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Toll-like receptors (TLRs) play a pivotal role in initiating immune responses, particularly in the context of inflammation. However, an excessive inflammation can detrimentally affect the immune homeostasis Thus, it is important to regulate TLR signaling pathways appropriately. Gingerenone A (GIA), a bioactive compound derived from ginger, has garnered significant attention due to its potential anti-inflammatory properties. In this study, we investigate modulatory effects of GIA on TLR signaling pathways. Results showed that GIA effectively suppressed TLR-mediated inflammatory responses by modulating key signaling molecules such as nuclear factor kappa B and interferon regulatory factor 3. These results indicate that GIA is a novel regulator of TLR signaling, offering promising avenues for the development of new anti-inflammatory agents.

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As perovskite solar device is burgeoning photoelectronic device, numerous studies to optimize perovskite solar device have been demonstrated. Amongst various advantages from perovskite light absorbing layer, attractive property of tunable bandgap allowed perovskite to be adopted in many different fields. Easily tunable bandgap property of perovskite opened the wide application and to get the most out of its potential, many researchers contributed as well. By precursor composition engineering, narrow bandgap with bandgap of less than 1.4 eV and wide bandgap with bandgap of more than 1.7 eV were achieved. Optimization of both narrow and wide bandgap perovskite solar cell could pave the way to all-perovskite tandem solar cell which is combination of top cell with wide bandgap and bottom cell with narrow bandgap. This review highlights numerous efforts to advance device performance of both narrow and wide bandgap perovskite solar cell and how they challenged the issues. And finally, efforts to operate and utilize all-tandem perovskite device in real world will be discussed.

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Metal oxide films are essential in most electronic devices, yet they are typically deposited at elevated temperatures by using slow, vacuum-based processes. We printed native oxide films over large areas at ambient conditions by moving a molten metal meniscus across a target substrate. The oxide gently separates from the metal through fluid instabilities that occur in the meniscus, leading to uniform films free of liquid residue. The printed oxide has a metallic interlayer that renders the films highly conductive. The metallic character of the printed films promotes wetting of trace amounts of evaporated gold that would otherwise form disconnected islands on conventional oxide surfaces. The resulting ultrathin (<10 nanometers) conductors can be patterned into flexible circuits that are transparent, mechanically robust, and electrically stable, even at elevated temperatures.

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Heat dissipation is a natural consequence of operating any electronic system. In nearly all computing systems, such heat is usually minimized by design and cooling. Here, we show that the temporal dynamics of internally produced heat in electronic devices can be engineered to both encode information within a single device and process information across multiple devices. In our demonstration, electronic NbOx Mott neurons, integrated on a flexible organic substrate, exhibit 18 biomimetic neuronal behaviours and frequency-based nociception within a single component by exploiting both the thermal dynamics of the Mott transition and the dynamical thermal interactions with the organic substrate. Further, multiple interconnected Mott neurons spatiotemporally communicate purely via heat, which we use for graph optimization by consuming over 106 times less energy when compared with the best digital processors. Thus, exploiting natural thermal processes in computing can lead to functionally dense, energy-efficient and radically novel mixed-physics computing primitives.

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Memristor devices have diverse physical models depending on their structure. In addition, the physical properties of memristors are described using complex differential equations. Therefore, it is necessary to integrate the various models of memristor into an unified physics-based model. In this paper, we propose a physics-informed neural network (PINN)-based compact memristor model. PINNs can solve complex differential equations intuitively and with ease. This methodology is used to conduct memristor physical analysis. The weight and bias extracted from the PINN are implemented in a Verilog-A circuit simulator to predict memristor device characteristics. The accuracy of the proposed model is verified using two memristor devices. The results show that PINNs can be used to extensively integrate memristor device models.

