A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.

Aptamer-Functionalized and Backbone Redox-Responsive Hyperbranched Polymer for Targeted Drug Delivery in Cancer Therapy.

A novel type of backbone redox-responsive hyperbranched poly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate) (HPAEG) has been designed and prepared successfully via the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and self-condensing vinyl polymerization (SCVP). Owing to the existence of surface vinyl groups, HPAEG could be efficiently functionalized by DNA aptamer AS1411 via Michael addition reaction to obtain an active tumor targeting drug delivery carrier (HPAEG-AS1411). The amphiphilic HPAEG-AS1411 could form nanoparticles by macromolecular self-assembly strategy. Cell Counting Kit-8 (CCK-8) assay illustrated that HPAEG-AS1411 nanoparticles had low cytotoxicity to normal cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) results demonstrated that HPAEG-AS1411 nanoparticles could be internalized into tumor cells via aptamer-mediated endocytosis. Compared with pure HPAEG nanoparticles, HPAEG-AS1411 nanoparticles displayed enhanced tumor cell uptake. When the HPAEG-AS1411 nanoparticles loaded with anticancer drug doxorubicin (DOX) were internalized into tumor cells, the disulfide bonds in the backbone of HPAEG-AS1411 were cleaved by glutathione (GSH) in the cytoplasm, so that DOX was released rapidly. Therefore, DOX-loaded HPAEG-AS1411 nanoparticles exhibited a high tumor cellular proliferation inhibition rate and low cytotoxicity to normal cells. This aptamer-functionalized and backbone redox-responsive hyperbranched polymer provides a promising platform for targeted drug delivery in cancer therapy.

State-of-the-art of lignin-derived carbon nanodots: Preparation, properties, and applications.

Lignin-derived carbon nanodots (LCNs) are nanometer-scale carbon spheres fabricated from naturally abundant lignin. Owing to rich and highly heritable graphene like π-π conjugated structure of lignin, to fabricate LCNs from it not only endows LCNs with on-demand tunable size and optical features, but also further broadens the green and chemical engineering of carbon nanodots. Recently, they have become increasingly popular in sensing, bioimaging, catalysis, anti-counterfeiting, energy storage/conversion, and others. Despite the enormous research efforts put into the ongoing development of lignin value-added utilization, few commercial LCNs are available. To have a deeper understanding of this issue, critical impacts on the preparation, properties, and applications of state-of-the-art LCNs are carefully reviewed and discussed. A concise analysis of their unique advantages, limitations for specific applications, and current challenges and outlook is conducted. We hope that this review will stimulate further advances in the functional material-oriented production of lignin.

Accuracy evaluation of a universal dental implant guide for simulating implantation in posterior area on dental molds.

OBJECTIVES: This study aims to compare the accuracy of self-developed universal implant guide (SDG), 3D printed digital guide (DG), and free hand (FH) simulated implantation in the posterior tooth area of dental models. METHODS: Ten junior dentists were selected to place three implants in the 35, 37, and 46 tooth sites of the mandibular models (35, 36, 37, and 46 missing teeth) by using SDG, DG, and FH, and the process was repeated again to take the average value. Cone beam computed tomography (CBCT) was used to evaluate the global coronal deviation, global apical deviation, depth deviation, and angular deviation between the actual position and preoperative planned position. RESULTS: The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly different from those in the two other groups (P>0.05). The depth deviation and angular deviation in the SDG group were smaller than those in the DG group (P<0.05) and FH group (P<0.05), respectively. All deviations at site 37 in the SDG group were not different from those at site 35 (P>0.05), while the depth and angular deviation at site 37 in the DG group were higher than those at site 35 (P<0.05). CONCLUSIONS: The precision of the self-developed universal dental implant guide can meet the requirements of clinical posterior implantation.

Temperature-induced emission enhancement of star conjugated copolymers with poly(2-(dimethylamino)ethyl methacrylate) coronas for detection of bacteria.

