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The alkyne-functionalized Frechet-type dendrons 2-Dm containing benzamine were synthesized by N-alkylation of the corresponding dendritic benzyl chlorides with 4-ethynylaniline. The oxidative homo-coupling reaction of the alkyne-functionalized Frechet-type dendrons 2-Dm was allowed to provide the first through fourth generation dendrimers 3-Gm with 1,4-diphenylbuta-1,3-diynes at chromophore core in high yields. Their structure of dendrimers was confirmed by 1H and 13C NMR spectroscopy, IR spectroscopy, mass spectrometry, and GPC analysis. The photophysical properties of the synthesized dendrimers was investigated.

In this study, we have prepared a composite adsorbent with highly dispersed Mn and Ag nanocatalyst on the surface of activated carbon (AC) by applying the Radio-Frequency (RF) thermal plasma technique for the efficient removal of VOCs. The ACs before and after metal impregnation with RF plasma treatment were characterized by SEM, TEM, EDS, and nitrogen adsorption analysis. Adsorption behaviors of toluene, acetaldehyde, and formaldehyde on ACs before and after modification were also investigated in fixed-bed systems. The experimental adsorption results for VOCs on parent ACs and metal impregnated ACs (Mn-AC and Mn/Ag-AC) were well explained by modified continuous sigmoidal (MCS) model.

Objectives:Heavy metals caused by industrialization have affected human society for several decades. Because of their toxicity for humans, lots of heavy metal treatments have been developed. However, many of those treatments have economic considerations and environmental disadvantages. This work explored an experimental assessment of adsorption of heavy metals using starfish (SF) biochar through quantitative and qualitative characterization and batch-tests.Methods:Biochar (NACSF) was produced at 300℃ for 2 h in anaerobic conditions. The NACSF was characterized with XRD, XRF, FT-IR, SEM-EDX and elemental analyses. Moreover, batch-tests for each heavy metal using NACSF were conducted with ICP-OES analyses in order to evaluate the adsorption characteristics.Results and Discussion:Based on the characterization results, the NACSF consisted of carbon and CaCO3 mainly. The adsorption rates of Pb, Cu, Zn and Cd decreased in the following order: Pb≫Cu>Zn≥Cd. Moreover, the Langmuir equation fit all adsorption data better than the Freundlich equation. Also, due to the alkalinity of NACSF, the measured pH values of all experimental groups were approximately 7~8.Conclusions:The NACSF treatment was the most effective for Pb removal and it was determined that precipitation and surface adsorption were the most likely mechanisms for Pb removal. Thus, NACSF derived from starfish could be an cost-effective and eco-friendly treatment for heavy metal contaminated wastewater.

Two-dimensional (2D) materials such as graphene, graphene oxide (GO), metal carbides and nitrides (MXenes), transition metal dichalcogenides (TMDS), boron nitride (BN), and layered double hydroxide (LDH) metal–organic frameworks (MOFs) have been widely investigated as potential candidates in various separation applications because of their high mechanical strength, large surface area, ideal chemical and thermal stability, simplicity, ease of functionalization, environmental comparability, and good antibacterial performance. Recently, MXene as a new member of the 2D polymer family has attracted significant attention in water purification, desalination, gas separation, antibacterial, and antifouling applications. Herein, we review the most recent progress in the fabrication, preparation, and modification methods of MXene-based lamellar membranes with the emphasis on applications for water purification and desalination. Moreover, the antibacterial properties of MXene-based membranes show a significant potential for commercial use in water purification. Thus, this review provides a directional guide for future development in this emerging technology.

The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease modeling. Conventionally, spheroid culture is carried out in static conditions, making the media nutrient-deficient around the spheroid periphery. The current approach tries to enhance the capacity of the spheroid culture platform by integrating the perfusion channel for dynamic culture conditions. A pro-inflammatory hepatic model was emulated using a coculture of HepG2 cell line, fibroblasts, and endothelial cells for validating the spheroid culture plate with a perfusable channel across the spheroid well. Enhanced proliferation and metabolic capacity of the microphysiological model were observed and further validated by metabolic assays. A comparative analysis of static and dynamic conditions validated the advantage of spheroid culture with dynamic media flow. Hepatic spheroids were found to have improved proliferation in dynamic flow conditions as compared to the static culture platform. The perfusable culture system for spheroids is more physiologically relevant as compared to the static spheroid culture system for disease and drug analysis.

