Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus.

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. STATEMENT OF SIGNIFICANCE: •The designed wound dressing combines the advantage of natural polysaccharide and polypeptide. •The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis. •The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

Prediction of lymph node metastasis in advanced gastric adenocarcinoma based on dual-energy CT radiomics: focus on the features of lymph nodes with a short axis diameter ≥6 mm.

Objective: To explore the value of the features of lymph nodes (LNs) with a short-axis diameter ≥6 mm in predicting lymph node metastasis (LNM) in advanced gastric adenocarcinoma (GAC) based on dual-energy CT (DECT) radiomics. Materials and methods: Data of patients with GAC who underwent radical gastrectomy and LN dissection were retrospectively analyzed. To ensure the correspondence between imaging and pathology, metastatic LNs were only selected from patients with pN3, nonmetastatic LNs were selected from patients with pN0, and the short-axis diameters of the enrolled LNs were all ≥6 mm. The traditional features of LNs were recorded, including short-axis diameter, long-axis diameter, long-to-short-axis ratio, position, shape, density, edge, and the degree of enhancement; univariate and multivariate logistic regression analyses were used to establish a clinical model. Radiomics features at the maximum level of LNs were extracted in venous phase equivalent 120 kV linear fusion images and iodine maps. Intraclass correlation coefficients and the Boruta algorithm were used to screen significant features, and random forest was used to build a radiomics model. To construct a combined model, we included the traditional features with statistical significance in univariate analysis and radiomics scores (Rad-score) in multivariate logistic regression analysis. Receiver operating curve (ROC) curves and the DeLong test were used to evaluate and compare the diagnostic performance of the models. Decision curve analysis (DCA) was used to evaluate the clinical benefits of the models. Results: This study included 114 metastatic LNs from 36 pN3 cases and 65 nonmetastatic LNs from 28 pN0 cases. The samples were divided into a training set (n=125) and a validation set (n=54) at a ratio of 7:3. Long-axis diameter and LN shape were independent predictors of LNM and were used to establish the clinical model; 27 screened radiomics features were used to build the radiomics model. LN shape and Rad-score were independent predictors of LNM and were used to construct the combined model. Both the radiomics model (area under the curve [AUC] of 0.986 and 0.984) and the combined model (AUC of 0.970 and 0.977) outperformed the clinical model (AUC of 0.772 and 0.820) in predicting LNM in both the training and validation sets. DCA showed superior clinical benefits from radiomics and combined models. Conclusion: The models based on DECT LN radiomics features or combined traditional features have high diagnostic performance in determining the nature of each LN with a short-axis diameter of ≥6 mm in advanced GAC.

Image quality assessment and feasibility of three-dimensional amide proton transfer-weighted imaging for hepatocellular carcinoma.

Background: With the continuous innovation of magnetic resonance imaging (MRI) hardware and software technology, amide proton transfer-weighted (APTw) imaging has been applied in liver cancer. However, to our knowledge, no study has evaluated the feasibility of a three-dimensional amide proton transfer-weighted (3D-APTw) imaging sequence for hepatocellular carcinoma (HCC). This study thus aimed to conduct an image quality assessment of 3D-APTw for HCC and to explore its feasibility. Methods: 3D-APTw MRI examinations were completed in 134 patients with clinically suspected HCC. According to the uniformity of APTw signal in the liver and within the lesion and the proportion of artifact and missing signal regions, APTw images were subjectively scored using a 5-point scale. The scanning success rate of liver APTw imaging was calculated as the ratio of the number of cases with a quality assurance measurement of more than 3 to the total number of HCC cases. The intra- and interobserver quality assurance measurements for APTw images were compared via the Kappa consistency test. Within the HCC cases with a minimum image quality threshold of 3 points, the APT values of HCC and the liver parenchyma, signal-to-noise ratio of APT-weighted images (SNRAPTw), and contrast-to-noise ratio of HCC (CNRHCC) were measured by two observers. The intra- and interobserver agreement was assessed using the intraclass correlation coefficient (ICC). The differences in APT values between HCC and liver parenchyma was determined using the Mann-Whitney test. Results: Sixty-six HCC cases with a quality assurance measurement of APTw imaging were included in the final analysis, and the calculated success rate was 70.21% (66/94). The subjective APT image quality scores of the two observers were consistent (3.66±1.18, 3.50±1.19, and 3.68±1.18), and no intergroup or intragroup statistical differences were found (P=0.594, and P=0.091), but the consistency of inter- and intraobserver was not as satisfactory (κ=0.594 and κ=0.580). The APT values in HCC lesion were significantly higher than those in liver parenchyma (2.73%±0.91% vs. 1.62%±0.55%; P<0.001). The APT values in HCC showed favorable intra- and interobserver consistency between the two observers (ICC =0.808 and ICC =0.853); the APT values in liver parenchyma, SNRAPTw, and CNRHCC values had moderate intraobserver consistency (ICC =0.578, ICC =0.568, and ICC =0.508) and interobserver consistency (ICC =0.599, ICC =0.199, and ICC =0.650). The coefficients of variation of the APTw values in the HCC lesion and in liver parenchyma were 33.4% and 34.4%, respectively. The SNRAPTw and CNRHCC were 30.75±18.74 and 3.56±3.19, with a coefficient of variation of 60.9% and 74.9%, respectively. Conclusions: Liver 3D-APTw imaging was preliminarily demonstrated to be clinically feasible for evaluating HCC.

