The effects of fucoidan-rich polysaccharides extracted from Sargassum horneri on enhancing collagen-related skin barrier function as a potential cosmetic product.

BACKGROUND: Sargassum horneri came ashore after flowing from the South China Sea to Jeju Island a few years ago. This caused a significant environmental impact on coastal areas where S. horneri has accumulated because of decomposition and the release of toxic substances, such as hydrogen sulfide. AIMS: In this study, we evaluated a biological ingredient prepared from fucoidan-rich S. horneri and demonstrated its antiwrinkle effects on ultraviolet B (UVB)-induced fibroblast cells. MATERIALS AND METHODS: Fucoidan samples from S. horneri were prepared according to a previously published process with modifications. The compositional analysis of S. horneri fucoidan extract (SHFE) as well as its effects on antiaging were examined to determine its utility as a functional material. RESULTS: SHFE exhibited antioxidant properties using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Treatment of UVB-induced fibroblasts with SHFE significantly increased the synthesis of procollagen compared with adenosine treatment and inhibited MMP-1 and MMP-3 expression. In a clinical study, SHFE lotion improved skin barrier effects in forearms and transepidermal water loss (TEWL) values were reduced after 3 weeks of use compared with a placebo. CONCLUSION: SHFE has utility as an additive with functional antiaging effects for a range of cosmetic products as it restores skin hydration in the epidermal barrier.

An S=1 Iron(IV) Intermediate Revealed in a Non-Heme Iron Enzyme-Catalyzed Oxidative C-S Bond Formation.

Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol-histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O2 -dependent C-S bond formation catalyzed by non-heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S=1 iron(IV) intermediate supported by a four-histidine ligand environment (three from the protein residues and one from the substrate) in enabling C-S bond formation in OvoA from Methyloversatilis thermotoleran, which represents the first experimentally observed intermediate spin iron(IV) species in non-heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C-S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure-function relationship of high-valent iron intermediates supported by a histidine rich ligand environment.

Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions.

Somatic stem cells contribute to normal tissue homeostasis, and their epigenomic features play an important role in regulating tissue identities or developing disease states. Enhancers are one of the key players controlling chromatin context-specific gene expression in a spatial and temporal manner while maintaining tissue homeostasis, and their dysregulation leads to tumorigenesis. Here, epigenomic and transcriptomic analyses reveal that forkhead box protein D2 (FOXD2) is a hub for the gene regulatory network exclusive to large intestinal stem cells, and its overexpression plays a significant role in colon cancer regression. FOXD2 is positioned at the closed chromatin and facilitates mixed-lineage leukemia protein-4 (MLL4/KMT2D) binding to deposit H3K4 monomethylation. De novo FOXD2-mediated chromatin interactions rewire the regulation of p53-responsive genes and induction of apoptosis. Taken together, our findings illustrate the novel mechanistic details of FOXD2 in suppressing colorectal cancer growth and suggest its function as a chromatin-tuning factor and a potential therapeutic target for colorectal cancer.

Light-driven Oxidative Demethylation Reaction Catalyzed by a Rieske-type Non-heme Iron Enzyme Stc2.

Rieske-type non-heme iron oxygenases/oxidases catalyze a wide range of transformations. Their applications in bioremediation or biocatalysis face two key barriers: the need of expensive NAD(P)H as a reductant and a proper reductase to mediate the electron transfer from NAD(P)H to the oxygenases. To bypass the need of both the reductase and NAD(P)H, using Rieske-type oxygenase (Stc2) catalyzed oxidative demethylation as the model system, we report Stc2 photocatalysis using eosin Y/sulfite as the photosensitizer/sacrificial reagent pair. In a flow-chemistry setting to separate the photo-reduction half-reaction and oxidation half-reaction, Stc2 photo-biocatalysis outperforms the Stc2-NAD(P)H-reductase (GbcB) system. In addition, in a few other selected Rieske enzymes (NdmA, CntA, and GbcA), and a flavin-dependent enzyme (iodotyrosine deiodinase, IYD), the eosin Y/sodium sulfite photo-reduction pair could also serve as the NAD(P)H-reductase surrogate to support catalysis, which implies the potential applicability of this photo-reduction system to other redox enzymes.