Whitening research is of particular interest in the cosmetics market. The main focus of whitening research is on melanogenesis inhibition through tyrosinase activity. The mechanism of melanogenesis is involved with tyrosinase activity and p-PKC signaling. In this study, we used Momordica cochinchinensis (Lour.) spreng, a tropical fruit found throughout Southeast Asia, to investigate the inhibitory effect of melanogenesis. M. cochinchinensis contains a high concentration of polyphenols, flavonoids, and unsaturated fatty acids, which might be related to antioxidant activity. This study aimed to determine whether M. cochinchinensis extracts inhibit melanin synthesis in melan-A cells by inhibiting tyrosinase activity and p-PKC signaling. M. cochinchinensis was divided into pulp and aril and extracted under various conditions, and it was confirmed that all pulp and aril extracts have high contents of both phenols and flavonoids. Melan-A cells were treated with PMA for three days to induce melanin synthesis. After PMA treatment, M. cochinchinensis extracts were added to cultured media in a dose-dependent manner. Melanin contents and MTS were used to determine the amount of melanin in live cells. M. cochinchinensis extracts were evaluated for their effects on tyrosinase activity and p-PKC signaling pathways by Western blotting. It was found that M. cochinchinensis extract treatment decreased the amount of melanin and suppressed p-PKC expression. Additionally, tyrosinase activity was reduced after M. cochinchinensis extract treatment in a dose-dependent manner. Therefore, it was concluded that M. cochinchinensis could be used in antimelanogenesis and functional cosmetic materials to improve whitening.

The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS.

Acute kidney injury (AKI) is a common clinical problem that is associated with high mortality due to multiple complex mechanisms. Cisplatin is the most important and highly effective chemotherapeutic agent used for the treatment of various solid tumors; however, it is associated with dose-dependent adverse effects, particularly in the kidney where it can cause severe nephrotoxicity. The pathophysiological basis of cisplatin-induced nephrotoxicity has been investigated over the last few decades, and the key pathological occurrences in cisplatin nephrotoxicity include renal tubular cell injury and death. Necrostatin-1 (Nec-1) has been confirmed to act as a specific and potent small-molecule inhibitor of necroptosis. However, the effects of three structurally distinct necrostatins on cisplatin-induced nephrotoxicity remain ambiguous. The aim of this study was to determine if three types of necrostatins (Nec-1, Nec-3-A, and/or Nec-3-B) can exert protective effects in regard to the AKI induced by cisplatin. Our results indicated that necrostatins can prevent cisplatin induced nephrotoxicity via modulating apoptotic pathways through the suppression of cleaved caspase-3 and also by influencing the function of mitogen-activated protein kinase pathway members, including extracellular signal-regulated kinases, c-Jun N-terminal kinases, and p38, in the renal tubular epithelial cell line LLC-PK1. These findings suggest that necrostatins exert beneficial anti-apoptotic effects in the context of AKI induced by cisplatin.

Cl--ion transporters (2a-2h) were synthesized based on the binding motifs of prodigiosin. Transporter 2e clearly displays Cl--ion transportation activity across both model and live cell membranes. Furthermore, 2e can disrupt Ca2+ homeostasis and increase the intracellular concentration of Ca2+ in the DLD-1 cell. This disruption can lead to Caspase-dependent apoptosis supported by CHOP expression (a marker of ER stress) and the appearance of the cleaved forms of Caspase 3 and PARP.

Algae biomass are suitable carbonaceous precursors. Hierarchical porous carbons were prepared from Chlorella ellipsoidea, one of algae through centrifugation, freeze-drying and carbonization. The activation was carried out by a simple process that involved H2O2 treatment followed by microwave pyrolysis. The adsorption equilibrium and kinetic data of methylene blue were fitted with isotherm and kinetic models, respectively. In addition, the electrochemical properties were measured by cyclic voltammetry. It was found that microwave-assisted porous carbons exhibited higher adsorption capacity and excellent electrochemical performance due to the well-developed hierarchical pore structures.

Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. We describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.

3,3'-Diindolylmethane (DIM), a digestive metabolite originating from cruciferous vegetables, has dietary potential for the treatment of various human intestinal diseases. Although intestinal permeability dysfunction is closely related to the initiation and progression of human intestinal inflammatory diseases (IBDs), the effect of DIM on intestinal permeability is unclear. We evaluated the effect of DIM on the intestinal permeability of human intestinal cell monolayers and the animal model Caenorhabditis elegans, which were treated with IL-1β and Pseudomonas aeruginosa, respectively, to mimic IBD conditions. DIM substantially restored the intestinal permeability of differentiated Caco-2 cells by enhancing the expression of tight junction proteins (including occludin and ZO-1). Compared to the IL-1β single treatment (551.0 ± 49.0 Ω·cm2), DIM (10 μM) significantly increased the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers (919.0 ± 66.4 Ω·cm2, p < 0.001). DIM also ameliorated the impaired intestinal permeability and extended the lifespan of C. elegans fed P. aeruginosa. The mean lifespan of DIM-treated worms (10.8 ± 1.3 days) was higher than that of control-treated worms (9.7 ± 1.1 days, p < 0.01). Thus, DIM is a potential nutraceutical candidate for the treatment of leaky gut syndrome by improving intestinal permeability.

MINI: Recent developments in near-infrared fluorescent imaging have revealed the usefulness of indocyanine green (ICG) for preoperative pulmonary nodule localization. However, it is difficult to determine the resection margins of deep-seated nodules using this technique, given the limited depth penetration and diffusion of ICG through the lung tissue without pooling around the lesion. The optimal fluorescent iodized emulsion, a mixture of ICG solution and Lipiodol (ethiodized oil), can overcome these limitations and may allow the accurate localization and resection of pulmonary nodules. Objective This study was conducted to develop a fluorescent iodized emulsion comprising indocyanine green (ICG) solution and lipiodol (ethiodized oil) and evaluate its feasibility for use in a clinical setting. Background ICG use for the preoperative localization of pulmonary nodules is limited in terms of penetration depth and diffusion. Methods First, fluorescent microscopy was used to investigate the distribution of ICG-lipiodol emulsions prepared using different methods. The emulsions were injected in 15 lung lobes of 3 rabbits under computed tomography fluoroscopy guidance; evaluation with imaging and radiography was conducted after thoracotomy. Subsequently, the emulsions were used to preoperatively localize 29 pulmonary nodules in 24 human subjects, and wedge resections were performed using fluorescent imaging and C-arm fluoroscopy. Results The optimal emulsion of 10% ICG and 90% lipiodol mixed through 90 passages had even distribution and the highest signal intensity under fluorescent microscopy; it also had the best consistency in the rabbit lungs, which persisted for 24 hours at the injection site. In human subjects, the mean diameter of pulmonary nodules was 0.9 ± 0.4 cm, and depth from the pleura was 1.2 ± 0.8 cm. All emulsion types injected were well localized around the target nodules without any side effects or procedure-related complications. Wedge resection with minimally invasive approach was successful in all pulmonary nodules with a free resection margin. Conclusions A fluorescent iodized emulsion prepared by mixing ICG with lipiodol enabled accurate localization and resection of pulmonary nodules.

This paper reports a fast, linear, all-range sensitive and biocompatible humidity sensor using poly lactic glycolic acid (PLGA) as a sensing layer for the first time. The device is fabricated using all printing methods. The high definition interdigitated electrode structure was printed on flexible PET substrate by reverse offset printing setup using silver ink, while PLGA ink was deposited using spin coating. IDEs with two different dimensions were printed with three samples of each. The output of sensor is impedance which decreases with increase in relative humidity in a controlled chamber. The results show excellent stability, obvious response to RH for full range from 0 to 100 %RH with fast response time of 3 s and recovery time of 6 s. Sensor data can be received continuously using smart phone with a Wi-Fi connection with ESP8266 MCUNODE. Sensor’s flexibility test was also performed for 5 mm mechanical bending radius which showed reasonable consistency with results of flat sensor. The biocompatibility of sensor’s active layer was analyzed and confirmed by culturing human small air way epithelial cells for 7 days. To utilize sensor’s feature of being biocompatible, it was then used for human respiration monitoring which enabled the proposed device to be strong candidate for wearable electronics and health monitoring applications.

Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of Ca2+ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2′,7′-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 (25.7 μM). Cellular Ca2+ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation. Keywords: Ginsenoside Rb2, Neurotoxicity, MAPK, Reactive oxygen species

Significance We have completed a screen of ∼106 small molecules to identify compounds that induce cell death in multipotent glioblastoma multiforme (GBM) cancer stem cells (CSCs). This resulted in the identification of a hit class (RIPGBM) that was found to induce apoptosis in GBM CSCs in a cell type-selective manner. Metabolite profiling experiments led to the identification of a proapoptotic derivative of RIPGBM (cRIPGBM), which was found to be selectively formed in GBM CSCs. Mechanistic studies revealed that cRIPGBM induces apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) in a mode that results in the formation of a proapoptotic RIPK2/caspase 1 complex. In a physiologically relevant orthotopic intracranial GBM CSC tumor xenograft mouse model, RIPGBM was found to significantly inhibit in vivo tumor formation., Glioblastoma multiforme (GBM; grade IV astrocytoma) is the most prevalent and aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation, tumor maintenance, metastasis, drug resistance, and recurrence following surgery. Here we report the identification of a small molecule, termed RIPGBM, from a cell-based chemical screen that selectively induces apoptosis in multiple primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of this compound appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an orthotopic intracranial GBM CSC tumor xenograft mouse model, RIPGBM was found to significantly suppress tumor formation in vivo. Our chemical genetics-based approach has identified a drug candidate and a potential drug target that provide an approach to the development of treatments for this devastating disease.

Circadian rhythms are controlled by transcriptional feedback loops of clock genes and proteins. The stability of clock proteins is regulated by post-translational modification, such as phosphorylation by kinases. In particular, casein kinase I (CKI) phosphorylates the PER protein to regulate proteasomal degradation and nuclear localization. Therefore, CKI inhibition can modulate mammalian circadian rhythms. In the present study, we have developed novel CKIα and CKIδ dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 μM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKIα and CKIδ with an IC(50) of 1.8 and 3.6 μM. We further demonstrated that NCC007 lengthened the period of mouse behavioral rhythms in vivo. Thus, NCC007 is a valuable tool compound to control circadian rhythms through CKI inhibition.

The neuroprotective activity of 2-heptyl-3-hydroxy-4(1H)-quinolone (compound 1) was evaluated using the neurotoxicity of glutamate in the HT22 cell line. Compound 1, known as a signal molecule of the bacterial quorum-sensing system, protects neuronal cells from glutamate-induced neurotoxicity by inhibiting cellular Ca2+ uptake and glutamate-triggered ROS accumulation. MAPK signaling pathway inhibition by compound 1 was evaluated by immunoblotting the phosphorylation status of the proteins. Furthermore, pro-apoptotic protein levels and AIF translocation to the nucleus were found to be reduced by compound 1. In conclusion, compound 1 showed neuroprotective effects by inhibiting apoptotic neuronal cell death.

INTRODUCTION Glioblastoma multiforme (GBM) is the most aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation and maintenance, drug resistance, and recurrence following surgery. New therapeutic strategies for the treatment of GBM have recently focused on targeting CSCs. Here we have used an unbiased large-scale screening approach to identify drug-like small molecules that induce apoptosis in GBM CSCs in a cell type-selective manner. METHODS A luciferase-based survival assay of patient-derived GBM CSC lines was established to perform a large-scale screen of ∼one million drug-like small molecules with the goal of identifying novel compounds that are selectively toxic to chemoresistant GBM CSCs. Compounds found to kill GBM CSC lines as compared to control cell types were further characterized. A caspase activation assay was used to evaluate the mechanism of induced cell death. A xenograft animal model using patient-derived GBM CSCs was employed to test the leading candidate for suppression of in vivo tumor formation. RESULTS We identified a small molecule, termed RIPGBM, from the cell-based chemical screen that induces apoptosis in primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of RIPGBM appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an intracranial GBM xenograft mouse model, RIPGBM was found to significantly suppress tumor formation. CONCLUSIONS Our chemical genetics-based approach has identified a small molecule drug candidate and a potential drug target that selectively targets cancer stem cells and provides an approach for the treatment of GBMs.

