AIMS:To investigate the molecular mechanisms by which magnesium (Mg)-based implants, specifically Mg-containing intramedullary nails (Mg-IMNs), promote femoral fracture healing. MATERIALS AND METHODS:Rats with femoral fractures were treated with Mg-IMNs. In vitro experiments were conducted to assess the impact of Mg2+ on osteoclastogenesis and histone lactylation. Histological analysis, Western blotting, and qRT-PCR were employed to evaluate osteoclast maturation and the molecular pathways involved. In vivo, lactate was administered to replicate Mg-IMN effects, and lactate production was inhibited to observe potential reversal effects. KEY FINDINGS:Mg-IMNs significantly enhanced fracture healing by inhibiting osteoclastogenesis. Mg2+ promoted intracellular lactate production, leading to histone lactylation, which suppressed osteoclast maturation by downregulating NFATc1. The P300/H3K18LA/HDAC1 pathway was identified as a key mediator in this process. Additionally, lactate administration mimicked the effects of Mg-IMNs, while blocking lactate reversed these effects. SIGNIFICANCE:This study uncovers a novel mechanism by which Mg2+ promotes fracture healing through histone lactylation-mediated inhibition of osteoclastogenesis. These findings offer new therapeutic strategies for enhancing fracture repair via epigenetic regulation.

Following damage to the skin and mucous membranes, bacterial infections, and excessive oxidative stress often lead to inflammatory responses and impaired wound healing, which can even be life-threatening. Surgical dressing combined with antimicrobial agent use is the major therapy. However, traditional gauze dressings are prone to causing secondary injuries, while systemic antibiotic therapy often fails to deliver sufficient drug concentrations at the wound site and carries the risk of systemic toxic side effects. Hydrogel dressing is a hot research field because of its breathability, biocompatibility, and easy access for modification. The healing of infected wounds is a complex process during which tough adhesion of the dressing to the wound and effective elimination of inflammation are both important for successful wound healing. To achieve this goal, we designed a "five-in-one" hydrogel wound dressing, CS/TA, using natural components including chitosan and tannic acid. Briefly, the CS/TA dressing was simultaneously characterized by five important capabilities, including tissue adhesion, self-healing property, extensibility, and antibacterial and antioxidant properties. The excellent adhesiveness, self-healing ability, and extensibility allowed the CS/TA dressing to conform to dynamic tissue changes and adhere closely to the wound. Moreover, the CS/TA dressing effectively eliminated bacteria and scavenged excess free radicals, thereby minimizing tissue inflammation. As a result, significantly accelerated wound healing was achieved in an infected wound model. To conclude, the study provided a novel perspective on hydrogel dressing design, and the five-in-one CS/TA dressing demonstrated great potential for infected wound treatment.

PURPOSE:Previous studies have demonstrated a role for oxidative stress in promoting osteoclastogenesis and bone loss. This study aimed to assess the ability of fullerol, a powerful nano-antioxidant, to prevent bone loss and promote osteogenesis, and additionally provide novel insight into mechanisms of action. METHODS:Osteoclastogenesis assays were conducted in murine progenitor cells stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL), with and without fullerol. The cells were stained to detect the presence of osteoclastic markers and RT-PCR was used to measure the expression of osteoclastic genes. To assess osteogenesis, stem cells were incubated in osteogenic medium with or without fullerol, as well as with an inhibitor of p38-MAPK, then stained to determine mineralization. RT-PCR was used to measure osteoblastic gene expression. In the animal model, rabbits were injected with methylprednisolone with or without fullerol, or a control. Animals were later euthanized and spine fragments underwent imaging assessment. RESULTS:Fullerol prevented formation of osteoclasts in RAW264.7 cells exposed to RANKL as well as the expression of osteoclastic genes TRAP, CATK, and MMP9. D1 cells exposed to fullerol displayed an increase in extracellular matrix mineralization and expression of osteoblastic genes. However, when fullerol was added in the presence of a p38-MAPK inhibitor, its effects on mineralization were attenuated. In a rabbit model of steroid-induced osteoporosis, simultaneous injection of fullerol reduced vertebral bone loss, decreased trabecular separation, and increased trabecular number. CONCLUSION:Fullerol shows early potential for use in osteoporosis therapy, due to its ability to inhibit osteoclast formation and stimulate osteogenesis.