A Development of the Self Shape Adjustment Cushion Mechanism for Improving Sitting Comfort.

The seat comfort of automobiles is one of the significant factors for determining the driver's fatigue, emotional experience, and individual space (which captures their individuality, rather than just a means of transportation in modern society). Conventional automobile seats could not provide seating comfort suitable for all drivers, in the form of seats that fit each driver's body type and the difficulty of meeting individual needs. This study proposes self-shape adjustable (the SSA seats) seats that improve the sitting comfort, safety, and secure the stability, by adjusting shape fit to the driver's body type. The SSA seats transforms the seat itself, in a way that improves the distribution of contact pressure and reduces sitting fatigue, with the pneumatic system. The transformed seats provide better sitting comfort and safety than the conventional automobile seat, by providing a seat shape suitable for the body shape of all users. It was verified that the SSA seats, proposed in this paper, have a uniform and improved pressure distribution, compared to the conventional seat, in various sitting postures; the contact area between the seat and user is enlarged, and the pressure concentrated on the ischial bone is lowered. In addition, it was proven (through user evaluation) that quantitative evaluation verification was the same as qualitative evaluation results.

Variable Admittance Control Based on Human-Robot Collaboration Observer Using Frequency Analysis for Sensitive and Safe Interaction.

A collaborative robot should be sensitive to the user intention while maintaining safe interaction during tasks such as hand guiding. Observers based on the discrete Fourier transform have been studied to distinguish between the low-frequency motion elicited by the operator and high-frequency behavior resulting from system instability and disturbances. However, the discrete Fourier transform requires an excessively long sampling time. We propose a human-robot collaboration observer based on an infinite impulse response filter to increase the intention recognition speed. By using this observer, we also propose a variable admittance controller to ensure safe collaboration. The recognition speed of the human-robot collaboration observer is 0.29 s, being 3.5 times faster than frequency analysis based on the discrete Fourier transform. The performance of the variable admittance controller and its improved recognition speed are experimentally verified on a two-degrees-of-freedom manipulator. We confirm that the improved recognition speed of the proposed human-robot collaboration observer allows us to timely recover from unsafe to safe collaboration.

hnRNP K supports the maintenance of RORγ circadian rhythm through ERK signaling.

Retinoic acid-related orphan receptor γ (RORγ) maintains the circadian rhythms of its downstream genes. However, the mechanism behind the transcriptional activation of RORγ itself remains unclear. Here, we demonstrate that transcription of RORγ is activated by heterogeneous nuclear ribonucleoprotein K (hnRNP K) via the poly(C) motif within its proximal promoter. Interestingly, we confirmed the binding of endogenous hnRNP K within RORγ1 and RORγ2 promoter along with the recruitment of RNA polymerase 2 through chromatin immunoprecipitation (ChIP). Furthermore, an assay for transposase accessible chromatin (ATAC)-qPCR showed that hnRNP K induced higher chromatin accessibility within the RORγ1 and RORγ2 promoter. Then we found that the knockdown of hnRNP K lowers RORγ mRNA oscillation amplitude in both RORγ and RORγ-dependent metabolic genes. Moreover, we demonstrated that time-dependent extracellular signal-regulated kinase (ERK) activation controls mRNA oscillation of RORγ and RORγ-dependent metabolic genes through hnRNP K. Taken together, our results provide new insight into the regulation of RORγ by hnRNP K as a transcriptional activator, along with its physiological significance in metabolism.

Stability of Quantum-Dot Light Emitting Diodes with Alkali Metal Carbonates Blending in Mg Doped ZnO Electron Transport Layer.

We report here the fabrication of highly efficient and long-lasting quantum-dot light emitting diodes (QLEDs) by blending various alkali metal carbonate in magnesium (Mg) doped zinc oxide (ZnO) (MZO) electron transport layer (ETL). Alkali metal carbonates blending in MZO, X2CO3:MZO, control the band-gap, electrical properties, and thermal stability. This can therefore enhance the operational lifetime of QLEDs. It is found that the conductivity of X2CO3:MZO film can be controlled and the thermal stability of ETLs could be improved by X2CO3 blending in MZO. The inverted red QLEDs (R-QLEDs) with Cs2CO3:MZO, Rb2CO3:MZO, and K2CO3:MZO ETLs exhibited the operational lifetime of 407 h for the R-QLEDs with Cs2CO3:MZO, 620 h with Rb2CO3:MZO and 94 h with K2CO3:MZO ETLs at T95 with the initial luminance of 1000 cd/m2. Note that all red QLEDs showed the high brightness over 150,000 cd/m2. But the R-QLEDs with Na2CO3:MZO and Li2CO3:MZO ETLs exhibited shorter operational lifetime and poor brightness than the R-QLED with pristine MZO ETL.

