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Background Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean red ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

Carbon dots (CDs) are unique light-emissive nanoparticles that are valuable for various applications. However, their complex chemical structures and the limited research interest in their visible-light emission hinder the understanding of their emission structures. Herein, we report the existence of near-infrared (NIR) emissive states originating from the graphitic cores in CDs, which exhibit a completely different behavior from their well-known visible emissive states. Using ultrafast spectroscopy and density functional theory (DFT) calculations, we elucidate the emission mechanism and suggest that small (1–2 nm) graphitic subregions in CDs produce the NIR emissive states, which are rarely affected by surface chemistry changes. Our proposed mechanism and its universality are investigated comprehensively by a comparative analysis with graphene oxide and other types of CDs obtained by different synthetic methods. Finally, we propose a comprehensive emission structure of CDs and redefine the role of structural components in visible-to-NIR emission.

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg(-1) IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg(-1) IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...

Channel-shortening effect (CSE) in oxide thin film transistors (TFTs) is a crucial issue that must be resolved for applications in ultra-high-resolution displays. One of the origins of the CSE is the diffusion of a shallow donor such as hydrogen from other layers into the channel. In this study, we investigated for the first time the CSE of self-aligned Al-doped In-Sn-Zn-O (Al-ITZO) TFTs with planar and trench structures. The TFTs with planar structures exhibited severe negative $\text{V}_{ {{ON}}}$ shifts after an annealing process, whereas the TFTs with trench structures were barely affected, thereby exhibiting excellent ON/ OFF characteristics. The vertical channel in the trench TFT had higher resistance than the horizontal channel because of a back-sidewall roughness and thin channel. The high resistance of vertical channels played a significant role in determining the ON/ OFF characteristics of Al-ITZO TFT, where $\text{V}_{ {{ON}}}$ remained constant until the diffused shallow donors made the resistive vertical channels become conductive. Based on these unique operation characteristics, the suppression of CSE in a trench TFT was demonstrated even under a high annealing temperature. Trench TFT exhibited higher mobility, higher drain currents, and higher stability than planar TFT, thus making it suitable for ultra-high-resolution displays.

Background Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response. Korean red ginseng (KRG) is a natural product with anti-inflammatory and anti-carcinogenic properties. Thus, the purpose of this study is to investigate the effects of KRG on DEHP-induced inflammatory response in endometrial cancer Ishikawa cells and a mouse model of endometriosis. Methods RNA-sequencing was performed and analyzed on DEHP-treated Ishikawa cells in the presence and absence of KRG. The effects of KRG on DEHP-induced cyclooxygenase-2 (COX-2) mRNA levels in Ishikawa cells were determined by RT-qPCR. Furthermore, the effects of KRG on the extracellular signal-regulated kinases (ERKs) pathway, COX-2, and nuclear factor-kappa B (NF-κB) p65 after DEHP treatment of Ishikawa cells were evaluated by western blotting. In the mouse model, the severity of endometriosis induced by DEHP and changes in immunohistochemistry were used to assess the protective effect of KRG. Results According to the RNA-sequencing data, DEHP-induced inflammatory response-related gene expression was downregulated by KRG. Moreover, KRG significantly inhibited DEHP-induced ERK1/2/NF-κB/COX-2 levels in Ishikawa cells. In the mouse model, KRG administration significantly inhibited ectopic endometriosis growth after DEHP-induced endometriosis. Conclusions Overall, these results suggest that KRG may be a promising lead for the treatment of endometrial cancer and endometriosis via suppression of the inflammatory response.

Background In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H2O2, and the keratinocyte cells were treated with SYR (0–200 μg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H2O2-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC50 value of 10.77 and 10.35 μg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H2O2-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion SYR showed antioxidant activity and up-regulated autophagy activity in H2O2-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

This paper presents a high-performance radio frequency (RF) power amplifier (PA) module for which an optimum chip-level packaging structure is proposed to reduce the operating temperature of the RF PA monolithic microwave integrated circuit (MMIC). Because the output power (Pout) and the efficiency of a RF PA module are strongly affected by the thermal characteristics of the PA MMIC, various types of heat spreader materials and thermal interface materials have been examined to implement the PA chip-level packaging structure, and the optimum combination is proposed for a performance enhancement of the PA module in this paper. In addition, the optimum form-factor of the heat spreader was suggested based on a thermal simulation. To verify the proposed PA chip-level packaging structure, a 10 W 618 GHz RF PA MMIC using a commercial 0.25-m gallium nitride high electron mobility transistor process was designed and implemented for radar applications. The operating temperature of the PA MMIC on the proposed chip-level packaging structure shows a dramatic reduction of 24.8 C, and accordingly, the average Pout and average power-added efficiency are enhanced by up to 9.2% and 2.8%, respectively, when compared with a PA module using the conventional chip-level packaging structure.

