Metal Toxicity across Different Thallus Sections of the Green Macroalga, Ulva australis.

We aimed to identify functional differences between different sections of the thallus of Ulva australis and develop tissue-endpoint combinations to assess the toxicity of six metals (i.e., Ag, As, Cd, Cr, Cu, and Ni). EC50 values for these metals in three sections of the thallus of Ulva were obtained for multiple endpoints: relative growth rate (RGR), chlorophyll a fluorescence, pigment contents, and the expression of the photosynthesis-related gene, rbcL. The responses of the endpoints varied across the respective thallus sections; overall, the most toxic metals were Ag and Cu. These endpoints were the best for evaluating metal toxicity: ETRmax of the middle thallus sections for Ag toxicity; RGR of the middle thallus section for As and Cd; ETRmax of the marginal thallus section for Cr; Chl b contents of the marginal thallus section for Cu; RGR of the basal thallus section for Ni. The EC50 values for the inhibition of ETRmax in middle (0.06 mg∙L-1) and Chl b in the marginal thallus sections (0.06 mg∙L-1) were all lower than those of the quality standard for wastewater discharge values of Ag and Cu in Republic of Korea and the US, pointing to the suitability of U. australis-based endpoints for risk assessment.

Evaluating the prebiotic effect of oligosaccharides on gut microbiome wellness using in vitro fecal fermentation.

We previously proposed the Gut Microbiome Wellness Index (GMWI), a predictor of disease presence based on a gut microbiome taxonomic profile. As an application of this index for food science research, we applied GMWI as a quantitative tool for measuring the prebiotic effect of oligosaccharides. Mainly, in an in vitro anaerobic batch fermentation system, fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS), inulin (IN), and 2'-fucosyllactose (2FL), were mixed separately with fecal samples obtained from healthy adult volunteers. To find out how 24 h prebiotic fermentation influenced the GMWI values in their respective microbial communities, changes in species-level relative abundances were analyzed in the five prebiotics groups, as well as in two control groups (no substrate addition at 0 h and for 24 h). The GMWI of fecal microbiomes treated with any of the five prebiotics (IN (0.48 ± 0.06) > FOS (0.47 ± 0.03) > XOS (0.33 ± 0.02) > GOS (0.26 ± 0.02) > 2FL (0.16 ± 0.06)) were positive, which indicates an increase of relative abundances of microbial species previously found to be associated with a healthy, disease-free state. In contrast, the GMWI of samples without substrate addition for 24 h (-0.60 ± 0.05) reflected a non-healthy, disease-harboring microbiome state. Compared to the original prebiotic index (PI) and α-diversity metrics, GMWI provides a more data-driven, evidence-based indexing system for evaluating the prebiotic effect of food components. This study demonstrates how GMWI can be applied as a novel PI in dietary intervention studies, with wider implications for designing personalized diets based on their impact on gut microbiome wellness.

Comparative analysis of prebiotic effects of four oligosaccharides using in vitro gut model: digestibility, microbiome, and metabolome changes.

Fructooligosaccharides (FOS), Ad-fructooligosaccharides (Ad-FOS), resistant maltodextrin (RMD), and maltooligosaccharides (MOS) are commercially available prebiotic oligosaccharides. In this study, the effects of prebiotics on the human gut microbial ecosystem were evaluated using an in vitro gut model. FOS and Ad-FOS showed tolerance to digestion, whereas RMD and MOS showed moderate digestion by digestive enzymes. In in vitro fecal fermentation, Bifidobacterium spp. increased in the following order: FOS, Ad-FOS, MOS, and RMD, whereas Bacteroides spp. increased in RMD medium. Bacteroides xylanisolvens exhibited cross-feeding by enabling the growth of other beneficial bacteria during co-culture in RMD medium. In metabolome analysis, total short-chain fatty acids (SCFAs) were highly produced in the following order: RMD, FOS, MOS, and Ad-FOS; acetate in the order of FOS, MOS/RMD, and Ad-FOS; butyrate in the order of RMD, MOS, FOS, and Ad-FOS; and propionate only in RMD. In addition, the conversion of betaine to trimethylamine was rarely affected in the following order: MOS, RMD, FOS, and Ad-FOS. Lastly, the four oligosaccharides inhibited the adhesion of pathogenic Escherichia coli to human epithelial cells to a similar extent. The comparative analysis results obtained in this study will provide comprehensive information of these substances to manufacturers and customers.

Evaluating ecotoxicological assays for comprehensive risk assessment of toxic metals present in industrial wastewaters in the Republic of Korea.

