Repair Strategies Research Articles

Enhancement of mechanical characteristics and novel damage assessment for timber post and beam structures with K-braces

Glued-laminated Timber Post and Beam Structural System (GTPBSS) gains widely application in timber engineering because of direct force transmission and simple construction. The present work investigates the influence of introducing K-bracing on the lateral performance of the GTPBSS. To this end, four full-scale GTPBSS specimens with and without braces under horizontal loading conditions were carried out. The obtained test results highlight that the GTPBSS without braces exhibited large deformation. The failure modes predominantly centered on the occurrence of wood cracking at both the column-base joint and beam-column joint. In contrast, the GTPBSS specimens equipped with K-bracing elements exhibited failure modes marked by the instability of the brace components. The inclusion of brace system within the GTPBSS structures yielded positive results, effectively reducing lateral deformations while concurrently augmenting both the elastic stiffness and the later maximum load-carrying capacity. However, it is essential to exercise caution with regard to potential out-of-plane instability. A dual-parameter damage assessment model was developed to evaluate structural damage, incorporating factors related to energy dissipation and deformation. The evaluation results derived from this model were consistent with the test results, affirming the rationality and validity of the proposed approach. This model is expected to provide a scientific foundation for formulating strategies for repair and maintenance.

Plant-Derived Chinese Herbal Hydrogel Microneedle Patches for Wound Healing.

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine.

Comparative Analysis and Regeneration Strategies for Three Types of Cartilage.

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body because of its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type. We explore the similarities and differences in the composition, structure, and biomechanical properties of the three cartilage types and their implications for tissue engineering. A significant emphasis is placed on innovative strategies for cartilage regeneration, including the potential for in situ transformation of cartilage types through microenvironmental manipulation, which may offer novel avenues for repair and rehabilitation. The review underscores the necessity of a nuanced approach to cartilage tissue engineering, recognizing the distinct requirements of each cartilage type while exploring the potential of transforming one cartilage type into another as a flexible and adaptive repair strategy. Through this detailed examination, we aim to broaden the understanding of cartilage tissue engineering and inspire further research and development in this promising field.

Epigenetic Dynamics in Meniscus Cell Migration and its Zonal Dependency in Response to Inflammatory Conditions: Implications for Regeneration Strategies.

Meniscus injuries pose significant challenges in clinical settings, primarily due to the intrinsic heterogeneity of the tissue and the limited efficacy of current treatments. Endogenous cell migration is crucial for the healing process, yet the regulatory mechanisms of meniscus cell migration and its zonal dependency within the meniscus are not fully understood. Thus, this study investigates the role of epigenetic mechanisms in governing meniscus cell migration under inflammatory conditions, with a focus on their implications for injury healing and regeneration. Here, we discovered that a proinflammatory cytokine, TNF-α treatment significantly impedes the migration speed of inner meniscus cells, while outer meniscus cells are unaffected, underscoring a zonal-dependent response within the meniscus. Our analysis identified distinct histone modification patterns and chromatin dynamics between inner and outer meniscus cells during migration, highlighting the necessity to consider these zonal-dependent properties in devising repair strategies. Specifically, we found that TNF-α differentially influences histone modifications, particularly H3K27me3, between the two cell types. Transcriptome analysis further revealed that TNF-α treatment induces substantial gene expression changes, with inner meniscus cells exhibiting more pronounced alterations than outer cells. Gene cluster analysis pointed to distinct responses in chromatin remodeling, extracellular matrix assembly, and wound healing processes between the zonal cell populations. Moreover, we identified potential therapeutic targets by employing existing epigenetic drugs, GSKJ4 (a histone demethylase inhibitor) and C646 (a histone acetyltransferase inhibitor), to successfully restore the migration speed of inner meniscus cells under inflammatory conditions. This highlights their potential utility in treating meniscus tear injuries. Overall, our findings elucidate the intricate interplay between epigenetic mechanisms and meniscus cell migration, along with its meniscus zonal dependency. This study provides insights into potential targets for enhancing meniscus repair and regeneration, which may lead to improved clinical outcomes for patients with meniscus injuries and osteoarthritis.

