a positive role in dentinogenesis. Studies have shown that tumor necrosis factor-α (TNF-α) is involved in the differentiation of DPSCs under pro-inflammatory stimuli, but the mechanism of action of TNF-α is unknown. Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK) is a biomarker of an early inflammatory response that plays a key role in modulating cell differentiation, but the role of RICK in DPSCs is still unclear. In this study, we identified that RICK regulates TNF-α-mediated odontogenic differentiation of DPSCs via the ERK signaling pathway. The expression of the biomarkers of odontogenic differentiation dental matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), biomarkers of odontogenic differentiation, increased in low concentration (1-10 ng/ml) of TNF-α and decreased in high concentration (50-100 ng/ml). Odontogenic differentiation increased over time in the odontogenic differentiation medium. In the presence of 10 ng/L TNF-α, the expression of RICK increased gradually over time, along with odontogenic differentiation. Genetic silencing of RICK expression reduced the expression of odontogenic markers DMP-1 and DSPP. The ERK, but not the NF-κB signaling pathway, was activated during the odontogenic differentiation of DPSCs. ERK signaling modulators decreased when RICK expression was inhibited. PD98059, an ERK inhibitor, blocked the odontogenic differentiation of DPSCs induced by TNF-α. These results provide a further theoretical and experimental basis for the potential use of RICK in targeted therapy for dentin regeneration.

Association between periodontitis and systemic lupus erythematosus: a meta-analysis.

OBJECTIVE: The objective of this study was to explore the association between periodontitis and systemic lupus erythematosus (SLE). METHODS: To identify eligible studies, the PubMed, EMBASE and Web of Science databases were searched from inception to 19 September 2019. Associations of periodontitis, and other periodontal parameters, with SLE were assessed. RESULTS: Ten studies involving 80,633 subjects were included in this meta-analysis. Pooled data showed a significant association between periodontitis and SLE (odds ratio=5.32, 95% confidence interval (CI) 1.69-16.78, p = 0.004). In addition, SLE patients had a higher prevalence of bleeding on probing (mean difference = 0.03, 95% CI 0.00-0.06, p = 0.02) and higher mean clinical attachment loss (mean difference = 0.69, 95% CI 0.39-1.00, p < 0.001). However, there were no significant differences between SLE and reference subjects in mean plaque index, gingival index, pocket depth or decayed, missing or filled teeth. CONCLUSIONS: This study demonstrates a significant association between periodontitis and SLE, which indicates that avoidance of periodontitis by maintaining oral health may be a simple and economical way to prevent SLE.

Protein Pretreatment of Microelectrodes Enables in Vivo Electrochemical Measurements with Easy Precalibration and Interference-Free from Proteins.

In vivo electrochemistry is one powerful strategy for probing brain chemistry. However, the decreases in sensitivity mainly caused by the adsorption of proteins onto electrode surface in short-term in vivo measurements unfortunately render great challenges in both electrode calibration and selectivity against the alternation of proteins. In this study, we observe that the pretreatment of carbon fiber microelectrodes (CFEs) with bovine serum albumin (BSA) would offer a simple but effective strategy to the challenges mentioned above. We verify our strategy for dopamine (DA) with conventionally used CFEs and for ascorbate with our previously developed carbon nanotube-modified CFEs. We find that, in artificial cerebral spinal fluid (aCSF) solution containing BSA, the current responses of the microelectrodes equilibrate shortly and the results for precalibration carried out in this solution are found to be almost the same as those for the postcalibration in pure aCSF. This observation offers a new solution to electrode calibration for in vivo measurements with a technical simplicity. Furthermore, we find that the use of BSA pretreated CFEs to replace bare CFEs would minimize the interference from the alternation of proteins in the brain. This study offers a new general and effective approach to in vivo electrochemistry with a high reliability and a simplified procedure.

Triterpenoid-Based Self-Healing Supramolecular Polymer Hydrogels Formed by Host-Guest Interactions.