A facile strategy for temperature-induced emission enhancement of star conjugated copolymers has been developed for biodetection. The star copolymers (HCP-star-PDMAEMAs) with different poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) chain lengths were synthesized from the hyperbranched conjugated polymer (HCP) macroinitiator by atom transfer radical polymerization (ATRP). The star conjugated copolymers exhibited interesting thermoresponsive phase transitions with adjustable lower critical solution temperature (LCST) depending on the pH of copolymer solution. Above the LCST, the emission of HCP-star-PDMAEMAs was enhanced greatly through restriction of intermolecular aggregation of conjugated polymer cores by the collapse of PDMAEMA arms. By changing the PDMAEMA length, the emission performance of HCP-star-PDMAEMAs could be readily adjusted. Correspondingly, this temperature-dependent emission enhancement of HCP-star-PDMAEMAs was successfully applied in the highly sensitive detection of bacteria. Due to the existence of a hyperbranched conjugated core and many thermo-responsive PDMAEMA arms, the detection limit of E. coli could reach 10(2) cfu mL(-1).

Dental implant failure rates with low insertion torque with a nonsubmerged surgical approach: A retrospective clinical study.

BACKGROUND: It is currently unclear if a low insertion torque (IT) should prompt a clinician to submerge the dental implant at time of placement. PURPOSE: This study aimed to analyze implant failure rates and marginal bone loss (MBL) as a function of IT and surgical approach. MATERIALS AND METHODS: A total of 197 patients who had received 295 Mozo Grau (MG) implants were included in this study. The healing of submerged or nonsubmerged implants was evaluated in regular IT (≥20-25 Ncm) or low IT (<20-25 Ncm) cases. Implant failure and MBL were evaluated before prosthesis placement and at 6 and 12 months after functional loading with generalized estimating equations. RESULTS: The overall 12-month implant failure rate was 4.8% (95% confidence interval [CI]: 2.7%-8.2%). When successful at 12 months, dental implants placed with low IT and nonsubmerging had the same MBL as implants dental implants placed with other approaches (mean difference = -0.02 mm; 95% CI -0.05 to 0.02). Low IT combined with nonsubmerging of the dental implant was associated with a 30-fold increased odds for dental implant failure (95% CI: 3.8-236.6). CONCLUSION: low IT and nonsubmerged healing was associated with a high failure rate.

An easily processable silver nanowires-dual-cellulose conductive paper for versatile flexible pressure sensors.

To date, flexible pressure sensors built on silver nanowires (AgNWs) have attracted tremendous attention, owing to their versatile applications in wearable, human-interactive, health-monitoring devices. Cellulose and its derivatives, which show great promise in serving flexible pressure sensors as the desired substrate due to their natural abundance, biocompatibility, easy processibility, and low costs. Herein, we reported a rational strategy to design a silver nanowires-dual-cellulose conductive paper. Its morphology, chemical and crystal structures, thermal stability, mechanical performances, and electrical properties were carefully studied. The results suggested that good tensile properties (tensile strength ≤8.10 MPa), high electrical conductivity (≤ 1.74 × 104 S·m-1) with long-term stability, and good adhesion stability (bending cycles over 500) were obtained. Furthermore, the use of such conductive paper as substrate for versatile flexible pressure sensors was demonstrated, which exhibited fast response (~ 0.48 s) and high sensitivity, in response to finger motion, voice recognition, and human pulse, etc.

Air conditioner filters become sinks and sources of indoor microplastics fibers.

Indoor airborne microplastics fibers (MPFs) are emerging contaminants of growing concern. Nowadays, air conditioners (ACs) are widely used in indoor environments. However, little is known about their impact on the distribution of indoor MPFs. In this study, we first disclosed the prevalence of MPF contamination in filters for indoor split ACs used in living rooms, dormitories, and offices. The average density of microfibers was 1.47-21.4 × 102 items/cm2, and a total 27.7-35.0% of fibers were MPFs. Of these fibers, the majority were polyester (45.3%), rayon (27.8%), and cellophane (20.1%). We further tracked the long-term accumulation of MPFs on AC filters in three types of rooms, and demonstrated that dormitories showed relatively heavy accumulation especially after running for 35-42 days. Furthermore, we found that simulative AC filters which had been lined with PET MPFs could effectively release those MPFs into indoor air, propelling them away from the ACs at varying distances. Statistical analysis showed that the estimated daily intake of MPFs (5-5000 µm length) from AC filters would increase gradually with their usage, with the intake volume reaching up to 11.2 ± 2.2-44.0 ± 8.9 items/kg-BW/day by the 70th day, although this number varied among people of different ages. Altogether, these findings suggest that AC filters can act as both a sink and a source of microplastics fibers. Therefore, AC filters should be evaluated not only for their substantial impact on the distribution of indoor airborne MPFs, but also for their role in the prevalence of the related health risks.

