Piezo1 promotes peripheral nerve fibrotic scar formation through Schwann cell senescence.

After peripheral nerve injury (PNI), the long-term healing process at the injury site involves a progressive accumulation of collagen fibers and the development of localized scar tissue. Excessive formation of scar tissue within nerves hinders the process of nerve repair. In this study, we demonstrate that scar formation following nerve injury induces alterations in the local physical microenvironment, specifically an increase in nerve stiffness. Recent research has indicated heightened expression of Piezo1 in Schwann cells (SCs). Our findings also indicate Piezo1 expression in SCs and its association with suppressed proliferation and migration. Transcriptomic data suggests that activation of Piezo1 results in elevated expression of senescence-associated genes. GO enrichment analysis reveals upregulation of the TGF-ß pathway. Overall, our study highlights the potential for Piezo1-induced signaling to regulate SC senescence and its potential significance in the pathophysiology of fibrotic scar formation surrounding peripheral nerves.

Injectable bioadhesive hydrogel as a local nanomedicine depot for targeted regulation of inflammation and ferroptosis in rheumatoid arthritis.

Medicine intervention is the major clinical treatment used to relieve the symptoms and delay the progression of rheumatoid arthritis (RA), but is limited by its poor targeted delivery and short therapeutic duration. Herein, we developed an injectable and bioadhesive gelatin-based (Gel) hydrogel as a local depot of leonurine (Leon)-loaded and folate-functionalized polydopamine (FA-PDA@Leon) nanoparticles for anti-inflammation and chondroprotection in RA. The nanoparticles could protect Leon and facilitate its entry into the M1 phenotype macrophage for intracellular delivery of Leon, while the hydrogel tightly adhered to the tissues in the joint cavity and prolonged the retention of FA-PDA@Leon nanoparticles, thus achieving higher availability and therapeutic efficiency of Leon. In vitro and in vivo experiments demonstrated that the Gel/FA-PDA@Leon hydrogel could strongly suppress the inflammatory response by down-regulating the JAK2/STAT3 signaling pathway in macrophages and protect the chondrocytes from ferritinophagy/ferroptosis. This contributed to maintaining the structural integrity of articular cartilage and accelerating the joint functional recovery. This work provides an effective and convenient strategy to achieve higher bioavailability and long-lasting therapeutic duration of medicine intervention in arthritis diseases.

Hierarchical Composite with Self-Adaptive Anisotropic Deformation for Thermal Protection System.

Rigid thermal protection materials such as ultra-high-temperature ceramics are desirable for applications in aerospace vehicles, but few materials can currently satisfy the emerging high-temperature sealing requirements for dynamic gaps created by the mismatch of the thermal expansion of different protection layers. Here, we design and fabricate a flexible biomimetic anisotropic deformation composite by multilayer cocuring onto fiber fabrics. It displays superior anisotropic deformation, whose longitudinal expansion ratio is 48 times greater than the transverse expansion ratio at specific temperatures. Furthermore, the ordered carbon structure created by transition-metal-catalyzed graphitization and the C/Si synergistic effect resulting from the combination of biomimetic fiber fabrics and SR enable the in situ formation of a high-temperature-resistant SiC crystalline phase within the char layer, ultimately resulting in exceptional thermal protection properties. By constructing hollow structures in situ, the back temperature of the composite, which is only 4.33 mm thick, is stabilized at 140 °C under the condition of continuous butane flame ablation (1300 °C) for 420 s. Multilayer structure and flexible features can facilitate large-scale preparation and arbitrary cutting and bending, adapted to different thermal protection areas.

Examining the Mechanism of Treatment for Primary Dysmenorrhea with Wenjing Huoxue Decoction Based on Transcriptomics, Metabolomics, and Network Pharmacology.