Toxicity tests represent a rapid, user-friendly and cost-effective means to assess the impact of wastewater quality on aquatic ecosystems. There are not many cases where wastewater management standards are set based on various bio-based ecotoxicity values. Here, we tested a novel multitaxon approach to compare standard water quality indices to toxicity metrics obtained from ecotoxicity tests, conducted using aquatic organisms representing several trophic levels (Aliivibrio, Ulva, Daphnia, and Lemna), for 99 industrial wastewater samples from South Korea. For five wastewater samples, the concentrations of Se, Zn, or Ni exceeded the permissible limits (1, 5, and 3 mg L-1, respectively). All the four physiochemical water quality indices tested were positively correlated with Se and Pb concentrations. The toxicity unit (TU) scores indicated a declining sensitivity to pollutants, in the order Lemna (2.87) >Daphnia (2.24) >Aliivibrio (1.78) >Ulva (1.42). Significant correlations were observed between (1) Cd and Ni, and Aliivibrio, (2) Cu and Daphnia, (3) Cd, Cu, Zn, and Cr and Lemna, and (4) Cu, Zn, and Ni and Ulva. Daphnia-Lemna and Lemna-Ulva were found to be good indicators of ecologically harmful Se and Ni contents in wastewater, respectively. We suggest that regulatory thresholds based on these bioassays should be set at TU = 1 for all the species or at TU = 1 for Aliivibrio and Ulva and TU = 2 for Daphnia and Lemna, if the number of companies whose wastewater discharge exceeds the allowable TU levels is <1 % or 5 % of the total number of industries, respectively. Taken together, these findings could help in establishing a rapid, ecologically relevant wastewater quality assessment system that would be useful for developing strategies to protect aquatic ecosystems.

Prebiotic activities of dextran from Leuconostoc mesenteroides SPCL742 analyzed in the aspect of the human gut microbial ecosystem.

The aim of this study was to investigate the prebiotic activities of dextran (LM742) produced by Leuconostoc mesenteroides SPCL742 in the aspect of the human gut microbial ecosystem focusing on microbiome and metabolome changes in in vitro colonic fermentation. LM742 dextran had a medium-chain structure with the molecular weight of 1394.87 kDa (DP = 7759.22) and α-1,6 and α-1,3 linkages with a 26.11 : 1 ratio. The LM742 dextran was resistent to digestive enzymes in the human gastrointestinal conditions. The individual cultivation of 30 intestinal bacteria with LM742 dextran showed the growth of Bacteroides spp., whereas in vitro human fecal fermentation with LM742 exhibited the symbiotic growth of Bacteroides spp. and beneficial bacteria such as Bifidobacterium spp. Further co-cultivation of Bacteroides xylanisolvens and several probiotics indicated that B. xylanisolvens provides a cross-feeding of dextran to probiotics. In fecal fermentation, LM742 dextran resulted in increased concentrations of short-chain fatty acids, valerate and pantothenate, but it rarely affected the conversion of betaine to trimethylamine. Lastly, LM742 dextran inhibited the adhesion of pathogenic E. coli to human epithelial cells. Taken together, these results demonstrate the prebiotic potential of LM742 dextran as a health-beneficial polysaccharide in the human intestine.

Electronic Skin Based on a Cellulose/Carbon Nanotube Fiber Network for Large-Area 3D Touch and Real-Time 3D Surface Scanning.

Electronic skin (E-skin) based on tactile sensors has great significance in next-generation electronics such as biomedical application and artificial intelligence that requires interaction with humans. To mimic the properties of human skin, high flexibility, excellent sensing capability, and sufficient spatial resolution through high-level sensor integration are required. Here, we report a highly sensitive pressure sensor matrix based on a piezoresistive cellulose/single-walled carbon nanotube-entangled fiber network, which forms its own porous structure enabling a superior pressure sensor with a high sensitivity (9.097 kPa-1), a fast response speed (<2 ms), and orders of magnitude detection range with a detection limit of 1 Pa. Furthermore, the remarkable device expandability based on the ease of patterning and scalability allows easy implementation of a large-area pressure sensor matrix which has 2304 (48 × 48) pixels. Combined with a real-time pressure distribution monitoring system, a flexible 3D touch sensor that simultaneously displays plane coordinates and pressure information and a scanning device that detects the morphology of the soft body 3D surface are successfully demonstrated.

Assessment of Various Toxicity Endpoints in Duckweed (Lemna minor) at the Physiological, Biochemical, and Molecular Levels as a Measure of Diuron Stress.

