Spatial and diel variations of bacterioplankton and pico-nanoeukaryote communities and potential biotic interactions during macroalgal blooms.

We investigated spatial heterogeneity and diel variations in bacterioplankton and pico-nanoeukaryote communities, and potential biotic interactions at the extinction stage of the Ulva prolifera bloom in the Jiaozhou Bay, Yellow Sea. It was found that the presence of Ulva canopies significantly promoted the cell abundance of heterotrophic bacteria, raised evenness, and altered the community structure of bacterioplankton. A diel pattern was solely significant for pico-nanoeukaryote community structure. >50 % of variation in the heterotrophic bacterial abundance was accounted for by the ratio of Bacteroidota to Firmicutes, and dissolved organic nitrogen effectively explained the variations in cell abundances of phytoplankton populations. The factors representing biotic interactions frequently contributed substantially more than environmental factors in explaining the variations in diversity and community structure of both bacterioplankton and pico-nanoeukaryotes. There were higher proportions of eukaryotic pathogens compared to other marine systems, suggesting a higher ecological risk associated with the Ulva blooms.

Development and validation of a nomogram for predicting the prognosis in children with spinal cord injuries.

AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.

Unveiling hidden interactions: Microorganisms, enzymes, and mangroves at different stages of succession in the Shankou Mangrove Nature Reserve, China.

Understanding the interactions between microorganisms, soil extracellular enzymes, and mangroves is crucial for conserving and restoring mangrove ecosystems. However, the unique environments associated with mangroves have resulted in a lack of pertinent data regarding the interactions between these components. Root, stem, leaf, and soil samples were collected at three distinct stages of mangrove succession. Stoichiometry was employed to analyze the carbon, nitrogen, and phosphorus contents of these samples and to quantify extracellular enzyme activities, microbial biomass, and various physicochemical factors in the soil. The results showed that the trends of C, N, and P in the mangrove plants were consistent. Microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and microbial biomass phosphorus (MBP) were the highest in the Kandelia obovate community. Catalase (CAT) and ß-D-G showed the highest content in K. obovate and Bruguiera gymnorrhiza, whereas cellulase showed the opposite trend. Urease was least abundant in the K. obovate community, whereas neutral protease (NPR) and acid phosphatase (ACP) were most abundant. The overall soil environment in mangroves exhibited a state of N limitation, with varying degrees of limitation observed across different succession stages. The demand for P became more intense in the later stages of succession, particularly in the K. obovate and B. gymnorrhiza communities. In conjunction with correlation analysis, it indicated that the input of mangrove plant litter had a significant regulatory influence on the C, N, and P contents in the soil. There was a significant positive correlation between MBC, MBN, and MBP, indicating synergistic effects of C, N, and P on soil microorganisms. Therefore, evaluating the nutrient ratios and sufficiency of mangroves allowed us to comprehensively understand the present environmental conditions. This study aims to develop sustainable management strategies for the conservation and restoration of mangroves.

Research on Performance Improvement of Emulsified Asphalt Mixture Based on Innovative Forming Process.

Bulk density and porosity have great influence on the technical performance of an emulsified asphalt mixture, so in order to enhance the strength of the asphalt mixture, bulk density should be improved and porosity should be reduced. Considering the forming process of the emulsified asphalt mixture, the decrease in porosity can ensure the state of the mixture. In order to reduce the porosity of the emulsified asphalt mixture, an innovative forming process is proposed to improve the performance of the emulsified asphalt mixture, and its strength formation mechanism is explored in this paper. Three groups of emulsified asphalt mixtures (ARC-8 + SBR, SMA-5 + EVA, SMA-5 + SBR) were prepared by a conventional mixing process and novel mixing process. Marshall test of the emulsified asphalt mixture, CT scanning test of the emulsified asphalt mixture, workability test and analysis were manufactured and tested. The results show that, compared with conventional methods, the innovative forming method can increase the bulk density of the mixture and reduce the porosity, and thus improve its technical performance. The reason is that most of the water in the mixture of the innovative forming method sticks to the outer surface of the fine aggregate, and the water is more easily discharged. Secondly, the fine aggregate of the innovative forming method is directly mixed with the emulsion, and the volume is smaller. The emulsion wraps the fine aggregate in it due to the surface tension, which enhances the adhesion effect, thus improving the strength of the mixture.

Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors.

Hyaluronidase is a promising target in drug discovery, given its overexpression in a range of physiological and pathological processes, including tumor migration, skin aging, sagging, and wrinkling, as well as inflammation and bacterial infections. In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulated macrophages. Remarkably, compound 6 significantly reduced NO release by 74 % at a concentration of 20 µM.

DeepAEG: a model for predicting cancer drug response based on data enhancement and edge-collaborative update strategies.

MOTIVATION: The prediction of cancer drug response is a challenging subject in modern personalized cancer therapy due to the uncertainty of drug efficacy and the heterogeneity of patients. It has been shown that the characteristics of the drug itself and the genomic characteristics of the patient can greatly influence the results of cancer drug response. Therefore, accurate, efficient, and comprehensive methods for drug feature extraction and genomics integration are crucial to improve the prediction accuracy. RESULTS: Accurate prediction of cancer drug response is vital for guiding the design of anticancer drugs. In this study, we propose an end-to-end deep learning model named DeepAEG which is based on a complete-graph update mode to predict IC50. Specifically, we integrate an edge update mechanism on the basis of a hybrid graph convolutional network to comprehensively learn the potential high-dimensional representation of topological structures in drugs, including atomic characteristics and chemical bond information. Additionally, we present a novel approach for enhancing simplified molecular input line entry specification data by employing sequence recombination to eliminate the defect of single sequence representation of drug molecules. Our extensive experiments show that DeepAEG outperforms other existing methods across multiple evaluation parameters in multiple test sets. Furthermore, we identify several potential anticancer agents, including bortezomib, which has proven to be an effective clinical treatment option. Our results highlight the potential value of DeepAEG in guiding the design of specific cancer treatment regimens.

A nomogram for predicting the hospital-acquired infections in children with spinal cord injuries: a retrospective, multicenter, observational study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Hospital-acquired infections (HAIs) pose a significant risk for pediatric patients with spinal cord injuries (SCIs), potentially leading to extended hospital stays and increased morbidity. This study aims to identify patients at higher risk for HAIs. SETTING: Hospitals from multiple areas in China. METHODS: This retrospective study included 220 pediatric SCI patients from Jan 2005 to Dec 2023, divided into a training set (n = 154) and a validation set (n = 66). We conducted a multivariate logistic regression analysis to identify risk factors associated with HAIs and constructed a predictive nomogram. The model's performance was assessed using receiver operating characteristic (ROC) curves, area under the ROC curve (AUC) and calibration plots, while decision curve analysis was utilized to determine clinical utility. RESULTS: The nomogram incorporated age, time from injury to the hospital, history of urinary and pulmonary infections, urobilinogen positivity, damaged segments, and admission American Spinal Injury Association (ASIA) scores. The model demonstrated excellent discrimination in the training set (AUC = 0.957) and good discrimination in the validation set (AUC = 0.919). Calibration plots indicated an acceptable fit between predicted probabilities and observed outcomes. Decision curve analysis confirmed the model's net benefit over clinical decision thresholds in both sets. CONCLUSION: We developed and validated a predictive nomogram for HAIs in pediatric SCI patients that shows promise for clinical application. The model can assist healthcare providers in identifying patients at higher risk for HAIs, potentially facilitating early interventions and improved patient care strategies.

Crystal Structure and Optical Properties Characterization in Quasi-0D Lead-Free Bromide Crystals (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12.

