Photoinduced On and Off Polymeric Room Temperature Phosphorescence Based On Polycyclic Aromatic Hydrocarbon Isomers.

As family members of polycyclic aromatic hydrocarbons, compound anthracene (Ant) and phenanthrene (Phe) as isomers are widely used in organic optical materials and electronic materials. But their photochemical and physical properties are very different. In this work, the room temperature phosphorescence (RTP) properties of PVA-B-Ant and PVA-B-Phe are discussed carefully which are prepared by B-O click reaction through polyvinyl alcohol (PVA) with 9-anthraceneboronic acid (B-Ant) and 9-phenanthrenylboronic acid (B-Phe), respectively. PVA-B-Phe 1% film exhibits excellent fluorescence (FL) emission at 374 nm and RTP emission at 523 nm with green afterglow and around 1.9 s phosphorescence lifetime. However, PVA-B-Ant 1% film only shows strong blue FL emission at 414 nm, and the emission intensity decreases seriously with the extension of irradiation time. Experimental and theoretical calculations results suggest that the photodimer of Ant which is formed in PVA matrix under the UV light irradiation would be competitive with the process of RTP emission. This work demonstrates that the RTP properties of organic molecules might be probably affected by the photostability of the organic phosphor under UV irradiation.

The promotion of vascular reconstruction by hierarchical structures in biodegradable small-diameter vascular scaffolds.

Tissue engineering of small-diameter vessels remains challenging due to the inadequate ability to promote endothelialization and infiltration of smooth muscle cells (SMCs). Ideal vascular graft is expected to provide the ability to support endothelial monolayer formation and SMCs infiltration. To achieve this, vascular scaffolds with both orientation and dimension hierarchies were prepared, including hierarchically random vascular scaffold (RVS) and aligned vascular scaffold (AVS), by utilizing degradable poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) and the blend of PCE/gelatin (PCEG) as raw materials. In addition to the orientation hierarchy, dimension hierarchy with small pores in the inner layer and large pores in the outer layer was also constructed in both RVS and AVS to further investigate the promotion of vascular reconstruction by hierarchical structures in vascular scaffolds. The results show that the AVS with an orientation hierarchy that consists with the natural vascular structure had better mechanical properties and promotion effect on the proliferation of vascular cells than RVS, and also exhibited excellent contact guidance effects on cells. While the dimension hierarchy in both RVS and AVS was favorable to the rapid infiltration of SMCs in a short culture time in vitro. Besides, the results of subcutaneous implantation further demonstrate that AVS achieved a fully infiltrated outer layer with wavy elastic fibers-mimic strips formation by day 14, ascribing to hierarchies of aligned orientation and porous dimension. The results further indicate that the scaffolds with both orientation and dimension hierarchical structures have great potential in the application of promoting the vascular reconstruction.

Understanding the Interface Enhancement Mechanisms of CFRP with the Polydopamine-Polyetheramine Interphase at the Molecular Level.

In this work, polydopamine (PDA) and polyetheramine D230 were selected to construct the PDA-D230 interphase between the carbon fiber (CF) and epoxy matrix. Density functional theory (DFT) and molecular dynamics (MD) simulations were performed to explore the interface enhancement mechanisms of a carbon fiber reinforced polymer (CFRP) with the PDA-D230 interphase from the molecular level. The adsorption characteristics of a PDA molecule on the CF surface were investigated using the DFT method. The results show that stronger π-π stacking interactions are formed due to the structure and orientation preference of the PDA molecule. The interfacial structures and properties of CFRP with the PDA-D230 interphase are derived from MD simulations. The PDA-D230 interphase on the CF surface induces stronger interfacial interaction energy, leading to the better load transfer between the CF and epoxy matrix. The existence of the PDA-D230 interphase on the CF surface can decrease the mean-square displacement (MSD) value and the free volume fraction of CFRP, which restricts the movement of epoxy atoms and inhibits the translational and rotational motion of epoxy chains. Compared with the epoxy using pristine CFs as reinforcement, the interfacial shear stress (ISS) of CFRP with the PDA-D230 interphase is improved by 13.1%. Our results provide valuable insights into the interface characteristics of CFRP with the PDA-D230 interphase, which are of great significance for exploring the strengthening mechanisms for CFRPs with the PDA-D230 interphase.

