Delocalization Engineering of Heme-Mimetic Artificial Enzymes for Augmented Reactive Oxygen Catalysis.

Developing artificial enzymes based on organic molecules or polymers for reactive oxygen species (ROS)-related catalysis has broad applicability. Herein, inspired by porphyrin-based heme mimics, we report the synthesis of polyphthalocyanine-based conjugated polymers (Fe-PPc-AE) as a new porphyrin-evolving structure to serve as efficient and versatile artificial enzymes for augmented reactive oxygen catalysis. Owing to the structural advantages, such as enhanced π-conjugation networks and π-electron delocalization, promoted electron transfer, and unique Fe-N coordination centers, Fe-PPc-AE showed more efficient ROS-production activity in terms of Vmax and turnover numbers as compared with porphyrin-based conjugated polymers (Fe-PPor-AE), which also surpassed reported state-of-the-art artificial enzymes in their activity. More interestingly, by changing the reaction medium and substrates, Fe-PPc-AE also revealed significantly improved activity and environmental adaptivity in many other ROS-related biocatalytic processes, validating the potential of Fe-PPc-AE to replace conventional (poly)porphyrin-based heme mimics for ROS-related catalysis, biosensors, or biotherapeutics. It is suggested that this study will offer essential guidance for designing artificial enzymes based on organic molecules or polymers.

Efficient photocatalytic degradation of ciprofloxacin by graphite felt-supported MnS/Polypyrrole composite: Dominant reactive species and reaction mechanisms.

The accumulation of antibiotics in aquatic environments poses a serious threat to human health. Photocatalytic degradation is a promising method for removing antibiotics from water, but its practical implementation requires improvements in photocatalyst activity and recovery. Here, a novel graphite felt-supported MnS/Polypyrrole composite (MnS/PPy/GF) was constructed to achieve effective adsorption of antibiotics, stable loading of photocatalyst, and rapid separation of spatial charge. Systematic characterization of composition, structure and photoelectric properties indicated the efficient light absorption, charge separation and migration of the MnS/PPy/GF, which achieved 86.2% removal of antibiotic ciprofloxacin (CFX), higher than that of MnS/GF (73.7%) and PPy/GF (34.8%). The charge transfer-generated 1O2, energy transfer-generated 1O2, and photogenerated h+ were identified as the dominant reactive species, which mainly attacked the piperazine ring in the photodegradation of CFX by MnS/PPy/GF. The •OH was confirmed to participate in the defluorination of CFX via hydroxylation substitution. The MnS/PPy/GF-based photocatalytic process could ultimately achieve the mineralization of CFX. The facile recyclability, robust stability, and excellent adaptability to actual aquatic environments further confirmed MnS/PPy/GF is a promising eco-friendly photocatalyst for antibiotic pollution control.

Clinical and computed tomographic evaluations of periodontal phenotypes in a Chinese population: a cross-sectional study.

OBJECTIVES: To investigate the diagnostic value of probe transparency related to gingival thickness (GT) and keratinized gingival width (KGW) at individual and site levels and explore the relationship of buccal bone plate thickness (BT) with GT and KGW. MATERIALS AND METHODS: A total of 1,606 teeth from 167 patients with periodontally healthy maxillary anterior region were included. GT was measured with probe transparency and transgingival probing. KGW was measured directly. BTs were assessed at the level 1 mm apical to the alveolar crest (BT1) and midpoint of the root (BT2) and evaluated at individual and tooth levels along with their mutual associations. RESULTS: The prevalence of thick gingiva was 53% with probe transparency measurement and 51% with transgingival probing. The cutoff gingival thickness was 0.8 mm, which correlated moderately with a Cohen's kappa of 0.386. The mean GT, KGW, and BTs (BT1 and BT2) in the maxillary anterior region were 0.97 ± 0.46, 5.51 ± 1.62, 0.85 ± 0.31, and 0.79 ± 0.32 mm, respectively. GT and KGW correlated mildly (r = 0.261), and GT and BTs correlated moderately (BT1: r = 0.298; BT2: r = 0.338). GT and BTs differed significantly between men and women and among different tooth sites. CONCLUSIONS: GT and BTs correlated positively in the maxillary anterior region and varied within and among individuals. Sex was a factor influencing the gingival phenotype and bone morphotype. CLINICAL RELEVANCE: GT measured with transgingival probing, with a cutoff of 0.8 mm, could serve as an objective measure to distinguish different gingival phenotypes.

