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Monitoring of plant hormone ethylene plays a crucial role in managing the growth and development of plants, especially in the ripening of fruits and the opening of flowers. Here, a highly sensitive ethylene sensor is demonstrated using silver nanoparticle (Ag NP)-decorated zinc oxide nanoflowers (ZnO NFs), prepared through a facile and low-temperature chemical synthesis. The results indicate that Ag NP decoration on the surface of ZnO NFs improved the ethylene sensing properties under ultraviolet (UV) illumination. With an optimized UV light intensity of 5 mW/cm², the sensing response to 40 ppm of ethylene gas increased from 13.27% to 52.83%. The sensors exhibit a strong linear response to ethylene gas within the range of 10-70 ppm, with a low detection limit of 5 ppm. Moreover, the Ag-decorated ZnO NFs sensors demonstrated good repeatability, excellent long-term stability, and high selectivity toward ethylene gas. The sensing mechanism is attributed to the catalytic effectiveness and localized surface plasmon resonance of Ag NPs. These results suggest that UV-induced Ag-decorated ZnO NFs are promising for practical application in fruit ripening monitoring for supply chain management. [ABSTRACT FROM AUTHOR]

Connected and automated vehicles (CAVs) require proper infrastructure for safer and more reliable operations. Many state and local planning agencies have developed multiyear capital programs to provide such infrastructure in a timely manner within their limited budgets. Meanwhile, the traffic environment will evolve over time as CAV technologies become available (i.e., toward the mixed environment of CAVs and human-driven vehicles), which requires infrastructure plans specific to different planning terms (i.e., short-, medium-, and longterm) to accommodate changing infrastructure needs. To develop an effective multiyear infrastructure plan, planning agencies need to understand changing infrastructure needs with time, identify alternative infrastructure options for different planning terms, and select the most appropriate ones based on their long-term vision. This study performed a systematic literature review to develop a knowledge base for multiyear infrastructure planning for CAVs. To be more specific, the literature review aims to develop the following knowledge areas: (1) identification of existing and future infrastructure options for the operation of CAVs, (2) understanding the role of infrastructure to support different functions of CAVs to realize safety, mobility, and environmental benefits, and (3) integration of the aforementioned findings into planning agencies’ multiyear infrastructure plans for CAVs. Based on the review, this study categorizes different CAV infrastructure into existing infrastructure and future infrastructure options while considering five system functions of CAVs (i.e., cooperative merging, platooning, intersection movement, dynamic routing, and cooperation and connected functions) to illustrate the role of these infrastructure options under different traffic scenarios. The implementation of the developed knowledge base is demonstrated through a case study of two selected state agencies’ long-term infrastructure planning for CAVs. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified. For insight, we investigated folic acid (FA)-induced AKI in mice. Interestingly, simultaneous with FGF23, orphan nuclear receptor ERR-γ expression is increased in the liver of FA-treated mice, and ectopic overexpression of ERR-γ was sufficient to induce hepatic FGF23 production. In patients and in mice, AKI is accompanied by up-regulated systemic IL-6, which was previously identified as an upstream regulator of ERR-γ expression in the liver. Administration of IL-6 neutralizing antibody to FAtreated mice or of recombinant IL-6 to healthy mice confirms IL-6 as an upstream regulator of hepatic ERR-γ-mediated FGF23 production. A significant (P < 0.001) interconnection between high IL-6 and FGF23 levels as a predictor of AKI in patients that underwent cardiac surgery was also found, suggesting the clinical relevance of the finding. Finally, liver-specific depletion of ERR-γ or treatment with an inverse ERR-γ agonist decreased hepatic FGF23 expression and plasma FGF23 levels in mice with FA-induced AKI. Thus, inverse agonist of ERR-γ may represent a therapeutic strategy to reduce adverse plasma FGF23 levels in AKI. [ABSTRACT FROM AUTHOR]

