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Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy.
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Antineoplásicos/farmacologia , Antígeno B7-H1/genética , Antígeno CTLA-4/genética , Regulação Neoplásica da Expressão Gênica , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Glicosilação , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/efeitos dos fármacos , Glândulas Mamárias Humanas/imunologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos NOD , Fosforilação , Serina/metabolismo , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologiaRESUMO
Although various types of bifacial solar cells exist, few studies have been conducted on bifacial semitransparent CuInSe2 solar cells (BS-CISe SCs) despite the attractive potential in power generation from both sides in an albedo environment. The optimized BS-CISe SCs with 300 and 800 nm-thick absorber via a streamlined single-stage co-evaporation process exhibit a power conversion efficiency (PCE) of 6.32% and 10.6%, respectively. When double-sided total 2.0 sun illumination is assumed in an albedo environment, the bifacial power generation densities (BPGD) of them increases to 9.41% and 13.9%. Four-terminal bifacial semitransparent tandem solar cells (4T-BST SCs) are fabricated to increase the BPGD by mechanically stacking a BS-perovskite (PVK) top cell on top of a BS-CISe bottom cell with the 300 and 800 nm-thick absorber layers. When summed up, the best top and bottom cell PCEs of the 4T-BST SC with 300 and 800 nm-thick BS-CISe SC are 18.8% and 21.1%, respectively. However, the practical BPGD values of the 4T-BST SC under total 2 sun illumination are interestingly 23.4% and 24.4%, respectively. This is because the BS-CISe bottom cell's thickness affects how much rear-side illumination is transmitted to the BS-PVK top cell, increasing its current density and BPGD.
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The Cu(II)/H2O2 system is recognized for its potential to degrade recalcitrant organic contaminants and inactivate microorganisms in wastewater. We investigated its unique dual oxidation strategy involving the selective oxidation of copper-complexing ligands and enhanced oxidation of nonchelated organic compounds. L-Histidine (His) and benzoic acid (BA) served as model compounds for basic biomolecular ligands and recalcitrant organic contaminants, respectively. In the presence of both His and BA, the Cu(II)/H2O2 system rapidly degraded His complexed with copper ions within 30 s; however, BA degraded gradually with a 2.3-fold efficiency compared with that in the absence of His. The primary oxidant responsible was the trivalent copper ion [Cu(III)], not hydroxyl radical (â¢OH), as evidenced by â¢OH scavenging, hydroxylated BA isomer comparison with UV/H2O2 (a â¢OH generating system), electron paramagnetic resonance, and colorimetric Cu(III) detection via periodate complexation. Cu(III) selectively oxidized His owing to its strong chelation with copper ions, even in the presence of excess tert-butyl alcohol. This selectivity extended to other copper-complexing ligands, including L-asparagine and L-aspartic acid. The presence of His facilitated H2O2-mediated Cu(II) reduction and increased Cu(III) production, thereby enhancing the degradation of BA and pharmaceuticals. Thus, the Cu(II)/H2O2 system is a promising option for dual-target oxidation in diverse applications.
Assuntos
Cobre , Histidina , Peróxido de Hidrogênio , Oxirredução , Cobre/química , Histidina/química , Peróxido de Hidrogênio/química , Catálise , Ferro/química , Radical Hidroxila/química , Ácido Benzoico/químicaRESUMO
We utilized amino acid (AA) and carbon stable isotope analyses to characterize phytoplankton-derived organic matter (OM) and trace the sources of organic carbon in the Amundsen Sea. Carbon isotope ratios of particulate organic carbon (δ13C-POC) range from -28.7‱ to -23.1‱, indicating that particulate organic matter originated primarily from phytoplankton. The dissolved organic carbon isotope (δ13C-DOC) signature (-27.1 to -21.0‱) observed in the sea-ice melting system suggests that meltwater contributes to the DOC supply of the Amundsen Sea together with OM produced by phytoplankton. A negative correlation between the degradation index and δ13C-POC indicates that the quality of OM significantly influences isotopic fractionation (r2 = 0.59, p < 0.001). The AA distribution in the Amundsen Sea (5.43 ± 3.19 µM) was significantly larger than previously reported in the Southern Ocean and was associated with phytoplankton biomass (r2 = 0.49, p < 0.01). Under conditions dominated by P. antarctica (DI = 2.29 ± 2.30), OM exhibited greater lability compared to conditions co-dominated by diatoms and D. speculum (DI = 0.04 ± 3.64). These results highlight the important role of P. antarctica in influencing the properties of OM, suggesting potential impacts on carbon cycling and microbial metabolic activity in the Amundsen Sea.
