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Objective: This study was performed to determine the effects of stress after road transportation and oral administration of chromium and meloxicam on growth performance, plasma cortisol, serum metabolites, and behavior in dairy calves.Methods: A total of 50 Holstein heifers (average body weight [BW]: 172±4.19 kg; average age: 5.53±0.12 months) were randomly assigned to five groups including NL (not transported + D-lactose; 1 mg/kg BW), TL (transported + D-lactose; 1 mg/kg BW), TC (transported + chromium; 0.5 mg/kg dry matter [DM] feed), TM (transported + meloxicam; 1 mg/kg BW), and TMC (transported + combination of meloxicam and chromium; 1 mg/kg BW and 0.5 mg/kg DM, respectively). Doses of D-lactose monohydrate, meloxicam, and chromium were prepared for oral administration by suspension in 15 mL of water in a 20-mL dosing syringe. Blood was collected before transportation, immediately after 120 km of transportation (IAT), and at 6, 24, and 48 h after transportation.Results: Neither transportation nor administration of meloxicam and/or chromium affected (p = 0.99) average daily gain and feed intake. Plasma cortisol concentrations in the NL group (average 0.13 and 0.18 nmol/L, respectively) were lower (p

Nickel (Ni) nanoparticles (NPs) prepared through vapor-phase synthesis (VPS) are preferred for multilayer ceramic capacitor electrodes due to their high purity and crystallinity advantages. Agglomerated Ni NPs are usually generated using VPS but are undesirable because they cause various problems such as low packing density and electrical shorts. This study proposes the use of coating-assisted chemical vapor synthesis (CVS) for agglomerate inhibition using NaCl or KCl as a coating agent. We have found that the agglomeration ratio, 34.40%, for conventional CVS, can be reduced to 4.80% in the proposed method by in-flight coating with KCl at 900 °C by image analysis using field-emission scanning electron microscopy. Furthermore, the X-ray diffraction and X-ray fluorescence analyses confirm that the NaCl and KCl coating agent can be removed by washing with distilled water. We believe that this coating process can be used to inhibit the formation of agglomerates during the CVS of Ni NPs.

Hydrogen sulfide (H 2 S) is an endogenous gaseous antioxidant and antihypertensive molecule produced during the homocysteine metabolism. MsrA (methionine sulfoxide reductase A) enables the metabolism of homocysteine by reducing methionine sulfoxide to methionine. Although HDAC (histone deacetylase) inhibition has been reported to show blood pressure lowering effects, their effects on endogenous H 2 S production are largely unknown. Here, we assessed the relevance of MsrA in high-fat diet (HFD)-induced hypertension and the effect of HDAC inhibition on MsrA expression, H 2 S production, and hypertension. Male C57BL/6 mice were fed a normal diet or HFD. HFD increased blood pressure and activities of HDAC3 and 6 but downregulated MsrA in the mesenteric arteries and the serum H 2 S level. HFD upregulated 4 hydroxynonenal, TNF (tumor necrosis factor)-α, and IL (interleukin)-6, and vasocontractile proteins. The histone H3 acetylation of the MsrA promoter was decreased by HFD. In hypertensive HFD-fed mice, administration of the HDAC inhibitor CG200745 lowered blood pressure and increased serum H 2 S level. CG200745 increased acetylation of histone H3 and MsrA levels in the mesenteric arteries while downregulating oxidative stress, inflammation, and vasocontractile proteins. Silencing of MsrA in the vascular smooth muscle cells recapitulated HFD-induced in vivo hypertensive effects. CG200745 increased the histone H3 acetylation of the MsrA promoter, MsrA expression, and H 2 S production in vascular smooth muscle cells, supporting the in vivo results. Collectively, HFD-induced downregulation of MsrA plays a pivotal role in HFD-induced hypertension by reducing H 2 S levels. MsrA expression is epigenetically regulated by HDAC inhibitors, providing HDAC inhibitors as a therapeutic option and MsrA and H 2 S as novel therapeutic targets. Graphic Abstract: An online graphic abstract is available for this article.

