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.

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.

Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging.

Collagen is a prominent target of nonenzymatic glycation, which is a hallmark of aging and causes functional alteration of the matrix. Here, we uncover glycation-mediated structural and functional changes in the collagen-enriched meningeal membrane of the human and mouse brain. Using an in vitro culture platform mimicking the meningeal membrane composed of fibrillar collagen, we showed that the accumulation of advanced glycation end products (AGEs) in the collagen membrane is responsible for glycation-mediated matrix remodeling. These changes influence fibroblast-matrix interactions, inducing cell-mediated ECM remodeling. The adherence of meningeal fibroblasts to the glycated collagen membrane was mediated by the discoidin domain-containing receptor 2 (DDR2), whereas integrin-mediated adhesion was inhibited. A-kinase anchoring protein 12 (AKAP12)-positive meningeal fibroblasts in the meningeal membrane of aged mice exhibited substantially increased expression of DDR2 and depletion of integrin beta-1 (ITGB1). In the glycated collagen membrane, meningeal fibroblasts increased the expression of matrix metalloproteinase 14 (MMP14) and less tissue inhibitor of metalloproteinase-1 (TIMP1). In contrast, the cells exhibited decreased expression of type I collagen (COL1A1). These results suggest that glycation modification by meningeal fibroblasts is intimately linked to aging-related structural and functional alterations in the meningeal membrane.

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.

Astrocyte-Encapsulated Hydrogel Microfibers Enhance Neuronal Circuit Generation.

Astrocytes, the most representative glial cells in the brain, play a multitude of crucial functions for proper neuronal development and synaptic-network formation, including neuroprotection as well as physical and chemical support. However, little attention has been paid, in the neuroregenerative medicine and related fields, to the cytoprotective incorporation of astrocytes into neuron-culture scaffolds and full-fledged functional utilization of encapsulated astrocytes for controlled neuronal development. In this article, a 3D neurosupportive culture system for enhanced induction of neuronal circuit generation is reported, where astrocytes are confined in hydrogel microfibers and protected from the outside. The astrocyte-encapsulated microfibers significantly accelerate the neurite outgrowth and guide its directionality, and enhance the synaptic formation, without any physical contact with the neurons. This astrocyte-laden system provides a pivotal culture scaffold for advanced development of cell-based therapeutics for neural injuries, such as spinal cord injury.

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.

Fluid-Matrix Interface Triggers a Heterogeneous Activation of Macrophages.

Spontaneous activation of macrophages in response to inflammation is a key part of innate immunity and host defense. Macrophages represent a heterogeneous population of cells with different phenotypic profiles performing distinct functions in host defense. Although a spectrum of macrophage activation stages exists in an inflamed region, the effect of local physical conditions on the heterotypic activation of macrophages is unknown. Here, we introduce an in vivo fluid-matrix interface analogous culture platform, an asymmetric microenvironment, facilitating the formation of macrophage aggregates (MAs). Macrophages were self-assembled to form MAs of ∼100 µm diameter at the collagen matrix-medium interface upon phorbol-12-myristate-13-acetate treatment. The macrophages within the half-embedded MAs into the matrix were heterogeneously activated, resulting in inhomogeneous cell-cell and cell-matrix interactions within the aggregates. Our demonstration may aid in a better understanding of the acquisition of macrophage heterogeneity in response to tissue-specific microenvironments.

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.

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.

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.

Factors Associated With Caregivers' Resilience in a Terminal Cancer Care Setting.

BACKGROUND: Resilience implies characteristics such as self-efficacy, adaptability to change, optimism, and the ability to recover from traumatic stress. Studies on resilience in family caregivers (FCs) of patients with terminal cancer are rare. This study aims to examine the factors associated with FCs' resilience in a terminal cancer care setting. METHODS: This is a cross-sectional study of 273 FCs from 7 hospice and palliative care units in Korea. Resilience was categorized as high and low, and factors associated with resilience were grouped or categorized into subscales. A multivariate logistic regression analysis was used to examine relevant factors. RESULTS: High FCs' resilience was significantly associated with FCs' health status, depression, and social support. In a multivariate regression model, FCs' perception of good health (adjusted odds ratio [aOR] = 2.26, 95% confidence interval [CI] = 1.16-4.40), positive social support (aOR = 3.70, 95% CI = 1.07-12.87), and absence of depression (aOR = 3.12, 95% CI = 1.59-6.13) remained significantly associated with high FCs' resilience. CONCLUSION: Lack of family support is associated with and may be a cause of diminished resilience. And more concern should be paid to FCs to improve FCs' health and emotional status. Education programs might be effective for improving caregivers' resilience. Further research with supportive interventions is indicated.

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.

[Associations between Body Mass Index and Chronic Atrophic Gastritis and Intestinal Metaplasia].

BACKGROUND/AIMS: Chronic atrophic gastritis (AG) and intestinal metaplasia (IM) of the stomach are premalignant lesions. The present study aimed to examine the associations between obesity and these lesions. METHODS: A total of 2,997 patients, who underwent gastroscopy, participated in this study, excluding those who had been diagnosed with gastric cancer. Participants were divided into four groups based on their body mass index (BMI). The risk of AG and IM with increasing BMI was analyzed in men and women, separately. RESULTS: The association between BMI and AG was not significant. After adjusting for age, smoking, alcohol, and AG, the odds ratios for IM in the overweight, obesity, and severe obesity groups were 2.25 (95% confidence interval [CI], 1.50-3.37), 2.32 (95% CI, 1.58-3.42), and 4.86 (95% CI, 2.04-11.5) in men, and 2.66 (95% CI, 1.29-5.47), 4.46 (95% CI, 2.28-8.75), and 9.57 (95% CI, 3.26-28.12) in women, compared with the normal BMI group. CONCLUSIONS: Gastric IM was significantly associated with increased BMI.