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The E3 enzyme in the UPS pathway is a crucial factor for inhibiting substrate specificity. In Solanaceae, the U-box E3 ubiquitin ligase has a complex relationship with plant growth and development, and plays a pivotal role in responding to various biotic and abiotic stresses. The analysis of the U-box gene family in Solanaceae and its expression profile under different stresses holds significant implications. A total of 116 tobacco NtU-boxs and 56 eggplant SmU-boxs were identified based on their respective genome sequences. Phylogenetic analysis of U-box genes in tobacco, eggplant, tomato, Arabidopsis, pepper, and potato revealed five distinct subgroups (I-V). Gene structure and protein motifs analysis found a high degree of conservation in both exon/intron organization and protein motifs among tobacco and eggplant U-box genes especially the members within the same subfamily. A total of 15 pairs of segmental duplication and 1 gene pair of tandem duplication were identified in tobacco based on the analysis of gene duplication events, while 10 pairs of segmental duplication in eggplant. It is speculated that segmental duplication events are the primary driver for the expansion of the U-box gene family in both tobacco and eggplant. The promoters of NtU-box and SmU-box genes contained cis-regulatory elements associated with cellular development, phytohormones, environment stress, and photoresponsive elements. Transcriptomic data analysis shows that the expression levels of the tobacco and eggplant U-box genes in different tissues and various abiotic stress conditions. Using cultivar Hongda of tobacco and cultivar Yanzhi of eggplant as materials, qRT-PCR analysis has revealed that 15 selected NtU-box genes and 8 SmU-box may play important roles in response to pathogen Ras invasion both in tobacco and eggplant.
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Background: Diffuse uterine leiomyomatosis (DUL) is a seldom-seen condition, with only a handful of cases of magnetic resonance imaging (MRI) findings documented. In clinical settings, it is often mistaken for multiple uterine leiomyomas due to a lack of adequate recognition of DUL. Objective: This study shows two instances of DUL, underscoring their MRI findings to improve preoperative diagnostic precision. Conclusion: For patients exhibiting multiple uterine leiomyomas with masses present in the parametrial and abdominal cavities, consideration should be given to diagnosing DUL with DPL. The discoveries outlined in this paper furnish insights that can assist in directing treatment choices.
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The inoculum has a crucial impact on bioreactor initialization and performance. However, there is currently a lack of guidance on selecting appropriate inocula for applications in environmental biotechnology. In this study, we applied microbial electrolysis cells (MECs) as models to investigate the differences in the functional potential of electroactive microorganisms (EAMs) within anodic biofilms developed from four different inocula (natural or artificial), using shotgun metagenomic techniques. We specifically focused on extracellular electron transfer (EET) function and stress resistance, which affect the performance and stability of MECs. Community profiling revealed that the family Geobacteraceae was the key EAM taxon in all biofilms, with Geobacter as the dominant genus. The c-type cytochrome gene imcH showed universal importance for Geobacteraceae EET and was utilized as a marker gene to evaluate the EET potential of EAMs. Additionally, stress response functional genes were used to assess the stress resistance potential of Geobacter species. Comparative analysis of imcH gene abundance revealed that EAMs with comparable overall EET potential could be enriched from artificial and natural inocula (P > 0.05). However, quantification of stress response gene copy numbers in the genomes demonstrated that EAMs originating from natural inocula possessed superior stress resistance potential (196 vs. 163). Overall, this study provides novel perspectives on the inoculum effect in bioreactors and offers theoretical guidance for selecting inoculum in environmental engineering applications.
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Biofilmes , Reatores Biológicos , Reatores Biológicos/microbiologia , Geobacter/fisiologia , Geobacter/genética , Metagenômica , Estresse Fisiológico , Fontes de Energia Bioelétrica , Transporte de ElétronsRESUMO
INTRODUCTION: Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo. METHODS: Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology. RESULTS: HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice. CONCLUSION: The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.
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Apoptose , Carcinoma de Células Escamosas , Neoplasias Laríngeas , Infecções por Papillomavirus , Tolerância a Radiação , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/virologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/virologia , Proteína Supressora de Tumor p53/metabolismo , Infecções por Papillomavirus/radioterapia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Apoptose/efeitos da radiação , Animais , Linhagem Celular Tumoral , Reação em Cadeia da Polimerase em Tempo Real , Masculino , Camundongos , Citometria de Fluxo , Western Blotting , Proteína do Retinoblastoma/metabolismoRESUMO
BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.
