Data-driven discovery of a universal indicator for metallic glass forming ability.

Despite the importance of glass forming ability as a major alloy characteristic, it is poorly understood and its quantification has been experimentally laborious and computationally challenging. Here, we uncover that the glass forming ability of an alloy is represented in its amorphous structure far away from equilibrium, which can be exposed by conventional X-ray diffraction. Specifically, we fabricated roughly 5,700 alloys from 12 alloy systems and characterized the full-width at half-maximum, Δq, of the first diffraction peak in the X-ray diffraction pattern. A strong correlation between high glass forming ability and a large Δq was found. This correlation indicates that a large dispersion of structural units comprising the amorphous structure is the universal indicator for high metallic glass formation. When paired with combinatorial synthesis, the correlation enhances throughput by up to 100 times compared to today's state-of-the-art combinatorial methods and will facilitate the discovery of bulk metallic glasses.

Biodegraded PCl and gelatin fabricated vascular patch in rat aortic and inferior vena cava angioplasty.

Novel synthetic prosthesis materials for patch angioplasty are continuously under development and optimization. When a nonwoven-based gelatin membrane is coupled with an electrospun layer of polycaprolactone (PCL), these biohybrid polymer membranes (BHMs) possess higher mechanical properties in aqueous environments. We hypothesized that BHMs can also be used as vascular patches, and we tested our hypothesis in a rat IVC venoplasty and aortic arterioplasty model. Patch venoplasty and arterioplasty were performed in SD rats (200 g), the patches were harvested at day 14, and samples were analyzed by immunohistochemistry and immunofluorescence. The BHM patches were almost degraded, with few parts remaining after 14 days. There was a line of CD34- and nestin-positive cells on the endothelium, with some cells were CD34 and nestin dual-positive, macrophages and leukocytes also participated in the patch healing process. There were PCNA-positive cells in the neointima and peri-patch area, with some cells were also PCNA and α-actin dual-positive. Arterial neointimal endothelial cells were Ephrin-B2- and dll-4-positive, and venous neointimal endothelial cells were Eph-B4- and COUP-TFII-positive. BHM shares a similar healing process like other patch materials, and BHM may have potential applications in vascular surgery.

Enhanced hydrolysis of lignocellulose in corn cob by using food waste pretreatment to improve anaerobic digestion performance.

This study aims to enhance hydrolysis and anaerobic digestion of corn cob (CC) by using food waste (FW) pretreatment. FW, which tends to be acidification in fermentation, was applied in this process as an acid-like agent to accelerate lignocellulose hydrolysis, aiming to promote methane yield in further digestion process. The effect of FW pretreatment on pH, soluble chemical oxygen demand (SCOD), volatile fatty acids (VFAs), cellulose/hemicellulose contents and cellulose crystallinity are specially focused. FW:CC = 1:3 based on volatile solid (VS) was found to be the optimal mixing ratio in pretreatment and its hydrolysis efficiency was 28% higher than the control group. An increase of 13.2% in cellulose reduction and a decrease of 6.7% in cellulose crystallinity was achieved at this ratio. Supplementation of FW increased VFA concentrations in slurry mixture that directly change the activities of enzymes and microorganisms. In the stage of methane production, the digester A3 (FW:CC = 1:6 based on VS) with higher hydrolysis efficiency presented the best performance in methane production with a specific methane yield of 401.6 mL/g·VS, due to the recovery of the pH in this digester to the optimal pH range for methanogens' metabolism (pH 6.3-7.2). Kinetics studies of cellulose/hemicellulose degradation indicated that the pretreatment of FW could improve the degradation of cellulose. Three-dimensional excitation emission matrix (3DEEM) results further confirmed that FW play an important role in lignocellulose hydrolysis. In addition, variations of lignocellulosic textures during the pretreatment were also cleared by using field emission-scanning electron microscopy (FE-SEM) analysis.

Effect of a novel prime-and-rinse approach on short- and long-term dentin bond strength of self-etch adhesives.

