Metabolic reprogramming: a new option for the treatment of spinal cord injury.

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

Confined Crystallization Polyether-Based Flexible Phase Change Film for Thermal Management.

Phase change materials (PCMs) possess the potential to regulate temperature by utilizing their thermal properties to absorb and release heat. Nevertheless, the application of PCMs in thermal management is constrained by issues such as liquid leakage and limited flexibility. In this study, we propose a novel approach to address these challenges by incorporating a pore structure within nanofibers to confine the crystallization of phase change molecules, thereby enhancing the flexibility of the composite material. Additionally, inspired by the adaptive mechanisms observed in plants, we have developed a form stable PCM based on polyether, which effectively mitigates the issue of liquid leakage at higher temperatures. Despite being a solid-liquid PCM at its core, this material exhibits molecular-scale flow and macroscopic shape stability as a result of intermolecular forces. The composite film material possesses remarkable flexibility, efficient thermal management capabilities, adjustable phase transition temperature, and the ability to undergo repeated processing and utilization. Consequently, it holds promising potential for applications in personal thermal energy management.

Current multi-scale biomaterials for tissue regeneration following spinal cord injury.

Spinal cord injury (SCI) may cause loss of motor and sensory function, autonomic dysfunction, and thus disrupt the quality of life of patients, leading to severe disability and significant psychological, social, and economic burden. At present, existing therapy for SCI have limited ability to promote neural function recovery, and there is an urgent need to develop innovative regenerative approaches to repair SCI. Biomaterials have become a promising strategy to promote the regeneration and repair of damaged nerve tissue after SCI. Biomaterials can provide support for nerve tissue by filling cavities, and improve local inflammatory responses and reshape extracellular matrix structures through unique biochemical properties to create the optimal microenvironment at the SCI site, thereby promoting neurogenesis and reconnecting damaged spinal cord tissue. Considering the importance of biomaterials in repairing SCI, this article reviews the latest progress of multi-scale biomaterials in SCI treatment and tissue regeneration, and evaluates the relevant technologies for manufacturing biomaterials.

Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT [OFT]) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

2D Information Security System Based on Polyurethane Inverse Photonic Glass Structure.

Information security has become a major global problem in recent years. Thus, people continue to exert much effort in developing new information security technologies based on encryption and storage. In this study, a 2D information security technology based on polyurethane optical devices with inverse photonic glass structure (PU-IPG) is introduced. Based on 1) the swelling and plasticizing effects of various solvents on PU-IPG and 2) the capillary force that can produce geometric deformation on micro/nanostructures when solvents evaporate, a 2D information security system with two modules of decryption (structural color information display) and anticounterfeiting (structural color transformation) is successfully constructed. The spraying method adopted can be simple and fast and can provide a large area to build photonic glass templates, which greatly improves the capacity and category of information in the encryption system. The prepared PU-IPG optical devices can produce large-area multicolor output capability of information. These devices also have excellent mechanical properties, strong cycle stability, environmental friendliness, and low price. Therefore, the preparation strategy has great reference value and application prospects in the field of information security.

A novel rat model of annulus fibrosus injury for intervertebral disc degeneration.

BACKGROUND CONTEXT: In clinical practice, acute trauma and chronic degeneration of the annulus fibrosus (AF) can promote further degeneration of the intervertebral disc (IVD). Therefore, it is critical to understand the AF repair process and its consequences on IVD. However, the lack of cost-effective and reproducible in vivo animal models of AF injury has limited research development in this field. PURPOSES: The purpose of this study was to establish and evaluate the utility of a novel animal model for full-thickness AF injury. Three foci were proposed: (1) whether this new modeling method can cause full-layer AF damage; (2) the repair processes and pathological changes in the damaged area after AF injury, and (3) the morphological and histological changes in the IVD are after AF injury. STUDY DESIGN/SETTING: In vivo rat AF injury model with characterization of AF damage repair, IVD degeneration. METHODS: A total of 72,300 g male rats were randomly assigned to one of the two groups: experimental or sham. Annulus fibrosus was separated layer by layer under the microscope with a #11 blade up to the AF- nucleus pulpous (NP) junction. The repair process of the horizontal AF and morphological changes in the sagittal IVD were evaluated with HE staining. Sirius red staining under polarized light. Immunofluorescence was conducted to analyze changes in the expression of COL1 and COL3 in the AF injury area and 8-OHdg, IL-6, MMP13, FSP1, and ACAN in the IVD. The disc height and structural changes after AF injury were measured using X-ray and contrast-enhanced micro-CT. Additionally, the resistance of the AF to stretching was analyzed using three-point bending. RESULTS: Annulus fibrosus-nucleus pulpous border was identified to stably induce the full-thickness AF injury without causing immediate NP injury. The AF repair process after injury was slow and expressed inflammation factors continuously, with abundant amounts of type III collagen appearing in the inner part of the AF. The scar at the AF lesion had decreased resistance to small molecule penetration and weakened tensile strength. Full-thickness AF injury induced disc degeneration with loss of disc height, progressive unilateral vertebral collapse, and ossification of the subchondral bone. Inflammatory-induced degeneration and extracellular matrix catabolism gradually appeared in the NP and cartilage endplate (CEP). CONCLUSIONS: We established a low-cost and reproducible small animal model of AF injury which accurately replicated the pathological state of the limited AF self-repair ability and demonstrated that injury to the AF alone could cause further degeneration of the IVD. CLINICAL RELEVANCE: This in vivo rat model can be used to study the repair process of the AF defect and pathological changes in the gradual degeneration of IVD after AF damage. In addition, the model provides an experimental platform for in vivo experimental research of potential clinical therapeutics.