Creation of bladder assembloids mimicking tissue regeneration and cancer.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder 'assembloids' by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1-BMP-hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

hnRNP K Supports High-Amplitude D Site-Binding Protein mRNA (Dbp mRNA) Oscillation To Sustain Circadian Rhythms.

Circadian gene expression is defined by the gene-specific phase and amplitude of daily oscillations in mRNA and protein levels. D site-binding protein mRNA (Dbp mRNA) shows high-amplitude oscillation; however, the underlying mechanism remains elusive. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that activates Dbp transcription via the poly(C) motif within its proximal promoter. Biochemical analyses identified hnRNP K as a specific protein that directly associates with the poly(C) motif in vitro Interestingly, we further confirmed the rhythmic binding of endogenous hnRNP K within the Dbp promoter through chromatin immunoprecipitation as well as the cycling expression of hnRNP K. Finally, knockdown of hnRNP K decreased mRNA oscillation in both Dbp and Dbp-dependent clock genes. Taken together, our results show rhythmic protein expression of hnRNP K and provide new insights into its function as a transcriptional amplifier of Dbp.

The Poly(C) Motif in the Proximal Promoter Region of the D Site-Binding Protein Gene (Dbp) Drives Its High-Amplitude Oscillation.

The D site-binding protein (Dbp) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian-clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that the poly(C) motif within the Dbp proximal promoter, in addition to an E-box element, provoked transcriptional activation. Furthermore, we generated a cell line with poly(C) deleted to demonstrate the endogenous effect of the poly(C) motif within the Dbp promoter. We investigated whether RNA polymerase 2 (Pol2) recruitment on the Dbp promoter was decreased in the cell line with poly(C) deleted. Next, assay for transposase-accessible chromatin (ATAC)-quantitative PCR (qPCR) showed that the poly(C) motif induced greater chromatin accessibility within the region of the Dbp promoter. Finally, we determined that the oscillation amplitude of endogenous Dbp mRNA of the cell line with poly(C) deleted was decreased, which affected the oscillation of other clock genes that are controlled by Dbp Taken together, our results provide new insights into the function of the poly(C) motif as a novel cis-acting element of Dbp, along with its significance in the regulation of circadian rhythms.

Wind, power, and the situatedness of community engagement.

Jeju, an island in Korea, became a place to site wind turbines with an unusually high level of public acceptance. Based on interviews, media analyses, and policy research, we found that the collective memory of socio-economic deprivation enabled community engagement to matter to residents, the provincial government, and environmental activists. It was within socio-historically contextualized processes of articulating the vision of a "good" society that an actual form of community engagement, however inadequate it might appear to some, became relevant to stakeholders in a particular locality. We emphasize that community engagement in renewable energy governance does not have one but multiple and situated ways of mattering depending on local contexts.

Surface Engineering of Room Temperature-Grown Inorganic Perovskite Quantum Dots for Highly Efficient Inverted Light-Emitting Diodes.

Inorganic cesium lead bromide quantum dots (CsPbBr3 QDs) are usually synthesized via a high-temperature process (hot injection, HI). This process is similar to that used for the synthesis of other semiconductor QDs (i.e., CdSe@ZnS), which limits their potential cost advantage. CsPbBr3 QDs can also be synthesized at room temperature (RT) in a low cost and easily scalable process, which, thus, is one of the greatest advantages of the CsPbBr3 QDs. However, light-emitting diodes (LEDs) fabricated using RT-QDs exhibit poor performance compared to those of HI-QDs. In fact, QDs are surrounded by insulating ligands to maintain their colloidal stability but these ligands need to be removed to obtain high-performance LEDs. Here, we show that ligand removal techniques used for HI-QDs are not sufficient in the case of RT-QDs. Additional ligand engineering and annealing steps are necessary to remove the excess of ligands from RT-QD films while preventing the coalescence of the QDs. The eventual surface defects induced by annealing can be healed by a subsequent photoactivation step. Moreover, the use of solution processable inorganic charge transport layers can reduce the fabrication costs of LEDs. We fabricated an inverted LED based on a metal oxide electron transport layer and a RT-QD emitting layer which exhibited a maximum current efficiency of 17.61 cd A-1 and a maximum luminance of 22 825 cd m-2.