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Aminoácidos , Isótopos de Carbono , Carbono , Fitoplâncton , Fitoplâncton/metabolismo , Isótopos de Carbono/análise , Aminoácidos/metabolismo , Aminoácidos/análise , Carbono/metabolismo , Oceanos e Mares , Água do Mar/química , Biomassa , Diatomáceas/metabolismoRESUMO
In traditional power grids, the unidirectional flow of energy and information has led to a decrease in efficiency. To address this issue, the concept of microgrids with bidirectional flow and independent power sources has been introduced. The components of a microgrid utilize various IoT protocols such as OPC-UA, MQTT, and DDS to implement bidirectional communication, enabling seamless network communication among different elements within the microgrid. Technological innovation, however, has simultaneously given rise to security issues in the communication system of microgrids. The use of IoT protocols creates vulnerabilities that malicious hackers may exploit to eavesdrop on data or attempt unauthorized control of microgrid devices. Therefore, monitoring and controlling security vulnerabilities is essential to prevent intrusion threats and enhance cyber resilience in the stable and efficient operation of microgrid systems. In this study, we propose an RBAC-based security approach on top of DDS protocols in microgrid systems. The proposed approach allocates roles to users or devices and grants various permissions for access control. DDS subscribers request access to topics and publishers request access to evaluations from the role repository using XACML. The overall implementation model is designed for the publisher to receive XACML transmitted from the repository and perform policy decision making and enforcement. By applying these methods, security vulnerabilities in communication between IoT devices can be reduced, and cyber resilience can be enhanced.
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Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe metabolic acidosis, acute kidney injury, and death. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. This study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations.
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Etilenoglicol , Glicolatos , Animais , Etilenoglicol/intoxicação , Gatos , República da Coreia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida/métodosRESUMO
BACKGROUND: The cerebellum is an area of the brain that is prone to damage in individuals with Alzheimer's disease (AD). As a non-pharmacological intervention for AD, exercise training has shown an ameliorating effect on AD pathology; however, the target regions have mostly been the cerebral cortex and hippocampus. The main aim of this study was to explore the influence of 12 weeks of treadmill running on the accumulation of AD-related proteins, dysfunction of mitochondria, and subsequent neuronal cell death in the cerebellum of triple transgenic (3xTg-AD) mice. METHODS: Four-month-old 3xTg-AD mice were allocated into two groups: an AD control group (AD, n = 10) and an AD exercise group (AD-Exe, n = 10). The AD-Exe mice underwent training on a motorized animal treadmill 5 days a week for 12 weeks. After sacrifice, the cerebellum was collected and biochemically analyzed. RESULTS: The AD-Exe mice expressed reduced levels of extracellular ß-amyloid plaques and phosphorylated tau (p-tau), and showed improved Purkinje cell survival and mitochondrial function compared with AD mice. CONCLUSIONS: These findings suggest that engaging in exercise training can offer protection against the progression of AD in the cerebellum by enhancing mitochondrial function and promoting cell survival.
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Doença de Alzheimer , Humanos , Animais , Camundongos , Lactente , Sobrevivência Celular , Cerebelo , Animais Geneticamente Modificados , MitocôndriasRESUMO
Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial-mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.
Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , RNA Interferente Pequeno/genéticaRESUMO
The development of biological technologies in genomics, proteomics, and bioinformatics has led to the identification and characterization of the complete set of coding genes and their roles in various cellular pathways in cancer. Nevertheless, the cellular pathways have not been fully figured out like a jigsaw puzzle with missing pieces. The discovery of noncoding RNAs including microRNAs (miRNAs) has provided the missing pieces of the cellular pathways. Likewise, miRNAs have settled many questions of inexplicable patches in the endoplasmic reticulum (ER) stress pathways. The ER stress-caused pathways typified by the unfolded protein response (UPR) are pivotal processes for cellular homeostasis and survival, rectifying uncontrolled proteostasis and determining the cell fate. Although various factors and pathways have been studied and characterized, the understanding of the ER stress requires more wedges to fill the cracks of knowledge about the ER stress pathways. Moreover, the roles of the ER stress and UPR are still controversial in cancer despite their strong potential to promote cancer. The noncoding RNAs, in particular, miRNAs aid in a better understanding of the ER stress and its role in cancer. In this review, miRNAs that are the more-investigated subtype of noncoding RNAs are focused on the interpretation of the ER stress in cancer, following the introduction of miRNA and ER stress.
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Estresse do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias/patologia , Resposta a Proteínas não Dobradas , Animais , Humanos , Neoplasias/etiologia , Neoplasias/metabolismoRESUMO
BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).
Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/cirurgia , Azia/tratamento farmacológico , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Baclofeno/uso terapêutico , Desipramina/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Fundoplicatura , Refluxo Gastroesofágico/complicações , Azia/etiologia , Azia/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/uso terapêutico , Qualidade de Vida , Inquéritos e Questionários , VeteranosRESUMO
As the measurement scale shrinks, the reliability of nanoscale measurement is even more crucial for a variety of applications, including semiconductor electronics, optical metamaterials, and sensors. Specifically, it is difficult to measure the nanoscale morphology at the exact location though it is required for novel applications based on hybrid nanostructures combined with 2D materials. Here, we introduce an advanced hybrid positioning system to measure the region of interest with enhanced speed and high precision. A 5-axis positioning stage (XYZ, R, gripper) makes it possible to align the sample within a 10-µm field of view (FOV) in both the scanning electron microscope (SEM) and the atomic force microscope (AFM). The reproducibility of the sample position was investigated by comparing marker patterns and denting points between the SEM and AFM, revealing an accuracy of 6.5 ± 2.1 µm for the x-axis and 4.5 ± 1.7 µm for the y-axis after 12 repetitions. By applying a different measurement process according to the characteristics of 2D materials, various information such as height, length, or roughness about MoTe2 rods and MoS2 film was obtained in the same measurement area. As a consequence, overlaid two images can be obtained for detailed information about 2D materials.
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The volatile compounds and sensory profiles of 18 different types of distilled soju, chosen with regard to various raw materials and distillation methods (atmospheric vs. vacuum), were explored using headspace solid-phase microextraction (HS-SPME) with gas chromatography-mass spectrometry (GC-MS) and descriptive analysis. General chemical properties such as pH, total acidity (TA), total soluble solids (°Brix), and lactic acid concentration were also determined. A total of 56 volatile compounds, comprising 31 esters, 11 alcohols, 1 acid, 4 aldehydes, 3 ketones, and 6 miscellaneous compounds, were identified. From the principal component analysis (PCA) of the volatile data, samples made using atmospheric distillation such as MSO and PJU showed a clear difference from decompressed distillation samples. Based on the PCA of the sensory data, there was also a clear distinction between samples by their distillation method. To explore relationships among chemical, volatile, and sensory data sets, multiple factor analysis (MFA) was applied. Yeasty and earthy flavors showed a close relationship with 1-nonanol, octatonic acid, and longer-chain esters such as ethyl phenylacetate and ethyl tetradecanoate, and with chemical parameters such as TA, °Brix, and lactic acid.