본 연구는 리튬이온 배터리의 음극재로 사용되는 실리콘의 팽창을 개선하기 위해 PVDF를 이용해 실리콘에 탄소를 코팅하고, 음극재로 사용하여 배터리의 충방전 용량 유지율을 개선하는 것을 목표하였다. 실리콘 덩어리를 밀링 처리하여 제조한 실리콘 입자에 탄소코팅 전구물질로 PVDF를 사용하여 탄소코팅된 실리콘 음극재를 제조했고, 이를 바탕으로 리튬이온 코인셀을 제작하고 테스트하여, 방전용량유지율 개선을 측정하고 고찰하였다. PVDF로 탄소코팅한 실리콘 입자에 결정질 탄소층이 존재하는 것을 SEM, EDS, Raman shift, TEM 분석 등을 통해 관찰하였으며, 충방전 실험을 통해 용량 유지율은 초기 용량 대비하여 실리콘 입자 탄소코팅 전 0.5%에서 탄소코팅 후 44.0%로 상승한 것을 측정할 수 있었다. 이를 통해 PVDF를 이용해 탄소코팅하여 실리콘을 개질하는 방법으로 리튬이온 2차전지의 용량유지율을 개선할 수 있음을 알 수 있었다. 향후 연구에서는 본 탄소코팅 방법을 최적화한 후 실리콘 산화물에 적용해 리튬이온 배터리용 음극재로 활용하고자 한다.

OBJECTIVE To investigate the effects of alcohol abstinence on prevention of new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS A total of 1,112,682 patients newly diagnosed with T2DM between 2011 and 2014 were identified from the Korean National Health Insurance Service database. After excluding those with a history of AF, 175,100 patients were included. The primary outcome was new-onset AF. RESULTS During a mean follow-up of 4.0 years, AF occurred in 4,174 patients. Those with heavy alcohol consumption (alcohol intake ≥40 g/day) before T2DM diagnosis had a higher risk of AF (adjusted hazard ratio [aHR] 1.22; 95% CI 1.06–1.41) compared with patients with no alcohol consumption. After T2DM diagnosis, those with moderate to heavy alcohol consumption (alcohol intake ≥20 g/day) who abstained from alcohol had a lower risk of AF (aHR 0.81; 95% CI 0.68–0.97) compared with constant drinkers. Alcohol abstinence showed consistent trends toward lower incident AF in all subgroups and was statistically significant in men (aHR 0.80; 95% CI 0.67–0.96), those aged >65 years (aHR 0.69; 95% CI 0.52–0.91), those with CHA2DS2-VASc score CONCLUSIONS In patients with newly diagnosed T2DM, alcohol abstinence was associated with a low risk of AF development. Lifestyle modifications, such as alcohol abstinence, in patients newly diagnosed with T2DM should be recommended to reduce the risk of AF.

All-solid-state zinc–air pouch cells promise high energy-to-cost ratios with inherent safety; however, finding earth-abundant high power/energy cathodes and super-ionic electrolytes remains a fundamental challenge. Here we present realistic zinc–air pouch cells designed by the (101)-facet copper phosphosulfide [CPS(101)] as a cathode as well as anti-freezing chitosan-biocellulosics as super-ionic conductor electrolytes. The proposed CPS(101) exhibits trifunctional activity and stability (>30,000 cycles) towards reversible oxygen reactions and hydrogen evolution reactions, outperforming commercial Pt/C and RuO2. Furthermore, hydroxide super-ion conductors utilizing polymerized chitosan-biocellulosics reveal exceptional conductivity (86.7 mS cm−1 at 25 °C) with high mechanical/chemical robustness. High cell-level energy densities of 460 Wh kgcell–1/1,389 Wh l−1 are normally measured in pouch cells (1 Ah) with a cycle lifespan of 6,000/1,100 cycles at 25 mA cm−2 for 20/70% depths of discharge, and the highest densities we could achieve were 523 Wh kgcell–1/1,609 Wh l−1. Flexible pouch cells operate well at rates of 5–200 mA cm−2 over a broad temperature range of −20 to 80 °C. Zinc–air batteries are viewed as a sustainable storage technology, but their commercialization requires a genuine performance leap forwards from the laboratory scale. Here the authors report a cell-level design and demonstrate an ampere-hour pouch cell with exceptionally high energy density and cycle lifespan.

