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A facile approach to prepare monodisperse polystyrene (PS) particles containing quaternary ammonium salts with long alkyl chain was reported. The PS particles containing quaternary ammonium salts are prepared by two-stage dispersion polymerization in ethanol/water (80/20 w/w) mixture with polyvinylpyrrolidone (PVP) as a steric stabilizer and fatty alcohol polyoxyethylene ether (AEO-9) as a co-stabilizer. Polymerizations are conducted using N′-dimethyl-N-n-dodecyl-N-2-methacryloyloxyethylammonium bromide (QDMDB) as a comonomer added in the second stage. We identify reaction conditions where one can obtain the functional polystyrene microspheres with a size distribution less than 3%. The influence of the initiator concentration, the styrene monomer concentration, the stabilizer concentration, and QDMDB comonomer concentration on the average particle size and the efficient of variation are investigated comprehensively. The novel particles are examined using scanning electron microscopy (SEM), gel permeation chromatography (GPC), zeta potential, and nuclear magnetic resonance (1H NMR). QDMDB comonomer not only functionalized the polystyrene particles but also proved to be effective in controlling the particle size and size distribution. According to these results, we show that two-stage dispersion polymerization is an effective pathway for the structure design of the functional microspheres. [ABSTRACT FROM AUTHOR]

• A novel data-driven reduced-order model framework combining proper orthogonal decomposition-based reduced-order modeling method and autoencoder neural network is proposed. • A data-driven POD-AE reduced-order model of 3D regenerative cooling channel is established for the first time. • This framework achieved acceptable accuracy in reconstruction of supercritical-pressure flow, compared with conventional proper orthogonal decomposition. • This framework improves computational efficiency by nearly 5000 times compared with ANSYS Fluent 2021 R1. In order to effectively estimate the physical fields of active cooling channel with supercritical pressure hydrocarbon fuel, a novel data-driven reduced-order model framework is firstly proposed in the present work, which is established via combining reduced-order modeling method based on proper orthogonal decomposition and autoencoder neural network (POD-AE) with Kriging surrogate model. This framework mainly contains offline stage and online stage. Preliminary dimension reduction and feature capture of high-dimensional physical fields data is conducted using POD in the offline stage, and low-dimensional reduced-order models (ROMs) are constructed by the linear combination of orthogonal bases and feature coefficients. Specially, feature coefficients of ROMs are used to trained an AE, and then lower-dimensional secondary reduced-order models (2nd-ROMs) are established by secondary compression for ROMs using the trained AE. Furthermore, the Kriging model is trained for implicitly mapping boundary conditions or temperature data from the sensors on the bottom surface to the established 2nd-ROMs. In the online stage, physical fields estimation under new boundary conditions or wall temperature monitoring based on temperature data of sensors can be quickly fulfilled using this framework. Fifty groups of test conditions are considered to demonstrate the accuracy and efficiency of the POD-AE ROM framework. The results prove that it shows good efficiency, accuracy in estimating and monitoring the physical fields of the cooling channel with supercritical pressure n-dodecane within sample space. Compared with the traditional POD-based ROM framework, the proposed framework still achieved acceptable accuracy under all testing conditions when the original data was compressed to extremely low dimensions. And the calculation time only slightly increased. [ABSTRACT FROM AUTHOR]

N-phenylmaleimide (N-PMI) and its precursor, (Z)-4-oxo-4-(phenylamino)but-2-enoic acid, were synthesized from aniline and maleic anhydride. Copolymerization between N-phenylmaleimide and styrene was initiated in micropores and outside surface of porous polyvinyl chloride (PVC) resin suspended in aqueous phase. The modified PVC was characterized with Gel Permeation Chromatography, thermal gravimetric analysis and scanning electron microscopy. The result of high performance liquid chromatography shows that the purity of N-PMI reached 97.3%. Thermal gravimetric analysis indicated that the introduction of N-PMI could clearly affect the thermal degradation behavior of PVC, and when PMI was at 6.25% of the PVC mass, the decomposition temperature T0.5 of modified polymer was increased to 314.2°C. The glass transition temperature of modified polymer was increased from 70°C to 80°C. [ABSTRACT FROM AUTHOR]

Functional limitation caused by spinal cord injury (SCI) has the problem of significant clinical and economic burden. Damaged spinal axonal connections and an inhibitory environment severely hamper neuronal function. Regenerative biomaterials can fill the cavity and produce an optimal microenvironment at the site of SCI, inhibiting apoptosis, inflammation, and glial scar formation while promoting neurogenesis, axonal development, and angiogenesis. Decellularization aims to eliminate cells from the ultrastructure of tissues while keeping tissue-specific components that are similar to the structure of real tissues, making decellularized extracellular matrix (dECM) a suitable scaffold for tissue engineering. dECM has good biocompatibility, it can be widely obtained from natural organs of different species, and can be co-cultured with cells for 3D printing to obtain the target scaffold. In this paper, we reviewed the pathophysiology of SCI, the characteristics of dECM and its preparation method, and the application of dECM in the treatment of SCI. Although dECM has shown its therapeutic effect at present, there are still many indicators that need to be taken into account, such as the difficulty in obtaining materials and standardized production mode for large-scale use, the effect of decellularization on the physical and chemical properties of dECM, and the study on the synergistic effect of dECM and cells. [ABSTRACT FROM AUTHOR]