Low dimensional organic inorganic metal halide materials have shown broadband emission and large Stokes shift, making them widely used in various fields and a promising candidate material. Here, the zero-dimensional lead-free bromide single crystals (C6H14N)3Bi2Br9·H2O (1) and (C6H14N)3Sb3Br12 (2) were synthesized. They crystallized in the monoclinic crystal system with the space group of P21 and P21/n, respectively. Through ultraviolet-visible-near-infrared (UV-vis-NIR) absorption analysis, the band gaps of (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12 are found to be 2.75 and 2.83 eV, respectively. Upon photoexcitation, (C6H14N)3Bi2Br9·H2O exhibit broad-band red emission peaking at 640 nm with a large Stokes shift of 180 nm and a lifetime of 2.94 ns, and the emission spectrum of (C6H14N)3Sb3Br12 are similar to those of (C6H14N)3Bi2Br9·H2O. This exclusive red emission is ascribed to the self-trapping exciton transition caused by lattice distortion, which is confirmed through both experiments and first-principles calculations. In addition, due to the polar space group structure and the large spin-orbit coupling (SOC) associated with the heavy elements of Bi and Br of crystal 1, an obvious Rashba effect was observed. The discovery of organic inorganic metal bromide material provides a critical foundation for uncovering the connection between 0D metal halide materials' structures and properties.

Corrigendum to "3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration" [Bioact. Mater. 31 (January 2024) 18-37].

[This corrects the article DOI: 10.1016/j.bioactmat.2023.07.004.].

Platelet-derived growth factor subunit-B mediating the effect of dickkopf-1 on acute myocardial infarction risk: a two-step Mendelian randomization study.

Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.

3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration.

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32-, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32- and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.

Terrestrial inputs and physical processes control the distributions of potentially toxic elements (PTEs) in the seawater of the large-range Beibu Gulf, the northern South China Sea.

The potentially toxic elements (PTEs), Cu, Pb, Zn, Cd, Cr, Hg and As in the water from the Beibu Gulf, were investigated to reveal the contaminant characteristics and assess the risks to human health. The results showed that the concentration of PTEs in the Beibu Gulf varies significantly both seasonally and spatially, with higher concentrations in summer and in the northern and southern gulf. Terrestrial inputs and local anthropogenic discharge are responsible for the higher level in the northern gulf, and the transportation of water masses is also an important factor for the higher concentrations in the southern gulf. Ecological risk assessment suggested that Hg is the main ecological risk factor. The health risk assessment revealed that dermal exposure to PTEs in the gulf presents potentially carcinogenic health effects for humans. This study provides new insight into the transport of PTEs over a large area of the Beibu Gulf.

Investigating the causal effect of Dickkopf-1 on coronary artery disease and ischemic stroke: a Mendelian randomization study.

Epidemiological investigations have indicated a correlation between elevated plasma levels of Dickkopf-related protein 1 (DKK1) and the presence of atherosclerosis. However, the exact causal relationship of DKK1 with the development of coronary artery disease (CAD) and ischemic stroke (IS) remains unclear. To address this gap, our study aimed to explore their causal association using a two-sample Mendelian randomization (MR) approach. We obtained summary statistics from genome-wide association studies (GWAS) meta-analyses conducted by Folkersen et al. and Nikpay et al., which included data from 21,758 individuals for DKK1 and 42,096 cases of CAD. Additionally, we obtained data from the FinnGen biobank analysis round 5, which included 10,551 cases of IS. Eight MR methods were employed to estimate causal effects and detect directional pleiotropy. Our findings demonstrated that genetic liability to DKK1 was associated with increased risks of CAD (odds ratio [OR]: 1.087; 95% confidence interval [CI]: 1.024-1.154; P = 0.006) and IS (OR: 1.096; 95% CI: 1.004-1.195; P = 0.039). These results establish a causal link between genetic liability to DKK1 and elevated risks of CAD and IS. Consequently, DKK1 may represent a promising therapeutic target for the prevention and treatment of CAD and IS.