Objective: We have tested our hypothesis that inclusion of purified glycerol as a replacer of portions of dried distillers grain with solubles (DDGS) would affect growth performance, rumen fermentation and blood parameters, carcass and sensory traits, reducing sugar and glycogen contents, and volatile compound profiles in longissimus thoracis (LT) in Korean cattle steers.Methods: A total of 20 Korean cattle steers (27.0±0.2 months old; 647±10.5 kg body weight [BW]) were assigned to a conventional control group or a glycerol group (3.17% purified glycerol addition as a replacement for DDGS and molasses). The steers were individually allowed to receive the experimental concentrate at the daily amount of 1.5% of their individual BW and a total 1.0 of kg/d of rice straw twice daily. The feeding trial was conducted for a period of 20 weeks.Results: Glycerol supplementation (GS) increased (p = 0.001) concentrate intake. However, GS did not affect (p>0.05) average daily gain, feed efficiency, and ruminal volatile fatty acid concentrations. GS tended to increase (p≤0.10) serum glucose concentrations at the 16th and 20th weeks. GS decreased (p = 0.001) LT pH. GS did not affect (p>0.05) carcass traits and the chemical or physicochemical compositions, reducing sugar or glycogen contents, sensory traits, and most of volatile compounds in the LT.Conclusion: The inclusion of purified glycerol as a replacement for DDGS in the finishing diet did not affect growth performance, rumen fermentation parameters, and carcass quality in Korean cattle. The purified glycerol could be used as a substitute for other energy sources such as DDGS in beef cattle, depending on the price.

Purpose: The risk of gastrointestinal bleeding (GIB) can be mitigated by proton pump inhibitor (PPI) co-therapy in patients with atrial fibrillation (AF) treated with anticoagulants. We aimed to evaluate the effect of PPIs on the risk of GIB in Asian patients with AF, treated with oral anticoagulants (OACs), and with a prior history of upper GIB. Methods: Using a nationwide claims database, OAC-naïve patients with AF and a history of upper GIB before initiating OAC treatment between January 2010 and April 2018 were included. Patients were categorized into 10 groups according to the index OAC (warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban) and whether or not they received PPI co-therapy, and were followed up for incidence of major GIB. Results: Among a total of 42,048 patients, 40% were prescribed PPIs as co-therapy with OACs. Over a median 0.6 years (interquartile ranges 0.2–1.7 years) of follow-up, rivaroxaban use without PPIs showed the highest crude incidence of major GIB (2.62 per 100 person-years), followed by the use of warfarin without a PPI (2.20 per 100 person-years). Compared to the patients without PPI use, PPI co-therapy was associated with a significantly lower risk of major GIB, by 40% and 36%, in the rivaroxaban and warfarin groups, respectively. In dabigatran, apixaban, and edoxaban users, PPI co-therapy did not show a significant reduction in the risk of major GIB. Conclusion: Among patients with AF receiving anticoagulant treatment and with a prior history of upper GIB, PPI co-therapy was associated with a significant reduction in the risk of major GIB in patients treated with rivaroxaban and warfarin.

Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac ®) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax) and the areas under the plasma concentration-time curve from 0 to the last concentration (AUClast) were 1.0845 (1.0107-1.1637) and 1.0220 (1.0005-1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation. Trial registration Clinical Research Information Service Identifier: KCT0005943.

ObjectiveTo investigate the longitudinal association among high-density lipoprotein cholesterol (HDL-C) level, HDL-C variability, and the risk of developing Parkinson disease (PD).MethodsWe conducted a nationwide, population-based cohort study. We included 382,391 patients aged ≥65 years who underwent at least 3 health examinations provided by the Korean National Health Insurance System from 2008 to 2013 and followed up until 2017. Individuals with a history of PD and missing values were excluded (n = 1,987). We assessed HDL-C variability using 3 indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed.ResultsAmong the 380,404 participants, 2,733 individuals were newly diagnosed with PD during a median follow-up period of 5 years. The lowest quartile (Q1) group of baseline HDL-C and mean HDL-C was associated with increased PD incidence as compared with the highest quartile (Q4) group (adjusted hazard ratio [aHR], 1.20; 95% confidence interval [CI], 1.08–1.34; and aHR, 1.16; 95% CI, 1.04–1.30, respectively). The Q4 group of HDL-C variability (VIM) was associated with increased PD incidence compared to the Q1 group (aHR, 1.19; 95% CI, 1.06–1.33). The group with the Q1 of baseline HDL-C and with the Q4 of HDL-C variability had the highest risk of PD incidence (aHR, 1.6; 95% CI, 1.31–1.96).ConclusionLower HDL-C level and greater HDL-C variability were associated with a higher incidence of PD.

