Search

Purpose: This study aimed to determine the optimal blending ratio of extracts of Hippophae rhamnoides (H. rhamnoides ) fruit, Rubus fruticosus (R. fruticosus ) leaf, and Perillae folium (P. folium) leaf as a potential functional material for antiwrinkle, antioxidant, anti-inflammatory, and whitening properties. Methods: We used the design of experiment (DOE) efficacy method to identify the optimal blend ratio for a natural extract complex. In addition, we tested the efficacy of the extract complex and the individual extracts by experiments, including elastase inhibition assay, NO inhibition assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay, tyrosinase inhibition assay, and ROS inhibition assay. Results: DOE methods using natural extracts showed that the most efficacious ratio of H. rhamnoides fruit: R. fruticosus leaf: P. folium leaf was 0.25:0.7:0.05. At this ratio, the elastase inhibitory effect, an indicator of wrinkle improvement, was 28% compared to the control. The antioxidant activity was 71.8% higher than the control. Additionally, NO formation was significantly suppressed by the extract complex. Tyrosinase inhibitory activity, a whitening index, showed 24.4% improvement over the control. Finally, hydrogen peroxide-induced cytotoxicity was significantly inhibited following treatment with the extract complex. Conclusion: The natural extract complex of H. rhamnoides , R. Fruticosus , and P. folium was found to have beneficial wrinkle improvement, antioxidant, anti-inflammatory, and whitening effects, and has potential as a functional cosmetic material.

As the wireless network market has been grown, high-performance and efficient communication technology are demanded for devices. Specifically, reference clock signal forms an essential part of designing devices such as wearable one or the Internet of Things. The conventional structure of XOR is used to multiply the reference frequency. The structure of DLL illustrates that how frequency is extracted from application based on various values of desired supply voltage.

Ulcerative colitis is a complex inflammatory bowel disorder disease that can induce rectal and colonic dysfunction. Although the prevalence of IBD in Western countries is almost 0.5% of the general population, genetic causes are still not fully understood. In a recent discovery, itaconate was found to function as an immune-modulating metabolite in mammalian immune cells, wherein it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. However, the association between the Acod1 (Aconitate decarboxylase 1)-itaconate axis and ulcerative colitis has rarely been studied. To elucidate this, we established a DSS-induced colitis model with Acod1-deficient mice and then measured the mouse body weights, colon lengths, histological changes, and cytokines/chemokines in the colon. We first confirmed the upregulation of Acod1 RNA and protein expression levels in DSS-induced colitis. Then, we found that colitis symptoms, including weight loss, the disease activity index, and colon shortening, were worsened by the depletion of Acod1. In addition, the extent of intestinal epithelial barrier breakdown, the extent of immune cell infiltration, and the expression of proinflammatory cytokines and chemokines in Acod1-deficient mice were higher than those in wild-type mice. Finally, we confirmed that 4-octyl itaconate (4-OI) alleviated DSS-induced colitis in Acod1-deficient mice and decreased the expression of inflammatory cytokines and chemokines. To our knowledge, this study is the first to elucidate the role of the Acod1-itaconate axis in colitis. Our data clearly showed that Acod1 deletion resulted in severe DSS-induced colitis and substantial increases in inflammatory cytokine and chemokine levels. Our results suggest that Acod1 may normally play an important regulatory role in the pathogenesis of colitis, demonstrating the potential for novel therapies using 4-OI.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-&alpha, in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1&beta, IL-6, IL-12p40, and TNF-&alpha, and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-&alpha, played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-&kappa, B pathway in macrophages. ADL extract prevented exogenous TNF-&alpha, induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

The I-V characteristics of two terminal planar VO2 film devices are investigated as the devices undergo the current induced metal insulator transition (I-MIT). The I-MIT occured when the device resistivity reached ∼7 Ωcm , where metallic grains formed initial conductive current path within insulating matrix. The transition time needed for the I-MIT increased with increasing external resistance, REXT, connected to the device in series, i.e. ∼390 μs (REXT = 5 kΩ) to ∼1400 μs (REXT = 20 kΩ). The transition time is closely related to the RC time delay from capacitance discharge of the VO2 device. During the I-MIT, the amount of discharge current was estimated as large as ∼100 mA, which was larger than the current just before the I-MIT. After the I-MIT, the current density decreased from 1.1 × 106 A/cm2 to 6.5 × 105 A/cm2, suggesting a large temperature changes up to ∼300 °C.