Inflammatory macrophages play a role in cartilage degeneration associated with osteoarthritis (OA) via signaling cascades that result in production of inflammatory substances. This study aims to characterize compound F2, C 60 (NCH 2 CH 2 OCH 2 CH 2 OH) 5 , a newly synthesized ethoxyethanol derivative of iminofullerene, and its potential to reduce inflammatory macrophage activity. First, compound F2 is synthesized and labeled with 99m Tc to create 99m Tc‐F2. It is then added to lipopolysaccharide (LPS)‐exposed bone marrow macrophages (BMMs) to determine its effect on macrophage activation, nitric oxide production, and expression of inflammatory markers iNOS, IL‐6, Fpr2, and TLR4. An animal model of osteoarthritis is also injected with 99m Tc‐F2 to visualize its localization in vivo. This study demonstrates successful synthesis and radiolabeling of the compound F2 molecule. It also demonstrates that compound F2 reduces nitrite production and suppresses the expression of TNF α, IL‐6, iNOS, Fpr2, and TLR4 in BMMs exposed to LPS. Additionally, in rats with surgically transected anterior cruciate ligaments, intravenous administration of radioisotope‐labeled compound F2 exhibits selective enrichment in the injured knee. These findings suggest that compound F2 mitigates macrophage activation, decreases inflammatory marker expression, and is located to damaged areas, highlighting its potential as a therapeutic option for OA management.

The packaging industry is transitioning towards sustainability in response to growing environmental concerns and evolving consumer expectations. While biodegradable packaging offers promise, issues such as potential microplastics and uncontrolled degradation hinder its widespread adoption as a perfect solution. Leveraging the water solubility of polyvinyl alcohol (PVA) and agricultural and forestry waste, i.e. straw, we demonstrated a PVA/gelatin/straw aerogel using ice-templating freeze-drying and solid state shear milling (S3M) technologies for packaging. The increased porosity of the aerogel enhances specific surface area of PVA, facilitating better interaction with the environment. Furthermore, the inclusion of biomass fillers reduces the phase domain size of PVA, improving water solubility. Gelatin further refines the pore structure, enhancing mechanical properties by providing physical crosslinking points. With an optimized composition, the aerogel achieves a compressive modulus of 0.96 MPa, meeting the strength criteria for polystyrene foam packaging according to QB/T 1649-1992 standards. Importantly, both the aerogel and its aqueous solution demonstrate non-toxicity and environmental friendliness. This study not only presents a series of eco-friendly aerogels but also explores novel applications for PVA in environmentally sustainable packaging.

AIMS:Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo.MATERIALS AND METHODS:Primary BMSCs were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A closed, transverse fracture at the femoral midshaft was created to compare bone healing between KO and WT mice. Biomechanical and structural properties of femur were compared between healthy WT and KO mice.KEY FINDINGS:FPR1 expression increased significantly during osteogenesis of both primary and cloned BMSCs. Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably improved compared to FPR1 KO mice analyzed by X-ray and micro-CT.SIGNIFICANCE:These findings indicated that FPR1 played a vital role in osteogenic differentiation and regenerative capacity of fractured bone, probably through the activation of FoxO1 related signaling pathways.

The double-shelled hollow polymer microspheres with a carboxylic acid in the inner shell and palladium metallic nanocolloids in the outer shell were prepared as a bi-functional catalyst for a tandem reaction including deacetalizationon-hydrogenation from benzaldehyde dimethyl acetate to benzyl alcohol. The double-shelled hollow poly(ethyleneglycol dimethacrylate-co-acrylic acid) (PAA) and poly(ethyleneglycol dimethacrylate-co-N-vinyl pyrrolidone) (PNVP) microspheres were synthesized by a two-stage refluxing precipitation copolymerization in presence of 3-(trimethoxysilyl) propyl methacrylate (MPS)-modified silica as seeds to get SiO2/Pt-BA/SiO2/PNVP tetra-layer microspheres with the subsequent hydrolysis of t-butyl ester to acid group and selective removal of the silica inner core and the sandwiched third layer. The palladium nano-colloids in outer-shell were prepared by the in-situ ethanol reduction of Pd(II) after the coordination of palladium acetate with N-pyrrolidone (NVP) groups in presence of SiO2/Pt-BA/SiO2/PNVP tetra-layer microspheres as stabilizers.