Background Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor. Methods We designed gintonin-biotin conjugates through gintonin biotinylation and examined whether gintonin-biotin conjugate binding sites co-localized with the LPA receptor subtype binding sites. We further examined whether gintonin-biotin transactivated the EGF receptor via LPA receptor regulation via phosphor-EGF and cell migration assays. Results Gintonin-biotin conjugates elicit [Ca2+]i transient similar to that observed with unbiotinylated gintonin in cultured PC3 cells, suggesting that biotinylation does not affect physiological activity of gintonin. We proved that gintonin-biotin conjugate binding sites co-localized with the LPA1/6 receptor binding sites. Gintonin-biotin binding to the LPA1 receptor transactivates the epidermal growth factor (EGF) receptor through phosphorylation, while the LPA1/3 receptor antagonist, Ki16425, blocked phosphorylation of the EGF receptor. Additionally, an EGF receptor inhibitor AG1478 blocked gintonin-biotin conjugate-mediated cell migration. Conclusions We observed the binding between ginseng-derived gintonin and the plasma membrane target proteins corresponding to the LPA1/6 receptor subtypes. Moreover, gintonin transactivated EGF receptors via LPA receptor regulation. Our results suggest that gintonin directly binds to the LPA receptor subtypes and transactivates the EGF receptor. It may explain the molecular basis of ginseng physiology/pharmacology in biological systems.

Background: Metabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index.Methods: The study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group.Results: During the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively.Conclusion: MHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.Conclusion: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Solid refuse fuels (SRF) and biomass contain significant amounts of KCl and NaCl which result in operation problems such as hard deposit formation in combustion. The effect of kaolinite in the decomposition of mineral chlorides in a commercial SRF-burning CFBC boiler is investigated. The injection of kaolinite with SRF in a commercial CFBC shows its effect on mineral chloride decomposition thus softens the hardness of the deposit on the heat exchanger tubes in the convection pass. By the reaction of molten salt with kaolinite, particles under 5 μm in the flue gas is significantly reduced. After 37 days operation with kaolinite use the PM 10 particle in flue gas is reduced originally 86 mg/Nm3 to 16 mg/Nm3, which is 81% reduction. The reaction of physical and chemical adsorption of metallic oxide component to kaolinite particle is also monitored by SEM images. This result is reflected to the particle side distribution of the fly ash in that the shift of the abundant particle size peak to a larger size cut after the use of the kaolinite.

DHP107 is a newly developed lipid‐based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope‐labeled [3H]DHP107 and [18F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole‐body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10–24 h after administration. Tissue [18F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs and excreta were determined using a beta‐counter and are expressed as the percentage of injected dose (ID). Oral [18F]DHP107 was well‐absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [3H]‐ and [18F]DHP107 in healthy mice. The [18F]DHP107 reached a peak distribution of 0.7–0.8%ID in the tumor at 5.6–7.3 h in the xenograft model. The [18F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3–4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope‐labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.

Atomic layer deposition (ALD) has attracted much attention, particularly for applications in nanoelectronics because of its atomic-level controllability and high-quality products. In this study, we developed a plasma-enhanced atomic layer deposition (PEALD) process to fabricate a homogeneous indium aluminum oxide (IAO) semiconductor film. Trimethylaluminum (TMA) and dimethylaluminum isopropoxide (DMAI) were used as Al precursors, which yielded different compositions. Density functional theory (DFT) calculations on the surface reactions between indium and aluminum precursors showed that while highly reactive TMA would etch In, DMAI with lower reactivity would allow indium to persist in the films, resulting in a more controlled doping of Al. The In/Al composition ratio could be further precisely controlled by adjusting the indium precursor dose time to sub-saturation. IAO based on DMAI was applied to fabricate thin-film transistors (TFTs), showing that Al can be a carrier suppressor of indium oxide. TFTs with PEALD IAO containing 3.8 atomic % Al showed a turn-on voltage of -0.4 ± 0.3 V, a subthreshold slope of 0.09 V/decade, and a field effect mobility of 18.9 cm2/(V s).

Unlike in normal cells, ursodeoxycholic acid (UDCA) causes apoptosis rather than protection in cancer cells. Aim of this study was to demonstrate whether UDCA actually inhibits proliferation and induces apoptosis in bile duct cancer cells; the effect of UDCA on the expression of COX-2, PI3K/AKT, ERK, and EGFR; how UDCA affects cancer cell invasiveness and metastasis, since these effects are not established in bile duct cancer cells. SNU-245 cells (human extrahepatic bile duct cancer cells) were cultured. MTT assays were performed to evaluate the effect of UDCA on the cell proliferation. A cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay were used to determine apoptosis. Western blot analysis measured expression levels of various proteins. The invasiveness of the cancer cells was evaluated by invasion assay. In cultured bile duct cancer cells, UDCA suppressed cell proliferation in bile duct cancer cells by inducing apoptosis and p53 activation, blocking deoxycholic acid (DCA)-induced activated EGFR-ERK signaling and COX-2, inhibiting DCA-induced activated PI3K-AKT signaling, and suppressing the invasiveness of bile duct cancer cells. In addition, a MEK inhibitor impaired UDCA-induced apoptosis in bile duct cancer cells. UDCA has antineoplastic and apoptotic effects in bile duct cancer cells. Thus, UDCA could be a chemopreventive agent in patients with a high risk of cancer, and/or a therapeutic option that enhances other chemotherapeutics.

