Repair Ability Research Articles

Microwave assisted black phosphorus-based core-shell composites with synergistic antibacterial and osteogenic ability for bone tissue repair

In clinics, repairing bone tissue with methicillin-resistant Staphylococcus aureus (MRSA) infections and bone defects remains a remarkable challenge. This study designs new core-shell composites of PMP/PVA (Fe3O4@APNs based on magnesium phosphate cement/Fe3O4@APNs-VAN-PLGA microspheres-agarose hydrogel). With Fe3O4@APNs (Phytic acid dodecasodium exfoliated BPNs (APNs) modified with Fe3O4) as an enhanced microwave (MW) sensitizer, the PMP/PVA system exhibits outstanding MW thermal performance. Under MW irradiation, the PMP/PVA exerts dual antibacterial activity through the MW thermal effect (MTE, quickly increased to 68.7 ± 2.4 °C in 5 min at 2.45 GHz, 10 W/cm2) and MW-triggered chemotherapy (CTH, in vitro: 99.98 ± 0.02 % (MRSA), 99.43 ± 0.73 % (E. coli); in vivo: 99.98 ± 0.02 %), which possesses antibacterial ability in vitro and anti-infective effects in vivo with low toxicity and side effects. In addition, PMP/PVA possesses biodegradability with Ca2+, Mg2+, and PO43− released, which not only facilitates the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSC) in vitro but also promotes new bone formation for bone defect sites with chronic osteomyelitis in vivo (the implantations were gradually replaced with a large area of new bone without apparent cortical reactions). Therefore, PMP/PVA with dual antibacterial activity, osteogenic performance, and low toxicity ability can potentially repair bone tissue with MRSA infections and refractory bone defects. The proposed system is promising for bone tissue repair of chronic osteomyelitis with bone defects.

Self-healing hydrogel reduces inflammation through ANT1/OPTN axis mediated mitophagy for spinal cord injury repair

Spinal cord injury is hard to repair due to the aggregated injury to neighbor cells caused by neuro-inflammation, which always results in severe outcomes. In this work, Tc peptide, which served as the antagonist of CXCR4 and the agonist of CXCR7, was loaded in a self-healing hydrogel. The hydrogel containing Tc was found to possess superior spinal cord injury repair abilities, including motor neuron regeneration, axon bridging repair and motor functions recovery, due to the inflammation inhibition. The mechanism analysis by RNA-sequencing and in vitro experiments found that the elevated ANT1 accelerates OPTN recruitment, which subsequently recognized by LC3 to form phagophore around dysfunctional mitochondria, resulting in a regressive NLRP3 expression. However, this regression was abolished after inhibiting OPTN. Beneficial from the mitophagy process, ROS was reduced and type 1 microglia activation was diminished. This positive feedback loop accelerated spinal cord injury repair. In summary, the hydrogel containing Tc could promote spinal cord injury repair through reducing neuro-inflammation via enhanced ANT1/OPTN axis mediated mitophagy, which may provide a new peptide containing hydrogel for repairing spinal cord injury.

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes that reside at the interface between the bone and soft tissues for bone repair attract increasing attention, but currently developed GBR membranes suffer from relatively poor osteogenic and antibacterial effects as well as limited mechanical property and biodegradability. We present here the design and fabrication of a bifunctional Janus GBR membrane based on a shear flow-driven layer by a layer self-assembly approach. The Janus GBR membrane comprises a calcium phosphate-collagen/polyethylene glycol (CaP@COL/PEG) layer and a chitosan/poly(acrylic acid) (CHI/PAA) layer on different sides of a collagen membrane to form a sandwich structure. The membrane exhibits good mechanical stability and tailored biodegradability. It is found that the CaP@COL/PEG layer and CHI/PAA layer contribute to the osteogenic differentiation and antibacterial function, respectively. In comparison with the control group, the Janus GBR membrane displays a 2.52-time and 1.84-time enhancement in respective volume and density of newly generated bone. The greatly improved bone repair ability of the Janus GBR membrane is further confirmed through histological analysis, and it has great potential for practical applications in bone tissue engineering.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of spinal cord injury by alleviating neuroinflammation

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.

NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

3D printed Nanohydroxyapatite/Polyamide 66 scaffolds with balanced mechanical property and osteogenic ability for bone repair

The biomaterial requirements for bone tissue repair are extremely strict. It not only requires the biomaterial to have good biocompatibility and biological activity, but also requires sufficient mechanical strength. Polyamide 66 (PA66) and nano-hydroxyapatite (n-HA) have been widely investigated in bone tissue engineering scaffold, however, its composites require further research. In this study, the 3D printing technology was utilized to fabricate personalized n-HA/PA66 bone tissue scaffold. The mechanical properties of n-HA/PA66 composite can be adjusted by configuring different raw material components and applying different porosity. It was found that 50 % porosity n-HA/PA66 composite scaffold showed a uniform porous structure and a compressive strength of 33.9 MPa. The composite scaffold also exhibited excellent biological properties while improving mechanical properties, in vitro cell tests indicated that the 3D printed n-HA/PA66 composite scaffold promoted differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. In in vivo animal model proved that the scaffold promoted endogenous bone regeneration in rabbit patellar bone defects, with newly formed bone volume of 20.9 % after two months of implantation. This research proposed a 3D printed polyamide/nano-hydroxyapatite composite with balanced mechanical property and osteogenic ability for customized bone tissue repair, and it has promising application prospects.

Analysis of DNA and RNA Genomic Profiles from Phase-II Clinical Trial NCT03398694 Showed Distinct Transcriptomic Profile for Patients With Local Failure

INTRODUCTION: Stereotactic radiosurgery (SRS) has become a standard of care for brain metastasis (BM). In the setting of lesions needing surgical intervention, it is typically delivered to the resection cavity after surgical resection to strike a balance between adverse effect from the dose of radiation and tumor recurrence. Pre-operative SRS is now being examined because of its ability to deliver radiation to all cells before surgical disruption and dispersion with added advantage of treating larger lesions with radiation. METHODS: We designed a phase II trial for patients with up to 4 BM and at least one resectable lesion. All lesions were treated with SRS and symptomatic lesions were resected. We examined both the clinical and biological outcomes. RESULTS: We performed whole genome DNA and RNA sequencing of the center and periphery of the resected lesion from the first 35 patients. We found that SRS causes significant and biologically observable damage to the tumor. Radiation induced DNA damage is qualitatively different between center and periphery of the tumor. Functionally distinct genetic profiles exist between both center and peripheral tumor locations as well as between different primary tumor types. Center of the tumor has higher functional mutation burden while peripheral samples initiate DNA repair pathways. Peripheral samples may interact more with surrounding environment when compared to central samples. Different radiation delivery modality has differential transcriptomic profile and patients who failed locally also had a distinct transcriptomic profile. CONCLUSIONS: In conclusion, radiation dosing fall-off has differential effect on the genomic landscape of the tumor and cells from the periphery are most likely gaining DNA repair abilities and that might explain tumor recurrence. Also, Gamma knife and LINAC as different genomic signature.

Dual-layer conduit containing VEGF-A – Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significanceNerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair.This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.

Cryptomphalus aspersa Egg Extract Protects against Human Stem Cell Stress-Induced Premature Senescence.

Cellular senescence is a tightly regulated pathophysiologic process and is caused by replicative exhaustion or external stressors. Since naturally derived bioactive compounds with anti-ageing properties have recently captured scientific interest, we analysed the anti-ageing and antioxidant efficacy of Cryptomphalus aspersa egg extract (CAEE). Its effects on stemness, wound-healing properties, antioxidant defense mechanisms, and DNA damage repair ability of Human Wharton's jelly mesenchymal stem cells (WJ-MSCs) were analysed. Our results revealed that CAEE fortifies WJ-MSCs stemness, which possibly ameliorates their wound-healing ability. Additionally, we show that CAEE possesses a strong antioxidant capacity as demonstrated by the elevation of the levels of the basic antioxidant molecule, GSH, and the induction of the NRF2, a major antioxidant regulator. In addition, CAEE alleviated cells' oxidative stress and therefore prevented stress-induced premature senescence (SIPS). Furthermore, we demonstrated that the prevention of SIPS could be mediated via the extract's ability to induce autophagy, as indicated by the elevation of the protein levels of all basic autophagic molecules and the increase in formation of autophagolysosomes in CAEE-treated WJ-MSCs. Moreover, CAEE-treated cells exhibited decreased Caveolin-1 levels. We propose that Cryptomphalus aspersa egg extract comprises bioactive compounds that can demonstrate strong antioxidant/anti-ageing effects by regulating the Caveolin-1-autophagy-senescence molecular axis.

