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During evolution, chloroplasts, which originated by endosymbiosis of a prokaryotic ancestor of today’s cyanobacteria with a eukaryotic host cell, were established as the site for photosynthesis. Therefore, chloroplast organelles are loaded with transition metals including iron, copper, and manganese, which are essential for photosynthetic electron transport due to their redox capacity. Although transport, storage, and cofactor-assembly of metal ions in chloroplasts are tightly controlled and crucial throughout plant growth and development, knowledge on the molecular nature of chloroplast metal-transport proteins is still fragmentary. Here, we characterized the soluble, ATP-binding ABC-transporter subunits ABCI10 and ABCI11 in Arabidopsis thaliana, which show similarities to components of prokaryotic, multisubunit ABC transporters. Both ABCI10 and ABCI11 proteins appear to be strongly attached to chloroplast-intrinsic membranes, most likely inner envelopes for ABCI10 and possibly plastoglobuli for ABCI11. Loss of ABCI10 and ABCI11 gene products in Arabidopsis leads to extremely dwarfed, albino plants showing impaired chloroplast biogenesis and deregulated metal homeostasis. Further, we identified the membrane-intrinsic protein ABCI12 as potential interaction partner for ABCI10 in the inner envelope. Our results suggest that ABCI12 inserts into the chloroplast inner envelope membrane most likely with five predicted α-helical transmembrane domains and represents the membrane-intrinsic subunit of a prokaryotic-type, energy-coupling factor (ECF) ABC-transporter complex. In bacteria, these multisubunit ECF importers are widely distributed for the uptake of nickel and cobalt metal ions as well as for import of vitamins and several other metabolites. Therefore, we propose that ABCI10 (as the ATPase A-subunit) and ABCI12 (as the membrane-intrinsic, energy-coupling T-subunit) are part of a novel, chloroplast envelope-localized, AAT energy-coupling module of a prokaryotic-type ECF transporter, most likely involved in metal ion uptake.

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. Anti-inflammatory effects of IVSK was evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of inflammatory mediators, interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) and the mRNA expression of IL-6, IL-8, MCP-1 and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, and nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

The conversion efficiency of energy-harvesting devices can be increased by utilizing hot-carriers (HCs). However, due to ultrafast carrier-carrier scattering and the lack of carrier injection dynamics, HC-based devices have low efficiencies. In the present work, we report the effective utilization of HCs at the nanoscale and their transfer dynamics from a non-noble metal to a metal oxide interface by means of real-space photocurrent mapping by using local probe techniques and conducting femtosecond transient absorption (TA) measurements. The photocurrent maps obtained under white light unambiguously show that the HCs are injected into the metal oxide layer from the TiN layer, as also confirmed by conductive atomic force microscopy. In addition, the increased photocurrent in the bilayer structure indicates the injection of HCs from both layers due to the broadband absorption efficiency of TiN layer, passivation of the surface states by the top TiN layer, and smaller barrier height of the interfaces. Furthermore, electrostatic force microscopy and Kelvin probe force microscopy provide direct evidence of charge injection from TiN to the MoOx film at the nanoscale. The TA absorption spectra show a strong photo-bleaching signal over wide spectral range and ultrafast decaying behavior at the picosecond time scale, which indicate efficient electron transfer from TiN to MoOx. Thus, our simple and effective approach can facilitate HC collection under white light, thereby achieving high conversion efficiency for optoelectronic devices.

The exciton behavior of a new synthetic material, 11-phenyl-11H-9,16-dioxa-11-aza-4b-boraindeno[1,2-a]naphtho[3,2,1-de]anthracene (Ph-OBNA), which displays a multi-resonance effect, and bis[4-(9,9-dimethyl-9,10-dihydroacridine)phenyl]sulfone (DMAC-DPS) with a donor–acceptor-donor structure was analyzed. First, we conducted quantum mechanical simulations based on long-range theory (LC-ωPBE) to predict kRISC, and we confirmed the effect of the luminescence behavior by analyzing aggregation-caused quenching (ACQ) according to π–π stacking and aggregation-induced emission (AIE) behavior. Actually, thermally activated delayed fluorescence materials showing ACQ and AIE behavior exhibited different triplet–triplet annihilation (TTA) and singlet–triplet annihilation (STA) rate constants. Interestingly, DMAC-DPS exhibited a restricted exciton concentration quenching behavior based on an observed AIE owing to its inhibited molecular stacking behavior. On the other hand, Ph-OBNA demonstrated somewhat reduced TTA and STA behavior due to an ACQ behavior originating from excimer formation at high concentrations. Despite this difference, both materials demonstrated a hyperfluorescence behavior that can be used to achieve moderately high device efficiency compared with that obtained from common fluorescence emitters.