This study investigated the effects of the prime-and-rinse approach, using a 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer, on the short- and long-term dentin microtensile bond strengths (MTBSs) of mild self-etch adhesives. Half of sixty human midcoronal dentin surfaces were polished as control (self-etch approach), and the other half were polished and further treated with a 15% MDP-containing primer and thoroughly sprayed with water as prime-and-rinse approach. The dentin surfaces were treated with a self-etch adhesive, and a composite resin was placed on the surfaces. The following materials were used: Clearfil S3 Bond+Clearfil Majesty; G-Bond+Gradia Direct; Adper Easy One+Z250; and i Bond+Charisma. The MTBS was examined after 24 h and 14 months in water storage. The resin-dentin interfaces were analysed using scanning electron microscopy/transmission electron microscopy. Pretreated dentin surfaces were further analysed using scanning electron microscopy and micro-Raman spectroscopy. Compared with the self-etch approach, the prime-and-rinse approach significantly increased the dentin MTBS, regardless of the duration of storage. The scanning electron microscopy/transmission electron microscopy findings revealed that the prime-and-rinse approach removed most of the dentin smear layer. The Raman spectra of the MDP-treated dentin reveal the characteristic spectra of collagen, hydroxyapatite, and the monomer. Therefore, the prime-and-rinse approach using MDP-containing primers prior to the application of mild self-etch adhesives significantly increases the short- and long-term MTBS of dentin.

O2-evolving and ROS-activable nanoparticles for treatment of multi-drug resistant Cancer by combination of photodynamic therapy and chemotherapy.

Herein, a novel nano-system IF7-ROSPCNP, which is O2-evolving and reactive oxygen species (ROS)-activable, was developed for enhancing the combination chemotherapy and photodynamic therapy (PDT). The nanoparticles composed of photosensitizers (disulfonated meso-tetraphenylporphine, TPPS2a) and catalase in the inner core, doxorubicin (DOX) in the polymeric shell and functionalized on its surface with IF7 peptide, which specially bind to annexin 1. As confirmed that the structure of IF7-ROSPCNP was able to remain intact under normal physiological conditions. After IF7-ROSPCNP was selectively entrapped by the annexin 1-positive and ROS-abundant MCF-7/ADR cells, the shell of nanoparticles was ruptured and the entrapped photosensitizers were completely released out. Under irradiation, ROS was continuously produced and the DOX, which was conjugated to the terminal of polylactic copolymer (mPEG-PLA) by a ROS-cleavable linkage, was subsequently released. With such strategy, cellular uptake of drugs was dramatically improved resulted in an enhanced cytotoxicity and anti-tumor effect on drug resistant cancer.

Effects of regional enamel and prism orientations on bovine enamel bond strength and cohesive strength.

This study investigated the regional microtensile bond strength (MTBS) and cohesive strength of bovine enamel. The crowns of bovine incisors were sectioned, either horizontally along incisal and cervical thirds to produce horizontal and tangential segments, or longitudinally along the midline to produce longitudinal segments. Half of the horizontal and longitudinal segments were prepared using a 45° bevel. Then, the differently sectioned enamel surfaces were treated with one- or two-step self-etch adhesives (Clearfil SE Bond or Clearfil S3 Bond) and a composite resin (Clearfil Majesty) was placed. Resin-bonded enamel samples were cut into beams for use in the MTBS tests. Labial horizontal and longitudinal segments of pure enamel beams were prepared for cohesive strength tests. Enamel microstructures were analyzed by scanning electron microscopy. Three-way anova followed by Tukey's post-hoc HSD multiple comparisons procedure showed that a 45° bevel cut did not statistically significantly improve enamel MTBS, which varied with the different regions. The longitudinally sectioned resin-bonded enamel samples had the lowest MTBS, and the horizontal enamel cohesive strength was weaker than that of the longitudinal enamel. The scanning electron microscopy fractographs indicated that rows of parallel prisms were detached from the fractured surfaces. In conclusion, the regional enamel MTBS and the cohesive strength are strongly related to the enamel microstructures and prism orientations.

Polyethyleneimine-functionalized magnetic sugarcane bagasse cellulose film for the efficient adsorption of ibuprofen.