Separating the immunosuppressive activity of FK506 (1) from its neurotrophic activity is required to develop FK506 analogues as drugs for the treatment of neuronal diseases. Two new FK506 analogues, 9-deoxo-36,37-dihydro-prolylFK506 (2) and 9-deoxo-31-O-demethyl-36,37-dihydro-prolylFK506 (3) containing a proline moiety instead of the pipecolate ring at C-1 and modifications at the C-9/C-31 and C-36-C-37 positions, respectively, were biosynthesized, and their biological activities were evaluated. The proline substitution in 9-deoxo-36,37-dihydroFK506 and 9-deoxo-31-O-demethyl-36,37-dihydroFK506 reduced immunosuppressive activity by more than 120-fold, as previously observed. Compared with FK506 (1), 2 and 3 exhibited ∼1.2 × 105- and 2.2 × 105-fold reductions in immunosuppressive activity, respectively, whereas they retained almost identical neurite outgrowth activity. Furthermore, these compounds significantly increased the strength of synaptic transmission, confirming that replacement of the pipecolate ring with a proline is critical to reduce the strong immunosuppressive activity of FK506 (1) while enhancing its neurotrophic activity.

The reduction of intrinsic defects, including vacancies and grain boundaries, remains one of the greatest challenges to produce high-performance transition metal dichalcogenides (TMDCs) electronic systems. A deeper comprehension of the underlying reaction mechanisms is also needed. In this work, we present a new sulfurization process of tungsten (W) film using a sulfur (S)-containing organic precursor for the growth of WS2 films on SiO2/Si substrates. The W film was deposited with precise layer thickness control by atomic layer deposition and uniformly sulfurized using diethyl sulfide (DES) as S precursor. Comprehensive optical and chemical analyses revealed that by using DES as S precursor, the S atoms were uniformly supplied, and sulfurization occurred accurately and delicately. Moreover, the WS2 film synthesized using DES showed outstanding electrical conductivity (∼37 mS cm−1), which was almost 17 times higher than that of the WS2 film synthesized using S powder. Based on the results of optical, electrical, and chemical analyses, we proposed and validated a hypothesis to explain the sulfurization mechanism. The fabricated TMDC materials using the method presented in this work show great potential for industrial application due to their highly uniform surface and improved electrical conductivity.

Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. Significance: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics.

Background This study aims to examine the association between alcohol consumption and the risk of pre- or type 2 diabetes mellitus (T2DM) by alcohol-induced flushing response in Korean male adults, particularly based on their body mass index (BMI). Methods This study selected 1,030 (158 non-drinkers, 364 flushers, and 508 non-flushers) male adults who had medical checkups. A logistic regression analysis was used to compare the association between alcohol consumption and the risk of pre- or T2DM. Results In both the normal-weight group (BMI 4 and ≤8 drinks: 2.64, 1.10–6.36; >8 drinks: 2.42, 1.11–5.27). However, obese non-flushers had only a significant higher risk of pre- or T2DM when consuming more than 8 drinks of alcohol per week than the non-drinkers (2.72, 1.39–5.30) Conclusion These results suggest that obese flushers have an increased risk of developing pre- or T2DM even with less alcohol consumption.