The common, broad-spectrum herbicide diuron poses some risks to the environment due to its long persistence and high toxicity. Therefore, the effective monitoring of diuron residues will inform efforts to assess its impacts on ecosystems. In this study, we evaluated the toxicity targets of diuron in the model aquatic macrophyte Lemna minor at the physiological (growth and photosynthetic efficiency), biochemical (pigment biosynthesis and reactive oxygen species (ROS) levels), and molecular (rbcL transcript) levels. The toxicity of diuron was detectable after 48 h of exposure and the order of sensitivity of toxicity endpoints was gene transcription > maximum electron transport rate (ETRmax) > non-photochemical quenching (NPQ) > maximum quantum yield (Fv/Fm) > ROS > fresh weight > chlorophyll b > chlorophyll a > total frond area > carotenoids. Under diuron stress, pigment, ROS, and gene transcript levels increased while frond area, fresh weight, and photosynthesis (Fv/Fm and ETRmax) gradually decreased with the increasing duration of exposure. Notably, ROS levels, Fv/Fm, frond area, and fresh weight were highly correlated with diuron concentration. The growth endpoints (frond area and fresh weight) showed a strong negative correlation with ROS levels and a positive correlation with Fv/Fm and ETRmax. These findings shed light on the relative sensitivity of different endpoints for the assessment of diuron toxicity.

3D printing-based mirrored image component for seamless modular curved-edge displays.

A facile method for designing and fabricating a concave mirror from a 3D printed mold is proposed for a seamless modular curved-edge display. The concave mirror is placed on the seam of modular curved-edge display, thereby reflecting images at the curved-edge area toward the observer direction. By investigating the concave mirror structures based on parametric modeling, we obtain a continuous image in a modular curved-edge display by optically concealing the seam. We also analyze the luminance distribution and the viewing angle of the seamless modular curved-edge display to show the capability of concealing the seam by the concave mirror.

Promoter engineering-mediated Tuning of esterase and transaminase expression for the chemoenzymatic synthesis of sitagliptin phosphate at the kilogram-scale.

Here, we report a bienzymatic cascade to produce ß-amino acids as an intermediate for the synthesis of the leading oral antidiabetic drug, sitagliptin. A whole-cell biotransformation using recombinant Escherichia coli coexpressing a esterase and transaminase were developed, wherein the desired expression level of each enzyme was achieved by promotor engineering. The small-scale reactions (30 ml) performed under optimized conditions at varying amounts of substrate (100-300 mM) resulted in excellent conversions of 82%-95% for the desired product. Finally, a kilogram-scale enzymatic reaction (250 mM substrate, 220 L) was carried out to produce ß-amino acid (229 mM). Sitagliptin phosphate was chemically synthesized from ß-amino acids with 82% yield and > 99% purity.

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition.

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial-mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

Interlaboratory Validation of Toxicity Testing Using the Duckweed Lemna minor Root-Regrowth Test.

The common duckweed (Lemna minor), a freshwater monocot that floats on the surfaces of slow-moving streams and ponds, is commonly used in toxicity testing. The novel Lemna root- regrowth test is a toxicity test performed in replicate test vessels (24-well plates), each containing 3 mL test solution and a 2-3 frond colony. Prior to exposure, roots are excised from the plant, and newly developed roots are measured after 3 days of regrowth. Compared to the three internationally standardized methods, this bioassay is faster (72 h), simpler, more convenient (requiring only a 3-mL) and cheaper. The sensitivity of root regrowth to 3,5-dichlorophenol was statistically the same as using the conventional ISO test method. The results of interlaboratory comparison tests conducted by 10 international institutes showed 21.3% repeatability and 27.2% reproducibility for CuSO4 and 21.28% repeatability and 18.6% reproducibility for wastewater. These validity criteria are well within the generally accepted levels of <30% to 40%, confirming that this test method is acceptable as a standardized biological test and can be used as a regulatory tool. The Lemna root regrowth test complements the lengthier conventional protocols and is suitable for rapid screening of wastewater and priority substances spikes in natural waters.

Design, Fabrication, and Performance Evaluation of Portable and Large-Area Blackbody System.