Polyethyleneimine-modified magnetic sugarcane bagasse cellulose film (P-SBC/Fe3O4 film) was simply fabricated for the removal of ibuprofen (IBP), a typical emerging organic contaminant. The P-SBC/Fe3O4 film exhibited an equilibrium adsorption amount of 370.52 mg/g for IBP and a corresponding removal efficiency of 92.63 % under following adsorption conditions: 318 K, pH 4, and 0.25 mg/mL dosage. Thermodynamic studies indicated that adsorption of IBP on the P-SBC/Fe3O4 film was spontaneous (∆G < 0) and endothermic (∆H > 0). The adsorption data conformed to the Freundlich isotherm model and multilayer adsorption model (two layers), and an average of 3-4 active sites on the P-SBC/Fe3O4 film share an IBP molecule. Both the EDR-IDR and AOAS models vividly described the dynamic characteristics of adsorption process. Model fitting results, theoretical calculations, and comprehensive characterization revealed that adsorption is driven by electrostatic interactions between the primary amine of P-SBC/Fe3O4 film and the carboxyl group of IBP molecule, while other weak interactions are also non-ignorable. Furthermore, quantitative calculations based on density functional theory (DFT) underscored the importance of PEI functionalization. In conclusion, P-SBC/Fe3O4 film is an environmentally friendly and cost-effective adsorbent with significant potential for effectively removing IBP, while maintaining its efficacy over multiple cycles.

Remineralization of Dentin with Cerium Oxide and Its Potential Use for Root Canal Disinfection.

Objective: This study was to investigate a novel antibacterial biomimetic mineralization strategy for exploring its potential application for root canal disinfection when stabilized cerium oxide was used. Material and Methods: A biomimetic mineralization solution (BMS) consisting of cerium nitrate and dextran was prepared. Single-layer collagen fibrils, collagen membranes, demineralized dentin, and root canal system were treated with the BMS for mineralization. The mineralized samples underwent comprehensive characterization using various techniques, including transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared spectroscopy (FTIR), scanning transmission electron microscopy (STEM), selected-area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and micro-CT. Additionally, the antimicrobial properties of the BMS and the remineralized dentin were also analyzed with broth microdilution method, live/dead staining, and SEM. Results: Cerium ions in the BMS underwent a transformation into cerium oxide nanoparticles, which were deposited in the inter- and intra-fibrillar collagen spaces through a meticulous bottom-up process. XPS analysis disclosed the presence of both Ce (III) and Ce (IV) of the generated cerium oxides. A comprehensive examination utilizing SEM and micro-CT identified the presence of cerium oxide nanoparticles deposited within the dentinal tubules and lateral canals of the root canal system. The BMS and remineralized dentin exhibited substantial antibacterial efficacy against E. faecalis, as substantiated by assessments involving the broth dilution method and live/dead staining technique. The SEM findings revealed the cell morphological changes of deceased E. faecalis. Conclusion: This study successfully demonstrated antibacterial biomimetic mineralization as well as sealing dentinal tubules and lateral branches of root canals using cerium nitrate and dextran. This novel biomimetic mineralization could be used as an alternative strategy for root canal disinfection.

A glycol chitosan derivative with extrafibrillar demineralization potential for self-etch dentin bonding.

OBJECTIVES: Extrafibrillar demineralization is an etching technique that removes only minerals from around the collagen fibrils for resin infiltration. The intrafibrillar minerals are left intact to avoid their replacement by water that is hard for adhesive resin monomers to displace. The present work reported the synthesis of a water-soluble methacryloyloxy glycol chitosan-EDTA conjugate (GCE-MA) and evaluated its potential as an extrafibrillar demineralization agent for self-etch dentin bonding. METHODS: Glycol chitosan-EDTA was functionalized with a methacryloyloxy functionality. Conjugation was confirmed using Fourier transform-infrared spectroscopy. The GCE-MA was used to prepare experimental self-etch primers. Extrafibrillar demineralization of the primers was evaluated with scaning electron microscopy and transmission electron microscopy. The feasibility of this new self-etch bonding approach was evaluated using microtensile bond strength testing and inhibition of dentin gelatinolytic activity. The antibacterial activity and cytotoxicity of GCE-MA were also analyzed. RESULTS: Conjugation of EDTA and the methacryloyloxy functionality to glycol chitosan was successful. The functionalized conjugate was capable of extrafibrillar demineralization of mineralized collagen fibrils. Tensile bond strength of the experimental self-etch primer to dentin was comparable to that of phosphoric acid-etched dentin and the commercial self-etch primer Clearfil SE Bond 2. The GCE-MA also inhibited soluble rhMMP-9. In-situ zymography detected minimal fluorescence in hybrid layers conditioned with the experimental primer. The GCE-MA was noncytotoxic and possessed antibacterial activities against planktonic bacteria. SIGNIFICANCE: Synthesis of GCE-MA brought into fruition a self-etch conditioner that selectively demineralizes the extrafibrillar mineral component of dentin. A self-etch primer prepared with GCE-MA achieved bond strengths comparable to commercial reference adhesive systems.