A two-stage synthesis of surface-functionalized monodisperse polystyrene (PS) microspheres in ethanol/water medium by introducing methacryloyloxyethyl dodecyl dimethyl ammonium bromide (QDMDB) to dispersion polymerization of styrene is reported. Polyvinylpyrrolidone (PVP) and fatty alcohol polyoxyethylene ether (AEO-9) are used as dispersion stabilizers. The novel microspheres are characterized by FT-IR, SEM, GPC, TGA, water contact angle (WCA), etc. The dispersion polymerization goes through successfully with the solid content up to 58.75%, in which the water content in the medium is 20%. The water content in the medium has a certain effect on the particle size and molecular weight of microspheres. Under the experimental conditions, the average diameters of the obtained microspheres are approximately 550-1200 nm with the number average molecular weight of up to 5.8 × 105. The introduction of QDMDB improves the wettability and thermal stability of the poly(St-co-QDMDB) microspheres. A mechanism of dispersion copolymerization based on XPS and 1H NMR is proposed.ᅟ [ABSTRACT FROM AUTHOR]

Tamoxifen is the most commonly used treatment for estrogen-receptor (ER) positive breast cancer patients, but its efficacy is severely hampered by resistance. PI3K/AKT/mTOR pathway inhibition was proven to augment the benefit of endocrine therapy and exhibited potential for reversing tamoxifen-induced resistance. However, the vast majority of PI3K inhibitors currently approved for clinical use are unsatisfactory in terms of safety and efficacy. We developed two-dimensional CuPd (2D-CuPd) nanosheets with oxidase and peroxidase nanozyme activities to offer a novel solution to inhibit the activity of the PI3K/AKT/mTOR pathway. 2D-CuPd exhibit superior dual nanozyme activities converting hydrogen peroxide accumulated in drug-resistant cells into more lethal hydroxyl radicals while compensating for the insufficient superoxide anion produced by tamoxifen. The potential clinical utility was further demonstrated in an orthotopically implanted tamoxifen-resistant PDX breast cancer model. Our results reveal a novel nanozyme ROS-mediated protein mechanism for the regulation of the PI3K subunit, illustrate the cellular pathways through which increased p85β protein expression contributes to tamoxifen resistance, and reveal p85β protein as a potential therapeutic target for overcoming tamoxifen resistance. 2D-CuPd is the first reported nanomaterial capable of degrading PI3K subunits, and its high performance combined with further materials engineering may lead to the development of nanozyme-based tumor catalytic therapy. [ABSTRACT FROM AUTHOR]

MiR-329 has been proved to be a tumor suppressor gene in various malignancies, however, its role in osteosarcoma remains elusive. We found that miR-329 is remarkably downregulated in osteosarcoma tissues and relates to advanced stages. MiR-329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest. In addition, miR-329 also suppresses wound-healing and migration ability of osteosarcoma cells and inhibits tumorigenicity in vivo. Rab10 was identified as a target of miR-329 in osteosarcoma and mediates its biofunction. These findings may shed light to the understanding of tumor development in osteosarcoma. [ABSTRACT FROM AUTHOR]