Background: Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements.Objective: We investigated the anti-inflammatory properties of two synthesized derivatives of Nacetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Methods: Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1 beta, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively.Results: Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF alpha and IL-1 beta expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. Conclusion: BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.

Purpose/Aim of the Study The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current literature on these roles before discussing the function of FPRs in the pathogenesis of musculoskeletal disorders including osteoarthritis (OA), degenerative disc disease (DDD), and rheumatoid arthritis (RA). Additionally, we discuss the potential diagnostic and therapeutic roles of FPRs in these domains.Methods PubMed and Ovid MEDLINE searches were performed from 1965 through March 2022. Keywords included “FPR, tissue expression, inflammation, infection, musculoskeletal disorder, bone, rheumatoid arthritis, osteoarthritis, degenerative disc disease, mitochondria.”Results Sixty-nine studies were included in this review article. FPRs appear to be ubiquitous in the pathogenesis, diagnosis, and treatment of common musculoskeletal disorders. They can potentially be utilized for the earlier diagnosis of OA and DDD. They may be employed with mesenchymal stem cells (MSCs) to reverse OA and DDD pathologies. With anti-inflammatory, anti-osteolytic, and pro-angiogenic functions, they may broaden treatment options in RA.Conclusions FPRs appear to be heavily involved in the pathogenesis of common musculoskeletal conditions, including arthritis, degenerative disc disease, and rheumatoid arthritis. Furthermore, they demonstrate much promise in the diagnosis and treatment of these conditions. Their roles should continue to be explored.

Yolk–shell nanoparticles (AIDNPs) with Ag nanoparticle core and imidazolium functionalized polymeric shell were prepared for CO 2 photo-catalytic reduction in a competitive and economical manner in absence of photo-sensitizer or sacrifice reducing agent.

Corilagin, extracted from the Euphorbiaceae and Phyllanthus plants, inhibits the growth of a number of types of tumors. Compared with temozolomide, the traditional chemotherapy drug, corilagin has demonstrated stronger antitumor activity. However, the pharmaceutical mechanism of corilagin in glioma remains unclear. Nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2) is positively associated with several types of tumor including glioma. In the present study, NRF2 expression was higher in glioma tissues compared with non-glioma specimens. Therefore, it was hypothesized that corilagin targets NRF2 regulation of U251 cell apoptosis. The present study used Hoechst 33258 staining to demonstrate that corilagin induced glioma cell apoptosis and observed that the expression of the apoptosis-related gene Bcl-2 was reduced. In addition, corilagin induced autophagy and promoted the conversion of light chain 3 (LC3) protein from LC3I to LC3II. NRF2 expression was downregulated by corilagin stimulation. Furthermore, the gene expression pattern following knockdown of NRF2 in U251 cells using siRNA was consistent with corilagin stimulation. Therefore, it was preliminarily concluded that corilagin induces apoptosis and autophagy by reducing NRF2 expression.

Transformation of microplastics in aquatic environments and engineered systems (e.g., wastewater treatment plants) significantly affects their transport, fate and effects. Here, we present the counterintuitive finding that sulfide, a prevalent nucleophile and reductant, can result in oxidation of microplastics, in addition to sulfide addition. Treating four model microplastics (thermoplastic polyurethane, polystyrene, polyethylene terephthalate and polyethylene) with 0.1 mM sulfide in a Tris-buffer solution (pH 7.2, 25 degrees C) resulted in physical damages (embrittlement and cracking) and chemical transformation (increased O/C ratio and formation of C-S bonds) of the materials. Pre-aging of the microplastics with O-3 or UV treatment had varied effects on their reactivities toward sulfide, depending on the specific structural and surface chemistry properties of the polymers. Electron paramagnetic resonance and radical trapping/quenching experiments showed that sulfide underwent spontaneous oxidation to form center dot OH radicals, which acted as the primary oxidant to attack the carbon atoms in the polymer chains, leading to surface oxidation and chain scission. Notably, sulfide addition, verified with X-ray photoelectron spectroscopy and 13C-nuclear magnetic resonance spectroscopy analyses, likely contributed to the physicochemical transformation of microplastics together with radical oxidation in a synergistic manner. The findings unravel an important transformation route (and a potential source) of microplastics in the environment. (C) 2021 Elsevier Ltd. All rights reserved.