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PURPOSE: Networking with other biodosimetry laboratories is necessary to assess the radiation exposure of many individuals in large-scale radiological accidents. The Korea biodosimetry network, K-BioDos, prepared harmonized scoring guidelines for dicentric chromosome assay to obtain homogeneous results within the network and investigated the efficiency of the guidelines. MATERIALS AND METHODS: Three laboratories in K-BioDos harmonized the scoring guidelines for dicentric chromosome assay. The results of scoring dicentric chromosomes using the harmonized scoring guidelines were compared with the laboratories' results using their own methods. Feedback was collected from the scorers following the three intercomparison exercises in 3 consecutive years. RESULTS: K-BioDos members showed comparable capacity to score dicentrics in the three exercises. However, the results of the K-BioDos guidelines showed no significant improvement over those of the scorers' own methods. According to the scorers, our harmonized guidelines led to more rejected metaphases and ultimately decreased the number of scorable metaphases compared with their own methods. Moreover, the scoring time was sometimes longer with the K-BioDos protocol because some scorers were not yet familiar with the guidelines, though most scorers reported that the time decreased or was unchanged. These challenges may cause low adherence to the guidelines. Most scorers expressed willingness to use the guidelines to select scorable metaphases or identify dicentrics for other biodosimetry works, whereas one did not want to use it due to the difference from their calibration curves. CONCLUSIONS: We identified potential resistance to following the harmonized guidelines and received requests for more detailed methods. Our findings suggest that the harmonized criteria should be continually updated, and education and training should be provided for all scorers. These changes could allow members within the biodosimetry network to successfully collaborate and support each other in large-scale radiological accidents.

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Energy-based computing is a promising approach for addressing the rising demand for solving NP-hard problems across diverse domains, including logistics, artificial intelligence, cryptography, and optimization. Probabilistic computing utilizing pbits, which can be manufactured using the semiconductor process and seamlessly integrated with conventional processing units, stands out as an efficient candidate to meet these demands. Here, we propose a novel pbit unit using an NbOx volatile memristor-based oscillator capable of generating probabilistic bits in a self-clocking manner. The noise-induced metal-insulator transition causes the probabilistic behavior, which can be effectively modeled using a multi-noise-induced stochastic process around the metal-insulator transition temperature. We demonstrate a memristive Boltzmann machine based on our proposed pbit and validate its feasibility by solving NP-hard problems. Furthermore, we propose a streamlined operation methodology that considers the autocorrelation of individual bits, enabling energy-efficient and high-performance probabilistic computing.

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Gamma-aminobutyric acid (GABA) is a crucial inhibitory neurotransmitter of the central nervous system. It modifies the signal threshold of the nociceptor, allowing it to react to external stimuli in various circumstances. Thus, GABAergic behaviors are critical characteristics of adaptive behavior in life. Here, a threshold-modulative artificial GABAergic nociceptor is reported for the first time at a Pt/Ti/Nb2 O5- x /Al2 O3- y /Pt/Ti (top to bottom) of the double charge trapping structure. The Al2 O3- y layer contains deep defect states that function similarly to the GABA neurotransmitter in modulating the signal threshold. Meanwhile, the Nb2 O5- x layer traps volatile charges and produces nociceptive behaviors. The combined dynamics of the two layers readily offer threshold-modulative GABAergic nociceptive behaviors. Based on these GABAergic behaviors, a method of implementing hot- and cold-sensitive thermoreceptors is demonstrated and shows its potential applications in advanced sensory devices.

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Since the heart pumps out the blood through the excitation-contraction coupling, simultaneous monitoring of the electrical and mechanical characteristics is beneficial for comprehensive diagnosis of cardiac disorders. Currently, these characteristics are monitored separately with electrocardiogram (ECG) and medical imaging techniques. This work presents a fully implantable device named mechano-electrocardiogram (MECG) sensor that can measure mechanocardiogram (MCG) and ECG together. The key to the success is fabrication of permeable electrodes on a single low-modulus porous nanofiber mat, which helps immediate adhesion of the sensor on the tissue. A strain-insensitive electrode is used as the ECG electrode and a strain-sensitive electrode is used for MCG. The MECG device is implanted subcutaneously in the skin above the heart of the rat. Through a vasopressor (phenylephrine) injection test, the MECG signals indicate that the MCG amplitude is related with blood pressure and the ECG peak interval is more related with heart rate. These results confirm that the MECG device is clinically meaningful for continuous and comprehensive monitoring of the electrical and mechanical characteristics of the heart.