3-Monochloro-1,2-propanediol (3-MCPD) is a chemical compound that is unintentionally produced during food processing such as acid hydrolysis. There has been reports regarding the role of this chemical compound in reproductive toxicity, as well as genotoxicity, neurotoxicity, and kidney toxicity. In this study, the in vitro muscle toxicity of 3-MCPD was assessed using C2C12 myoblast cells. The reduction in muscle regulatory factors (MRFs), which is related to muscle differentiation, was identified as significant with the increase concentration of 3-MCPD. Also, significantly decreased protein expression in mTOR and p70S6 kinase, which are the downstream targets of the pathway associated with muscle synthesis, was also confirmed. Therefore, the inhibitory effect of 3-MCPD on muscle differentiation is considered to be the cause of suppressing mTOR and p70S6 kinase expression. In conclusion, it was confirmed that 3-MCPD inhibits muscle differentiation in C2C12 myoblasts through suppressing the expression of several genetic factors involving muscle differentiation.

Crocin, one of the major carotenoid pigments of Crocus sativus (saffron), is responsible for antioxidant activity, neuroprotection, and the inhibition of tumor cell proliferation. In order to improve the functionality of crocin, α-glucosyl-(1→6)-trans-crocins (C-Gs) were synthesized using sucrose and dextransucrase from Leuconostoc mesenteroides. High hydrostatic pressure (HHP) technique was applied to the synthesis process of C-Gs in order to improve its transglucosylation yield. A 100 MPa HHP condition enhanced the production yield of C-Gs by 1.95 times compared to that of 0.1 MPa atmospheric pressure. Novel C-Gs were purified by HPLC, and their chemical structures were determined using NMR analysis. Novel C-Gs increased water solubility 4.6-5.7 times and antioxidant activity 1.5-2.6 times, respectively, compared to crocin, and their neuroprotections (cell viability 92.5-100.4 %) on HT22 mouse hippocampal neuronal cells were significantly higher than that of crocin (cell viability 84.6 %). This advanced neuroprotection of novel C-Gs could be highly associated with their enhanced antioxidant activity. Thus, the enhanced water solubility and functionality of novel C-Gs can induce better clinical efficacy of neuroprotection than trans-crocin.

In this study, we investigated changes in the isoflavone content, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activities (DPPH, ABTS), and anti-inflammatory activities of small-seeded and large-seeded soybean cultivars during germination (light/dark conditions). Total isoflavone content was higher at the seed stage in large-seeded soybeans, while it increased after 7 days of germination in small-seeded soybeans, particularly in response to light conditions, under which they had high TPC, TFC, and antioxidant activities. In large-seeded soybeans, the germination environment did not significantly affect TFC or DPPH inhibition, whereas TPC and ABTS inhibition were high under dark germination conditions. Extracts of sprouts exhibited superior anti-inflammatory activities. Nitric oxide production was slightly lower in small-seeded and large-seeded soybeans germinated under light and dark conditions, respectively. Our findings indicate that germinated soybeans improved nutritionally, and that enhancement of bioactivity under different germination environments could contribute to the selection of appropriate soybean cultivars.

Glutamate-induced neurotoxicity is characterized by cellular Ca2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.