Although inflammation has been recognized as a key process in the pathogenesis of osteoarthritis (OA), there remains no clinical noninvasive imaging modality that can specifically diagnose inflammatory activity of OA. In this study, a formyl peptide receptor 1 (Fpr1) targeting probe cFLFLF-PEG-HYNIC-99mTc and single-photon emission computed tomography (SPECT) imaging was used to detect inflammatory activity by targeting macrophages involved in the pathogenesis of OA. In vitro experiments were performed to evaluate Fpr1 expression during macrophage inflammatory response. In the in vivo studies, anterior cruciate ligament transection (ACLT) surgery was performed, and magnetic resonance imaging (MRI) and histological data were assessed to analyze the OA model in both mice and rats. The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging were used to corroborate OA-related inflammation and compare ACLT vs sham knees. In vitro macrophage activation resulted in a remarkable increase in Fpr1 expression. In vivo experiments in mice and rats produced similar results. MRI and histological analysis demonstrated significant joint degeneration in the ACLT knee. The ACLT knee produced a much stronger signal from the probe when compared to the sham knee. It is important to note that the ratio of ACLT/sham knee signal intensity decreased with OA progression, indicating greater differences earlier in the progression of OA. The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging are effective for detecting and monitoring inflammation during OA progression by targeting Fpr1 expression in the knee joint.

Star multiple block copolymer of poly (4-vinylpyridine)-block-polystyrene (s-P4VP-b-PS) is synthesized via initial synthesis of linear poly (4-vinylpyridine)-block-polystyrene (l-P4VP-b-PS) by dispersion RAFT polymerization to form l-P4VP-b-PS nano-assemblies and then cross-linking within the l-P4VP-b-PS nano-assemblies. The synthesized s-P4VP-b-PS has a high molecular weight and exists 25-47 nm nanospheres in the common solvent of N,Ndimethylformamide. The self-assembly of s-P4VP-b-PS in two block selective solvents, e.g., toluene and methanol, is investigated, and great difference from l-P4VP-b-PS is demonstrated. In methanol, s-P4VP-b-PS forms corecorona nanospheres. In toluene, s-P4VP-b-PS forms dispersed nanoparticles or nanoparticle clusters dependent on polymer concentration. In the s-P4VP-b-PS nanoparticle clusters, poly (4-vinylpyridine) forms dispersed nanodomains, the size of which is firmly dependent on the degree of polymerization of the P4VP block. It is thought that the great difference between s-P4VP-b-PS and l-P4VP-b-PS will arouse new interest on self-assembly of block copolymers.

Surface charge switchable nanoparticles for NO-releasing as acidity associated bacterial infection target treatment were described.

Objective:To evaluate the influence of adrenocorticotropic hormone on osteogenic differentiation of a mouse bone marrow-derived multipotent cell line, D1.Methods:D1 cells were divided into six groups: control group; control group treated with low concentration of adrenocorticotropic hormone (ACTH); control group treated with high concentration of ACTH; osteogenic medium group; osteogenic medium treated with low concentration of ACTH; osteogenic medium treated with high concentration of ACTH. Mineralization of mouse bone marrow-derived multipotent cell line (D1) cells were assessed by Alizarin Red staining at day 6; The gene expression of related transcription factor-2 (Runx2), alkaline phosphatase (ALP), melanocortin receptor 3 (MC3R) and vascular endothelial growth factor a (VEGFa) were detected by real-time quantitative polymerase chain reaction (Real-time PCR) when D1 cells were cultured at day 1, day 3 and day 6; Western blotting was used to detect the protein expression of Runx2 and BSP at day 3 and day 6. SPSS 17.0 software was used for all statistical analyses. All results are expressed as the mean±standard deviation. Student′s t-test and one-way analysis of variance were used for comparisons of means. Results:At day 3, osteogenic medium treated with ACTH (1×10 -8 mol/L) group (1.33±0.01) could suppress the gene expresssion of MC3R compared with osteogenic medium group (1.82±0.11) significantly ( t=5.039, P<0.05); At day 6, compared with osteogenic medium group (1.16±0.08), the gene expression of Runx2 (0.72±0.01) in osteogenic medium treated with ACTH (1×10 -8 mol/L) group was reduced significantly ( t=5.542, P<0.05), the gene expression of VEGFa (0.58±0.02) were downregulated by ACTH (1×10 -8 mol/L) compared with osteogenic medium group (2.23±0.06) significantly ( t=7.238, P<0.05); The mineralization of D1 cells in osteogenic medium treated with ACTH (1×10 -8 mol/L) group (0.270±0.012) was decreased in comparison with osteogenic medium group (0.361±0.015 ) significantly ( t=4.435, P<0.05); Western blotting analysis showed that the protein expression of Runx2 and BSP have been decreased correspondingly. The Alizarin Red staining results showed that there is no significant difference in low concentration of ACTH (1×10 -9 mol/L) group (0.363±0.013) compared with osteogenic medium group (0.360±0.016), the expression of osteogenic genes and proteins were no statistical significance correspondingly. Conclusion:Adrenocorticotropic Hormone (1×10 -8 mol/L) is able to suppress osteogenic differentiation of a mouse bone marrow-derived multipotent cell line, in addition, Runx2 was significantly inhibited at gene and protein levels.