Purpose: Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F.Methods: RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting.Results: Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells.Conclusion: We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.

Immunogenic cell death (ICD) is a key factor for generating antitumor immunity. Endoplasmic reticulum (ER) stress triggers the release of damage-associated molecular patterns (DAMPs), thus inducing...

Lagerstroemia ovalifolia Teijsm. & Binn. (LO) (crape myrtle) has reportedly been used as traditional herbal medicine (THM) in Java, Indonesia. Our previous study revealed that the LO leaf extract (LOLE) exerted anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Based on this finding, the current study aimed to evaluate the protective effects of LOLE in a mouse model of LPS-induced acute lung injury (ALI). The results showed that treatment with LPS enhanced the inflammatory cell influx into the lungs and increased the number of macrophages and the secretion of the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of mice. However, these effects were notably abrogated with LOLE pretreatment. Furthermore, the increase of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression in the lung tissues of mice with ALI was also reversed by LOLE. In addition, LOLE significantly suppressed the LPS-induced activation of the MAPK/NF-κB signaling pathway and led to heme oxygenase-1 (HO-1) induction in the lungs. Additionally, in vitro experiments showed that LOLE enhanced the expression of HO-1 in RAW264.7 macrophages. The aforementioned findings collectively indicate that LOLE exerts an ameliorative effect on inflammatory response in the airway of ALI mice.

The objective of this study was to determine biological effects of Cirsium japonicum extract and its main component cirsimaritin on high‐fat diet (HFD)‐induced metabolic dysfunction‐associated fatty liver disease (MAFLD) in a mouse model. Mice were fed with a HFD to induce MAFLD and simultaneously administered with C. japonicum extract (CJE) or cirsimaritin. Various MAFLD biomarkers were evaluated using biological methods. Results demonstrated that triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels in the liver of mice were significantly reduced upon administration of CJE or cirsimaritin. Treatment with CJE or cirsimaritin also reduced the severity of liver injury in the experimental mouse model of MAFLD by inhibiting hepatic steatosis, oxidative stress, inflammation, and liver fibrosis. These results demonstrate that CJE and cirsimaritin as its main compound have a preventive action against the progression of hepatic steatosis to fibrosis and cirrhosis. Our study suggests that CJE and cirsimaritin might be promising agents for preventing and/or treating MAFLD., Cirsium japonicum and Cir improved HFD‐induced MAFLD through inhibition of hepatic steatosis, oxidative stress, and inflammation.

Melamine was grafted to a polyurethane (PU) frame and utilized for cross-linking PU via amino groups. The degree of crosslinking and the solution viscosity increased notably after grafting melamine due to the formation of crosslinks. The thermal transition of the soft segment was not significantly affected, but the glass transition was observed at a slightly higher temperature in case of the grafted melamine. Melamine-mediated crosslinking increased not only the breaking tensile stress but also the shape recovery performance of PU. In addition, crosslinked PU was more flexible at low temperature than unmodified PU. Overall, melamine-mediated crosslinking improved the tensile resistance to stress, the recovery tendency to the initial shape, and the flexibility with minor changes in the thermal transition, tensile strain, and shape retention at a low temperature.

Conjugate vaccine platform is a promising strategy to overcome the poor immunogenicity of bacterial polysaccharide antigens in infants and children. A carrier protein in conjugate vaccines works not only as an immune stimulator to polysaccharide, but also as an immunogen; with the latter generally not considered as a measured outcome in real world. Here, we probed the potential of a conjugate vaccine platform to induce enhanced immunogenicity of a truncated rotavirus spike protein ΔVP8*. ΔVP8* was covalently conjugated to Vi capsular polysaccharide (Vi) of Salmonella Typhi to develop a bivalent vaccine, termed Vi-ΔVP8*. Our results demonstrated that the Vi-ΔVP8* vaccine can induce specific immune responses against both antigens in immunized mice. The conjugate vaccine elicits high antibody titers and functional antibodies against S. Typhi and Rotavirus (RV) when compared to immunization with a single antigen. Together, these results indicate that Vi-ΔVP8* is a potent and immunogenic vaccine candidate, thus strengthening the potential of conjugate vaccine platform with enhanced immune responses to carrier protein, including ΔVP8*.

