Search

Methiozolin is a novel herbicide used to control annual bluegrass. It has low vapor pressure and high hydrophobicity, which could result in persistence in water and bioaccumulation. We measured the bioconcentration factors (BCFs) of methiozolin in ricefish (Oryzias latipes). Two radiolabels were used to quantify the parent compound and identify its metabolites. Ricefish were exposed to 2.0 and 20.0 ng/L methiozolin for 28 days in the uptake phase with a 96-h LC50 of 2.2 mg/L(95% confidence limit: 2.1-2.5 mg/L) and water solubility of 4.2 mg/L after 48 h was observed. On the basis of total radioactivity residues (TRRs), BCFss and BCFk values of 797.0-851.9 and 992.9-1077.4 were observed, respectively, while BCFss values for methiozolin were 251.9-257.5. Several minor metabolites with TRR < 3.4% were detected. Among them, 4-(2,6-difluorobenzyloxy-methyl)-3-hydroxy-3-methyl-1-(3-methylthiophen-2-yl)butan-1-one, 2,6-difluorobenzyl alcohol, and 4,5-dihydro-5-methyl-3-(3-methylthiophen-2-yl)isoxazol-5-yl)methanol were identified. Methiozolin is metabolized into numerous minor metabolites with potentially low bioaccumulation capacity in ricefish. These findings can facilitate risk assessments regarding methiozolin use, particularly its movements and final stages in aquatic environments.

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca2+ flux via coupling to Gαi and Gαq families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gαq/11 and Gα12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

Methiozolin is a novel herbicide for controlling annual bluegrass. After applying 14C labelled methiozolin in two sediment (clay loam and sand)-water systems under aerobic conditions, its distribution, half-life, and metabolites within 300 days were investigated. The mass balance ranged within 92.0%–104.4% of applied radioactivity (AR). Radioactivity in the water declined sharply from 94.4% to 0.5% AR, while in the sediment it increased to 83.9% AR at 14 days before declining to 9.1% AR. The volatiles were minimal (

BACKGROUND Non-invasive body-sculpting procedures are becoming increasingly popular. The application of 1,060 nm of laser energy transcutaneously to hyperthermically induce the disruption of fat cells in the abdomen is a type of non-invasive procedure. AIMS The purpose of this study was to compare the treatment results from two parameters of the same system, each with different energy output levels, in an in vivo porcine model to determine the most effective application. METHODS Female pigs (n = 3) were used in this study. We examined the effects of the treatment using photography, ultrasonography, gross and microscopic pathology, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. Blood chemistry analysis was performed before each session to check lipid levels and to monitor for any adverse changes in markers that may indicate liver damage. Biopsies were taken and routinely processed with hematoxylin and eosin and Oil Red O stains to examine for tissue damage at baseline and after each treatment. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assays were performed to check for apoptotic-related DNA damage. RESULTS Ultrasonic imaging of the same area before and after the application of 1,060 nm of laser energy at outputs of 0.9 and 1.4 W/cm2 showed that the density of the fat layer changed immediately after irradiation due to the transient heat transfer in the fat layer. Preclinical evaluation was performed to obtain comparison data on the safety and efficacy of subcutaneous fat reduction after applying the different energy outputs of 0.9 and 1.4 W/cm2 . CONCLUSION Based on our findings, we suggest that long-term histologic changes through the use of these devices suggest a comparative effectiveness of the treatment energy.

Benzalkonium chloride (BAC) is a cationic surfactant commonly used as a disinfectant, and is discharged into the aquatic environment by various water sources such as wastewater. BAC may also intera...

The fate of methiozolin under anaerobic conditions was investigated in clay loam with a high organic carbon content and sandy loam with a low carbon content using [dihydroisoxazole ring-14C] and [phenyl-14C] radiolabels. The sediment/water ratio was 1:3 based on the dry weight:volume (w/v) ratio; the incubations lasted up to 355 days after the treatment (DAT) and were performed in the dark at 20.4 ± 0.7 °C. The overlying water flow-through systems consisted of glass vessels containing sediment with traps for [14C]carbon dioxide and [14C]volatiles. The samples were collected and analyzed at 0, 3, 7, 14, 50, 100, 200, and 355 DAT. The water and sediment samples were extracted with solvent systems, centrifuged, concentrated, and analyzed by liquid scintillation counting and a high-performance liquid chromatography (HPLC) system equipped with a flow scintillation analyzer. Following extraction, the sediments were air-dried, and the subsamples were combusted. [14C]Methiozolin was degraded in the water phase and partitioned rapidly into the sediments, where it was further degraded to other metabolites, which were identified by HPLC and liquid chromatography- or gas chromatography-tandem mass spectrometry (MS/MS) with authentic standards. The dissipation of methiozolin from the overlying water was rapid (with half-lives of 1.1-1.8 and 3.6-4.9 days in the clay loam and sandy loam, respectively). However, methiozolin dissipation from the sediment phase and the whole system was much slower than from the water phase (with half-lives of 122.0-220.0 and 110.0-130.0 days in the sediment phase of the clay loam and sandy loam and 116.0-166.0 and 70.8-85.7 days in the whole system of the clay loam and sandy loam, respectively).

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of β-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.