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Cardiomiopatias , Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Cardiomiopatias/tratamento farmacológico , Sepse/tratamento farmacológico , Sepse/complicações , Camundongos , Masculino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Lipoilação/efeitos dos fármacos , Ratos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Lipopolissacarídeos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-18/metabolismoRESUMO
In contemporary autonomous driving systems relying on sensor fusion, traditional digital processors encounter challenges associated with analogue-to-digital conversion and iterative vector-matrix operations, which are encumbered by limitations in terms of response time and energy consumption. In this study, we present an analogue Kalman filter circuit based on molybdenum disulfide (MoS2) memtransistor, designed to accelerate sensor fusion for precise localization in autonomous vehicle applications. The nonvolatile memory characteristics of the memtransistor allow for the storage of a fixed Kalman gain, which eliminates the data convergence and thus accelerates the processing speeds. Additionally, the modulation of multiple conductance states by the gate terminal enables fast adaptability to diverse autonomous driving scenarios by tuning multiple Kalman filter gains. Our proposed analogue Kalman filter circuit accurately estimates the position coordinates of target vehicles by fusing sensor data from light detection and ranging (LiDAR), millimeter-wave radar (Radar), and camera, and it successfully solves real-word problems in a signal-free crossroad intersection. Notably, our system achieves a 1000-fold improvement in energy efficiency compared to that of digital circuits. This work underscores the viability of a memtransistor for achieving fast, energy-efficient real-time sensing, and continuous signal processing in advanced sensor fusion technology.
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The production of short-chain fatty acids (SCFAs) is constrained by substrate availability and the increased fractional pressure of H2 emitted by acidogenic/fermentative bacteria during anaerobic fermentation of waste activated sludge (WAS). This study introduced a novel approach employing zero-valent iron (ZVI)-activated sulfite pretreatment combined with H2-consuming sulfate-reducing bacteria (SRB) mediation to improve SCFAs, especially acetate production from WAS fermentation. Experimental results showed that the combined ZVI-activated sulfite and incomplete-oxidative SRB (io-SRB) process achieved a peak SCFAs production of 868.11 mg COD/L, with acetate accounting for 80.55 %, which was 7.90- and 2.18-fold higher than that obtained from raw WAS fermentation, respectively. This could be firstly attributed to the SO4- and OH generated by ZVI-activated sulfite, which significantly promoted WAS decomposition, e.g., soluble proteins and carbohydrates increased 14.3- and 10.8-fold, respectively, over those in raw WAS. The biodegradation of dissolved organic matter was subsequently enhanced by the synergistic interaction and H2 transfer between anaerobic fermentation bacteria (AFB) and io-SRB. The positive and negative correlations among AFB, nitrate-reducing bacteria (NRB) and the io-SRB consortia were revealed by molecular ecological network (MEN) and Mantel test. Moreover, the expression of functional genes was also improved, for instance, in relation to acetate formation, the relative abundances of phosphate acetyltransferase and acetate kinase was 0.002 % and 0.005 % higher than that in the control test, respectively. These findings emphasized the importance of sulfate radicals-based oxidation pretreatment and the collaborative relationships of multifunctional microbes on the value-added chemicals and energy recovery from sludge fermentation.
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Ácidos Graxos Voláteis , Fermentação , Esgotos , Sulfitos , Eliminação de Resíduos Líquidos , Esgotos/microbiologia , Sulfitos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Eliminação de Resíduos Líquidos/métodos , Sulfatos/metabolismo , Hidrogênio/metabolismo , Bactérias/metabolismo , Ferro/metabolismoRESUMO
In this paper we propose an approach for solving systems of nonlinear equations without computing function derivatives. Motivated by the application area of tomographic absorption spectroscopy, which is a highly-nonlinear problem with variables coupling, we consider a situation where straightforward translation to a fixed point problem is not possible because the operators that represent the relevant systems of nonlinear equations are not self-mappings, i.e., they operate between spaces of different dimensions. To overcome this difficulty we suggest an "alternating common fixed points algorithm" that acts alternatingly on the different vector variables. This approach translates the original problem to a common fixed point problem for which iterative algorithms are abound and exhibits a viable alternative to translation to an optimization problem, which usually requires derivatives information. However, to apply any of these iterative algorithms requires to ascertain the conditions that appear in their convergence theorems. To circumvent the need to verify conditions for convergence, we propose and motivate a derivative-free algorithm that better suits the tomographic absorption spectroscopy problem at hand and is even further improved by applying to it the superiorization approach. This is presented along with experimental results that demonstrate our approach.
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ETHNOPHARMACOLOGICAL RELEVANCE: The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. AIM OF THE STUDY: This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. MATERIALS AND METHODS: Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthriticï¼CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. RESULTS: Metabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-κB, and STAT3 through hydrogen bonds, C-H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. CONCLUSION: GLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1ß signaling pathway and reduction in M1 macrophage polarization.