Wet peroxide oxidation process catalyzed by Cu/Al2O3: phenol degradation and Cu2+ dissolution behavior.

Catalytic wet peroxide oxidation (CWPO) has become an important deep oxidation technology for organics removal in wastewater treatments. Supported Cu-based catalysts belong to an important type of CWPO catalyst. In this paper, two Cu catalysts, namely, Cu/Al2O3-air and Cu/Al2O3-H2 were prepared and evaluated through catalytic degradation of phenol. It was found that Cu/Al2O3-H2 had an excellent catalytic performance (TOC removal rate reaching 96%) and less metal dissolution than the Cu/Al2O3-air case. Moreover, when the organic removal rate was promoted at a higher temperature, the metal dissolution amounts was decreased. Combined with hydroxyl radical quenching experiments, a catalytic oxidation mechanism was proposed to explain the above-mentioned interesting behaviors of the Cu/Al2O3-H2 catalyst for CWPO. The catalytic test results as well as the proposed mechanism can provide better guide for design and synthesis of good CWPO catalysts.

Understanding the Effect of Grain Boundaries on the Mechanical Properties of Epoxy/Graphene Composites.

This work presents a molecular dynamics (MD) simulation study on the effect of grain boundaries (GBs) on the mechanical properties of epoxy/graphene composites. Ten types of GB models were constructed and comparisons were made for epoxy/graphene composites containing graphene with GBs. The results showed that the tensile and compressive behaviors, the glass transition temperature (Tg), and the configurations of epoxy/graphene composites were significantly affected by GBs. The tensile yield strength of epoxy/graphene composites could be either enhanced or weakened by GBs under a tensile load parallel to the graphene sheet. The underlying mechanisms may be attributed to multi-factor coupling, including the tensile strength of the reinforcements, the interfacial interaction energy, and the inflection degree of reinforcements. A balance exists among these effect factors, resulting in the diversity in the tensile yield strength of epoxy/graphene composites. The compressive yield strength for epoxy/graphene composites is higher than their counterpart in tension. The tensile/compressive yield strength for the same configuration presents diversity in different directions. Both an excellent interfacial interaction and the appropriate inflection degree of wrinkles for GB configurations restrict the translational and rotational movements of epoxy chains during volume expansion, which eventually improves the overall Tg. Understanding the reinforcing mechanism for graphene with GBs from the atomistic level provides new physical insights to material design for epoxy-based composites containing defective reinforcements.

Endogenous Electric Field-Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration through Sensory Nerve via Fanconi Anemia Signaling Pathway.

To treat bone defects, repairing the nerve-rich periosteum is critical for repairing the local electric field. In this study, an endogenous electric field is coupled with 2D black phosphorus electroactive periosteum to explore its role in promoting bone regeneration through nerves. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are used to characterize the electrically active biomimetic periosteum. Here, the in vitro effects exerted by the electrically active periosteum on the transformation of Schwann cells into the repair phenotype, axon initial segment (AIS) and dense core vesicle (DCV) of sensory neurons, and bone marrow mesenchymal stem cells are assessed using SEM, immunofluorescence, RNA-sequencing, and calcium ion probes. The electrically active periosteum stimulates Schwann cells into a neuroprotective phenotype via the Fanconi anemia pathway, enhances the AIS effect of sensory neurons, regulates DCV transport, and releases neurotransmitters, promoting the osteogenic transformation of bone marrow mesenchymal stem cells. Microcomputed tomography and other in vivo techniques are used to study the effects of the electrically active periosteum on bone regeneration. The results show that the electrically active periosteum promotes nerve-induced osteogenic repair, providing a potential clinical strategy for bone regeneration.

Clinical features and response to systemic therapy in NRAS-mutant Chinese melanoma patients.