Chemo‐biological upcycling of poly(ethylene terephthalate) (PET) developed in this study includes the following key steps: chemo‐enzymatic PET depolymerization, biotransformation of terephthalic acid (TPA) into catechol, and its application as a coating agent. Monomeric units were first produced through PET glycolysis into bis(2‐hydroxyethyl) terephthalate (BHET), mono(2‐hydroxyethyl) terephthalate (MHET), and PET oligomers, and enzymatic hydrolysis of these glycolyzed products using Bacillus subtilis esterase (Bs2Est). Bs2Est efficiently hydrolyzed glycolyzed products into TPA as a key enzyme for chemo‐enzymatic depolymerization. Furthermore, catechol solution produced from TPA via a whole‐cell biotransformation (Escherichia coli) could be directly used for functional coating on various substrates after simple cell removal from the culture medium without further purification and water‐evaporation. This work demonstrates a proof‐of‐concept of a PET upcycling strategy via a combination of chemo‐biological conversion of PET waste into multifunctional coating materials., PETit four: A proof‐of‐concept upcycling strategy to convert poly(ethylene terephthalate) (PET) into multifunctional catechol coating materials is presented: (1) PET glycolysis without purification; (2) one‐step enzymatic hydrolysis of glycolyzed products into terephthalic acid (TPA); (3) whole‐cell biotransformation of TPA into catechol using an engineered Escherichia coli; (4) application of crude catechol solution as a multifunctional coating material without purification.

Background: Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors.Conclusion: CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Background/Aims: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.Methods: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.Results: LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.Conclusions: These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Background Non-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients. Methods Two clinical algorithms were applied to 152 CHB patients: (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results. Results In both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118). Conclusions Both ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.

Objective Two series of experiments were conducted to determine how the incremental levels of sodium metabisulfite (SMB)-treated fruit and vegetable discards (FVD) in diet of Hanwoo heifers and cows affect their performance and health. Methods In Exp. 1, 36 Hanwoo heifers were stratified by age (13.3 ± 0.83 mo) and initial body weight (305 ± 19.7 kg), and divided randomly to one of three diets containing 0, 10, or 20% SMB-treated FVD (as-fed basis). The experiment lasted 110 d, including 20 d of adaptation. In Exp. 2, 24 multiparous Hanwoo cows were divided into three groups based on age (48.2 ± 2.81 mo) and initial body condition score (2.64 ± 0.33). Cows in each block were assigned randomly to one of three diets containing 0, 11, or 22% SMB-treated FVD (as-fed basis). The experiment lasted 80 d, including a 20-d adaptation period. In both experiments, SMB-treated FVD was used as a replacement for wet brewers grain in total mixed ration (TMR). Results Growing heifers exhibited no differences in their daily feed intake (6.58 ± 0.61 kg/d DM), average daily gain (0.60 ± 0.07 kg/d), and body condition score when they consumed the incremental levels of SMB-treated FVD. Although the majority of blood metabolites were unaffected by treatments, blood urea-N and s-hydroxybutyrate levels decreased linearly as the SMB-treated FVD level increased in TMR. Similar to Exp. 1, minor differences were found in daily feed intake (8.27 ± 0.72 kg DM/d) and body condition score of Hanwoo cows. The majority of blood metabolites remained unaffected by treatments, but blood urea-N decreased as the SMB-treated FVD level in TMR increased. Conclusion Our findings suggest that SMB-treated FVD could be safely incorporated into the diet of Hanwoo heifers and cows, potentially improving N-use efficiency in the body while not impairing performance or health.

Tritium was extracted from tritium-contaminated aluminum samples by heating it in a high-temperature furnace at 200, 300, or 400 °C for 15 h. The extracted tritium was analyzed by using a liquid scintillation counter (LSC); the sample thicknesses were 0.4 and 2 mm. The differences in tritium extraction over time were also investigated by cutting aluminum stick samples into several pieces (1, 5, 10, and 15) with the same thickness, and subsequently heating them. The results revealed that there are most of the hydrated material based on tritium on the surface of aluminum. When the temperature was increased from 200 or 300 °C–400 °C, there are no large differences in the heating duration required for the radioactivity concentration to be lower than the MDA value. Additionally, at the same thickness, because the surface of aluminum is only contaminated to tritiated water, cutting the aluminum samples into several pieces (5, 10, and 15) did not have a substantial effect on the tritium extraction fraction at any of the applied heating temperatures (200, 300, or 400 °C). The proportion of each tritium-release materials (aluminum hydrate based on tritium) were investigated via diverse analyses (LSC, XRD, and SEM-EDS).

The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8 HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p = 0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.