BACKGROUND: Wenjing Huoxue Decoction (WJHXD) is a traditional treatment for primary dysmenorrhea (PD) that can quickly relieve various symptoms caused by PD. Previous clinical studies have shown that WJHXD has better long-term efficacy than ibuprofen in the treatment of PD and can reverse the disorder of T cell subsets. OBJECTIVE: To investigate the effect of WJHXD on serum-related factors in the treatment of PD, including the identification of key targets, pathways, and active ingredients. METHODS: In order to study the effects of the WJHXD intervention in Parkinson's Disease (PD) rats, we used transcriptomics and metabolomics methods to examine the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). We also utilized network pharmacology to predict the target and effective route of WJHXD in treating PD. Finally, we employed molecular docking (MD) technology to confirm the placement of important targets and metabolites. RESULTS: WJHXD has been found to be effective in prolonging the onset time and decreasing the number of writhing episodes in PD rats after oxytocin injection. It has also been observed to reduce the levels of PGF2, COX-2, AVP, and PGE2 in the serum of PD rats to different degrees. Transcriptomics analysis has revealed that the core targets of WJHXD include KRT1, KRT16, CCL5, F2, NOS2, RAC2, and others, while the core pathways are Calcium signaling and cAMP signaling. The Estrogen signaling pathway was found to be downregulated in PD rats compared to normal uterine tissue, but WJHXD was able to up-regulate the pathway. A combined transcriptomics and metabolomics analysis suggested that WJHXD may be involved in eight metabolism-related pathways, with the most reliable ones being mucin-type O-glycan biosynthesis and glycolysis or gluconeogenesis. MD has shown that Hydroxyisocaproic acid may bind to important targets such as SLC6A4, PTGER3, IGFBP3, and IGF2. CONCLUSION: In WJHXD, the most targeted herbs were Corydalis rhizoma, licorice, and Myrrha. The most targeted active ingredients include quercetin, 3'-Hydroxy-4'-O-methylglabridin, shinpterocarpin, and isorhamnetin. Potential targets include PTGS2, NOS2, AR, SCN5A, and GAS6. Analysis revealed 72 highly reliable relationships between group A and B DEGs and DEMs, with 23 positive correlations and 49 negative correlations among them. A combined analysis of transcriptomics, metabolomics, and network pharmacology was used to identify possible targets, pathways, and active ingredients of WJHXD in PD treatment, and the correlation between DEGs and DEMs was investigated. However, further research is required to confirm the relationship between active ingredients, targets, and metabolites.

The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six-day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single-dose administration but may be significant in horses receiving long-term MMF treatment.

In Situ Ceramization of Nanoscale Interface Enables Aerogel with Thermal Protection at 1950 °C.

Conventional carbon fiber felt-reinforced aerogel composites are often used as lightweight thermal protection systems (TPSs) for aerospace craft. However, due to their poor oxidation resistance, they have gradually failed to handle increasingly harsh thermal environments. In this work, a nanoscale composite coating interface of SiC-ZrC ceramic precursor is first constructed on the fiber surface. Subsequently, using the coated fiber felt as a three-dimensional skeleton and through polymerization-induced phase separation, an aerogel composite with excellent thermal protection in extreme thermal environments is prepared. Owing to the in situ ceramization of this nanoscale interface at ultrahigh temperatures, the back temperature of the 12 mm thick aerogel is only 147 °C after exposure to an oxyacetylene flame at 1950 °C for 70 s. Meanwhile, the central region of the aerogel recedes by only 7%. Not only does this work provide a way to enhance aerogels by constructing a self-ceramizable nanoscale interface it is also expected that the developed aerogel composite can be applied in the ultrahigh-temperature thermal protection of future aerospace craft.

A single-cell atlas depicting the cellular and molecular features in human anterior cruciate ligamental degeneration: A single cell combined spatial transcriptomics study.

Background: To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression. Methods: Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining. Results: We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease. Conclusions: This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies. Funding: This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

A Metal-Organic Framework-Incorporated Hydrogel for Delivery of Immunomodulatory Neobavaisoflavone to Promote Cartilage Regeneration in Osteoarthritis.

