Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-ß Axis in Dendritic Cells.

The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1α expression, a transcription factor that amplifies TGF-ß production and inhibits the effective T cell function. In vivo, knock-out of HIF-1α in DCs or using a HIF-1α inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1α protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1α-TGF-ß axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration.

Engineered Macrophage Membrane-Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death.

Spinal cord injury (SCI) is a severe neurological disorder characterized by significant disability and limited treatment options. Mitigating the secondary inflammatory response following the initial injury is the primary focus of current research in the treatment of SCI. CCL2 (C─C motif chemokine ligand 2) serves as the primary regulator responsible for inflammatory chemotaxis of the majority of peripheral immune cells, blocking the CCL2-CCR2 (C─C chemokine receptor type 2) axis has shown considerable therapeutic potential for inflammatory diseases, including SCI. In this study, it presents a multifunctional biomimetic nanoplatform (CCR2-MM@PLGA/Cur) specifically designed to target the CCL2-CCR2 axis, which consisted of an engineered macrophage membrane (MM) coating with enhanced CCR2 expression and a PLGA (poly (lactic-co-glycolic acid)) nanoparticle that encapsulated therapeutic drugs. CCR2 overexpression on MM not only enhanced drug-targeted delivery to the injury site, but also attenuated macrophage infiltration, microglia pro-inflammatory polarization, and neuronal apoptosis by trapping CCL2. Consequently, it facilitated neural regeneration and motor function recovery in SCI mice, enabling a comprehensive treatment approach for SCI. The feasibility and efficacy of this platform are confirmed through a series of in vitro and in vivo assays, offering new insights and potential avenues for further exploration in the treatment of SCI.

Comparative transcriptome analysis reveals significant differences in gene expression between pathogens of apple Glomerella leaf spot and apple bitter rot.

BACKGROUND: Apple Glomerella leaf spot (GLS) and apple bitter rot (ABR) are two devastating foliar and fruit diseases on apples. The different symptoms of GLS and ABR could be related to different transcriptome patterns. Thus, the objectives of this study were to compare the transcriptome profiles of Colletotrichum gloeosporioides species complex isolates GC20190701, FL180903, and FL180906, the pathogen of GLS and ABR, and to evaluate the involvement of the genes on pathogenicity. RESULTS: A relatively large difference was discovered between the GLS-isolate GC20190701 and ABR-isolates FL180903, FL180906, and quite many differential expression genes associated with pathogenicity were revealed. The DEGs between the GLS- and ABR-isolate were significantly enriched in GO terms of secondary metabolites, however, the categories of degradation of various cell wall components did not. Many genes associated with secondary metabolism were revealed. A total of 17 Cytochrome P450s (CYP), 11 of which were up-regulated while six were down-regulated, and five up-regulated methyltransferase genes were discovered. The genes associated with the secretion of extracellular enzymes and melanin accumulation were up-regulated. Four genes associated with the degradation of the host cell wall, three genes involved in the degradation of cellulose, and one gene involved in the degradation of xylan were revealed and all up-regulated. In addition, genes involved in melanin syntheses, such as tyrosinase and glucosyltransferase, were highly up-regulated. CONCLUSIONS: The penetration ability, pathogenicity of GLS-isolate was greater than that of ABR-isolate, which might indicate that GLS-isolate originated from ABR-isolates by mutation. These results contributed to highlighting the importance to investigate such DEGs between GLS- and ABR-isolate in depth.

MiR-149-3p can improve the osteogenic differentiation of human adipose-derived stem cells via targeting AKT1.

