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Garnet solid electrolyte Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is an excellent inorganic ceramic-type solid electrolyte; however, the presence of Li2 CO3 impurities on its surface hinders Li-ion transport and increases the interface impedance. In contrast to traditional methods of mechanical polishing, acid corrosion, and high-temperature reduction for removing Li2 CO3 , herein, a straightforward "waste-to-treasure" strategy is proposed to transform Li2 CO3 into Li3 PO4 and LiF in LiPF6 solution under 60 °C. It is found that the formation of Li3 PO4 during LLZTO pretreatment facilitates rapid Li-ion transport and enhances ionic conductivity, and the LLZTO/PAN composite polymer electrolyte shows the highest Li-ion transference number of 0.63. Additionally, the dense LiF layer serves to safeguard the internal garnet solid electrolyte against solvent decomposition-induced chemical adsorption. Symmetric Li/Li cells assembled with treated LLZTO/PAN composite electrolyte exhibit a critical current density of 1.1 mA cm-2 and a long lifespan of up to 700 h at a current density of 0.2 mA cm-2 . The Li/LiFePO4 solid-state cells demonstrate stable cycling performances for 141 mAh g-1 at 0.5 C, with capacity retention of 93.6% after 190 cycles. This work presents a novel approach to converting waste into valuable resources, offering the advantages of simple processes, and minimal side reactions.
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Reactive oxygen species (ROS)-dependent monotherapy usually demonstrates poor therapeutic outcomes, due to the accompanied activation of protective autophagy in tumor cells, which results in ROS tolerance and immune suppression. In this study, a bimetallic electro-sensitizer, Pt-Ir NPs is constructed, loaded with the autophagy inhibitor chloroquine (Pt-Ir-CQ NPs), to enhance the effectiveness of electrotherapy by inhibiting autophagy and activating anti-tumor immune responses. This novel electrotherapy platform demonstrates unique advantages, particularly in the treatment of hypoxic and immunosuppressive tumors. First, the electro-sensitizer catalyzes water molecules into ROS under electric field, achieving tumor ablation through electrotoxicity. Second, the incorporated CQ inhibits the protective autophagy induced by electrotherapy, restoring the sensitivity of tumor cells to ROS and thereby enhancing the anti-tumor effects of electrotherapy. Third, Pt-Ir-CQ NPs enhance the functionality of antigen-presenting cells and immunogenic cells through inhibiting autophagy, synergistically activating the anti-tumor immune responses along with the immunogenic cell death (ICD) effect induced by electrotherapy. This study provides a novel approach for the effective ablation and long-term inhibition of solid tumors through flexible modulation by an exogenous electric field.
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INTRODUCTION: The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI) is a topic of significant clinical interest. This meta-analysis aims to provide a comprehensive evaluation of this relationship. CONTENT: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to October 11, 2023. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). Weighted mean differences (WMD) and odds ratios (OR) were calculated using random-effects models. Sensitivity analysis, funnel plots, and Egger's test were used to assess the robustness and publication bias of the findings. Subgroup analyses were performed to explore potential variations between adults and children. SUMMARY: Eighteen studies encompassing a total of 7,453 participants were included. The analysis revealed a significant elevation in serum angiopoietin-2 levels in patients with AKI compared to those without (WMD: 4.85; 95â¯% CI: 0.75 to 0.27; I²=93.2â¯%, p<0.001). Subgroup analysis indicated significantly higher angiopoietin-2 levels in adults with AKI (WMD: 5.17; 95â¯% CI: 3.51 to 6.83; I²=82.6â¯%, p<0.001), but not in children. Additionally, high serum angiopoietin-2 levels were associated with an increased risk of AKI (OR: 1.58; 95â¯% CI: 1.39 to 1.8; I²=89.1â¯%, p<0.001). Sensitivity analysis validated the robustness of these results, showing no substantial change in the overall effect size upon the exclusion of individual studies. OUTLOOK: This meta-analysis supports a significant association between elevated serum angiopoietin-2 levels and increased risk of AKI. The observed differential association between adults and children highlights the need for further targeted research to understand these age-specific variations.