X-irradiated umbilical cord blood cells retain their regenerative effect in experimental stroke

Although regenerative therapy with stem cells is believed to be affected by their proliferation and differentiation potential, there is insufficient evidence regarding the molecular and cellular mechanisms underlying this regenerative effect. We recently found that gap junction-mediated cell–cell transfer of small metabolites occurred very rapidly after stem cell treatment in a mouse model of experimental stroke. This study aimed to investigate whether the tissue repair ability of umbilical cord blood cells is affected by X-irradiation at 15 Gy or more, which suppresses their proliferative ability. In this study, X-irradiated mononuclear (XR) cells were prepared from umbilical cord blood. Even though hematopoietic stem/progenitor cell activity was diminished in the XR cells, the regenerative activity was surprisingly conserved and promoted recovery from experimental stroke in mice. Thus, our study provides evidence regarding the possible therapeutic mechanism by which damaged cerebrovascular endothelial cells or perivascular astrocytes may be rescued by low-molecular-weight metabolites supplied by injected XR cells in 10 min as energy sources, resulting in improved blood flow and neurogenesis in the infarction area. Thus, XR cells may exert their tissue repair capabilities by triggering neo-neuro-angiogenesis, rather than via cell-autonomous effects.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Rheumatoid Arthritis Symptoms via Shuttling Proteins.

Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collagen-induced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.

Three-dimensional printed sodium alginate clay nanotube composite scaffold for bone regeneration

Nanoparticles can regulate the rheological behavior of polymers during three-dimensional (3D) printing. To overcome the poor molding performance of pure sodium alginate (SA), the present study introduced clay halloysite nanotubes (HNTs), and a novel SA/HNTs ink with good formability was obtained. Subsequently, a high-performance SA/HNTs composite scaffold for bone defect repair was prepared using 3D printing and high-temperature sintering. The rheological properties, interfacial interactions, and mechanical performance of the SA/HNTs ink demonstrated hydrogen bonds and electrostatic attractions between SA and the HNTs, and the ink exhibited good shape fidelity, printability, and mechanical properties after 3D printing. The SA/HNTs composite hydrogel scaffold can transfer into a rigid ceramic scaffold after high-temperature treatment at 1200 °C. The cell experiments confirmed that the SA/HNTs ceramic scaffold exhibited good biocompatibility and osteogenic activity. In addition, a rat calvarial repair experiment showed that the SA/HNTs scaffolds exhibited good bone repair abilities in vivo. Overall, the SA/HNTs composite scaffolds have excellent formability, biocompatibility, and osteogenic activity and have broad application prospects in the field of bone defect repair.

Aging-Induced Reduction in Safflower Seed Germination via Impaired Energy Metabolism and Genetic Integrity Is Partially Restored by Sucrose and DA-6 Treatment.

Seed storage underpins global agriculture and the seed trade and revealing the mechanisms of seed aging is essential for enhancing seed longevity management. Safflower is a multipurpose oil crop, rich in unsaturated fatty acids that are at high risk of peroxidation as a contributory factor to seed aging. However, the molecular mechanisms responsible for safflower seed viability loss are not yet elucidated. We used controlled deterioration (CDT) conditions of 60% relative humidity and 50 °C to reduce germination in freshly harvested safflower seeds and analyzed aged seeds using biochemical and molecular techniques. While seed malondialdehyde (MDA) and fatty acid content increased significantly during CDT, catalase activity and soluble sugar content decreased. KEGG analysis of gene function and qPCR validation indicated that aging severely impaired several key functional and biosynthetic pathways including glycolysis, fatty acid metabolism, antioxidant activity, and DNA replication and repair. Furthermore, exogenous sucrose and diethyl aminoethyl hexanoate (DA-6) treatment partially promoted germination in aged seeds, further demonstrating the vital role of impaired sugar and fatty acid metabolism during the aging and recovery processes. We concluded that energy metabolism and genetic integrity are impaired during aging, which contributes to the loss of seed vigor. Such energy metabolic pathways as glycolysis, fatty acid degradation, and the tricarboxylic acid cycle (TCA) are impaired, especially fatty acids produced by the hydrolysis of triacylglycerols during aging, as they are not efficiently converted to sucrose via the glyoxylate cycle to provide energy supply for safflower seed germination and seedling growth. At the same time, the reduced capacity for nucleotide synthesis capacity and the deterioration of DNA repair ability further aggravate the damage to DNA, reducing seed vitality.