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OBJECTIVES: Although pericardiectomy is an effective treatment for constrictive pericarditis (CP), clinical outcomes are not always successful. Pericardial calcification is a unique finding in CP, although the amount and localization of calcification can vary. We investigated how the pattern and amount of pericardial calcification affect mid-term postoperative outcomes after pericardiectomy to treat CP. METHODS: All patients of total pericardiectomy in our hospital from 2010 to 2020 were enrolled. Preoperative Computed tomography (CT) scans of 98 consecutive patients were available and analyzed. Medical records were reviewed retrospectively. Cardiovascular events were defined as cardiovascular death or hospitalization associated with a heart failure symptom, and all-cause events were defined as any event that required admission. CT scans were analyzed, and the volume and localization pattern of peri-calcification were determined. Pericardium calcium scores are presented using Agatston scores. RESULTS: Of the 98 patients, 25 (25.5%) were hospitalized with heart failure symptoms after pericardiectomy. The median follow-up duration for all patients was 172 weeks. The group with a cardiovascular event had a lower calcium score than patients without an event. Multivariate Cox proportional analysis showed that high ln(calcium score+1) before pericardiectomy was a dependent predictor of cardiovascular event (hazard ratio, 0.90; p = 0.04) after pericardiectomy. When we set the cut-off value (ln(calcium score+1) = 7.22), there was a significant difference in cardiovascular events in the multivariate Cox proportional analysis (p = 0.04). CONCLUSION: A low burden of pericardial calcification was associated with a high rate of mid-term clinical events after pericardiectomy to treat CP.

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People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long-term survivors. Extracellular vesicles (EVs) are involved in radiation-induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell-derived EVs containing miRNAs initiate monocyte activation in radiation-induced vascular inflammation. In vitro co-culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose-dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell-cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR-126-5p and miR-212-3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR-126-5p could be detected in the circulating endothelial EVs of radiation-induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR-126-5p and miR-212-3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation-induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.

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Radiation dose estimations performed by automated counting of micronuclei (MN) have been studied for their utility for triage following large-scale radiological incidents; although speed is essential, it also is essential to estimate radiation doses as accurately as possible for long-term epidemiological follow-up. Our goal in this study was to evaluate and improve the performance of automated MN counting for biodosimetry using the cytokinesis-block micronucleus (CBMN) assay. We measured false detection rates and used them to improve the accuracy of dosimetry. The average false-positive rate for binucleated cells was 1.14%; average false-positive and -negative MN rates were 1.03% and 3.50%, respectively. Detection errors seemed to be correlated with radiation dose. Correction of errors by visual inspection of images used for automated counting, called the semi-automated and manual scoring method, increased accuracy of dose estimation. Our findings suggest that dose assessment of the automated MN scoring system can be improved by subsequent error correction, which could be useful for performing biodosimetry on large numbers of people rapidly, accurately, and efficiently.

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The γ-H2AX assay is a sensitive and reliable method to evaluate radiation-induced DNA double-strand breaks. The conventional γ-H2AX assay detects individual nuclear foci manually, but is labor-intensive and time-consuming, and hence unsuitable for high-throughput screening in cases of large-scale radiation accidents. We have developed a high-throughput γ-H2AX assay using imaging flow cytometry. This method comprises (1) sample preparation from small volumes of blood in the Matrix™ 96-tube format, (2) automated image acquisition of cells stained with immunofluorescence-labeled γ-H2AX using ImageStream®X, and (3) quantification of γ-H2AX levels and batch processing using the Image Data Exploration and Analysis Software (IDEAS®). This enables the rapid analysis of γ-H2AX levels in several thousand of cells from a small volume of blood with accurate and reliable quantitative measurements for γ-H2AX foci and mean fluorescence levels. This high-throughput γ-H2AX assay could be a useful tool not only for radiation biodosimetry in mass casualty events, but also for large-scale molecular epidemiological studies and individualized radiotherapy.