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Challenges such as shuttle effect have hindered the commercialization of lithium-sulfur batteries (LSBs), despite their potential as high-energy-density storage devices. To address these issues, we explore the integration of solar energy into LSBs, creating a photo-assisted lithium-sulfur battery (PA-LSB). The PA-LSB provides a novel and sustainable solution by coupling the photocatalytic effect to accelerate sulfur redox reactions. Herein, a perovskite quantum dot-loaded MOF material serves as a cathode for the PA-LSB, creating built-in electric fields at the micro-interface to extend the lifetime of photo-generated charge carriers. The band structure of the composite material aligns well with the electrochemical reaction potential of lithium-sulfur, enabling precise regulation of polysulfides in the cathode of the PA-LSB system. This is attributed to the selective catalysis of the liquid-solid reaction stage in the lithium-sulfur electrochemical process by photocatalysis. These contribute to the outstanding performance of PA-LSBs, particularly demonstrating a remarkably high reversible capacity of 679â mAh g-1 at 5â C, maintaining stable cycling for 1500â cycles with the capacity decay rate of 0.022 % per cycle. Additionally, the photo-charging capability of the PA-LSB holds the potential to compensate for non-electric energy losses during the energy storage process, contributing to the development of lossless energy storage devices.
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The Zn//V2 O5 system not only faces the incontrollable growth of zinc (Zn) dendrites, but also withstands the cross-talk effect of by-products produced from the cathode side to the Zn anode, inducing interelectrode talk and aggravating battery failure. To tackle these issues, we construct a rapid Zn2+ -conducting hydrogel electrolyte (R-ZSO) to achieve Zn deposition modulation and side reaction inhibition in Zn//V2 O5 full cells. The polymer matrix and BN exhibit a robust anchoring effect on SO4 2- , accelerating Zn2+ migration and enabling dense Zn deposition behavior. Therefore, the Zn//Zn symmetric cells based on the R-ZSO electrolyte can operate stably for more than 1500â h, which is six times higher than that of cells employing the blank electrolyte. More importantly, the R-ZSO hydrogel electrolyte effectively decouples the cross-talk effects, thus breaking the infinite loop of side reactions. As a result, the Zn//V2 O5 cells using this modified hydrogel electrolyte demonstrate stable operation over 1,000â cycles, with a capacity loss rate of only 0.028 % per cycle. Our study provides a promising gel chemistry, which offers a valuable guide for the construction of high-performance and multifunctional aqueous Zn-ion batteries.
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Solid-state electrolytes (SSEs) are the core material of solid-state lithium metal batteries (SLMBs), which are being researched urgently owing to their high energy and safety. Both high ionic conductivity and excellent cycling stability remain the primary goal of solid-state electrolytes. Herein, inspired by K+ /Na+ ion channels in cell membrane of eukaryotes, a novel hollow UiO-66 with biomimetic ion channels based on quasi-solid-state electrolytes (QSSEs) is designed. The hollow UiO-66 spheres containing biomimetic ion channels can spontaneously combine anions and incorporate more lithium ions, creating improved ionic conductivity (1.15 × 10-3 S cm-1 ) and lithium-ion transference number (0.70) at room temperature. The long-term cycling of symmetric batteries and COMSOL simulations demonstrate that this biomimetic strategy enables uniform ion flux to suppress Li dendrites. Furthermore, the Li metal full cells paired with LiFePO4 cathode exhibit excellent cycling stability and rate performance. Consequently, the strategy of designing biomimetic QSSEs opens up a new path for developing high-performance electrolytes for SLMBs.
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Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC50 = 4.03 ± 0.03 µM, eqBuChE: IC50 = 5.64 ± 0.53 µM; hAChE: IC50 = 8.30 ± 0.04 µM, hBuChE: IC50 = 1.91 ± 0.06 µM) and hMAO-B (IC50 = 3.29 ± 0.09 µM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 µM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.