The study aims to investigate the role of microRNA-149-3p (miR-149-3p) in regulating osteogenic differentiation of human adipose-derived stem cells (hADSCs) by targeting v-akt murine thymoma viral oncogene homolog 1 (AKT1). Bioinformatics websites and a dual luciferase reporter assay were used to predict and verify the targeting relationship between miR-149-3p and AKT1. The hADSCs were divided into the blank, negative control (NC), mimic, control siRNA, AKT1 siRNA, and miR-149-3p inhibitors + AKT1 siRNA groups and then subjected to Alizarin Red staining, Alkaline phosphatase (ALP) staining, ALP activity detections, MTT assay, and EdU cell proliferation assay. Gene or protein expression was quantified using quantitative real-time PCR (qRT-PCR) or Western blotting, respectively. The miR-149-3p expression increased gradually and AKT1 expression decreased gradually during osteogenic differentiation of hADSCs. The prediction of bioinformatics websites miRTarBase and TargetScan and the dual luciferase reporter assay indicated that miR-149-3p can directly target AKT1. After hADSCs were transfected with miR-149-3p mimic, AKT1 expression was significantly downregulated. However, transfection with AKT1 siRNA did not have an impact on miR-149-3p in hADSCs. In comparison with the AKT1 siRNA group, the miR-149-3p inhibitors + AKT1 siRNA group showed decreased miR-149-3p expression but increased AKT1 expression. In addition, AKT1 siRNA enhanced the cell viability and proliferation of hADSCs and increased mineral calcium deposition and ALP activity, resulting in higher expression of osteogenic differentiation-related genes, which was reversed by miR-149-3p inhibition. The miR-149-3p can increase the expression of osteogenic differentiation-related genes by targeting AKT1 and thereby enhance the osteogenic differentiation of hADSCs.

Robust Matrix Effect-Free Method for Simultaneous Determination of Legacy and Emerging Per- and Polyfluoroalkyl Substances in Crop and Soil Matrices.

Increasing use of emerging per- and polyfluoroalkyl substances (PFASs) has caused extensive concerns around the world. Effective detection methods to trace their pollution characteristics and environmental behaviors in complex soil-crop systems are urgently needed. In this study, a reliable and matrix effect (ME)-free method was developed for simultaneous determination of 14 legacy and emerging PFASs, including perfluorooctanoic acid, perfluorooctane sulfonate, 6 hydrogenous PFASs, 3 chlorinated PFASs, and 3 hexafluoropropylene oxide homologues, in 6 crop (the edible parts) and 5 soil matrices using ultrasonic extraction combined with solid-phase extraction and ultraperformance liquid chromatography-mass spectrometry (MS)/MS. The varieties of extractants and cleanup cartridges, the dosage of ammonia hydroxide, and the ME were studied to obtain an optimal pretreatment procedure. The developed method had high sensitivity and accuracy with satisfactory method detection limits (2.40-83.03 pg/g dry weight) and recoveries (72-117%) of all target analytes in matrices at five concentrations, that is, 0.1, 1, 10, 100, and 1000 ng/g. In addition, the ME of this method (0.82-1.15) was negligible for all PFASs, even considering 11 different matrices. The successful application of the ME-free method to simultaneously determine the legacy and emerging PFASs in crop and soil samples has demonstrated its excellent practicability for monitoring emerging PFASs in soil-crop systems.

Is a Three-Dimensional Printing Model Better Than a Traditional Cardiac Model for Medical Education? A Pilot Randomized Controlled Study.

BACKGROUND: Three-dimensional (3D) printing is a newly-emerged technology converting a series of two-dimensional images to a touchable 3D model, but no studies have investigated whether or not a 3D printing model is better than a traditional cardiac model for medical education. METHODS: A 3D printing cardiac model was generated using multi-slice computed tomography datasets. Thirty-four medical students were randomized to either the 3D Printing Group taught with the aid of a 3D printing cardiac model or the Traditional Model Group with a commonly used plastic cardiac model. Questionnaires with 10 medical questions and 3 evaluative questions were filled in by the students. RESULTS: A 3D printing cardiac model was successfully generated. Students in the 3D Printing Group were slightly quicker to answer all questions when compared with the Traditional Model Group (224.53 ± 44.13 s vs. 238.71 ± 68.46 s, p = 0.09), but the total score was not significantly different (6.24 ± 1.30 vs. 7.18 ± 1.70, p = 0.12). Neither the students'satisfaction (p = 0.48) nor their understanding of cardiac structures (p = 0.24) was significantly different between two groups. More students in the 3D Printing Group believed that they had understood at least 90% of teaching content (6 vs. 1). Both groups had 12 (70.6%) students who preferred a 3D printing model for medical education. CONCLUSIONS: A 3D printing model was not significantly superior to a traditional model in teaching cardiac diseases in our pilot randomized controlled study, yet more studies may be conducted to validate the real effect of 3D printing on medical education.