Herein, apoptotic mechanism of Moracin D was explored in prostate cancer cells in association with peroxisome proliferator-activated receptor gamma (PPAR-γ)-related signaling involved in lipid metabolism. Moracin D augmented cytotoxicity and sub G1 population in PC3 and DU145 prostate cancer cells, while DU145 cells were more susceptible to Moracin D than PC3 cells. Moracin D attenuated the expression of caspase-3, poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma-extra-large (Bcl-xL) in DU145 cells. Consistently, Moracin D significantly augmented the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in DU145 cells. Interestingly, Moracin D activated PPAR-γ and phospho-protein kinase C delta (p-PKC-δ) and inhibited phospho-protein kinase C alpha (p-PKC-α) in DU145 cells. Furthermore, STRING bioinformatic analysis reveals that PPAR-γ interacts with nuclear factor-κB (NF-κB) that binds to PKC-α/PKC-δ or protein kinase B (AKT) or extracellular signal-regulated kinase (ERK). Indeed, Moracin D decreased phosphorylation of NF-κB, ERK, and AKT in DU145 cells. Conversely, PPAR-γ inhibitor GW9662 reduced the apoptotic ability of Moracin D to activate caspase 3 and PARP in DU145 cells. Taken together, these findings provide a novel insight that activation of PPAR-γ/p-PKC-δ and inhibition of p-PKC-α are critically involved in Moracin D-induced apoptosis in DU145 prostate cancer cells.

A substantial amount of research effort has been directed toward the development of Pt-based catalysts with higher performance and durability than conventional polycrystalline Pt nanoparticles to achieve high-power and innovative energy conversion systems. Currently, attention has been paid toward expanding the electrochemically active surface area (ECSA) of catalysts and increase their intrinsic activity in the oxygen reduction reaction (ORR). However, despite innumerable efforts having been carried out to explore this possibility, most of these achievements have focused on the rotating disk electrode (RDE) in half-cells, and relatively few results have been adaptable to membrane electrode assemblies (MEAs) in full-cells, which is the actual operating condition of fuel cells. Thus, it is uncertain whether these advanced catalysts can be used as a substitute in practical fuel cell applications, and an improvement in the catalytic performance in real-life fuel cells is still necessary. Therefore, from a more practical and industrial point of view, the goal of this review is to compare the ORR catalyst performance and durability in half- and full-cells, providing a differentiated approach to the durability concerns in half- and full-cells, and share new perspectives for strategic designs used to induce additional performance in full-cell devices.

Non-enzymatic nitric oxide (NO) generation via the reduction of nitrate and nitrite ions, along with remarkably high levels of nitrate ions in skeletal muscle, have been recently described. Skeletal muscle nitrate storage may be critical for maintenance of NO homeostasis in healthy ageing and nitrate supplementation may be useful for treatment of specific pathophysiologies as well as enhancing normal functions.

The development of high-performance Ni catalysts including the formation and stabilization of active Ni nanoparticles with high surface areas by increasing their metal dispersion at the high metal loading have been major issues in the design of a compact reformer for hydrogen production. Herein, we first report a facile method based on the sequential melt infiltration process for creating highly dispersed Ni nanoparticles (~7.5 nm) incorporated into alumina support (Ni/Al2O3) with high Ni load (45 wt%). They showed much higher hydrogen productivity and reaction rate than that of the incipient wet-impregnated Ni catalyst and commercial Ni catalyst as well as good thermal stability in steam-methane reforming under harsh conditions.

Conjugation of carbohydrate antigens with a carrier protein is a clinically proven strategy to overcome the poor immunogenicity of bacterial polysaccharide. In addition to its primary role, which is to help generate a T cell-mediate long-lasting immune response directed against the carbohydrate antigen, the carrier protein in a glycoconjugate vaccine can also play an important role as a protective antigen. Among carrier proteins currently used in licensed conjugate vaccines, non-typeable Haemophilus influenzae protein D has been used as an antigenically active carrier protein. Our previous studies also indicate that some carrier proteins provide B cell epitopes, along with T cell helper epitopes. Herein we investigated the dual role of truncated rotavirus spike protein ΔVP8* as a carrier and a protective antigen. Capsular polysaccharide lipoarabinomannan (LAM), purified from Mycobacterium tuberculosis (M.tb), was chemically conjugated with ΔVP8*. Mouse immunization experiments showed that the resultant conjugates elicited strong and specific immune responses against the polysaccharide antigen, and the responses were comparable to those induced by Diphtheria toxoid (DT)-based conjugates. The conjugate vaccine induced enhanced antibody titers and functional antibodies against ΔVP8* when compared to immunization with the unconjugated ΔVP8*. Thus, these results indicate that ΔVP8* can be a relevant carrier protein for glycoconjugate vaccine and the glycoconjugates consisting of ΔVP8* with LAM are effective bivalent vaccine candidates against rotavirus and tuberculosis.

