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Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with Staphylococcus aureus infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.
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Micro-Ondas , Fotoquimioterapia , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Tecnologia sem Fio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Luz , Staphylococcus aureus/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Camundongos Endogâmicos BALB C , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02â¯% is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.
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Cálcio , Glicólise , Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Animais , Cálcio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Fototerapia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/tratamento farmacológico , Humanos , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Camundongos , Raios InfravermelhosRESUMO
Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2O3/Fe3S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2O3/Fe3S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2O3/Fe3S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2O3/Fe3S4 displays a larger electromagnetism field enhancement parameter than Fe2O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2O3/Fe3S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.
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Staphylococcus aureus Resistente à Meticilina , Micro-Ondas , Osteomielite , Oxigênio , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Osteomielite/terapia , Osteomielite/tratamento farmacológico , Oxigênio/química , Elétrons , Animais , CamundongosRESUMO
Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.
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Nanopartículas , Osteomielite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Cobre/química , Micro-Ondas/uso terapêutico , Nanopartículas/química , Infecções Estafilocócicas/terapia , Osteomielite/terapiaRESUMO
Chronic osteomyelitis (COM), is a long-term, constant, and intractable disease mostly induced by infection from the invasion of Staphylococcus aureus (S. aureus) into bone cells. Here, we describe a highly effective microwave (MW) therapeutic strategy for S. aureus-induced COM based on the in situ growth of interfacial oxygen vacancy-rich molybdenum disulfide (MoS2)/titanium carbide (Ti3C2Tx) MXene with oxygen-deficient titanium dioxide (TiO2-x) on Ti3C2Tx (labeled as HU-MoS2/Ti3C2Tx) by producing reactive oxygen species (ROS) and heat. HU-MoS2/Ti3C2Tx produced heat and ROS, which could effectively treat S. aureus-induced COM under MW irradiation. The underlying mechanism determined by density functional theory (DFT) and MW vector network analysis was that HU-MoS2/Ti3C2Tx formed a high-energy local electric field under MW irradiation, consequently generating more high-energy free electrons to pass and move across the interface at a high speed and accelerate by the heterointerface, which enhanced the charge accumulation on both sides of the interface. Moreover, these charges were captured by the oxygen species adsorbed at the HU-MoS2/Ti3C2Tx interface to produce ROS. MoS2 facilitated multiple reflections and scattering of electromagnetic waves as well as enhanced impedance matching. Ti3C2Tx enhanced the conduction loss of electromagnetic waves, while functional groups induced dipole polarization to enhance attenuation of MW.
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Micro-Ondas , Osteomielite , Humanos , Micro-Ondas/uso terapêutico , Staphylococcus aureus , Molibdênio , Espécies Reativas de Oxigênio , Osteomielite/terapia , OxigênioRESUMO
The ability to effectively treat deep bacterial infections while promoting osteogenesis is the biggest treatment demand for diseases such as osteomyelitis. Microwave therapy is widely studied due to its remarkable ability to penetrate deep tissue. This paper focuses on the development of a microwave-responsive system, namely, a zinc ion (Zn2+ ) doped graphite carbon nitride (CN) system (BZCN), achieved through two high-temperature burning processes. By subjecting composite materials to microwave irradiation, an impressive 99.81% eradication of Staphylococcus aureus is observed within 15 min. Moreover, this treatment enhances the growth of bone marrow stromal cells. The Zn2+ doping effectively alters the electronic structure of CN, resulting in the generation of a substantial number of free electrons on the material's surface. Under microwave stimulation, sodium ions collide and ionize with the free electrons generated by BZCN, generating a large amount of energy, which reacts with water and oxygen, producing reactive oxygen species. In addition, Zn2+ doping improves the conductivity of CN and increases the number of unsaturated electrons. Under microwave irradiation, polar molecules undergo movement and generate frictional heat. Finally, the released Zn2+ promotes macrophages to polarize toward the M2 phenotype, which is beneficial for tibial repair.