Background: Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion–positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). While drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. Methods: We used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. Molecular biology was used to characterize the role of CDA in drug resistance. Integrated analysis of scRNA-seq and scATAC-seq identified gene regulatory networks in resistant cells. Clinical relevance of CDA was evaluated using TCGA datasets, patient-derived cells, and tumor biopsies. Results: CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the na¨ıve cell population by scRNA-seq, and their abundance increased in the acquired-resistance population. Knockdown of CDA had antiproliferative e↵ects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2’-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Conclusions: Targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK-inhibitor resistance in NSCLC.

Gastritis refers to inflammation caused by injury to the gastric epithelium, which is usually due to excessive alcohol consumption and prolonged use of nonsteroidal anti-inflammatory drugs. Millions of individuals worldwide suffer from this disease. However, the lack of safe and promising treatments makes it urgent to explore and develop leads from natural resources. Therefore, food as medicine may be the best approach for the treatment of these disorders. The present study described the protective effects of food-polydeoxyribonucleotides (f-PDRNs) in a rat model of gastric mucosal injury induced by HCl-EtOH. Administration of f-PDRN was performed with low-PRF002 (26 mg/kg/day), medium-PRF002 (52 mg/kg/day) and high-PRF002 (78 mg/kg/day) on the day of autopsy. The site of damage to the mucous membrane was also analysed. In addition, an increase in gastric juice pH, total acidity of gastric juice and decrease in gastric juice secretion were confirmed, and gastric juice secretion-related factors corresponding to the administration of f-PDRN were analysed. Administration of f-PDRN reduced the mRNA expression of histamine H2 receptor, muscarinic acetylcholine receptor M3, cholecystokinin 2 receptor and H+/K+ ATPase related to gastric acid secretion and downregulation of histamine, myeloperoxidase and cyclic adenosine monophosphate. In addition, it was histologically confirmed that the loss of epithelial cells and the distortion of the mucosa were recovered in the group in which f-PDRN was administered compared to the model group with gastric mucosa damage. In summary, the present study suggested that f-PDRN has therapeutic potential and may have beneficial effects if taken regularly as a food supplement.

The applicability of gas chromatography–triple quadrupole mass spectrometry (GC–MS/MS) for determination of dioxins in soil was investigated. The analytical method was validated based on US Environ...

An improved method was developed for determining highly toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in sanitary napkins. Samples were ...

The development of fillers for wrinkle prevention is growing to meet rising demands to reduce the aging of skin. In this experiment, we confirmed the effects of human collagen and hyaluronic acid filler biodegradation for wrinkle reduction using a photo-aging mouse model. A total of 10 hairless mice (SKH1-Hrhr) were randomly divided into two groups and injected with hyaluronic acid and human-derived collagen filler. At 0, 2, 4, 8, and 12 weeks, PRIMOSlite®, folliscope, and MRI were used to evaluate the biodegradability of the fillers after the injections. We also studied the photo-aging mouse model for skin roughness and histological evaluation and confirmed that the filler injection had excellent anti-wrinkle effects. Human-derived collagen fillers had excellent biodegradability compared to that of hyaluronic acid fillers. The skin surface roughness in the photo-aging mouse models was significantly reduced after injections of human-derived collagen filler. Our results showed that the human-derived collagen filler had excellent biodegradability and effectively reduced wrinkle formation in a photo-aging mouse model. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dermal fillers have become popular due to the increased demand for skin rejuvenation products. Polycaprolactone (PCL), a newly developed bioresorbable medical polymer, has emerged as a durable and safe dermal filler. However, available PCL fillers cause irritation; carrier gels can coagulate PCL particles, block the injection needle, and cause nonhomogeneity of particle suspensions that could be responsible for the observed side effects. To relieve pain, premixing PCL filler with lidocaine. However, this formulation changes the property of the CMC portion of the PCL filler, and possibly results in an uneven suspension of the PCL particles. Hence, a particle-free PCL homogeneously solubilized in water was developed to overcome these limitations. This study aimed to assess the in vivo safety, biodegradability, and neocollagenesis ability of a novel PCL filler, DLMR01 using a rat model. Fillers were characterized after injecting a vehicle control or DLMR01 using a digital camera, folliscope, and a three-dimensional profiling system. Biopsy was performed to evaluate biocompatibility and neocollagenesis. Skin elasticity was measured using a Cutometer. DLMR01 caused no needle occlusion by particle aggregation or laborious injectability. Filler nodules dispersed to surrounding tissues within 6 hours without further granuloma formation. Histological inspection revealed no tissue residual material or foreign body reaction during the 12-week test period. DLMR01 increased dermal thickness, collagen regeneration, and skin elasticity. In conclusion, this study demonstrates the potential of DLMR01 for dermal rejuvenation in a rat model.

