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Preventing corrosion in the steel reinforcement of concrete structures is crucial for maintaining structural integrity and load-bearing capacity as it directly impacts the safety and lifespan of concrete structures. By preventing rebar corrosion, the durability and seismic performance of the structures can be significantly enhanced. This study investigates the hysteresis behavior of both corroded and non-corroded engineered cementitious composite (ECC)-glass-fiber-reinforced polymer (GFRP) spiral-confined reinforced-concrete (RC) columns. Employing experimental methods and finite element analysis, this research explores key seismic parameters such as crack patterns, failure modes, hysteretic responses, load-bearing capacities, ductility, stiffness degradation, and energy dissipation. The results demonstrate that ECC-GFRP spiral-confined RC columns, compared to traditional RC columns, show reduced corrosion rates, smaller crack widths, and fewer corrosion products, indicating superior crack control and corrosion resistance. Hysteresis tests revealed that ECC-GFRP columns, at a 20% target corrosion rate, exhibit an enhanced load-bearing capacity, ductility, and energy dissipation, suggesting improved durability and seismic resilience. Parametric and sensitivity analyses confirm the finite element model's accuracy and highlight the significant influence of concrete compressive strength on load-bearing capacity. The findings suggest that ECC-GFRP spiral-confined RC columns offer promising applications in coastal and seismic-prone regions, enhancing corrosion resistance and mechanical properties, thus potentially reducing formwork costs and improving construction quality and efficiency.
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Natural polysaccharides exhibit a wide range of biological activities, which are closely related to their structural characteristics, including their molecular weight distribution, size, monosaccharide composition, glycosidic bond types and spatial conformation, etc. Size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4), as two potent separation techniques, both harbor potential for continuous development and enhancement. This manuscript reviewed the fundamental principles and separation applications of SEC and AF4. The structural information and spatial conformation of polysaccharides can be obtained using SEC or AF4 coupled with multiple detectors. In addition, this manuscript elaborates in detail on the shear degradation of samples such as polysaccharides separated by SEC. In addition, the abnormal elution that occurs during the application of the two methods is also discussed. Both SEC and AF4 possess considerable potential for ongoing development and refinement, thereby offering increased possibilities and opportunities for polysaccharide separation and characterization.
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Cromatografía en Gel , Fraccionamiento de Campo-Flujo , Peso Molecular , Polisacáridos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Cromatografía en Gel/métodos , Fraccionamiento de Campo-Flujo/métodos , Monosacáridos/química , Monosacáridos/análisisRESUMEN
BACKGROUND: The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis. METHODS: Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1. RESULTS: UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis. CONCLUSIONS: UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.
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Carcinogénesis , Carcinoma Hepatocelular , Homeostasis , Neoplasias Hepáticas , Mitocondrias , Prohibitinas , Animales , Humanos , Ratones , Apoptosis , Carcinogénesis/patología , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Mitocondrias/metabolismo , Unión Proteica , Proteínas Represoras/metabolismoRESUMEN
Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked ß-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked ß-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1ß and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10-5 and 2.08 × 10-6, respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect.
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Astragalus propinquus , Galactanos , Galactanos/farmacología , Galactanos/química , Polisacáridos/farmacología , Polisacáridos/química , Transducción de SeñalRESUMEN
The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.
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PURPOSE: Erectile dysfunction (ED) is a common postoperative complication of pelvic surgery for which there is currently no effective treatment. This study investigated the therapeutic effects and potential mechanisms of adipose derived mesenchymal stem cells-derived mitochondria (ADSCs-mito) transplantation in a rat model of bilateral cavernous nerve injury (CNI) ED. MATERIALS AND METHODS: We isolated mitochondria from ADSCs and tested their quality. In vivo, twenty male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI groups that received intracavernous injection of either phosphate buffer solution, ADSCs-mito or ADSCs. Two weeks after therapy, the erectile function of the rats was evaluated and the penile tissues were harvested for histologic analysis and western blotting. In vitro, the apoptosis rate, reactive oxygen species (ROS), mitochondria derived active oxygen (mtROS) and adenosine triphosphate (ATP) levels were detected in corpus cavernosum smooth muscle cells (CCSMCs) after the incubation with ADSCs-mito. In addition, intercellular mitochondrial transfer was visualized by co-culture of ADSCs and CCSMCs. RESULTS: The ADSCs, ADSCs-mito and CCSMCs were isolated and identified successfully. ADSCs-mito transplantation notably restored the erectile function and smooth muscle content of CNI ED rats. Moreover, the levels of ROS, mtROS and cleaved-caspase 3 were reduced and the levels of superoxide dismutase and ATP were increased after ADSCs-mito transplantation. In CNI ED rats, the mitochondrial structure of cells in penile tissues was destroyed. ADSCs could transfer its own mitochondria to CCSMCs. Pre-treatment with ADSCs-mito could significantly decrease apoptosis rate, ROS levels and mtROS levels as well as restore the ATP level in CCSMCs. CONCLUSIONS: ADSCs-mito transplantation significantly ameliorated ED induced by CNI, with similar potency to ADSCs treatment. The ADSCs-mito might exert their effects via anti-oxidative stress, anti-apoptosis and modulating energy metabolism of CCSMCs. Mitochondrial transplantation should be a promising therapeutic method for treating CNI ED in the future.