The pear genomics database (PGDB): a comprehensive multi-omics research platform for Pyrus spp.

BACKGROUND: Pears are among the most important temperate fruit trees in the world, with significant research efforts increasing over the last years. However, available omics data for pear cannot be easily and quickly retrieved to enable further studies using these biological data. DESCRIPTION: Here, we present a publicly accessible multi-omics pear resource platform, the Pear Genomics Database (PGDB). We collected and collated data on genomic sequences, genome structure, functional annotation, transcription factor predictions, comparative genomics, and transcriptomics. We provide user-friendly functional modules to facilitate querying, browsing and usage of these data. The platform also includes basic and useful tools, including JBrowse, BLAST, phylogenetic tree building, and additional resources providing the possibility for bulk data download and quick usage guide services. CONCLUSIONS: The Pear Genomics Database (PGDB, http://pyrusgdb.sdau.edu.cn ) is an online data analysis and query resource that integrates comprehensive multi-omics data for pear. This database is equipped with user-friendly interactive functional modules and data visualization tools, and constitutes a convenient platform for integrated research on pear.

Deep Semi-Supervised Ultrasound Image Segmentation by Using a Shadow Aware Network With Boundary Refinement.

Accurate ultrasound (US) image segmentation is crucial for the screening and diagnosis of diseases. However, it faces two significant challenges: 1) pixel-level annotation is a time-consuming and laborious process; 2) the presence of shadow artifacts leads to missing anatomy and ambiguous boundaries, which negatively impact reliable segmentation results. To address these challenges, we propose a novel semi-supervised shadow aware network with boundary refinement (SABR-Net). Specifically, we add shadow imitation regions to the original US, and design shadow-masked transformer blocks to perceive missing anatomy of shadow regions. Shadow-masked transformer block contains an adaptive shadow attention mechanism that introduces an adaptive mask, which is updated automatically to promote the network training. Additionally, we utilize unlabeled US images to train a missing structure inpainting path with shadow-masked transformer, which further facilitates semi-supervised segmentation. Experiments on two public US datasets demonstrate the superior performance of the SABR-Net over other state-of-the-art semi-supervised segmentation methods. In addition, experiments on a private breast US dataset prove that our method has a good generalization to clinical small-scale US datasets.

A Novel Method for Treating Distal Radius Diaphyseal Metaphyseal Junction Fracture in Children.

BACKGROUND The treatment of distal radius diaphyseal metaphyseal junction (DMJ) fracture in children is a clinical problem; several treatments are available, but none are very effective. Therefore, this study aimed to report a novel method for treating this fracture using limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire. MATERIAL AND METHODS From January 2018 to December 2019, a total of 15 children (13 boys and 2 girls) with distal radius DMJ fractures with a mean age of 10 years (range: 6-14 years) were included in the study. The operation time, incision length, and X-ray radiation exposure were precisely recorded. All children were followed up regularly. At the final follow-up, clinical outcomes were evaluated according to Price criteria, and complications were recorded. RESULTS The mean operation time of the 15 children was 21.4 min, and the mean incision length was 1.9 cm. The intraoperative X-ray was performed 3.7 times on average. The mean radiographic union of fracture was 4.7 weeks, and the mean time to remove the Kirschner wire was 4.8 weeks for radial instrumentation and 4.7 months for ulnar instrumentation. According to the Price grading evaluation system, clinical outcome was excellent in 14 cases and good in 1 case. Moreover, there were no major complications related to loss of reduction, malunion, nonunion, and physeal arrest of the distal radius. CONCLUSIONS Limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire are effective for treating distal radius DMJ fracture in children, which has the advantages of simple surgical procedures, short operation time, small incision, and less radiation exposure, making it an excellent choice for treating this fracture.

Risk factor analysis for tibial tubercle avulsion fractures in children.

