Inflammation caused by the excessive secretion of inflammatory mediators in abnormally activated macrophages promotes many diseases along with oxidative stress. Loganin, a major iridoid glycoside ...isolated from Cornus officinalis, has recently been reported to exhibit anti-inflammatory and antioxidant effects, whereas the underlying mechanism has not yet been fully clarified. Therefore, the aim of the present study is to investigate the effect of loganin on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results indicated that loganin treatment markedly attenuated the LPS-mediated phagocytic activity and release of nitric oxide (NO) and prostaglandin E2, which was associated with decreased the expression of inducible NO synthase and cyclooxygenase-2. In addition, loganin suppressed the expression and their extracellular secretion of LPS-induced pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Furthermore, loganin abolished reactive oxygen species (ROS) generation, and promoted the activation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated macrophages. However, zinc protoporphyrin, a selective HO-1 inhibitor, reversed the loganin-mediated suppression of pro-inflammatory cytokines in LPS-treated macrophages. In conclusion, our findings suggest that the upregulation of the Nrf2/HO-1 signaling pathway is concerned at least in the protective effect of loganin against LPS-mediated inflammatory and oxidative stress, and that loganin can be a potential functional agent to prevent inflammatory and oxidative damage.
•Antioxidative activity of plant based food improved by fermentation.•Release of antioxidant compounds increased by fermentation.•Liberation or synthesis of antioxidant compounds increased by ...fermentation.
This study provides an overview of the factors that influence the effect of fermentation on the antioxidant activity and the mechanisms that augment antioxidative activities in fermented plant-based foods. The ability of fermentation to improve antioxidant activity is primarily due to an increase in the amount of phenolic compounds and flavonoids during fermentation, which is the result of a microbial hydrolysis reaction. Moreover, fermentation induces the structural breakdown of plant cell walls, leading to the liberation or synthesis of various antioxidant compounds. These antioxidant compounds can act as free radical terminators, metal chelators, singlet oxygen quenchers, or hydrogen donors to radicals. The production of protease, α-amylase and some other enzymes can be influenced by fermentation that may have metal ion chelation activity. Because the mechanisms that affect antioxidant activity during fermentation are extremely varied, further investigation is needed to establish the precise mechanisms for these processes.
Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains ...challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI).
We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC).
Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists (
< .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and ≥ 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP.
The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.
Advances in material science and nanotechnology have fostered the miniaturization of devices. Over the past two decades, the form‐factor of these devices has evolved from 3D rigid, volumetric devices ...through 2D film‐based flexible electronics, finally to 1D fiber electronics (fibertronics). In this regard, fibertronic strategies toward wearable applications (e.g., electronic textiles (e‐textiles)) have attracted considerable attention thanks to their capability to impart various functions into textiles with retaining textiles' intrinsic properties as well as imperceptible irritation by foreign matters. In recent years, extensive research has been carried out to develop various functional devices in the fiber form. Among various features, lighting and display features are the highly desirable functions in wearable electronics. This article discusses the recent progress of materials, architectural designs, and new fabrication technologies of fiber‐shaped lighting devices and the current challenges corresponding to each device's operating mechanism. Moreover, opportunities and applications that the revolutionary convergence between the state‐of‐the‐art fibertronic technology and age‐long textile industry will bring in the future are also discussed.
1D fiber‐based electronics have attracted considerable attention by virtue of their capability to impart various electronic features into textiles naturally during the weaving process. A detailed overview of recent development of lighting devices in fiber electronics is provided. Some strong and weak points by different structural designs and emission mechanisms as well as future applications are also described.
A 3.0 Gsymbol/s/lane receiver is proposed herein to acquire near-grounded high-speed signals for the mobile industry processor interface (MIPI) C-PHY version 1.1 specification used for CMOS image ...sensor interfaces. Adaptive level-dependent equalization is also proposed to improve the signal integrity of the high-speed receivers receiving three-level signals. The proposed adaptive level-dependent equalizer (ALDE) is optimized by adjusting the duty cycle ratio of the clock recovered from the received data to 50%. A pre-determined data pattern transmitted from a MIPI C-PHY transmitter is established to perform the adaptive level-dependent equalization. The proposed MIPI C-PHY receiver with three data lanes is implemented using a 65 nm CMOS process with a 1.2 V supply voltage. The power consumption and area of each lane are 4.9 mW/Gsymbol/s/lane and 0.097 mm2, respectively. The proposed ALDE improves the peak-to-peak time jitter of 12 ps and 34 ps, respectively, for the received data and the recovered clock at a symbol rate of 3 Gsymbol/s/lane. Additionally, the duty cycle ratio of the recovered clock is improved from 42.8% to 48.3%.