PURPOSE: The prognosis of patients with NRAS-mutant melanoma is rather poor. Immunotherapy and targeted therapy have revolutionized anti-tumor therapy, especially for melanoma. In this study, we retrospectively summarized the real-world experience of systematic treatment for NRAS-mutant melanoma patients in this new era. PATIENTS AND METHODS: The respective cohort included NRAS-mutant melanoma patients with metastatic or unresectable disease of Sun Yat-sen University Cancer Center (SYSUCC) from January 2018 to July 2022. The data about the clinical features and impact for systemic therapy of NRAS-mutant patients were collected and analyzed. RESULTS: At data cutoff, 44 patients (19, 11, and 14 for acral, cutaneous, and mucosal ones, respectively) with NRAS-mutant were assessed. In addition, the median time of follow-up was 22.0 months. The immunotherapy-based combined treatment not only significantly improved the progression-free survival (PFS) (P = 0.006, HR 0.322), but was also accompanied by a higher objective response rate (ORR) (18.2%), disease control rate (DCR) (72.7%) than those of cytotoxic therapy or immunotherapy alone for advanced patients as first-line treatment. Nab-paclitaxel combined with anti-PD-1 inhibitor tended to produce better clinical benefit for the first-line treatment, especially for patients with acral melanoma. In addition, the tyrosine kinase inhibitor (TKI) combined with anti-PD-1 inhibitor also seemed to provide longer duration of response (DOR) for some patients. But combined therapy did not prolong the overall survival (OS) of NRAS-mutant patients. The combined therapy was well tolerated. Most adverse events were moderate and controllable. CONCLUSION: In conclusion, PD-1 inhibitor-based combined therapy increased clinical benefit for advanced patients with NRAS-mutant melanoma.

Photosensitive and Conductive Hydrogel Induced Innerved Bone Regeneration for Infected Bone Defect Repair.

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP+ nerve fiber regeneration. The phototherapy conductive hydrogel provides a novel strategy based on skeletal-associated innervation for infected bone defect repair.

HHLA2 predicts improved prognosis of anti-PD-1/PD-L1 immunotherapy in patients with melanoma.

Background: As a recognized highly immunogenic tumor, immune checkpoint blockades (ICB) have been widely used as a systemic treatment option for melanoma. However, only about half of treated patients could benefit from it in Caucasians, and only about 15% in Chinese melanoma patients. Robust predictive biomarkers are needed. HHLA2, a new-found member of B7 family, is generally expressed in kinds of tumors, such as melanoma. This study focuses on illustrating the prognostic value of HHLA2 in melanoma immunotherapy and its association with tumor-infiltrating lymphocytes. Methods: HHLA2 expression in pan-cancer and the association with prognosis and immune microenvironment were identified by analyzing gene expression profiles from TCGA database with selected bioinformatics tools and methods. Tumor tissues from 81 cases with advanced and unresectable melanoma were collected for detecting HHLA2 and CD8 levels by immunohistochemistry. Results: HHLA2 was found to be ubiquitously expressed in pan-cancer with high level and correlate with the prognosis of patients. Further comprehensive analysis from TCGA database demonstrated that the highly expressed HHLA2 was remarkably correlated with better prognosis, high infiltration status of various immune-active cells and immune activated pathways in skin cutaneous melanoma (SKCM). Moreover, immunohistochemistry (IHC) analyses of FFPE tissue from melanoma patients revealed that HHLA2 high expression was strongly related to improved response to ICB and indicated a longer progression-free survival (PFS) and overall survival (OS). Besides, HHLA2 expression was found to have a positive association with the density of CD8+ TILs. Conclusion: Our findings revealed that high expression of HHLA2 has important values in predicting the response to ICB and indicating improved PFS and OS in patients with advanced and unresectable melanoma, suggesting that HHLA2 may serve as a costimulatory ligand in melanoma, which renders it as an ideal biomarker for immunotherapy.

Small Intestinal Submucosa Biomimetic Periosteum Promotes Bone Regeneration.