Pentacyclic triterpenoids, a class of naturally bioactive products having multiple functional groups, unique chiral centers, rigid skeletons, and good biocompatibility, are ideal building blocks for fabricating versatile supramolecular structures. In this research, the natural pentacyclic triterpenoid glycyrrhetinic acid (GA) was used as a guest molecule for ß-cyclodextrin (ß-CD) to form a GA/ß-CD (1:1) inclusion complex. By means of GA and ß-CD pendant groups in N,N'-dimethylacrylamide copolymers, a supramolecular polymer hydrogel can be physically cross-linked by host-guest interactions between GA and ß-CD moieties. Moreover, self-healing of this hydrogel was observed and confirmed by step-strain rheological measurements, whereby the maximum storage modulus occurred at a [GA]/[ß-CD] molar ratio of 1:1. Additionally, these polymers displayed outstanding biocompatibility. The introduction of a natural pentacyclic triterpenoid into a hydrogel system not only provides a biocompatible guest-host complementary GA/ß-CD pair, but also makes this hydrogel an attractive candidate for tissue engineering.

Ferricyanide-backfilled cylindrical carbon fiber microelectrodes for in vivo analysis with high stability and low polarized potential.

The development of stable and reproducible methods for in vivo electrochemical monitoring of neurochemicals is of great physiological importance. In this study, we demonstrate ferricyanide-filled cylindrical carbon fiber microelectrodes (CFEs) of high stability and low polarized potential for in vivo electrochemical analysis. We first studied the voltammetric behavior of cylindrical CFEs by using a model system consisting of two separated cells each containing potassium ferricyanide (K3Fe(CN)6) or potassium ferrocyanide (K4Fe(CN)6). We observed that E1/2 values of the system were dependent on the ratio of the lengths of the cylindrical CFEs and of the concentrations of the redox species on both poles. Based on this property, we prepared the ferricyanide-backfilled cylindrical CFEs, and found that this kind of electrode exhibits a more stable current response and a lower polarized potential than the CFEs backfilled with KCl or Ru(NH3)6Cl3. Animal experiments with the ferricyanide-backfilled cylindrical CFEs demonstrate that this kind of electrode could be used for in vivo monitoring of neurochemical release with a high stability under some physiological conditions.

Evaluation of the influence exerted by different dental specialty backgrounds and measuring instrument reproducibility on esthetic aspects of maxillary implant-supported single crown.

OBJECTIVE: To evaluate the influence exerted by different dental specialty backgrounds as well as the validity and reproducibility of the Pink Esthetic Score/White Esthetic Score (PES/WES) and the modified Implant Crown Aesthetic Index (mod-ICAI) on the assessment of esthetic aspects of maxillary implants supported single-tooth prosthesis. MATERIAL AND METHODS: A total of fourteen examiners (Two orthodontists, two prosthodontists, two oral surgeons, two periodontists, two dental technicians, two dental assistants, and two postgraduate students in Implant Dentistry evaluated 20 photographs of single-implant-supported crowns and five photographs of unrestored teeth of esthetic zone in a two part study. The examiners assessed the photographs with each index (Pink Esthetic Score/White Esthetic Score and modified Implant Crown Aesthetic Index), twice with a week's interval. Orders of photographs were rearranged in the second assessment. RESULTS: Kruskal-Wallis test results showed significant differences among all the six specialties (P ≤ 0.001). DAs and periodontists had significantly better ratings than other specialties with both indices. Prosthodontists had the lowest mean rank scores regardless of the index. Interobserver agreement was also lowest between the two prosthodontists (4-28%), rest of the groups had low-to-moderate agreement (20-80%) when limited allowance was accepted. With mod-ICAI, more interobserver agreement was noted within the specialty group than with PES/WES. CONCLUSIONS: The PES/WES and the modified ICAI can be reliable estimates of esthetic outcomes. The assessor degree of specialization affected the esthetic evaluation with both the PES/WES and the modified ICAI. DAs and periodontists were identified to provide more favorable ratings than other specialties while prosthodontists were most critical in this study. With modified ICAI, more interobserver agreement within specialty resulted. The interexaminer agreement may be increased if more tolerance of 1-2 points is considered.