Li and Mg Co-Doped Zinc Oxide Electron Transporting Layer for Highly Efficient Quantum Dot Light-Emitting Diodes.

Zinc-oxide (ZnO) is widely used as an n-type electron transporting layer (ETL) for quantum dot (QD) light-emitting diode (QLED) because various metal doping can be possible and ZnO nanoparticle can be processed at low temperatures. We report here a Li- and Mg-doped ZnO, MLZO, which is used for ETL of highly efficient and long lifetime QLEDs. Co-doping, Mg and Li, in ZnO increases its band gap and electrical resistivity and thus can enhance charge balance in emission layer (EML). It is found also that the O-H concentration at the oxide surface decreases and exciton decay time of QDs on the metal oxide increases by co-doping in ZnO. The inverted green QLEDs with MLZO ETL exhibits the maximum current efficiency (CEmax) of 69.1 cd/A, power efficiency (PEmax) of 73.8 lm/W, and external quantum efficiency (EQEmax) of 18.4%. This is at least two times higher compared with the efficiencies of the QLEDs with Mg-doped ZnO ETL. The optimum Li and Mg concentrations are found to be 10% each. The deep-red, red, light-blue, and deep-blue QLEDs with MLZO ETLs exhibit the CEmax of 6.0, 22.3, 1.9, and 0.5 cd/A, respectively. The MLZO introduced here can be widely used as ETL of highly efficient QLEDs.

Aucubin Promotes Differentiation of Neural Precursor Cells into GABAergic Neurons.

Aucubin is a small compound naturally found in traditional medicinal herbs with primarily anti-inflammatory and protective effects. In the nervous system, aucubin is reported to be neuroprotective by enhancing neuronal survival and inhibiting apoptotic cell death in cultures and disease models. Our previous data, however, suggest that aucubin facilitates neurite elongation in cultured hippocampal neurons and axonal regrowth in regenerating sciatic nerves. Here, we investigated whether aucubin facilitates the differentiation of neural precursor cells (NPCs) into specific types of neurons. In NPCs cultured primarily from the rat embryonic hippocampus, aucubin significantly elevated the number of GAD65/67 immunoreactive cells and the expression of GAD65/67 proteins was upregulated dramatically by more than three-fold at relatively low concentrations of aucubin (0.01 µM to 10 µM). The expression of both NeuN and vGluT1 of NPCs, the markers for neurons and glutamatergic cells, respectively, and the number of vGluT1 immunoreactive cells also increased with higher concentrations of aucubin (1 µM and 10 µM), but the ratio of the increases was largely lower than GAD expression and GAD immunoreactive cells. The GABAergic differentiation of pax6-expressing late NPCs into GABA-producing cells was further supported in cortical NPCs primarily cultured from transgenic mouse brains, which express recombinant GFP under the control of pax6 promoter. The results suggest that aucubin can be developed as a therapeutic candidate for neurodegenerative disorders caused by the loss of inhibitory GABAergic neurons.

Low Work Function 2.81 eV Rb2CO3-Doped Polyethylenimine Ethoxylated for Inverted Organic Light-Emitting Diodes.

We report a low work function (2.81 eV), Rb2CO3-doped polyethyleneimine ethoxylated (PEIE) which is used for highly efficient and long-lifetime, inverted organic light-emitting diodes (OLEDs). Doping Rb2CO3 into PEIE decreases the work function of Li-doped ZnO (LZO) by 1.0 eV and thus significantly improves electron injection ability into the emission layer (EML). The inverted OLED with PEIE:Rb2CO3 interfacial layer (IL) exhibits higher efficiency and longer operation lifetime than those of the device with a PEIE IL. It is found also that Mg-doped ZnO (MZO) can be used instead of LZO as electron transporting layer. MZO/PEIE: Rb2CO3 shows a low work function of 2.81 eV. The OLED with MZO/PEIE:Rb2CO3 exhibits low operating voltage of 5.0 V at 1000 cd m-2 and low efficiency roll-off of 11.8% at high luminance of 10 000 cd m-2. The results are due to the suppressed exciton quenching at the MZO/organic EML interface.