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Grafite , Osteomielite , Humanos , Grafite/química , Carbono , Micro-Ondas , Antibacterianos/farmacologia , Antibacterianos/química , Osteomielite/tratamento farmacológicoRESUMO
Owing to its deep penetration capability, microwave (MW) therapy has emerged as a promising method to eradicate deep-seated acute bone infection diseases such as osteomyelitis. However, the MW thermal effect still needs to be enhanced to achieve rapid and efficient treatment of deep focal infected areas. In this work, the multi-interfacial core-shell structure barium sulfate/barium polytitanates@polypyrrole (BaSO4/BaTi5O11@PPy) was prepared, which exhibited enhanced MW thermal response via the well-designed multi-interfacial structure. To be specific, BaSO4/BaTi5O11@PPy achieved rapid temperature increases in a short period and efficient clearance of Staphylococcus aureus (S. aureus) infections under MW irradiation. After 15 min MW irradiation, the antibacterial efficacy of BaSO4/BaTi5O11@PPy can reach up to 99.61 ± 0.22%. Their desirable thermal production capabilities originated from enhanced dielectric loss including multiple interfacial polarization and conductivity loss. Additionally, in vitro analysis illuminated that the underlying antimicrobial mechanism was attributed to the noticeable MW thermal effect and changes in energy metabolic pathways on bacterial membrane instigated by BaSO4/BaTi5O11@PPy under MW irradiation. Considering remarkable antibacterial efficiency and acceptable biosafety, we envision that it has significant value in broadening the pool of desirable candidates to fight against S. aureus-infected osteomyelitis. STATEMENT OF SIGNIFICANCE: The treatment of deep bacterial infection remains challenging due to the ineffectiveness of antibiotic treatment and the susceptibility to bacterial resistance. Microwave (MW) thermal therapy (MTT) is a promising approach with remarkable penetration to centrally heat up the infected area. This study proposes to utilize the core-shell structure BaSO4/BaTi5O11@PPy as an MW absorber to achieve localized heating under MW radiation for MTT. In vitro experiments demonstrated that the disrupted bacterial membrane is primarily due to the localized high temperature and interrupted electron transfer chain. As a consequence, its antibacterial rate is as high as 99.61% under MW irradiation. It is shown that the BaSO4/BaTi5O11@PPy is a promising candidate for eliminating bacterial infection in deep-seated tissues.
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Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Polímeros/farmacologia , Polímeros/química , Micro-Ondas , Pirróis/farmacologia , Pirróis/uso terapêutico , Pirróis/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
Microwave (MV)-trigged dynamic therapy based on MV-responsive materials is promising for treating deep infection diseases that cannot be effectively treated by antibiotics, like life-threatening osteomyelitis. Surface states of materials affect the generation of free charges under the excitation source with energy less than the band gap, consequently influencing the MV dynamic effects. Herein, an MV responsive system with interface confined 2D metal-organic framework (2D MOF) on oxidized carbon nanotube (CNT) is prepared, in which the ultrasmall Cu-based 2D MOF possesses sufficient surface/interface defects, endowing the system a large number of surface states. Under MV irradiation, the synthesized CNT-2D MOF not only efficiently absorbs and converts the microwave into heat for microwaveocaloric therapy (MCT) via enhanced hetero-interfacial polarization, but also generates excited electrons via surface state for microwave dynamic therapy (MDT). This biocompatible CNT-2D MOF exhibits highly effective broad-spectrum antimicrobial activity against seven pathogenic bacteria, including Gram-negative and Gram-positive pathogens, under 7 min MV irradiation. And this system is proven to efficiently eradicate Staphylococcus aureus infected rabbit tibia osteomyelitis. Significantly, MV-excited MCT and MDT of CNT-CuHHTP developed in this study makes a major step forward in antibiotic-free MV therapy in deep tissue bacterial infection diseases.