Vertically aligned carbon nanotube-sheathed carbon fibers as pristine microelectrodes for selective monitoring of ascorbate in vivo.

Using as-synthesized vertically aligned carbon nanotube-sheathed carbon fibers (VACNT-CFs) as microelectrodes without any postsynthesis functionalization, we have developed in this study a new method for in vivo monitoring of ascorbate with high selectivity and reproducibility. The VACNT-CFs are formed via pyrolysis of iron phthalocyanine (FePc) on the carbon fiber support. After electrochemical pretreatment in 1.0 M NaOH solution, the pristine VACNT-CF microelectrodes exhibit typical microelectrode behavior with fast electron transfer kinetics for electrochemical oxidation of ascorbate and are useful for selective ascorbate monitoring even with other electroactive species (e.g., dopamine, uric acid, and 5-hydroxytryptamine) coexisting in rat brain. Pristine VACNT-CFs are further demonstrated to be a reliable and stable microelectrode for in vivo recording of the dynamic increase of ascorbate evoked by intracerebral infusion of glutamate. Use of a pristine VACNT-CF microelectrode can effectively avoid any manual electrode modification and is free from person-to-person and/or electrode-to-electrode deviations intrinsically associated with conventional CF electrode fabrication, which often involves electrode surface modification with randomly distributed CNTs or other pretreatments, and hence allows easy fabrication of highly selective, reproducible, and stable microelectrodes even by nonelectrochemists. Thus, this study offers a new and reliable platform for in vivo monitoring of neurochemicals (e.g., ascorbate) to largely facilitate future studies on the neurochemical processes involved in various physiological events.

Plastic debris mediates bacterial community coalescence by breaking dispersal limitation in the sediments of a large river.

Plastic debris has recently been proposed as a novel habitat for bacterial colonization, which can raise perturbations in bacterial ecology after burial in riverine sediments. However, community coalescence, as a prevalent process involving the interrelationships of multiple communities and their surrounding environments, has been rarely discussed to reveal the impact of the plastisphere on sedimentary bacterial community. This study analyzed the bacterial community in plastic debris and sediment along the Nujiang River, elucidating the role of the plastisphere in mediating community coalescence in sediments. Our results demonstrated that the plastisphere and sedimentary bacterial communities exhibited distinct biogeography along the river (r = 0.694, p < 0.01). Based on overlapped taxa and SourceTracker, the extent of coalescence between adjacent communities was in following orders: plastic-plastic (0.589) > plastic-sediment (0.561) > sediment-sediment (0.496), indicating the plastisphere promoted bacterial community coalescence along the river. Flow velocity and geographic distance were the major factors driving the plastisphere changes, suggesting that the plastisphere were vulnerable to dispersal. The null model and the neutral model provided additional support for the higher immigration ability of the plastisphere to overcome dispersal limitation, highlighting the potential importance of the plastisphere in community coalescence. Network analysis indicated the critical role of keystone species (Proteobacteria, Bacteroidetes, and Gemmatimonadetes) in mediating the coalescence between sedimentary bacterial community and the plastisphere. In summary, the plastisphere could mediate the coalescence of bacterial communities by overcoming dispersal limitation, which provides new perspectives on the plastisphere altering bacterial ecology in riverine sediments.

Enhancing diabetic wound healing with a pH/glucose dual-responsive hydrogel for ROS clearance and antibacterial activity.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

NOD2 is involved in regulating odontogenic differentiation of DPSCs suppressed by MDP through NF-κB/p65 signaling.