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Enfermedad de Alzheimer , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Clorgilina/uso terapéutico , Inhibidores de la Colinesterasa , Cinética , Diseño de Fármacos , Inhibidores de la Monoaminooxidasa , Monoaminooxidasa/metabolismo , Colinesterasas/metabolismo , Acetilcolinesterasa/metabolismo , Relación Estructura-ActividadRESUMEN
The high-temperature strain gauge is a sensor for strain measurement in high-temperature environments. The measurement results often have a certain divergence, so the uncertainty of the high-temperature strain gauge system is analyzed theoretically. Firstly, in the conducted research, a deterministic finite element analysis of the temperature field of the strain gauge is carried out using MATLAB software. Then, the primary sub-model method is used to model the system; an equivalent thermal load and force are loaded onto the model. The thermal response of the grid wire is calculated by the finite element method (FEM). Thermal-mechanical coupling analysis is carried out by ANSYS, and the MATLAB program is verified. Finally, the stochastic finite element method (SFEM) combined with the Monte Carlo method (MCM) is used to analyze the effects of the physical parameters, geometric parameters, and load uncertainties on the thermal response of the grid wire. The results show that the difference of temperature and strain calculated by ANSYS and MATLAB is 1.34% and 0.64%, respectively. The calculation program is accurate and effective. The primary sub-model method is suitable for the finite element modeling of strain gauge systems, and the number of elements is reduced effectively. The stochastic uncertainty analysis of the thermal response on the grid wire of a high-temperature strain gauge provides a theoretical basis for the dispersion of the measurement results of the strain gauge.
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Lithium-oxygen batteries (LOBs) are well known for their high energy density. However, their reversibility and rate performance are challenged due to the sluggish oxygen reduction/evolution reactions (ORR/OER) kinetics, serious side reactions and uncontrollable Li dendrite growth. The electrolyte plays a key role in transport of Li+ and reactive oxygen species in LOBs. Here, we tailored a dilute electrolyte by screening suitable crown ether additives to promote lithium salt dissociation and Li+ solvation through electrostatic interaction. The electrolyte containing 100â mM 18-crown-6 ether (100-18C6) exhibits enhanced electrochemical stability and triggers a solution-mediated Li2 O2 growth pathway in LOBs, showing high discharge capacity of 10 828.8â mAh gcarbon -1 . Moreover, optimized electrode/electrolyte interfaces promote ORR/OER kinetics on cathode and achieve dendrite-free Li anode, which enhances the cycle life. This work casts new lights on the design of low-cost dilute electrolytes for high performance LOBs.
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Dual-ion batteries (DIBs) is a promising technology for large-scale energy storage. However, it is still questionable how material structures affect the anion storage behavior. In this paper, we synthesis graphite with an ultra-large interlayer distance and heteroatomic doping to systematically investigate the combined effects on DIBs. The large interlayer distance of 0.51â nm provides more space for anion storage, while the doping of the heteroatoms reduces the energy barriers for anion intercalation and migration and enhances rapid ionic storage at interfaces simultaneously. Based on the synergistic effects, the DIBs composed of carbon cathode and lithium anode afford ultra-high capacity of 240â mAh g-1 at current density of 100â mA g-1 . Dual-carbon batteries (DCBs) using the graphite as both of cathode and anode steadily cycle 2400 times at current density of 1â A g-1 . Hence, this work provides a reference to the strategy of material designs of DIBs and DCBs.
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Based on a single-beam injection distributed feedback semiconductor laser (DFB-SL) combining with optical heterodyne, a photonic scheme for generating dual-linear chirp microwave (dual-LCM) signal with identical or complementary chirp is proposed and experimentally demonstrated. For such a scheme, a continuous-wave (CW) light with a frequency of finj is split into two parts. One part is passing through a Mach-Zehnder modulator (MZM) driven by a modified sawtooth signal, and then its intensity varies with time as a sawtooth wave. Such a light is injected to a DFB-SL for generating a single linearly chirped microwave (single-LCM) signal. The other part of the CW light with frequency of finj is sent to a phase modulator (PM) driven by a sinusoidal signal, and one of higher-order sidebands is selected by a tunable optical filter and taken as the referenced light. Through heterodyning the referenced light with the single-LCM signal, a dual-LCM signal with identical (or complementary) chirp can be obtained. The experimental results demonstrate that, by adjusting the injection parameters and the frequency of the sinusoidal signal loaded on the PM, the central frequency of the generated dual-LCM signal can be widely tuned. For the period of the sawtooth signal at 10 µs, the bandwidth for each frequency band included in the generated dual-LCM signal is 19.36â GHz under identical chirp and 16.98â GHz under complementary chirp, respectively. Correspondingly, the time bandwidth product (TBWP) for each frequency band can reach 1.936 × 105 under identical chirp and 1.698 × 105 under complementary chirp, respectively.