Dentin surface modification by MDP to improve dentin bonding stability: Topological enhancement and mineralization of collagen structure in hybrid layers.

Decades of research have been conducted on 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) through numerous studies. The mechanisms by which its residual calcium salts benefit dentin bonding remain undetermined. The objective of the research was to investigate the role and process of remaining calcium salts in the priming procedure and their capacity for remineralization. The investigation focused on the variations in topological structure, mechanical properties, and chemical interactions between the main agent and the dentin surface. Two adhesive modes including prime-and-rinse(P&R) and prime-and-nonrinse (P&NR) utilized to evaluate the bonding performance and remineralization ability. The findings indicated that both P&R and P&NR methods could eliminate the smear-layer, uncover dentinal-tubules, and generate a textured/rough surface on the dentin. Collagen fibrils exhibited a greater presence of inorganic minerals in the P&NR mode. Compared to control group, both P&R and P&NR groups improved immediate and aging bond strength significantly (P < 0.05). AFM and 3D-STORM revealed MDP and its residual calcium salts distributed in collagen fibrils and expanded collagen matrix. In the P&NR group, TEM revealed that the dentin collagen matrix experienced some remineralization, and there was also mineralization within the collagen fibrils embedded in the bonding interface. Thus, MDP priming improved dentin bonding stability. Residual calcium salts of P&NR process can enhance topological structure of the collagen matrix and induce intrafibrillar mineralization.

High capacity and selective adsorption of Congo red by cellulose-based aerogel with mesoporous structure: Adsorption properties and statistical data simulation.

Large quantities of organic dyes are discharged into the environment, causing serious damage to the ecosystem. Therefore, it is urgent to develop inexpensive adsorbents to remove organic dyes. A novel cellulose-based aerogel (MPPA) with 3D porous structure was prepared by using cassava residue (cellulose) as basic construction blocks, doping ferroferric oxide (Fe3O4) for magnetic separation, and applying polyethyleneimine (PEI) as functional material for highly efficient and selective capture of Congo red (CR). MPPA exhibited porous network structure, numerous active capture sites, nontoxicity, high hydrophilicity, and excellent thermal stability. MPPA showed superior adsorption property for CR, with an equilibrium adsorption capacity of 2018.14 mg/g, and still had an adsorption property of 1189.31 mg/g after five recycling procedures. In addition, MPPA has excellent selectivity for CR in four binary dye systems. The adsorption behavior of MPPA on CR was further explored using a multilayer adsorption model, EDR-IDR hybrid model and AOAS model. Electrostatic potential and independent gradient models were used to further verify the possible interaction between MPPA and CR molecules. In conclusion, MPPA is a promising adsorbent in the field of treating anionic dyes.

(3-Chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel for remelt syrup decolorization in sugar refining.

The crucial need for quality refined sugar has led to the development of advanced adsorbents, with a focus on the decolorization of remelt syrup. In this study, (3-chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel (CP-PPA) was fabricated, and synthetic melanoidins were used as model colorants of remelt syrup to evaluate the validity and practicality of CP-PPA for eliminating colored impurities. Integrating abundant amine-functionalized groups (quaternary ammonium and protonated amine) within the pomelo peel-derived aerogel directionally captured electronegative melanoidins via electrostatic interactions. Furthermore, the active sites, types, and relative strength of the weak interactions between CP-PPA and melanoidins were determined using density functional theory simulations. CP-PPA exhibited an excellent equilibration adsorbing capacity for capturing melanoidins of 749.51 mg/g, and a removal efficiency of 93.69 %. Additionally, the adsorption mechanism was thoroughly examined in an effort to improve the economy of the sugar refinement industry.