Good proton conductivity and water retention are essential for proton exchange membranes (PEMs). However, proton conductivity of existing PEMs decreases sharply at low humidity, which seriously restricts the efficient and stable operation of fuel cell system. In this study, we design a spherical bell-typed superabsorbent microsphere with imidazole groups (SBSM) using the distillation-precipitation polymerization method, and incorporate it into sulfonated poly ether ether ketone (SPEEK) matrix to enhance proton conductivity. Benefited from the hygroscopic 3D framework of the superabsorbent core and the special hollow structure of SBSM, the composite membrane remarkably raises the water retention and proton conductivity. Meanwhile, the carboxylic acid, sulfonic acid and Lewis basic imidazole generate two types of "acid-base pairs", which serves as proton acceptors and donors to accelerate the formation of low energy paths at the membrane interfaces. The composite membrane with 15 wt% fillers exhibits the highest water retention of 15.72% and the highest proton conductivity of 0.0284 S cm(-1) at room temperature and 20% relative humidity (RH). These improvements are attributed to the unique structure of the SBSMs that provides a stable aqueous environment and additional proton conduction pathways in the membrane.

Acid/base bi-functional polymeric materials were prepared using physically mixed porous polymers P(DVB-VBS) with sulfonic acid and P(DVB-VBA) with amino groups for various cascade reactions.

The disulfide bond-crosslinked polymer nanoparticles based on iopamidol were prepared and then surface-modified with cRGD peptide through the linkages of PEG to acquire a CT contrast agent for breast cancer-targeted imaging.

In recent years, the fabrication of well-organized proteinosomes has been a popular topic due to the potential applications of the structures in materials science and nanotechnology. A big challenge in the fabrication of proteinosomes is to maintain the structures and the functionalities of proteins on the proteinosomes. In this research, a new concept of polymerization-induced formation of proteinosomes is proposed. In thermal dispersion polymerization of N-isopropyl acrylamide (NIPAM) in the presence of bovine serum albumin (BSA), the growing PNIPAM chains experience phase transition from hydrated coils to dehydrated globules, and the dehydrated PNIPAM chains have hydrophobic interaction with BSA, leading to the formation of hollow proteinosomes. Kinetics studies indicate that there is a transition from the homogeneous polymerization of NIPAM in solution to the heterogeneous polymerization in the proteinosomes. Transmission electron microscopy, atomic force microscopy, confocal laser scanning microscopy and dynamic light scattering all demonstrate the formation of hollow structures. The results of circular dichroism spectroscopy indicate that the secondary structure of BSA remains unchanged in the polymerization process. The formation of proteinosomes is reversible. Upon cooling of the solution to a temperature below the phase transition temperature of PNIPAM, the proteinosomes are dissociated due to the absence of the hydrophobic interaction. The proteinosomes can be used in the encapsulation of hydrophilic compounds in aqueous solution. In this research, not only BSA but also ovalbumin (OVA) is used as a model protein for the fabrication of proteinosomes by the polymerization-induced approach.