To investigate the characteristics of particulate methanesulfonic acid (MSA(p)), non-sea-salt sulfate (nss SO42-) and organic carbon (OC) aerosols, aerosol and seawater samples were collected over the Southern Ocean (43–70∘ S) and the Amundsen Sea (70–75∘ S) during the ANA06B cruise conducted in the austral summer of 2016 aboard the Korean icebreaker IBR/V Araon. Over the Southern Ocean, the atmospheric MSA(p) concentration was low (0.10±0.002 µg m−3), whereas its concentration increased sharply up to 0.57 µg m−3 in the Amundsen Sea where Phaeocystis antarctica (P. antarctica), a producer of dimethylsulfide (DMS), was the dominant phytoplankton species. Unlike MSA(p), the mean nss SO42- concentration in the Amundsen Sea was comparable to that in the Southern Ocean. Water-soluble organic carbon (WSOC) concentrations over the Southern Ocean and the Amundsen Sea varied from 0.048 to 0.16 and 0.070 to 0.18 µgC m−3, with averages of 0.087±0.038 and 0.097±0.038 µgC m−3, respectively. For water-insoluble organic carbon (WIOC), its mean concentrations over the Southern Ocean and the Amundsen Sea were 0.25±0.13 and 0.26±0.10 µgC m−3, varying from 0.083 to 0.49 and 0.12 to 0.38 µgC m−3, respectively. WIOC was the dominant organic carbon species in both the Southern Ocean and the Amundsen Sea, accounting for 73 %–75 % of the total aerosol organic carbon. WSOC/Na+ and WIOC/Na+ ratios in the fine-mode aerosol particles were higher, especially in the Amundsen Sea where biological productivity was much higher than the Southern Ocean. The fluorescence properties of water-soluble organic aerosols investigated using a fluorescence excitation–emission matrix coupled with parallel factor analysis (EEM–PARAFAC) revealed that protein-like components were dominant in our marine aerosol samples, representing 69 %–91 % of the total intensity. Protein-like components also showed a significant positive relationship with the relative biomass of diatoms; however, they were negatively correlated with the relative biomass of P. antarctica. These results suggest that the protein-like component is most likely produced as a result of biological processes of diatoms in the Amundsen Sea.

Objectives:The purpose of this study was to investigate key operating parameters for partial nitritation in the nitritation reactor packed with PVA (polyvinyl alcohol)/alginate carrier.Methods:Partial nitritation was conducted in a 2 L reactor packed with PVA/alginate carrier of 30%. Dissolved oxygen (DO) concentration was considered as the main operating parameters. Raw reject water was used as the influent, and the ammonium concentration of the influent was adjusted with dilution at the beginning of operation. The DO concentration in the reactor was maintained at 3~4 mg O2/L. The activity test of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) was conducted periodically. The effect of the operating parameters applied in this study was verified through analysis of microbial community.Results and Discussion:The stable performance for partial nitritation was achieved at operation time of 17 days. Thereafter, the reject water containing 683.6±73.5 mg NH4+-N/L was introduced without dilution. Although the DO concentration was maintained at 3~4 mg O2/L, stable partial nitritation was achieved for a long time, resulting in effluent NO2-N/NH4+-N of 0.94±0.07 and maximum nitrite production rate of 2.24 kgN/m3/d. This was confirmed to be due to DO diffusion limitation inside PVA/alginate carrier, whereby the NOB activity could be effectively inhibited. Microbial community analysis also showed that NOB fraction inside the carrier was reduced to 0.09%. It indicated that partial nitritation using the PVA/alginate carrier was effective for selective inhibition of the NOB.Conclusions:In the case of using the whole cell entrapment technique, effective inhibition of NOB was possible by keeping the DO concentration inside the carrier low despite the fluctuation of DO in the reactor. The results of these findings may help improve the stability of the process in the field.

In creating the next generation of crystalline silicon (c-Si) solar cells, the goals are to improve energy conversion efficiency and reduce costs. Here, we demonstrate all-room-temperature-processe...

Nintedanib, a receptor tyrosine kinase (RTK) inhibitor has been developed as therapeutics for idiopathic pulmonary fibrosis and non-small lung cancer. We found that the expression levels of RTK, especially VEGFR1 is increased in skin biopsies of dermatitis patients from multiple independent datasets. Moreover, VEGFR1 is highly expressed by infiltrated cells in dermis from oxazolone (OXA) treated mice. Interestingly, nintedanib alleviates dermatitis symptom in OXA-induced animal model. Especially, levels of epidermis thickness, infiltrated immune cells including mast cells and eosinophils were decreased from mice cotreated with nintedanib and OXA compared with OXA treated mice. Moreover, serum IgE and Th2 cytokines including IL-4 and IL-13 were decreased by nintedanib treatment. These results suggest an evidence that nintedanib alleviates animal model of dermatitis.