BACKGROUND: Critical bone defects are a significant problem in clinics. The periosteum plays a vital role in bone regeneration. A tissue-engineered periosteum (TEP) has received increasing attention as a novel strategy for bone defect repairs. METHODS: In this experiment, a biomimetic periosteum was fabricated by using coaxial electrospinning technology with decellularized porcine small intestinal submucosa (SIS) as the shell and polycaprolactone (PCL) as the core. In vitro, the effects of the biomimetic periosteum on Schwann cells, vascular endothelial cells, and bone marrow mesenchymal stem cells were detected by a scratch test, an EdU, a tube-forming test, and an osteogenesis test. In vivo, we used HE staining to evaluate the effect of the biomimetic periosteum on bone regeneration. RESULTS: In vitro experiments showed that the biomimetic periosteum could significantly promote the formation of angiogenesis, osteogenesis, and repaired Schwann cells (SCs). In vivo experiments showed that the biomimetic periosteum could promote the repair of bone defects. CONCLUSIONS: The biomimetic periosteum could simulate the structural function of the periosteum and promote bone repair. This strategy may provide a promising method for the clinical treatment of skull bone defects.

Multifunctional hydrogel loaded with 4-octyl itaconate exerts antibacterial, antioxidant and angiogenic properties for diabetic wound repair.

Cutaneous wound healing, especially diabetic wound healing, is a common clinical problem. Reactive oxygen species (ROS) and bacterial infection are two major factors in the induction of oxidative stress and inflammation, leading to impeded angiogenesis and wound healing. However, it is still very difficult to reverse the harsh microenvironment of chronic inflammation and excessive oxidative stress on diabetic wound. Itaconate, an endogenous metabolite, has recently attracted extensive attention as a critical immune-regulator. In this study, we used 4-octyl itaconate (4OI), a cell-permeable itaconate derivative, to have antioxidative and anti-inflammatory functions for diabetic wound regeneration. Simultaneously, an injectable, self-healing, and antibacterial dynamic coordinative hydrogel was manufactured by binding the 4-arm polyethylene glycol (PEG) with silver nitrate to deliver the bioactive molecule. In vitro experiments confirmed that 4OI@PEG hydrogel could inhibit bacterial growth, protect human umbilical vein endothelial cells from ROS damage and enhance neovascularization. In addition, the hydrogel increased mitochondrial polarization and reduced mitochondrial fragmentation by activating the Keap1-Nrf2 antioxidant defense system. In vivo experiments proved that this multifunctional hydrogel facilitated diabetic wound healing by inhibiting local inflammation and promoting angiogenesis. Collectively, 4OI-loaded multifunctional materials could reverse various unfavorable microenvironments, such as excessive oxidative stress, inflammation, and infection, and can promote neovascularization; thus, such materials show great promise for the treatment of diabetic ulcers.

Physicochemical Properties and in vitro Digestibility of Myofibrillar Proteins From the Scallop Mantle (Patinopecten yessoensis) Based on Ultrahigh Pressure Treatment.

The utilization of myofibrillar proteins (MPs) from the scallop mantle was limited due to its poor digestibility in vitro. In this study, structural properties and in vitro digestibility of MP were evaluated after modified by ultra-high pressure (UHP) at different pressures (0.1, 100, 200, 300, 400, and 500 MPa). The results showed that high pressure could significantly increase the ordered structure content like α-helix, inhibit the formation of disulfide bonds, and decrease surface hydrophobicity. Moreover, MP possessed the optimal solubility and in vitro digestibility properties at 200 MPa due to the minimum particle size and turbidity, relatively dense and uniform microstructure. The results indicated that the UHP treatment was an effective method to improve the digestibility of MP from scallop mantle and lay a theoretical basis for the functional foods development of poor digestion people and comprehensive utilization of scallop mantles.

Bioinspired Multifunctional Black Phosphorus Hydrogel with Antibacterial and Antioxidant Properties: A Stepwise Countermeasure for Diabetic Skin Wound Healing.