Evaluation of salivary biomarkers for the diagnosis of periodontitis.

BACKGROUND: Salivary interleukin (IL)-1ß, matrix metalloproteinase (MMP)-8, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Porphyromonas gingivalis (Pg) are related to periodontitis. This study aimed to investigate the diagnostic potential of these biomarkers and to build a prediction panel for diagnosing periodontal disease. METHODS: A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (n = 25), gingivitis (n = 24), and periodontitis (n = 31) groups based on their periodontal exam results. A full mouth periodontal examination was performed and unstimulated saliva was collected. Salivary IL-1ß, MMP-8, ICTP, and Pg were assessed using enzyme-linked immunosorbent assay (ELISA) and quantitative real time PCR (qPCR). Their potentials for diagnosing periodontal disease were analyzed and combined prediction panels of periodontal disease were evaluated. RESULTS: As a single marker, IL-1ß showed the best diagnostic value of the four markers evaluated and exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects, an AUC value of 0.80 with 83% sensitivity and 76% specificity for discriminating gingivitis subjects from healthy subjects and an AUC value of 0.66 with 68% sensitivity and 64% specificity for differentiating periodontitis subjects from gingivitis subjects. The combination of IL-1ß, ICTP, and Pg exhibited the highest efficacy for discriminating periodontitis subjects from healthy subjects (AUC = 0.94) and gingivitis subjects (AUC = 0.77). The combination of IL-1ß and MMP-8 exhibited the best ability to discriminate gingivitis from healthy subjects (AUC = 0.84). CONCLUSIONS: Salivary IL-1ß, MMP-8, ICTP, and Pg showed significant effectiveness for diagnosing periodontal disease. The combination of IL-1ß, ICTP, and Pg can be used to discriminate periodontitis subjects from healthy subjects and gingivitis subjects, and the combination of IL-1ß and MMP-8 can be used to discriminate gingivitis subjects from healthy subjects.

Exogenous Vitamin C-Triggered Surface Charge Conversion of pH/Reduction-Responsive Micelles for the Enhanced Tumor-Specific Activity of Loaded Doxorubicin.

The effective accumulation at tumor sites and endocytosis by tumor cells for anticancer agents in carriers are essential in successful cancer therapy, and both of the processes are affected by the surface charge of drug carriers. In this study, vitamin C (VC) was employed as an "exogenous switch" to trigger the surface charge conversion of DOX-loaded micelles to obtain a better antitumor effect. T micelles formed by poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-PDEA-ss-PMPC) turned their ζ potentials from +1 mV to +18 mV under treatment of 20 mM VC, while the ζ potentials of control R micelles formed by PCL-ss-P(DEA-r-MPC) almost remained unchanged under the same condition. DOX-loaded T@DOX and R@DOX had high DLCs of 12% and 13.8%, respectively, and both showed an accelerated drug release in a reductive environment (10 mM GSH or 20 mM VC) at pH 5.0. Notably, due to the surface charge conversion and fast drug release triggered by VC, T@DOX/VC (T@DOX was pretreated by VC) showed an enhanced cytotoxicity and cellular uptake superior to T@DOX, R@DOX, and R@DOX/VC. T@DOX/VC also displayed the in vivo antitumor effect well, which was comparable to DOX·HCl but with less toxic side effects than DOX·HCl. In summary, VC as an exogenous trigger can induce a better antitumor effect of drug-loaded micelles with a suitable polymer structure by charge conversion, and T@DOX/VC has shown to be as a promising approach to achieve potent treatment of tumors.

Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells.