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BACKGROUND: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. RESULTS: The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiated earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGFß and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27-0.33 up to 28 days and declined to 0.1 by day 56. CONCLUSIONS: Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.

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Induced pluripotent stem cell (iPSC) technology is an emerging technique to reprogram somatic cells into iPSCs that have revolutionary benefits in the fields of drug discovery, cellular therapy, and personalized medicine. However, these applications are just the tip of an iceberg. Recently, iPSC technology has been shown to be useful in not only conserving the endangered species, but also the revival of extinct species. With increasing consumer reliance on animal products, combined with an ever-growing population, there is a necessity to develop alternative approaches to conventional farming practices. One such approach involves the development of domestic farm animal iPSCs. This approach provides several benefits in the form of reduced animal death, pasture degradation, water consumption, and greenhouse gas emissions. Hence, it is essentially an environmentally-friendly alternative to conventional farming. Additionally, this approach ensures decreased zoonotic outbreaks and a constant food supply. Here, we discuss the iPSC technology in the form of a "Frozen Ark", along with its potential impact on spreading awareness of factory farming, foodborne disease, and the ecological footprint of the meat industry.

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The dicentric chromosome assay (DCA) is considered the gold standard for radiation biodosimetry, but it is limited by its long dicentric scoring time and need for skilled scorers. The automation of scoring dicentrics has been considered a strategy to overcome the constraints of DCA. However, the studies on automated scoring methods are limited compared to those on conventional manual DCA. Our study aims to assess the performance of a semi-automated scoring method for DCA using ex vivo and in vivo irradiated samples. Dose estimations of 39 blind samples irradiated ex vivo and 35 industrial radiographers occupationally exposed in vivo were estimated using the manual and semi-automated scoring methods and subsequently compared. The semi-automated scoring method, which removed the false positives of automated scoring using the dicentric chromosome (DC) scoring algorithm, had an accuracy of 94.9% in the ex vivo irradiated samples. It also had more than 90% accuracy, sensitivity, and specificity to distinguish binary dose categories reflecting clinical, diagnostic, and epidemiological significance. These data were comparable to those of manual DCA. Moreover, Cohen's kappa statistic and McNemar's test showed a substantial agreement between the two methods for categorizing in vivo samples into never and ever radiation exposure. There was also a significant correlation between the two methods. Despite of comparable results with two methods, lower sensitivity of semi-automated scoring method could be limited to assess various radiation exposures. Taken together, our findings show the semi-automated scoring method can provide accurate dose estimation rapidly, and can be useful as an alternative to manual DCA for biodosimetry in large-scale accidents or cases to monitor radiation exposure of radiation workers.

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Although the red pepper and its seeds have been studied for metabolic diseases, the effects and potential mechanisms of red pepper seed extract (RPS) on hepatic lipid accumulation are not yet completely understood. This study aimed to evaluate the inhibitory effect of RPS on hepatic lipid accumulation via autophagy. C57BL/6 mice were fed a high-fat diet (HFD) or a HFD supplemented with RPS. RPS treatment inhibited hepatic lipid accumulation by suppressing lipogenesis, inducing hepatic autophagic flux, and activating AMPK in HFD-fed mice. To investigate the effect of RPS on an oleic acid (OA)-induced hepatic steatosis cell model, HepG2 cells were incubated in a high-glucose medium and OA, followed by RPS treatment. RPS treatment decreased OA-induced lipid accumulation and reduced the expression of lipogenesis-associated proteins. Autophagic flux dramatically increased in the RPS-treated group. RPS phosphorylated AMPK in a dose-dependent manner, thereby dephosphorylated mTOR. Autophagy inhibition with 3-methyladenine (3-MA) antagonized RPS-induced suppression of lipogenesis-related protein expressions. Moreover, the knockdown of endogenous AMPK also antagonized the RPS-induced regulation of lipid accumulation and autophagy. Our findings provide new insights into the beneficial effects of RPS on hepatic lipid accumulation through the AMPK-dependent autophagy-mediated downregulation of lipogenesis.