Mori Ramulus, the dried twigs of
L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to ...evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H
O
) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H
O
-induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H
O
-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H
O
-triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome
release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H
O
. Furthermore, AEMR diminished H
O
-induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H
O
-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H
O
-induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy.
Extracellular vesicles (EVs) derived from plants have emerged as potential candidates for cosmetic and therapeutic applications. In this study, we isolated EVs from Aloe vera peels (A-EVs) and ...investigated the antioxidant and wound healing potential of A-EVs.
A-EVs were isolated by ultracentrifugation and tangential flow filtration and were characterized using transmission electron microscopy, nanoparticle tracking analysis. The cytotoxicity and cellular uptake of A-EVs were investigated by WST-1 assay and flow cytometry. The antioxidant effect of A-EVs was evaluated by superoxide dismutase (SOD) activity assay and cellular antioxidant activity (CAA) assay. The wound healing potential was assessed by in vitro scratch assay using human keratinocytes (HaCaT) and fibroblasts (HDF). The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and their associated genes was analyzed by quantitative RT-PCR.
A-EVs displayed a round shape and had diameters from 50 to 200 nm. A-EVs showed good cytocompatibility on human skin cells and were internalized into HaCaT cells via clathrin-, caveolae-mediated endocytosis, and membrane fusion. The SOD activity and CAA assays exhibited that A-EVs had antioxidant activity and reduced intracellular ROS levels in H
O
-treated HaCaT cells in a dose-dependent manner. A scratch assay showed that A-EVs enhanced the migration ability of HaCaT and HDF. Moreover, A-EVs significantly upregulated the mRNA expression of Nrf2, HO-1, CAT, and SOD genes in H
O
-treated HaCaT cells. Our findings reveal that A-EVs could activate the antioxidant defense mechanisms and wound healing process via the Nrf2 activation.
Overall results suggest that the A-EVs are promising as a potential agent for skin regeneration.
Coptisine is isoquinoline alkaloid derived from Coptidis Rhizoma and is known to have potential anti-cancer activity toward various carcinomas. Targeting autophagy is one of the main approaches for ...cancer therapy, but whether the anti-cancer efficacy of coptisine involves autophagy is still unclear. Therefore, this study investigated the effect of coptisine on autophagy in hepatocellular carcinoma (HCC) Hep3B cells, and identified the underlying mechanism. Our results showed that coptisine increased cytotoxicity and autophagic vacuoles in a concentration-dependent manner. Furthermore, the expressions of light chain 3 (LC3)-I/II, Beclin-1 and autophagy genes were markedly increased by coptisine, while the expression of p62 decreased. In addition, we found that pretreatment with bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, markedly reduced coptisine-mediated autophagic cell death, but 3-methyladenine, an inhibitor for autophagosome formation did not. Moreover, our results showed that although coptisine up-regulated AMP-activated protein kinase (AMPK) that partially induced LC3-I/II, coptisine-mediated AMPK signaling did not directly regulate autophagic cell death. Additionally, we found that coptisine suppressed the phosphorylation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), and this effect was notably enhanced by PI3K inhibitor LY294002. Meanwhile, coptisine significantly increased both the production of mitochondrial reactive oxygen species (ROS) and the recruitment of mitophagy-regulated proteins to mitochondria. Furthermore, N‐acetylcysteine, a potential ROS scavenger, substantially suppressed the expression of mitophagy-regulated proteins and LC3 puncta by coptisine. Overall, our results demonstrate that coptisine-mediated autophagic cell death was regulated by PI3K/Akt/mTOR signaling and mitochondrial ROS production associated with mitochondrial dysfunction. Taken together, these findings suggest that coptisine exerts its anti-cancer effects through induction of autophagy in HCC Hep3B cells.
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•Coptisine promotes cytotoxicity and autophagy.•Coptisine induces autophagy via inhibition of PI3K/Akt/mTOR signaling pathway.•Coptisine induces mitophagy through up-regulation of intracellular ROS.•Coptisine-induced apoptosis and autophagy is associated in mitochondrial dysfunction.