Tumor targeting has revolutionized cancer research, especially active cellular targeting of nanoparticles, where they are specifically homed to the pathological site to deliver the therapeutics. This strategy, which involves the utilization of affinity ligands on the surface of the nanocarriers, minimizes the nonspecific uptake of nanocarriers and the subsequent harmful side effects in healthy cells. Estrone, one of the mammalian estrogens, has affinity for estrogen receptors (ERα), which are overexpressed in hormone-responsive breast cancers. Despite holding promise, the potential of estrone in active targeting of nanoparticles has barely been explored. Herein, we developed an estrone-appended polyion complex (PIC) micelle to deliver melittin, a cytotoxic peptide, to breast cancer cells. Amino functionalization of estrone was performed to conjugate estrone to the diblock polymer synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Estrone-conjugated poly(ethylene glycol) methyl ether methacrylate-b-poly tert-butyl methacrylate (POEGMEMA-PtBuMA) could complex with melittin to form PIC micelles of size around 60 nm ensuing from the electrostatic interaction of the deprotected polymer and melittin in aqueous media. Poly(ethylene glycol) methyl ether acrylate-b-poly acrylic acid (POEGMEA-PAA) was also later incorporated to afford PIC micelles that could exhibit similar cytotoxicity to free melittin in the cytotoxicity studies. The estrone-attached PIC micelles exhibited improved cytotoxicity in two-dimensional (2D) and three-dimensional (3D) cellular models of MCF-7 cells. Cross-linking of the PIC micelles was also performed to improve the stability of the micelles and prevent melittin degradation from enzymatic attack. Flow cytometry demonstrated an enhanced cellular uptake greater than sixfold with the estrone-conjugated PIC micelles, thereby establishing a profound difference in the targeting efficacy of the PIC micelles between MCF-7 and MDA-MB-231 cells. Furthermore, the distribution of the PIC micelles in the spheroids was revealed by light sheet microscopy. The results demonstrate the potential of estrone-anchored PIC micelles for targeted delivery of therapeutics to hormone-responsive breast cancer cells.

Direct Comparison of Poly(ethylene glycol) and Phosphorylcholine Drug-Loaded Nanoparticles In Vitro and In Vivo.

Phosphorylcholine is known to repel the absorption of proteins onto surfaces, which can prevent the formation of a protein corona on the surface of nanoparticles. This can influence the fate of nanoparticles used for drug delivery. This material could therefore serve as an alternative to poly(ethylene glycol) (PEG). Herein, the synthesis of different particles prepared by polymerization-induced self-assembly (PISA) coated with either poly(ethylene glycol) (PEG) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and 4-(N-(S-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was reported. The anticancer drug 4-(N-(S-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was conjugated to the shell-forming block. Interactions of the different coated nanoparticles, which present comparable sizes and size distributions (76-85 nm, PDI = 0.067-0.094), with two-dimensional (2D) and three-dimensional (3D) cultured cells were studied, and their cytotoxicities, cellular uptakes, spheroid penetration, and cell localization profiles were analyzed. While only a minimal difference in behaviour was observed for nanoparticles assessed using in vitro experiment (with PEG-co- PENAO-coated micelles showing slightly higher cytotoxicity and better spheroid penetration and cell localization ability), the effect of the different physicochemical properties between nanoparticles had a more dramatic effect on in vivo biodistribution. After 1 h of injection, the majority of the MPC-co-PENAO-coated nanoparticles were found to accumulate in the liver, making this particle system unfeasible for future biological studies.

Polyion Complex Micelles for Protein Delivery Benefit from Flexible Hydrophobic Spacers in the Binding Group.

Although a range of polymer-protein polyion complex (PIC) micelle systems have been developed in the literature, relatively little attention has been paid to the influence of polymer structure on the assembly, or to the mechanism of disassembly. In this work, Förster resonance energy transfer is used in combination with light sheet fluorescence microscopy and isothermal calorimetry to monitor the formation and stability of PIC micelles with various carboxylic-acid-based binding blocks in MCF-7 cancer spheroid models. All micelles are stable in the presence of free protein, but are unstable in solutions with an ionic strength >200 mm and prone to disassembly at reduced pH. Introducing carbon spacers between the backbone and the binding carboxylic acid results in improved PIC micelle stability at physiological pH, but also increases the pKa of the binding moiety, resulting in improved protein release upon cell uptake. These results give important insights into how to tune PIC micelle stability for controlled protein release in biological environments.

Meta-analysis on the association between the frequency of tooth brushing and diabetes mellitus risk.

