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Fucoidan, a sulfated polysaccharide with a complex structure, has gradually become the focus of biomedical research due to its remarkable biological activity and low toxicity. In this research, it was noted that low molecular weight fucoidan (LMWF) exhibited significant antimicrobial effects on Methicillin-resistant Staphylococcus aureus (MRSA) and promoted polarization towards M2 macrophages, leading to a substantial reduction in inflammatory responses within the lipopolysaccharide (LPS)-activated macrophages. We further explored the mechanism underlying the anti-inflammation activity. Our findings indicated that LMWF significantly enhanced the phosphorylation level of AMP-activated protein kinase (AMPK), inhibited the phosphorylation of the mammalian target of rapamycin (mTOR), and enhanced the expression of LC3II. Meanwhile, Compound C (CC) substantially reversed the anti-inflammation effect of LMWF, indicating that the AMPK pathway plays a pivotal role in this effect. In in vivo research, LMWF revealed impressive anti-inflammatory potential. LMWF treatment significantly eliminated MRSA and ameliorated inflammatory symptoms in mice's MRSA-infected skin wound model. Further analysis using Western Blot (WB) indicated significant AMPK/mTOR signaling pathway activation in mice treated with LMWF, which led to accelerated polarization of macrophages from the M1 to the M2 phenotype. In summary, we systematically explored the mechanism by which LMWF exerts anti-inflammatory effects through in vitro and in vivo experiments. It was confirmed that LMWF effectively induced the conversion of macrophages to an anti-inflammatory M2 phenotype by activating the AMPK/mTOR pathway. Simultaneously, LMWF effectively eradicated MRSA and accelerated wound healing in mice. This finding provides an important theoretical basis for further research on fucoidan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis., (© 2024. The Author(s).)

Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niu chengcheng reports financial support was provided by Niu, Chengcheng., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes., (© 2023 Wiley-VCH GmbH.)

Purpose: To investigate whether tranexamic acid (TXA) is cytotoxic in chondrocyte and cartilage tissues, as well as explore the mechanisms behind the possible toxicity in detail., Methods: We detected the cell viability of chondrocytes in vitro and the change of morphology and specific in vivo contents of cartilage after TXA treatment. Furthermore, we detected apoptosis in cartilage. We used apoptosis-specific staining, reactive oxygen species detection, mitochondrial membrane potential detection, flow cytometry, and western blot for apoptosis detection. Finally, we detected the activation of endoplasmic reticulum stress (ERS) in TXA-treated chondrocytes to clarify the mechanism behind chondrocyte apoptosis., Results: TXA presented an increasing toxic effect with increasing concentrations, especially in the 100 mg/mL group. In addition, we found that 50 mg/mL and 100 mg/mL TXA significantly increased apoptosis in cartilage and subchondral bone. TXA could induce chondrocyte apoptosis in cell and protein levels with reactive oxygen species generation and mitochondrial membrane depolarization. An apoptosis inhibitor could inhibit the induced apoptosis. Next, TXA induced calcium overload in chondrocytes and increased ERS-specific protein expression, whereas ERS inhibitor blocked ERS activation and further inhibited chondrocyte apoptosis., Conclusions: We concluded that TXA had a toxic effect on chondrocytes by inducing apoptosis through ERS activation, especially in 50 mg/mL and 100 mg/mL groups. We recommend TXA concentrations of less than 50 mg/mL in joint surgeries., Clinical Relevance: It is still unclear whether TXA has a toxic effect on cartilage when topically used in joint surgeries. The concentration also varies. This study provides additional evidence that TXA at high concentrations will cause cartilage damage, which will help to provide a new understanding of the clinical administration of TXA., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis., (© 2023. The Author(s).)

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great practical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruction, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage "homing" into periprosthetic osteolysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camouflage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exosome delivery system for preventing wear particles-induced osteolysis. STATEMENT OF SIGNIFICANCE: Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri‑prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs., Competing Interests: Declaration of Competing Interest All other authors declare no competing interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Differentiating the type and cause of shock is crucial for intensive care. The rapid aggravation of lactic acidosis in patients often indicates a severe impairment of oxygen uptake in tissues. Herein, we presented a rare case of refractory distributive shock with severe wet beriberi. A 40-year-old male was admitted to the emergency department (ED) with recurrent chest tightness and lower extremity edema. The condition of the patient continued to deteriorate after symptomatic treatments. After several turnovers, the medical history of the patient was requested again and finally obtained. Our emergency management team hypothesized that the thiamine-deficient diet caused an aerobic metabolism disorder in the patient. Overall, we aimed to alert clinicians to unusual causes of distributive shock and further discussed the application of thiamine supplementary therapy in critical care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USC EXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USC EXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USC EXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USC EXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USC EXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Ion-exchange materials, currently dominated by resins, are widely used in a plethora of areas. However, the drawbacks of conventional resins necessitate the creation of a new model of ion exchange materials that feature controllable swelling, easily accessible ion exchange sites, high ion exchange capacity, fast ion exchange kinetics, and high chemical stability as illustrated herein in the context of functionalizing a porous organic polymer (POP) with ion exchange groups. The advantages of POP-based ion exchange materials in comparison with conventional resins and other types of ion exchange materials have been highlighted through an evaluation of their performances in scavenging precious metals at trace concentrations, removal of nuclear waste model ions, and size-selective ion capture. Our work thereby provides a new perspective to develop ion functionalized POPs as a versatile type of ion exchange materials for various applications.

In this work, a new strategy is developed to encapsulate a metal-functionalized guest molecule into a metal-organic framework (MOF) via metal-cation-directed de novo assembly from the component fragments of the guest molecule. This strategy, as illustrated in proof-of-principle studies on the de novo assembly of metal(II) phthalocyanine molecules into bio-MOF-1, can circumvent some drawbacks of existing approaches for encapsulating guest molecules into MOFs, such as inaccessibility for larger guest molecules due to limitations of the MOF window size and disruption of the MOF framework structure by functionalized guest molecules. Overall, this work provides a general yet versatile approach for encapsulating a broader range of metal-functionalized guest molecules into MOFs for various applications.

Metal-organic polyhedra (MOP) nanocages were successfully surface functionalized via ionic self-assembly and the ordered honeycomb architecture of the encapsulated MOP nanocages was also fabricated at the air/water surface. The results provide a novel synthetic method and membrane processing technique of amphiphilic MOP nanocages for various applications.