Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on ...histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase iNOS), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Orbital torque in magnetic bilayers Lee, Dongjoon; Go, Dongwook; Park, Hyeon-Jong ...
Nature communications,
11/2021, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The orbital Hall effect describes the generation of the orbital current flowing in a perpendicular direction to an external electric field, analogous to the spin Hall effect. As the orbital current ...carries the angular momentum as the spin current does, injection of the orbital current into a ferromagnet can result in torque on the magnetization, which provides a way to detect the orbital Hall effect. With this motivation, we examine the current-induced spin-orbit torques in various ferromagnet/heavy metal bilayers by theory and experiment. Analysis of the magnetic torque reveals the presence of the contribution from the orbital Hall effect in the heavy metal, which competes with the contribution from the spin Hall effect. In particular, we find that the net torque in Ni/Ta bilayers is opposite in sign to the spin Hall theory prediction but instead consistent with the orbital Hall theory, which unambiguously confirms the orbital torque generated by the orbital Hall effect. Our finding opens a possibility of utilizing the orbital current for spintronic device applications, and it will invigorate researches on spin-orbit-coupled phenomena based on orbital engineering.
Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of ...metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.
Social interest in autonomous navigation systems for autonomous ships is also increasing. For a robust autonomous navigation system, the location, speed, and direction of the ship and other ships ...must be identified in real time, and collision avoidance should be performed at an appropriate time by considering the collision risk. In this study, we proposed a collision avoidance method that quantitatively assesses the collision risk and then generates an avoidance path. First, to assess the collision risk, a collision risk assessment method based on the ship domain and the closest point of approach (CPA) was proposed. The ship domain is created with an asymmetric shape considering manoeuvring performance and the COLREGs. The CPA is used to assess quantitative collision risk value. Subsequently, a path generation algorithm based on deep reinforcement learning (DRL) was proposed to determine the avoidance time and to generate an avoidance path complying the COLREGs for the most dangerous ship in terms of collision risk. The information of own ship and target ship such as location, speed, heading, collision risk is used as the input state, and the rudder angle of own ship is set as the output action of the DRL. The cost function related to the path following and the collision avoidance is defined as the reward of the DRL-based collision avoidance method. Additionally, the DRL modes are defined to navigate the flexible avoidance path by changing the ratio between the path following and the collision avoidance. To verify the proposed method, we compared the collision avoidance method with the A* algorithm, which is a traditional path planning algorithm, and analyzed the results for various scenarios. The proposed method reliably avoided collisions through flexible paths for complex and unexpected changes in situations compared to the A* algorithm.
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•This study deals with a ship collision avoidance method considering COLREGs.•The proposed method considers both path following and collision avoidance.•Deep reinforcement learning is used to handle unexpected changes in situations.•The proposed method shows good performance for various validation situations.
To compare the accuracy and computational efficiency of two of the latest deep-learning algorithms for automatic identification of cephalometric landmarks.
A total of 1028 cephalometric radiographic ...images were selected as learning data that trained You-Only-Look-Once version 3 (YOLOv3) and Single Shot Multibox Detector (SSD) methods. The number of target labeling was 80 landmarks. After the deep-learning process, the algorithms were tested using a new test data set composed of 283 images. Accuracy was determined by measuring the point-to-point error and success detection rate and was visualized by drawing scattergrams. The computational time of both algorithms was also recorded.
The YOLOv3 algorithm outperformed SSD in accuracy for 38 of 80 landmarks. The other 42 of 80 landmarks did not show a statistically significant difference between YOLOv3 and SSD. Error plots of YOLOv3 showed not only a smaller error range but also a more isotropic tendency. The mean computational time spent per image was 0.05 seconds and 2.89 seconds for YOLOv3 and SSD, respectively. YOLOv3 showed approximately 5% higher accuracy compared with the top benchmarks in the literature.
Between the two latest deep-learning methods applied, YOLOv3 seemed to be more promising as a fully automated cephalometric landmark identification system for use in clinical practice.
Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of ...hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and/or clinical trials.
Tight regulation of Toll‐like receptor (TLR)‐mediated inflammatory responses is important for innate immunity. Here, we show that T‐cell death‐associated gene 51 (TDAG51/PHLDA1) is a novel regulator ...of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)‐induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow‐derived macrophages (BMMs). LPS‐induced inflammatory mediator production was significantly decreased in TDAG51‐deficient BMMs. In TDAG51‐deficient mice, LPS‐ or pathogenic Escherichia coli infection‐induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14‐3‐3ζ to FoxO1 was competitively inhibited by the TDAG51‐FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby strengthening FoxO1 nuclear accumulation. TDAG51/FoxO1 double‐deficient BMMs showed significantly reduced inflammatory mediator production compared with TDAG51‐ or FoxO1‐deficient BMMs. TDAG51/FoxO1 double deficiency protected mice against LPS‐ or pathogenic E. coli infection‐induced lethal shock by weakening the systemic inflammatory response. Thus, these results indicate that TDAG51 acts as a regulator of the transcription factor FoxO1, leading to strengthened FoxO1 activity in the LPS‐induced inflammatory response.