BACKGROUND AND OBJECTIVE: Epidemiological studies suggested that the frequency of tooth brushing might be associated with the risk of diabetes mellitus (DM), but the results were inconsistent, and no systematic review was conducted to focus on this topic. In this meta-analysis, we synthesized available observational epidemiological evidences to identify the association between tooth brushing and DM risk and investigate the potential dose-response relationship of them. METHODS: We searched PubMed and Embase from their inception through December 2017 to identify observational studies examining the association between tooth brushing and the risk of DM. Reference lists from retrieved articles were also reviewed. We quantitatively combined results of the included studies using a random-effects model. Dose-response meta-analysis was conducted to further examine the effect of tooth brushing frequency on DM risk. RESULTS: We identified 20 relevant studies (one cohort study, 14 case-control studies, and 5 cross-sectional studies) involving 161 189 participants and 10 884 patients with DM. Compared with the highest tooth brushing frequency, the lowest level was significantly associated with an increased risk of DM (OR 1.32; 95% CI, 1.19-1.47), and there was no significant heterogeneity across the included studies (p = 0.119, I2  = 28.1%). Exclusion of any single study did not materially alter the combined risk estimate. The dose-response analysis indicated that the summary odds of DM for an increment of one time of tooth brushing per day was 1.20 (95% CI, 1.16-1.24). CONCLUSIONS: Integrated epidemiological evidence supports the hypothesis that low frequency of tooth brushing may be a risk factor of DM, and lower frequencies of tooth brushing were significantly associated with higher risk of DM.

Sugar Concentration and Arrangement on the Surface of Glycopolymer Micelles Affect the Interaction with Cancer Cells.

Glycopolymer-coated nanoparticles have attracted significant interest over the past few years, because of their selective interaction with carbohydrate receptors found on the surface of cells. While the type of carbohydrate determines the strength of the ligand-receptor interaction, the presentation of the sugar can be highly influential as the carbohydrate needs to be accessible in order to display good binding. To shine more light on the relationship between nanoparticle structure and cell uptake, we have designed several micelles based on fructose containing block copolymers, which are selective to GLUT5 receptors found on breast cancer cell lines. The polymers were based on poly-d,l-lactide (PLA), poly(2-hydroxyethyl) acrylate (PHEA), and poly(1- O-acryloyl-ß-d-fructopyranose) (P[1- O-AFru]). A set of six micelles was synthesized based on four fructose containing micelles (PLA242- b-P[1- O-AFru]41, PLA242- b-P[1- O-AFru]179, PLA242- b-P[1- O-AFru46-c-HEA214], PLA242- b-PHEA280- b-P[1- O-AFru]41) and two neutral controls (PLA247- b-PHEA53 and PLA247- b-PHEA166). SAXS analysis revealed that longer hydrophilic polymers led to lower aggregation numbers and larger hydrophilic shells, suggesting more glycopolymer mobility. Cellular uptake studies via flow cytometry and confocal laser scanning microscopy (CLSM) confirmed that the micelles based on PLA242- b-P[1- O-AFru]179 show, by far, the highest uptake by MCF-7 and MDA-MB-231 breast cancer cell lines while the uptake of all micelles by RAW264.7 cell is negligible. The same micelle displayed was far superior in penetrating MCF-7 cancer spheroids (three-dimensional (3D) model). Taking the physicochemical characterization obtained by SAXS and the in vitro results together, it could be concluded that the glycopolymer chains on the surface of micelle must display high mobility. Moreover, a high density of fructose was found to be necessary to achieve good biological activity as lowering the epitope density led immediately to lower cellular uptake. This work showed that it is crucial to understand the micelle structure in order to maximize the biological activity of glycopolymer micelles.

Design and Synthesis of a Novel n-Type Polymer Based on Asymmetric Rylene Diimide for the Application in All-Polymer Solar Cells.

A novel n-type polymer of PTDI-T based on asymmetric rylene diimide and thiophene is designed and synthesized. The highest power conversion efficiency of 4.70% is achieved for PTB7-Th:PTDI-T-based devices, which is obviously higher than those of the analogue polymers of PPDI-2T and PDTCDI. When using PBDB-T as a donor, an open-circuit voltage (VOC ) as high as 1.03 V is obtained. The results indicate asymmetric rylene diimide is a kind of promising building block to construct n-type photovoltaic polymers.

Softening and Shape Morphing of Stiff Tough Hydrogels by Localized Unlocking of the Trivalent Ionically Cross-Linked Centers.