Polymeric micelles with water-insoluble drug as hydrophobic moiety for drug delivery.

The hydrophobic block of polymeric micelles formed by amphiphilic copolymers has no direct therapeutical effect, and the metabolites of these hydrophobic segments might lead to some unexpected side effects. Here the hydrophobic core of polymeric micelles is replaced by highly water-insoluble drugs themselves, forming a new micellar drug delivery system. By grafting hydrophobic drugs of paclitaxel (PTX) onto the surface of hydrophilic hyperbranched poly(ether-ester) (HPEE), we constructed an amphiphilic copolymer (HPEE-PTX). HPEE-PTX could self-assemble into micellar nanoparticles in aqueous solution with tunable drug contents from 4.1 to 10.7%. Moreover, the hydrolysis of HPEE-PTX in serum resulted in the cumulative release of PTX. In vivo evaluation indicated that the dosage toleration of PTX in mice had been improved greatly and HPEE-PTX micellar nanoparticles could be used as an efficient prodrug with satisfactory therapeutical effect. We believe that most of the lipophilic drugs could improve their characters through this strategy.

Recyclable deep eutectic solvent coupling sodium hydroxide post-treatment for boosting woody/herbaceous biomass conversion at mild condition.

A novel recyclable deep eutectic solvent (DES) consisting of p-toluene sulfonic acid (p-TsOH) and choline chloride (ChCl) was developed for efficient woody poplar sawdust (PL) and herbaceous miscanthus (MC) conversion at mild condition. The extraction of leftover lignin on the surface of DES pretreated residues using NaOH solution at room temperature greatly improved the enzymatic hydrolysis efficiency. Near complete cellulose conversion of PL and MC residues were obtained with a degree of delignification and xylan removal over 90% at 100 °C within 40 min. The strong correlations between xylan (R2 = 0.95) and lignin (R2 = 0.82) removal with cellulose conversion were observed in MC as well as positive correlations (R2 > 0.77) in PL. The results demonstrated that the DES system coupling NaOH post-treatment was a promising method to achieve an economically feasible biomass conversion process, which was effective for both woody PL residues and herbaceous MC.

Natural lignocellulosic nanofibril film with excellent ultraviolet blocking performance and robust environment resistance.

Due to the current state of ozone layer depletion and potential risk of skin cancer, researches on sustainable cellulose-based films with ultraviolet (UV) blocking capabilities has attracted widespread attention. However, pure cellulose-based film required UV absorbent to be incorporated because of its poor UV blocking ability. In this work, natural lignocellulosic nanofibril (LCNF) film was fabricated by vacuum filtration and pressing process without any complex chemical modification or adding UV absorbers. The residual lignin retained in LCNF was found to act as natural macro-molecular UV absorber. LCNF film with lignin content of 4.89-15.68% exhibited excellent thermal stability, and their UVA and UVB blocking were in the range of 81.4-99.5% and 96.7-100%, respectively. Moreover, LCNF film exhibited stable UV shielding performance under high temperature, UV irradiation, acidic or alkaline conditions, providing LCNF film with a long-term use capacity. Overall, LCNF film is more environmentally friendly and harmless, which shows high potentials in anti-counterfeiting materials, UV protection, and windshields for vehicles.

Synthesis, characterization, and in vitro evaluation of long-chain hyperbranched poly(ethylene glycol) as drug carrier.