Synopsis
Toll‐like receptor (TLR) signaling is tightly controlled during inflammatory responses. Here, TDAG51/PHLDA1 is identified as a new interactor and regulator of transcription factor FoxO1, stimulating inflammatory mediator production upon LPS challenge.
TDAG51 expression is induced during the LPS‐induced inflammatory response in macrophages.
TDAG51 interacts with the transcription factor FoxO1 and competitively inhibits 14‐3‐3𝝵 binding
TDAG51‐FoxO1 interaction and reduced 14‐3‐3𝝵 binding enhances FoxO1 nuclear accumulation, thereby promoting inflammatory mediator expression.
TDAG51 deficiency attenuates LPS‐induced lethal shock by weakening the inflammatory response in mice.
TLR‐mediated expression of inflammatory mediators is fine‐tuned by T‐cell death‐associated gene 51, which competes with inhibitory 14‐3‐3𝝵 binding to FoxO1.
Wetting by fouling is phenomenon specific to membrane distillation (MD) and are regarded as challenges to the seawater membrane distillation (SWMD) process. To understand fouling and wetting, the ...influence of Mg and Sr crystals, which can potentially cause scaling, as well as Ca crystals deposited on the membrane surface were investigated. Mg(OH)2 and CaSO4 had significant impact on fouling and wetting. Even if CaCO3 and SrSO4 had no effects on fouling and wetting as single salts, CaCO3 and CaSO4 were dominant in synthetic seawater without Mg(OH)2. However, the occurrence of Mg(OH)2 scales became a cause for concern if Ca ion was removed from seawater for the prevention of fouling and wetting. Therefore, Mg as well as Ca should be removed for proper fouling and wetting control. NaOH/Na2CO3 softening was used for the removal of Ca and Mg ions. In addition, based on the inhibition effects of Mg ions on Ca scales, a new pretreatment method involving the injection of MgCl2 to increase the Mg /Ca ratio was examined.
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•Wetting in MD process using a seawater was observed by visualization system.•Wetting by Mg(OH)2 occurred during the MD process was firstly suggested.•Retardation of the wetting in MD process was achieved by a Mg addition to the feed.•The SrCO3 scalant was formed when major components of seawater were removed.•The CaCO3 and CaSO4 scalants resulted in the partial and full wettings, respectively.
Abstract
Precise control of morphology and optical response of 3-dimensional chiral nanoparticles remain as a significant challenge. This work demonstrates chiral gold nanoparticle synthesis using ...single-stranded oligonucleotide as a chiral shape modifier. The homo-oligonucleotide composed of Adenine nucleobase specifically show a distinct chirality development with a dissymmetric factor up to g ~ 0.04 at visible wavelength, whereas other nucleobases show no development of chirality. The synthesized nanoparticle shows a counter-clockwise rotation of generated chiral arms with approximately 200 nm edge length. The molecular dynamics and density functional theory simulations reveal that Adenine shows the highest enantioselective interaction with Au(321)
R/S
facet in terms of binding orientation and affinity. This is attributed to the formation of sequence-specific intra-strand hydrogen bonding between nucleobases. We also found that different sequence programming of Adenine-and Cytosine-based oligomers result in chiral gold nanoparticles’ morphological and optical change. These results extend our understanding of the biomolecule-directed synthesis of chiral gold nanoparticles to sequence programmable deoxyribonucleic acid and provides a foundation for programmable synthesis of chiral gold nanoparticles.
Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance ...of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA‐21 and lncRNA‐ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA‐21 and lncRNA‐ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA‐21 and higher lncRNA‐ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C‐reactive protein (all p < 0.05). The overall survival and progression‐free survival were significantly lower in patients with higher circulating levels of exosomal miRNA‐21 (≥0.09) and lncRNA‐ATB (≥0.0016) (log‐rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA‐21 and lncRNA‐ATB) are novel prognostic markers and therapeutic targets for HCC.
What's new?
A growing body of evidence indicates that noncoding RNAs (ncRNAs), such as miRNAs and lncRNAs, play an important role in tumor progression and metastasis. Could particular ncRNAs also serve as serum biomarkers for cancer prognosis? In our study, the authors found that two specific ncRNAs in circulating exosomes were independent predictors of overall survival and disease progression in human hepatocellular carcinoma (HCC). These molecules might therefore provide valuable biomarkers to improve the clinical management of HCC, as well as potential therapeutic targets.
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