The mechanical properties (e.g., stiffness, stretchability) of prefabricated hydrogels are of pivotal importance for diverse applications in tissue engineering, soft robotics, and medicine. This study reports a feasible method to fabricate ultrasoft and highly stretchable structures from stiff and tough hydrogels of low stretchability and the application of these switchable hydrogels in programmable shape-morphing systems. Stiff and tough hydrogel structures are first fabricated by the mechanical strengthening of Ca2+ -alginate/polyacrylamide tough hydrogels by addition of Fe3+ ions, which introduces Fe3+ ionically cross-linked centers into the Ca2+ divalent cross-linked hydrogel, forming an additional and much less flexible trivalent ionically cross-linked network. The resulting stiff and tough hydrogels are exposed to an L-ascorbic acid (vitamin C, VC) solution to rapidly reduce Fe3+ to Fe2+ . As a result, flexible divalent ionically cross-linked networks are formed, leading to swift softening of the stiff and tough hydrogels. Moreover, localized stiffness variation of the tough hydrogels can be realized by precise patterning of the VC solution. To validate this concept, sequential steps of VC patterning are carried out for local tuning of the stiffness of the hydrogels. With this strategy, localized softening, unfolding, and sequential folding of the tough hydrogels into complex 3D structures is demonstrated.

Influencing Selectivity to Cancer Cells with Mixed Nanoparticles Prepared from Albumin-Polymer Conjugates and Block Copolymers.

Albumin-based nanoparticles are widely used to delivery anticancer drug because they promote the accumulation of drugs in tumor sites. Nanoparticles with surface immobilized albumin are widely described in literature, although mixed nanoparticles with systematically modified ratios between albumin and PEG-based material are less common. In this work, hybrid nanoparticles were prepared by coassembly of a PEG-based amphiphilic block copolymer together with a polymer-protein conjugate. Poly(oligo(ethylene glycol) methyl ether acrylate)-poly(ε-caprolactone) (POEGMEA-PCL) was prepared by a combination of ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, while the polymer-protein conjugate was obtained by reacting poly(ε-caprolactone) with bovine serum albumin (BSA-PCL). Co-assembly of both amphiphiles at different ratios, with and without curcumin as a drug, led to hybrid nanoparticles with various amount of albumin on the particle surface. The resulting hybrid nanoparticles were similar in size (100-120 nm), but increasing the amount of albumin on the surface led to a more-negative ζ potential. The cytotoxicity of the curcumin-loaded nanoparticles was examined on several cell lines. The curcumin-loaded nanoparticles with high amount of albumin led to high cytotoxicity against breast cancer cell lines (MDA-MB-231 and MCF-7), which coincided with high cellular uptake. However, the cytotoxicity of the curcumin-loaded nanoparticles against CHO cells and RAW264.7 cells was reduced, suggesting that albumin can facilitate selectivity toward cancer cells.

Binding and Release between Polymeric Carrier and Protein Drug: pH-Mediated Interplay of Coulomb Forces, Hydrogen Bonding, van der Waals Interactions, and Entropy.

The accelerating search for new types of drugs and delivery strategies poses challenge to understanding the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and carrier is quintessential. Although many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counterions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiments, we shed light herein on the binding in aqueous solution between a protein drug and polymeric carrier. We examined the complexation between the polymer poly(ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein egg white lysozyme, a system that acts as a model for polymer-vector/protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by Coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behavior at low pH. Intracomplex hydrogen bonds, van der Waals interactions, as well as water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2 even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behavior. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen bonding, to search for adequate descriptors to predict binding and release properties of polymer-protein complexes. Advances in computational power over the past decade make atomistic molecular dynamics simulations such as implemented here one of the few avenues currently available to elucidate the complexity of these interactions and provide insights toward finding adequate descriptors. Thus, there remains much room for improvement of design principles for efficient capture and release delivery systems.

High post-treatment absolute monocyte count predicted hepatocellular carcinoma risk in HCV patients who failed peginterferon/ribavirin therapy.

Salient studies have investigated the association between host inflammatory response and cancer. This study was conducted to test the hypothesis that peripheral absolute monocyte counts (AMC) could impart an increased risk of hepatocellular carcinoma (HCC) development in hepatitis C virus (HCV)-infected patients after a failed peginterferon/ribavirin (PR) combination therapy. A total of 723 chronic HCV-infected patients were treated with PR, of which 183 (25.3 %) patients did not achieve a sustained virological response (non-SVR). Post-treatment AMC values were measured at 6 months after end of PR treatment. Fifteen (2.8 %) of 540 patients with an SVR developed HCC during a median follow-up period of 41.4 months, and 14 (7.7 %) of 183 non-SVR patients developed HCC during a median follow-up of 36.8 months (log rank test for SVR vs. non-SVR, P = 0.002). Cox regression analysis revealed that post-treatment AFP level (HR 1.070; 95 % CI = 1.024-1.119, P = 0.003) and post-treatment aspartate aminotransferase (AST)-to-platelet ratio index (APRI) ≥0.5 (HR 4.401; 95 % CI = 1.463-13.233, P = 0.008) were independent variables associated with HCC development for SVR patients. For non-SVR patients, diabetes (HR 5.750; 95 % CI = 1.387-23.841, P = 0.016), post treatment AMC ≥370 mm(-3) (HR 5.805; 95 % CI = 1.268-26.573, P = 0.023), and post-treatment APRI ≥1.5 (HR 10.905; 95 % CI = 2.493-47.697, P = 0.002) were independent risks associated with HCC. In conclusion, post-treatment AMC has a role in prognostication of HCC development in HCV-infected patients who failed to achieve an SVR after PR combination therapy.