In living organisms, intestinal hyperpermeability is a serious symptom that leads to many inflammatory bowel diseases (IBDs). Caenorhabditis elegans is a nonmammalian animal model that is widely used as an assay system due to its short lifespan, transparency, cost-effectiveness, and lack of animal ethics issues. In this study, a method was developed to investigate the effects of different bacteria and 3,3'-diindolylmethane (DIM) on the intestinal permeability of C. elegans with a high-throughput image analysis system. The worms were infected with different gut bacteria or cotreated with DIM for 48 h and fed with fluorescein isothiocyanate (FITC)-dextran overnight. Then, the intestinal permeability was examined by comparing the fluorescence images and the fluorescence intensity inside the worm bodies. This method may also have the potential to identify probiotic and pathogenic intestinal bacteria that affect intestinal permeability in the animal model and is effective for examining the effects of harmful or health-promoting chemicals on intestinal permeability and intestinal health. However, this protocol also has some considerable limitations at the genetic level, especially for determining which genes are altered to control illness, because this method is mostly used for phenotypic determination. In addition, this method is limited to determining exactly which pathogenic substrates cause inflammation or increase the permeability of the worms' intestines during infection. Therefore, further in-depth studies, including investigation of the molecular genetic mechanism using mutant bacteria and nematodes as well as chemical component analysis of bacteria, are required to fully evaluate the function of bacteria and chemicals in determining intestinal permeability.

Environment-friendly and cost-effective carbons were prepared for application in high-performance supercapacitors using bean dregs via carbonization and activation. The prepared samples were characterized using scanning electron microscopy and Brunauer–Emmett–Teller analysis. Furthermore, the electrochemical properties and capacitive behavior of the electrodes were systematically studied using cyclic voltammetry and AC impedance analysis. The porous carbon activated at 900 °C for 60 min had the largest specific surface area (3700 m2 g−1) and the highest capacitance (260 F g−1) at a scan rate of 1 mV s−1.

Background Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene (Aqp2).Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell-specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II.Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein-β (C/EBPβ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBPβ, a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2 However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2 Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect.Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBPβ (but not CREB) binding.

A zeolitic 4A type material was successfully prepared from natural basalt rock by applying an alkali fusion process and hydrothermal synthesis. In particular, the optimum synthetic conditions were examined at different crystallization times. Several methods such as XRD, SEM, EDX, and N2 and CO2 adsorption analysis were used to characterize the synthesized 4A type zeolite. In addition, CO2 adsorption equilibrium capacities for this basalt base zeolite were measured over temperature ranges from 283 to 303 K and pressure ranges from 0.1 to 1500 kPa in a volumetric adsorption apparatus. Then the results were compared to those of commercial zeolite. Moreover, to further investigate the surface energetic heterogeneity of the prepared zeolite, the isosteric heat of adsorption and adsorption energy distribution was determined. We found that basalt based zeolite 4A shows a CO2 adsorption equilibrium capacity of 5.9 mmol g−1 (at 293 K and 1500 kPa) which is much higher than the 3.6 mmol g−1 of the commercial zeolite as its micro-pore surface area, micro-pore volume and surface heterogeneity indicate.

The consumption of sprouts has been steadily increasing due to their being an excellent source of nutrition. It is known that the bioactive constituents of legumes can be increased after germination. In this study, the extract from Senna tora sprouts is shown to exhibit improved radical scavenging activities and better neuroprotective effects in HT22 hippocampal neuronal (HT22) and R28 retina precursor (R28) cells than those from seeds due to an increased content of phenolic constituents, especially compounds 1 and 3-6. A phytochemical investigation of S. tora sprouts resulted in the isolation of two new naphthopyrone glycosides (1-2) with 27 previously reported compounds. Their structures were determined via interpreting spectroscopic data. Compounds 1 and 3-6 were found to possess radical scavenging activities and neuroprotective effects against oxidative stress in both neuronal cells. Hence, Senna tora sprouts and their constituents may be developed as natural neuroprotective agents via antioxidative effects.