The Impact of Affective Repair Strategies on Brand Trust: The Mediating Role of Positive Emotions

As online brand transactions surge, trust crises are increasingly common, posing significant challenges to brand-consumer relationships. This study investigates the impact of affective repair strategies on brand trust mediated by positive emotions. Specifically, the research focuses on four common affective repair strategies: apology, denial, promise, and their combinations. Through empirical analysis, it was found that apology and promise combinations exhibit the strongest positive effect on brand trust, surpassing the impact of singular strategies. Conversely, reliance on denial alone weakens consumer trust in the brand over time. In addition, positive emotions emerge as a critical mediator in trust restoration, particularly evident in denial combined with promise strategies. Based on these findings, managerial recommendations advocate for prioritizing apology and promise combinations, caution against the exclusive use of denial, and highlight the importance of fostering positive emotions to rebuild brand trust. This study provides actionable insights for brands seeking to effectively navigate trust crises and restore consumer confidence in the digital marketplace.

Nanoparticle-Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia-Reperfusion Injury.

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

Children’s conversational voice search as learning: a literature review

Purpose This paper aims to critically review the intersection of searching and learning among children in the context of voice-based conversational agents (VCAs). This study presents the opportunities and challenges around reconfiguring current VCAs for children to facilitate human learning, generate diverse data to empower VCAs, and assess children’s learning from voice search interactions. Design/methodology/approach The scope of this paper includes children’s use of VCAs for learning purposes with an emphasis on conceptualizing their VCA use from search as learning perspectives. This study selects representative works from three areas of literature: children’s perceptions of digital devices, children’s learning and searching, and children’s search as learning. This study also includes conceptual papers and empirical studies focusing on children from 3 to 11 because this age spectrum covers a vital transitional phase in children’s ability to understand and use VCAs. Findings This study proposes the concept of child-centered voice search systems and provides design recommendations for imbuing contextual information, providing communication breakdown repair strategies, scaffolding information interactions, integrating emotional intelligence, and providing explicit feedback. This study presents future research directions for longitudinal and observational studies with more culturally diverse child participants. Originality/value This paper makes important contributions to the field of information and learning sciences and children’s searching as learning by proposing a new perspective where current VCAs are reconfigured as conversational voice search systems to enhance children’s learning.

Surgical treatment of a teenager with an extensive wound defect of soft tissues against the background of severe combined injury

Extensive posttraumatic wounds, affecting functionally active areas and complicated by a purulent–necrotic process, are a serious problem in the acute period of injury due to a critical condition and in reconstructive surgical treatment. This study presents the case of a 16-year-old victim of a transport accident on a ferry who underwent a surgical treatment. Due to a truck collision, the girl was crushed against the metal structure of the ship and received a severe combined injury: closed craniocerebral injury, moderate brain contusion, linear fracture of the occipital bone on the right, closed chest injury, fracture of 9–11 ribs on the right, closed abdominal injury, rupture of the right kidney, damage to the bladder, retroperitoneal hematoma on the right, closed spinal injury, fracture of the spinous processes of the L4–L5 vertebrae, open fractures of the pelvic bones, and extensive posttraumatic wounds of the right half of the pelvic girdle and hip joints. During the initial hospitalization, the following were performed within 2 days: laparotomy, nephrectomy of a crushed kidney on the right, suturing of the bladder, primary surgical treatment of the wound in the sacrogluteofemoral region on the right and the wound of the left thigh with their primary suturing, and external osteosynthesis of the pelvic bones with a rod-based external fixation device. The early postoperative period was complicated by necrosis of injured soft tissues and a new surgical infection (polyantibiotic-resistant strains of microorganisms), which led to an increase in the size of the wound defect and loss of soft tissues due to their purulent melting. Complex surgical treatment aimed at eliminating surgical infection and transferring the wound process to the regeneration phase included repeated surgical treatments and the use of modern dressings and negative pressure therapy. An extensive wound defect of soft tissues caused by and injury or surgical treatment for purulent–necrotic complication was found in the functionally active zone of the hip joint and in the sacral region, which required the restoration of the skin of these areas. A strategy for surgical repair of a soft tissue wound defect is presented. Nonfree (rotated) blood-supply flaps were used: fasciocutaneous muscle flap based on the musculus tensor fascia lata from the right thigh and gluteal fasciocutaneous flap from the left gluteal region. After multistage surgical treatment, it was possible to replace an extensive wound defect of soft tissues and restore full skin in the hip joint and sacrogluteal region, which enabled avoiding trophic disorders and joint contractures and ensured a satisfactory cosmetic and functional result during 5-year followup.