•In a national cohort of over 10,273 patients with COVID-19, more than 60% of all cases in South Korea reported no symptoms at the time of diagnosis.•Our findings suggest that symptom-based screening ...alone may fail to control transmission during the infected but asymptomatic stage.•Expanding criteria for contact tracing and testing should be urgently considered.
To delineate clinical characteristics of asymptomatic and symptomatic patients confirmed with COVID-19 in South Korea.
Data were obtained from the Korean National Health Insurance Service database linked to the Korea Centers for Disease Control and Prevention data.
Among 10,237 patients (mean SD age, 45.0 19.8 years; 60.1% female) who met the eligibility criteria for the study, 6,350 (62.0%) patients were asymptomatic, and 3,887(38.0%) patients were symptomatic. The mean and median age were similar between asymptomatic and symptomatic patients. Notably, we observed a U-shaped association between age group and the proportion of asymptomatic patients, with the nadir at 57.3% in the 40-49 age group. This U-shaped distribution was largely similar between men and women. The overall prevalence of asymptomatic individuals was higher, regardless of sex, residential area, income levels, and comorbid conditions.
In this national cohort of over 10,000 patients with COVID-19, more than 60% of all cases in South Korea reported no symptoms at the time of diagnosis. Expanding criteria for contact tracing and testing to capture potential transmission before symptom onset should be urgently considered to inform control strategies for COVID-19.
•TiO2 long-lasting hydrophilicity mechanism is investigated.•X-ray photoelectron spectroscopy for the source mechanism on rutile and anatase.•Films with oxygen or argon plasma treatment, with or ...without ultraviolet irradiation.•The positive binding energy shifting of the rutile progressed faster than anatase.•Donor-Acceptor complex characteristics cause different relaxation behavior.
When the surface of TiO2 is exposed to ultraviolet (UV) light, its hydrophilicity increases initially and then contact angle relaxation progresses over time. We investigated the source mechanism and working principles of long-lasting hydrophilicity in an ambient environment. Previously, we reported that the amount of donor-acceptor complexes (DACs) generated by polarizable OH groups with strong charge polarity is critical for maintaining long-lasting hydrophilicity (>90 days) on an anatase surface. In less reactive TiO2 films with low surface energy, a fast relaxation occurs due to the loss of polarizable OH groups. In this research, quantitative four-peak X-ray photoelectron spectroscopy analysis with TiO2 O 1 s spectra surface analysis was used to determine the relative amount of DACs and the binding energy shifting of water adsorbates on single crystal rutile (110) and polycrystalline anatase after UV exposure or plasma treatment. Films treated with oxygen or argon plasma and/or UV were analyzed and compared to suggested mechanisms that can occur on the surface of the TiO2 phase. All treated rutile (110) films except those treated with an Ar plasma exhibited rapid contact angle relaxation during the first 3 days, and the angle increased gradually to >50° over 14 days. In contrast, all anatase films retained long-lasting hydrophilicity, demonstrating a <∼10° contact angle over 56 days. At the first measurement, the binding energies were shifted for rutile (110) treated with O2 plasma and O2 plasma+UV films, demonstrating Ti–OH and DAC values of +0.15 eV each. However, the Ti–OH and DACs of all anatase films were located in the negative binding energy position, indicating that the DACs of rutile (110) were unstable due to a relatively weak bonding. In addition, the IOH/Ibulk intensity ratio of Ti–OH for rutile (110) treated with an O2 plasma increased significantly from 20 % to 37 %. However, the intensity ratio for O2 plasma+UV increased only from 20 % to 23.8 %. This result in combination with the binding energy shifting tendency indicates that relaxed OH groups increased rapidly without UV treatment. When rutile (110) was irradiated with UV, the effect of photoinduced electron-hole pairs shown with Ti 2p spectra was much shorter than that of anatase. Differences in relaxation occurred in both phases due to the charge polarity effect between rutile (110) and anatase, the unstable DACs related to weak OH groups, and the difference in surface characteristics. Using single crystal rutile (110) with a well-defined surface, these experiments validated further the DAC mechanism and theory presented by our group. Specifically, we confirmed that both the amount of DACs and the binding energy position shifting are important for long-term hydrophilicity.
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