In this study, the binary sintering additives Y 2 O 3 -Sc 2 O 3 , were first applied to the Si 3 N 4 system to investigate their effects on microstructure and thermal conductivity. The microstructure and thermal conductivity of both sintered silicon nitride (SSN) and sintered reaction-bonded silicon nitride (SRBSN) were found to be significantly dependent on the additive composition. Among various combinations of Y 2 O 3 and Sc 2 O 3 , 1 mol% Y 2 O 3 −3 mol% Sc 2 O 3 prominently enhanced thermal conductivity, and the enhancement could not be attributed to any difference in microstructure or lattice defects. TEM observation revealed that this composition was more liable to devitrify the glassy phase with a lower degree of stress accumulation, and to possibly produce a grain boundary that was cleaner or with a higher order of atomic arrangement. A microstructure model for thermal conductivity was proposed which took the thermal resistance of the grain boundaries into account. The grain boundary state exerted a remarkable influence on the thermal conductivity of fine microstructures, and the experimentally measured thermal conductivity values were consistent with those given by the proposed model.

Pancreatic insulin-producing β-cell dysfunction and death plays central roles in the onset and progression of both type 1 and type 2 diabetes. Current antidiabetic drugs cannot halt the ongoing progression of β-cell dysfunction and death. In diabetes, a major cause for the decline in β cell function and survival is endoplasmic reticulum (ER) stress. Here, we identified quinazoline derivatives as a novel class of β cell protective agents against ER stress-induced dysfunction and death. A series of quinazoline derivatives were synthesized from dichloroquiazoline utilizing a sequence of nucleophilic reactions. Through SAR optimization, a 2,4-diaminoquinazoline compound 9c markedly protects β cells against ER stress-induced dysfunction and death with 80% maximum rescue activity and an EC50 value of 0.56 µM. Importantly, 9c restores the ER stress-impaired glucose-stimulated insulin secretion response and survival in primary human islet β cells. We showed that 9c protects β cells by alleviating ER stress through the suppression of the induction of key genes of the unfolded protein response and apoptosis.

Hydrocarbon resins, which are defined as low molecular weight, amorphous, and thermoplastic polymers, are widely used as tackifiers for various types of adhesives, as processing aids in rubber compounds, and as modifiers for paint and ink products, and for use in plastics polymers such as isotactic polypropylene. Recently, the quantities of the hydrocarbon resin׳ raw materials which are the side products from naphtha cracking process have decreased because of light-feed cracking such as gas cracking, so new raw materials for hydrocarbon resin production are essential. To be satisfied with the previously mentioned factors, the substitution of hydrocarbon resin raw materials with renewable resources is a worthy consideration. Moreover, new hydrocarbon resin having high adhesion performance, low specific gravity, and good compatibility with various polymers has been requested in various adhesives. To meet those requests, in this study, propylene instead of side product from naphtha cracking as main raw material of hydrocarbon resin were partially used. The propylene serves as a new, sustainable raw material and was successfully grafted onto dicyclopentadiene. The reaction of the propylene with dicyclopentadiene was confirmed because, according to NMR and FT-IR analyses, a pendant methyl-propylene group exists in the structure of the propylene-grafted, hydrogenated dicyclopentadiene hydrocarbon resin. To establish an optimal production condition regarding the propylene-grafted, hydrogenated dicyclopentadiene hydrocarbon resin, numerous experiments were conducted according to the mole ratio of the raw materials and the polymerization temperature. The propylene-grafted, hydrogenated dicyclopentadiene hydrocarbon resin that was manufactured according to optimal conditions results in a lower specific gravity and a high molecular weight, whereby the advantages of the adhesion properties of an SIS-based pressure-sensitive-adhesive are exploited. When the propylene-grafted, hydrogenated dicyclopentadiene hydrocarbon resin was formulated with the SIS-based pressure-sensitive-adhesive, both the heat stability and the shear-adhesion strength are sound.

The catalytic effect of ytterbium oxide (Yb 2 O 3 ) on the nitriding reaction of Si compacts was investigated. Si powder mixtures containing Yb 2 O 3 were prepared and nitrided in the form of compacts with a multi-step heating schedule over the range of 1200 °C–1450 °C. The nitriding profiles of the powder mixture with increasing temperature indicated that Yb 2 O 3 clearly promoted the nitridation of Si compacts at 1200 °C compared with the pure Si compact containing no additives. The critical role of Yb 2 O 3 on the nitridation of Si, was elucidated that Yb 2 O 3 promotes the loss of initial SiO 2 of the raw Si powder via the measurement of the weight changes at low temperature (1100 °C) and thermogravimetric analysis under N 2 atmosphere. It was also found that the β-ratio of fully nitrided Si was closely related to the intermediate degree of nitridation at 1200 °C and 1300 °C.