An ear-shaped film with a "leg".

Background: The reconstructed auricle projection is an essential element of ear reconstruction. The novel use of an ear-shaped film with one or two "legs" can successfully provide a healthy auricular contour, length, and width, hence improving the three-dimensional (3D) contour of the reconstructed auricle. Methods: Sixty-one patients (31 men and 30 women) with unilateral ear reconstruction (22 on the left and 39 on the right side) who underwent auricular reconstruction using the novel ear-shaped film at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences between February 2021 and June 2022 were enrolled in this retrospective study. Results: Using the Jarque-Bera and paired t-test, we found no statistically significant differences between the reconstructive and healthy ears in terms of length (5.93±0.56 vs. 5.89±0.49 cm, P=0.208), width (3.15±0.31 vs. 3.13±0.30 cm, P=0.224), height (2.48±0.33 vs. 2.51±0.36 cm, P=0.079), and perimeter (10.83±1.06 vs. 10.69±0.95 cm, P=0.164), using the novel ear-shaped film. The reconstructed auricle location was deemed satisfactory for all patients and their families. Conclusions: The novel ear-shaped film may reflect the structure and height of the auricle during ear reconstruction surgery. Implementing this method is easy, and its impact is significant. This technique can be widely used in all types of otoplasties.

3D-bioprinted human lipoaspirate-derived cell-laden skin constructs for healing of full-thickness skin defects.

29Three-dimensional (3D)-printed bioactive scaffolds that can be produced rapidly could offer an individualized approach for treating full-thickness skin defects. Decellularized extracellular matrix (dECM) and mesenchymal stem cells have been proven to support wound healing. Adipose tissues obtained by liposuction are rich in adipose-derived dECM (adECM) and adipose-derived stem cells (ADSCs) and thus represent a natural source of bioactive materials for 3D bioprinting. Herein, ADSC-laden 3D-printed bioactive scaffolds consisting of gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), and adECM were fabricated with dual properties of photocrosslinking in vitro and thermosensitive crosslinking in vivo. adECM was prepared by decellularization of human lipoaspirate and mixed as a bioactive material with GelMA and HAMA to form a bioink. Compared with the GelMA-HAMA bioink, the adECM-GelMA-HAMA bioink had better wettability, degradability, and cytocompatibility. Full-thickness skin defect healing in a nude mouse model showed that ADSC-laden adECM-GelMA-HAMA scaffolds accelerated wound healing by promoting faster neovascularization, collagen secretion, and remodeling. ADSCs and adECM collectively conferred bioactivity on the prepared bioink. This study represents a novel approach to enhancing the biological activity of 3D-bioprinted skin substitutes by adding adECM and ADSCs derived from human lipoaspirate and may provide a promising therapeutic option for full-thickness skin defects.

A comparison of the use of contrast media with different iodine concentrations for enhanced computed tomography.