Seaweed fibre is usually discarded as biomass waste after extraction of useful ingredients from seaweed. However this seaweed fibre, a natural abundant cellulose material with uniform dimensions 10 times smaller than other plant-based fibre can be utilized as electrode material for energy storage. In this work, we converted seaweed fibre into conductive carbon electrodes by a thermal carbonisation method. The morphology, chemical composition and conductivity are highly influenced by the carbonisation temperature. In comparison to other biomass sources such as cotton pulp, seaweed fibre is finer, smoother and more conductive at low carbonisation temperature. These carbonized seaweeds were then used as a supercapacitor, giving a high supercapacitance (226.3 Fg−1) at the carbonisation temperature of 900°C, and good stability within 2400 cycles. This specific capacitance is significantly higher than values obtained from filter paper or cotton pulp.

The purpose of this study is to investigate the surface activity of starch nanocrystals (SNC), material derived from starch, and confirm their usefulness as a surfactant. In order to evaluate the surface activity, the surface tension change of suspended SNC solution via the Wilhelmy plate method was measured and the values were compared with various synthetic surfactants. The effect of SNC as emulsifier was evaluated on emulsion formation and physical stability. The surface tension of the SNC-dispersed solution was decreased while its concentration was increased. When the 5.0% (w/v) of SNC was added, the surface tension was decreased from 70.3 to 49.5 mN/m. It was confirmed that the physical stability of the emulsion prepared by adding the SNC was improved compared to that of surface inactivity material (PEG 400). The phase separation was observed within 1 hour after preparation of the emulsion containing PEG 400, but the emulsion containing SNC was stable for 5 hours or more. To summarize this study, SNC, a natural-derived and non-toxic material, exhibits sufficient surface activity, thereby confirming the possibility of being applied to the food and pharmaceutical industry.

The purpose of this study is to produce nanostructured lipid carrier (NLC) that can solubilize poorly water-soluble velutin and verify an improved tyrosinase synthesis inhibition. A solubility test for velutin was conducted. Cetyl palmitate and caprylic/capric triglyceride were selected as solubilizer. The lipid matrix was produced using the ultrasound dispersion method. The morphology and size distribution of the produced NLC was analyzed through scanning electron microscopy (SEM) and dynamic light scattering (DLS), and the release and tyrosinase inhibition of velutin was evaluated through the Franz diffusion cell method and tyrosinase inhibition assay. Lipid matrix nanoparticles showed an average size of approximately 250 nm and polydispersity of 0.2, and it was confirmed that the velutin incorporated within nanoparticles sustained release at a constant rate over 36 hours. Due to extremely low aqueous solubility, the tyrosinase synthesis inhibition of velutin suspension was 0%, and the value of velutin incorporated within the NLC formulation was greatly improved 56.5% (40 μg/mL). As a result, it was verified that lipid-based NLC nanoparticles are an efficient formulation for the topical delivery of poorly water-soluble flavonoids such as velutin.

Sugarcane molasses was examined for the production of poly(3-hydroxybutyrate) [P(3HB)] and poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] in recombinant Ralstonia eutropha strains expressing Mannheimia succiniciproducens sacC gene encoding β-fructofuranosidase, which can hydrolyze sucrose into glucose and fructose in the culture medium. When crude sugarcane molasses was added to the culture medium to support 20 g/L of sucrose in flask cultivation, the growth of R. eutropha NCIMB11599 expressing the sacC gene was significantly inhibited, which resulted in OD600 of 1.2 with P(3HB) content of 0.1wt%. The inhibition of cell growth due to the usage of the crude sugarcane molasses was relieved by pretreatment of sugarcane molasses with activated charcoal. Sugarcane molasses pretreated with activated charcoal could support the growth of R. eutropha NCIMB11599 expressing the sacC gene to OD600 of 87.2 with P(3HB) content of 82.5 wt% in batch fermentation when it was added to culture medium to support 20 g/L of sucrose. Also, R. eutropha 437–540 expressing Escherichia coli ldhA gene encoding lactate dehydrogenase along with the sacC gene produced P(3HB-co-6.2 mol%LA) with 29.1 wt% polymer content from sugarcane molasses in batch fermentation.

For organ transplantation patients, the therapeutic drug monitoring (TDM) of immunosuppressive drugs is essential to prevent the toxicity or rejection of the organ. Currently, TDM is done by immunoassays or liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods; however, these methods lack specificity or are expensive, require high levels of skill, and offer limited sample throughput. Although matrix-assisted (MA) laser desorption ionization (LDI) mass spectrometry (MS) can provide enhanced throughput and cost-effectiveness, its application in TDM is limited due to the limitations of the matrixes such as a lack of sensitivity and reproducibility. Here, we present an alternative quantification method for the TDM of the immunosuppressive drugs in the blood of organ transplant patients by utilizing laser desorption ionization mass spectrometry (LDI-MS) based on a tungsten disulfide nanosheet, which is well-known for its excellent physicochemical properties such as a strong UV absorbance and high electron mobility. By adopting a microliquid inkjet printing system, a high-throughput analysis of the blood samples with enhanced sensitivity and reproducibility was achieved. Furthermore, up to 80 cases of patient samples were analyzed and the results were compared with those of LC-MS/MS by using Passing-Bablok regression and Bland-Altman analysis to demonstrate that our LDI-MS platform is suitable to replace current TDM techniques. Our approach will facilitate the rapid and accurate analysis of blood samples from a large number of patients for immunosuppressive drug prescriptions.