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BACKGROUND/OBJECTIVES: Poorly regulated inflammation is believed to be the most predominant factor that can result in a wide scope of diseases including atopic dermatitis (AD). Despite many studies on the effect of pear pomace in obesity-related disorders including dysregulated gut microbiota, the protective effect of pear pomace in AD is still unknown. This study aimed to evaluate the effect of pear pomace ethanol extract (PPE) on AD by inhibiting inflammation. MATERIALS/METHODS: In the in vivo experiment, 2, 4-dinitrochlorobenzene (DNCB) was applied to NC/Nga mice to induce AD-like skin lesions. After the induction, PPE was administered daily by oral gavage for 4 weeks. The clinical severity score, serum IgE levels, spleen weight, histological changes in dorsal skin, and inflammation-related proteins were measured. In the cell study, RAW 264.7 cells were pretreated with PPE before stimulation with lipopolysaccharide (LPS). Nitrite oxide (NO) production and nuclear factor kappa B (NF-kB) protein expression were detected. RESULTS: Compared to the AD control (AD-C) group, IgE levels were dramatically decreased via PPE treatment. PPE significantly reduced scratching behavior, improved skin symptoms, and decreased ear thickness compared to the AD-C group. In addition, PPE inhibited the DNCB-induced expression of inducible nitrite oxide synthase (iNOS), the receptor for advanced glycation end products, extracellular signal-regulated kinase (ERK) 1/2, and NF-κB. PPE inhibited the LPS-induced overproduction of NO and the enhanced expression of iNOS and cyclooxygenase-2. Moreover, the phosphorylation of ERK1/2 and NF-κB in RAW 264.7 cells was suppressed by PPE. CONCLUSIONS: These results suggest that PPE could be explored as a therapeutic agent to prevent AD.

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Valence change-type resistance switching behaviors in oxides can be understood by well-established physical models describing the field-driven oxygen vacancy distribution change. In those models, electroformed residual oxygen vacancy filaments are crucial as they work as an electric field concentrator and limit the oxygen vacancy movement along the vertical direction. Therefore, their movement outward by diffusion is negligible. However, this situation may not be applicable in the electroforming-free system, where the field-driven movement is less prominent, and the isotropic oxygen vacancy diffusion by concentration gradient is more significant, which has not been given much consideration in the conventional model. Here, we propose a modified physical model that considers the change in the oxygen vacancies' charged state depending on their concentrations and the resulting change in diffusivity during switching to interpret the electroforming-free device behaviors. The model suggests formation of an hourglass-shaped filament constituting a lower concentration of oxygen vacancies due to the fluid oxygen diffusion in the thin oxide. Consequently, the proposed model can explain the electroforming-free device behaviors, including the retention failure mechanism, and suggest an optimized filament configuration for improved retention characteristics. The proposed model can plausibly explain both the electroformed and the electroforming-free devices. Therefore, it can be a standard model for valence change memristors.

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Duffy antigen receptor for chemokines (DARC)/CD234, also known as atypical chemokine receptor 1 (ACKR1), is a seven-transmembrane domain protein expressed on erythrocytes, vascular endothelium, and a subset of epithelial cells (Peiper et al., 1995). Previously, we reported that ACKR1 was expressed in bone marrow macrophages. ACKR1 interacts with CD82 on long-term repopulating hematopoietic stem cells (LT-HSCs) to maintain the dormancy of LT-HSCs during homeostasis (Hur et al., 2016). We also demonstrated that ACKR1 interacts with CD82 in HSCs from human umbilical cord blood (hUCB). These findings demonstrated that CD82 is a functional surface marker of LT-HSCs and this molecule maintains LT-HSC quiescence by interactions with ACKR1-expressing macrophages in mice and humans.

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