In this study, a portable and large-area blackbody system was developed following a series of processes including design, computational analysis, fabrication, and experimental analysis and evaluation. The blackbody system was designed to be lightweight (5 kg), and its temperature could exceed the ambient temperature by up to 15 °C under operation. A carbon-fiber-based heat source was used to achieve a uniform temperature distribution. A heat shield fabricated from an insulation material was embedded at the opposite side of the heating element to minimize heat loss. A prototype of the blackbody system was fabricated based on the design and transient coupled electro-thermal simulation results. The operation performance of this system, such as the thermal response, signal transfer function, and noise equivalent temperature difference, was evaluated by employing an infrared imaging system. In addition, emissivity was measured during operation. The results of this study show that the developed portable and large-area blackbody system can be expected to serve as a reliable reference source for the calibration of aerial infrared images for the application of aerial infrared techniques to remote sensing.

Whole-Genome Sequence of Lactobacillus plantarum SPC-SNU 72-2 as a Probiotic Starter for Sourdough Fermentation.

We report the whole-genome sequence of Lactobacillus plantarum SPC-SNU 72-2, a probiotic starter for sourdough. Genome sequencing was completed using the Pacific Biosciences RS II and Illumina platforms. This study will facilitate the understanding of microbial characteristics of L. plantarum SPC-SNU 72-2 and its roles during sourdough fermentation.

Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1.

Constitutive activation of the ß-catenin dependent canonical Wnt signaling pathway, which enhances tumor growth and progression in multiple types of cancer, is commonly observed in melanoma. LEF1 activates ß-catenin/TCF4 transcriptional activity, promoting tumor growth and progression. Although several reports have shown that LEF1 is highly expressed in melanoma, the functional role of LEF1 in melanoma growth is not fully understood. While A375, A2058, and G361 melanoma cells exhibit abnormally high LEF1 expression, lung cancer cells express lower LEF1 levels. A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed ß-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression. Cinobufagin decreases LEF1 expression in a dose-dependent manner and Wnt/ß-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines. Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells. In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells. Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/ß-catenin signaling via LEF1 inhibition.

Ursolic Acid Suppresses Cholesterol Biosynthesis and Exerts Anti-Cancer Effects in Hepatocellular Carcinoma Cells.

Abnormally upregulated cholesterol and lipid metabolism, observed commonly in multiple cancer types, contributes to cancer development and progression through the activation of oncogenic growth signaling pathways. Although accumulating evidence has shown the preventive and therapeutic benefits of cholesterol-lowering drugs for cancer management, the development of cholesterol-lowering drugs is needed for treatment of cancer as well as metabolism-related chronic diseases. Ursolic acid (UA), a natural pentacyclic terpenoid, suppresses cancer growth and metastasis, but the precise underlying molecular mechanism for its anti-cancer effects is poorly understood. Here, using sterol regulatory element (SRE)-luciferase assay-based screening on a library of 502 natural compounds, this study found that UA activates sterol regulatory element-binding protein 2 (SREBP2). The expression of cholesterol biosynthesis-related genes and enzymes increased in UA-treated hepatocellular carcinoma (HCC) cells. The UA increased cell cycle arrest and apoptotic death in HCC cells and reduced the activation of oncogenic growth signaling factors, all of which was significantly reversed by cholesterol supplementation. As cholesterol supplementation successfully reversed UA-induced attenuation of growth in HCC cells, it indicated that UA suppresses HCC cells growth through its cholesterol-lowering effect. Overall, these results suggested that UA is a promising cholesterol-lowering nutraceutical for the prevention and treatment of patients with HCC and cholesterol-related chronic diseases.

HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways.

Heat shock factor 1 (HSF1) is an essential transcription factor in cellular adaptation to various stresses such as heat, proteotoxic stress, metabolic stress, reactive oxygen species, and heavy metals. HSF1 promotes cancer development and progression, and increased HSF1 levels are frequently observed in multiple types of cancers. Increased activity in the mevalonate and cholesterol biosynthesis pathways, which are very important for cancer growth and progression, is observed in various cancers. However, the functional role of HSF1 in the mevalonate and cholesterol biosynthesis pathways has not yet been investigated. Here, we demonstrated that the activation of RAS-MAPK signaling through the overexpression of H-RasV12 increased HSF1 expression and the cholesterol biosynthesis pathway. In addition, the activation of HSF1 was also found to increase cholesterol biosynthesis. Inversely, the suppression of HSF1 by the pharmacological inhibitor KRIBB11 and short-hairpin RNA (shRNA) reversed H-RasV12-induced cholesterol biosynthesis. From the standpoint of therapeutic applications for hepatocellular carcinoma (HCC) treatment, HSF1 inhibition was shown to sensitize the antiproliferative effects of simvastatin in HCC cells. Overall, our findings demonstrate that HSF1 is a potential target for statin-based HCC treatment.