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils., Asthma: A physiological cannabinoid promotes inflammation Oleoylethanolamide (OEA), an endocannabinoid similar to those found in cannabis, occurs naturally in the body, and has now been implicated in promoting symptoms of asthma. OEA activates white blood cells called eosinophils and ILC2 cells, which are both parts of our immune response. Researchers in South Korea, led by Ga-Young Ban at Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, studied the effect of OEA on respiratory system cells from people with asthma and in mice used to model the condition in humans. OEA-induced inflammatory responses associated with asthma by stimulating the release of signaling molecules called cytokines. However, some other endocannabinoids have anti-inflammatory effects. Studying the effects of all endocannabinoids could yield new insights into asthma, with this study opening new possibilities for treating asthma by interfering with OEA-induced signaling responses.

Achieving high ionic conductivity, wide voltage window, and good mechanical strength in a single material remains a key challenge for polymer-based electrolytes for use in solid-state supercapacitors (SCs). Herein, we report cross-linked composite gel polymer electrolytes (CGPEs) based on multi-cross-linkable H-shaped poly(ethylene oxide)–poly(propylene oxide) (PEO-PPO) tetrablock copolymer precursors, SiO2 nanoparticles, and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, an ionic liquid (IL). Self-standing CGPE membranes with a high IL content were prepared using in situ cross-linking reactions between the silane groups present in the precursor and the SiO2 surface. The incorporation of an optimal amount of SiO2 increased the cross-linking density of the resulting CGPE while reducing polymer-chain ordering and, consequently, increasing both ionic conductivity and mechanical strength. As a result, the CGPE with 0.1 wt % SiO2 exhibited a high ionic conductivity (2.22 × 10–3 S cm–1 at 25 °C), good tensile strength (453 kPa), and high thermal stability up to 330 °C. Finally, an all-solid-state SC assembled with the prepared CGPE showed a high operating voltage (3 V), a large specific capacitance (103.9 F g–1 at 1 A g–1), and excellent durability (94% capacitance retention over 10,000 charge/discharge cycles), which highlights its strong potential as a solid-state electrolyte for SCs.

Ceramic cores are essential for manufacturing hollow mechanical parts, such as impellers and blades, in the casting process. High temperature heat treatment, which causes dimensional deformation and breakage, is required to reveal the effective strength of ceramic cores. Therefore, in this study, a new 3D printing-based process, combined with an organic-inorganic binder conversion process, is proposed to fabricate a ceramic core with high dimensional stability using dual polymers with different chemical properties. The ceramic core was prepared using an extrusion-type 3D printer with a slurry prepared by mixing a starting powder with hydrophilic and hydrophobic polymers. The extruded samples molded from the heterogeneous polymers were immersed in water at 60 °C for 3 min to remove the hydrophilic polymer to create space for impregnating an inorganic binder. The core samples were then dipped in an inorganic binder solution composed of tetraethyl orthosilicate and sodium methoxide and then dried at 80 °C for 1h, followed by a heat treatment at 1000 °C for 1h. Using dual polymers, the amount of inorganic binder coating converted into the glass phase during heat treatment was increased, which resulted in improved core strength. These results confirm that the dual polymer can be used to manufacture ceramic cores with excellent dimensional stability and firing strength through 3D printing combined with the organic-inorganic binder conversion process.

The biosorption characteristics of SRCM 120569 biomass on anionic Congo red (CR) dye. SRCM 120569 strain isolated from Korean turbid rice wine (makgeolli) was identified by 16S rRNA sequence analysis as Bacillus licheniformis. Bacillus licheniformis SRCM 120569 (Genbank Accession No. MW819861) showed superior CR dye biosorption capacity in an aqueous solution. Maximum adsorption capacities of 61.2 and 133.1 mg/g were obtained at pH 3.41 and 0.01 g/50 mL dried cell dosage, respectively. The CR dye adsorption properties by the Bacillus licheniformis SRCM120569 strain were characterized by Fourier transform infrared spectroscopy (FT-IR), point of zero charge (pHpzc) analysis, and phylogenetic analysis. The biosorption isotherm and kinetic models are well described with the Langmuir adsorption isotherm and pseudo-second-order kinetic models.