The Evolution of Hand Injuries at a State's Only Level I Trauma Center: A Look From the 1980s Through the Global Pandemic.

The purpose of this study is to evaluate any changes to hand trauma in the past three decades and through the COVID-19 pandemic. We hypothesized that improved consumer safety regulations, changes in access to care, and the impact of a global pandemic, among other variables, have significantly influenced the mechanisms and treatment of hand injuries between the 1980s, 2010s (pre-COVID-19), and 2020s (post-COVID-19). A retrospective single-center review was performed at the only level I trauma center in Mississippi, identifying all hand trauma consultations between 2012-2019 and 2020-2021, compared to aggregated data from 1989. Car accidents, gunshots, saw injuries, door injuries, and falls increased in 2012-2019 and 2020-2021 compared to 1989, whereas knife injuries, glass injuries, industrial injuries, and burns decreased. Crush injuries, de-gloving injuries, and lacerations with irregular edges were increased in recent cohorts, corresponding with increased amputations and tissue loss. Skin and subcutaneous injuries decreased in modern cohorts, corresponding with a decreased ability for primary skin repair and the need for more flaps. Additionally, while hospitalizations have increased, patients have improved follow-up. The nature of hand trauma has changed significantly over the past three decades. Increased numbers of cars and greater access to firearms might have led to increased rates of high-energy trauma, whereas burn and industrial injuries have decreased, potentially secondary to improved safety efforts. Despite increased overall hand trauma, time to treatment and follow-up have improved. Through this study, we can be more cognizant of the evolution of hand trauma in the modern era. This can allow improved access to care and further refine management to optimize functionality for hand injuries.

ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.

In this study, we investigated the roles of ROCK1 in regulating structural and functional features of caveolae located at the cell membrane of cardiomyocytes, adipocytes, and mouse embryonic fibroblasts (MEFs) as well as related physiopathological effects. Caveolae are small bulb-shaped cell membrane invaginations, and their roles have been associated with disease conditions. One of the unique features of caveolae is that they are physically linked to the actin cytoskeleton that is well known to be regulated by RhoA/ROCKs pathway. In cardiomyocytes, we observed that ROCK1 deficiency is coincident with an increased caveolar density, clusters, and caveolar proteins including caveolin-1 and -3. In the mouse cardiomyopathy model with transgenic overexpressing Gαq in myocardium, we demonstrated the reduced caveolar density at cell membrane and reduced caveolar protein contents. Interestingly, coexisting ROCK1 deficiency in cardiomyocytes can rescue these defects and preserve caveolar compartmentalization of β-adrenergic signaling molecules including β1-adrenergic receptor and type V/VI adenylyl cyclase. In cardiomyocytes and adipocytes, we detected that ROCK1 deficiency increased insulin signaling with increased insulin receptor activation in caveolae. In MEFs, we identified that ROCK1 deficiency increased caveolar and total levels of caveolin-1 and cell membrane repair ability after mechanical or chemical disruptions. Together, these results demonstrate that ROCK1 can regulate caveolae plasticity and multiple functions including compartmentalization of signaling molecules and cell membrane repair following membrane disruption by mechanical force and oxidative damage. These findings provide possible molecular insights into the beneficial effects of ROCK1 deletion/inhibition in cardiomyocytes, adipocytes, and MEFs under certain diseased conditions.