In order to explore the effect of bulky side chain substituted benzodithiophene (BDT) based polymers on optoelectronic properties, here we have designed and synthesized two new 2D conjugated donor–acceptor (D–A) copolymers P1 and P2 via Stille coupling of 2,3-bis(4-(2-ethylhexyloxy)phenyl)thiophene (BAPT) substituted BDT as (D) unit and 1,3-di(2-bromothien-5-yl)-5-(2-ethylhexyl)thieno[3,4-c]pyrrole-4,6-dione (TPD) or 2,5-ethylhexyl-3,6-bis(5-bromothiophen-2-yl)pyrrolo[3,4-c]-pyrrole-1,4-dione (DPP) as (A) units. The new polymers P1 and P2 showed broad absorption windows with vibronic shoulders indicate π–π stacking of polymer backbones. In addition P1 and P2 showed deep highest occupied molecular orbital (HOMO) energy levels of −5.50, −5.35 eV, respectively which allow delivering high open-circuit voltages (V oc) in bulk heterojunction polymer solar cells (BHJ PSCs). The donor photon energy loss (E g–eV oc) of P1 and P2 are 0.87 and 0.57 which is comparable to the previous reports. BHJ PSCs were fabricated with P1 and P2, and they displayed high V oc of 0.99 and 0.78 V, respectively, with maximum power conversion efficiency of 2.05 and 0.96 % in additive free BHJ PSCs. The polymer field effect transistor mobilities of P1 and P2 are 8.0 × 10−3, 9.2 × 10−5 cm2/V s, respectively.

Recently, the studies about rock physics model (RPM) in shale reservoir are widely performed. In shale reservoir, the degree of the maturity can be estimated by kerogen and GOR (Gas-Oil Ratio). The researches on the rock physics model of shale reservoir with the amount of kerogen have been actively carried out but not with GOR. Thus, in this study, we analyzed the changes in seismic velocity and density, and AVO (Amplitude Variation with Offset) response depending on changes in GOR and the amount of kerogen. Since the shale consists of plate-like particles, it has vertical transverse isotropy (VTI). Therefore we estimated the seismic velocity and density by using Backus averaging method and analyzed AVO responses based on these estimated properties. The results of analysis showed that the changes in the velocity with the GOR variation are small but the velocity changes with the variation in kerogen amount are relatively larger. In case, GOR 180 (Litre/Litre) which is boundary between heavy oil and light oil, when volume fraction of kerogen increased from 5% to 35%, the P-wave velocity normal to the layering increased 51%. That is, it helps estimating maturity of kerogen through the velocity. Meanwhile, when rates of oil-gas mixture are large, the effect of GOR variation on the velocity change became larger. In case volume fraction of kerogen is 5%, the P-wave velocity normal to the layering was estimated in heavy oil (GOR 40) but in light oil (GOR 300). The AVO responses analysis showed class 4 regardless of the GOR and amount of kerogen because variation of poisson`s ratio is small. Therefore, shale reservoir has possibility to have class 4.

The synthesis of pyrazines by the baker’s yeast-mediated reaction of β-keto-α-oximino esters and amides is described. Baker’s yeast reduced oximes selectively over ketones of β-keto-α-oximino esters to give the corresponding β-keto-α-amino ester intermediates, which underwent spontaneous dimerization followed by air-induced aromatization to yield pyrazines. The chemoselective reduction of β-keto-α-oximino amides using baker’s yeast also afforded the corresponding pyrazines. Interestingly, both hydroximes and alkoximes gave the pyrazines by the baker’s yeast-mediated reduction via the corresponding amino ketones, the known precursors of pyrazines. The reaction was strongly dependent upon pH of reaction medium, and gave optimum yields at pH 5. These results demonstrate that pyrazines were synthesized efficiently and eco-friendly using a whole-cell biocatalytic system as an alternative to chemical reduction.