We have investigated the effect of over oxidized surface layer on the characteristics of metal-insulator transition (MIT) of vanadium dioxide (VO 2 ) films grown by thermal oxidation method. During the oxidation, the over-oxidized V 6 O 13 layer was formed, which increased contact resistance and thus reduced the resistivity ratio before and after MIT. The contact resistivity of the VO 2 film with over-oxidized surface layer was in the range 4.2 × 10 −2 ∼ 9.4 × 10 −4 Ωcm 2 . Interestingly, the over-oxidized surface layer was removed by simply cooling the film under reduced oxygen pressure. Upon the removal of the over-oxidized layer, the resistivity ratio across MIT increased up to 1.2 × 10 4 . The ratio of contact resistance to sample resistance was small (large) at low (high) temperature.

We investigated the control of two important parameters of vanadium dioxide (VO2) microcrystals, the phase transition temperature and speed, by varying microcrystal width. By using the reflectivity change between insulating and metallic phases, phase transition temperature is measured by optical microscopy. As the width of square cylinder-shaped microcrystals decreases from ∼70 to ∼1 μm, the phase transition temperature (67 °C for bulk) varied as much as 26.1 °C (19.7 °C) during heating (cooling). In addition, the propagation speed of phase boundary in the microcrystal, i.e., phase transition speed, is monitored at the onset of phase transition by using the high-speed resistance measurement. The phase transition speed increases from 4.6 × 10(2) to 1.7 × 10(4) μm/s as the width decreases from ∼50 to ∼2 μm. While the statistical description for a heterogeneous nucleation process explains the size dependence on phase transition temperature of VO2, the increase of effective thermal exchange process is responsible for the enhancement of phase transition speed of small VO2 microcrystals. Our findings not only enhance the understanding of VO2 intrinsic properties but also contribute to the development of innovative electronic devices.

Although Mycobacterium abscessus ( M. abscessus ) is becoming more prevalent in patients without overt immunodeficiency, little is known about the factors that contribute to disease susceptibility. This study was undertaken to investigate how Toll-like receptor 2 (TLR2) functionally contributes to the generation of protective immunity against M. abscessus in a morphotype-specific manner. We found that Tlr2 −/− mice were extremely susceptible to an intravenous (i.v.) model of infection by M. abscessus rough variants, displaying uncontrolled infection in the lungs and a significantly lower survival rate than with wild-type (WT) mice. This uncontrolled infection resulted from failures in the following processes: (i) production of the crucial cytokines gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70); (ii) early infiltration of neutrophils, monocytes, and dendritic cells (DCs) in the lungs of Tlr2 −/− mice; (iii) rapid influx of CD4 + and CD8 + T cells; and (iv) the expansion of memory/effector T cells. Notably, systemic administration of M. abscessus culture filtrate-treated syngeneic DCs from WT mice greatly strengthened immune priming in vivo , resulting in a dramatic reduction in bacterial growth and improved long-term survival in Tlr2 −/− mice, with a recovery of protective immunity. Our findings demonstrate that TLR2 is an essential contributor to instructive and effector immunity during M. abscessus infection in a morphotype-specific manner.

Sulfide- and azide-selective optical signaling using a single nitrobenzoxadiazole (NBD)-based probe was investigated. NBD-pivalate showed colorimetric signaling for sulfide ions via cleavage of the NBD–O bond to generate NBD–SH. It also showed chromogenic and fluorogenic signaling for azide ions by O–COBut cleavage to yield NBD–OH under the same conditions.