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Nanofiber is the critical building block for many biological systems to perform various functions. Artificial assembly of molecules into nanofibers in a controllable and reversible manner will create "smart" functions to mimic those of their natural analogues and fabricate new functional materials, but remains an open challenge especially for nature macromolecules. Herein, the controllable and reversible assembly of nanofiber (CSNF) from natural macromolecules with oppositely charged groups are successfully realized by protonation and deprotonation of charged groups. By controlling the electrostatic interaction via protonation and deprotonation, the size and morphology of the assembled nanostructures can be precisely controlled. A strong electrostatic interaction contributes to large nanofiber with high strength, while poor electrostatic interaction produces finer nanofiber or nanoparticle. And especially, the assembly, disassembly, and reassembly of the nanofiber occurs reversibly through protonation and deprotonation, thereby paving a new way for precisely controlling the assembly process and structure of nanofiber. The reversible assembly allows the nanostructure to dynamically reorganize in response to subtle perturbation of environment. The as-prepared CSNF is mechanical strong and can be used as a nano building block to fabricate high-strength film, wire, and straw. This study offers many opportunities for the biomimetic synthesis of new functional materials.
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Tumor immunotherapy has become a research hotspot in cancer treatment, with macrophages playing a crucial role in tumor development. However, the tumor microenvironment restricts macrophage functionality, limiting their therapeutic potential. Therefore, modulating macrophage function and polarization is essential for enhancing tumor immunotherapy outcomes. Here, a supramolecular peptide amphiphile drug-delivery system (SPADS) is utilized to reprogram macrophages and reshape the tumor immune microenvironment (TIM) for immune-based therapies. The approach involved designing highly specific SPADS that selectively targets surface receptors of M2-type macrophages (M2-Mφ). These targeted peptides induced M2-Mφ repolarization into M1-type macrophages by dual inhibition of endoplasmic reticulum and oxidative stresses, resulting in improved macrophagic antitumor activity and immunoregulatory function. Additionally, TIM reshaping disrupted the immune evasion mechanisms employed by tumor cells, leading to increased infiltration, and activation of immune cells. Furthermore, the synergistic effect of macrophage reshaping and anti-PD-1 antibody (aPD-1) therapy significantly improved the immune system's ability to recognize and eliminate tumor cells, thereby enhancing tumor immunotherapy efficacy. SPADS utilization also induced lung metastasis suppression. Overall, this study demonstrates the potential of SPADS to drive macrophage reprogramming and reshape TIM, providing new insights, and directions for developing more effective immunotherapeutic approaches in cancer treatment.