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Given the breadth of currently arising opportunities and concerns associated with nanoparticles for biomedical imaging, various types of nanoparticles have been widely exploited, especially for cellular/subcellular level probing. However, most currently reported nanoparticles either have inefficient delivery into cells or lack specificity for intracellular destinations. The absence of well-defined nanoplatforms remains a critical challenge hindering practical nano-based bio-imaging. Herein, the authors elaborate on a tailorable membrane-penetrating nanoplatform as a carrier with encapsulated actives and decorated surfaces to tackle the above-mentioned issues. The tunable contents in such a versatile nanoplatform offer huge flexibility to reach the expected properties and functions. Aggregation-induced emission luminogen (AIEgen) is applied to achieve sought-after photophysical properties, specific targeting moieties are installed to give high affinity towards different desired organelles, and critical grafting of cell-penetrating cyclic disulfides (CPCDs) to promote cellular uptake efficiency without sacrificing the specificity. Hereafter, to validate its practicability, the tailored nano products are successfully applied to track the dynamic correlation between mitochondria and lysosomes during autophagy. The authors believe that the strategy and described materials can facilitate the development of functional nanomaterials for various life science applications.
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Nanopartículas , Nanoestructuras , Lisosomas , Mitocondrias , Orgánulos/metabolismoRESUMEN
Intracellular lipid metabolism occurs in lipid droplets (LDs), which is critical to the survival of cells. Imaging LDs is an intuitive way to understand their physiology in live cells. However, this is limited by the availability of specific probes that can properly visualize LDs in vivo. Here, an LDs-specific red-emitting probe is proposed to address this need, which is not merely with an ultrahigh signal-to-noise (S/N) ratio and a large Stokes shift (up to 214 nm) but also with superior resistance to photobleaching. The probe has been successfully applied to real-time tracking of intracellular LDs behaviors, including fusion, migration, and lipophagy processes. We deem that the proposed probe here offers a new possibility for deeper understanding of LDs-associated behaviors, elucidation of their roles and mechanisms in cellular metabolism, and determination of the transition between adaptive lipid storage and lipotoxicity as well.
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Colorantes Fluorescentes/química , Luz , Gotas Lipídicas/química , Animales , Transporte Biológico , Color , Transporte de Electrón , Colorantes Fluorescentes/metabolismo , Células HeLa , Células Hep G2 , Humanos , Gotas Lipídicas/metabolismo , Imagen Molecular , Pez CebraRESUMEN
The open-circuit voltage of organic solar cells is usually lower than the values achieved in inorganic or perovskite photovoltaic devices with comparable bandgaps. Energy losses during charge separation at the donor-acceptor interface and non-radiative recombination are among the main causes of such voltage losses. Here we combine spectroscopic and quantum-chemistry approaches to identify key rules for minimizing voltage losses: (1) a low energy offset between donor and acceptor molecular states and (2) high photoluminescence yield of the low-gap material in the blend. Following these rules, we present a range of existing and new donor-acceptor systems that combine efficient photocurrent generation with electroluminescence yield up to 0.03%, leading to non-radiative voltage losses as small as 0.21 V. This study provides a rationale to explain and further improve the performance of recently demonstrated high-open-circuit-voltage organic solar cells.