This paper demonstrates eggshell membrane protein hydrolysate (ESMH), a critical food waste worldwide, can be harnessed as a multifunctional agent for eco-friendly reduction and functionalization of graphene oxide (GO) based on its diverse and abundant functional groups. The resulting GO reduced and functionalized with ESMH (ESMH-RGO) exhibits an aqueous dispersibility and applicability as a 2-dimensional support for synthesis of catalytic Au nanoparticles (Au NPs) with a high density. The AuNPs synthesized on ESMH-RGO (AuNPs@ESMH-RGO) presents a high catalytic activity for conversion of environmental pollutant (4-nitrophenol) to an industrially useful raw material (4-aminophenol). Those results clearly indicate that ESMH has a strong potential in environmental and materials chemistry.

Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut–liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host’s immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut–liver axis in ALD and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) can lead to hepatocellular carcinoma (HCC). The level of the transcription factor SOX2 correlates with HCC progression, but its role in fat accumulation remains unclear. Here, a high-fat diet, with and without fructose, significantly upregulated SOX2 in murine liver tissue. Treatment with free fatty acids (FFAs) and fructose upregulated SOX2 in murine FL83B hepatocytes. SOX2 overexpression or knockdown regulated triglyceride synthesis and lipid accumulation after FFA stimulation. CD36, a fatty acid transporter, and Yes-associated protein (YAP), a downstream molecule of the Hippo signaling pathway, were upregulated by FFA/fructose in vivo and in vitro. Transcriptional regulation of CD36 by SOX2 suggested the involvement of CD36 in SOX2-mediated hepatic steatosis. Thus, SOX2 may be a target to prevent NAFLD development.

Accurate calculation of the electronic band structure is essential to material screening and design. Hybrid density functional has been recently widely used to describe the electronic structure of semiconductors; however, it is difficult to locate the band edge positions of indirect band gap materials due to heavy computational cost especially when the band edges are not located at special k-points. We suggest how to investigate three-dimensional band structure efficiently with hybrid density functionals and to find the band edge positions. The band edge position of diamond Si, SbSI, and MoS2 are investigated using the proposed method.

Large-eddy simulation with the thickened flame model (LES/TFM) is conducted to simulate a three-dimensional dual swirl partially premixed methane/air gas turbine model combustor. Finite-rate chemis...

Inorganic materials such as SiOx and SiNx are commonly used as dielectric layers in thin-film transistors (TFTs), but recent advancements in TFT devices, such as inclusion in flexible electronics, require the development of novel types of dielectric layers. In this study, CVD-deposited poly(p-xylylene) (PPx)-based polymers were evaluated as alternative dielectric layers. CVD-deposited PPx can produce thin, conformal, and pinhole-free polymer layers on various surfaces, including oxides and metals, without interfacial defects. Three types of commercial polymers were successfully deposited on various substrates and exhibited stable dielectric properties under frequency and voltage sweeps. Additionally, TFTs with PPx as a dielectric material and an oxide semiconductor exhibited excellent device performance; a mobility as high as 22.72 cm2/(V s), which is the highest value among organic gate dielectric TFTs, to the best of our knowledge. Because of the low-temperature deposition process and its unprecedented mechanical flexibility, TFTs with CVD-deposited PPx were successfully fabricated on a flexible plastic substrate, exhibiting excellent durability over 10000 bending cycles. Finally, a custom-synthesized functionalized PPx was introduced into top-gated TFTs, demonstrating the possibility for expanding this concept to a wide range of chemistries with tunable gate dielectric layers.

This study examined biochemical components, fatty acids, antioxidant dipeptides, and muscle fiber density of breast and thigh muscles from Korean new native chicken strains (A and B) at two slaughter ages, compared with white semi-broiler (W) or broilers. The pH values were different by chicken breed. The new native strains had the lowest fat content in the breast at 12 wk (p

A 60-d feeding trial was conducted to evaluate the effects of diets supplemented with two concentrations (0% and 0.3%) of black raspberry (Rubus coreanus Miquel) fruit by-product (RCFB) on the physicochemical characteristics, oxidative stability, antioxidant capacity, antioxidant enzyme activity, and fatty acid profile of M. longissimus dorsi (LL) porcine muscle from Berkshire finishing pigs meat. Results revealed that regardless of the sex, diets supplemented with 0.3% RCFB reduced (p 0.05) on meat color, WHC, shear force, and fatty acid contents while fed diet supplemented with 0% or 0.3% RCFB for male or female pigs. Overall, this study suggests that a diet supplemented with 0.3% RCFB may beneficially affect owing to better oxidative stability, higher antioxidant capacity, and antioxidant enzyme activity (blood plasma) in pigs which could be a promising natural antioxidant without affecting meat quality traits.