Dental pulp stem cells (DPSCs) are well known for their capable of both self-renewal and multilineage differentiation. Dental tissue diseases, include caries, are often accompanied by inflammatory microenvironment, and muramyl dipeptide (MDP) is involved in the inflammatory stimuli to influence the differentiation of DPSCs. Nucleotide-binding oligomerization domain 2 (NOD2), a member of the cytosolic Nod-like receptor (NLR) family, plays a key role in inflammatory homeostasis regulation, but the role of NOD2 in DPSCs differentiation under inflammatory is still unclear. In this study, we identified that MDP suppressed odontogenic differentiation of DPSCs via NOD2/ NF-κB/p65 signaling pathway. Alizarin red staining and ALP activity showed the odontogenic differentiation was suppressed by MDP in a concentration-dependent manner, and the expression of dentin differentiation marker protein dentin matrix protein 1 (DMP-1) and dentin Sialophosphoprotein (DSPP) also indicated the same results. The expression of NOD2 increased gradually with the concentration of MDP as well as the phosphorylation and nuclear translocation of p65, which meant NF-κB signaling pathway was activated. Further, the interference of NOD2 inhibited the phosphorylation and nuclear translocation of p65 and reversed the MDP-mediated decrease of odontoblast differentiation of DPSCs. Our study showed that MDP can inhibit the odontoblast differentiation of DPSCs in a concentration-dependent manner. The NF-κB signaling pathway was activated by increasing expression of NOD2. Interference of NOD2 reversed the negative ability odontoblast differentiation of DPSCs in the inflammatory environment. Our study might provide a theoretical basis for the clinical treatment for dentinogenesis of DPSCs.

A Uterus-Inspired Niche Drives Blastocyst Development to the Early Organogenesis.

The fundamental physical features such as the mechanical properties and microstructures of the uterus need to be considered when building in vitro culture platforms to mimic the uterus for embryo implantation and further development but have long been neglected. Here, a uterus-inspired niche (UN) constructed by grafting collagen gels onto polydimethylsiloxane based on a systematic investigation of a series of parameters (varying concentrations and thicknesses of collagen gel) is established to intrinsically specify and simulate the mechanics and microstructures of the mouse uterus. This brand-new and unique system is robust in supporting embryo invasion, as evidenced by the special interaction between the embryos and the UN system and successfully promoting E3.5 embryo development into the early organogenesis stage. This platform serves as a powerful tool for developmental biology and tissue engineering.

Fabrication of Host-Guest Complexes between Adamantane-Functionalized 1,3,4-Oxadiazoles and ß-Cyclodextrin with Improved Control Efficiency against Intractable Plant Bacterial Diseases.

Supramolecular chemistry provides huge potentials and opportunities in agricultural pest management. In an attempt to develop highly bioactive, eco-friendly, and biocompatible supramolecular complexes for managing intractable plant bacterial diseases, herein, a type of interesting adamantane-functionalized 1,3,4-oxadiazole was rationally prepared to facilitate the formation of supramolecular complexes via ß-cyclodextrin-adamantane host-guest interactions. Initial antibacterial screening revealed that most of these adamantane-decorated 1,3,4-oxadiazoles were obviously bioactive against three typically destructive phytopathogens. The lowest EC50 values could reach 0.936 (III18), 0.889 (III18), and 2.10 (III19) µg/mL against the corresponding Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Next, the representative supramolecular binary complex III18@ß-CD (binding mode 1:1) was successfully fabricated and characterized by 1H nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), high-resolution mass spectrometry (HRMS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Eventually, correlative water solubility and foliar surface wettability were significantly improved after the formation of host-guest assemblies. In vivo antibacterial evaluation found that the achieved supramolecular complex could distinctly alleviate the disease symptoms and promote the control efficiencies against rice bacterial blight (from 34.6-35.7% (III18) to 40.3-43.6% (III18@ß-CD)) and kiwi canker diseases (from 41.0-42.3% (III18) to 53.9-68.0% (III18@ß-CD)) at 200 µg/mL (active ingredient). The current study can provide a feasible platform and insight for constructing biocompatible supramolecular assemblies for managing destructive bacterial infections in agriculture.