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Photodynamic therapy (PDT) utilizing light-induced singlet oxygen has achieved attractive results in anticancer fields; however, its development is hindered by limited light penetration depth, skin phototoxicity, tumor hypoxia, and PDT-induced hypoxia. Inspired by our previous research work and the limitations of PDT, we introduce a small-molecule-targeted drug erlotinib into the singlet-oxygen chemical source endoperoxide to achieve an EGFR-targeted PDT-mimetic sensitizer (Y3-1) for anticancer therapy. We demonstrated the erlotinib-based precise delivery of the singlet-oxygen chemical source (in vitro photosensitization) to EFGR-overexpressing tumor cells and tissues. Moreover, the anticancer assays validated that the enhanced anticancer efficacy (in vitro and in vivo) of Y3-1 was due to reversible singlet-oxygen thermal release. This study is expected to provide a smart strategy to break through the current roadblock in targeted PDT and achieve a more efficient anticancer therapy model.
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Portadores de Fármacos/farmacología , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Oxígeno Singlete/administración & dosificación , Animales , Línea Celular Tumoral/trasplante , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/farmacología , Femenino , Humanos , Inyecciones Intravenosas , Ratones , Neoplasias/patología , Fármacos Fotosensibilizantes/farmacocinética , Oxígeno Singlete/farmacocinéticaRESUMEN
Since Burkholderia thailandensis is included in the reference spectra of the VITEK MS libraries rather than Burkholderia pseudomallei, B. pseudomallei cannot be correctly identified in the current version of VITEK MS. This study was undertaken to evaluate the utility of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with the VITEK MS plus system in the detection of B. pseudomallei and B. thailandensis isolates. For each species, we increased the reference spectra, and then, a SuperSpectrum was created based on the selection of 39 specific masses. In a second step, we validated the SuperSpectra with 106 isolates identified by 16S rRNA gene sequencing. The results showed that there was 100% agreement between the validation strains analyzed by MALDI-TOF MS and those evaluated using 16S rRNA gene sequencing analysis methods. Therefore, MALDI-TOF MS is a promising, rapid, and economical method to monitor the outbreaks and spread of B. pseudomallei and B. thailandensis isolates.
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Infecciones por Burkholderia/microbiología , Burkholderia/química , Burkholderia/clasificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Burkholderia/genética , Burkholderia/aislamiento & purificación , Infecciones por Burkholderia/diagnóstico , Análisis por Conglomerados , ADN Bacteriano , Humanos , Tipificación Molecular , ARN Ribosómico 16S , Reproducibilidad de los ResultadosRESUMEN
Tubiechong (Eupolyphaga sinensis) is an important material used in traditional Chinese medicine (TCM). However, the immunoregulation effects of E. sinensis Lyophilized Powder (ESL) are unclear. The in vivo study thus designed to elucidate the immuno-enhancement effects of ESL in immunosuppressed mice induced by cyclophosphamide (CTX). Mice were treated with three doses of ESL (0.5, 1.0 and 2.0 g/kg). Compared with model group, ESL notably increased the immune organ index, mononuclear macrophages function and the level of nature killer cell (NK) (p < 0.05 or p < 0.01), delayed type hypersensitivity (DTH) was also improved (p < 0.05). The level of superoxide dismutase (SOD) and catalase (CAT) were enhanced (p < 0.05), while malonyldialdehyde (MDA) and nitrogen monoxide (NO) were reduced (p < 0.05 or p < 0.01). Meanwhile, cluster determinant (CD)3+ T cell, CD4+ T cell and CD4+/CD8+ ratio were increased (p < 0.01). The cytokines secretion such as interleukin (IL)-2 and tumor necrosis factor alpha (TNF-α) were notably increased (p < 0.05 or p < 0.01), and IL-6 and IL-16 were also enhanced (p < 0.05). Furthermore, ESL significantly inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), down-regulated the expression of Bcl-2 associated X protein (Bax), up-regulated the B cell lymphoma-2 protein (Bcl-2) expression and decreased the Bax/Bcl-2 ratio in spleen tissues (p < 0.05). In brief, all these findings suggest that ESL could effectively improve immune functions via modulating oxidative systems and innate immune cells. Abbreviations: TCM: Traditional Chinese Medicine; ESL: Eupolyphaga sinensis Lyophilized Powder; CCl4: Carbon tetrachloride; ERK: Extracellular regulated protein kinases; CTX: Cyclophosphamide; DTH: Delayed type hypersensitivity; SOD: Superoxide dismutase; CAT: Catalase; MDA: Malonyldialdehyde; NO: Nitrogen monoxide; NK: Nature killer cell; CD: Cluster determinant interleukin; TNF-α: Tumor Necrosis Factor alpha; JNK: c-Jun N-terminal kinase; Bax: Bcl-2 associated X protein; Bcl-2: B cell lymphoma-2 protein; Th1: Type-1 helper; Th2: Type-2 helper; FAMEs: Fatty acid methyl esters; DNFB: 2,4 - Dinitrofluorobenzene; ELISA: Enzyme-linked immuno sorbent assay; MAPK: Mitogen activated protein kinase; Cyt-c: Cytochrome c; SCFAs: Short-chain fatty acids; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis.