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Neoplasias de la Mama , Inmunoterapia , Nanosferas , Péptidos , Microambiente Tumoral , Macrófagos Asociados a Tumores , Microambiente Tumoral/efectos de los fármacos , Inmunoterapia/métodos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Animales , Nanosferas/química , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Péptidos/química , Péptidos/farmacología , Femenino , Ratones , Línea Celular Tumoral , Humanos , Ratones Endogámicos BALB CRESUMEN
BACKGROUND AND AIMS: Liver tumorigenesis encompasses oncogenic activation and self-adaptation of various biological processes in premalignant hepatocytes to circumvent the pressure of cellular stress and host immune control. Ubiquitin regulatory X domain-containing proteins (UBXNs) participate in the regulation of certain signaling pathways. However, whether UBXN proteins function in the development of liver cancer remains unclear. APPROACH AND RESULTS: Here, we demonstrated that UBXN9 (Alveolar Soft Part Sarcoma Chromosomal Region Candidate Gene 1 Protein/Alveolar Soft Part Sarcoma Locus) expression was decreased in autochthonous oncogene-induced mouse liver tumors and ~47.7% of human HCCs, and associated with poor prognosis in patients with HCC. UBXN9 attenuated liver tumorigenesis induced by different oncogenic factors and tumor growth of transplanted liver tumor cells in immuno-competent mice. Mechanistically, UBXN9 significantly inhibited the function of the RNA exosome, resulting in increased expression of RLR-stimulatory RNAs and activation of the retinoic acid-inducible gene-I-IFN-Ι signaling in tumor cells, and hence potentiated T cell recruitment and immune control of tumor growth. Abrogation of the CD8 + T cell response or inhibition of tumor cell retinoic acid-inducible gene-I signaling efficiently counteracted the UBXN9-mediated suppression of liver tumor growth. CONCLUSIONS: Our results reveal a modality in which UBXN9 promotes the stimulatory RNA-induced retinoic acid-inducible gene-I-interferon signaling that induces anti-tumor T cell response in liver tumorigenesis. Targeted manipulation of the UBXN9-RNA exosome circuit may have the potential to reinstate the immune control of liver tumor growth.
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BACKGROUND: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood. METHODS: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. RESULTS: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxia-telangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity. CONCLUSION: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.
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Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine.
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Grifola , Grifola/química , Polisacáridos/química , HígadoRESUMEN
Using Brownian dynamics simulations, we study the ejection dynamics of spherically confined active polymers through a small pore. Although the active force can provide a driving force other than the entropy drive, it also causes the collapse of the active polymer, which in turn reduces the entropy drive. Thus, our simulation results confirm that the active polymer's ejection process can be divided into three stages. In the first stage, the influence of the active force is small, and the ejection is mainly an entropy-driven process. In the second stage, the ejection time satisfies the scaling relationship with the chain length, and the value of obtained scaling exponent is less than 1.0, indicating that the active force accelerates the ejection process. In the third stage, the scaling exponent is maintained at about 1.0, where the active force dominates the ejection process, and the ejection time is inversely proportional to the Péclet number. Furthermore, we find that the ejection velocity of the trailing particles has significant differences at different stages and is the core factor of the ejection mechanism at different stages. Our work helps us understand this non-equilibrium dynamic process and enhances our prediction of the relevant physiological phenomena.
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BACKGROUND: This study was conducted to investigate the therapeutic potential of the skin-derived precursor Schwann cells for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerve injury. RESULTS: The skin-derived precursor Schwann cells-treatment significantly restored erectile functions, accelerated the recovery of endothelial and smooth muscle tissues in the penis, and promoted nerve repair. The expression of p-Smad2/3 decreased after the treatment, which indicated significantly reduced fibrosis in the corpus cavernosum. CONCLUSIONS: Implantation of skin-derived precursor Schwann cells is an effective therapeutic strategy for treating erectile dysfunction induced by bilateral cavernous nerve injury.
RéSUMé: CONTEXTE: Cette étude a été menée pour étudier le potentiel thérapeutique des cellules de Schwann dérivées de la peau pour le traiter la dysfonction érectile survenue dans un modèle de lésion bilatérale du nerf caverneux chez le rat. RéSULTATS: Le traitement par des cellules de Schwann dérivées de la peau a significativement restauré les fonctions érectiles, accéléré la récupération des tissus endothéliaux et des tissues musculaires lisses du pénis, et a favorisé la réparation nerveuse. L'expression de p-Smad2/3 a diminué après le traitement, ce qui indique une fibrose significativement réduite dans le corps caverneux. CONCLUSION: L'implantation de cellules de Schwann dérivées de la peau est une stratégie thérapeutique efficace pour traiter la dysfonction érectile induite par une lésion bilatérale du nerf caverneux.