Objective: In this study, we compared the enhancement of blood vessels and liver parenchyma on enhanced computed tomography (CT) of the upper abdomen with two concentrations of contrast media (400 and 300 mg I/mL) based on similar iodine delivery rate (IDR) of 0.88 and 0.9 g I/s and iodine load of 450 mg I/kg. Methods: We randomly assigned 160 patients into two groups: iomeprol 400 mg I/mL (A group) and iohexol 300 mg I/mL (B group). The CT attenuation values of the main anatomical structures in the two groups with different scanning phases were measured and the image quality of the two groups was analyzed and compared. The peak pressure and local discomfort (including fever and pain) during contrast medium injection were recorded. Results: The mean attenuation value of the abdominal aorta was 313.6 ± 29.6 in the A group and 322.4 ± 30.1 in the B group during the late arterial phase (p = 0.8). Meanwhile, the mean enhancement values of the portal vein were 176.2 ± 19.3 and 165.9 ± 24.5 in the A and B groups, respectively, during the portal venous phase (p = 0.6). The mean CT values of liver parenchyma were 117.1 ± 15.3 and 108.8 ± 18.7 in the A and B groups, respectively, during the portal venous phase (p = 0.9). There was no statistical difference in image quality, peak injection pressure (psi), and local discomfort between the two groups (p > 0.05). Conclusion: When a similar IDR and the same iodine load are used, CT images with different concentrations of contrast media have the same subjective and objective quality, and can meet the diagnostic needs.

Bacterial nanocellulose-reinforced gelatin methacryloyl hydrogel enhances biomechanical property and glycosaminoglycan content of 3D-bioprinted cartilage.

Tissue-engineered ear cartilage scaffold based on three-dimensional (3D) bioprinting technology presents a new strategy for ear reconstruction in individuals with microtia. Natural hydrogel is a promising material due to its excellent biocompatibility and low immunogenicity. However, insufficient mechanical property required for cartilage is one of the major issues pending to be solved. In this study, the gelatin methacryloyl (GelMA) hydrogel reinforced with bacterial nanocellulose (BNC) was developed to enhance the biomechanical properties and printability of the hydrogel. The results revealed that the addition of 0.375% BNC significantly increased the mechanical properties of the hydrogel and promoted cell migration in the BNC-reinforced hydrogel. Constructs bioprinted with chondrocyte-laden BNC/GelMA hydrogel bio-ink formed mature cartilage in nude mice with higher Young's modulus and glycosaminoglycan content. Finally, an auricle equivalent with a precise shape, high mechanics, and abundant cartilage-specific matrix was developed in vivo. In this study, we developed a potentially useful hydrogel for the manufacture of auricular cartilage grafts for microtia patients.

Bioresource Upgrade for Sustainable Energy, Environment, and Biomedicine.

We conceptualize bioresource upgrade for sustainable energy, environment, and biomedicine with a focus on circular economy, sustainability, and carbon neutrality using high availability and low utilization biomass (HALUB). We acme energy-efficient technologies for sustainable energy and material recovery and applications. The technologies of thermochemical conversion (TC), biochemical conversion (BC), electrochemical conversion (EC), and photochemical conversion (PTC) are summarized for HALUB. Microalgal biomass could contribute to a biofuel HHV of 35.72 MJ Kg-1 and total benefit of 749 $/ton biomass via TC. Specific surface area of biochar reached 3000 m2 g-1 via pyrolytic carbonization of waste bean dregs. Lignocellulosic biomass can be effectively converted into bio-stimulants and biofertilizers via BC with a high conversion efficiency of more than 90%. Besides, lignocellulosic biomass can contribute to a current density of 672 mA m-2 via EC. Bioresource can be 100% selectively synthesized via electrocatalysis through EC and PTC. Machine learning, techno-economic analysis, and life cycle analysis are essential to various upgrading approaches of HALUB. Sustainable biomaterials, sustainable living materials and technologies for biomedical and multifunctional applications like nano-catalysis, microfluidic and micro/nanomotors beyond are also highlighted. New techniques and systems for the complete conversion and utilization of HALUB for new energy and materials are further discussed.

Direct Z-scheme heterojunction Bi/Bi2S3/α-MoO3 photoelectrocatalytic degradation of tetracycline under visible light.

A hot research topic in visible-light-driven photoelectrocatalytic (PEC) oxidation technology is the development of superior photoanode materials. The design of the photoanode system with a direct Z-scheme charge transfer mechanism is crucial to achieving effective charge separation for sustainable photoelectrocatalysis. Here, a novel Bi/Bi2S3/α-MoO3 heterostructure was successfully assembled by a simple and feasible strategy. The direct Z-scheme heterogeneous formed between Bi2S3 and α-MoO3 has the advantages of low resistance, high optical response current and the surface plasmon resonance (SPR) effect of Bi nanoparticles (Bi NPs). Thus, the efficiency of photogenerated carrier separation and transfer is further enhanced, and the catalytic activity is significantly improved. It is impressive that the unique photoanode has achieved a maximum removal efficiency of 85.8% of tetracycline (TC) pollutants under visible light irradiation within 60 min and has excellent stability, which is expected to degrade antibiotics efficiently and environmentally in harsh environments. These characteristics give Bi/Bi2S3/α-MoO3 promising candidates for practical applications in antibiotic degradation.