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Estruturas Metalorgânicas , Osteomielite , Animais , Coelhos , Micro-Ondas , Antibacterianos , Elétrons , Osteomielite/tratamento farmacológicoRESUMO
The actual 5-year survival rates for Gynecological Endometrioid Adenocarcinoma with Squamous Differentiation (GE-ASqD) are rarely reported. The purpose of this study was to evaluate how histological subtypes affected long-term survivors of GE-ASqD (> 5 years). We conducted a retrospective analysis of patients diagnosed GE-ASqD from the Surveillance, Epidemiology, and End Results database (2004-2015). In order to conduct the studies, we employed the chi-square test, univariate cox regression, and multivariate cox proportional hazards model. A total of 1131 patients with GE-ASqD were included in the survival study from 2004 to 2015 after applying the inclusion and exclusion criteria and the sample randomly split into a training set and a test set at a ratio of 7:3. Five machine learning algorithms were trained based on nine clinical variables to predict the 5-year overall survival. The AUC of the training group for the LR, Decision Tree, forest, Gbdt, and gbm algorithms were 0.809, 0.336, 0.841, 0.823, and 0.856 respectively. The AUC of the testing group was 0.779, 0.738, 0.753, 0.767 and 0.734, respectively. The calibration curves confirmed good performance of the five machine learning algorithms. Finally, five algorithms were combined to create a machine learning model that forecasts the 5-year overall survival rate of patients with GE-ASqD.
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Carcinoma Endometrioide , Carcinoma de Células Escamosas , Humanos , Feminino , Estudos Retrospectivos , Algoritmos , Aprendizado de MáquinaRESUMO
Interlayer interactions in two dimensional (2D) materials promote catalytic performance but often depend on the transport of inter rather than intralayer electrons. In this study, it is found that asymmetric metal-nanocluster-doped 2D g-C3 N4 greatly enhances catalytic performance by inducing microwave excitation of interlayer electron delocalization, resulting in a polarization of interlaminar charge transport for microwave disinfection and pneumonia therapy. Asymmetric Fe and Cu nanocluster doping (DCN-FeCu) enables g-C3 N4 to generate interlayer electrons under microwave irradiation, leading to interlayer polarization processes and electron delocalization effects, thus enhancing the interlayer migration efficiency of electrons. It also improves impurity energy levels and leads to a decrease in work function, allowing DCN-FeCu to produce microwave carriers across the photoelectric potential barrier under low-energy microwave radiation (2.45 GHz). This asymmetric doping modulation produces layer number-dependent microwave electron excitations that are verified using multi-metal doping. Therefore, structurally modulated asymmetric doping of 2D materials with interfacial spatial effects can provide efficient microwave disinfection and pneumonia therapy.
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Osteomyelitis caused by bacteria is a deep-seated lesion and is often treated clinically with antibiotics. Long-term use of antibiotics may predispose bacteria to develop resistance. Here, CuCeOx material is applied to treat infectious bacterial osteomyelitis using microwave (MW)-assisted bacterial killing. Heat generation occurs as a result of the dielectric properties of the material under MW irradiation, and the material generates reactive oxygen species (ROS) under MW irradiation. Heat and ROS increase the thermal sensitivity and permeability of bacterial cell membranes, and the released copper ions easily penetrate the bacterial membrane and react with H2 O2 to produce a toxic hydroxyl group inside the bacteria, leading to the bacteria's eventual death. This is due to the synergistic effect of the MW thermal effect, ROS, and the breaking of the equilibrium within the bacteria. CuCeOx can effectively treat osteomyelitis caused by Staphylococcus aureus using MW irradiation. This study can safely and effectively address the challenge of deep tissue infections by shedding light on non-invasive antimicrobial systems and using MW thermal therapy and MW dynamics to achieve therapeutic results.
Assuntos
Osteomielite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Espécies Reativas de Oxigênio , Micro-Ondas/uso terapêutico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , CatáliseRESUMO
While conventional nanosystems can target infected lung tissue, they cannot achieve precise cellular targeting and enhanced therapy by modulating inflammation and microbiota for effective therapy. Here, we designed a nucleus-targeted nanosystem with adenosine triphosphate (ATP) and reactive oxygen species stimuli-response to treat pneumonia coinfected with bacteria and virus that is enhanced through inflammation and microbiota regulation. The nucleus-targeted biomimetic nanosystem was prepared through the combined bacteria-macrophage membrane and loaded hypericin and ATP-responsive dibenzyl oxalate (MMHP) subsequently. The MMHP despoiled the Mg2+ of intracellular cytoplasm in bacteria to achieve an effective bactericidal performance. Meanwhile, MMHP can target the cell nucleus and inhibit the H1N1 virus duplication by inhibiting the activity of nucleoprotein. MMHP possessed an immunomodulatory ability to reduce the inflammatory response and activate CD8+ T cells for assisted infection elimination. During the mice model, the MMHP effectively treated pneumonia coinfected with Staphylococcus aureus and H1N1 virus. Meanwhile, MMHP mediated the composition of gut microbiota to enhance the pneumonia therapy. Therefore, the dual stimuli-responsive MMHP possessed promising clinical translational potential to therapy infectious pneumonia.