PEGylated Albumin-Based Polyion Complex Micelles for Protein Delivery.

An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.

Investigation of colloidal biogenic sulfur flocculation: Optimization using response surface analysis.

The colloidal properties of biogenic elemental sulfur (S(0)) cause solid-liquid separation problems, such as poor settling and membrane fouling. In this study, the separation of S(0) from bulk liquids was performed using flocculation. Polyaluminum chloride (PAC), polyacrylamide (PAM) and microbial flocculant (MBF) were compared to investigate their abilities to flocculate S(0) produced during the treatment of sulfate-containing wastewater. A novel approach with response surface methodology (RSM) was employed to evaluate the effects and interactions of flocculant dose, pH and stirring intensity, on the treatment efficiency in terms of the S(0) flocculation and the supernatant turbidity removal. The dose optimization results indicated that the S(0) flocculation efficiency decreased in the following order PAC>MBF>PAM. Optimum S(0) flocculation conditions were observed at pH4.73, a stirring speed of 129 r/min and a flocculant dose of 2.42 mg PAC/mgS. During optimum flocculation conditions, the S(0) flocculation rate reached 97.53%. Confirmation experiments demonstrated that employing PAC for S(0) flocculation is feasible and RSM is an efficient approach for optimizing the process of S(0) flocculation. The results provide basic parameters and conditions for recovering sulfur during the treatment of sulfate-laden wastewaters.

Evaluation of salivary interleukin-17 and developmental endothelial locus-1 in patients with periodontitis with and without type 2 diabetes mellitus.

BACKGROUND: Bidirectional positive relationship between periodontitis and type 2 diabetes mellitus (T2DM) has been recognized, interleukin 17 (IL-17) and developmental endothelial locus-1 (Del-1) are proposed to play roles in periodontitis and T2DM. This study aims to investigate the association of IL-17 and Del-1 in patients with periodontitis with and without T2DM by measuring their salivary levels. METHODS: A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (H, n = 27), periodontitis (P, n = 29) and periodontitis with diabetes (PDM, n = 24) groups based on their periodontal and diabetic examination results. Periodontal parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD], and clinical attachment level [CAL]) as well as diabetic parameters (fasting plasma glucose [FG] and glycated hemoglobin [HbA1c]) were documented and unstimulated saliva was collected. Salivary IL-1ß, active-matrix metalloproteinase-8 (aMMP-8), tumor necrosis factor-α (TNF-α), IL-6, IL-8, IL-17, and Del-1 were determined through enzyme-linked immunosorbent assay (ELISA) and their relationships with periodontal and diabetic parameters were examined. RESULTS: The periodontitis and periodontitis with diabetes groups showed significantly higher levels of IL-17 and lower levels of Del-1 compared with healthy group. The periodontitis with diabetes group exhibited higher levels of IL-17 and lower levels of Del-1 compared with the periodontitis group. After correlation analysis, there were significant correlations between salivary IL-17 and Del-1 and clinical parameters, IL-17 and Del-1 were correlated with PD (r = 0.36, -0.39, p < 0.01), CAL (r = 0.40, -0.42, p < 0.01) and BOP (r = 0.35, -0.37, p < 0.01), they were correlated with FG (r = 0.26, -0.25, p < 0.05) and HbA1c (r = 0.28, -0.40, p < 0.05). Positive relationships were observed between IL-17 and IL-1ß and between IL-17 and aMMP-8 (r = 0.80, 0.77, p < 0.01), while Del-1 exhibited negative correlations with IL-1ß and aMMP-8 (r = 0.59, 0.69 p < 0.01). Comparison between IL-17 and Del-1 confirmed an inverse relationship (r = -0.71, p < 0.01). Salivary Del-1 levels in the older group were lower compared with young group across the H, P and PDM groups, although these differences were not statistically significant (p > 0.05). CONCLUSIONS: Salivary IL-17 and Del-1 levels in the periodontitis with diabetes group showed significant changes compared with the periodontitis group, they exhibited an inverse relationship and were both correlated with periodontal parameters (PD, CAL, and BOP) and diabetic parameters (FG and HbA1c). PLAIN LANGUAGE SUMMARY: Periodontitis and type 2 diabetes mellitus (T2DM) are two common diseases all over the world, some inflammatory mediators (interleukin 17 [IL-17] and developmental endothelial locus-1 [Del-1]) regulate neutrophil production, recruitment and clearance when the body becomes infected and believed to be involved in the progress of diseases of periodontitis and diabetes. In this study, we enrolled healthy subjects, patients with periodontitis, patients with periodontitis and diabetes. We performed dental examinations and evaluated their blood glucose levels, collected their saliva, and detected IL-17 and Del-1 levels in their saliva. We found both patients with periodontitis and patients with periodontitis and diabetes showed higher IL-17 levels and lower Del-1 levels compared with healthy subjects. Patients with periodontitis and diabetes showed higher IL-17 levels and lower Del-1 levels compared with patients with periodontitis. Salivary IL-17 and Del-1 levels were both correlated with dental examination results and blood glucose levels, and salivary IL-17 and Del-1 displayed an inverse relationship.