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Artrite Experimental , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Ratos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Artrite Reumatoide/tratamento farmacológico , Ratos Sprague-Dawley , Camundongos , Antirreumáticos/farmacologia , Antirreumáticos/isolamento & purificação , Antirreumáticos/química , AcetatosRESUMO
CaWRKY40 coordinately activates pepper immunity against Ralstonia solanacearum infection (RSI) and high temperature stress (HTS), forms positive feedback loops with other positive regulators and is promoted by CaWRKY27b/CaWRKY28 through physical interactions; however, whether and how it is regulated by negative regulators to function appropriately remain unclear. Herein, we provide evidence that CaWRKY40 is repressed by a SALT TOLERANCE HOMOLOG2 in pepper (CaSTH2). Our data from gene silencing and transient overexpression in pepper and epoptic overexpression in Nicotiana benthamiana plants showed that CaSTH2 acted as negative regulator in immunity against RSI and thermotolerance. Our data from BiFC, CoIP, pull down, and MST indicate that CaSTH2 interacted with CaWRKY40, by which CaWRKY40 was prevented from activating immunity or thermotolerance-related genes. It was also found that CaSTH2 repressed CaWRKY40 at least partially through blocking interaction of CaWRKY40 with CaWRKY27b/CaWRKY28, but not through directly repressing binding of CaWRKY40 to its target genes. The results of study provide new insight into the mechanisms underlying the coordination of pepper immunity and thermotolerance.
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This Letter reports a novel, to our knowledge, event-triggered background-oriented schlieren (EBOS) technique using a combination of an event-triggered camera and pulsed laser speckle projection. The BOS images are reconstructed using the event data generated by the pulsed laser speckle projection and then processed to obtain the density and temperature distribution of the flow. This technique enables continuous visualization and recording of flows at kFPS frame rates with a very low cost, breaking through the short operating times of existing high-frame-rate BOSs. To examine the event-triggered BOS technique, tests are conducted on a hot air gun. The measured temperature distribution coincides with the thermocouple data with an error of no more than 10.8%. Measurements taken during the start-up of the hot air gun demonstrate that the presented technique can measure the evolution of the jet temperature for at least 150â s, as well as capture the localized unsteady turbulent structure in the heated jet flow.
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BACKGROUND: At present, there are few studies on the technical requirements of manual bedside placement of post-pyloric tube in Intensive Care Unit patients. OBJECTIVE: To investigate the application value of downward tract adherence method in the manual bedside placement of jejunal tubes. METHODS: In the downward group, 160 patients underwent manual bedside placement of jejunal tubes by a downward tract adherence method. In the conventional group, 144 patients were treated with conventional gas injection during the placement. The success rate, average time, and adverse reactions of the placement in the two groups were investigated and compared. RESULTS: The success rate of the placement in the downward group was significantly higher (95% vs. 75%, P< 0.001) and the average time for the successful placement was shortened (23 ± 5.91 min vs. 26 ± 5.49 min, P= 0.025) than that in the conventional group. No treatment-related adverse reactions occurred in either group, and there were also no significant differences in vital sign changes. CONCLUSIONS: The use of the downward tract adherence method in the manual bedside placement of postpyloric tubes for the intensive care patients at the bedside has a higher success rate, effectivity and safety.
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Unidades de Terapia Intensiva , Intubação Gastrointestinal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Intubação Gastrointestinal/métodos , Intubação Gastrointestinal/instrumentação , Idoso , Adulto , Nutrição Enteral/métodos , Nutrição Enteral/instrumentação , Cuidados Críticos/métodosRESUMO
To challenge the invasion of various pathogens, plants re-direct their resources from plant growth to an innate immune defence system. However, the underlying mechanism that coordinates the induction of the host immune response and the suppression of plant growth remains unclear. Here we demonstrate that an auxin response factor, CaARF9, has dual roles in enhancing the immune resistance to Ralstonia solanacearum infection and in retarding plant growth by repressing the expression of its target genes as exemplified by Casmc4, CaLBD37, CaAPK1b and CaRROP1. The expression of these target genes not only stimulates plant growth but also negatively impacts pepper resistance to R. solanacearum. Under normal conditions, the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 is active when promoter-bound CaARF9 is complexed with CaIAA2. Under R. solanacearum infection, however, degradation of CaIAA2 is triggered by SA and JA-mediated signalling defence by the ubiquitin-proteasome system, which enables CaARF9 in the absence of CaIAA2 to repress the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 and, in turn, impeding plant growth while facilitating plant defence to R. solanacearum infection. Our findings uncover an exquisite mechanism underlying the trade-off between plant growth and immunity mediated by the transcriptional repressor CaARF9 and its deactivation when complexed with CaIAA2.
