In engineering practice, recycled asphalt pavement (RAP) is often obtained from various sources and is mixed and stockpiled in a disorderly manner, which is defined as a hybrid RAP. Thus, the material component of hybrid RAP shows great variability, possibly preventing the plant hot-mix recycled asphalt mixture (RHMA) from achieving stable quality. To address this problem, the German TL Asphalt-StB 07 guideline introduced an approach for evaluating the variability of RAP stockpile characteristics and subsequently determined the maximum permissible content of RAP in RHMA for different pavement layers based on the variability of the RAP stockpile. This study adopted this method in the Fuzhou–Yinchuan expressway maintenance project, Jiangxi Province, and reported a homogenization treatment measure for hybrid RAP. The results show that the material composition of hybrid RAP is characterized by significant heterogeneity in gradation and asphalt content, effectively reducing the heterogeneity of hybrid RAP, and the maximum permissible content of RAP in the binder layer can be increased by approximately 10% in the mass of RHMA. The homogenization treatment scale should comprehensively consider indices such as efficiency, cost, and expected dosage. The results of this study can serve as a reference value for determining a reasonable content of hybrid RAP in RHMA and ensuring stable RHMA quality.
Nanoparticles (NPs) functionalized with targeting ligands have shown promise, but are still limited by their nonspecific uptake by certain healthy tissues and cells that express low or even comparable levels of receptors. To increase their accumulation at tumor sites while decreasing the unintended toxicity, a possible solution is the involvement of two separate tumor-specific ligands in the localization. In this study, a dual tumor-targeting drug-loaded NP system was self-assembled by the amphiphilic conjugate of methotrexate-hyaluronic acid-octadecylamine (MTX-HA-OCA) with curcumin (CUR) encapsulated within the hydrophobic core (designated as MTX-HA-OCA/CUR NPs). The advantages of this nanosystem are that the anticancer drug MTX can be utilized as a tumor-targeting ligand toward folate receptors due to its structural similarity to folic acid (FA), and HA can serve as another tumor-targeting ligand toward CD44 receptors. The MTX-HA-OCA/CUR NPs are ∼70 nm in diameter and have sustained/controlled drug release behavior. An in vitro cellular uptake and competition inhibition study exhibited that MTX-HA-OCA/CUR NPs could significantly enhance the internalization efficiency in HeLa cells via folate/CD44 receptor-mediated endocytosis as compared to HA-OCA/CUR NPs. More importantly, the in vitro cytotoxicity of MTX-HA-OCA/CUR NPs was significantly enhanced as compared to those of the HA-OCA/CUR NPs, both free drugs, and individual free drug. Furthermore, the real-time in vivo and ex vivo fluorescence imaging of HeLa tumor-bearing mice showed that MTX-HA-OCA/CUR NPs could more efficiently enhance their accumulation and improve the penetration at the tumor site as compared to HA-OCA/CUR NPs. Therefore, these dually folate/CD44 receptor-targeted self-assembled HA NPs for the co-delivery of both anticancer drugs might provide a promising strategy for dual-targeted combination cancer therapy.
Recently, the global trend in the field of nanomedicine has been toward the design of combination of nature active constituents and phospholipid (PC) to form a therapeutic drug-phospholipid complex. As a particular amphiphilic molecular complex, it can be a unique bridge of traditional dosage-form and novel drug delivery system. In thisarticle, on the basis of drug-phospholipid complex technique and self-assembly technique, we chose a pharmacologically safe and low toxic drug curcumin (CUR) to increase drug-loading ability, achieve controlled/sustained drug release and improve anticancer activity. A novel CUR-soybean phosphatidylcholine (SPC) complex and CUR-SPC complex self-assembled nanoparticles (CUR-SPC NPs) were prepared by a co-solvent method and a nanoprecipitation method. DSPE-PEG-FA was further functionalized on the surface of PEG-CUR-SPC NPs (designed as FA-PEG-CUR-SPC NPs) to specifically increase cellular uptake and targetability. The FA-PEG-CUR-SPC NPs showed a spherical shape, a mean diameter of about 180 nm, an excellent physiological stability and pH-triggered drug release. The drug entrapment efficiency and drug-loading content was up to 92.5 and 16.3%, respectively. In vitro cellular uptake and cytotoxicity studies demonstrated that FA-PEG-CUR-SPC NPs and CUR-SPC NPs presented significantly stronger cellular uptake efficacy and anticancer activity against HeLa cells and Caco-2 cells compared to free CUR, CUR-SPC NPs and PEG-CUR-SPC NPs. More importantly, FA-PEG-CUR-SPC NPs showed the prolonged systemic circulation lifetime and enhanced tumor accumulation compared with free CUR and PEG-CUR-SPC NPs. These results suggest that the FA targeted PEGylated CUR-SPC complex self-assembled NPs might be a promising candidate in cancer therapy.