Ultraviolet light-emitting diodes (UV-LEDs) are a novel light source for phototherapy. This study aimed to evaluate the therapeutic effects of UV-LEDs on psoriasis. Importantly, 310 nm UV-LEDs have not been studied in psoriasis in vitro and in vivo. Effects due to 310 nm UV-LED and 311 nm narrowband ultraviolet B (NBUVB) irradiation were compared for suppressing IL-22-induced activation of STAT3 expression using cell viability assay, western blotting, and immunocytochemistry. C57BL/6 mice were topically treated with imiquimod (IMQ) for 6 consecutive days and degenerative changes were observed. Test groups were irradiated with a 310 nm UV-LED and 311 nm NBUVB. Phenotypic observations, histopathological examinations, and ELISA were conducted with skin and blood samples. STAT3-dependent IL-22 signalling and effects in keratinocytes are negatively regulated by the 310 nm UV-LED, which significantly ameliorated IMQ-induced psoriasis-like dermatitis development and reduced Th17 cytokine levels (IL-17A, IL-22) in serum and dorsal skin. Histopathological findings showed decreases in epidermal thickness and inflammatory T-cell infiltration in the UV-LED-irradiated groups. Quantitative PCR confirmed a UV radiation energy-dependent decrease in IL-17A and IL-22 mRNA levels. The results demonstrated that UV-LEDs had anti-inflammatory and immunoregulatory effects. So, UV-LED phototherapy inhibits psoriasis development by suppressing STAT3 protein and inflammatory cytokines and could be useful in treating psoriasis.

Gram-negative bacteria have an outer membrane inhibiting the entry of antibiotics. Porins, found within the outer membrane, are involved in regulating the permeability of &beta, lactam antibiotics. &beta, lactamases are enzymes that are able to inactivate the antibacterial properties of &beta, lactam antibiotics. Interestingly, porins and &beta, lactamase are found in outer membrane vesicles (OMVs) of &beta, lactam-resistant Escherichia coli and may be involved in the survival of susceptible strains of E. coli in the presence of antibiotics, through the hydrolysis of the &beta, lactam antibiotic. In this study, OMVs isolated from &beta, lactam-resistant E. coli and from mutants, lacking porin or &beta, lactamase, were evaluated to establish if the porins or &beta, lactamase in OMVs were involved in the degradation of &beta, lactam antibiotics. OMVs isolated from E. coli deficient in &beta, lactamase did not show any degradation ability against &beta, lactam antibiotics, while OMVs lacking OmpC or OmpF showed significantly lower levels of hydrolyzing activity than OMVs from parent E. coli. These data reveal an important role of OMVs in bacterial defense mechanisms demonstrating that the OmpC and OmpF proteins allow permeation of &beta, lactam antibiotics into the lumen of OMVs, and antibiotics that enter the OMVs can be degraded by &beta, lactamase.

Friction stir welding has the advantages of producing less material deformation and of simple joining of relatively thick materials, but the disadvantages of forming relatively large heat-affected zones around weld areas. In addition, in research on reductions in bulletproof performance in heat-affected zones, it is necessary to evaluate the ballistic limit velocity (V50), which measures bulletproof performance, and this requires specimens of a certain minimum size and has only limited application to local areas such as heat-affected zones. Instrumented indentation testing (IIT), a method of measuring material properties by utilizing load-depth curves measured by a small indenter leaving fine marks on the material, has no specimen size requirements; in addition, it has simple test procedures and is nondestructive. Here a theoretical model is proposed for evaluating V50 of aluminum alloys by ductile hole formation using IIT. Heat-affected zones generated after friction stir welding of for 7000-series aluminum alloys were simulated, and the model was validated through comparison with the conventional V50 test. In addition, there is currently no way to directly evaluate V50 for welded areas in 7000-series aluminum, but here IIT was used to assess V50 for each local part of the welded specimen. The conventional V50 test takes 15 min per shot and cannot be reused of specimens, but the test using IIT takes 1 min to complete one test and has benefits in terms of time, cost and safety.

HA (Hyaluronic acid) filler, the most commonly used dermal filler, causes several side effects. HA-PN (Hyaluronic acid-Polynucleotide), a new composite filler, has excellent biocompatibility and induces tissue regeneration. In this study, we compare the efficacies and safety profiles of these fillers. The characteristics of HA and HA–PN fillers were compared using scanning electron microscopy and rheometry. No morphological difference was noted between the fillers. However, the latter had higher viscosity and elasticity values. The HA-PN filler induced higher cell migration than the HA filler in a wound healing assay. It was also found to stimulate better collagen synthesis in human and mouse fibroblasts. The HA and HA–PN fillers were injected into SKH1 hairless mice to determine changes in their volume for up to 24 weeks. Increased cell migration and collagen synthesis were observed in mice injected with the HA–PN complex filler. Although the safety and durability of the HA and HA–PN fillers were similar, the latter induced a lower transient receptor potential vanilloid 4 expression and caused less stimulation upon injection. In conclusion, HA–PN complex fillers can stimulate fibroblast growth and facilitate volume growth and skin regeneration.