PURPOSE: Tibial tubercle avulsion fractures (TTAFs) are rare in children, particularly bilateral TTAFs. This study aimed to elucidate the associating factors of TTAF, and compare the risk factor profiles of unilateral and bilateral injuries, thus provide clinical theoretical basis for reducing the occurrence of TTAFs. METHODS: TTAF paediatric patients who were hospitalized between April 2017 and November 2022 were retrospectively analysed. Children who presented for physical examination during the same period were randomly selected, and were age- and sex-matched as controls. A subgroup analysis based on endocrine function was also performed. A risk factor analysis for bilateral TTAF was performed as well. Data were collected via medical records and a questionnaire. All variables were assessed for association with TTAF using univariate and multiple logistic regression analyses. RESULTS: A total of 64 TTAF patients and controls were respectively included. Multivariate analysis demonstrated BMI (P = 0.000，OR = 3.172), glucose (P = 0.016，OR = 20.878), and calcium (P = 0.034，OR = 0.000) as independent associating factors of TTAF. Subgroup analysis showed significant differences in oestradiol (P = 0.014), progesterone (P = 0.006) and insulin levels (P = 0.005) between the TTAF and control groups. Bilateral TTAF was found to significantly associate with a history of knee joint pain (P = 0.026). CONCLUSION: High BMI, hyperglycaemia, and low calcium levels were found as independent risk factors for TTAF in children. In addition, decreased oestradiol, elevated progesterone, and insulin resistance were identified as potential risk factors for TTAF. A history of knee pain may be suggestive of bilateral TTAF.

Tissue engineering in growth plate cartilage regeneration: Mechanisms to therapeutic strategies.

The repair of growth plate injuries is a highly complex process that involves precise spatiotemporal regulation of multiple cell types. While significant progress has been made in understanding the pathological mechanisms underlying growth plate injuries, effectively regulating this process to regenerate the injured growth plate cartilage remains a challenge. Tissue engineering technology has emerged as a promising therapeutic approach for achieving tissue regeneration through the use of functional biological materials, seed cells and biological factors, and it is now widely applied to the regeneration of bone and cartilage. However, due to the unique structure and function of growth plate cartilage, distinct strategies are required for effective regeneration. Thus, this review provides an overview of current research on the application of tissue engineering to promote growth plate regeneration. It aims to elucidates the underlying mechanisms by which tissue engineering promotes growth plate regeneration and to provide novel insights and therapeutic strategies for future research on the regeneration of growth plate.

Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis.

Background: Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival. Method: Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356). Results: We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; Z = -2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; Z = -1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; Z = -3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; Z = -2.23; P = 0.0256). Conclusion: Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.

Injectable hydrogel loaded with bilayer microspheres to inhibit angiogenesis and promote cartilage regeneration for repairing growth plate injury.

Introduction: The repair and regeneration of growth plate injuries using tissue engineering techniques remains a challenge due to large bone bridge formation and low chondrogenic efficiency. Methods: In this study, a bilayer drug-loaded microspheres was developed that contains the vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, on the outer layer and insulin-like growth factor-1 (IGF-1), a cartilage repair factor, on the inner layer. The microspheres were then combined with bone marrow mesenchymal stem cells (BMSCs) in the gelatin methacryloyl (GelMA) hydrogel to create a composite hydrogel with good injectability and biocompatibility. Results: The in vitro drug-release profile of bilayer microspheres showed a sequential release, with Bevacizumab released first followed by IGF-1. And this hydrogel simultaneously inhibited angiogenesis and promoted cartilage regeneration. Finally, in vivo studies indicated that the composite hydrogel reduced bone bridge formation and improved cartilage regeneration in the rabbit model of proximal tibial growth plate injury. Conclusion: This bilayer microsphere-based composite hydrogel with sequential controlled release of Bevacizumab and IGF-1 has promising potential for growth plate injury repair.