Rational correction of pathogenic conformational defects in HTRA1

Loss-of-function mutations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy. Here, we establish independent approaches to achieve the functional correction of trimer assembly defects. Focusing on the prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer formation thus restoring enzymatic activity in vitro. Genetic experiments in Htra1R274Q mice further demonstrate that expression of this protein-based corrector in trans is sufficient to stabilize HtrA1-R274Q and restore the proteomic signature of the brain vasculature. An alternative approach employs supramolecular chemical ligands that shift the monomer-trimer equilibrium towards proteolytically active trimers. Moreover, we identify a peptidic ligand that activates HTRA1 monomers. Our findings open perspectives for tailored protein repair strategies.

Cartilage-derived cells display heterogeneous pericellular matrix synthesis in agarose microgels

The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-β1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-β1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.

Fabrication of ECM protein coated hollow collagen channels to study peripheral nerve regeneration

Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin’s superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches.

Integrating Bioactive Graded Hydrogel with Radially Aligned Nanofibers to Dynamically Manipulate Wound Healing Process.

Skin wound healing is a complex process that requires appropriate treatment and management. Using a single scaffold to dynamically manipulate angiogenesis, cell migration and proliferation, and tissue reconstruction during skin wound healing is a great challenge. We developed a hybrid scaffold platform that integrates the spatiotemporal delivery of bioactive cues with topographical cues to dynamically manipulate the wound-healing process. The scaffold comprised gelatin methacryloyl hydrogels and electrospun poly(ε-caprolactone)/gelatin nanofibers. The hydrogels had graded cross-linking densities and were loaded with two different functional bioactive peptides. The nanofibers comprised a radially aligned nanofiber array layer and a layer of random fibers. During the early stages of wound healing, the KLTWQELYQLKYKGI peptide, which mimics vascular endothelial growth factor, was released from the inner layer of the hydrogel to accelerate angiogenesis. During the later stages of wound healing, the IKVAVS peptide, which promotes cell migration, synergized with the radially aligned nanofiber membrane to promote cell migration, while the nanofiber membrane also supported further cell proliferation. In an in vivo rat skin wound-healing model, the hybrid scaffold significantly accelerated wound healing and collagen deposition, and the ratio of type I to type III collagen at the wound site resembled that of normal skin. The prepared scaffold dynamically regulated the skin tissue regeneration process in stages to achieve rapid wound repair with clinical application potential, providing a strategy for skin wound repair.

Paeoniae Decoction restores intestinal barrier dysfunction by promoting the interaction between ILC3 and gut flora