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ETHNOPHARMACOLOGICAL RELEVANCE: The imbalance between M1-and M2-polarized macrophages is one of the major pathophysiological changes in RA. Therefore, targeted macrophage polarization may be an effective therapy for RA. Koumine, an alkaloid monomer with the highest content and low toxicity in Gelsemium elegans Benth., has the effect of treating RA by playing an immunomodulatory role by influencing various immune cells. However, whether koumine affects macrophage polarization in RA and the associated molecular mechanisms remain unknown. AIM OF THE STUDY: To investigate the mechanism of the anti-RA effect of koumine on macrophage polarization. MATERIALS AND METHODS: The effect of koumine on macrophage polarization was investigated in vivo and in vitro. We first explored the effects of koumine on AIA rats and detected the levels of M1/M2 macrophage polarization markers in the spleen by western blotting. Then, we explored the regulatory effect of koumine on M1/M2 macrophage polarization and the effect on the PI3K/AKT signaling pathway in vitro. Finally, we verified the effects of koumine on macrophage polarization in CIA mice. RESULTS: We found that koumine alleviated symptoms, including relieving pain, reducing joint redness and swelling in AIA rats and restoring the M1/M2 macrophage balance in vivo. Interestingly, koumine had an inhibitory effect on both M1 and M2 macrophage polarization in vitro, but it had a stronger inhibitory effect on M1 macrophage. In a mixed polarization experiment, koumine mainly inhibited M1 macrophage polarization and had an inhibitory effect on the PI3K/AKT signaling pathway. Finally, we found that koumine had therapeutic effects on CIA mice, regulated macrophage polarization and inhibited the PI3K/AKT signaling pathway. CONCLUSIONS: Our results reveal that koumine regulates macrophage polarization through the PI3K/AKT signaling pathway. This may be one of the important mechanisms of its anti-RA effect, which provides a theoretical and scientific basis for the possible clinical application of koumine.
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Artritis Reumatoide , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , MacrófagosRESUMEN
Hydroxyl radical (OH) is considered the dominant reactive species in the electro-Fenton (EF) and Fered-Fenton (EF-Fere) processes for wastewater treatment. However, in chloride-rich media, this is arguable due to the obscure mechanisms for the oxidant speciation and pollutant degradation. Herein, the role of active chlorine and Fe(IV)-oxo species (FeIVO2+) as primary oxidizing agents in HClO-mediated Fered-Fenton (EF-Fere-HClO) process is discussed, along with the dependence of their contribution on the pollutant structure. HClO generated from anodic oxidation of Cl- can be consumed by added H2O2 to form singlet oxygen (1O2), which is detrimental because this species is quickly deactivated by water. The reaction between HClO and Fe2+ was proved to generate FeIVO2+, rather than OH or Cl suggested in the literature. The yield of FeIVO2+ species was proportional to the Cl- concentration and barely affected by solution pH. The long-lived HClO and FeIVO2+ can selectively react with electron-rich compounds, which occurs simultaneously to the non-selective attack of OH formed from Fenton's reaction. The FeIVO2+ and OH concentration profiles were successfully modelled. Although the accumulation of toxic chlorinated by-products from HClO-mediated oxidation might cause new environmental concerns, the toxicity of pesticide wastewater with 508 mM Cl- was halved upon EF-Fere-HClO treatment.
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Nanocelluloses, derived from various plants or specific bacteria, represent the renewable and sophisticated nano building blocks for emerging functional materials. Especially, the assembly of nanocelluloses as fibrous materials can mimic the structural organization of their natural counterparts to integrate various functions, thus holding great promise for potential applications in various fields, such as electrical device, fire retardance, sensing, medical antibiosis, and drug release. Due to the advantages of nanocelluloses, a variety of fibrous materials have been fabricated with the assistance of advanced techniques, and their applications have attracted great interest in the past decade. This review begins with an overview of nanocellulose properties followed by the historical development of assembling processes. There will be a focus on assembling techniques, including traditional methods (wet spinning, dry spinning, and electrostatic spinning) and advanced methods (self-assembly, microfluidic, and 3D printing). In particular, the design rules and various influencing factors of assembling processes related to the structure and function of fibrous materials are introduced and discussed in detail. Then, the emerging applications of these nanocellulose-based fibrous materials are highlighted. Finally, some perspectives, key opportunities, and critical challenges on future research trends within this field are proposed.