[The relationship between serum level of leptin and oxidative stress in patients with hyperglycemia crisis].

OBJECTIVE: To investigate the relationship between the levels of serum leptin and oxidative stress in patients with hyperglycemia crisis. METHODS: A total of 96 patients with diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH) were treated on a low-dose insulin protocol using intravenous infusion of insulin with the established rate of 0.1 Uxkg(-1)xh(-1), with the patients on intravenous fluids and receiving nutrition by mouth and vein. The levels of serum leptin, 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)), the activities of superoxide dismutase (SOD), total antioxidant capacity (TAC) and the contents of malondialdehyde (MDA) in 96 patients with hyperglycemia crisis on admission and after insulin therapy with resolution of hyperglycemia and ketoacidosis (72 hours) were measured. Another 35 healthy individuals served as normal control. RESULTS: The activities of SOD, TAC and the levels of leptin before treatment were lower in patients with hyperglycemia crisis than in normal controls, and the levels of MDA and 8-iso-PGF(2 alpha) were more markedly elevated than those in normal controls (all P<0.05). The activities of SOD, TAC and the levels of leptin in patients after treatment were significantly higher than those in patients before treatment, and the levels of MDA and 8-iso-PGF(2 alpha) were significantly lower than those in patients on admission (all P<0.05). There was significant positive correlation between leptin and MDA in patients before treatment (r=0.38, P<0.05), and the level of leptin was negatively correlated with MDA and 8-iso-PGF(2 alpha) in patients after treatment (r(1)=-0.35, r(2)=-0.37, both P<0.05). In stepwise regression analysis, MDA and 8-iso-PGF(2 alpha) showed a significant association with leptin. CONCLUSION: The levels of leptin are significantly lowered in patients with hyperglycemia crisis. Oxidative stress may participate in determining the leptin level in hyperglycemia crisis.

Biobased polymeric surfactant: Natural glycyrrhizic acid-appended homopolymer with multiple pH-responsiveness.

Even though amphiphilic natural products have been widely employed in cosmetics, food, and pesticide formulations, the development of a compound with stimuli-responsiveness is still highly significant. Inspired by the low cost, biocompatibility, pH resistance and amphiphilicity of natural glycyrrhizic acid (Gly), we designed and synthesized an amphiphilic homopolymer, namely, poly(glycyrrhizic acid) (PGly), via reversible addition-fragmentation chain transfer (RAFT) polymerization. The two carboxylic groups on the side chain of PGly promoted it as a multiple pH-responsive polymeric surfactant. As the pH was decreased from 5.0 to 2.0, the PGly transformed from the extension to the coil state and further aggregated into nano/micro particles. During this process, the surface charge, surfactivity and diffusion rate of PGly decreased along with the decreasing pH. Moreover, with ultrasonic treatment (UT), the aggregates that formed at lower pH values decreased (pH 3.0 and 2.0) or almost disappeared (pH 4.0), indicating that these insoluble aggregates at lower pH were broken by UT and were then reassembled into the compacted PGly nanoparticles. Based on the above results, the emulsion (20 wt% xylene) stabilized by 0.1 wt% PGly was fabricated using ultrasonic emulsification for which the diameter distribution and the dispersion state can be reversibly regulated by pH (2.0-5.0). This natural polymeric surfactant exhibited a favorable surfactivity and multiple pH responsiveness in the preparation of emulsions, showing its potential for application in the controlled release of pesticide formulations and in the recovery of organic pollution.

[Arg-Gly-Asp-containing peptide combining with the biomimetic and modified PLGA-(ASP-PEG)].