The treatment of osteoarthritis (OA)-related cartilage defects is a great clinical challenge due to the complex pathogenesis of OA and poor self-repair ability of cartilage tissue. Combining local and long-term anti-inflammatory therapies to promote cartilage repair is an effective method to treat OA. In this study, a zinc-organic framework-incorporated extracellular matrix (ECM)-mimicking hydrogel platform was constructed for the inflammatory microenvironment-responsive delivery of neobavaisoflavone (NBIF) to promote cartilage regeneration in OA. The NBIF was encapsulated in situ in zeolitic imidazolate frameworks (ZIF-8 MOFs). The NBIF@ZIF-8 MOFs were decorated with polydopamine and incorporated into a methacrylate gelatin/hyaluronic acid hybrid network to form the NBIF@ZIF-8/PHG hydrogel. The hydrogel featured excellent cell/tissue affinity, providing a favorable microenvironment for recruiting cells and cytokines to the defect sites. The hydrogel enabled the on-demand NBIF released in response to a weakly acidic microenvironment at the injured joint site to resolve inflammatory responses during the early stages of OA. Consequently, the cooperativity of the loaded NBIF and hydrogel synergistically modulated the immune response and assisted in cartilage defect repair. In summary, the NBIF@ZIF-8/PHG hydrogel delivery platform represents an effective treatment strategy for OA-related cartilage defects and may attract attentions for applications in other inflammatory diseases.

Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.

BACKGROUND: Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. ANIMALS: Six healthy Standardbred mares. METHODS: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. RESULTS: Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0-12 ) of 12 594 h × ng/mL (8567-19 488 h × ng/mL) and terminal half-life (T1/2 ) of 11.3 hours (7.5-15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. CONCLUSION AND CLINICAL IMPORTANCE: Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.

Fabrication of Highly Thermally Resistant and Self-Healing Polysiloxane Elastomers by Constructing Covalent and Reversible Networks.

The fabrication of self-healing elastomers with high thermal stability for use in extreme thermal conditions such as aerospace remains a major challenge. A strategy for preparing self-healing elastomers with stable covalent bonds and dynamic metal-ligand coordination interactions as crosslinking sites in polydimethylsiloxane (PDMS) is proposed. The added Fe (III) not only serves as the dynamic crosslinking point at room temperature which is crucial for self-healing performance, but also plays a role as free radical scavenging agent at high temperatures. The results show that the PDMS elastomers possessed an initial thermal degradation temperature over 380 °C and a room temperature self-healing efficiency as high as 65.7%. Moreover, the char residue at 800 °C of PDMS elastomer reaches 7.19% in nitrogen atmosphere, and up to 14.02% in air atmosphere by doping a small amount (i.e., 0.3 wt%) of Fe (III), which is remarkable for the self-healing elastomers that contain weak and dynamic bonds with relatively poor thermal stability. This study provides an insight into designing self-healing PDMS-based materials that can be targeted for use as high-temperature thermal protection coatings.

Promotive role of eukaryotic translation initiation factor 4A isoform 3 in ovarian cancer cell growth and aerobic glycolysis through the pyruvate dehydrogenase kinase 4 signaling.

Ovarian cancer (OC) represents one of the most detrimental gynecological malignancies. RNA-binding protein eukaryotic translation initiation factor 4A isoform 3 (EIF4A3) is well-regarded as a definitive oncogene that contributes to the development of multiple malignant tumors. This study sought to elucidate the molecular mechanism of EIF4A3 in OC growth and aerobic glycolysis by regulation of pyruvate dehydrogenase kinase 4 (PDK4) mRNA stability. We determined the EIF4A3 and PDK4 expression levels in OC cell lines and normal ovarian epithelial cells, and subsequently evaluated the cell viability and colony formation by cell counting kit-8 and colony formation assays. The degree of cell aerobic glycolysis was evaluated by measurements of lactic acid production, glucose intake, adenosine triphosphate level, extracellular oxygen consumption, and protein levels of pyruvate kinase isozymes M2 and hexokinase-2. Afterwards, we verified the binding of EIF4A3 and PDK4 mRNA via RNA immunoprecipitation, and determined the mRNA stability after actinomycin D treatment. Finally, a series of rescue experiments was performed with pcDNA3.1-PDK4. EIF4A3 and PDK4 were upregulated in OC cells. Silencing EIF4A3 obstructed cell proliferation and aerobic glycolysis, while the same was annulled by EIF4A3 overexpression. Mechanically, EIF4A3 could bind to PDK4 mRNA to stabilize its mRNA and upregulate its protein levels. PDK4 overexpression inverted the inhibitory role of silencing EIF4A3 in proliferation and aerobic glycolysis. Overall, our findings highlighted that EIF4A3 induced OC progression by stabilizing PDK4 mRNA.