Purpose Phosphodiesterase type 5 (PDE5) inhibitors are effective treatments for erectile dysfunction, and several recent studies have reported positive effects of PDE5 inhibitors on semen parameters as well. However, the data are still controversial. We investigated the effect of PDE5 inhibitors on sperm function by analyzing sperm motility and acrosome reaction. Materials and methods This study included young healthy men who underwent fertility evaluation; 32 cases were finally included. Men were excluded if they used a PDE5 inhibitor within 2 weeks or if they had insufficient semen volume (≤2 mL), leukocytospermia, or a genitourinary infection. Changes in sperm motility and acrosome reaction were determined after in vitro exposure to the maximal semen concentration of oral intake of sildenafil (100 mg) or tadalafil (20 mg). Results Mean age of the participants was 35.4±4.9 years, mean sperm concentration was 68.7±32.4 ×10⁶/mL, and mean sperm motility was 50.38%±8.41%. All three groups (control, sildenafil, tadalafil) experienced trends of decreased average sperm motility over time, but these changes were not significant. There were no significant differences between the three groups in the acrosome reaction after 120 minutes of drug exposure, either. The maximal semen concentration of oral intake of sildenafil (100 mg) or tadalafil (20 mg) did not substantially affect sperm motility or acrosome reaction. Conclusions Our results suggest that on-demand use of a PDE5 inhibitor is safe and useful for the male partner of an infertile couple; however, further studies are warranted for daily PDE5 inhibitor use.

The post-combustion capture (PCC) process using amines is one of the most representative technologies for separating CO2 from huge CO2 emisions. However, the achievement of reasonable costs for capturing CO2 requires continuous studies on absorbent development, process optimization, and energy saving. Among these, the absorbent development is the most essential factor in reducing the operating cost and equipment cost of the PCC process. In this study, piperidine (PD) solution is used as an alternative absorbent to overcome the disadvantage of commercial monoethanolamine (MEA) solution. The absorption rate, absorption capacity and regeneration energy of PD solution were measured to confirm its performance as an alternative absorbent. It was found that PD solution shows key advantages, compared with MEA solution. First, the overall mass transfer of CO2 in PD solution was 2.69 times faster than in MEA solution at 313 K. Second, PD solution was capable of absorbing 1.5 times more of CO2 than MEA solution. Third, the reboiler heat duty of PD solution showed 1.16 times better energy-efficiency than that of MEA because the sensible heat of PD was 75.8 kJ·mol−1 lower than that of MEA. From these results, PD solution is deemed to be a good alternative absorbent to replace MEA solution.

Background We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

Background: Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.Methods: DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.Results: After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.Conclusion: Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.

Gallic acid (GA) is a functional ingredient abundant in Chinese pu-erh tea. The aim of this study was to increase the GA content in green tea extracts using acid hydrolysis. (-)-Epigallocatechin gallate treated with 1 M hydrochloric acid at 110°C for 1 h resulted in a GA yield of 45.6%. However, under these conditions, (-)-epigallocatechin was easily oxidized and rendered undetectable. On applying the same treatment to green tea extracts of Korea-cultivated Chamnok, a native species, and Yabukita, the GA contents increased from 0.17 to 4.87, 0.28 to 5.33 and 0.17 to 4.44 mM, respectively. In Chamnok extracts prepared following harvesting at three different time points, the GA contents increased from 0.17 to 4.48, 0.12 to 5.16 and 0.06 to 5.71 mM. Therefore, it is possible to produce green tea extracts with high GA concentrations using simple acid hydrolysis. This will greatly benefit the production of functional ingredients and will be useful in the beverage industry. Key words: Domestic cultivar, EGCG, EGC, tannase.

Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice.

Poly(ethylene terephthalate) (PET) has been widely used in various industries due to its unique physical properties. However, PET causes major environmental problems globally due to its low degrada...

Background Gintonin is a ginseng-derived exogenous G-protein–coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood–brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

Glutamate is an important excitatory neurotransmitter, and vesicular glutamate transporters (VGLUTs) are critical in regulating the extent of glutamate release. Because initial increase and late stage decrease in VGLUT expression were implicated in progressive Alzheimer’s disease (AD), VGLUTs can be a new imaging target for diagnosing AD. In this study, we have designed and synthesized a new multimodal gadolinium contrast agent conjugated with rose bengal to target VGLUTs (Gd-DO3A-RB). In addition to high kinetic and pH stability, magnetic resonance and fluorescence imaging using Gd-DO3A-RB showed high affinity to VGLUT1. Using the AD animal model (5XFAD), in vivo MRI with a Gd-DO3A-RB showed less MR signal enhancement in 5XFAD mouse brain than that of age-matched normal C57BL/6 mouse, suggesting a late stage decrease in VGLUT expression in AD animal model. Therefore, this new VGLUT targeting gadolinium contrast agent demonstrated a strong potential as a new diagnostic tool for AD with multimodal imaging capability.

Aims: Polymyxin B (PMB) is known to require reactive oxygen species (ROS) for its bactericidal activity, but the mechanism of PMB resistance in various Pseudomonas aeruginosa strains has been poorl...