Background Extrinsic skin aging caused by atmospheric pollutants is associated with a sustained inflammatory response which is a significant risk factor for lentigines and melasma. Aims The aim of this study was to evaluate the efficacy of topical application of combination formulation of vitamin C, vitamin E, and ferulic acid as an adjuvant to Q-switched Nd:YAG (QSNY) lasers treatment in individuals with lentigines and melasma. Methods A single blinded, prospective, randomized split-face trial was conducted. Eighteen men and women between 26 and 53 years old were treated with a combination antioxidant serum on one randomized side of their face immediately after QSNY laser and twice daily for 2 weeks. Patients were evaluated using digital photography and spectrometry to assess the melanin index and erythema index. Melasma severity score and global improvement scores also were assessed. Results The treated side of the face exhibited a significantly greater reduction in the melanin index. There was no significant difference in post-treatment erythema. More clinical improvement was observed on the treated side compared with the untreated side. Conclusions Our study suggests that topical application of a combination vitamins C, E, and ferulic acid antioxidant formula may be effective as an adjuvant option in QSNY lasers.

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

A tumor-targeted near-infrared (NIR) fluorophore CA800SO3 was developed for fluorescence-guided phototherapy. This new type of NIR fluorophore showed high tumor targetability based on the structure-inherent targeting approach. This fluorophore generated sufficient hyperthermia and reactive oxygen species (ROS) simultaneously for synergistic cancer phototherapy, induced by an 808 nm laser irradiation.

We evaluated whether castration affects bone morphogenetic protein 2 (BMP2) level and the expression of its signaling molecules in Korean cattle bulls. We also checked whether castration affects the expression of muscle fiber type and oxidative and glycolytic enzyme genes. Enzyme-linked immunosorbent assays revealed that steers had higher plasma BMP2 and leptin concentrations than bulls. Quantitative real-time PCR showed that steers had higher mRNA levels of the lysyl oxidase gene, a downstream target of the BMP signaling pathway, in the longissimus thoracis (LT) muscle. Steers had higher adipogenic peroxisome proliferator-activated receptor gamma and lipogenic fatty acid binding protein 4 mRNA levels in the LT than bulls. Steers had lower mRNA levels for several muscle fiber type 1 genes and fiber type 2A myosin heavy chain 2 gene than bulls. Steers had higher mRNA levels of the glycolytic enzyme phosphoglycerate kinase 1 gene than bulls. Transcript levels of oxidative enzyme genes did not differ between bulls and steers. Regression analysis revealed a positive association between plasma BMP2 levels and intramuscular fat (IMF) content in the steer group. These findings suggest that upregulation of the BMP signaling pathway in response to castration induces increased adipogenic gene expression, contributing to the increased IMF deposition observed in castrated animals.

Background/Aims There are inconsistencies in the effects of low to moderate dose alcohol consumption on the development of hypertension in adult men. We hypothesized that a region-specific effect might participate in this heterogeneity. Methods We conducted a systematic review and meta-analysis to evaluate the effect of alcohol dose on hypertension incidence using contemporary data through December 2017. Subjects were categorized according to their level of alcohol consumption as non-drinkers (reference) and low- (0.01 to 20.0 g/day), moderate- (20.1 to 40.0 g/day), moderate- to high- (40.1 to 60.0 g/day), and high-dose (> 60.0 g/day) drinkers. We defined hypertension as a blood pressure ≥ 140/90 mmHg and/or the use of anti- hypertensive drugs. Results In total, 11 articles (seven Asian and four Western) were selected for our analysis. Among Asian men, a significantly elevated risk was observed even in the low alcohol dose group in comparison with the group with no alcohol consumption, and the risk increased in a dose-dependent manner (pooled relative risks [95% confidence intervals (CI)]: 1.25 [1.13 to 1.38], 1.48 [1.27 to 1.72], 1.75 [1.43 to 2.15], and 1.78 [1.51 to 2.09]). Among Western men, a similar dose-response relationship was noted in general (p for subgroup difference > 0.1), but a significantly elevated risk was evident only in the high-dose group (pooled relative risks [95% CI]: 1.22 [0.85 to 1.74], 1.57 [0.90 to 2.75], 1.47 [0.44 to 4.91], and 1.49 [1.02 to 2.18]). Conclusions Even low doses of alcohol can lead to the development of hypertension, particularly in Asian men. Our findings could serve as additional evidence for developing an appropriate preventive strategy in each region.

