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BACKGROUND: Post-traumatic capsular contracture is a common complication of joint injury and surgery. Post-traumatic capsular contracture is associated with fibrosis characterized by excessive differentiation and proliferation of myofibroblasts and abnormal secretion and accumulation of extracellular matrix. Previous studies have suggested that IL11 plays a role in myocardial fibrosis. We thus hypothesized that IL11 may play a fibrotic role during capsular contracture, in order to discover new targets for preventing joint capsule contracture METHODS: We constructed a post-traumatic contracture model by excessively extending the knee joint and fixing the joint in the flexion position, and a post-traumatic joint capsule contracture model was constructed in the wild-type, IL11-/-, IL11R -/-, α-SMA-cre-IL11fl/fl, α-SMA-cre-IL11Rfl/fl mouse strain, with wild-type mice without any treatment of the knee joint as the control group. Fibrotic markers and the expression of IL11 and IL11R in knee joint tissue were detected in each group of mice. The NIH3T3 cell line was used for in vitro analyses. The expression of fibrosis markers, IL11, TGFß and ERK1/2 were detected by western blot, ELISA and RT-qPCR. RESULTS: Inhibition of IL11 inhibited ERK1/2 phosphorylation, reduced the secretion of collagen in the joint capsule, and inhibited the excessive differentiation and proliferation of myofibroblasts in the post-traumatic joint capsule contracture, thus alleviating the joint capsule contracture and obtaining better joint mobility. CONCLUSION: Downregulation of IL11 in traumatic joint capsule contracture inhibits ERK1/2 phosphorylation, thus significantly relieving joint capsule contracture. Our findings indicate the TGFß/IL11/ERK1/2 axis is an important pathway for the differentiation of fibroblasts into myofibroblasts. Anti-IL11 treatment is an effective means to prevent traumatic joint capsule contracture.
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Carbon dots (CDs), as a kind of zero-dimensional nanomaterials, have been widely synthesized by bottom-up methods from various precursors. However, the formation mechanism is still unclear and controversial, which also brings difficulty to the regulation of structures and properties. Only some tentative formation processes were postulated by analyzing the products obtained at different reaction times and temperatures. Here, the effect of crosslinking on the formation of carbonized polymer dots (CPDs) is explored. Crosslinking-induced nucleation and carbonization (CINC) is proposed as the driving force for the formation of CPDs. Under hydrothermal synthesis, the precursors are initiated to polymerize and crosslink. The crosslinking brings higher hydrophobicity to generate the hydrophilic/hydrophobic microphase separation, which promotes dehydration and carbonization resulting in the formation of CPDs. Based on the principle of CINC, the influence factors of size are also revealed. Moreover, the dissipative particle dynamics (DPD) simulation is employed to support this formation mechanism. This concept of CINC will bring light to the formation process of CPDs, as well as facilitate the regulation of CPDs' size and photoluminescence.
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Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-ß1 (TGF-ß1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-ß1, and polidocanol (POL) combined with TGF-ß1. The results showed that injection of TGF-ß1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-ß1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-ß1 combination produced pathological changes and curvature comparable to STS + TGF-ß1 and led to fewer complications. In conclusion, fibrin, STS + TGF-ß1, and POL + TGF-ß1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-ß1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
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Self-protective carbonized polymer dots (CPDs) with advantageous crosslinked nano-structures have attracted considerable attention in metal-free room temperature phosphorescence (RTP) materials, whereas, their RTP emissions are still limited to short wavelength. Expanding their RTP emission to Near-Infrared (NIR) range is attractive but suffers from the difficulties in constructing narrow energy levels and inhibiting intense nonradiative decay. Herein, a crosslink-enhanced emission (CEE)-dominated construction strategy was proposed, achieving desired NIR RTP (710 nm) in self-protective CPDs for the first time. Structural factors, i.e.ï¼crosslinking (covalent-bond CEE), conjugation (conjugated amine with bridging N-H and C=C group), and steric hindrance (confined-domain CEE), were confirmed indispensable for triggering NIR RTP emission in CPDs. Contrast experiments and theoretical calculations further revealed the rationality of the design strategy originating from CEE in terms of promoting the narrow energy level emission of triplet excitons and inhibiting the nonradiative quenching. This work not only firstly achieves NIR RTP in self-protective CPDs, but also helps understand the NIR RTP origin to further guide the synthesis of diverse CPDs with efficient long-wavelength RTP emission.