The mammalian Target of Rapamycin (mTOR) pathway regulates a variety of physiological processes, including cell growth and cancer progression. The regulatory mechanisms of these signals are extremely complex and comprise many feedback loops. Here, we identified the deubiquitinating enzyme ovarian tumor domain-containing protein 5 (OTUD5) as a novel positive regulator of the mTOR complex (mTORC) 1 and 2 signaling pathways. We demonstrated that OTUD5 stabilized β-transducin repeat-containing protein 1 (βTrCP1) proteins via its deubiquitinase (DUB) activity, leading to the degradation of Disheveled, Egl-10, and pleckstrin domain-containing mTOR-interacting protein (DEPTOR), which is an inhibitory protein of mTORC1 and 2. We also showed that mTOR directly phosphorylated OTUD5 and activated its DUB activity. RNA sequencing analysis revealed that OTUD5 regulates the downstream gene expression of mTOR. Additionally, OTUD5 depletion elicited several mTOR-related phenotypes such as decreased cell size and increased autophagy in mammalian cells as well as the suppression of a dRheb-induced curled wing phenotype by RNA interference of Duba, a fly ortholog of OTUD5, in Drosophila melanogaster. Furthermore, OTUD5 knockdown inhibited the proliferation of the cancer cell lines with mutations activating mTOR pathway. Our results suggested a positive feedback loop between OTUD5 and mTOR signaling pathway.

Ultraviolet (UV) light produces an immunomodulatory effect on the skin and is widely used for the treatment of chronic inflammatory skin diseases. UV light emitting diodes (UV-LEDs) are a new and promising source of UV radiation. However, their mechanism of action remains largely unknown. In this study, we tested the safety and effectiveness of UV-LED irradiation for the treatment of atopic dermatitis (AD) in an NC/Nga mouse model. Mice were divided into seven groups of eight mice each. Application of Dermatophagoides farinae (Df) extract ointment for four weeks induced AD-like skin lesions. Subsequently, the mice were exposed to UV-LEDs, narrow band UVB, or UVA irradiation three times per week. We assessed the immunosuppressive effects of 310 nm (50 mJ cm-2) and 340 nm (5 J cm-2) UV-LED irradiation. Histological analyses using hematoxylin-eosin, toluidine blue, and immunohistochemical staining were performed. In addition, the serum levels of IgE, inflammatory cytokines and chemokines were measured using enzyme-linked immunosorbent assays (ELISAs). UV-LED irradiation significantly alleviated AD-like skin symptoms, including edema, erythema, dryness, and itching, by modulating Th1 and Th2 responses, transepidermal water loss (TEWL), and scratching behavior in NC/Nga mice. These results suggest that UV-LEDs can improve the treatment of inflammatory skin diseases.

Background and objective Various studies have investigated treatment for vaginal laxity with microablative fractional carbon dioxide CO2 laser in humans; however, this treatment has not yet been studied in an animal model. Herein, we evaluate the therapeutic effects of fractional CO2 laser for tissue remodeling of vaginal mucosa using a porcine model, with the aim of improving vaginal laxity. Study design/materials and methods The fractional CO2 laser enables minimally invasive and non-incisional procedures. By precisely controlling the laser energy pulses, energy is sent to the vaginal canal and the introitus area to induce thermal denaturation and contraction of collagen. We examined the effects of fractional CO2 laser on a porcine model via clinical observation and ultrasound measurement. Also, thermal lesions were histologically examined via hematoxylin-eosin staining, Masson's trichrome staining, and Elastica van Gieson staining and immunohistochemistry. Results The three treatment groups, which were determined according to the amount of laser-energy applied (60, 90, and 120 mJ), showed slight thermal denaturation in the vaginal mucosa, but no abnormal reactions, such as excessive hemorrhaging, vesicles, or erythema, were observed. Histologically, we also confirmed that the denatured lamina propria induced by fractional CO2 laser was dose-dependently increased after laser treatment. The treatment groups also showed an increase in collagen and elastic fibers due to neocollagenesis and angiogenesis, and the vaginal walls became firmer and tighter because of increased capillary and vessel formation. Also, use of the fractional CO2 laser increased HSP (heat shock protein) 70 and collagen type I synthesis. Conclusion Our results show that microablative fractional CO2 laser can produce remodeling of the vaginal connective tissue without causing damage to surrounding tissue, and the process of mucosa remodeling while under wound dressings enables collagen to increase and the vaginal wall to become thick and tightened. Lasers Surg. Med. 50:940-947, 2018. © 2018 Wiley Periodicals, Inc.

Altered expression of suppressor of cytokine signaling (SOCS) is found in various tumors. However, regulation of SOCS2 by upstream molecules has yet to be clearly elucidated, particularly in tumor cells. SCOCS2 expression was examined in tumor cells transfected with an inducible p53 expression system. The impact of SOCS2 on cell proliferation was measured with in vitro assays. Inhibition of tumorigenicity by SOCS2 knockdown was assessed via a mouse model. Expression profiles were compared and genes differentially expressed were identified using four types of p53-null cells (Saos, HLK3, PC3, and H1299) and the same cells stably expressing p53. Twelve kinds of target genes were simultaneously upregulated or downregulated by p53 in three or more sets of p53-null cells. SOCS2 expression was reciprocally inhibited by inducible p53 expression in p53-null cells, even colon cancer cells. SOCS2 promoter activity was inhibited by wild type but not mutant p53. SOCS2 knockdown inhibited tumor growth in vitro and in an animal xenograph model. SOCS2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. SOCS2 expression was heterogeneously upregulated in some human colon cancers. Thus, SOCS2 was upregulated by p53 dysfunction and seemed to be associated with the tumorigenic potential of colon cancer., Colon cancer: A delicate balance to regulate growth Insights into a signaling protein’s role in cell growth could inform new therapeutic strategies for treating colon cancer. SOCS-2 acts as an ‘off switch’ for cell signaling pathways. It has been identified as possibly protective against many cancers, although some cancers are associated with elevated SOCS-2 levels. Researchers led by Daeghon Kim at Chonbuk National University Hospital in South Korea have now shown that the effects of SOCS-2 are apparently dependent on how much of it is present. Moderate levels of SOCS-2 can suppress growth in colon cancer cells, but Kim’s team showed that excessive SOCS-2 has the opposite effect, promoting proliferation. The researchers also identified a gene commonly mutated in cancer cells that can drive overproduction of SOCS-2. Drugs that inhibit SOCS-2 or block its production may therefore offer useful treatments for colorectal cancer.