Multiple sclerosis (MS) treatment via cytokine-mediated immunomodulation has been hampered by the difficulty with which cytokines can be stably and noninvasively delivered to the central nervous system. Here, we show that interleukin (IL)-13 packaged in extra-large-pore mesoporous silica nanoparticles (XL-MSNs) is protected from degradation and directs the alternative activation of macrophages both in vitro and in vivo. Furthermore, the noninvasive intranasal delivery of IL-13-loaded XL-MSNs ameliorated the symptoms of experimental autoimmune encephalomyelitis, a murine model of MS, accompanied by the induction of chemokines orchestrating immune cell infiltration. These results demonstrate the therapeutic potential of IL-13-loaded XL-MSNs for MS patients.

When primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial–mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.

Spermatogonial stem cells (SSCs) are crucial for maintaining spermatogenesis, studying germ line stem cell biology, and producing transgenic animals. Growth factors, including leukemia inhibitory factor (LIF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and glial cell line-derived neurotrophic factor (GDNF), are essential for in vitro culture of SSCs as well as their self-renewal and maintenance. In this study, we investigated the effects of these growth factors on porcine spermatogonial germ cell (pSGC) colony formation. We determined round alkaline phosphatase (AP)-positive pSGC colonies in the presence and absence of growth factors after 7 days of pSGC culture. EGF was found to be essential to support the formation of AP-positive pSGC colonies. The expression of epidermal growth factor receptor (EGFR) and Erb-B2 receptor tyrosine kinase 2 (ERBB2) was also altered in cultured pSGCs compared to that in feeder cells. We verified the effect of EGF signaling on pSGC colony formation using AG1478 as an EGFR inhibitor and AG879 as an ERBB2 inhibitor. pSGC colonies were observed in low dose AG1478-treated groups with EGF, whereas a high dose of AG1478 suppressed pSGC colony formation. AP-positive colonies were also observed in all AG879-treated groups. Taken together, EGFR and EGF signaling play a critical role in the initiation of colony formation of pSGCs. Our study provides insights into the mechanisms of EGF-mediated colony formation by SGCs derived from porcine testes, and will aid the development of transplantation techniques for the production of transgenic offspring.

Lignocellulose nanofibrils (LCNFs) were produced from the biomass of Mongolian oak for the first time using deep eutectic solvent pretreatment and mechanical defibrillation. Three Choline chloride (CC)-based DESs were selected and the effect of various DES pretreatment conditions on the chemical composition of wood sample was studied first. CC/lactic acid (CC/LA) pretreatment caused high lignin and hemicellulose removal whereas CC/urea (CC/U) and CC/glycerin (CC/GLY) pretreatment increased the fiber’s susceptibility to defibrillation. With the significant influence of temperature, its effect on the subsequent mechanical defibrillation was also studied. For all three DESs, pretreatment condition of 1:2 mol ratio, 6 h time, and 140 °C was found optimal for LCNF preparation. LCNFs with diameter

The present study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of L. curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density (BMD) in ovariectomized (OVX) mice in μ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

The efficient nonviral delivery of nucleic acids into the cytoplasm is needed to fully realize the potential of gene therapy. Although cationic lipids and nanoparticles have been widely used to improve the intracellular delivery of nucleic acids, they suffer from cytotoxicity and poor endosomal escape, thus limiting the transfection efficacy. Here, we developed a photothermal transfection platform for efficient and biosafe intracellular delivery of nucleic acids. Photothermal transfection was carried out by irradiation of cells co-treated with Lipofectamine-plasmid DNA complexes and PEGylated gold nanorods (GNRs) using an NIR laser for 30 min and subsequent incubation of the cells for 30 min without laser irradiation. Compared to conventional Lipofectamine-based transfection, our photothermal transfection platform significantly improved the transfection efficiency in difficult-to-transfect human primary cells including human dermal fibroblasts while maintaining the cell viability. The photothermal heating did not leave the GNRs inside the cell, thereby minimizing the cellular damage. Furthermore, the photothermal transfection platform showed superior genome editing abilities (both gene cleavage and insertion) in human dermal fibroblasts than conventional Lipofectamine-based transfection.

In order to reduce the amount of excess silicon and carbon, reaction-bonded silicon carbide was fabricated by liquid silicon infiltration using a porous carbon preform prepared by chemical vapor deposition. A carbon preform was fabricated at 1100−1400 ℃ at 6.6 kPa for 1 h using acetylene. The deposited carbon preform has a porous structure with nano-sized carbon particles and uniform pore size distribution. Depending on the deposition temperature of the carbon preform, the porosity, the pore size, and the size of the carbon particles were controlled. As the deposition temperature increased, the porosity and average pore size increased, but the average carbon particle size decreased. The residual silicon of the prepared reaction-bonded silicon carbide was 2.7 % when the porosity of the carbon preform deposited at 1100 °C was 51.1 %. The hardness increased up to 21.7 GPa as the amount of the residual silicon reduced.