Flexible Thermal Protection Polymeric Materials with Self-Sensing and Self-Adaptation Deformation Abilities.

Based on the strategy of killing two birds with one stone, we introduce thermally expandable microspheres into a silicone rubber matrix to fabricate temperature-responsive controllable deformation materials, which exhibit intelligent deformation properties as well as enhanced thermal protection performance, for dynamic thermal protection in the next-generation morphing aircrafts. The formation of hollow structures endows the material with intelligent thermal management ability and makes the thermal conductivity controllable, meeting the requirements of rapid deformation and excellent thermal insulation. The dimensions of the material adaptively expand with increasing temperature, and a constant 50N force can be provided to ensure reliable sealing. Moreover, benefiting from the synergistic effect of the hollow structure and zinc borate in the ceramization process of the silicone rubber, the 10 mm thick material can reduce the temperature from 2000 to 63 °C, and the mass ablation rate is only 4.8 mg/s. To broaden the application of our material, a sensor with a sandwich structure composed of different functional layers is designed. It is pleasantly surprising to observe that the sensor can provide real-time remote warning of fire and overheating sites with a response time as short as 1 s. This synergistic strategy opens a new possibility to fabricate intelligent thermal protection materials.

Improving the Ablation Properties of Liquid Silicone Rubber Composites by Incorporating Hexaphenoxycyclotriphosphonitrile.

The ablative properties of epoxy-modified vinyl silicone rubber (EMVSR) composites containing hexaphenoxycyclotriphosphonitrile (HPCTP) have been systematically studied. The strength of the ablation char layer was greatly enhanced with the addition of HPCTP, which induced the formation of a more complete, denser, and thicker char during oxyacetylene ablation tests. Moreover, the HPCTP-containing EMVSR composites demonstrated lower thermal conductivity and pyrolysis rate when compared with those without HPTCP. At the same time, the thermal insulation properties of HPCTP-filled composites were improved under low heat flow ablation scenarios. The reduction of graphitic carbon content, the formation of phosphate-like crystals as well as the increase of SiC content contributed to strengthening the char layer, which was critical for improving the ablation properties. The optimum char layer strength and thermal insulation properties were achieved when the content of HPCTP was 15 phr, whereas an optimum ablation resistance was achieved at 25 phr HPCTP. This suggests that HPCTP-modified EMVSR composites can be used for thermal protection purposes, especially in the fields of aerospace and aeronautics.

MR microneurography of human peripheral fascicles using a clinical 3T MR scanner.

BACKGROUND AND PURPOSE: Knowledge of nerve fascicular structures is essential for managing peripheral nerve disorders. This study aimed to investigate the feasibility of z-axis high-resolution magnetic resonance (MR) microneurography (zH-MRMN) in displaying the three-dimensional structures of tibial nerve fascicles in vivo using a 3T MR scanner. MATERIALS AND METHODS: Twelve volunteers underwent z-axis conventional-resolution MR microneurography (zC-MRMN) and zH-MRMN of tibial nerves. The visibility scores of the nerve fascicles (VSNFs) on axial zC-MRMN images and axial zH-MRMN multiplanar reformation (MPR) images were compared. The nerve fascicle appearances on the longitudinal zH-MRMN MPR images were described. RESULTS: In the nerve segments whose long axes were perpendicular to the imaging planes of both zC-MRMN and zH-MRMN, the VSNFs were not significantly different between the axial images of the two modalities (P = 0.083). In the nerve segments whose long axes were not perpendicular to the imaging planes of zC-MRMN, the VSNFs on the axial zC-MRMN images were significantly lower than those on the axial zH-MRMN MPR images that were angled perpendicular to the long axis of the tibial nerve (P < 0.001). CONCLUSIONS: The longitudinal zH-MRMN MPR images clearly displayed the changing features of the intraneural fascicles as well as the gross morphology of the tibial nerves. zH-MRMN can clearly delineate the topography of the tibial nerve fascicles in vivo through use of a 3T MR scanner.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury.