Emerging evidence suggests that breast cancer stem cells (BCSCs), and epithelial–mesenchymal transition (EMT) may be involved in resistance to doxorubicin. However, it is unlear whether the doxorubicin-induced EMT and expansion of BCSCs is related to cancer dormancy, or outgrowing cancer cells with maintaining resistance to doxorubicin, or whether the phenotypes can be transferred to other doxorubicin-sensitive cells. Here, we characterized the phenotype of doxorubicin-resistant TNBC cells while monitoring the EMT process and expansion of CSCs during the establishment of doxorubicin-resistant MDA-MB-231 human breast cancer cells (DRM cells). In addition, we assessed the potential signaling associated with the EMT process and expansion of CSCs in doxorubicin-resistance of DRM cells. DRM cells exhibited morphological changes from spindle-shaped MDA-MB-231 cells into round-shaped giant cells. They exhibited highly proliferative, EMT, adhesive, and invasive phenotypes. Molecularly, they showed up-regulation of Cyclin D1, mesenchymal markers (β-catenin, and N-cadherin), MMP-2, MMP-9, ICAM-1 and down-regulation of E-cadherin. As the molecular mechanisms responsible for the resistance to doxorubicin, up-regulation of EGFR and its downstream signaling, were suggested. AKT and ERK1/2 expression were also increased in DRM cells with the advancement of resistance to doxorubicin. Furthermore, doxorubicin resistance of DRM cells can be transferred by autocrine signaling. In conclusion, DRM cells harbored EMT features with CSC properties possessing increased proliferation, invasion, migration, and adhesion ability. The doxorubicin resistance, and doxorubicin-induced EMT and CSC properties of DRM cells, can be transferred to parental cells through autocrine signaling. Lastly, this feature of DRM cells might be associated with the up-regulation of EGFR.

Matching of charge periodicity between a guest and a host enabled effective immobilization of highly water-soluble antibiotic drug, gentamicin C, in a bentonite clay by cation exchange. X-ray diffraction, infrared spectroscopy and CHNS analysis revealed the immobilization manner of gentamicin C, which was immobilized between bentonite layers via periodic charge-charge interaction with tilted arrangement, as a trication. Both gentamicin alone and a gentamicin/bentonite hybrid were coated onto a polyurethane substrate using water-borne polyurethane binder. The antibiotic character of both films was investigated as prepared or after immersion in phosphate-buffered saline till 5 days against E. coli and B. subtilis bacteria. It was clearly shown that the gentamicin/bentonite hybrid-coated film showed sustained antibacterial efficacy even after exposure to phosphate-buffered saline, while gentamicin only-coated film gradually lost its performance under the same condition.

International audience; Immobilization of antimicrobial drug is one of the fascinating approach to expand the application of antibacterial property to consumer product. In order to stabilize antimicrobial agent, levofloxacin (LVX), into polymer substrate for sustained antibacterial activity, the drug molecules were immobilized in layered double hydroxide (LDH) and embedded in polyurethane substrate. As prepared MgAl-LDH was calcined at 400C and reconstructed with LVX for intercalation. The X-ray diffraction patterns and cross-sectional transmission electron microscopy images showed lattice expansion along the crystallographic c-axis upon LVX intercalation, suggesting the successful loading of the drug. Fourier-transformed infrared spectra revealed that intact structure of LVX was well preserved between LDH layers. Elemental analysis indicated that the loading capacity of LVX in the hybrid was 41.7%. Bacterial colony forming inhibitory assay of exhibited ~100% antibacterial activity for both LVX alone and LVX-LDH hybrid (LL) on Bacillus subtilis. To determine sustainability of antibacterial activity by the hybrid, either LVX alone or LL hybrid was loaded in polyurethane (PU) substrate of which antibacterial activity was evaluated before and after immersing in phosphate buffered saline for 3 days. The LVX composited PU showed dramatic decrease in antibacterial activity down to 0% after buffer treatment; however, LL composited PU still contained antibacterial activity (~34% of colony suppression) after phosphate buffered saline immersion.