Hyperbranched polyethyleneimine-functionalised chitosan aerogel for highly efficient removal of melanoidins from wastewater.

Melanoidins are hazardous dark-coloured substances contained in molasses-based distillery wastewater. Adsorption is an effective approach to eliminate melanoidins from wastewater. However, melanoidin adsorption capacities of available adsorbents are unsatisfactory, which seriously limits their practical application. A hyperbranched polyethyleneimine-functionalised chitosan aerogel (HPCA) was fabricated as an effective adsorbent for melanoidin scavenging. HPCA demonstrated superior melanoidin adsorption efficiency because of its high specific surface area, abundant amino functional groups, and high hydrophilicity. Melanoidin removal rate of HPCA was 94.95%, which remained at 91.45% after 5 cycles. Notably, using the Langmuir isothermal model, the maximum melanoidin adsorption capacity of HPCA was determined to be 868.36 mg/g, surpassing those of most of previously reported adsorbents. Toxicity experiments indicated that HPCA can be considered a safe adsorbent with excellent biocompatibility that hardly threatens aquatic organisms. The efficient melanoidin removal of HPCA was attributed to electrostatic attraction, H-bonding, and van der Waals force. However, the adsorption might be predominantly controlled by electrovalent interaction between protonated amino groups of HPCA and carboxyl/carboxylate groups of melanoidins. Two novel models, namely, external diffusion resistance-internal diffusion resistance mixed model and adsorption on active site model, were employed to describe the dynamic mass transfer characteristics of melanoidin adsorption by HPCA.

A resilient and lightweight cellulose/graphene oxide/polymer-derived multifunctional carbon aerogel generated from Pickering emulsion toward a wearable pressure sensor.

In the new era of competitive smart electronics, the development of compressible multifunctional carbon aerogels is highly needed, but still faces enormous challenges. Here we demonstrate a robust strategy to fabricate multifunctional carbon aerogel via freeze-drying of cellulose nanofibers (CNF) and graphene oxide (GO) co-stabilized Pickering emulsion gel followed by high-temperature annealing. The resulting carbon aerogel exhibits tunable mechanical, hydrophilic and hydrophobic properties due to varying the elemental composition and the pyrolysis of introduced polymers. The carbon aerogel is resilient against high compression strain up to 99 % and has ultralow density (1.82 mg/cm3). The CNF/GO/acrylonitrile butadiene styrene-derived carbon aerogel (CRA)-based sensor has shown desirable sensitivity (17.65 kPa-1), ultralow detection limit of pressure (60 Pa), and fast responsive time (130 ms), which is capable of detecting human activity, identifying spatial pressure distribution, and communicating with smartphones via Wi-Fi. Moreover, the carbon aerogel reveals effective thermal insulation and photothermal conversion performance. These results suggest the great potentials for developing lightweight and compressible carbon aerogels with multiple functions to meet various applications.

Optimization Method of Tool Parameters and Cutting Parameters Considering Dynamic Change of Performance Indicators.

In the process of metal cutting, the cutting performance of cutting tools varies with different parameter combinations, so the results of the performance indicators studied are also different. So in order to achieve the best performance indicator it is necessary to get the best parameter matching combination. In addition, in the process of metal cutting, the value of the performance index is different at each stage of the processing process. In order to consider the cutting process more comprehensively, it is necessary to use a comprehensive evaluation method that can evaluate the dynamic process of performance indicators. This paper uses a dynamic evaluation method that considers the dynamic change of performance indicators in each stage of the cutting process to comprehensively evaluate the tool parameters and cutting parameters at each level. For the purpose of high processing efficiency and long tool life, tool wear rate and material removal rate are used as performance indicators. In the case of specified rake angle, cutting speed and cutting width, titanium alloy is studied by end milling cutter side milling. The tool parameters and cutting parameters in milling process are optimized by using a dynamic comprehensive evaluation method based on gain horizontal excitation. Finally, the parameter matching combination that can make the performance indicator reach the best is obtained. The results show that when the rake angle is 8°, the cutting speed is 37.68 m/min, and the cutting width is 0.2 mm, the tool wear rate and material removal rate are the best when the clearance angle is 9°, the helix angle is 30°, the feed per tooth is 0.15 mm/z, and the cutting depth is 2.5 mm.

