Enzyme-Activated Biomimetic Vesicles Confining Mineralization for Bone Maturation.

Inspired by the crucial role of matrix vesicles (MVs), a series of biomimetic vesicles (BVs) fabricated by calcium glycerophosphate (CaGP) modified polyurethane were designed to mediate the mineralization through in situ enzyme activation for bone therapy. In this study, alkaline phosphatase (ALP) was harbored in the porous BVs by adsorption (Ad-BVs) or entrapment (En-BVs). High encapsulation of ALP on En-BVs was effectively self-activating by calcium ions of CaGP-modified PU that specifically hydrolyzed the organophosphorus (CaGP) to inorganic phosphate, thus promoting the formation of the highly oriented bone-like apatite in vitro. Enzyme-catalyzed kinetics confirms the regulation of apatite crystallization by the synergistic action of self-activated ALP and the confined microcompartments of BVs. This leads to a supersaturated microenvironment, with the En-BVs group exhibiting inorganic phosphate (Pi) levels 4.19 times higher and Ca2+ levels 3.67 times higher than those of simulated body fluid (SBF). Of note, the En-BVs group exhibited excellent osteo-inducing differentiation of BMSCs in vitro and the highest maturity with reduced bone loss in rat femoral defect in vivo. This innovative strategy of biomimetic vesicles is expected to provide valuable insights into the enzyme-activated field of bone therapy.

Composite hydrogels with antioxidant and robust adhesive properties for the prevention of radiation-induced dermatitis.

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.

Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design.

Previous studies have confirmed that intervertebral disc degeneration (IDD) is closely associated with inflammation-induced reactive oxygen species (ROS) and resultant cell mitochondrial membrane potential (MMP) decline. Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline. Additionally, re-energizing the mitochondria damaged in the inflammatory milieu to restore their function, is equally important. Herein, we proposed an interesting concept of mitochondrion-engine equipped with coolant, which enables first to "cool-down" the inflammatory environment, next to restore the MMP, finally to allow cells to regain normal energy metabolism through materials design. As such, we developed a multi-functional composite composed of a reactive oxygen species (ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane (TPU) scaffold. The TPU scaffold was coated with conductive polypyrrole (PPy) to electrophoretically deposit l-arginine, which could upregulate the Mammalian target of rapamycin (mTOR) pathway, thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair. While the ROS-responsive hydrogel acting as the "mito-engine coolant" could scavenge the excessive ROS to create a favorable environment for IVD cells recovery. Demonstrated by in vitro and in vivo evaluations, the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress. Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair. This unique bioinspired design integrated biomaterial science with mitochondrial biology, presents a promising paradigm for IDD treatment.

In situ comparison of osteogenic effects of polymer-based scaffolds with different degradability by integrated scaffold model.

Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds.

Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8.

Introduction: Equid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control. Methods: In this study, we investigated the in vitro and in vivo antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8. Results: Our results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, in vivo experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model. Conclusion: Collectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge.

A Novel Strategy for Fabrication of Polyamide 66/Nanohydroxyapatite Composite Bone Repair Scaffolds by Low-Temperature Three-Dimensional Printing.

Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide.

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.

Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure.

Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.

Mechanistic study of heat shock protein 60-mediated apoptosis in DF-1 cells.

Heat shock proteins (HSP) are a group of highly conserved molecular chaperones found in various organisms and have been associated with tumorigenesis, tumor progression, and metastasis. However, the relationship between HSP60 and apoptosis remains elusive. The aim of this study was to explore the role and regulatory mechanisms of apoptosis in response to altered HSP60 expression. We generated DF-1 cell lines of both HSP60 overexpression and knockdown and assessed their impact on apoptosis levels using ELISA and flow cytometry analyses. Additionally, we examined the transcription and protein expression levels of apoptosis-related signaling factors using fluorescence quantitative PCR (qPCR) and Western blotting analyses. Heat shock proteins 60 overexpression led to a significant decrease in apoptosis levels in DF-1 cells, which could be attributed to the downregulation of BAX and BAK expression, the upregulation of Bcl-2, and the decreased expression of Caspase 3. Conversely, HSP60 knockdown led to a substantial increase in apoptosis levels in DF-1 cells, facilitated by the downregulation of BAX and Bcl-2 expression, and the upregulation of BAK expression, which increased Caspase 3 levels, thereby promoting apoptosis. The findings of our study provide the first evidence of the inhibitory effect of HSP60 on apoptosis in DF-1 cells. These observations have significant implications for disease progression and cancer research, with potential medical applications.

Phages in sludge from the A/O wastewater treatment process play an important role in the transmission of ARGs.