Assuntos
Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Ésteres/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácido Láctico/análise , República da Coreia , Microextração em Fase Sólida/métodos , Compostos Orgânicos Voláteis/análiseRESUMO
The precise self-assembly of block copolymers (BCPs) and inorganic nanoparticles (NPs) under 3D confinement offers microparticles with programmable nanostructures and functionalities. Here, fluorescence-switchable hybrid microspheres are developed by forming doubly alternating arrays of Au NPs and CdSe/ZnS quantum dots (QDs) within polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) BCP domains. These doubly alternating arrays afford controlled nonradiative energy transfer (NRET) between the QDs and Au NPs that is dependent on the layer-to-layer distance. Solvent-selective swelling of the hybrid particles tunes the distance between layers, modulating their NRET behavior and affording switchable fluorescence. The particle fluorescence is "OFF" in water through strong NRET from the QDs to Au NPs, but is "ON" in alcohols due to the increased distance between the Au NP and QD arrays in the swollen P4VP domains. The experimentally observed NRET intensity as a function of interparticle distance shows larger quenching efficiencies than those theoretically predicted due to the enhanced quenching within a 3D-confined system. Finally, the robust and reversible fluorescence switching of the hybrid particles in different solvents is demonstrated, highlighting their potentials for bioimaging, sensing, and diagnostic applications.
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Nanopartículas , Nanoestruturas , Pontos Quânticos , Fluorescência , PolímerosRESUMO
A Gram-negative, aerobic, and long rod-shaped bacterium, designated as H33E-04T, was isolated from the soil of reclaimed land, Republic of Korea. The strain grew at a temperature range of 15-40 °C, pH 5.0-10.0, and 0-2% NaCl (w/v). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain H33E-04T was in the same clade with Chitinophaga pinensis DSM 2588T, Chitinophaga filiformis IFO 15056T, and Chitinophaga ginsengisoli Gsoil 052T with 98.4%, 97.9%, and 97.8% sequence similarities, respectively. The de novo genome assembly revealed that the DNA G + C content of the strain was 46.2 mol%. Comparative genome analysis between strain H33E-04T and C. pinensis DSM 2588 T showed that the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values were 79.9% and 23.4%, respectively. The major respiratory quinone was menaquinone-7 (MK-7) and the predominant cellular fatty acids were iso-C15:0 (31.7%), C16:1 ω5c (31.2%), and iso-C17:0 3-OH (11.8%), supporting the affiliation of strain H33E-04T with the genus Chitinophaga. Based on phylogenetic, physiological, and chemotaxonomic characteristics, strain H33E-04T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga agri sp. nov. is proposed. The type strain of Chitinophaga agri is H33E-04T (= KACC 21303T = NBRC114512T).
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Gammaproteobacteria/classificação , Filogenia , Microbiologia do Solo , Bacteroidetes/classificação , Bacteroidetes/genética , Composição de Bases , Gammaproteobacteria/genética , RNA Ribossômico 16S/genética , Especificidade da EspécieRESUMO
A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated KIS59-12T, was isolated from a soil sample collected on Hodo island, Boryeong, Republic of Korea. The strain grew at 10-33 °C, pH 6.0-7.5 and with 0-4â% NaCl (w/v). Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain KIS59-12T was in the same clade as Arachidicoccus rhizosphaerae Vu-144T and Arachidicoccus ginsenosidivorans Gsoil809T with 97.5 and 97.2â% sequence similarity, respectively. Comparative genome analysis between strain KIS59-12T and A. rhizosphaerae Vu-144T showed that average nucleotide identity value was 69.4â% and the digital DNA-DNA hybridization value was 19.1â%. The major respiratory quinone was menaquinone-7. The major polar lipids were phosphatidylethanolamine and an unknown polar lipid. The predominant cellular fatty acids were iso-C15â:â0, iso-C15â:â1 G and iso-C17â:â0 3-OH, which supported the affiliation of strain KIS59-12T with the genus Arachidicoccus. The major polyamines were homospermidine and putrescine. The genomic DNA G+C content was 36.4âmol%. On the basis of phylogenetic, physiological and chemotaxonomic characteristics, strain KIS59-12T represents a novel species of the genus Arachidicoccus, for which the name Arachidicoccus soli sp. nov. is proposed. The type strain of Arachidicoccus soli is KIS59-12T (=KACC 17340T=NBRC 113161T).