A novel porous silica-zirconia coating for improving bond performance of dental zirconia.

OBJECTIVES: To coat a zirconia surface with silica-zirconia using a dip-coating technique and evaluate its effect on resin-zirconia shear bond strength (SBS). METHODS: A silica-zirconia suspension was prepared and used to coat a zirconia surface using a dip-coating technique. One hundred and eighty-nine zirconia disks were divided into three groups according to their different surface treatments (polishing, sandblasting, and silica-zirconia coating). Scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and X-ray diffraction (XRD) were used to analyze the differently treated zirconia surfaces. Different primer treatments (Monobond N, Z-PRIME Plus, and no primer) were also applied to the zirconia surfaces. Subsequently, 180 composite resin cylinders (Filtek Z350) were cemented onto the zirconia disks with resin cement (RelyX Ultimate). The SBS was measured after water storage for 24 h or 6 months. The data were analyzed by two-way analysis of variance (ANOVA). RESULTS: SEM and EDX showed that the silica-zirconia coating produced a porous layer with additional Si, and XRD showed that only tetragonal zirconia was on the silica-zirconia-coating surface. Compared with the control group, the resin-zirconia SBSs of the sandblasting group and silica-zirconia-coating group were significantly increased (P<0.05). The silica-zirconia coating followed by the application of Monobond N produced the highest SBS (P<0.05). Water aging significantly reduced the resin-zirconia SBS (P<0.05). CONCLUSIONS: Dip-coating with silica-zirconia might be a feasible way to improve resin-zirconia bonding.

Biomimetic fabrication and application of fibrous-like nanotubes.

AIMS: To investigate the biomimetic fabrication of fibrous-like organic-inorganic hybrid structures via a simple bottom-up approach, viz. self-assembly of simple molecules, and apply fibrous-like composites as a novel primer to improve dentin bond strengths of self-etch adhesives. MATERIALS AND METHODS: The resultants of commercial amorphous calcium phosphate (ACP) nanoparticles and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) ethanol-aqueous solution were analyzed by TEM, SEM, XRD, DLS and AFM. The acid and alkali resistance of abovementioned self-assembled composites were analyzed with TEM. Micro-tensile bond strengths (MTBS) tests were performed after polished dentin surfaces were pretreated with self-assembled composites. The pretreated dentin surfaces and dentin-resin interfaces were characterized by SEM/TEM. KEY FINDINGS: ACP nanoparticles in MDP solution could self-assemble into fibrous-like nanotube structures in 8 nm diameter. Self-assembly and self-proliferation process went from ACP nanoparticles, dissolved ACP nanoparticles (less than 50 nm), twig-like structures and fibrous-like nanotubes to cellular networks. The fibrous-like nanotubes were only detected when the amount of ACP in reaction system were more than 0.01 g. The more ACP interacted with MDP, the more fibrous-like nanotubes were formed. After the dentin surfaces were treated with fibrous-like nanotube composites, MTBS could be significantly improved. Moreover, the fibrous-like nanotube structures could be resistant to acidic challenge, and were stable at least for 3 months. SIGNIFICANCE: The fibrous-like nanotube structures could be self-assembled via a bottom-up approach at certain ratio of MDP and commercial ACP nanoparticles. The application of fibrous-like nanotube composites as a novel primer prior to self-etch adhesives greatly improved dentin bond strengths.

Immune checkpoint programmed death-1 mediates abdominal aortic aneurysm and pseudoaneurysm progression.