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Epigenetic regulation and therapeutic strategies in ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.

An experimental and numerical study of the microstructural and biomechanical properties of human peripheral nerve endoneurium for the design of tissue scaffolds.

Biomimetic design of scaffold architectures represents a promising strategy to enable the repair of tissue defects. Natural endoneurium extracellular matrix (eECM) exhibits a sophisticated microstructure and remarkable microenvironments conducive for guiding neurite regeneration. Therefore, the analysis of eECM is helpful to the design of bionic scaffold. Unfortunately, a fundamental lack of understanding of the microstructural characteristics and biomechanical properties of the human peripheral nerve eECM exists. In this study, we used microscopic computed tomography (micro-CT) to reconstruct a three-dimensional (3D) eECM model sourced from mixed nerves. The tensile strength and effective modulus of human fresh nerve fascicles were characterized experimentally. Permeability was calculated from a computational fluid dynamic (CFD) simulation of the 3D eECM model. Fluid flow of acellular nerve fascicles was tested experimentally to validate the permeability results obtained from CFD simulations. The key microstructural parameters, such as porosity is 35.5 ± 1.7%, tortuosity in endoneurium (X axis is 1.26 ± 0.028, Y axis is 1.26 ± 0.020 and Z axis is 1.17 ± 0.03, respectively), tortuosity in pore (X axis is 1.50 ± 0.09, Y axis is 1.44 ± 0.06 and Z axis is 1.13 ± 0.04, respectively), surface area-to-volume ratio (SAVR) is 0.165 ± 0.007 µm-1 and pore size is 11.8 ± 2.8 µm, respectively. These were characterized from the 3D eECM model and may exert different effects on the stiffness and permeability. The 3D microstructure of natural peripheral nerve eECM exhibits relatively lower permeability (3.10 m2 × 10-12 m2) than other soft tissues. These key microstructural and biomechanical parameters may play an important role in the design and fabrication of intraluminal guidance scaffolds to replace natural eECM. Our findings can aid the development of regenerative therapies and help improve scaffold design.

Realizing the high energy density and flexibility of a fabric electrode through hierarchical structure design.

The exploration of high-energy density flexible electrodes through reasonable structural design is the key to realizing the overall portability and wearability of devices. Herein, a free-standing hybrid nanofabric with superior mechanical and electrochemical stabilities is reported for flexible lithium-ion batteries (LIBs). The hybrid nanofabric is prepared by electrospinning and carbonization, during which the self-cyclization of polyacrylonitrile (PAN) is hindered by its reaction with melamine, resulting in a highly disordered and expanded turbostratic carbon structure with nickel metal thiophosphate (NiPS3) nanosheets embedded in it. The coordinated movement of the electrospun-derived 1D nanofiber, the super toughness of the hard carbon structure and the interlayer slipping of NiPS3 endow the hybrid nanofabric with excellent tolerance to large-scale deformation. It can be folded three times in half and quickly return to its original state. When used as the anode for LIBs, no additional binder, conducting agent and current collector are needed. The free-standing anode not only shows excellent cycling (797.5 mA h g-1 after 1000 cycles at 1 A g-1) and rate (more than 56% capacity retained from 0.1 to 2 A g-1) performances, but also maintains its original electrochemical properties after being folded 300 times at 120°, 180° and 360°. This work provides a synergistic strategy to simultaneously enhance the energy density and flexibility of a fabric electrode, paving the way for the application of advanced flexible energy storage systems.