Background: Young-PEARL study showed median progression-free survival (PFS) of 20·1 months in the palbociclib plus endocrine therapy group versus 14·4 months in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], log-rank p=0·0235). We conducted exploratory biomarker analysis to predict the efficacy of the trial. Methods: This was a phase II trial that randomized 184 patients with HR+ MBC in premenopausal women to palbociclib plus exemestane with GNRH agonist (Arm A, n=79) versus capecitabine (Arm B, n=62). We performed targeted sequencing (CancerSCANTM) containing 375 cancer-related genes (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response in terms of PFS. Result: By research-based PAM50 subtyping, 73% of patients classified as Luminal (Luminal A and Luminal B), and showed better prognosis in all patients and Arm A (p Conclusions: The alteration of a few genes including Rb1 loss may be associated with resistance of palbociclib in HR-positive premenopausal population with MBC. Luminal type showed better prognosis, and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. ESR1 mutation was found in low population frequency because all patients didn’t received AI therapy. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy. Clinical trial information: NCT02592746. Citation Format: Kyunghee Park, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Woong-Yang Park, Seock-Ah Im, Yeon Hee Park. Exploratory biomarker analysis of Young-PEARL [palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with HR (hormone receptor)-positive, HER2-negative metastatic breast cancer (MBC)] study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-19.

3D printing technologies using photo polymerization of photo-curable monomer and oligomers as an organic binder have been studied to fabricate ceramics with a complicated shape. For minimizing distortion of ceramics during the manufacturing process and fast 3D printing of ceramic green body, high mechanical strength of ceramic green body and fast photo polymerization of the photo-curable resin are required, respectively. In this study, the ceramic green bodies with various compositions were fabricated by photo radical polymerization of the slurry-type resin composed of fused silica bead, and tri- or (and) mono-functional acrylate. Photo radical polymerization behaviors of mono-, tri-functional acrylate monomer, and blend of two monomers were analyzed by photo-DSC and FT-IR measurements. The structure analysis of photo-cured polymers made by each monomer was performed by thermo-mechanical analysis. Through mixing of mono- and tri-functional acrylate monomer, we confirmed that polymerization rate more increased compared with those of only mono-, tri-functional monomer. Unreacted vinyl groups in the polymers prepared with blend of two monomers decreased by an addition of mono-functional monomer in tri-functional monomer. The polymers prepared with the blend showed higher storage modulus and broader viscoelastic behavior compared to those fabricated with tri-functional monomer. Thus, to achieve high fracture strength of the green body, we verified that the photo-cured polymer in the green body should have high crosslinking density and low free volume based on reduction of unreacted vinyl groups in the polymer. Additionally, through analysis of cross-sectional SEM of the green body, we confirmed that acrylate monomer should include proper content in the slurry-type resin to maximize the fracture strength of the body regardless of the type of the used acrylate monomer. This was because low content of acrylate monomer in the slurry-type resin makes it difficult to form neckings composed with photo-cured polymers between the silica beads.

In this study, we developed a simple screening procedure for the determination of 18 anthelmintics (including benzimidazoles, macrocyclic lactones, salicylanilides, substituted phenols, tetrahydropyrimidines, and imidazothiazoles) in five animal-derived food matrices (chicken muscle, pork, beef, milk, and egg) using liquid chromatography-tandem mass spectrometry. Analytes were extracted using acetonitrile/1% acetic acid (milk and egg) and acetonitrile/1% acetic acid with 0.5 mL of distilled water (chicken muscle, pork, and beef), and purified using saturated n-hexane/acetonitrile. A reversed-phase analytical column and a mobile phase consisting of (A) 10 mM ammonium formate in distilled water and (B) methanol were used to achieve optimal chromatographic separation. Matrix-matched standard calibration curves (R2≥0.9752) were obtained for concentration equivalent to ×1/2, ×1, ×2, ×3, ×4, and ×5 fold the maximum residue limit (MRL) stipulated by the Korean Ministry of Food and Drug Safety. Recoveries of 61.2–118.4%, with relative standard deviations (RSDs) of ≤19.9% (intraday and interday), were obtained for each sample at three spiking concentrations (×1/2, ×1, and ×2 the MRL values). Limits of detection, limits of quantification, and matrix effects were 0.02–5.5 μg/kg, 0.06–10 μg/kg, and −98.8 to 13.9% (at 20 μg/kg), respectively. In five samples of each food matrix (chicken muscle, pork, beef, milk, and egg) purchased from large retailers in Seoul that were tested, none of the target analytes were detected. It has therefore been shown that this protocol is adaptable, accurate, and precise for the quantification of anthelmintic residues in foods of animal origin., Graphical abstract Image 1, Highlights • Multi-class determination of 18 anthelmintics in animal-derived food matrices were screened. • Samples were extracted using LLE and analyzed by LC-MS/MS. • The developed method provided satisfactory sensitivity and linearity. • None of the market samples was found to contain any measurable residues of the tested analytes. • The developed protocol is adaptable, accurate, and precise for quantification in foods of animal origin.