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Neurogenic erectile dysfunction (NED) is a common and serious complication after pelvic surgery. The clinical translation of adipose-derived mesenchymal stem cell (ADSC) therapies in NED remains a major challenge due to their low survival rate and limited therapeutic effect. Peroxiredoxin 2 (PRDX2) is a member of the peroxidase family that exerts its therapeutic effects by inhibiting oxidative stress (OS) and ferroptosis, and PRDX2 is expected to enhance the therapeutic effect of ADSCs in treating NED. The purpose of this study was to investigate whether PRDX2 could improve the survival of ADSCs and determine whether overexpression of PRDX2 in ADSCs (PRDX2-ADSCs) could enhance the therapeutic effect of NED. This study investigated the potential role of PRDX2-ADSCs through a NED model induced by bilateral cavernous nerve injury (BCNI) and three in vitro models established by H2O2-stimulated ADSCs, H2O2-stimulated corpus cavernosum smooth muscle cells (CCSMCs), and RSL3-stimulated CCSMCs. We found that PRDX2 could significantly improve the viability of ADSCs by suppressing apoptosis and OS in H2O2-stimulated ADSCs. We also found that BCNI triggered ferroptosis of the corpus cavernosum, which was manifested by increased reactive oxygen species (ROS), total iron content, and MDA as well as decreased SOD and GSH. Our results further demonstrated changes in the expression of key proteins (GPX4 and ACSL4) in the ferroptosis pathway, whereas PRDX2-ADSCs ameliorated BCNI-induced erectile dysfunction and ferroptosis of the corpus cavernosum in NED rats. Consistently, PRDX2-ADSCs attenuated OS in H2O2-stimulated CCSMCs and inhibited ferroptosis in RSL3-stimulated CCSMCs, as evidenced by the decrease in ROS, total iron content, and MDA and the increase in SOD and GSH together with changes in ferroptosis-related protein (GPX4 and ACSL4) expression. In conclusion, overexpression of PRDX2 in ADSCs enhanced the therapeutic effect in a rat model of neurogenic erectile dysfunction by inhibiting ferroptosis via regulation of the GPX4/ACSL4 axis.
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Disfunción Eréctil , Ferroptosis , Células Madre Mesenquimatosas , Masculino , Humanos , Ratas , Animales , Disfunción Eréctil/etiología , Ratas Sprague-Dawley , Peróxido de Hidrógeno/farmacología , Peroxirredoxinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Madre Mesenquimatosas/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Monteggia variant fracture is a Monteggia fracture (proximal third ulna fracture with radial head dislocation) with an associated radial head fracture, coronoid fracture or complex pattern of injury. We report a rare case of an 80-year-old lady with a right Monteggia variant fracture with an ipsilateral distal radius and ulna fracture leading to a floating forearm injury. To our knowledge, this is the first case report to describe this injury pattern. We describe the multidisciplinary team approach and detailed surgical technique in managing this rare and complex injury.
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Erectile dysfunction (ED) is an adverse side effect of pelvic surgery with no effective treatment. In this study, it is explored whether melatonin could improve the therapeutic effects of small extracellular vesicles (sEVs), derived from mesenchymal stem cells (MSCs), on cavernous nerve injury (CNI) ED, and the underlying mechanisms are investigated. The sEVs from melatonin-pretreated MSCs (MT-EVs) and MSCs (NC-EVs) are isolated and applied to CNI ED. Transplantation of MT-EVs remarkably increases erectile function and reduces phenotypic modulation in CNI ED rats. The therapeutic effects of MT-EVs are superior to those of NC-EVs. Sequencing implies that miR-10a-3p is enriched in MT-EVs, and directly targets the protein kinase inhibitor α (PKIA). After the suppression of miR-10a-3p, the therapeutic actions of MT-EVs are abolished, but are rescued by PKIA. Similarly, RhoA/ROCK is inhibited by MT-EVs, but this action is reversed by suppressing miR-10a-3p, accompanied by corresponding changes in PKIA. In conclusion, transplantation of MT-EVs could significantly alleviate CNI ED. MT-EVs may relieve the phenotypic modulation of the corpora cavernosum smooth muscle cells via the miR-10a-3p/PKIA/RhoA/ROCK signaling axis. These nanovesicles should be potential therapeutic vectors or bioactive materials for CNI ED.
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Disfunción Eréctil , Vesículas Extracelulares , Melatonina , Células Madre Mesenquimatosas , MicroARNs , Masculino , Humanos , Ratas , Animales , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/metabolismo , Melatonina/farmacología , Melatonina/metabolismo , Melatonina/uso terapéutico , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Single-atom catalysts (SACs) show great potential for rechargeable Zn-air batteries (ZABs); however, scalable production of SACs from sustainable resources is difficult owing to poor control of the local coordination environment. Herein, lignosulfonate, a by-product of the papermaking industry, is utilized as a multifunctional bioligand for the mass production of SACs with highly active MN4 S sites (M represents Fe, Cu, and Co) via strong metalnitrogen/sulfur coordination. This effectively adjusts the charge distribution and promotes the catalytic performance, leading to highly durable and excellent performance in oxygen reduction and evolution reactions for ZABs. This study paves the way for the industrial production of cost-effective SACs in a sustainable manner.