The splitting of quasi-Fermi levels (QFLs) represents a key concept utilized to describe finite-bias operations of semiconductor devices, but its atomic-scale characterization remains a significant challenge. Herein, the nonequilibrium QFL or electrochemical potential profiles within single-molecule junctions obtained from the first-principles multispace constrained-search density-functional formalism are presented. Benchmarking the standard nonequilibrium Green’s function calculation results, it is first established that algorithmically the notion of separate electrode-originated nonlocal QFLs should be maintained within the channel region during self-consistent finite-bias electronic structure calculations. For the insulating hexandithiolate junction, the QFL profiles exhibit discontinuities at the left and right electrode interfaces and across the molecule the accompanying electrostatic potential drops linearly and Landauer residual-resistivity dipoles are uniformly distributed. For the conducting hexatrienedithiolate junction, on the other hand, the electrode QFLs penetrate into the channel region and produce split QFLs. With the highest occupied molecular orbital entering the bias window and becoming a good transport channel, the split QFLs are accompanied by the nonlinear electrostatic potential drop and asymmetric Landauer residual-resistivity dipole formation. Our findings underscore the importance of the first-principles extraction of QFLs in nanoscale junctions and point to a future direction for the computational design of nextgeneration semiconductor devices. [ABSTRACT FROM AUTHOR]

Objective: There is a scarcity of comparative studies between Endeavor Resolute®-zotarolimus-eluting stent (R-ZES) and Resolute Integrity®-ZES (l-ZES) during long-term follow-up periods. Although the stent alloy and the polymer of these two ZESs are similar, the platform and the design of these two stents are different. This study was conducted to compare the efficacy and safety of these two different ZESs in the all-comer Korean patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period. Methods: This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In this single-center, retrospective, and all-comer patients' cohort study, a total of 889 patients who underwent PCI with R-ZES (n=394) or l-ZES (n=495) were enrolled. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, nonfatal myocardial infarction (Ml), any repeat revascularization including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR, and the secondary endpoint was stent thrombosis (ST) at 3 years. Results: To adjust for any potential confounders, the propensity score-adjusted multivariable analysis was performed using the logistic regression model (C-statistics=0.689). The cumulative incidence rates of MACEs [adjusted hazard ratio (aHR), 1.341; 95% confidence interval (CI), 0.615-2.922; p=0.461], all-cause death, nonfatal Ml, any repeat revascularization, and ST (aHR, 2.090; 95% CI, 0.163-26.77; p=0.571) were similar between the two groups during the 3-yearfollow-up period. Conclusion: R-ZES and l-ZES demonstrated comparable efficacy and safety after PCI during a 3-yearfollow-up period. However, these results can perhaps be more precisely defined by other large and long-term follow-up studies in the future. [ABSTRACT FROM AUTHOR]

Objective: Currently, there are limited comparative data concerning long-term major clinical outcomes following the angiotensin-convertingenzyme inhibitors (ACEIs) and angiotensin II type 1 (AT1) receptor blockers (ARBs) therapy in patients with acute myocardial infarction (AMI) with dyslipidemia after a successful stent implantation. Therefore, we investigated major clinical outcomes for 2 years following the ACEIs and ARBs therapy in these patients. Methods: A total of 3015 patients with AMI who underwent a successful stent implantation and were prescribed ACEIs (n=2175) or ARBs (n=840) were enrolled into the study from the Korea AMI Registry (KAMIR). The major clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat-revascularization-comprised target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. Results: After the adjustment, the cumulative incidence of all-cause death in the ARBs group was significantly higher than in the ACEIs group [adjusted hazard ratio (aHR), 2.277; 95% confidence interval (CI), 1.154-4.495; p=0.018]. The cumulative incidences of MACEs (aHR, 1.305; 95% CI, 0.911-1.869; p=0.146), cardiac death, Re-MI, any repeat revascularization, TLR, TVR, and non-TVR were similar between the two groups. In addition, an advanced age (=65 years), decreased left ventricular ejection fraction (<50%), and cardiopulmonary resuscitation on admission were meaningful independent predictors for all-cause death in this study. Conclusion: ACEIs were a preferred treatment modality when compared to ARBs for patients with AMI with dyslipidemia who underwent a successful stent implantation to reduce the incidences of all-cause death during a 2-year follow-up. However, additional research is required to determine the clinical implications of these results. [ABSTRACT FROM AUTHOR]