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Patterned arrays of perovskite single crystals can avoid signal cross-talk in optoelectronic devices, while precise crystal distribution plays a crucial role in enhancing device performance and uniformity, optimizing photoelectric characteristics, and improving optical management. Here, we report a strategy of droplet-assisted self-alignment to precisely assemble the perovskite single-crystal arrays (PSCAs). High-quality single-crystal arrays of hybrid methylammonium lead bromide (MAPbBr3) and methylammonium lead chloride (MAPbCl3), and cesium lead bromide (CsPbBr3) can be precipitated under a formic acid vapor environment. The crystals floated within the suspended droplets undergo movement and rotation for precise alignment. The strategy allows us to deposit PSCAs with a pixel size range from 200 to 500 micrometers on diverse substrates, including indium tin oxide, glass, quartz, and poly(dimethylsiloxane), and the area can reach up to 10 centimeters by 10 centimeters. The PSCAs exhibit excellent photodetector performance with a large responsivity of 24 amperes per watt.
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In vitro tumor models were successfully constructed by 3D bioprinting; however, bioinks with proper viscosity, good biocompatibility, and tunable biophysical and biochemical properties are highly desirable for tumor models that closely recapitulated the main features of native tumors. Here, we developed a nanocomposite hydrogel bioink that was used to construct ovarian and colon cancer models by 3D bioprinting. The nanocomposite bioink was composed of aldehyde-modified cellulose nanocrystals (aCNCs), aldehyde-modified hyaluronic acid (aHA), and gelatin. The hydrogels possessed tunable gelation time, mechanical properties, and printability by controlling the ratio between aCNCs and gelatin. In addition, ovarian and colorectal cancer cells embedded in hydrogels showed high survival rates and rapid growth. By the combination of 3D bioprinting, ovarian and colorectal tumor models were constructed in vitro and used for drug screening. The results showed that gemcitabine had therapeutic effects on ovarian tumor cells. However, the ovarian tumor model showed drug resistance for oxaliplatin treatment.
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Bioimpresión , Ácido Hialurónico , Hidrogeles , Nanocompuestos , Neoplasias Ováricas , Impresión Tridimensional , Humanos , Nanocompuestos/química , Hidrogeles/química , Bioimpresión/métodos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Ácido Hialurónico/química , Celulosa/química , Línea Celular Tumoral , Gelatina/química , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/farmacología , Oxaliplatino/farmacología , Oxaliplatino/química , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Compuestos Organoplatinos/química , Compuestos Organoplatinos/farmacología , AnimalesRESUMEN
The ankle joint, which connects the lower limbs and the sole of the foot, is prone to sprain during walking and sports, which leads to ankle arthritis. Supratroleolar osteotomy is an ankle preserving operation for the treatment of ankle arthritis, in which the osteotomy is an important fixing and supporting part. In order to avoid stress shielding effect as much as possible, the osteotomy block is designed as a porous structure. In this study, the osteotomy block was designed based on three-period minimal surface, and the designed structure was manufactured by 3D printing. The mechanical properties of different structures were studied by mechanical test and finite element simulation. In mechanical tests, the Gyroid structure showed a progressive failure mechanism from bottom to bottom, while the Diamond structure showed a shear failure zone at 45° Angle, which was not conducive to energy absorption and was more prone to brittle fracture than the Gyroid structure. Therefore, the Gyroid structure is valuable for further research in the development of porous osteotomy.
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Análisis de Elementos Finitos , Osteotomía , Impresión Tridimensional , Osteotomía/métodos , Humanos , Pie/cirugía , Articulación del Tobillo/cirugíaRESUMEN
The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (â¼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.
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Técnicas Biosensibles , Antígenos de Superficie de la Hepatitis B , Hepatitis B , Redes Neurales de la Computación , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/inmunología , Humanos , Hepatitis B/diagnóstico , Hepatitis B/virología , Hepatitis B/inmunología , Hepatitis B/sangre , Técnicas Biosensibles/métodos , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Límite de Detección , Oro/química , Aprendizaje Profundo , Resonancia por Plasmón de Superficie/métodos , Sistemas de Atención de PuntoRESUMEN
Hydrophilic coating can prevent surface from fogging but its application is limited by low mechanical performance. In this study, a hydrophilic coating was prepared by crosslinking the Si-doped carbonized polymer dot (Si-CPD) with 3-glycidyloxypropyltrimethoxysilane (GPTMS) and ethylene oxide (EO). The hydrophilic coating can be used as robust hydrophilic anti-fogging coating. The Si-CPD derived from ethylene diamine tetraacetic acid (EDTA) and aminopropyl oligosiloxanes (APOS) was successfully prepared via one-step hydrothermal method. Then, a resin solution was prepared by mixing Si-CPD, GPTMS and EO. Epoxy group of GPTMS and EO can react with amino group of Si-CPD. Finally, a composite coating with antifogging function can be obtained by simple heating curing. Due to the introduction of hydroxyl which derived from EO, the coating shows excellent antifogging performance. Meanwhile, the presence of inorganic component endows the coating with outstanding mechanical performance. The coating has great potential in related applications, such as optical lenses, mirrors and other transparency substrates.