Thermosensitive hydrogel-based GPR124 delivery strategy for rebuilding blood-spinal cord barrier.

Spinal cord injury (SCI) causes blood-spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient. Accordingly, we provide a thermosensitive hydrogel-based G protein-coupled receptor 124 (GPR124) delivery strategy for rebuilding BSCB. Herein, we firstly found that the expression of GPR124 decreased post-SCI and demonstrated that treatment with recombinant GPR124 could partially alleviate the disruption of BSCB post-SCI by restoring tight junctions (TJs) and promoting migration and tube formation of endothelial cells. Interestingly, GPR124 could also boost the energy metabolism of endothelial cells. However, the absence of physicochemical stability restricted the wide usage of GPR124. Hence, we fabricated a thermosensitive heparin-poloxamer (HP) hydrogel that demonstrated sustained GPR124 production and maintained the bioactivity of GPR124 (HP@124) for rebuilding the BSCB and eventually enhancing functional motor recovery post-SCI. HP@124 hydrogel can encapsulate GPR124 at the lesion site by injection, providing prolonged release, preserving wounded tissues, and filling injured tissue cavities. Consequently, it induces synergistically efficient integrated regulation by blocking BSCB rupture, decreasing fibrotic scar formation, minimizing inflammatory response, boosting remyelination, and regenerating axons. Mechanistically, giving GPR124 activates energy metabolism via elevating the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), and eventually restores the poor state of endothelial cells. This research demonstrated that early intervention by combining GPR124 with bioactive multifunctional hydrogel may have tremendous promise for restoring locomotor recovery in patients with central nervous system disorders, in addition to a translational approach for the medical therapy of SCI.

Controlled extracellular vesicles release from aminoguanidine nanoparticle-loaded polylysine hydrogel for synergistic treatment of spinal cord injury.

Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a lack of a precise, multitemporal, integrated drug delivery system for medications administered in both phases. In this study, we prepare a hybrid polylysine-based hydrogel (PBHEVs@AGN) comprising short-term release of pH-responsive aminoguanidine nanoparticles (AGN) and sustained release of extracellular vesicles (EVs) for synergistic SCI treatment. When AGN is exposed to the acidic environment at the injury site, it quickly diffuses out of the hydrogel and releases the majority of the aminoguanidine within 24 h, reducing oxidative stress in lesion tissues. Enriched EVs are gradually released from the hydrogel and remain in the tissue for weeks, providing a long-term anti-inflammatory effect and further ensuring axonal regeneration. Fast-releasing aminoguanidine can cooperate with slow-release EVs to treat SCI more effectively by reducing the production of proinflammatory cytokines and blocking the TLR4/Myd88/NF-κB inflammatory pathway, creating a sustained anti-inflammatory microenvironment for SCI recovery. Our in vivo experiments demonstrate that PBHEVs@AGN reduces the occurrence of scar tissue, encourages remyelination, and speeds up axonal regeneration. Herein, this multi-drug delivery system, which combines the acute release of aminoguanidine and the sustained release of EVs is highly effective for synergistically managing the challenging pathological processes after SCI.

Experimental training in molecular pharmacology education based on drug-target interactions.

INTRODUCTION: Drug development has been challenged by the dual drawbacks involving unpredictable disease outcomes and drug resistance, which has placed greater demands on pharmacology education. Molecular pharmacology, as a frontier crossover field of pharmacology, focuses on the research of new drugs and targets. However, due to the lack of a systematic experimental training system, molecular pharmacology has not made a corresponding contribution in promoting the training of innovative talent in pharmacology. We aim to establish an experimental training program suitable for molecular pharmacology to improve students' ability to engage in drug development in future. METHODS: Based on the feasibility of drug-target projects, a comprehensive training program containing molecular docking, target stability experiment, and fluorescent probe detection of protein expression in living cells and mice was conducted among 20 pharmacy graduate students. The experimental training was assessed by the experimental training report and the student recognition questionnaires. RESULTS: All 20 students mastered the experimental principles and operations required for the training program. The experimental reports proved that the students were in good command of the experimental principles, operations and applications. The results of the Likert questionnaire indicated that the training program promoted the understanding of the drug research process and increased motivation to learn. CONCLUSION: The designed experimental training program has a positive effect on the training of pharmacology talents, and can be implemented as a part of molecular pharmacology education.