Quantum-dot light-emitting diodes with a perfluorinated ionomer-doped copper-nickel oxide hole transporting layer.

Herein, we report all solution-processed green quantum-dot light-emitting diodes (G-QLEDs) by introducing a perfluorinated ionomer (PFI, Nafion 117) into quantum dots (QDs) to improve hole injection. To reduce the energy level mismatch between the hole transporting layer (HTL) and QDs and exciton quenching on the metal-oxide surface, a PFI-mixed copper-doped nickel oxide (Cu-NiO) HTL was introduced for G-QLEDs. Mixing Cu-NiO with a PFI increases the work function and induces phase separation between Cu-NiO and PFI; thus, energy band bending occurs on the surface such that effective hole injection can be possible. The phase-separated PFI molecules on HTL affect the thickness and compactness of G-QDs and make a smooth interface between G-QDs and HTL. The G-QLED with a PFI and Cu-NiO mixture HTL exhibits the maximum current efficiency (CEmax), power efficiency (PEmax), and external quantum efficiency (EQEmax) of 7.3 cd A-1, 2.1 lm W-1, and 2.14%, respectively, which are about 4 times those of the QLED with a Cu-NiO HTL.

Beneficial Effects of Appropriate Sleep Duration on Depressive Symptoms and Perceived Stress Severity in a Healthy Population in Korea.

BACKGROUND: Recently, several institutions, including the American Academy of Sleep Medicine, the Sleep Research Society, and the National Sleep Foundation, have made consensus recommendations concerning appropriate sleep duration for adults. Although numerous studies conducted in Western populations have provided evidence of the harmful effects of short or long sleep duration on mental health, it is still unclear whether these consensus recommendations are appropriate in Korean culture. METHODS: Data from 1,892 subjects with no history of medical or psychiatric diagnoses were selected from the Korea National Health and Nutrition Examination Survey of 2014. Subjects were divided into seven groups based on their sleep duration (≤4, 5, 6, 7, 8, 9, and ≥10 hours). Depressive symptoms were measured using the Patient Health Questionnaire-9 and perceived stress severity was evaluated using a Likert-type scale. Group differences in depressive symptoms and severity of stress were analyzed using an analysis of covariance. RESULTS: Depressive symptoms in subjects with sleep duration of ≤4 hours (5.7±5.9) or 5 hours (3.4±3.9) were higher than in subjects with a sleep duration of 7 (2.2±2.9) or 8 hours (2.2±2.9) (corrected P<0.05). Furthermore, subjects with a short sleep duration (5 hours or below) had greater perceived stress severity than subjects with a sleep duration of 7 or 8 hours (corrected P<0.05). CONCLUSION: Our results suggest that maintaining an appropriate sleep duration as found in the recent consensus recommendation is important for mental health, even in healthy subjects without any medical or psychiatric illnesses, in Korea.

Solution-Processed Metal-Oxide p-n Charge Generation Junction for High-Performance Inverted Quantum-Dot Light-Emitting Diodes.

We report solution-processed metal-oxide p-n junction, Li-doped CuO (Li:CuO) and Li-doped ZnO (Li:ZnO), as a charge generation junction (CGJ) in quantum-dot light-emitting diode (QLED) at reverse bias. Efficient charge generation is demonstrated in a stack of air-annealed Li:CuO and Li:ZnO layers in QLEDs. Air annealing of Li:ZnO on Li:CuO turns out to be a key process to decrease oxygen vacancy (Vo) and increase the copper (II) oxide (CuO) fraction at the Li:CuO/Li:ZnO interface for efficient charge generation. Green QLEDs incorporating Li:CuO/Li:ZnO CGJ show the maximum current and power efficiencies of 35.4 cd/A and 33.5 lm/W, respectively.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.

BACKGROUND: Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. METHODS: We recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. RESULTS: Based on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome. CONCLUSION: Our results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.