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Acne is an inflammatory skin disease mainly caused by Propionibacterium acnes, which can cause local inflammatory reactions and develop into chronic inflammatory diseases in severe cases. To avoid the use of antibiotics and to effectively treat the site of acne, we report a sodium hyaluronate microneedle patch that mediates the transdermal delivery of ultrasound-responsive nanoparticles for the effective treatment of acne. The patch contains nanoparticles formed by zinc porphyrin-based metal-organic framework and zinc oxide (ZnTCPP@ZnO). We demonstrated activated oxygen-mediated killing of P. acnes with an antibacterial efficiency of 99.73% under 15 min of ultrasound irradiation, resulting in a decrease in levels of acne-related factors, including tumor necrosis factor-α, interleukins, and matrix metalloproteinases. The zinc ions up-regulated DNA replication-related genes, promoting the proliferation of fibroblasts and, consequently, skin repair. This research leads to a highly effective strategy for acne treatment through the interface engineering of ultrasound response.
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Acne Vulgar , Infecções Bacterianas , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Propionibacterium acnes , Interleucinas , Antibacterianos/farmacologiaRESUMO
Infectious pneumonia and colitis are hard to be treated due to tissue infection, mucosal immune disorders, and dysbacteriosis. Although conventional nanomaterials can eliminate infection, they also damage normal tissues and intestinal flora. Herein, this work reports bactericidal nanoclusters formed through self-assembly for efficient treatment of infectious pneumonia and enteritis. The ultrasmall (about 2.3 nm) cortex moutan nanoclusters (CMNCs) has excellent antibacterial, antiviral, and immune regulation activity. The formation of nanoclusters is analyzed from the molecular dynamics mainly through the binding between polyphenol structures through hydrogen bonding and ππ stacking interaction. CMNCs have enhanced tissue and mucus permeability ability compared with natural CM. CMNCs precisely targeted bacteria due to polyphenol-rich surface structure and inhibited broad spectrum of bacteria. Besides, they killed H1N1 virus mainly through the inhibition of the neuraminidase. These CMNCs are effective in treating infectious pneumonia and enteritis relative to natural CM. In addition, they can be used for adjuvant colitis treatment by protecting colonic epithelium and altering the composition of gut microbiota. Therefore, CMNCs showed excellent application and clinical translation prospects in the treatment of immune and infectious diseases.
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Colite , Vírus da Influenza A Subtipo H1N1 , Pneumonia , Humanos , Colite/tratamento farmacológico , Mucosa Intestinal/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pneumonia/metabolismoRESUMO
Sonodynamic therapy (SDT) with non-invasiveness and high tissue-penetrating ability has attracted widespread interest in treating deep-seated tumors or infections. To enhance the treatment efficacy of SDT, the development of high-efficiency and stable sonosensitizers are still needed. Herein, a defective homojunction porphyrin-based metal-organic framework (MOF) with greatly enhanced sonocatalytic ability is easily prepared and used for SDT of osteomyelitis infected by methicillin-resistant Staphylococcus aureus (MRSA). Acetic acid and benzoic acid are chosen as modulators during the hydrothermal synthesis of porphyrin-based MOF. It is found that the crystal structure of MOF shifts from PCN-222 to PCN-224 as the amount of acetic acid increases. Interestingly, the defective PCN (D-PCN) contains a two-phase homojunction structure of PCN-222/PCN-224. The sonocatalytic reactive oxygen species production presents a volcano-type trend with increased acetic acid, among which D-PCN-2 with more content of PCN-224 has the best sonocatalytic antibacterial ability. The reduced band gap introduced a defect, and type-II homojunction structures of D-PCN-2 improve the separation of the ultrasound-triggered electron hole, which significantly enhances the SDT effect. Through a mixed linker approach, this work develops a new defect-induced homojunction MOF with great performance for SDT of MRSA-infected osteomyelitis.