Cutaneous wound healing, especially diabetic wound healing, is a common clinical challenge. Reactive oxygen species (ROS) and bacterial infection are two major detrimental states that induce oxidative stress and inflammatory responses and impede angiogenesis and wound healing. A derivative of the metabolite itaconate, 4-octyl itaconate (4OI) has attracted increasing research interest in recent years due to its antioxidant and anti-inflammatory properties. In this study, 4OI-modified black phosphorus (BP) nanosheets are incorporated into a photosensitive, multifunctional gelatin methacrylamide hydrogel to produce a new photothermal therapy (PTT) and photodynamic therapy (PDT) system with antibacterial and antioxidant properties for diabetic wound regeneration. Under laser irradiation, the 4OI-BP-entrapped hydrogel enables rapid gelation, forming a membrane on wounds, and offers high PTT and PDT efficacy to eliminate bacterial infection. Without laser irradiation, BP acts as a carrier and controls the release of 4OI, with which it synergistically enhances antioxidant activity, thus alleviating excessive ROS damage to endothelial cells, promoting neovascularization, and facilitating faster diabetic wound closure. These findings indicate that 4OI-BP-entrapped multifunctional hydrogel provides a stepwise countermeasure with antibacterial and antioxidant properties for enhanced diabetic wound healing and may lead to novel therapeutic interventions for diabetic ulcers.

Effect of ultrasonic treatment on the structure and functional properties of mantle proteins from scallops (Patinopecten yessoensis).

In this study, scallop mantle protein was treated by ultrasound at different powers, and then analyzed by ANS fluorescent probes, circular dichroism spectroscopy, endogenous fluorescence spectrum, DNTB colorimetry and in-vitro digestion model to elucidate the structure-function relationship. The results indicated that ultrasound can significantly affect the secondary structure of scallop mantle protein like enhancing hydrophobicity, lowering the particle size, increasing the relative contents of α-helix and decreasing contents of ß-pleated sheet, ß-turn and random coil, as well as altering intrinsic fluorescence intensity with blue shift of maximum fluorescence peak. But ultrasound had no effect on its primary structure. Moreover, the functions of scallop mantle protein were regulated by modifying its structures by ultrasound. Specifically, the protein had the highest performance in foaming property and in-vitro digestibility under ultrasonic power of 100 W, oil binding capacity under 100 W, water binding capacity under 300 W, solubility and emulsification capacity under 400 W, and emulsion stability under 600 W. These results prove ultrasonic treatment has the potential to effectively improve functional properties and quality of scallop mantle protein, benefiting in comprehensive utilization of scallop mantles.

Controlled delivery of bone morphogenic protein-2-related peptide from mineralised extracellular matrix-based scaffold induces bone regeneration.

Ideal bone tissue engineering scaffolds composed of extracellular matrix (ECM) require excellent osteoconductive ability to imitate the bone environment. We developed a mineralised tissue-derived ECM-modified true bone ceramic (TBC) scaffold for the delivery of aspartic acid-modified bone morphogenic protein-2 (BMP-2) peptide (P28) and assessed its osteogenic capacity. Decellularized ECM from porcine small intestinal submucosa (SIS) was coated onto the surface of TBC, followed by mineralisation modification (mSIS/TBC). P28 was subsequently immobilised onto the scaffolds in the absence of a crosslinker. The alkaline phosphatase activity and other osteogenic differentiation marker results showed that osteogenesis of the P28/mSIS/TBC scaffolds was significantly greater than that of the TBC and mSIS/TBC groups. In addition, to examine the osteoconductive capability of this system in vivo, we established a rat calvarial bone defect model and evaluated the new bone area and new blood vessel density. Histological observation showed that P28/mSIS/TBC exhibited favourable bone regeneration efficacy. This study proposes the use of mSIS/TBC loaded with P28 as a promising osteogenic scaffold for bone tissue engineering applications.

In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed "super-affinity" to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.

Supported Pt-Cu bimetallic catalysts: preparation and synergic effects in their catalytic oxidative degradation of aniline.