Crumble rubber (CR) can be used to prepare CR and styrene-butadiene-styrene (SBS) composite modified asphalt with a good high-and low-temperature performance, meanwhile the addition of CR could work as the substitute for SBS and help reduce the content of SBS. This study contains three main parts: effect of preparation and effect of material composition as well as rheological performance characterization. Factors during the preparation, including shearing temperature, shearing time, mixing time and swelling time, were selected, while base binder, CR content, CR particle size and SBS content in material composition were considered. The effects of these factors were assessed in terms of the conventional performance (penetration, softening point, ductility and storage stability). After identifying these effects, the sample of CR and SBS modified asphalt at the selected preparing condition and material composition (CR/SBSMA) was made, and the corresponding SBS modified and CR modified asphalt (SBSMA and CRMA) were produced for the comparing reason. Subsequently, temperature sweeps from 0°C to 80°C were utilized to depict the viscoelasticity of these modified asphalt binders by complex modulus and phase angle. Multiple stress creep recovery tests (MSCR) at 64°C and bending beam rheometer tests (BBR) at various low temperatures were employed to evaluate the high-and low-temperature performance, respectively. Results highlight that that CR/SBSMA could exhibit an excellent high-temperature performance (better than SBSMA), and a good low-temperature performance (reaching the level of base binder).
Photoacoustic computed tomography (PACT) is a fast-developing biomedical imaging modality and has immense potential for clinical translation. It utilizes laser excitation and acoustic detection to achieve high spatial resolution and considerable imaging depth in biological tissues. Current PACT primarily treats the absorption coefficient of tissues as a scalar variable while reconstructing the image, which limits its use for anisotropic evaluation of the tissues. Thus, by incorporating polarized imaging methods to evaluate anisotropy, applications of PACT can be further enhanced. So far, dichroism-sensitive PACT has been suggested for polarization detection of biological tissues. However, this approach is unsuitable for intraoperative imaging, since high-power spatial light is needed for excitation, which is dangerous and inconvenient to operate. Thus, there is a need to develop a polarized PACT system suitable for clinical use.Herein, we have proposed a specially designed handheld polarized PACT (HP-PACT) system, which was designed to promote intraoperative anisotropy detection of biological tissues. Excitation light was delivered by an optical fiber and reshaped by a compact set of lenses at the output end of the optical fiber. A polarizer was applied to generate linearly polarized light, and the polarization direction was adjusted by simply rotating the half-wave plate. Photoacoustic imaging (PAI) using excitation with several different polarization directions was carried out. Optical axes and the structure of the anisotropic objects were obtained using the principle of polarization detection with the PAI.We experimentally demonstrated the performance of HP-PACT by imaging both the polarized and unpolarized plastic films. The results showed that HP-PACT can successfully detect the direction of the optical axes of polarized plastic films and has the ability to image at different depths. When linearly polarized light with different polarization directions was used as excitation, PAI studies on a highly anisotropic bovine tendon and relatively low anisotropic mouse leg showed the structural differences between the 2 tissues. The quantified degrees of anisotropy of the bovine tendon and mouse legs were 0.6 and 0.3, respectively.The proposed HP-PACT is able to determine the anisotropic substances' optical axes and distinguish anisotropic substances from isotropic ones. Thus, HP-PACT has the potential for intraoperative diagnosis and treatment of anisotropic tissues, including nerves and tendons.
Self-assembly of multifunctional integrated nanoparticles loaded with methotrexate-phospholipid complex have both targeting and anticancer effect to FA receptors overexpressed cancer cells.
Both mechanical loading and autophagy play important roles in regulating bone growth and remodeling, but the relationship between the two remains unclear. In this study, we examined bone structure with micro-CT imaging and measured bone mechanical properties with three-point bending experiments using bones from wild-type (WT) mice and conditional knockout (cKO) mice with Atg7 deletion in their osteoblasts. We found that the knockout mice had significantly less bone volume, bone thickness, bone ultimate breaking force, and bone stiffness compared to wild-type mice. Additionally, bone marrow cells from knockout mice had reduced differentiation and mineralization capacities in terms of alkaline phosphatase and calcium secretion, as well as Runx2 and osteopontin expression. Knockout mice also had significantly less relative bone formation rate due to mechanical loading. Furthermore, we found that the osteoblasts from wild-type mice had stronger responses to mechanical stimulation compared to autophagy-deficient osteoblasts from knockout mice. When inhibiting autophagy with 3 MA in wild-type osteoblasts, we found similar results as we did in autophagy-deficient osteoblasts. We also found that mechanical loading-induced ATP release is able to regulate ERK1/2, Runx2, alkaline phosphatase, and osteopontin activities. These results suggest that the ATP pathway may play an important role in the possible involvement of autophagy in osteoblast mechanobiology.
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