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Bacteroidetes/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Ilhas , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Oxidation of micropollutants (MPs) by ozonation proceeds via the reactions with molecular ozone (O3) and hydroxyl radicals (â¢OH). To predict MP abatement during ozonation, a model that can accurately predict oxidant exposures (i.e., ∫0t[O3]dt⢠and⢠∫0t[Oâ¢H]dt) needs to be developed. This study demonstrates machine learning models based on the random forest (RF) algorithm to output oxidant exposures from water quality parameters (input variables) that include pH, alkalinity, dissolved organic carbon concentration, and fluorescence excitation-emission matrix (FEEM) data (to characterize organic matter). To develop the models, 60 different samples of natural waters and wastewater effluents were collected and characterized, and the oxidant exposures in each sample were determined at a specific O3 dose (2.5 mg/L). Four RF models were developed depending on how FEEM data were utilized (i.e., one model free of FEEM data, and three other models that used FEEM data of different resolutions). The regression performance and Akaike information criterion (AIC) were evaluated for each model. The models using high-resolution FEEM data generally exhibited high prediction accuracy with reasonable AIC values, implying that organic matter characteristics quantified by FEEM can be important factors to improve the accuracy of the prediction model. The developed models can be applied to predict the abatement of MPs in drinking water and wastewater ozonation processes and to optimize the O3 dose for the intended removal of target MPs. The machine learning models using higher-resolution FEEM data offer more accurate prediction by better calculating the complex nonlinear relationship between organic characteristics and oxidant exposures.
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Ozônio , Poluentes Químicos da Água , Purificação da Água , Aprendizado de Máquina , Oxidantes , Oxirredução , Águas Residuárias/análise , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND AND AIM: We aimed to develop a convolutional neural network (CNN)-based object detection model for the discrimination of gastric subepithelial tumors, such as gastrointestinal stromal tumors (GISTs), and leiomyomas, in endoscopic ultrasound (EUS) images. METHODS: We used 376 images from 114 patients with histologically confirmed gastric GIST or leiomyoma to train the EUS-CNN. We constructed the EUS-CNN using an EfficientNet CNN model for feature extraction and a weighted bi-directional feature pyramid network for object detection. We assessed the performance of our EUS-CNN by calculating its accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC) using a validation set of 170 images from 54 patients. Four EUS experts and 15 EUS trainees were asked to judge the same validation dataset, and the diagnostic yields were compared between the EUS-CNN and human assessments. RESULTS: In the per-image analysis, the sensitivity, specificity, accuracy, and AUC of our EUS-CNN were 95.6%, 82.1%, 91.2%, and 0.9234, respectively. In the per-patient analysis, the sensitivity, specificity, accuracy, and AUC for our object detection model were 100.0%, 85.7%, 96.3%, and 0.9929, respectively. The EUS-CNN outperformed human assessment in terms of accuracy, sensitivity, and negative predictive value. CONCLUSIONS: We developed the EUS-CNN system, which demonstrated high diagnostic ability for gastric GIST prediction. This EUS-CNN system can be helpful not only for less-experienced endoscopists but also for experienced ones. Additional EUS image accumulation and prospective studies are required alongside validation in a large multicenter trial.