PURPOSE: The causes and pathogenetic mechanisms underlying abdominal aortic aneurysms (AAAs) and pseudoaneurysms are not fully understood. We hypothesized that inhibiting programmed death-1 (PD-1) can decrease AAA and pseudoaneurysm formation in mouse and rat models. METHODS: Human AAA samples were examined in conjunction with an adventitial calcium chloride (CaCl2) application mouse model and an aortic patch angioplasty rat model. Single-dose PD-1 antibody (4 mg/kg) or BMS-1 (PD-1 inhibitor-1) (1 mg/kg) was administered by intraperitoneal (IP) or intraluminal injection. In the intramural injection group, PD-1 antibody was injected after CaCl2 incubation. The rats were divided into three groups: (1) the control group was only decellularized without other special treatment, (2) the PD-1 antibody-coated patch group, and (3) the BMS-1 coated patch group. Patches implanted in the rat abdominal aorta were harvested on day 14 after implantation and analyzed. RESULTS: Immunohistochemical analysis showed PD-1-positive cells, PD-1 and CD3, PD-1 and CD68, and PD-1 and α-actin co-expressed in the human AAA samples. Intraperitoneal (IP) injection or intraluminal injection of PD-1antibody/BMS-1 significantly inhibited AAA progression. PD-1 antibody and BMS-1 were each successfully conjugated to decellularized rat thoracic artery patches, respectively, by hyaluronic acid. Patches coated with either humanized PD-1 antibody or BMS-1 can also inhibit pseudoaneurysm progression and inflammatory cell infiltration. CONCLUSION: PD-1 pathway inhibition may be a promising therapeutic strategy for inhibiting AAA and pseudoaneurysm progression.

Inhibition of programmed death-1 decreases neointimal hyperplasia after patch angioplasty.

Neointimal hyperplasia remains an obstacle after vascular interventions. Programmed death-1 (PD-1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against neointimal hyperplasia. We hypothesized that inhibition of PD-1 inhibits neointimal hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD-1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD-1 antibody-coated patches, and BMS-1 (PD-1 inhibitor)-coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD-1-positive cells were present. Inhibition of PD-1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased neointimal thickness (p = 0.0199). There were significantly fewer PD-1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)-positive cells, and PCNA/α-actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS-1 showed similarly decreased neointimal thickness and accumulation of inflammatory cells. Inhibition of PD-1 using PD-1 antibody or its inhibitor BMS-1 can significantly decrease neointimal thickness in vascular patches. Inhibition of the PD-1 pathway may be a promising therapeutic strategy to inhibit neointimal hyperplasia.

A novel prime-&-rinse mode using MDP and MMPs inhibitors improves the dentin bond durability of self-etch adhesive.

OBJECTIVES: The study investigated the effects of novel prime-&-rinse mode using MDP (10-methacryloyloxydecyl dihydrogenphosphate) and matrix metalloproteinase (MMPs) inhibitors on dentin microtensile bond strengths (MTBS) of self-etch adhesive, resin-dentin interface degradations, and activity of recombinant human (rh) MMP-8, -9. MATERIALS AND METHODS: Eight experimental primers were prepared using 5% and 15% of MDP ethanol-aqueous (1:1) solution in combination with/without MMPs inhibitors (1%benzalkonium chloride (BAC), 1000 µm/mL polyvinylphosphonic acid (PVPA) and 15%proanthocyanidin (PA)). Ninety human mid-coronal dentin surfaces were applied with the experimental primers, water-sprayed and gently air-dried (prime-&-rinse mode), or not (control, self-etch mode). The specimens were bonded with self-etch adhesive (Clearfil S3 Bond) and composite resin (Clearfil Majesty). The resin-bonded specimens were prepared into multiple micro-beams for MTBS tests after 24 h and 1 yr of water storage. The resin-dentin interfaces were analyzed with SEM/TEM. The inhibitory effects of eight primers on rhMMP-8, 9 were determined. The data were analyzed using two-way ANOVA and LSD multiple comparisons tests. RESULTS: Compared with control, all the primers used in prime-&-rinse mode could significantly improve long-term dentin MTBS (P < 0.05), while 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short-term dentin MTBS (P < 0.05). The SEM/TEM findings revealed that the resin-dentin interfaces were stable over time when the prime-&-rinse mode used. Eight primers possessed the high inhibitory ratio of rh MMP-8, 9. CONCLUSIONS: The novel prime-&-rinse mode using 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short- and long-term dentin MTBS of self-etch adhesive. This might be a supplement to contemporary dentin bonding strategies.