Sorafenib (SF) is a standard, clinically-recognized therapy for treating hepatocellular carcinoma (HCC) patients. However, as a multikinase inhibitor, SF causes a systemic side effect. Therefore, there is an urgent need to selectively deliver the optimum dose of SF to the tumor site. The present study aimed to selectively target SF to HCC using a biocompatible drug carrier to increase the therapeutic efficacy, in turn, minimize the adverse effects. To this end, methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) di-block copolymer was selected as an amphiphilic carrier for SF that hydrophobic PCL core can encapsulate SF through self-assembly. Cyclic RGDfK (cRGD) was conjugated to the end of PEG-PCL (cRGD-PEG-PCL) for HCC targeting. Sulfo-Cyanine5.5 (S-Cy5.5) was also incorporated to PEG-PCL (S-Cy5.5-PEG-PCL) for near-infrared fluorescence (NIRF) imaging. The composition, morphology and size distribution of nanoparticles (NPs) were characterized by 1H NMR, transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In addition, the ability of the integrin-mediated targeting of NPs for the selective delivery of SF was systemically investigated with Hep3B cell line and a nude mouse xenograft model. Consequently, it was found that S-Cy5.5-cRGD-PEG-PCL leads to the selective accumulation of SF into the tumor site and improve anticancer activity against HCC.

Purpose: This study investigated the antioxidant and enzymatic activities of 20 species of the most widely consumed edible flowers in South Korea to provide basic data on their bioactivity. Methods: After the selected edible flowers were processed based on the tea manufacturing method, the antioxidant activities (total polyphenol, flavonoid content, DPPH, and ABTS radical scavenging activities) were evaluated. Two species of edible flowers exhibiting exceptional antioxidant activities were selected and their enzymatic activities (tyrosinase, elastase, α-glucosidase, and ACE inhibitory activities) were assessed. Results: Among the 20 species of edible flowers used for tea manufacturing, Viola tricolor L. (V. tricolor L.) and Chamomilla recutita (C. recutita ) were found to have the highest overall antioxidant activity. Based on these results, V. tricolor L. and C. recutita were selected to determine their enzymatic activities; V. tricolor L. showed higher levels of tyrosinase, elastase, and ACE inhibitory activities, whereas C. recutita showed a higher level of α-glucosidase inhibitory activity. Conclusion: Based on their exceptional antioxidant and enzymatic activities among the 20 species of edible flowers, V. tricolor L. and C. recutita are predicted to be of greater use in the development of inner beauty products.

Background: Lung epithelial cells serve as first line of defense against various inhaled pollutant particles. This study focused on assessing the impact of organic extracts of PM2.5 collected in Seoul, South Korea on primary human lung epithelial cells and identifying the relevant components and sources which induced lung epithelial cell injury.Results: We used primary lung epithelial cells isolated directly from healthy donors and evaluated the effects of organic compounds of twelve selected, seasonal PM2.5 on inflammation, cellular aging, and macroautophagy in primary lung epithelial cells. Organic extracts of PM2.5 specifically induced neutrophilic chemokine, interleukin-8, via extracellular signal regulated kinase activation. Moreover, PM2.5 significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations, OC and EC, had no significant correlations with PM2.5 effects. However, regression analysis showed that polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM2.5 correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources were strongly correlated with neutrophilic inflammation, aging and macroautophagy activation.Conclusions: These data suggest that the chemical composition of PM2.5 is crucially important to determine the adverse health effects of PM2.5. Our study provides encouraging evidence to regulate the harmful components of PM2.5 in Seoul.

Poly(acrylic acid) and poly(2-(dimethylamino)ethyl acrylate) chains were grafted to polyurethane (PU) using the graft-polymerization method in order to enhance the water compatibility of PU. The grafted chains were ionized into cationic or anionic form depending on the addition of strong acid or base. The grafted polymer chains did not affect the melting, crystallization, and glass transition of the soft segment of PU due to the softness of the chain. The cross-link density and solution viscosity increased due to the linking between the grafted chains, but the slight cross-linking did not disturb the solvation of PU. The slight cross-linking notably enhanced the maximum tensile stress and shape recovery capability, and the water compatibility of PU could be notably enhanced by the grafted ionized chains. Overall, the grafting of ionized polymeric chains onto PU could enhance the hydrophilicity of PU surface, tensile strength, and shape recovery capability.