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Tumores do Estroma Gastrointestinal , Redes Neurais de Computação , Endossonografia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Humanos , Reprodutibilidade dos TestesRESUMO
Visual function depends on the intimate structural, functional and metabolic interactions between the retinal pigment epithelium (RPE) and the neural retina. The daily phagocytosis of the photoreceptor outer segment tips by the overlaying RPE provides essential nutrients for the RPE itself and photoreceptors through intricate metabolic synergy. Age-related retinal changes are often characterized by metabolic dysregulation contributing to increased lipid accumulation and peroxidation as well as the release of proinflammatory cytokines. LGM2605 is a synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant and anti-inflammatory properties demonstrated in diverse in vitro and in vivo inflammatory disease models. In these studies, we tested the hypothesis that LGM2605 may be an attractive small-scale therapeutic that protects RPE against inflammation and restores its metabolic capacity under lipid overload. Using an in vitro model in which loss of the autophagy protein, LC3B, results in defective phagosome degradation and metabolic dysregulation, we show that lipid overload results in increased gasdermin cleavage, IL-1 ß release, lipid accumulation and decreased oxidative capacity. The addition of LGM2605 resulted in enhanced mitochondrial capacity, decreased lipid accumulation and amelioration of IL-1 ß release in a model of defective lipid homeostasis. Collectively, these studies suggest that lipid overload decreases mitochondrial function and increases the inflammatory response, with LGM2605 acting as a protective agent.
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Lignanas/metabolismo , Metabolismo dos Lipídeos , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Pigmentos da Retina/metabolismo , Antioxidantes/metabolismo , Autofagia , Butileno Glicóis/farmacologia , Linhagem Celular , Citocinas , Expressão Gênica , Glucosídeos/farmacologia , Humanos , Inflamação/metabolismo , Lignanas/química , Lipídeos , Mitocôndrias/metabolismo , Oxirredução , Fagocitose , Fagossomos/metabolismo , Pigmentos da Retina/genéticaRESUMO
Quantum dots (QDs) are emerging photovoltaic materials that display exclusive characteristics that can be adjusted through modification of their size and surface chemistry. However, designing a QD-based optoelectronic device requires specialized approaches compared with designing conventional bulk-based solar cells. In this paper, design considerations for QD thin-film solar cells are introduced from two different viewpoints: optics and electrics. The confined energy level of QDs contributes to the adjustment of their band alignment, enabling their absorption characteristics to be adapted to a specific device purpose. However, the materials selected for this energy adjustment can increase the light loss induced by interface reflection. Thus, management of the light path is important for optical QD solar cell design, whereas surface modification is a crucial issue for the electrical design of QD solar cells. QD thin-film solar cell architectures are fabricated as a heterojunction today, and ligand exchange provides suitable doping states and enhanced carrier transfer for the junction. Lastly, the stability issues and methods on QD thin-film solar cells are surveyed. Through these strategies, a QD solar cell study can provide valuable insights for future-oriented solar cell technology.
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The exchange interaction governs static and dynamic magnetism. This fundamental interaction comes in two flavours-symmetric and antisymmetric. The symmetric interaction leads to ferro- and antiferromagnetism, and the antisymmetric interaction has attracted significant interest owing to its major role in promoting topologically non-trivial spin textures that promise fast, energy-efficient devices. So far, the antisymmetric exchange interaction has been found to be rather short ranged and limited to a single magnetic layer. Here we report a long-range antisymmetric interlayer exchange interaction in perpendicularly magnetized synthetic antiferromagnets with parallel and antiparallel magnetization alignments. Asymmetric hysteresis loops under an in-plane field reveal a unidirectional and chiral nature of this interaction, which results in canted magnetic structures. We explain our results by considering spin-orbit coupling combined with reduced symmetry in multilayers. Our discovery of a long-range chiral interaction provides an additional handle to engineer magnetic structures and could enable three-dimensional topological structures.