We report a computational study of conformations and charge transport characteristics of biphenyldithiol (BPDT) monolayers in the (√3 × √3)R30° packing ratio sandwiched between Au(111) electrodes. From force-field molecular-dynamics and annealing simulations of BPDT self-assembled monolayers (SAMs) with up to 100 molecules on a Au(111) substrate, we identify an energetically favorable herringbone-type SAM packing configuration and a less-stable parallel packing configuration. Both SAMs are described by the (2√3 × √3)R30° unit cell including two molecules. With subsequent density-functional theory calculations of one unit cell of the (i) herringbone SAM with the molecular tilt angle θ ≈ 15°, (ii) herringbone SAM with θ ≈ 30°, and (iii) parallel SAM with θ≈ 30°, we confirm that the herringbone packing configuration is more stable than the parallel one but find that the energy variation with respect to the molecule tilting within the herringbone packing is very small. Next, by capping these SAMs with the top Au(111) electrode, we prepare three molecular electronic device models and calculate their coherent charge transport properties within the matrix Green's function approach. Current-voltage (I-V) curves are then obtained via the Landauer-Büttiker formula. We find that at low-bias voltages (∣V∣ ≲0.2 V) the I-V characteristics of models (ii) and (iii) are similar and the current in model (i) is smaller than that in (ii) and (iii). On the other hand, at higher-bias voltages (∣V∣ ≳0.5 V), the I-V characteristics of the three models show noticeable differences due to different phenyl band structures. We thus conclude that the BPDT SAM I-V characteristics in the low-bias voltage region are mainly determined by the Si-Au interaction within the individual molecule-electrode contact, while both intramolecular conformation and intermolecular interaction can affect the BPDT SAM I-V characteristics in the high-bias voltage region. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT), as a mechanical support, has been reported to systemically regulate vascular physiology by secreting adipokines and cytokines. How PVAT spatially and locally changes as atherosclerosis progresses is not known, however. We aimed to reveal the molecular changes in PVAT in advanced atherosclerosis based on multimodal nonlinear optical (MNLO) imaging. First, using an atherogenic apolipoprotein E knockout mouse model, we precisely assessed the browning level of thoracic PVAT via a correlative analysis between the size and number of lipid droplets (LDs) of label-free MNLO images. We also biochemically demonstrated the increased level of brown fat markers in the PVAT of atherosclerosis. In the initial stage of atherosclerosis, the PVAT showed a highly activated brown fat feature due to the increased energy expenditure; however, in the advanced stage, only the PVAT in the regions of the atherosclerotic plaques, not that in the nonplaque regions, showed site-specific changes. We found that p-smad2/3 and TGF-β signaling enhanced the increase in collagen to penetrate the PVAT and the agglomeration of LDs only at the sites of atherosclerotic plaques. Moreover, atherosclerotic thoracic PVAT (tPVAT) was an increased inflammatory response. Taken together, our findings show that PVAT changes differentially from the initial stages to advanced stages of atherosclerosis and undergoes spatial impairment focused on atherosclerotic plaques. Our study may provide insight into the local control of PVAT as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background There are limited data comparing long-term clinical outcomes between first-generation (1G) and second-generation (2G) drug-eluting stents (DESs) in patients who underwent successful percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) lesion. Methods A total of 840 consecutive patients who underwent PCI with DESs for CTO lesion from January 2004 to November 2015 were enrolled. Finally, a total of 324 eligible CTO patients received 1G-DES (Paclitaxel-eluting stent or Sirolimus-eluting stent, n = 157) or 2G-DES (Zotarolimus-eluting stent or Everolimus-eluting stent, n = 167) were enrolled. The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), total repeat revascularization [target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR]. We investigated the 5-year major clinical outcomes between 1G-DES and 2G-DES in patient who underwent successful CTO PCI. Results After propensity score matched (PSM) analysis, two well-balanced groups (111 pairs, n = 222, C-statistic = 0.718) were generated. Up to the 5-year follow-up period, the cumulative incidence of all-cause death, re-MI, TLR, TVR and non-TVR were not significantly different between the two groups. Finally, MACE was also similar between the two groups (HR = 1.557, 95% CI: 0.820-2.959, P = 0.176) after PSM. Conclusions In this study, 2G-DES was not associated with reduced long-term MACE compared with 1G-DES following successful CTO revascularization up to five years. [ABSTRACT FROM AUTHOR]

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity-matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700-1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544-1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion. [ABSTRACT FROM AUTHOR]