While it has long been known that contraction robustly stimulates skeletal muscle glucose uptake, the molecular steps regulating this increase remain incompletely defined. The mammalian ortholog of Sir2, sirtuin 1 (SIRT1), is an NAD(+)-dependent protein deacetylase that is thought to link perturbations in energy flux associated with exercise to subsequent cellular adaptations. Nevertheless, its role in contraction-stimulated glucose uptake has not been described. The objective of this study was to determine the importance of SIRT1 to contraction-stimulated glucose uptake in mouse skeletal muscle. Using a radioactive 2-deoxyglucose uptake (2DOGU) approach, we measured ex vivo glucose uptake in unstimulated (rested) and electrically stimulated (100 Hz contraction every 15 s for 10 min; contracted) extensor digitorum longus (EDL) and soleus from ∼15-wk-old male and female mice with muscle-specific knockout of SIRT1 deacetylase activity and their wild-type littermates. Skeletal muscle force decreased over the contraction protocol, although there were no differences in the rate of fatigue between genotypes. In EDL and soleus, loss of SIRT1 deacetylase activity did not affect contraction-induced increase in glucose uptake in either sex. Interestingly, the absolute rate of contraction-stimulated 2DOGU was ∼1.4-fold higher in female compared with male mice, regardless of muscle type. Taken together, our findings demonstrate that SIRT1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle. Moreover, to our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in mouse skeletal muscle. NEW & NOTEWORTHY Here, we demonstrate that glucose uptake in response to ex vivo contractions is not affected by the loss of sirtuin 1 (SIRT1) deacetylase function in muscle, regardless of sex or muscle type. Interestingly, however, similar to studies on insulin-stimulated glucose uptake, we demonstrate that contraction-stimulated glucose uptake is robustly higher in female compared with the male skeletal muscle. To our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in skeletal muscle.

Background Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. Methods This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. Results Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. Conclusion Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

Dextran, a homologous polysaccharide with the main chain of glucose units composed by an α-1,6 glycosidic bond, is synthesized from dextrin by dextran-dextrinase (DDase), a transglucosidase, derived from acetic acid bacteria Gluconobacter oxydans and lactic acid bacteria (LAB). The effective culture conditions were examined for producing dextran via bio-conversion with acetic acid bacteria (AAB) demonstrating DDase activity in various medium compositions during 0 to 7 days with or without glycerol addition (2%, v/v) and different degrees of dextrin polymerization (D.E.) based on the addition level (1,5%, w/v). On day 7, the G. oxydans growth was almost tripled in presence of glycerol as observed via a cell growth curve (OD). After culturing for 7 days, the pH decreased from 6 to 3.1-3.5, and the acidity increased from 0.12% to 0.4-0.62%, depending on the dextrin D.E. and the addition level. The reducing sugar decreased continuously. The medium containing 5% dextrin showed shear-thinning characteristics. The apparent viscosity of the 5% dextrin DE4-7 culture solution was 5.6 mPa·s, which was similar to that of the 20% dextran aqueous solution. The analysis of constituent saccharides contained in the culture medium (HPAEC-PAD) showed a substance with a high degree of polymerization. 1H-NMR analysis showed that α-1,6 glycosidic bond existed as the intermolecular bond of this substance. Therefore, efficient production of dextran was possible by culturing in a medium containing 5% dextrin and glycerol during culture of AAB.

Biotin (vitamin B7) is a water-soluble vitamin used as a co-enzyme for carboxylases essential for human metabolism. The high affinity to streptavidin makes biotin an important substance in immunoassays. Excessive biotin intake due to over-the counter supplements has become problematic because of the effects on laboratory test results. There have been no reports of biotin-induced thyroid immunoassay interference in Korea. We report three patients with papillary thyroid cancer who showed false thyrotoxicosis on follow-up laboratory examinations with a literature review. The patients’ medical history should be thoroughly questioned and patients should be informed to curtail consuming biotin before laboratory tests to avoid assay interference. Non-biotinylated assays can be considered if it is impossible to withhold the supplements. These methods will prevent physicians from making incorrect decisions that could result in an inappropriate treatment for their patients.