Outer membrane vesicles (OMVs) containing various bacterial compounds are released from mainly gram-negative bacteria. Secreted OMVs play important roles in the ability of a bacterium to defend itself, and thus contribute to the survival of bacteria in a community. In this study, we collected OMVs from β-lactam antibiotic-resistant Escherichia coli established by conjugation assay and the parental β-lactam antibiotic-susceptible strain, and performed comparative proteomic analysis to examine whether these OMVs carried β-lactam-resistant compounds. We also investigated whether both types of OMVs could protect susceptible cells from β-lactam-induced death and/or directly degrade β-lactam antibiotics. Several proteins that can be involved in degrading β-lactam antibiotics were more abundant in OMVs from β-lactam-resistant E. coli, and thus OMVs from β-lactam resistant E. coli could directly and dose-dependently degrade β-lactam antibiotics and fully rescue β-lactam-susceptible E. coli and other bacterial species from β-lactam antibiotic-induced growth inhibition. Taken together, present study demonstrate that OMVs from β-lactam-resistant E. coli play important roles in survival of antibiotic susceptible bacteria against β-lactam antibiotics. This finding may pave the way for new efforts to combat the current global spread of antibiotic resistances, which is considered to be a significant public health threat.

Cabbage reference material for pesticide multi-residue analysis was developed in accordance with the ISO Guide 35, ISO Guide 13528 and European Union Reference Laboratories-Proficiency Test standard protocols. Ten pesticides (acetamiprid, azoxystrobin, boscalid, buprofezin, carbendazim, difenoconazole, ethofenprox, imidacloprid, pyraclostrobin and tebuconazole) detected at relatively high levels in agricultural products in Korea were selected for this study. The developed material was evaluated for homogeneity and stability according to the statistical assessment method specified by international standards. Analysis of variance was carried out to calculate the within-bottle standard variation (s wb) and the between-bottle standard variation (s bb). Values of s wb and s bb varied by less than 4.7% of assigned values. Homogeneity was also assessed using Cochrane testing of outliers. All pesticides in the material were uniformly distributed within or between all bottles. Stability tests were conducted at room temperature (20–30 °C) for 12 days, under cold conditions (4–8 °C) for 40 days, under freezing conditions (− 20 °C) for 70 days and under deep freezer conditions (− 80 °C) for 234 days. Stability was evaluated based on the ISO Guide 35 statistical model, and results showed no significant decrease in stability during storage for any pesticide under any condition. We therefore conclude that the cabbage material could be used for future proficiency tests and/or validation of pesticide residue analysis.

Uranium-zirconium-rare earth (U-Zr-RE) fuel slugs for a sodium-cooled fast reactor were manufactured using a modified injection casting method, and investigated with respect to their uniformity, distribution, composition, and phase behavior according to RE content. Nd, Ce, Pr, and La were chosen as four representative lanthanide elements because they are considered to be major RE components of fuel ingots after pyroprocessing. Immiscible layers were found on the top layers of the melt-residue commensurate with higher fuel slug RE content. Scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS) data showed that RE elements in the melt-residue were distributed uniformly throughout the fuel slugs. RE element agglomeration did not contaminate the fuel slugs but strongly affected the RE content of the slugs.

Background Numerous fillers are increasingly used for augmentation of volume loss and relaxation of facial wrinkles. Collagen stimulators are the latest next-generation dermal fillers that can induce neocollagenesis. To investigate biophysical characteristics, safety, and efficacy of newly developed polydioxanone (PDO) filler in comparison with poly-l lactic acid (PLLA) and polycaprolactone (PCL) fillers. Methods In vitro assay, morphology of particles, and rheological property of fillers were measured. A total of 24 female hairless mice (SKH1-Hrhr ) were randomly divided into three groups and injected with PDO, PLLA, or PCL fillers. Durability of fillers was assessed at 0, 3 days, and 1, 4, 8, 12 weeks after injection using folliscope and PRIMOS. To determine biocompatibility and neocollagenesis, histologic evaluation was performed at 1, 4, 8, and 12 weeks after injection. Efficacy was also evaluated based on skin surface roughness changes using PRIMOS in a hairless mouse photoaging model. Results In the particle morphology test, PDO microspheres had an irregular surface and were spherical and uniformly sized. PDO filler demonstrated similar neocollagenesis and inflammatory response to other collagen stimulators. PDO filler showed better biodegradability than PLLA and PCL fillers. In the hairless mouse photoaging model, there was a statistically significant decrease in skin surface roughness after PDO filler injection. Conclusions Our data suggest that newly developed collagen stimulating PDO filler might be a safe and effective option for correction of volume loss and rejuvenation of photoaging skin.