Arg-Gly-Asp-(RGD) containing peptide characterized as the non-viral gene vector was synthesized to modify the surface of PLGA-(ASP-PEG). The Peptide (K16-GRGDSPC) was synthesized. PLGA-(ASP-PEG) was executed into chips A, B and C. Chip C was regarded as control. Chips A and B reacted with the cross-linker, then Chip A reacted with peptide. Mass spectrometry (MS) and high performance liquid chromatography (HPLC) detected the molecular weight and the purity of peptide. Sulphur in the surface of materials was detected by X-ray photoelectron spectrometry (XPS). The peptide content in the residual solution was detected by Spectrometer. HPLC showed the peptide purity was 94.13%; MS showed the molecular weight was 2741.26. XPS revealed the binding energy of the sulphur in reacted Chip A was 164 eV in reacted Chip B, 164eV and 162 eV; the ratios of carbon to sulphur in reacted Chip A and B were 99.746:0.1014 and 99.574:0.4255, respectively. There was no sulphur in Chip C. The optical density value (OD) of the resident solution was 0.069. The peptide density of reacted Chip A was 0.04 mg/mm2. The peptide was manufactured and linked to the surface of the biomimetic PLGA-(ASP-PEG) with the cross-linker.

Crosstalk between Toll-like receptor 3 and Notch signaling contributes to CD14+ monocytes activity in enterovirus 71 infected hand, foot, and mouth disease.

Interaction between Toll-like receptor (TLR) and Notch signaling contributes to inflammatory response in nephropathy and fungicidal infection, however, the role of this crosstalk remains not fully elucidated in enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). The aim of this study was to investigate the crosstalk between TLR and Notch in inflammatory regulation in EV71 infection. Thirty-seven EV-71-indcued HFMD (16 mild and 21 severe cases) and eleven normal control (NC) were enrolled. CD14+ monocytes were purified, and were stimulated with either TLR3/4 agonists [poly(I: C) or LPS] or Notch signaling inhibitor. TLRs and Notch receptors expression, proinflammatory cytokines production, and important molecules in signaling pathways were measured by real-time PCR, ELISA, and Western blot. TLR3 and TLR4 was significantly elevated in CD14+ monocytes from HFMD patients than NC. Notch1 and Notch2 mRNA was also remarkably increased in CD14+ monocytes from severe HFMD. Poly(I: C) stimulation resulted in robust increase of IL-8, IL-6, and TNF-α by CD14+ monocytes in severe HFMD compared to NC. Activation of Notch1, Notch2, and target genes, Hes1 and Hes5 was also enhanced upon ploy(I: C) treatment. Although inhibition of Notch signaling did not affect TLR3 expression, poly(I: C)-induced inflammatory response was robustly attenuated, which was accompanied by silencing Src phosphorylation in CD14+ monocytes from severe HFMD patients. The current data indicated that crosstalk between TLR3 and Notch signaling modulated CD14+ monocytes function and inflammatory responses in the progression of EV71-induced HFMD.

Resveratrol delivery by ultrasound-mediated nanobubbles targeting nucleus pulposus cells.

AIM: To improve nucleus pulposus cell-targeted therapy for intervertebral disc degeneration (IDD) by fabricating a novel kind of ultrasound (US)-mediated poly(lactic-co-glycolic acid) nanobubbles (NBs) as a means of targeted drug delivery. MATERIALS & METHODS: The resveratrol (RES)-embedded NBs were synthesized using a double-emulsion method. The active NP cell-targeting biomarker CDH2 antibody (AbCDH2) was further conjugated to the NBs using a carbodiimide method. Then, this RES/AbCDH2 NBs were examined by physical properties, specifc cell-targeting ability, anticatabolism effect in vitro and in vivo. RESULTS: RES/AbCDH2 NBs exhibited high RES-loading efficiency, and US triggered accelerated RES release. Furthermore, RES/AbCDH2 NB treatment exhibited excellent anticatabolic ability in vitro; and in an IDD rabbit model, US-mediated RES/AbCDH2 NB injection effectively retarded the degenerative process of the intervertebral disc in vivo. CONCLUSION: The combination of US irradiation and drug delivery through RES/AbCDH2 NBs can be considered as a novel treatment option for IDD.