The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg
2+
) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg
2+
-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The
in vivo
results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of
in situ
immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.
Functional bioelectronic implants require energy storage units as power sources. Current energy storage implants face challenges of balancing factors including high‐performance, biocompatibility, conformal adhesion, and mechanical compatibility with soft tissues. An all‐hydrogel micro‐supercapacitor is presented that is lightweight, thin, stretchable, and wet‐adhesive with a high areal capacitance (45.62 F g−1) and energy density (333 μWh cm−2, 4.68 Wh kg−1). The all‐hydrogel micro‐supercapacitor is composed of polyaniline@reduced graphene oxide/Mxenes gel electrodes and a hydrogel electrolyte, with its interfaces robustly crosslinked, contributing to efficient and stable electrochemical performance. The in vitro and in vivo biocompatibility of the all‐hydrogel micro‐supercapacitor is evaluated by cardiomyocytes and mice models. The latter is systematically conducted by performing histological, immunostaining, and immunofluorescence analysis after adhering the all‐hydrogel micro‐supercapacitor implants onto hearts of mice for two weeks. These investigations offer promising energy storage modules for bioelectronics and shed light on future bio‐integration of electronic systems.
As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems.
The diversity of class D β-lactamases mediating resistance to β-lactams has been increasingly reported recently. In this study, a novel class D oxacillinase named OXA-830 was identified in a fully sequenced Aeromonas simiae strain, which was isolated from sewage discharged from a farm in southern China. OXA-830 shares the highest amino acid identity of 79.3% with an OXA-12-like variant named OXA-725. When expressed in E. coli DH5α, OXA-830 conferred resistance to penicillins and selected β-lactamase inhibitors but not to cephalosporins and carbapenems. Kinetic analysis of OXA-830 revealed a broad substrate profile including penicillins, cefazolin, cefoxitin, and ceftazidime but not carbapenems. The hydrolytic activity was significantly inhibited by sulbactam, followed by tazobactam, but was less effectively inhibited by clavulanic acid. The blaOXA–830 gene was located on the A. simiae A6 chromosome and the blaOXA–830-related region was bracketed by a pair of perfect inverted repeats.
Pancreatic adenocarcinoma (PAAD) is the 10th most common cancer worldwide and the outcomes for patients with the disease remain extremely poor. Precision biomarkers are urgently needed to increase the efficiency of early diagnosis and to improve the prognosis of patients. The tumor microenvironment (TME) and tumor immune infiltration are thought to impact the occurrence, progression, and prognosis of PAAD. Novel biomarkers excavated originating from the TME and immune infiltration may be effective in predicting the prognosis of PAAD patients. In the current study, the ESTIMATE and CIBERSORT algorithms were applied to estimate the division of immune and stromal components and the proportion of tumor-infiltrating immune cells in 182 PAAD cases downloaded from The Cancer Genome Atlas database. Intersection analyses of the Protein-Protein Interaction networks and Cox regression analysis identified the chemokine (CXC-motif) ligand 10 (CXCL10) as a predictive biomarker. We verified that CXCL10 in the TME negatively correlates with prognosis in PAAD and positively correlates with tumor cell differentiation. GSE62452 from the GEO database and cumulative survival analysis were performed to validate CXCL10 expression as an independent prognostic indicator. We also found that memory B cells, regulatory T cells, and macrophages M0 and M1 were correlated with the expression of CXCL10 indicating that expression of CXCL10 influenced the immune activity of the TME. Our data suggest that CXCL10 is beneficial as a prognostic indicator in PAAD patients and highlights the potential for immune targeted therapy in the treatment of PAAD.
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