Cl-amidine, which is a small-molecule inhibitor of PAD, has therapeutic potential for inflammation-mediated diseases. However, little is known regarding the manner by which PAD inhibition by Cl-amidine regulates inflammatory conditions. Here, we investigated the effects of PAD inhibition by Cl-amidine on the functioning of DCs, which are pivotal immune cells that mediate inflammatory diseases. When DC maturation was induced by TLR agonists, reduced cytokine levels (IL-6, IL-1β, and IL-12p70) were observed in Cl-amidine-treated DCs. Cl-amidine-treated, LPS-activated DCs exhibited alterations in their mature and functional statuses with up-regulated antigen uptake, down-regulated CD80, and MHC molecules. In addition, Cl-amidine-treated DCs dysregulated peptide-MHC class formations. Interestingly, the decreased cytokines were independent of MAPK/NF-κB signaling pathways and transcription levels, indicating that PAD inhibition by Cl-amidine may be involved in post-transcriptional steps of cytokine production. Transmission electron microscopy revealed morphotypical changes with reduced dendrites in the Cl-amidine-treated DCs, along with altered cellular compartments, including fragmented ERs and the formation of foamy vesicles. Furthermore, in vitro and in vivo Cl-amidine treatments impaired the proliferation of nai¨ve CD4+ and CD8+ T cells. Overall, our findings suggest that Cl-amidine has therapeutic potential for treating inflammation-mediated diseases.

Hyperammonemia associated with overt hepatic encephalopathy (OHE) causes excitotoxic neuronal death through activation of the cytochrome C (CytC)-mediated mitochondria-dependent apoptotic pathway. We tested the therapeutic effect of nortriptyline (NT), a mitochondrial permeability transition pore (mPTP) blocker that can possibly inhibit mitochondrial CytC efflux to the cytosol on in vivo and in vitro OHE models. After ensuring the generation of OHE rats, established by bile duct ligation (BDL), they were intraperitoneally administered either 20 mg/kg NT (i.e., BDL+NT) or another vehicle (i.e., BDL+VEH) for 14 days. Compared with the control, BDL+VEH showed an increment of motor deficits, cell death, synaptic loss, apoptosis, and mitochondria with aberrant morphology in substantia nigra compacta dopaminergic (DA-ergic) neurons. However, the extent was significantly reversed in BDL+NT. Subsequently, we studied the neuroprotective mechanism of NT using PC-12 cells, a DA-ergic cell line, which exposed glutamate used as an excitotoxin. Compared with the control, the cells exposed to 15 mM glutamate (i.e., GLU) showed incremental cell death, apoptosis, and demise in mitochondrial respiration. Importantly, efflux of CytC from mitochondria to cytosol and the dissipation of mitochondrial membrane potential (△Ψm), an indicator of mPTP opening, were prominent in GLU. However, compared with the GLU, the cells cotreated with 10 μM NT (i.e., GLU+NT) showed a significant reduction in the aforementioned phenomenon. Together, we concluded that NT can be used for OHE therapeutics, mitigating the excitotoxic death of substantia nigra compacta DA-ergic neurons via mPTP-associated mitochondrial dysfunction inhibition.

Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. Significance The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells.

The characteristics of onset voltages and conduction channel temperatures in the metal-insulator transition (MIT) of vanadium dioxide (VO2) devices are investigated as a function of dimensions and ambient temperature. The MIT onset voltage varies from 18 V to 199 V as the device length increases from 5 to 80 μm at a fixed width of 100 μm. The estimated temperature at local conduction channel increases from 110 to 370 °C, which is higher than the MIT temperature (67 °C) of VO2. A simple Joule-heating model is employed to explain voltage-induced MIT as well as to estimate temperatures of conduction channel appearing after MIT in various-sized devices. Our findings on VO2 can be applied to micro- to nano-size tunable heating devices, e.g., microscale scanning thermal cantilevers and gas sensors.

We report a Fabry–Perot interferometer (FPI)-based infrared (IR) spectrometer designed for long-wavelength infrared (LWIR) region. To fabricate the proposed FPI-based LWIR spectrometer, we developed a novel poly(dimethylsiloxane) (PDMS) patterning technique by combining photolithography and dry etching. The proposed PDMS patterning technique has advantages such as clear shape of PDMS pattern and no damage to the silicon (Si) substrate. Especially, the final height of PDMS pattern is easily adjusted by controlling the thickness of spin-coated photoresist. The proposed FPI-based IR spectrometer, which is composed of upper and lower substrate were fabricated separately utilizing newly proposed PDMS patterning technique. Experimental results show that maximum transmittance of filtered wavelength component by the proposed FPI-based IR spectrometer lies at the wavelength of 16 µm. The proposed IR spectrometer can detect a specific wavelength at LWIR region by controlling the air etalon gap that is adjusted by utilizing the proposed PDMS patterning technique.