BackgroundIntestinal barrier dysfunction is a significant contributor to the recurrence and refractory of ulcerative colitis (UC). Promoting the interaction between group 3 innate lymphoid cells (ILC3s) and gut flora is a valuable strategy for mucosal repair. Paeoniae decoction (PD) is a compound commonly used in clinical treatment of UC, but its exact mechanism remains unclear. PurposeWe aimed to investigate the protective effect of PD on intestinal mucosal injury induced by dextran sulfate sodium (DSS) in chronic colitis, as well as to elucidate its potential mechanism. MethodsC57BL/6 mice were induced with chronic colitis by 2 % DSS and divided into four groups: control group, model group, PD low dose (4 g/kg), and high dose (8 g/kg) group. The effectiveness of PD in treating chronic colitis mice was evaluated based on changes in body weight, colon length, colon pathological tissue scores, and the mRNA levels of inflammatory factors IL-6 and IL-1β. The expressions of intestinal epithelial tight junction proteins (ZO-1 and Occludin), IL-22, and MUC2 were observed using immunofluorescence and RT-PCR. Additionally, the proportion of ILC3 and natural cytotoxicity receptor (NCR)+ ILC3 in the colon were detected using flow cytometry. Furthermore, UHPLC-QE-MS was utilized to identify chemical components of PD and network pharmacology was employed to predict potential pathways for PD intervention in UC. Subsequently, MNK-3 cells (ILC3 in vitro cell line) and NCM460 cells were used to verify the network pharmacology results. Finally, the effects of PD on UC gut flora have been explored using in vitro fermentation and 16S rDNA techniques. ResultsThe results showed that PD significantly restored body weight and colon length in mice with chronic colitis, while also reducing colon inflammatory cell infiltration and the expression of IL-6 and IL-1β. Additionally, PD notably promoted the expression of MUC2, ZO-1, Occludin, and IL-22, as well as increasing the ratio of ILC3 and NCR+ILC3. UHPLC-QE-MS analysis identified 443 components of PD, and network pharmacology suggested that PD could target the aryl hydrocarbon receptor (AHR) signaling pathway, which was confirmed by MNK-3 cells and in vitro fermentation experiments. Furthermore, MNK-3-conditioned medium (CM) increased the expression of ZO-1 and Occludin in NCM460 cells. In addition, 16S rDNA results indicated that PD promoted the abundance of Lactobacillales, thus contributing to mucosal damage repair by activating the AHR signal in ILC3s. ConclusionIn summary, our study demonstrates that PD repairs intestinal mucosal damage in chronic colitis by regulating the interaction of gut flora with ILC3, and the specific mechanism is related to the activation of AHR signaling pathway.

Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models.

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency. A multimodal platform to quantitatively evaluate the effect of shape, size, and material on clinical outcomes could optimize monocusp design. This study introduces a benchtop soft biorobotic heart model, a computational fluid model of the RVOT, and a monocusp valve made from an entirely biological cell-assembled extracellular matrix (CAM) to tackle the multifaceted issue of monocusp failure. The hydrodynamic and mechanical performance of RVOT repair strategies was assessed in biorobotic and computational platforms. The monocusp valve design was validated in vivo in ovine models through echocardiography, cardiac magnetic resonance, and catheterization. These models supported assessment of surgical feasibility, handling, suturability, and hemodynamic and mechanical monocusp capabilities. The CAM-based monocusp offered a competent pulmonary valve with regurgitation of 4.6 ± 0.9% and a transvalvular pressure gradient of 4.3 ± 1.4 millimeters of mercury after 7 days of implantation in sheep. The biorobotic heart model, in silico analysis, and in vivo RVOT modeling allowed iteration in monocusp design not now feasible in a clinical environment and will support future surgical testing of biomaterials for complex congenital heart malformations.

DNA Tetrahedron Delivering miR-21-5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis.

Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone-related miRNA, miRNA-21-5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR-21-5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN-miR-21-5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O-BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O-EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN-miR-21-5p mediated osteogenesis and senescence of O-BMSCs. Also, TDN-miR-21-5p can indirectly mediate osteogenesis and senescence of O-BMSCs through pro-angiogenic growth factors secreted from O-EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN-miR-21-5p to fabricate delivery scaffolds. TDN-miR-21-5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic- and angiogenic-related markers in senescent critical-size cranial defects in vivo. Collectively, TDN-miR-21-5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs-based gene therapy.

The Characteristics of Long-Wave Irregularities in High-Speed Railway Vertical Curves and Method for Mitigation.