Advanced Phase Change Materials from Natural Perspectives: Structural Design and Functional Applications.

Phase change materials have garnered extensive interest in heat harvesting and utilization owing to their high energy storage density and isothermal phase transition. Nevertheless, inherent leakage problems and low heat storage efficiencies hinder their widespread utilization. Nature has served as a great source of inspiration for addressing these challenges. Natural strategies are proposed to achieve advanced thermal energy management systems, and breakthroughs are made in recent years. This review focuses on recent advances in the structural design and functions of phase change materials from a natural perspective. By highlighting the structure-function relationship, advanced applications including human motion, medicine, and intelligent thermal management devices are discussed in detail. Finally, the views on the remaining challenges and future prospects are also provided, that is, phase change materials are advancing around the biomimicry design spiral.

Spatial-temporal features-based EEG emotion recognition using graph convolution network and long short-term memory.

Objective. Emotion recognition on the basis of electroencephalography (EEG) signals has received a significant amount of attention in the areas of cognitive science and human-computer interaction (HCI). However, most existing studies either focus on one-dimensional EEG data, ignoring the relationship between channels, or only extract time-frequency features while not involving spatial features.Approach. We develop spatial-temporal features-based EEG emotion recognition using a graph convolution network (GCN) and long short-term memory (LSTM), named ERGL. First, the one-dimensional EEG vector is converted into a two-dimensional mesh matrix, so that the matrix configuration corresponds to the distribution of brain regions at EEG electrode locations, thus to represent the spatial correlation between multiple adjacent channels in a better way. Second, the GCN and LSTM are employed together to extract spatial-temporal features; the GCN is used to extract spatial features, while LSTM units are applied to extract temporal features. Finally, a softmax layer is applied to emotion classification.Main results. Extensive experiments are conducted on the A Dataset for Emotion Analysis using Physiological Signals (DEAP) and the SJTU Emotion EEG Dataset (SEED). The classification results of accuracy, precision, and F-score for valence and arousal dimensions on DEAP achieved 90.67% and 90.33%, 92.38% and 91.72%, and 91.34% and 90.86%, respectively. The accuracy, precision, and F-score of positive, neutral, and negative classifications reached 94.92%, 95.34%, and 94.17%, respectively, on the SEED dataset.Significance. The above results demonstrate that the proposed ERGL method is encouraging in comparison to state-of-the-art recognition research.

Sprayable alginate hydrogel dressings with oxygen production and exosome loading for the treatment of diabetic wounds.

Chronic wound unhealing is a common complication in diabetic patients, which is mainly caused by tissue hypoxia, slow vascular recovery, and a long period of inflammation. Here we present a sprayable alginate hydrogel (SA) dressing consisting of oxygen-productive (CP) microspheres and exosomes (EXO) to promote local oxygen generation, accelerate macrophage towards M2 polarization, and improve cell proliferation in diabetic wounds. Results show that the release of oxygen continues for up to 7 days, reducing the expression of hypoxic factors in fibroblasts. In vivo, the diabetic wounds experiment showed that the CP/EXO/SA dressing apparently accelerated full-thickness wound healing characteristics such as the promotion of wound healing efficiency, rapid re-epithelization, favorable collagen deposition, abundant angiogenesis at the wound beds, and shortened inflammation period. EXO synergistic oxygen (CP/EXO/SA) dressing suggests a promising treatment measure for diabetic wounds.

Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment.

Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drug-releasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/(Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the double-loaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.

Evaluation of 18F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis.

PURPOSE: Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[18F] F-NOTA-labeled FAP inhibitor 04(18F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis. METHODS: Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between 18F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24 h following 18F-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining. RESULTS: 18F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of 18F-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of 18F-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, 18F-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment. CONCLUSIONS: These findings suggest that PET imaging of 18F-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.

Form-Stable Phase Change Material with Wood-Based Materials as Support.

Building shape-stable phase change materials (PCMs) are crucial for their practical applications. Particularly, it is vital to utilize renewable/recyclable biomass media as the support material of form-stable PCMs. In this review article, we summarized the recent developments for building form-stable PCMs consisting of wood as a supporting material, either carbonized wood or wood composites. Moreover, the electrothermal conversion and photothermal conversion of form-stable PCMs based on carbonized wood are also demonstrated. In addition, the current technical problems and future research developments of wood-based PCMs are discussed, especially the leakage problem of PCMs during the phase change transition process. All of this information will be helpful for the in-depth understanding and development of new PCMs suitable for wide application perspectives.

Metabolic Glycoengineering: A Promising Strategy to Remodel Microenvironments for Regenerative Therapy.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called "microenvironments." Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering.

Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMsin vitroand NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCsin vitro. In addition, the results of MRI, x-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NPin vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide-co-acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.

An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.