Background/aimsEvaluation of the retinal nerve fibre layer (RNFL) is important for identifying glaucomatous damage. Ultrawide-field fundus photography (UWP) imaging is increasingly used in the ophthalmological field; however, it is unknown whether it can be used for detecting RNFL defects (RNFLDs). We investigated whether RNFLD can be detected with UWP images and compared the clinical effectiveness of three types of images for detecting RNFLD: conventional red-free RNFL photography (RFP), non-mydriatic UWP and digitally converted green separation of non-mydriatic UWP (G-UWP).MethodsEyes with glaucoma or glaucoma suspect and normal control eyes meeting the eligibility criteria were consecutively enrolled from September 2019 to April 2020. Their conventional RFP, non-mydriatic UWP and G-UWP images were assessed for detecting RNFLD to evaluate the sensitivity and specificity for detecting RNFLD.ResultsThree image sets of 196 participants (84 normal control, 25 glaucoma suspect and 87 glaucoma) were obtained. The sensitivity of G-UWP (94.6%; 95% CI 88.7 to 98.0) and RFP (92.9%; 95% CI 86.4 to 96.9) was higher than that of UWP (82.1%; 95% CI 73.8 to 88.7; pConclusionNon-mydriatic UWP images can be used to detect RNFLD. Non-mydriatic G-UWP showed comparable sensitivity but lower specificity to conventional RFP. Non-mydriatic G-UWP could be used as a convenient and useful diagnostic tool for screening glaucoma in clinical settings.

Cyanidin 3-O-glucoside (C3G), which has various health-promoting functions, is contained in black soybean (BSB). In Japan and Korea, BSB is cooked with rice and the cooked rice appears purplish in ...

Background Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. Objective This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). Methods The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. Results PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/− AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase–dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. Conclusions PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

s Terpenoids are a class of natural compounds with many important functions and applications. They are synthesized from a long synthetic pathway of isoprenyl unit coupling with the myriads of terpene synthases. Owing to the catalytic divergence of terpenoids synthesis, microbial production of terpenoids is compromised to the complexity of pathway engineering and suffers from the metabolic engineering burden. In this work, the adaptive Escherichia coli HP variant exhibited a general cell fitness in terpenoid synthesis. Especially, it could yield taxadiene of 193.2 mg/L in a test tube culture, which is a five-fold increase over the production in the wild type E. coli DH5α. Mutational analyses indicated that IS10 insertion in adenylate cyclase CyaA (CyaAHP) resulted in lowering intracellular cyclic AMP (cAMP), which could regulate its receptor protein CRP to rewire cell metabolism and contributed to the improved cell fitness. Our results suggested a way to manipulate cell fitness for terpenoids production and other products.

Background: Activation of mitogen-activated protein kinases (MAPKs) is regulated by a phosphorylation cascade comprising three kinases, MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK. MAP2K1 and MAPK2K2, also known as MEK1 and MEK2, activate ERK1 and ERK2. The structure of the MAPK signaling cascade has been studied, but high-resolution structural studies of MAP2Ks have often focused on kinase domains or docking sites, but not on full-length proteins. Objective: To understand the conformational dynamics of MEK1. Methods: Full-length MEK1 was purified from Escherichia coli (BL21), and its conformational dynamics were analyzed using hydrogen/deuterium exchange mass spectrometry (HDX-MS). The effects of ATP binding were examined by coincubating MEK1 and adenylyl-imidodiphosphate (AMP-PNP), a non-hydrolysable ATP analog. Results: MEK1 exhibited mixed EX1/EX2 HDX kinetics within the N-terminal tail through β1, αI, and the C-terminal helix. AMP-PNP binding was found to reduce conformational dynamics within the glycine-rich loop and regions near the DFG motif, along with the activation lip. Conclusion: We report for the first time that MEK1 has regions that slowly change its folded and unfolded states (mixed EX1/EX2 kinetics) and also report the conformational effects of ATP-binding to MEK1.

The roles of nitrate and nitrite ions as nitric oxide (NO) sources in mammals, complementing NOS enzymes, have recently been the focus of much research. We previously reported that rat skeletal muscle serves as a nitrate reservoir, with the amount of stored nitrate being highly dependent on dietary nitrate availability, as well as its synthesis by NOS1 enzymes and its subsequent utilization. We showed that at conditions of increased NO need, this nitrate reservoir is used in situ to generate nitrite and NO, at least in part via the nitrate reductase activity of xanthine oxidoreductase (XOR). We now further investigate the dynamics of nitrate/nitrite fluxes in rat skeletal muscle after first increasing nitrate levels in drinking water and then returning to the original intake level. Nitrate/nitrite levels were analyzed in liver, blood and several skeletal muscle samples, and expression of proteins involved in nitrate metabolism and transport were also measured. Increased nitrate supply elevated nitrate and nitrite levels in all measured tissues. Surprisingly, after high nitrate diet termination, levels of both ions in liver and all muscle samples first declined to lower levels than the original baseline. During the course of the overall experiment there was a gradual increase of XOR expression in muscle tissue, which likely led to enhanced nitrate to nitrite reduction. We also noted differences in basal levels of nitrate in the different types of muscles. These findings suggest complex control of muscle nitrate levels, perhaps with multiple processes to preserve its intracellular levels.