Phages can influence the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) through transduction, but their profiles and effects on the transmission of ARGs are unclear, especially in complex swine sludge. In this study, we investigated the characterization of phage and ARG profiles in sludge generated from anoxic/oxic (A/O) wastewater treatment processes on swine farms using metagenomes and viromes. The results demonstrated that 205-221 subtypes of ARGs could be identified in swine sludge, among which sul1, tet(M), and floR were the dominant ARGs, indicating that sludge is an important reservoir of ARGs, especially in sludge (S) tanks. The greater abundance of mobile genetic elements (MGEs) in the S tank could significantly contribute to the greater abundance of ARGs there compared to the anoxic (A) and oxic (O) tanks (P < 0.05). However, when we compared the abundances of ARGs and MGEs in the A and O tanks, we observed opposite significant differences (P < 0.05), suggesting that MGEs are not the only factor influencing the abundance of ARGs. The high proportion of lysogenic phages in sludge from the S tank can also have a major impact on the ARG profile. Siphoviridae, Myoviridae, and Podoviridae were the dominant phage families in sludge, and a network diagram of bacteria-ARG-phages revealed that dominant phages and bacteria acted simultaneously as potential hosts for ARGs, which may have led to phage-mediated HGT of ARGs. Therefore, the risk of phage-mediated HGT of ARGs cannot be overlooked.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

Biological characteristics of the bacteriophage LDT325 and its potential application against the plant pathogen Pseudomonas syringae.

Bud blight disease caused by Pseudomonas syringae is a major bacterial disease of tea plants in China. Concerns regarding the emergence of bacterial resistance to conventional copper controls have indicated the need to devise new methods of disease biocontrol. Phage-based biocontrol may be a sustainable approach to combat bacterial pathogens. In this study, a P. syringae phage was isolated from soil samples. Based on morphological characteristics, bacteriophage vB_PsS_LDT325 belongs to the Siphoviridae family; it has an icosahedral head with a diameter of 53 ± 1 nm and nonretractable tails measuring 110 ± 1 nm. The latent period and burst size of the phage were 10 min and 17 plaque-forming units (PFU)/cell, respectively. Furthermore, an analysis of the biological traits showed that the optimal multiplicity of infection (MOI) of the phage was 0.01. When the temperature exceeded 60°C, the phage titer began to decrease. The phage exhibited tolerance to a wide range of pH (3-11) and maintained relatively stable pH tolerance. It showed a high tolerance to chloroform, but was sensitive to ultraviolet (UV) light. The effects of phage LDT325 in treating P. syringae infections in vivo were evaluated using a tea plant. Plants were inoculated with 2 × 107 colony-forming units (CFU)/mL P. syringae using the needle-prick method and air-dried. Subsequently, plants were inoculated with 2 × 107 PFU/mL LDT325 phage. Compared with control plants, the bacterial count was reduced by 1 log10/0.5 g after 4 days in potted tea plants inoculated with the phage. These results underscore the phage as a potential antibacterial agent for controlling P. syringae.

Diltiazem HCl suppresses porcine reproductive and respiratory syndrome virus infection in susceptible cells and in swine.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen for swine, resulting in substantial economic losses to the swine industry. However, there has been little success in developing effective vaccines or drugs for PRRSV control. In the present study, we discovered that Diltiazem HCl, an inhibitor of L-type Ca2+ channel, effectively suppresses PRRSV replication in MARC-145, PK-15CD163 and PAM cells in dose-dependent manner. Furthermore, it demonstrates a broad-spectrum activity against both PRRSV-1 and PRRSV-2 strains. Additionally, we explored the underlying mechanisms and found that Diltiazem HCl -induced inhibition of PRRSV associated with regulation of calcium ion homeostasis in susceptible cells. Moreover, we evaluated the antiviral effects of Diltiazem HCl in PRRSV-challenged piglets, assessing rectal temperature, viremia, and gross and microscopic lung lesions. Our results indicate that Diltiazem HCl treatment alleviates PRRSV-induced rectal temperature spikes, pulmonary pathological changes, and serum viral load. In conclusion, our data suggest that Diltiazem HCl could serve as a novel therapeutic drug against PRRSV infection.

Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.

Heme oxygenase-1 is an equid alphaherpesvirus 8 replication restriction host protein and suppresses viral replication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathway.

Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)ß/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

A comparative analysis of phage classification methods in light of the recent ICTV taxonomic revisions.