We developed a pH-activatable cell-penetrating peptide dimer LH2 with histidine residues, which can penetrate cells, specifically in weak acidic conditions, even at few tens of nanomolar concentrations. LH2 effectively delivered paclitaxel into triple-negative breast cancer cells, MDA-MB-231, via formation of non-covalent complexes (PTX-LH2(M)) or covalent conjugates (PTX-LH2(C)). Moreover, LH2 showed prolonged circulation in the body and enhanced accumulation in tumors. Both PTX-LH2(M) and PTX-LH2(C) showed strong antitumor effects in a triple-negative breast cancer grafted mouse model at an extremely low dosage.

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.

Ginseng has been widely studied due to its various therapeutic properties on various diseases such as cardiovascular disease (CVD). Cardiovascular disease has been canonically known to be caused by high levels of low-density lipoproteins (LDL) in the bloodstream, in addition to the impaired vasodilatory effects of cholesterol. However, current research on CVD has revealed a cascade of mechanisms involving a series of events that contribute to the progression of CVD. Although this has been elucidated and summarized in previous studies the detailed correlation between platelet aggregation and innate immunity that plays an important role in CVD progression has not been thoroughly summarized. Furthermore, immune cell subtypes also contribute to the progression of plaque formation in the subendothelial layer. Thrombus formation and the coagulation cascade also have a vital role in the progression of atherosclerosis. Hence, in this mini review we aim to elucidate, summarize, and propose the potent therapeutic effect of ginseng on CVD, mainly on platelet aggregation, plaque formation, and thrombus formation., Graphical abstract Image 1

Bipolar plates (BPs) for fuel cell applications must meet minimum conductivity requirements while maintaining light weight and sufficient mechanical strength to be thinned and easily fabricated. Here, we prepare BPs comprising fluorinated ethylene–propylene (FEP), graphite flakes (GFs), graphite nanoplates (GnPs), and silicon carbide (SiC) particles for fuel cell applications. SiC particles decorated on large GFs and GnPs improve the flexural strength of the composites relative to the corresponding composites without SiC, resulting in increases of ∼24% and ∼130%, respectively. The improved mechanical properties of the FEP/GnP/SiC and FEP/GF/SiC composites are due to the uniform dispersion of SiC particles and strong chemical bonding between GF (or GnP) and SiC particles in the FEP matrix. Incorporating SiC particles into the FEP/GnP (or GF) composite plate provides a robust, scalable strategy for realizing high-performance, high-temperature fuel cell BPs.

The microbial conversion of glycerol into value-added commodity products has emerged as an attractive means to meet the demands of biosustainability. However, glycerol is a non-preferential carbon source for productive fermentation because of its low energy density. We employed evolutionary and metabolic engineering in tandem to construct an Escherichia coli strain with improved GABA production using glycerol as the feedstock carbon. Adaptive evolution of E. coli W under glycerol-limited conditions for 1300 generations harnessed an adapted strain with a metabolic system optimized for glycerol utilization. Mutation profiling, enzyme kinetic assays, and transcriptome analysis of the adapted strain allowed us to decipher the basis of glycerol adaptation at the molecular level. Importantly, increased substrate influx mediated by the mutant glpK and modulation of intracellular cAMP levels were the key drivers of improved fitness in the glycerol-limited condition. Leveraging the enhanced capability of glycerol utilization in the strain, we constructed a GABA-producing E. coli W-derivative with superior GABA production compared to the wild-type. Furthermore, rationally designed inactivation of the non-essential metabolic genes, including ackA, mgsA, and gabT, in the glycerol-adapted strain improved the final GABA titer and specific productivity by 3.9- and 4.3-fold, respectively, compared with the wild-type.

Silica-coated gold nanorods (AuNRs) exhibit significantly enhanced photothermal effects and photoacoustic (PA) signal intensities, which is beneficial for various nanophotonic applications in materials science. However, the silica shell thickness for optimum enhancement is not fully understood and is even controversial depending on the physical state of the silica shell. This is because of the lack of systematic investigations of the nanoscale silica shell thickness and the photothermal effect. This study provides a robust synthetic method to control the silica shell thickness at the nanoscale and the physical state-dependent heat diffusion property. The selected base and solvent system enabled the production of silica-coated AuNRs (AuNR@SiO2) with silica shell thicknesses of 5, 10, 15, 20, 25, 30, 35, and 40 nm. AuNRs with a 20 nm silica shell showed the highest photothermal effect with a 1.45-times higher photothermal efficiency than that of AuNRs without a silica shell. The low density of the silica shell on the AuNRs showed a low photothermal effect and photostability. It was found that the disruption of cetyltrimethyl ammonium bromide (CTAB) layers on the AuNRs was responsible for the low photostability of the AuNRs. The simulation study for the heat diffusion property showed facilitated heat diffusion in the presence of a 20 nm silica shell. In a cell-based study, AuNRs with a 20 nm silica shell showed the most sensitive photothermal effect for cell death. The results of this robust study can provide conclusive conditions for the optimal silica shell thickness to obtain the highest photothermal effect, which will be useful for the future design of nanomaterials in various fields of application.