Catalytic Fenton oxidation is an effective way to remove organic pollutants in water, and the performance of the catalyst is a key issue for the competiveness of this method. In this work, various supported bimetallic Pt-Cu catalysts were prepared by different impregnation methods and their performances for catalytic Fenton oxidation of aniline in water were investigated. In the different impregnation methods employed, factors including the reduction method of the metal precursor, type of catalytic support, and loading of metal were investigated. The effect of different reduction methods on actual loadings of the active components on the supported Pt-Cu catalysts showed the order of (i) H2 reduction > (ii) liquid phase methanal reduction. Meanwhile, compared with the monometallic catalysts, the Pt-Cu alloy phase (mainly in the form of PtCu3) was generated and the specific surface area was significantly reduced for the bimetallic catalysts. In the process of Fenton catalytic oxidation of aniline, it was found that most of the prepared catalysts had a certain catalytic activity for H2O2 accompanied with aniline degradation. It was found that Pt0.5Cu1.5/AC (where AC denotes activated carbon) exhibited superb catalytic activity compared with all other prepared catalysts. In particular, aniline was almost completely mineralized in a neutral solution (500 mg L-1 aniline, 0.098 mol L-1 H2O2) after 60 min at 50 °C using Pt-Cu/AC (Pt: 0.5%, Cu: 1.5%). The characterization results showed that the Pt and Cu components were rather evenly distributed on the AC support for this catalyst. More importantly, there was an obvious synergic effect on the supported bimetallic catalyst between the Pt and Cu components for the catalytic oxidation of aniline.

Magnesium-based materials in orthopaedics: material properties and animal models.

As a new generation of medical metal materials, degradable magnesium-based materials have excellent mechanical properties and osteogenic promoting ability, making them promising materials for the treatment of refractory bone diseases. Animal models can be used to understand and evaluate the performance of materials in complex physiological environments, providing relevant data for preclinical evaluation of implants and laying the foundation for subsequent clinical studies. To date, many researchers have studied the biocompatibility, degradability and osteogenesis of magnesium-based materials, but there is a lack of review regarding the effects of magnesium-based materials in vivo. In view of the growing interest in these materials, this review briefly describes the properties of magnesium-based materials and focuses on the safety and efficacy of magnesium-based materials in vivo. Various animal models including rats, rabbits, dogs and pigs are covered to better understand and evaluate the progress and future of magnesium-based materials. This literature analysis reveals that the magnesium-based materials have good biocompatibility and osteogenic activity, thus causing no adverse reaction around the implants in vivo, and that they exhibit a beneficial effect in the process of bone repair. In addition, the degradation rate in vivo can also be improved by means of alloying and coating. These encouraging results show a promising future for the use of magnesium-based materials in musculoskeletal disorders.

PTBP1 modulates osteosarcoma chemoresistance to cisplatin by regulating the expression of the copper transporter SLC31A1.

Chemoresistance is the main obstacle of treatment in patients with osteosarcoma. RNA-binding protein PTBP1 has been identified as an oncogene in various cancers. However, the role of PTBP1 in osteosarcoma, especially in chemoresistant osteosarcoma, and the underlying mechanism remain unclear. In this study, we aimed to explore the functions of PTBP1 in chemoresistance of osteosarcoma. We found that PTBP1 was significantly increased in chemotherapeutically insensitive osteosarcoma tissues and cisplatin-resistant osteosarcoma cell lines (MG-63CISR and U-2OSCISR ) as compared to chemotherapy-sensitive osteosarcoma tissues and cell lines. Knock-down of PTBP1 can enhance the anti-proliferation and apoptosis-induced effects of cisplatin in MG-63CISR and U-2OSCISR cells. Moreover, PTBP1 knock-down significantly up-regulated the expression of the copper transporter SLC31A1, as indicated by transcriptome sequencing. Through RNA immunoprecipitation, dual-luciferase reporter assay and RNA stability detection, we confirmed that PTBP1 binds to SLC31A1 mRNA and regulates the expression level of SLC31A1 by affecting mRNA stability. Additionally, SLC31A1 silencing abrogated the chemosensitizing effect of PTBP1 knock-down in MG-63CISR and U-2OSCISR cells. Using a nude mouse xenograft model, we further confirmed that PTBP1 knock-down enhanced chemoresistant osteosarcoma responsiveness to cisplatin treatment in vivo. Collectively, the present study suggests that PTBP1 is a crucial determinant of chemoresistance in osteosarcoma.

LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial-mesenchymal transition via Wnt/ß-catenin signaling pathway.

Long noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real-time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N-cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E-cadherin and ZO-1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase-3ß phosphorylation to activate the Wnt/ß-catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelial-mesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.