Bragg scattering from a millimeter-scale periodic structure with extremely small aspect ratios.

The periodic structure on the optical surface affects the beam shape and its propagation. As the size of the optical elements becomes larger and its shape becomes complicated, the quantitative analysis of the effect of the periodic structure on the optical surface becomes indispensable given that it is very difficult to completely eliminate the microscopic periodic structures. Herein, we have experimentally investigated Bragg scattering from an optical surface with extremely small aspect ratios (~10-5) and groove densities (0.5 lines/mm). We observed the period of the constructive interference formed due to the propagation of the 0th, 1st, and -1st beam modes caused by Bragg scattering. When the periodic structure has a modulation depth of ± 50 nm, the intensity increase of constructive interference between the beam modes formed by Bragg scattering was > 10 times greater than the intensity of a flat surface at the propagation distance at which constructive interference was most pronounced. This study is envisaged to open new avenues for the quantification of the effect of periodic structures based on the observation of the interference on the beam profile formed by Bragg scattering during the beam propagation.

Broadband tuning of ring-type cavity-dumped femtosecond optical parametric oscillator in the near-infrared.

We report a cavity-dumped optical parametric oscillator (OPO) with a ring-type cavity configuration, which is based on periodically poled lithium niobate gain synchronously pumped by a mode-locked Ti:sapphire laser. Because of reduced cavity loss and group velocity dispersion inherent to ring-cavity employment, a wide wavelength tuning capability from 1.02 to 1.65 µm was achieved by the simple displacement of a cavity mirror. At a wavelength of 1.28 µm, the cavity-dumped system provides femtosecond pulses with 42 nJ energy and 50% dumping efficiency. The group delay dispersion (GDD) of the OPO cavity could be characterized through the wavelength tuning behavior with cavity displacement, and its validity was confirmed by the numerical GDD calculation of each optical component within the cavity.

IDH1R132H Causes Resistance to HDAC Inhibitors by Increasing NANOG in Glioblastoma Cells.

The R132H mutation in isocitrate dehydrogenase 1 (IDH1R132H) is commonly observed and associated with better survival in glioblastoma multiforme (GBM), a malignant brain tumor. However, the functional role of IDH1R132H as a molecular target for GBM treatment is not completely understood. In this study, we found that the overexpression of IDH1R132H suppresses cell growth, cell cycle progression and motility in U87MG glioblastoma cells. Based on cell viability and apoptosis assays, we found that IDH1R132H-overexpressing U87MG and U373MG cells are resistant to the anti-cancer effect of histone deacetylase inhibitors (HDACi), such as trichostatin A (TSA), vorinostat (SAHA), and valproic acid. Octyl-(R)-2-hydroxyglutarate (Octyl-2HG), which is a membrane-permeable precursor form of the oncometabolite (R)-2-hydroxyglutarate (R-2HG) produced in IDH1-mutant tumor cells, significantly increased HDACi resistance in glioblastoma cells. Mechanistically, IDH1R132H and Octyl-2HG enhanced the promoter activation of NANOG via increased H3K4-3Me, consequently increasing NANOG mRNA and protein expression. Indeed, HDACi resistance was attenuated in IDH1R132H-expressing glioblastoma cells by the suppression of NANOG using small interfering RNAs. Furthermore, we found that AGI-5198, a selective inhibitor of IDH1R132H, significantly attenuates HDACi resistance and NANOG expression IDH1R132H-expressing glioblastoma cells. These results suggested that IDH1R132H is a potential molecular target for HDACi-based therapy for GBM.

Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis.

Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel HIF-1α inhibitor through hypoxia response element (HRE)-luciferase assay-based large screening by using 502 natural compounds containing chemical library. TQ reduced HIF-1α protein levels in renal cancer cells; however, it did not affect the HIF-1α protein levels in the presence of proteasome inhibitor, MG132, indicating that the reduction effects of TQ on HIF-1α protein are mediated via the ubiquitination-proteasome dependent pathway. TQ boosted HIF-1α protein degradation, and the mechanism was revealed by inhibiting interaction between HSP90 and HIF-1α. TQ suppressed downstream genes of HIF-1α, indicating negative impact of TQ on HIF-1α transcriptional activities. In addition, TQ altered glucose, lactate, and ATP levels, leading to anaerobic metabolic disturbance. TQ induced apoptosis in hypoxic cancer cells as determined by crystal violet staining and flow cytometry for annexin V-stained cells. Taken together, we suggested that TQ is a potential anticancer agent targeting HIF-1α.