A series of novel long-chain hyperbranched poly(ethylene glycol)s (LHPEGs) with biodegradable connections were designed and synthesized in one pot through proton-transfer polymerization using PEG and commercial glycidyl methacrylate as monomers and potassium hydride as catalyst. The LHPEGs were hydrolyzed at neutral pH resulting in the decrease of molecular weights. In vitro evaluation demonstrated that LHPEGs were biocompatible and displayed negligible hemolytic activity. The efficient cellular uptake of LHPEGs was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, conjugation of a model hydrophobic anticancer drug methotrexate to LHPEGs inhibited the proliferation of a human cervical carcinoma Hela cell line. MTT assay indicated that the conjugated methotrexate dose required for 50% cellular growth inhibition against Hela cells was 20 µg/mL. By combining the advantages of long-chain hyperbranched structure and PEG, LHPEG provides a promising drug carrier for therapeutic fields.

Controlling the particle size of interpolymer complexes through host-guest interaction for drug delivery.

A new method to adjust the particle size of interpolymer complexes has been developed by introduction of host-guest interaction into the dilute aqueous solution of poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG). Because of the cooperative hydrogen-bonding interaction, PAA can form the interpolymer complexes with PEG. Putting beta-cyclodextrin (beta-CD) into dilute PAA/PEG aqueous solution, the competition between host-guest and hydrogen-bonding interactions happens. The beta-CD/PAA/PEG ternary systems have been well characterized by ultraviolet-visible absorption spectroscopy (UV-vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), diffusion NMR spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and solid-state (13)C NMR spectroscopy. The results indicate that the hydrophobic cavity of beta-CD is threaded by linear polymers so that the hydrophilicity of PAA/PEG interpolymer complexes is improved greatly. Adjusting the amounts of beta-CD, the particle size of the interpolymer complexes can be readily controlled. The low cytotoxicity of various beta-CD/PAA/PEG ternary complexes has been confirmed using the MTT assay in COS-7 cell line. Doxorubicin (DOX), an anticancer drug, has been encapsulated into the beta-CD/PAA/PEG ternary complexes. The DOX-loaded beta-CD/PAA/PEG ternary complexes have been analyzed by confocal laser scanning microscopy (CLSM), flow cytometry analysis, and the MTT assay against human cervical carcinoma cell (Hela). The results indicate that beta-CD/PAA/PEG ternary complexes with controlled particle size could be used as safe and promising drug carriers.

In situ preparation of magnetic nonviral gene vectors and magnetofection in vitro.

Magnetic nonviral gene vectors were in situ prepared in the presence of ferrous salts and hyperbranched poly(ethylenimine)s (HPEI) with different molecular weights. HPEI, one of the most promising nonviral vectors, was not only utilized as the nanoreactor and stabilizer to prepare magnetic nanoparticles, but also skillfully used as a base supplier to avoid introducing alkali hydroxide or ammonia. Magnetic nonviral gene vectors with various magnetite contents and saturation magnetizations were obtained by changing the weight ratio of HPEI to FeSO(4).7H(2)O and the molecular weight of HPEI. MTT assays suggested that the resulting magnetite/HPEI gene vectors had lower cytotoxicity compared with pure HPEI. The magnetite/HPEI nonviral gene vectors were used for magnetofection. It was found that the luciferase expression level mediated by magnetite/HPEI in COS-7 cells under a magnetic gradient field was approximately 13-fold greater than that of standard HPEI transfection.

Diisocyanate modifiable commercial filter paper with tunable hydrophobicity, enhanced wet tensile strength and antibacterial activity.

Paper made of cellulose has the advantages of substantial resource, good biocompatibility, large operation scale, and low production cost, however, it is usually hindered to replace plastic due to its inferior stability to water and poor mechanical strength. Herein, commercial filter paper (FP) was reacted with methylene diphenyl diisocyanate (MDI) to fabricate modified paper with tunable hydrophobicity and enhanced wet tensile strength. Due to the formation of urethane linkages in the reaction, both hydrophobicity and wet mechanical properties can be tuned and improved by varying the MDI cross-linking agent, exhibiting highest water contact angle of 137.0° and wet tensile strength of 4.8 MPa. In addition, the modified MDI-FPs exhibited excellent antibacterial performance against Escherichia coli compared with the original FP. Overall, this study provides a more simple approach to modify cellulose paper to produce versatile cellulose-based materials that can potentially replace the non-biodegradable plastics.