Recent ICTV taxonomy updates significantly changed phage taxonomy, yet a thorough phage classification workflow doesn't exist. This study compares six categorization tools and establishes a novel multi-method approach, combining genome similarity and specialized protein analysis. Applying the method to APEC phage P151 showed consistent categorization across platforms. A possible workflow for phage classification is proposed; offering a versatile tool for phage research and development.

Core-Shell Structured Nanozyme with PDA-Mediated Enhanced Antioxidant Efficiency to Treat Early Intervertebral Disc Degeneration.

Early intervention during intervertebral disc degeneration (IDD) plays a vital role in inhibiting its deterioration and activating the regenerative process. Aiming at the high oxidative stress (OS) in the IDD microenvironment, a core-shell structured nanozyme composed of Co-doped NiO nanoparticle (CNO) as the core encapsulated with a polydopamine (PDA) shell, named PDA@CNO, was constructed, hoping to regulate the pathological environment. The results indicated that the coexistence of abundant Ni3+/Ni2+and Co3+/Co2+redox couples in CNO provided rich catalytic sites; meanwhile, the quinone and catechol groups in the PDA shell could enable the proton-coupled electron transfer, thus endowing the PDA@CNO nanozyme with multiple antioxidative enzyme-like activities to scavenge •O2-, H2O2, and •OH efficiently. Under OS conditions in vitro, PDA@CNO could effectively reduce the intracellular ROS in nucleus pulposus (NP) into friendly H2O and O2, to protect NP cells from stagnant proliferation, abnormal metabolism (senescence, mitochondria dysfunction, and impaired redox homeostasis), and inflammation, thereby reconstructing the extracellular matrix (ECM) homeostasis. The in vivo local injection experiments further proved the desirable therapeutic effects of the PDA@CNO nanozyme in a rat IDD model, suggesting great potential in prohibiting IDD from deterioration.

Guiding the Path to Healing: CuO2 -Laden Nanocomposite Membrane for Diabetic Wound Treatment.

Diabetic chronic wounds pose significant clinical challenges due to their characteristic features of impaired extracellular matrix (ECM) function, diminished angiogenesis, chronic inflammation, and increased susceptibility to infection. To tackle these challenges and provide a comprehensive therapeutic approach for diabetic wounds, the first coaxial electrospun nanocomposite membrane is developed that incorporates multifunctional copper peroxide nanoparticles (n-CuO2 ). The membrane's nanofiber possesses a unique "core/sheath" structure consisting of n-CuO2 +PVP (Polyvinylpyrrolidone)/PCL (Polycaprolactone) composite sheath and a PCL core. When exposed to the wound's moist environment, PVP within the sheath gradually disintegrates, releasing the embedded n-CuO2 . Under a weakly acidic microenvironment (typically diabetic and infected wounds), n-CuO2 decomposes to release H2 O2 and Cu2+ ions and subsequently produce ·OH through chemodynamic reactions. This enables the anti-bacterial activity mediated by reactive oxygen species (ROS), suppressing the inflammation while enhancing angiogenesis. At the same time, the dissolution of PVP unveils unique nano-grooved surface patterns on the nanofibers, providing desirable cell-guiding function required for accelerated skin regeneration. Through meticulous material selection and design, this study pioneers the development of functional nanocomposites for multi-modal wound therapy, which holds great promise in guiding the path to healing for diabetic wounds.

Propelling Multi-Modal Therapeutics of PEEK Implants through the Power of NO evolving Covalent Organic Frameworks (COFs).

The design and fabrication of NO-evolving core-shell nanoparticles (denoted as NC@Fe), comprised of BNN6-laden COF@Fe3 O4 nanoparticles, are reported. This innovation extends to the modification of 3D printed polyetheretherketone scaffolds with NC@Fe, establishing a pioneering approach to multi-modal bone therapy tailored to address complications such as device-associated infections and osteomyelitis. This work stands out prominently from previous research, particularly those relying on the use of antibiotics, by introducing a bone implant capable of simultaneous NO gas therapy and photothermal therapy (PPT). Under NIR laser irradiation, the Fe3 O4 NP core (photothermal conversion agent) within NC@Fe absorbs photoenergy and initiates electron transfer to the loaded NO donor (BNN6), resulting in controlled NO release. The additional heat generated through photothermal conversion further propels the NC@Fe nanoparticles, amplifying the therapeutic reach. The combined effect of NO release and PPT enhances the efficacy in eradicating bacteria over a more extensive area around the implant, presenting a distinctive solution to conventional challenges. Thorough in vitro and in vivo investigations validate the robust potential of the scaffold in infection control, osteogenesis, and angiogenesis, emphasizing the timeliness of this unique solution in managing complicated bone related infectious diseases.