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As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.
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Despite high sensitivity of nanoparticle-on-mirror cavities, a crucial branch of plasmonic nanomaterials, complex preparation and readout processes limit their extensive application in biosensing. Alternatively, liquid metals (LMs) combining fluidity and excellent plasmonic characteristics have become potential candidates for constructing plasmonic nanostructures. Herein, we propose a microfluidic-integration strategy to construct LM-based immunoassay platform, enabling LM-based nanoplasmonic sensors to be used for point-of-care (POC) clinical biomarker detection. Flowable LM is introduced onto protein-coated Au nanoparticle monolayer to form a "mirror-on-nanoparticle" nanostructure, simplifying the fabrication process in the conventional nanoparticle-on-mirror cavities. When antibodies were captured by antigens coated on the Au nanoparticle monolayer, devices respond both thickness and refractive index change of biomolecular layers, outputting naked-eye readable signals with high sensitivity (limit of detection: â¼ 604 fM) and a broad dynamic range (6 orders). This new assay, which generates quantitative results in 30 min, allows for high-throughput, smartphone-based detection of SARS-CoV-2 antibodies against multiple variants in clinical serum or blood samples. These results establish an advanced avenue for POC testing with LM materials, and demonstrate its potential to facilitate diagnostics, surveillance and prevalence studies for various infectious diseases.
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Anticuerpos Antivirales , Técnicas Biosensibles , COVID-19 , Oro , Nanopartículas del Metal , Sistemas de Atención de Punto , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Oro/química , Nanopartículas del Metal/química , Técnicas Biosensibles/instrumentación , COVID-19/diagnóstico , COVID-19/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunoensayo/instrumentación , Inmunoensayo/métodos , Límite de Detección , Dispositivos Laboratorio en un Chip , Diseño de Equipo , Pruebas en el Punto de Atención , Técnicas Analíticas Microfluídicas/instrumentación , Teléfono InteligenteRESUMEN
In traditional optical wireless communication (OWC) systems, the simultaneous use of multiple sets of light-emitting diodes (LEDs) and photodetectors (PDs) increases the system complexity and instability. Here we report bifunctional light-emitting photodetectors (LEPDs) fabricated with quasi-2D perovskite (F-PEA)2Cs4Pb5I11Br5 as light-emitting/detecting layers for efficient, miniaturized, and intelligent bidirectional OWC. By simply changing the solvent composition of the precursor solution and using antisolvent engineering, we manipulated the crystal orientation and phase distribution of (F-PEA)2Cs4Pb5I11Br5, realizing high irradiance (4.36 µW cm-2) and a -3 dB refresh rate (0.21 MHz) of electroluminescence in LED mode as well as low noise (below 1 pA Hz-1/2) and high responsivity (0.1 A W-1) in PD mode. The rapid and accurate OWC process was demonstrated through interaction of LEPDs. We also demonstrated the high-fidelity compression and digitization of high-resolution (256 × 256 pixels) color images using the four-step phase shift method to realize intelligent encrypted image OWC.
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BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.
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Light management is critical to maximizing the external quantum efficiency of perovskite light-emitting diodes (PeLEDs), but strategies for enhancing light out-coupling are typically complex and expensive. Here, using a facile solvent treatment strategy, we create a layer of lithium fluoride (LiF) nanoislands that serve as a template to reconstruct the light-extracting interfaces for PeLEDs. The nanoisland interface rearranges the near-field light distribution in order to maximize the efficiency of internal light extraction. With the proper adjustment of the nanoisland size and distribution, we have achieved an optimal balance between charge injection and light out-coupling, resulting in bright, pure-red quasi-two-dimensional PeLEDs with a 21.8% peak external quantum efficiency.
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Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, it is aimed to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" is synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and is delivered via a glucose/pH-responsive microneedle bandage (PDGa@GMB). The PDGa@GMB downregulates the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrates insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (>90%) against resistant strains of both S. aureus and E. coli, and accelerates tissue recovery (<20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity.