Remarkable immune and clinical value of novel ferroptosis-related genes in glioma.

Ferroptosis is a neoteric model of regulated cell death that shows great potential for the understanding of tumor immunology and as a target for therapy. The present study aimed to identify ferroptosis-related differentially expressed genes (DEGs) in glioma and to explore their value through systematic analysis. Ferroptosis-related DEGs were identified through the Gene Expression Omnibus database in combination with the FerrDb database and analyzed in the Genotype-Tissue Expression database and The Cancer Genome Atlas database. Possible signaling pathways involved were explored by construction of enrichment analysis and protein-protein interaction of these DEGs. Potential regulation of the immune microenvironment, immune checkpoint and chemokine was postulated by immune analysis. A prognosis model for glioma was developed using survival analysis, exhibited by the nomogram and evaluated by the calibration curve. The prognostic value of the model was validated by using an independent cohort. A total of 15 ferroptosis-related DEGs were identified, including 7 down-regulated and 8 up-regulated, with ATP6V1G2, GABARAPL1 and GOT1 as hub genes. The expression of all 3 hub genes was positively correlated with T follicular helper cells and natural killer CD56bright cells. These hub genes were negatively correlated with the macrophage cell type as well as B7H3, PDCD1, LAG3 and CXCL16, CXCR4, CCR5. Low expression of all 3 hub genes was associated with poor prognosis in glioma cases. ATP6V1G2 might be an independent prognostic factor and, as such, a high-precision prognostic model of glioma was constructed. We identified novel ferroptosis-related genes with clinical value in glioma and revealed their possible tumor immune relevance. Furthermore, in glioma, we pinpointed underlying critical elements of the chemokine, immune microenvironment and immune checkpoint, and were able to develop a predictive model of prognosis.

Acellular cartilage matrix biomimetic scaffold with immediate enrichment of autologous bone marrow mononuclear cells to repair articular cartilage defects.

Functional repair of articular cartilage defects is always a great challenge in joint surgery clinically. Tissue engineering strategies that combine autologous cell implantation with three-dimensional scaffolds have proven effective for repairing articular cartilage tissue. However, it faces the problem of cell sources and scaffold materials. Autologous chondrocytes and bone marrow are difficult to popularize clinically due to limited donor sources and low mononuclear cell (MNC) concentrations, respectively. The density gradient centrifugation method can increase the concentration of MNCs in fresh bone marrow by nearly a hundredfold and achieve immediate enrichment. In addition, acellular cartilage matrix (ACM), with good biocompatibility and a cartilage-specific microenvironment, is considered to be an ideal candidate scaffold for cartilage regeneration. In this study, hybrid pigs were used to establish articular cartilage defect models of different sizes to determine the feasibility and maximum scope of application of ACM-based biomimetic scaffolds combined with MNCs for inducing articular cartilage regeneration. Importantly, ACM-based biomimetic scaffolds instantly enriched MNCs could improve the repair effect of articular cartilage defects in situ, which established a new model of articular cartilage regeneration that could be applied immediately and suited for large-scale clinical promotion. The current study significantly improves the repair effect of articular cartilage defects, which provides scientific evidence and detailed insights for future clinical applications of ACM-based biomimetic scaffolds combined with MNCs.

Surgical management of auricular arteriovenous malformations: A literature review.

Auricular arteriovenous malformations (AVMs) can cause a variety of symptoms that seriously impact the patient's appearance, life, and mental well-being. Surgery is the primary management method for auricular AVMs, but there is no consensus on how to surgically manage auricular AVMs. In this article, we document a comprehensive review of the characteristics, classification, and surgical interventions to treat auricular AVMs.

Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix.

Tissue engineering provides a promising strategy for auricular reconstruction. Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds, this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy. This is mainly since reconstruction constructs easily cause inflammation and deformation. In this study, we present a novel strategy for the development of biological auricle equivalents with precise shapes, low immunogenicity, and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix (ACMMA) with the assistance of gelatin methacrylate (GelMA), poly(ethylene oxide) (PEO), and polycaprolactone (PCL) by integrating multi-nozzle bioprinting technology. Photocrosslinkable ACMMA is used to emulate the intricacy of the cartilage-specific microenvironment for active cellular behavior, while GelMA, PEO, and PCL are used to balance printability and physical properties for precise structural stability, form the microporous structure for unhindered nutrient exchange, and provide mechanical support for higher shape fidelity, respectively. Finally, mature auricular cartilage-like tissues with high morphological fidelity, excellent elasticity, abundant cartilage lacunae, and cartilage-specific ECM deposition are successfully regenerated in vivo, which provides new opportunities and novel strategies for the fabrication and regeneration of patient-specific auricular cartilage.

Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients.

Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein-protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.

Ultrafast, tough, and adhesive hydrogel based on hybrid photocrosslinking for articular cartilage repair in water-filled arthroscopy.

A hydrogel scaffold for direct tissue-engineering application in water-irrigated, arthroscopic cartilage repair, is badly needed. However, such hydrogels must cure quickly under water, bind strongly and permanently to the surrounding tissue, and maintain sufficient mechanical strength to withstand the hydraulic pressure of arthroscopic irrigation (~10 kilopascal). To address these challenges, we report a versatile hybrid photocrosslinkable (HPC) hydrogel fabricated though a combination of photoinitiated radical polymerization and photoinduced imine cross-linking. The ultrafast gelation, high mechanical strength, and strong adhesion to native tissue enable the direct use of these hydrogels in irrigated arthroscopic treatments. We demonstrate, through in vivo articular cartilage defect repair in the weight-bearing regions of swine models, that the HPC hydrogel can serve as an arthroscopic autologous chondrocyte implantation scaffold for long-term cartilage regeneration, integration, and reconstruction of articular function.

Immune-Inflammatory Responses of an Acellular Cartilage Matrix Biomimetic Scaffold in a Xenotransplantation Goat Model for Cartilage Tissue Engineering.

The rapid development of tissue engineering and regenerative medicine has introduced a new strategy for ear reconstruction, successfully regenerating human-ear-shaped cartilage and achieving the first clinical breakthrough using a polyglycolic acid/polylactic acid (PGA/PLA) scaffold. However, its clinical repair varies greatly among individuals, and the quality of regenerated cartilage is unstable, which seriously limits further clinical application. Acellular cartilage matrix (ACM), with a cartilage-specific microenvironment, good biocompatibility, and potential to promote cell proliferation, has been used to regenerate homogeneous ear-shaped cartilage in immunocompromised nude mice. However, there is no evidence on whether ACM will regenerate homogeneous cartilage tissue in large animals or has the potential for clinical transformation. In this study, xenogeneic ACM assisted with gelatin (GT) with or without autologous chondrocytes was implanted subcutaneously into goats to establish a xenotransplantation model and compared with a PGA/PLA scaffold to evaluate the immune-inflammatory response and quality of regenerated cartilage. The results confirmed the superiority of the ACM/GT, which has the potential capacity to promote cell proliferation and cartilage formation. Although there is a slight immune-inflammatory response in large animals, it does not affect the quality of the regenerated cartilage and forms homogeneous and mature cartilage. The current study provides detailed insights into the immune-inflammatory response of the xenogeneic ACM/GT and also provides scientific evidence for future clinical application of ACM/GT in cartilage tissue engineering.

SP600125, a JNK-Specific Inhibitor, Regulates in vitro Auricular Cartilage Regeneration by Promoting Cell Proliferation and Inhibiting Extracellular Matrix Metabolism.

In vitro construction is a major trend involved in cartilage regeneration and repair. Satisfactory in vitro cartilage regeneration depends on a suitable culture system. Current chondrogenic culture systems with a high content of transforming growth factor beta-1 effectively promote cartilaginous extracellular matrix (ECM) production but inhibit chondrocyte survival. As is known, inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway acts in blocking the progression of osteoarthritis by reducing chondrocyte apoptosis and cartilage destruction. However, whether inhibiting JNK signaling resists the inhibitory effect of current chondrogenic medium (CM) on cell survival and affects in vitro auricular cartilage regeneration (including cell proliferation, ECM synthesis, and degradation) has not been investigated. In order to address these issues and optimize the chondrogenic culture system, we generated a three-dimensional in vitro auricular cartilage regeneration model to investigate the effects of SP600125 (a JNK-specific inhibitor) on chondrocyte proliferation and ECM metabolism. SP600125 supplementation efficiently promoted cell proliferation at both cellular and tissue levels and canceled the negative effect of our chondrogenic culture system on cell survival. Moreover, it significantly inhibited ECM degradation by reducing the expressions of tumor necrosis factor-alpha, interleukin-1-beta, and matrix metalloproteinase 13. In addition, SP600125 inhibited ECM synthesis at both cellular and tissue levels, but this could be canceled and even reversed by adding chondrogenic factors; yet this enabled a sufficient number of chondrocytes to be retained at the same time. Thus, SP600125 had a positive effect on in vitro auricular cartilage regeneration in terms of cell proliferation and ECM degradation but a negative effect on ECM synthesis, which could be reversed by adding CM. Therefore, a combination of SP600125 and CM might help in optimizing current chondrogenic culture systems and achieve satisfactory in vitro cartilage regeneration by promoting cell proliferation, reducing ECM degradation, and enhancing ECM synthesis.