Survival of nonsurgically splinted mandibular anterior teeth during supportive maintenance care in periodontitis patients.

Background/purpose: Splinting mobile teeth is a choice to improve the patient's oral comfort. The purpose of this study was to assess the survival and stability of mobile anterior mandibular teeth after splinting in patients with periodontitis undergoing supportive periodontal therapy (SPT). Materials and methods: Patients with splinted mobile anterior mandibular teeth were assessed retrospectively. Periodontal statuses were recorded at baseline and follow-up visits. Tooth and splint survival as well as splint repairs were recorded. Multilevel Cox regression analyses were performed to evaluate patient- and tooth-related factors that might have influenced the survival rates of splints. Results: Sixty-one patients, collectively having 161 splints, were followed for an average of 5.44 years. On average, probing depth (PD) of splinted teeth decreased from 4.31 mm to 2.93 mm and clinical attachment loss (CAL) decreased from 5.02 mm to 4.58 mm. Alveolar bone was stable in the follow-up period. None of the splinted teeth were extracted, The overall survival rate of the splints was 65.2%. Splints made of composite resin alone were associated with a higher risk of breakage when compared to splints composed of composite resin with mesh grid strips. Conclusion: Splinting showed long-term survival and splinting combined with periodontal supportive treatment is a feasible option to maintain mobile mandibular anterior teeth.

Tangential Ultrasonic-Vibration Assisted Forming Grinding Gear: An Experimental Study.

This study used a forming grinding wheel to machine an involute spur gear with ultrasonic vibration applied to the gear in order to improve the gear processing technology and enhance the gear processing effect. Conventional grinding and ultrasonic vibration-assisted forming grinding gear (TUVA-FGG) tests were carried out. The effects of grinding parameters, such as spindle speed, feed rate, radial grinding depth, and ultrasonic amplitude, on grinding force, grinding temperature, residual stress, surface roughness, and surface morphology were analyzed. The TUVA-FGG significantly improved processing efficiency. With the increase in spindle speed, the maximum reductions in the normal and tangential grinding forces, grinding temperature, and surface roughness reached 33.6, 24.5, 23.9, and 21.6%, respectively. With the increase in feed rate, the respective maximum reductions were 21.4, 19.7, 20.3, and 16.1%. With the increase in radial grinding depth, these values attained 24.6, 20.3, 21.5, and 17.6%, respectively. Finally, with the increase in ultrasonic amplitude, these reductions reached 21.4, 19.7, 21.5, and 19.4%. The maximum residual compressive stress grew by 30.3, 27.5, 30.9, and 27.5% with the increase of wheel rotation speed, feed speed, radial grinding depth, and ultrasonic amplitude, respectively. TUVA-FGG changed the conventional continuous cutting mechanism between the abrasive grain and workpiece into intermittent cutting, reducing grinding forces, grinding temperature, and surface roughness. Moreover, it increased residual compressive stress and improved the micromorphology of the tooth surface, thus enhancing gear machining efficiency.