Conditioned media from various sources comprise numerous growth factors and cytokines and are known to promote the regeneration of damaged tissues. Among these, natural killer cell conditioned medium (NK‑CdM) has been shown to stimulate collagen synthesis and the migration of fibroblasts during the wound healing process. With a long‑term aim of developing a treatment for skin photoaging, the ability of NK‑CdM to prevent ultraviolet‑B (UV‑B) damage was assessed in neonatal human dermal fibroblasts (NHDFs) and an in vitro reconstructed skin model. The factors present in NK‑CdM were profiled using an antibody array analysis. Protein and mRNA levels in UV‑B exposed NHDFs treated with NK‑CdM were measured by western blotting and quantitative reverse transcription‑PCR, respectively. The total antioxidant capacity of NK‑CdM was determined to assess its ability to suppress reactive oxygen species. The anti‑photoaging effect of NK‑CdM was also assessed in a 3D reconstituted human full skin model. NK‑CdM induced proliferation of UV‑B‑treated NHDFs, increased procollagen expression, and decreased matrix metalloproteinase (MMP)‑1 expression. NK‑CdM also exhibited a potent antioxidant activity as measured by the total antioxidant capacity. NK‑CdM inhibited UV‑B‑induced collagen degradation by inactivating MAPK signaling. NK‑CdM also elicited potential anti‑wrinkle effects by inhibiting the UV‑B‑induced increase in MMP‑1 expression levels in a 3D reconstituted human full skin model. Taken together, the suppression of both UV‑B‑induced MMP‑1 expression and JNK activation by NK‑CdM suggests NK‑CdM as a possible candidate anti‑skin aging agent.

Silicone is used widely for tissue augmentation in humans. However, late complications, such as delayed inflammation and capsular contracture, remain uncharacterized, despite their importance. In the present study, we aimed to determine whether mechanical and thermal damage induce capsular inflammation around a foreign body, and elucidate the biological mechanism underlying this phenomenon. We injected silicone into the subcutaneous layer of the skin of New Zealand white rabbits. The rabbits were divided into two groups: the control group received no treatment; in the experimental group, external force was applied near the injection silicone using high-intensity focused ultrasound (HIFU). Tissues near the injected silicone were harvested from both groups on Days 4, 7, and 30 after HIFU treatment for comparative analysis. Visual and histological examinations showed clearly increased inflammation in the experimental group compared with that in the control group. Furthermore, capsular tissue from the experimental group displayed markedly increased collagen production. Immunofluorescence revealed marked activation of macrophages in the early stages of inflammation (Days 4 and 7 after HIFU treatment), which decreased on Day 30. Assessment of cytokine activation showed significantly increased expression of heat shock protein (HSP)27, HSP60, HSP70, toll-like receptor (TLR)2, TLR4, and interleukin-8 in the experimental group. The expression of transforming growth factor-β1 did not increase significantly in the experimental group. In conclusion, damage to tissues around the injected silicone induced capsular inflammation. Macrophages and damage-associated molecular pattern molecules were involved in the early stages of inflammation. HSP release activated TLRs, which subsequently activated innate immunity and induced the inflammatory response.

The U–Zr alloy is a candidate for fuel to be used as metallic fuel in sodium-cooled fast reactors (SFRs). Its chemical composition before and after annealing at the operational temperature of SFRs (610°C) was investigated using X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction. The original alloy surface contained uranium oxides with the U(IV) and U(VI) oxidation states, Zr2O3 , and a low amount of uranium metal. After annealing at 610°C, the alloy was composed of uranium metal, uranium carbide, uranium oxide with the U(V) valence state, zirconium metal, and amorphous carbon. Meanwhile, X-ray diffraction data indicate that the bulk composition of the alloy remained unchanged.

In heterojunction silicon solar cells (HJ-SCs), there is a possibility to reduce contact resistance at the front electrode by using a high-conductivity ( ${\sigma _d}$ ) emitter. A hydrogen bonding configuration in the doped layers shows an increase in defect density with the doping, although the doping increases ${\sigma _d}$ within a certain limit. Hence, a two-layer stacked emitter was used: one with a higher ${\sigma _d}$ and the other with a reduced defect density. The emitter was stacked as a 3-nm-thick 3% doped (p2) layer with 7-nm-thick 0.5% doped (p1) double layer. A higher hydrogenation of the p2 layer showed better device performance, as it reduces series resistance from 2.4 to 1.5 Ω⋅cm2. Furthermore, the carrier lifetime measurement, the atomic distribution across various layers, and the high-resolution transmission electron microscopy images show that the higher hydrogenation of the p2 layer might also have improved the a-Si:H/c-Si interface passivation, consequently improving the open-circuit voltage ( ${V_{{\rm{oc}}}}$ ) and efficiency ( η ) of the HJ-SCs. The experimental results were found to be consistent with simulation results. Finally, the HJ-SCs with the hydrogen diluted p2/p1 stacked emitter show ${V_{{\rm{oc}}}}$ of 710 mV, fill factor of 75.43%, and η close to 21%.

Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), regulates genes involved in cell lineage and differentiation through methylating lysine 27 on histone H3 (H3K27me3). Recurrent gain-of-function mutations of EZH2 have been identified in various cancer types, in particular, diffuse large B-cell lymphoma (DLBCL), through large-scale genome-wide association studies and EZH2 depletion or pharmacological inhibition has been shown to exert an antiproliferative effect on cancer cells, both in vitro and in vivo. In the current study, a combination of pomalidomide and GSK126 synergistically inhibited the growth of EZH2 gain-of-function mutant Diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, this synergistic effect appeared to be dependent on cereblon (CRBN), a cellular receptor of pomalidomide, but not degradation of IKAROS family zinc finger 1 (IKZF1) or IKAROS family zinc finger 3 (IKZF3). RNA sequencing analyses revealed that co-treatment with GSK126 and pomalidomide induced specific gene sets involved in B-cell differentiation and apoptosis. Synergistic growth inhibition and B-cell differentiation were further validated in xenograft mouse models. Our collective results provide a molecular basis for the mechanisms underlying the combined therapeutic effects of PRC2 inhibitors and pomalidomide on EZH2-mutated DLBCL.

The direct interactions of bacterial membranes and polycyclic aromatic hydrocarbons (PAHs) strongly influence the biological processes, such as metabolic activity and uptake of substrates due to changes in membrane lipids. However, the elucidation of adaptation mechanisms as well as membrane phospholipid alterations in the presence of phenanthrene (PHE) from α-proteobacteria has not been fully explored. This study was conducted to define the degradation efficiency of PHE by Sphingopyxis soli strain KIT-001 in a newly isolated from Jeonju river sediments and to characterize lipid profiles in the presence of PHE in comparison to cells grown on glucose using quantitative lipidomic analysis. This strain was able to respectively utilize 1-hydroxy-2-naphthoic acid and salicylic acid as sole carbon source and approximately 90% of PHE (50 mg/L) was rapidly degraded via naphthalene route within 1 day incubation. In the cells grown on PHE, strain KIT-001 appeared to dynamically change profiles of metabolite and lipid in comparison to cells grown on glucose. The levels of primary metabolites, phosphatidylethanolamines (PE), and phosphatidic acids (PA) were significantly decreased, whereas the levels of phosphatidylcholines (PC) and phosphatidylglycerols (PG) were significantly increased. The adaptation mechanism of Sphingopyxis sp. regarded mainly the accumulation of bilayer forming lipids and anionic lipids to adapt more quickly under restricted nutrition and toxicity condition. Hence, these findings are conceivable that strain KIT-001 has a good adaptive ability and biodegradation for PHE through the alteration of phospholipids, and will be helpful for applications for effective bioremediation of PAHs-contaminated sites.

Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

For constructing marine liquefied natural gas (LNG) fuel/storage tanks, high manganese steel is being recognized as an alternative to stainless steel, nickel alloy, and aluminum alloy. In this study, the nonlinear tensile behavior of high manganese steel was investigated and numerically simulated at cryogenic temperatures at which natural gas exists as a liquid. Physical experimental tensile tests were carried out for a flat test specimen at 293 K and 110 K. In particular, the tensile behavior of a flat hole-notched high manganese steel specimen was experimentally obtained. A specimen with a hole was readily fractured compared to one without a hole. Tensile behavior of high manganese steel at the two cryogenic temperatures was compared to that of stainless steel, nickel, and aluminum alloy. In addition, numerical tests were performed for flat tensile specimens under identical experimental conditions. The elastoplastic damage model was derived and implemented using an Abaqus user-defined subroutine to appropriately simulate material behavior and degradation. The influence of some parameters on tensile behavior was investigated. The simulation results satisfactorily replicated the nonlinear tensile behavior of high manganese steel. The proposed numerical method, which is based on the damage-coupled material constitutive model, can be applied to structural analysis on the finite element analysis platform considering mechanical nonlinearities induced by severe conditions such as cryogenic temperature.

OBJECTIVE High cholesterol level is a risk factor for coronary artery disease, and coronary artery disease is a major risk factor for out-of-hospital cardiac arrest (OHCA). However, the effect of cholesterol level on outcomes of OHCA has been poorly studied. This study aimed to determine the effect of cholesterol level on outcomes of OHCA. METHODS This cross-sectional study used the CAPTURES (Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance) project database in Korea. Multivariable conditional logistic regression analysis was performed to estimate the effect of cholesterol level on outcomes in OHCA. RESULTS In all, 584 cases of OHCA were analyzed; those with cholesterol levels