Assessment of self-healing performance of cement-based materials incorporating ion chelator and industrial wastes

Ion chelator can enhance the self-healing of cracks and pores in concrete. To further improve the self-healing capability of cement-based materials, different industrial wastes (i.e. fly ash, limestone powder and blast furnace slag (BFS)) and ion chelator were mixed into mortar. The crack closure index, water permeability, water absorption, impermeability, compressive strength recovery and healing products of mortar were studied. The results showed that the mortar mixed with BFS and ion chelator possessed the best repair ability on cracks, the crack with a maximum width of 0.55 mm can be closed within 14 d. Meanwhile, the water permeability and water absorption of mortar incorporating ion chelator and BFS were obviously smaller than that of control mortar. After curing for 56 d, the chloride diffusion coefficient of mortar containing ion chelator and BFS was reduced by 73.7% compared with control mortar. The compressive strength recovery ratio of mortar containing ion chelator and BFS was 63.7% greater than that of control mortar after pre-loading 80% of the failure strength. In addition, scanning electron microscopy and energy dispersive spectroscopy displayed a large number of calcites at the edge of crack section in mortar containing ion chelator and BFS, the inside of crack was mainly repaired by the combined effect of calcium carbonate precipitation and hydration product.

TIMP3/Wnt axis regulates gliosis of Müller glia

BackgroundPrevious studies have confirmed the expression of tissue inhibitor of metalloproteinase-3 (TIMP3) in Müller glia (MG). However, the role of TIMP3 in MG remains unknown. MethodsA mouse model of laser-induced retinal damage and gliosis was generated using wild-type C57BL/6 mice. TIMP3 and associated proteins were detected using Western blotting and immunofluorescence microscopy. RNA sequencing (GSE132140) of mouse laser-induced gliosis was utilized for pathway analysis. TIMP3 overexpression was induced in human MG. Human vitreous samples were obtained from patients with proliferative diabetic retinopathy (PDR) and healthy controls for protein analysis. ResultsTIMP3 levels increased in mouse eyes after laser damage. Morphology and spatial location of TIMP3 indicated its presence in MG. TIMP3-overexpressing MG showed increased cellular proliferation, migration, and cell nuclei size, suggesting TIMP3-induced gliosis for retinal repair. Glial fibrillary acidic protein (GFAP) and vimentin levels were elevated in TIMP3-overexpressing MG and laser-damaged mouse retinas. RNA sequencing and Western blotting suggested a role for β-catenin in mediating TIMP3 effects on the retina. Human vitreous samples from patients with PDR showed a positive correlation between TIMP3 and GFAP levels, both of which were elevated in patients with PDR. ConclusionsTIMP3 is associated with MG gliosis to enhance the repair ability of damaged retinas and is mediated by the canonical Wnt/β-catenin. Changes in TIMP3 could potentially be used to control gliosis in a range of retinal diseases However, given the multifaceted nature of TIMP3, care must be taken when developing treatments that aim solely to boost the function of TIMP3. FundingNational Cheng Kung University Hospital, Taiwan (NCKUH-10604009 and NCKUH-11202007); the Ministry of Science and Technology (MOST 110-2314-B-006-086-MY3).

Exploration and practice of novel models of cellular therapy and hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation provides an effective cure for various hematological diseases, especially malignant hematological diseases, its treatment system has been continuously optimized, the source of donors has been expanding, the indications have been expanding, and the therapeutic effect has also made breakthroughs to a certain extent. At present, the status of hematopoietic stem cell transplantation technology in most hematological diseases is still unshakable, but the recurrence of the primary disease and complications related to hematopoietic stem cell transplantation are still two major clinical challenges that affect the long-term survival and quality of life of patients. Cell therapy represented by chimeric antigen receptor T (CAR-T) has made breakthrough progress in the treatment of refractory/recurrent B-cell malignancies. Compared with traditional drugs, cell therapy has unique in vivo metabolic characteristics, relying on immune specific recognition and the repair ability of stem cells. It is currently emerging in the treatment of blood tumors and the management of transplant complications. Multiple clinical studies have preliminarily demonstrated a new diagnostic and therapeutic model combining cell therapy with hematopoietic stem cell transplantation.

The novel disulfide-containing diols synthesis and applied in self-healing fluorescent polyurethane elastomers

Polyurethane elastomers with repair abilities and robust mechanical properties remain a great challenge under mild conditions. Numerous studies have shown that dynamic disulfide bonds are the important chemical chain unit...