Role of branching architecture on the glass transition of hyperbranched polyethers.

The influence of branching architecture on the glass transition of hyperbranched polyethers has been investigated. For amorphous samples, the glass transition temperature (T(g)) first increases with the degree of branching (DB), passes through a maximum, and then decreases sharply. An attempt is made to explain this by the competition between the junction density and the free volume of terminal units. For the crystalline samples, the crystallization of polymer chains makes the relationship of DB and T(g) more complicated. By the introduction of branching architecture, the crystallization ability of the branched polymer is weakened gradually. When the samples are isothermally crystallized for a long time, the T(g) of polyethers decreases monotonically with DB.

A wheat MYB transcriptional repressor TaMyb1D regulates phenylpropanoid metabolism and enhances tolerance to drought and oxidative stresses in transgenic tobacco plants.

MYB transcription factors are involved in the regulation of plant development and response to biotic and abiotic stress. In this study, TaMyb1D, a novel subgroup 4 gene of the R2R3-MYB subfamily, was cloned from wheat (Triticum aestivum L.). TaMyb1D was localized in the nucleus and functioned as a transcriptional repressor. The overexpression of TaMyb1D in tobacco (Nicotiana tabacum) plants repressed the expression of genes related to phenylpropanoid metabolism and down-regulated the accumulation of lignin in stems and flavonoids in leaves. These changes affected plant development under normal conditions. The expression of TaMyb1D was ubiquitous and up-regulated by PEG6000 and H2O2 treatments in wheat. TaMyb1D-overexpressing transgenic tobacco plants exhibited higher relative water content and lower water loss rate during drought stress, as well as higher chlorophyll content in leaves during oxidative stress. The transgenic plants showed a lower leakage of ions as well as reduced malondialdehyde and H2O2 levels during conditions of drought and oxidative stresses. In addition, TaMyb1D up-regulated the expression levels of ROS- and stress-related genes in response to drought stress. Therefore, the overexpression of TaMyb1D enhanced tolerance to drought and oxidative stresses in tobacco plants. Our study demonstrates that TaMyb1D functions as a negative regulator of phenylpropanoid metabolism and a positive regulator of plant tolerance to drought and oxidative stresses.

Highly efficient intracellular drug delivery with a negatively charged hyperbranched polysulfonamine.

Efficient intracellular translocation is achieved using an easily prepared hyperbranched polysulfonamine that remains negatively charged at physiological pH. Investigations on the cellular uptake mechanism and the subcellular distribution of PSA are reported. The in vitro cytotoxicity of PSA is found to be low. Using doxorubicin as a model drug, a PSA/drug complex is prepared by electrostatic interaction with a high drug payload that exhibits a controlled release in response to pH. Efficient intracellular drug delivery, strong growth inhibition of tumor cells, and low cytotoxicity to normal cells are observed. The results suggest a possible way to utilize anionic polymers for intracellular delivery of therapeutic moieties or drugs.

Preparation of CdS nanocrystals within supramolecular self-assembled nanoreactors and their phase transfer behavior.

A new strategy for the synthesis of CdS nanocrystals (NCs) within supramolecular self-assembly nanoreactors has been described. The self-assembly nanoreactors were readily constructed through the electrostatic interactions and ion pairs between palmitic acid and the terminal amine groups of hyperbranched polymer. In a chloroform/water two-phase system, aqueous Cd (2+) ions were spontaneously encapsulated into the cavities of self-assembly nanoreactors in chloroform. After reaction with S (2-) ions, the CdS NCs with high stability were obtained. By the addition of excess triethylamine, CdS NCs formed in the self-assembly nanoreactors were transferred from organic phase into aqueous phase. After dialysis and rotorary evaporation, aqueous CdS NCs could be redispersed into chloroform solution containing palmitic acid.