• A gelatin-based bilayer scaffold with Cur/GT as upper and DS/GT as bottom layer was developed. • Cur/GT exerted antiangiogenic activity to the stable chondrogenesis of BMSCs. • DS/GT endowed proangiogenic effects to promote osteogenesis of BMSCs. • The BMSC-loaded bilayer scaffold achieved subcutaneous osteochondral regeneration. Bone marrow stem cell (BMSC) therapy is a promising method to achieve subcutaneous osteochondral regeneration. However, it remains obscure due to the incorrect angiogenic niche. Studies have demonstrated that an antiangiogenic niche promotes cartilage regeneration, whereas a proangiogenic niche facilitates bone formation. Considering that curcumin (Cur) is an antiangiogenic drug and Danshen (DS) is a proangiogenic drug, this study is the first to develop a gelatin-based bilayer porous scaffold, where curcumin-loaded gelatin (Cur/GT) was used as the upper layer and DanShen-loaded gelatin (DS/GT) was used as the bottom layer. The data revealed that both Cur and DS could be sustained and released from Cur/GT and DS/GT, respectively. When cocultured with human umbilical vein endothelial cells, Cur/GT inhibited tube formation, whereas DS/GT promoted tube formation. Furthermore, the findings demonstrated that the Cur addition in the upper layer exerted antiangiogenic activity to the stable chondrogenesis of BMSCs, the DS addition in the bottom layer endowed proangiogenic effects to promote osteogenesis of BMSCs, and the bilayer scaffold successfully achieved subcutaneous osteochondral regeneration when recolonized with BMSCs. This study provides new insight into subcutaneous osteochondral regeneration by leveraging the angiogenic microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to prove that it is feasible to diagnose discoid lateral meniscus in radiographs. Plain radiographic findings of discoid lateral menisci with matched controls were analysed and compared in a quantitative method.Methods: Sixty consecutive patients (60 knees) who were diagnosed with discoid lateral meniscus (discoid group) by magnetic resonance imaging (MRI) were included. Another 60 age- and sex-matched controls with normal medial and lateral menisci on the basis of MRI findings were included as the control group. Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the fibular head (HFH), lateral joint space distance (LJSD), height of the lateral tibial spine (HLTS), obliquity of the lateral tibial plateau, obliquity of the lateral femoral condyle, distance from the lateral tibial spine to the lateral femoral condyle, height of the medial tibial spine, chordal distance of the femoral condyle (CDLF, CDMF), the HFH/LJSD, LJSD/HLTS and the CDLF/CDMF.Results: A significant difference was found in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS between the two groups. The cut-off values of the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS were 12.9 mm, 6.6 mm, 7.8 mm, 3.0 mm, 2.7 mm, 2.0 and 0.9, respectively. Among the cut-off values in diagnosing discoid lateral meniscus, the sensitivity, specificity and ROC curve area of LJSD/HLTS were as high as 73.6 %, 83.0 % and 0.8, respectively. The corresponding values of the HFH/LJSD were as high as 66.0 %, 86.8 % and 0.8. For the first two indicators, the results of the HFH/LJSD and LJSD/HLTS were higher than that of most other parameters. At the same time, the ROC curve area of the HFH/LJSD and LJSD/HLTS ranked highest among all the results.Conclusion: There were significant differences in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS, especially the HFH/LJSD and the LJSD/HLTS, between plain radiographic findings of discoid lateral meniscus patients and normal controls. The results of the HFH/LJSD and the LJSD/HLTS showed a positive impact on the diagnosis of discoid lateral meniscus in this research. These findings enable radiographs to screen for discoid lateral meniscus.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Background: Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient's current mental state is suitable enough to accept a TKA surgery. Methods: Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated. Results: Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA. Conclusion: Our outcomes can help clinicians evaluate whether a patient's current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS. [ABSTRACT FROM AUTHOR]

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg 2+ /Ca 2+ balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP–P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg 2+ on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg 2+ ([Mg 2+ ] e ) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 μM ATP reversed this inhibitory effect in vitro . In addition, the spontaneous release of ATP was inhibited by high [Mg 2+ ] e levels. A high [Mg 2+ ] e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg 2+ and Ca 2+ is therefore contradictory, Mg 2+ inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca 2+ . JC-1 staining verified the protective effect of Mg 2+ on mitochondrial membrane potential and the decrease induced by Ca 2+ . Taken together, these results indicate that high [Mg 2+ ] e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg 2+ and Ca 2+ influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs. [ABSTRACT FROM AUTHOR]

Point mutations within the DNA-binding domain of the TP53 gene occur in a significant percentage of human cancer, leading to cellular accumulation of highly stabilized mutant p53 proteins (mutp53) with tumor-promoting properties. Depletion of mutp53, through inducing either autophagic or proteasomal degradation, is an attractive strategy for the therapy of p53-mutated cancer, but the currently-known degradation inducers, almost exclusively small molecules, are inadequate. Here we show that pH-responsive zeolitic imidazolate framework-8 (ZIF-8) offers a novel solution to mutp53 degradation. ZIF-8 facilitated ubiquitination-mediated and glutathionylation-dependent proteasomal degradation of all of the nine mutp53 we tested, including six hot-spot mutp53, but not the wild-type p53 protein. Sustained elevation of intracellular Zn++ level, resulted from decomposition of the internalized ZIF-8 in the acidic endosomes, decreased the intracellular reduced glutathione (GSH): oxidized glutathione (GSSG) ratio and was essential for mutp53 glutathionylation and degradation. ZIF-8 modified with an Z1-RGD peptide, exhibiting enhanced cellular internalization and improved decomposition behavior, preferentially killed mutp53-expressing cancer cells and demonstrated remarkable therapeutic efficacy in a p53 S241F ES-2 ovarian cancer model as well as in a p53 Y220C patient-derived xenograft (PDX) breast cancer model. The ability to induce wide-spectrum mutp53 degradation gives ZIF-8 a clear advantage over other degradation-inducers, and engineered nanomaterials may be promising alternatives to small molecules for the development of mutp53-targeting drugs. [Display omitted] [ABSTRACT FROM AUTHOR]