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Estruturas Metalorgânicas , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Porfirinas , Humanos , Estruturas Metalorgânicas/farmacologia , Ácido AcéticoRESUMO
Deep tissue infection, such as osteomyelitis, caused by methicillin-resistant Staphylococcus aureus (MRSA) infection, poses a serious threat to public health and cannot be effectively treated by antibiotics. In this study, we report a microwave (MW)-responsive MoO2/WO3 heterojunction that can be utilized to effectively treat MRSA-infected osteomyelitis under MW irradiation because of the enhanced MW thermal effect and MW catalysis of the composite. The underlying mechanism is as follows: A myriad of oxygen vacancies forms on the surface of MoO2 and WO3 by deoxidization effect with hydrogen from the decomposition of sodium borohydride, which induces a mass of free electrons on the surface of the composite and consequently promotes a localized surface plasmon resonance effect (LSPR) under MW irradiation. Furthermore, the conjugation of Mo and W at the interface enhances the LSPR effect. Thus, the LSPR effect not only induces the formation of radical oxygen species, thereby enhancing MW catalysis, but also results in the formation of an interfacial electrical field, which strengthens dipole polarization through synergistic action with oxygen vacancies and contributes to better MW thermal effects. The characteristics of MoO2/WO3 prove to be promising for the treatment of deep-tissue infections under MW irradiation.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Micro-Ondas/uso terapêutico , Oxigênio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Osteomielite/tratamento farmacológicoRESUMO
Background: This study aimed to establish and validate an accurate prognostic model, based on demographic and clinical parameters, for predicting the cancer-specific survival (CSS) of patients with poorly differentiated thyroid carcinoma (PDTC). Materials and methods: Patients diagnosed with PDTC between 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Randomly split the data into training and validation sets. Kaplan-Meier analysis with the log-rank test was performed to compare the survival distribution among cases. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent prognostic factors, which were subsequently utilized to construct a nomogram for predicting the 5- and 10-year cancer-specific survival of patients with PDTC. The discriminative ability and calibration of the nomogram model were assessed using the concordance index and calibration plots, respectively. In addition, we performed a decision curve analysis to assess the clinical value of the nomogram. Simultaneously, we compared the predictive performance of the nomogram model against that of the American Joint Committee on Cancer (AJCC) T-, N-, M-stage. Results: A total of 970 eligible patients were randomly assigned to either a training cohort (n = 679) or a validation cohort (n = 291). The Kaplan-Meier analysis revealed that there were no significant differences in cumulative survival based on the race, radiation, and marital status of patients. The stepwise Cox regression model showed that the model was optimal when the following five variables were included: age, tumor size, T-, N-, and M-stage. A nomogram was developed as a graphical representation of the model and exhibited good calibration and discriminative ability in the study. Compared to the T-, N-, and M-stage, the C-index of nomogram (training group: 0.807, validation group: 0.802), the areas under the receiver operating characteristic curve of the training set (5-year AUC: 0.843, 10-year AUC:0.834) and the validation set (5-year AUC:0.878, 10-year AUC:0.811), and the calibration plots of this model all exhibited better performance. At last, compared with T-, N-, and M-stage, the decision curve analysis indicated that the nomogram had excellent clinical net benefit. Conclusions: The nomogram developed by us can accurately predict the CSS of PDTC patients. It can help clinicians determine appropriate treatment strategies for poorly differentiated thyroid carcinoma patients.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Adenocarcinoma/patologia , Humanos , Estadiamento de Neoplasias , Nomogramas , Programa de SEER , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/terapiaRESUMO
It is difficult to effectively treat bacterial osteomyelitis using photothermal therapy or photodynamic therapy due to poor penetration of light. Here, a microwave (MW)-excited magnetic composite of molybdenum disulfide (MoS2 ) / iron oxide (Fe3 O4 ) is reported for the treatment of bacteria-infected osteomyelitis. In in vitro and in vivo experiments, MoS2 /Fe3 O4 is shown to effectively eradicate bacteria-infected mouse tibia osteomyelitis, due to MW thermal enhancement and reactive oxygen species (ROS) (1 O2 and ·O2 - ) production under MW radiation. In addition, the mechanism of MW heat generation is proposed by MW network vector analysis. By the density functional theory and finite element method, the ROS generation mechanism is proposed. The synergy or conductive network between dielectric MoS2 and magnetic Fe3 O4 can reach both enhancement of the dielectric and magnetic attenuation capability. In addition, abundant interfaces are generated to enhance the attenuation of electromagnetic waves by MoS2 and Fe3 O4, introducing multiple reflections and interfacial polarization. Therefore, MoS2 /Fe3 O4 has excellent MW absorption ability based on the synergy or conductive network between MoS2 and magnetic Fe3 O4 as well as multiple dielectric reflections and interfacial polarization.