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Capsicum , Regulação da Expressão Gênica de Plantas , Doenças das Plantas , Imunidade Vegetal , Proteínas de Plantas , Ralstonia solanacearum , Ralstonia solanacearum/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Capsicum/genética , Capsicum/imunologia , Capsicum/crescimento & desenvolvimento , Capsicum/microbiologia , Capsicum/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Doenças das Plantas/genética , Imunidade Vegetal/genética , Resistência à Doença/genéticaRESUMO
The production of formic acid via electrochemical CO2 reduction may serve as a key link for the carbon cycle in the formic acid economy, yet its practical feasibility is largely limited by the quantity and concentration of the product. Here we demonstrate continuous electrochemical CO2 reduction for formic acid production at 2â M at an industrial-level current densities (i.e., 200â mA cm-2 ) for 300â h on membrane electrode assembly using scalable lattice-distorted bismuth catalysts. The optimized catalysts also enable a Faradaic efficiency for formate of 94.2 % and a highest partial formate current density of 1.16â A cm-2 , reaching a production rate of 21.7â mmol cm-2 h-1 . To assess the practicality of this system, we perform a comprehensive techno-economic analysis and life cycle assessment, showing that our approach can potentially substitute conventional methyl formate hydrolysis for industrial formic acid production. Furthermore, the resultant formic acid serves as direct fuel for air-breathing formic acid fuel cells, boasting a power density of 55â mW cm-2 and an exceptional thermal efficiency of 20.1 %.
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Miniaturized spectrometers are of immense interest for various on-chip and implantable photonic and optoelectronic applications. State-of-the-art conventional spectrometer designs rely heavily on bulky dispersive components (such as gratings, photodetector arrays, and interferometric optics) to capture different input spectral components that increase their integration complexity. Here, we report a high-performance broadband spectrometer based on a simple and compact van der Waals heterostructure diode, leveraging a careful selection of active van der Waals materials- molybdenum disulfide and black phosphorus, their electrically tunable photoresponse, and advanced computational algorithms for spectral reconstruction. We achieve remarkably high peak wavelength accuracy of ~2 nanometers, and broad operation bandwidth spanning from ~500 to 1600 nanometers in a device with a ~ 30×20 µm2 footprint. This diode-based spectrometer scheme with broadband operation offers an attractive pathway for various applications, such as sensing, surveillance and spectral imaging.
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For reliable tomographic measurements the underlying 2D images from different viewing angles must be matched in terms of signal detection characteristics. Non-linearity effects introduced by intensified cameras and spatial intensity variations induced from inhomogeneous transmission of the optical setup can lead, if not corrected, to a biased tomographic reconstruction result. This paper presents a complete correction procedure consisting of a combination of a non-linearity and flatfield correction for a tomographic optical setup employing imaging fiber bundles and four intensified cameras. Influencing parameters on the camera non-linearity are investigated and discussed. The correction procedure is applied to 3D temperature measurements by two-color pyrometry and compared to results without correction. The present paper may serve as a guideline for an appropriate correction procedure for any type of measurement involving optical tomography and intensified cameras.
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The intrinsic roadblocks for designing promising Pt-based oxygen reduction reaction (ORR) catalysts emanate from the strong scaling relationship and activity-stability-cost trade-offs. Here, a carbon-supported Pt nanoparticle and a Mn single atom (PtNP-MnSA/C) as in situ constructed PtNP-MnSA pairs are demonstrated to be an efficient catalyst to circumvent the above seesaws with only â¼4 wt % Pt loadings. Experimental and theoretical investigations suggest that MnSA functions not only as the "assist" for Pt sites to cooperatively facilitate the dissociation of O2 due to the strong electronic polarization, affording the dissociative pathway with reduced H2O2 production, but also as an electronic structure "modulator" to downshift the d-band center of Pt sites, alleviating the overbinding of oxygen-containing intermediates. More importantly, MnSA also serves as a "stabilizer" to endow PtNP-MnSA/C with excellent structural stability and low Fenton-like reactivity, resisting the fast demetalation of metal sites. As a result, PtNPs-MnSA/C shows promising ORR performance with a half-wave potential of 0.93 V vs reversible hydrogen electrode and a high mass activity of 1.77 A/mgPt at 0.9 V in acid media, which is 19 times higher than that of commercial Pt/C and only declines by 5% after 80,000 potential cycles. Specifically, PtNPs-MnSA/C reaches a power density of 1214 mW/cm2 at 2.87 A/cm2 in an H2-O2 fuel cell.
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BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.
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Artrite Experimental , Artrite Reumatoide , Berberina , MicroRNAs , Animais , Camundongos , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Berberina/farmacologia , Linfócitos T CD4-Positivos , Modelos Animais de Doenças , Macrófagos , MicroRNAs/metabolismoRESUMO
High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.