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Ciclofosfamida/toxicidad , Sistema Inmunológico/efectos de los fármacos , Tolerancia Inmunológica/efectos de los fármacos , Medicina Tradicional China , Neoptera/química , Polvos/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas Reguladoras de la Apoptosis/metabolismo , Liofilización , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Tolerancia Inmunológica/inmunología , Inmunosupresores/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones Endogámicos ICR , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismoRESUMEN
Inter-shaft bearing as a key component of turbomachinery is a major source of catastrophic accidents. Due to the requirement of high sampling frequency and high sensitivity to impact signals, AE (Acoustic Emission) signals are widely applied to monitor and diagnose inter-shaft bearing faults. With respect to the nonstationary and nonlinear of inter-shaft bearing AE signals, this paper presents a novel fault diagnosis method of inter-shaft bearing called the multi-domain entropy-random forest (MDERF) method by fusing multi-domain entropy and random forest. Firstly, the simulation test of inter-shaft bearing faults is conducted to simulate the typical fault modes of inter-shaft bearing and collect the data of AE signals. Secondly, multi-domain entropy is proposed as a feature extraction approach to extract the four entropies of AE signal. Finally, the samples in the built set are divided into two subsets to train and establish the random forest model of bearing fault diagnosis, respectively. The effectiveness and generalization ability of the developed model are verified based on the other experimental data. The proposed fault diagnosis method is validated to hold good generalization ability and high diagnostic accuracy (~0.9375) without over-fitting phenomenon in the fault diagnosis of bearing shaft.
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OBJECTIVE: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. METHODS: The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues. RESULTS: We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment. CONCLUSIONS: This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.
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Flavonoides/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Lamiaceae/química , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Citocinas/biosíntesis , Citocinas/metabolismo , Flavonoides/química , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/biosíntesis , Infecciones por Orthomyxoviridae/patología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/patología , Ribavirina/uso terapéutico , Transducción de Señal/efectos de los fármacosRESUMEN
An enzyme-free electrochemical immunoassay is described for the neutrophil gelatinase-associated lipocalin (NGAL; a biomarker of kidney disease). Prussian Blue (PB) nanoparticles with redox activity were deposited on graphitic C3N4 nanosheets (g-C3N4) by in-situ reduction. A screen printed electrode (SPCE) was modified with antibody against NGAL, and the PB-g-C3N4 nanohybrid was used as the signal-generating tag for the secondary antibody against NGAL. Upon addition of target NGAL and of secondary antibody, a sandwich is formed on the SPCE. At an applied potential of typically 0.13 V (vs. Ag/AgCl), a well-defined voltammetric peak is observed that results from the presence of PB on the secondary antibody. Under optimal conditions, the peak current increases linearly in the 0.01 to 10 ng·mL-1 NGAL concentration range, and the detection limit is 2.8 pg·mL-1. An average precision of <12% was accomplished in the batch-to-batch mode. Other disease-related biomarkers do not interfere. The accuracy and inter-laboratory validation of this method were evaluated for target NGAL detection in spiked human serum by using a commercial ELISA. The results obtained by the two methods are in good accordance. Graphical abstract An enzyme-free electrochemical immunoassay was used for detection of neutrophil gelatinase-associated lipocalin by Prussian blut/graphitic-C3N4 nanohybrids as the signal-generation tags.