3D Cartilage Regeneration With Certain Shape and Mechanical Strength Based on Engineered Cartilage Gel and Decalcified Bone Matrix.

Scaffold-free cartilage-sheet technology can stably regenerate high-quality cartilage tissue in vivo. However, uncontrolled shape maintenance and mechanical strength greatly hinder its clinical translation. Decalcified bone matrix (DBM) has high porosity, a suitable pore structure, and good biocompatibility, as well as controlled shape and mechanical strength. In this study, cartilage sheet was prepared into engineered cartilage gel (ECG) and combined with DBM to explore the feasibility of regenerating 3D cartilage with controlled shape and mechanical strength. The results indicated that ECG cultured in vitro for 3 days (3 d) and 15 days (15 d) showed good biocompatibility with DBM, and the ECG-DBM constructs successfully regenerated viable 3D cartilage with typical mature cartilage features in both nude mice and autologous goats. Additionally, the regenerated cartilage had comparable mechanical properties to native cartilage and maintained its original shape. To further determine the optimal seeding parameters for ECG, the 3 d ECG regenerated using human chondrocytes was diluted in different concentrations (1:3, 1:2, and 1:1) for seeding and in vivo implantation. The results showed that the regenerated cartilage in the 1:2 group exhibited better shape maintenance and homogeneity than the other groups. The current study established a novel mode of 3D cartilage regeneration based on the design concept of steel (DBM)-reinforced concrete (ECG) and successfully regenerated homogenous and mature 3D cartilage with controlled shape and mechanical strength, which hopefully provides an ideal cartilage graft for the repair of various cartilage defects.

Deep eutectic solvent-based liquid-phase microextraction coupled with reversed-phase high-performance liquid chromatography for determination of α-, ß-, γ-, and δ-tocopherol in edible oils.

For simultaneous analysis of four fat-soluble tocopherols (α-, ß-, γ-, and δ-) in edible oils, an efficient and green method using deep eutectic solvent-based liquid-phase microextraction (DES-LPME) coupled with reversed-phase high-performance liquid chromatography (RP-HPLC) was developed. The DESs formed by different quaternary ammonium salts and ethanol were used as the extractants. Tetrabutylammonium chloride (TBAC)-ethanol DES at a molar ratio of 1:2 achieved the best extraction efficiency. Under the optimized conditions, the detection limits were in the range of 2.1-3.0 ng mL-1. The intra-day and inter-day repeatability were in the ranges of 3.9-5.3% and 4.8-7.1%, respectively, and the recoveries for the real samples varied from 80.7% to 105.4%. The developed method was successfully employed for the determination of all four tocopherol homologues with an RP-HPLC system containing a COSMOSIL π-NAP column in five edible oils collected locally. Graphical abstract.

SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway.

Gastric cancer is a major cause of mortality worldwide. The glutamate/aspartate transporter SLC1A3 has been implicated in tumour metabolism and progression, but the roles of SLC1A3 in gastric cancer remain unclear. We used bioinformatics approaches to analyse the expression of SLC1A3 and its role in gastric cancer. The expression levels of SLC1A3 were examined using RT-qPCR and Western bolting. SLC1A3 overexpressing and knock-down cell lines were constructed, and the cell viability was evaluated. Glucose consumption, lactate excretion and ATP levels were determined. The roles of SLC1A3 in tumour growth were evaluated using a xenograft tumour growth model. SLC1A3 was found to be overexpressed in gastric cancer, and this overexpression was associated with poor prognosis. In vitro and in vivo assays showed that SLC1A3 affected glucose metabolism and promoted gastric cancer growth. GSEA analysis suggested that SLC1A3 was positively associated with the up-regulation of the PI3K/AKT pathway. SLC1A3 overexpression activated the PI3K/AKT pathway and up-regulated GLUT1, HK II and LDHA expression. The PI3K/AKT inhibitor LY294002 prevented SLC1A3-induced glucose metabolism and cell proliferation. Our findings indicate that SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. SLC1A3 is therefore a potential therapeutic target in gastric cancer.