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Osteomielite , Infecções Estafilocócicas , Animais , Camundongos , Micro-Ondas , Molibdênio , Osteomielite/terapia , Espécies Reativas de Oxigênio , Infecções Estafilocócicas/terapia , Staphylococcus aureusRESUMO
Purpose: To explore clinical and non-clinical characteristics affecting the prognosis of patients with differentiated thyroid cancer with distant metastasis (DTCDM) and establish an accurate overall survival (OS) prognostic model. Patients and methods: Study subjects and related information were obtained from the National Cancer Institute's surveillance, epidemiology, and results database (SEER). Kaplan-Meier analysis, log-rank test, and univariate and multivariate Cox analysis were used to screen for factors influencing the OS of patients with DTCDM. Nine variables were introduced to build a machine learning (ML) model, receiver operating characteristic (ROC) was used to evaluate the recognition ability of the model, calibration plots were used to obtain prediction accuracy, and decision curve analysis (DCA) was used to estimate clinical benefit. Results: After applying the inclusion and exclusion criteria, a total of 3,060 patients with DTCDM were included in the survival analysis from 2004 to 2017. A machine learning prediction model was developed with nine variables: age at diagnosis, gender, race, tumor size, histology, regional lymph node metastasis, primary site surgery, radiotherapy, and chemotherapy. After excluding patients who survived <120 months, variables were sub-coded and machine learning was used to model OS prognosis in patients with DTCDM. Patients 6-50 years of age had the highest scores in the model. Other variables with high scores included small tumor size, male sex, and age 51-76. The AUC and calibration curves confirm that the XGBoost model has good performance. DCA shows that our model can be used to support clinical decision-making in a 10-years overall survival model. Conclusion: An artificial intelligence model was constructed using the XGBoost algorithms to predict the 10-years overall survival rate of patients with DTCDM. After model validation and evaluation, the model had good discriminative ability and high clinical value. This model could serve as a clinical tool to help inform treatment decisions for patients with DTCDM.
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This work presents a novel signal amplification strategy for electrochemiluminescence (ECL) biosensor based on liposome-assisted chemical redox cycling for in situ formation of Au nanoparticles (Au NPs) on TiO2 nanotubes (TiO2 NTs) electrode. The system was exemplified by ascorbic acid (AA)-loaded liposome, the redox cycling of AA utilizing tris (2-carboxyethyl) phosphine (TCEP) as reductant, and the use of Au nanoclusters (Au NCs)/TiO2 NTs as working electrode to implement the ECL detection of prostate specific antigen (PSA). Specifically, the AA-loaded liposomes were used as tags to label the captured PSA through a sandwich immunoreaction. After the lysate of the liposome was transferred onto the interface of Au NCs/TiO2 NTs in the presence of Au3+ and TECP, the chemical redox cycling was triggered. In the cycling, Au3+ was directly reduced in situ by AA to form Au NPs on Au NCs/TiO2 NTs electrode, whereas the oxidation product of AA was reduced by TCEP to regenerate AA. The large loading capacity of the liposome and chemical redox cycling resulted in the incomplete reduction of the Au NCs to Au NPs on the TiO2 NTs electrode, enhancing the ECL intensity greatly. The multiple signal amplification strategy achieved an ultrasensitive detection for PSA with a detection limit down to 6.7 × 10-15 g mL-1 and a wide linear concentration range from 1.0 × 10-14 to 1.0 × 10-8 g mL-1. It is believed that this work is anticipated to extend the employment of advanced chemical redox cycling reaction in the field of ECL bioassays.