DYRK1A is a major causative gene in Down syndrome (DS). Reduced incidence of solid tumors such as neuroblastoma in DS patients and increased vascular anomalies in DS fetuses suggest a potential role of DYRK1A in angiogenic processes, but in vivo evidence is still scarce. Here, we used zebrafish dyrk1aa mutant embryos to understand DYRK1A function in cerebral vasculature formation. Zebrafish dyrk1aa mutants exhibited cerebral hemorrhage and defects in angiogenesis of central arteries in the developing hindbrain. Such phenotypes were rescued by wild-type dyrk1aa mRNA, but not by a kinase-dead form, indicating the importance of DYRK1A kinase activity. Chemical screening using a bioactive small molecule library identified a calcium chelator, EGTA, as one of the hits that most robustly rescued the hemorrhage. Vascular defects of mutants were also rescued by independent modulation of calcium signaling by FK506. Furthermore, the transcriptomic analyses supported the alterations of calcium signaling networks in dyrk1aa mutants. Together, our results suggest that DYRK1A plays an essential role in angiogenesis and in maintenance of the developing cerebral vasculature via regulation of calcium signaling, which may have therapeutic potential for DYRK1A-related vascular diseases., Summary: The roles of DYRK1A in angiogenesis and maintenance of the developing cerebral vasculature mediated by calcium signaling were revealed using zebrafish dyrk1aa knockout mutants.

Ethnopharmacological relevance Stichopus japonicus (sea cucumber), edible traditional food in Asia, and its extracts are renowned for their wound healing, pain relieving, and cosmetic effects in traditional medicine. Holothurins, toxins isolated from sea cucumber, are thought to be active components for their beneficial effects. However, researchers have yet to outline specific mechanisms thereof. Aim of the study The present study was designed to evaluate the anti-melanogenic and anti-wrinkle properties of S. japonicus viscera extracts (VF) on the skin via in vitro and ex vivo experiments and to assess the anti-aging effects of S. japonicus viscera extracts in relation to known wound healing and cosmetic processes. Materials and methods The viscera of live S. japonicus specimens were freeze dried and ground into a powder. Aqueous extracts were subsequently prepared from the concentrated powder using a water extraction method. To investigate the inhibitory effects of VF on melanogenesis, mushroom tyrosinase activity assay and melanin assay were performed on Melan-A cells. To further delineate the anti-melanogenic properties of VF, western blot analysis for tyrosinase, TRP-1, TRP-2, MITF, and ERK was conducted. Changes in collagen synthesis in human dermal fibroblast (HDF) were evaluated via CCK-8 assay and immunocytochemistry to determine the anti-wrinkle effects of VF. Finally, anti-aging properties were examined in a human skin equivalent ex vivo model. Results In Melan-A cells, VF treatment reduced melanin contents in a concentration-dependent manner. The anti-melanogenic effects of VF appeared to be due to enzymatic inhibition of tyrosinase. In CCK-8 assay, VF also significantly increased the viability of HDFs in a concentration-dependent manner. Immunoblot analysis revealed phosphorylation of ERK in HDFs treated with VF. In a human skin equivalent ex vivo model (Neoderm®-ED), VF treatment at a concentration of 50 μg/ml enhanced collagen type IV and Ki-67 expression and downregulated MMP-9 expression. Conclusion This study demonstrated that aqueous extracts from S. japonicus viscera are effective whitening and anti-aging agents that stimulate ERK signaling to inhibit melanin synthesis and promote collagen synthesis.

In this study, we verified the relationship among the electrical conductivity, chemical durability, and structure of conductive vanadate glass in which BO₃ and BO₄ and V 4+ and V 5+ coexist simultaneously. We prepared samples of vanadium borophosphate glass with various compositions, given by 50V₂O 5 -xB₂O₃-(50-x)P₂O 5 (x = 0 ~ 20 mol%) and 70V₂O 5 -xB₂O₃-(70-x)P₂O 5 (x = 0 ~ 10 mol%), and analyzed the electrical conductivity, chemical durability, FT-IR spectroscopy, thermal properties, density, and molar volume. Substituting B₂O₃ for P₂O 5 was found to improve the electrical conductivity, chemical durability, and thermal properties. From these results, we can draw the following conclusions. First, the electrons shift from the electron rich V 4+ to the electron deficient BO₃ as the B₂O₃ content increases. Second, the improvement in chemical durability and thermal properties is attributed to an increase in cross-linked structures by changing from a BO₃ structure to a BO₄ structure.

In this study, we prepared cadmium phosphate glasses with various compositions, given by χCdO-(100 - χ)P₂O 5 (χ = 10.55 mol%), and analyzed their Fourier transform infrared spectra, dissolution rate, thermal expansion coefficient, glass transition temperature, glass softening temperature, and optical band gap. We found that the thermal expansion coefficient and dissolution rate increased while the glass transition temperature and glass softening temperature decreased with increasing CdO content. These results suggest that CdO acts as a network modifier in binary phosphate glass and weakens its structure.

Although Danggui is the root of Angelica gigas NAKAI in the Korean Pharmacopoeia, it is determined that Danggui is also the root of Angelica sinensis (OLIV.) DIELS in China and Hong Kong, as well as the root of Angelica acutiloba KITAGAWA in Japan. Accordingly, we tried to develop an identification method using the main compounds in A. gigas, A. sinensis, and A. acutiloba through HPLC/diode-array detector (DAD). This method was fully validated for linearity, accuracy, precision, recovery, and robustness. Multivariate analysis was also implemented after pattern analysis and monitoring. As a result, each compound pattern of A. gigas, A. sinensis, and A. acutiloba was identified, making it possible to distinguish them from each other.