Track geometry measurements (TGMs) are a critical methodology for assessing the quality of track regularities and, thus, are essential for ensuring the safety and comfort of high-speed railway (HSR) operations. TGMs also serve as foundational datasets for engineering departments to devise daily maintenance and repair strategies. During routine maintenance, S-shaped long-wave irregularities (SLIs) were found to be present in the vertical direction from track geometry cars (TGCs) at the beginning and end of a vertical curve (VC). In this paper, we conduct a comprehensive analysis and comparison of the characteristics of these SLIs and design a long-wave filter for simulating inertial measurement systems (IMSs). This simulation experiment conclusively demonstrates that SLIs are not attributed to track geometric deformation from the design reference. Instead, imperfections in the longitudinal profile's design are what cause abrupt changes in the vehicle's acceleration, resulting in the measurement output of SLIs. Expanding upon this foundation, an additional investigation concerning the quantitative relationship between SLIs and longitudinal profiles is pursued. Finally, a method that involves the addition of a third-degree parabolic transition curve (TDPTC) or a full-wave sinusoidal transition curve (FSTC) is proposed for a smooth transition between the slope and the circular curve, designed to eliminate the abrupt changes in vertical acceleration and to mitigate SLIs. The correctness and effectiveness of this method are validated through filtering simulation experiments. These experiments indicate that the proposed method not only eliminates abrupt changes in vertical acceleration, but also significantly mitigates SLIs.

Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

Influence of wind-blown sand content on the mechanical quality state of ballast bed in sandy railways

During the operation of sandy railways, the challenge posed by wind-blown sand is a persistent issue. An in-depth study on the influence of wind-blown sand content on the macroscopic and microscopic mechanical properties of the ballast bed is of great significance for understanding the potential problems of sandy railways and proposing reasonable and adequate maintenance and repair strategies. Building upon existing research, this study proposes a new assessment indicator for sand content. Utilizing the discrete element method (DEM) and fully considering the complex interactions between ballast and sand particles, three-dimensional (3D) multi-scale analysis models of sandy ballast beds with different wind-blown sand contents are established and validated through field experiments. The effects of varying wind-blown sand content on the microscopic contact distribution and macroscopic mechanical behavior (such as resistance and support stiffness) of ballast beds are carefully analyzed. The results show that with the increase in sand content, the average contact force and coordination number between ballast particles gradually decrease, and the disparity in contact forces between different layers of the ballast bed diminishes. The longitudinal and lateral resistance of the ballast bed initially decreases and then increases, with a critical point at 10% sand content. At 15% sand content, the lateral resistance is mainly shared by the ballast shoulder. The longitudinal resistance sharing ratio is always the largest on the sleeper side, followed by that at the sleeper bottom, and the smallest on the ballast shoulder. When the sand content exceeds 10%, the contribution of sand particles to stiffness significantly increases, leading to an accelerated growth rate of the overall support stiffness of the ballast bed, which is highly detrimental to the long-term service performance of the ballast bed. In conclusion, it is recommended that maintenance and repair operations should be promptly conducted when the sand content of the ballast bed reaches or exceeds 10%.

An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment

Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.

Performance of the open-first repair strategy in type A aortic dissection with mesenteric malperfusion syndrome eligible for delayed repair

ObjectiveFor patients with type A aortic dissection complicated by mesenteric malperfusion syndrome, some centers advocate a nontraditional approach based on up-front endovascular intervention and delayed open repair. However, the efficacy of this strategy cannot be understood without first understanding outcomes of the traditional open-first strategy in the same select patient population eligible for delayed repair, applying modern techniques of hybrid aortic surgery. MethodsPatients with acute type A aortic dissection and mesenteric malperfusion syndrome were queried from a single institution. Those presenting with aortic rupture, tamponade, or cardiogenic shock (ineligible for delayed repair) were excluded. Patients were managed with immediate open aortic repair. Short-term and long-term outcomes are reported. ResultsA total of 1228 patients were treated for acute type A dissection in the study period, of whom 77 were included in the mesenteric malperfusion syndrome cohort. In-hospital mortality was 29% compared with 39% in an identically selected mesenteric malperfusion syndrome population undergoing delayed repair reported previously. Among patients with mesenteric malperfusion syndrome, 32% underwent additional procedures addressing distal malperfusion in a hybrid operating room during or after open repair. Concomitant proximal malperfusion (coronary, cerebral, or upper extremity) was common in the mesenteric malperfusion syndrome cohort, present in 35% of cases. Although early mortality was greater in the mesenteric malperfusion syndrome cohort compared with all acute type A dissections, 10-year survival among those discharged alive was similar (65% vs 59%, P = .18). ConclusionsThe traditional open-first repair strategy performs equal to or better than the delayed repair strategy for patients with mesenteric malperfusion syndrome eligible for delayed repair.