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Antibacterianos , Escherichia coli , Galio , Homeostasis , Hierro , Staphylococcus aureus , Hierro/metabolismo , Hierro/química , Galio/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Animales , Escherichia coli/efectos de los fármacos , Hemoglobinas/metabolismo , Protoporfirinas/química , Protoporfirinas/farmacología , Protoporfirinas/uso terapéutico , Humanos , Dopamina/metabolismo , Farmacorresistencia Microbiana/efectos de los fármacos , Ratones , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismoRESUMEN
Bacterial infection is a serious challenge in the treatment of open bone defects, and reliance on antibiotic therapy may contribute to the emergence of drug-resistant bacteria. To solve this problem, this study developed a mineralized hydrogel (PVA-Ag-PHA) with excellent antibacterial properties and osteogenic capabilities. Silver nanoparticles (CNC/TA@AgNPs) were greenly synthesized using natural macromolecular cellulose nanocrystals (CNC) and plant polyphenolic tannins (TA) as stabilizers and reducing agents respectively, and then introduced into polyvinyl alcohol (PVA) and polydopamine-modified hydroxyapatite (PDA@HAP) hydrogel. The experimental results indicate that the PVA-Ag-PHA hydrogel, benefiting from the excellent antibacterial properties of CNC/TA@AgNPs, can not only eliminate Staphylococcus aureus and Escherichia coli, but also maintain a sustained sterile environment. At the same time, the HAP modified by PDA is uniformly dispersed within the hydrogel, thus releasing and maintaining stable concentrations of Ca2+ and PO43- ions in the local environment. The porous structure of the hydrogel with excellent biocompatibility creates a suitable bioactive environment that facilitates cell adhesion and bone regeneration. The experimental results in the rat critical-sized calvarial defect model indicate that the PVA-Ag-PHA hydrogel can effectively accelerate the bone healing process. Thus, this mussel-inspired hydrogel with antibacterial properties provides a feasible solution for the repair of open bone defects, demonstrating the considerable potential for diverse applications in bone repair.
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Regeneración Ósea , Celulosa , Hidrogeles , Nanopartículas del Metal , Plata , Cráneo , Taninos , Plata/química , Plata/farmacología , Animales , Regeneración Ósea/efectos de los fármacos , Celulosa/química , Celulosa/farmacología , Nanopartículas del Metal/química , Ratas , Hidrogeles/química , Hidrogeles/farmacología , Cráneo/efectos de los fármacos , Cráneo/lesiones , Taninos/química , Taninos/farmacología , Bivalvos/química , Antibacterianos/farmacología , Antibacterianos/química , Alcohol Polivinílico/química , Staphylococcus aureus/efectos de los fármacos , Durapatita/química , Durapatita/farmacología , Ratas Sprague-Dawley , Escherichia coli/efectos de los fármacosRESUMEN
High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.
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Oro , Traumatismos de la Médula Espinal , Humanos , Especies Reactivas de Oxígeno , Oro/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Estrés Oxidativo , Materiales Biocompatibles/uso terapéuticoRESUMEN
Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.
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Ferroptosis , Neoplasias , Radioterapia Guiada por Imagen , Humanos , Especies Reactivas de Oxígeno , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Apoptosis , Peróxido de Hidrógeno , Línea Celular TumoralRESUMEN
Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate the inflammatory response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned for its potent antioxidant and anti-inflammatory characteristics, is frequently employed as an ROS scavenger in inflammatory diseases. However, the therapeutic efficacy of MT remains unsatisfactory due to the low water solubility and poor bioavailability. Carbon dots have emerged as a promising and innovative nanomaterial with facile synthesis, environmental friendliness, and low cost. In this study, melatonin-derived carbon dots (MT-CDs) were successfully synthesized via the hydrothermal method. The MT-CDs have good water solubility and biocompatibility and feature excellent ROS-scavenging capacity without additional modification. The in vitro experiments proved that MT-CDs efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis and suppressed the production of inflammatory mediators. Furthermore, findings from the mouse model of periodontitis indicated that MT-CDs significantly inhibited the deterioration of alveolar bone and reduced osteoclast activation and inflammation, thereby contributing to the regeneration of damaged tissue. In terms of the mechanism, MT-CDs may scavenge ROS, thereby preventing cellular damage and the production of inflammatory factors by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. The findings will offer a vital understanding of the advancement of secure and effective ROS-scavenging platforms for more biomedical applications.
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Melatonina , Periodontitis , Ratones , Animales , Melatonina/farmacología , Melatonina/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hemo-Oxigenasa 1 , Periodontitis/tratamiento farmacológico , Agua , CarbonoRESUMEN
Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.