Background Because limited comparative data are available, we decided to compare 2-year major clinical outcomes between beta-blockers (BB) with angiotensin converting enzyme inhibitors (ACEI) and BB with angiotensin receptor blockers (ARB) therapy in patients with non-ST-segment elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods A total 11,288 NSTEMI patients who underwent PCI with DES were enrolled and they were divided into two groups, the BB with ACEI group (n = 7600) and the BB with ARB group (n = 3688). The major clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), total revascularization [target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR] rate during the 2-year follow-up period. Results After propensity score-matched (PSM) analysis, two PSM groups (3317 pairs, n = 6634, C-statistic = 0.695) were generated. Although the cumulative incidences of all-cause death, cardiac death, TLR, and non-TVR were similar between the two groups, MACE (HR = 0.832, 95% CI: 0.704-0.982, P = 0.030), total revascularization rate (HR = 0.767, 95% CI: 0.598-0.984, P = 0.037), and TVR rate (HR = 0.646, 95% CI: 0.470-0.888, P = 0.007) were significantly lower in the BB with ACEI group after PSM. Conclusions In this study, we suggest that the combination of BB with ACEI may be beneficial for reducing the cumulative incidences of MACE, total revascularization rate, and TVR rather than the BB with ARB after PCI with DES in NSTEMI patients. [ABSTRACT FROM AUTHOR]

Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela. [ABSTRACT FROM AUTHOR]

Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE-/-) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE-/- mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor α (Tnfα) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE-/- mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1β in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE-/- mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE-/- mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: The appropriate selection of elderly patients for revascularization has become increasingly important because these subsets of patients are more likely to experience a major cardiac or cerebrovascular event-percutaneous coronary intervention (PCI). The objective of this study was to determine important independent risk factor for predicting clinical outcomes in the elderly patients after successful PCI, particularly in a series of South Korean population. Methods: This study is prospective, multicenter, observational cross-sectional study. A total of 1,884 consecutive patients who underwent successful PCI with Nobori® Biolimus A9-eluting stents were enrolled between April 2010 and December 2012. They were divided into two groups according to the age: patients <75 years old (younger patient group) and ≥75 years old (elderly patient group). The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE) at 1-year after index PCI. Results: The 1-year cumulative incidence of MACCE (12.9% vs. 4.3%, p<0.001) and total death (7.1% vs. 1.5%, p<0.001) was significantly higher in the elderly group than in younger group. Previous cerebrovascular disease was significantly correlated with MACCE in elderly patients 1-year after PCI (hazard ratio, 2.804; 95% confidence interval, 1.290–6.093 p=0.009). Conclusion: Previous cerebrovascular disease is important independent predictor of the MACCE in elderly patients at 1-year after PCI with Nobori® Biolimus A9-eluting stents especially in a series of South Korean population. Therefore, careful PCI with intensive monitoring and management can improve major clinical outcomes after successful PCI in elderly patients with previous cerebrovascular disease compared with younger patients. [ABSTRACT FROM AUTHOR]

The excess noise ratio (ENR) of a noise source is largely dependent on the ambient temperature variation. In this paper, we discuss a method to compensate for the ENR of a noise source with respect to ambient temperature variations. From the measured quantities of the receiver and noise source from the setup, calibration coefficients of the noise source are extracted according to the relationship between bias voltage at the noise diode, the ENR, and the physical temperature of noise diode in the noise source by means of a least square estimation. From the result, the ENR of the noise source is compensated by the bias voltage at the noise diode controlled by a microcontroller and a digital-to-analog converter in the noise source. The compensated ENR variation is 0.167 dB for 1.4 dB ENR at 5.4 GHz in an ambient temperature range of 290-320 K. Specifically, the calibrated noise source shows the characteristics of 0.0016 dB/° C in a short ambient temperature range of 310-320 K. The time stability is about 0.007 dB/h for 1.4 dB ENR at 5.4 GHz. The uncertainty is evaluated in the experimental results, and the critical uncertainty contribution is confirmed by reading the power from a spectrum analyzer. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate high mobility solution-processed metal-oxide thin-film transistors (TFTs) by using a high-frequency-stable ionic-type hybrid gate dielectric (HGD). The HGD gate dielectric, a blend of sol-gel aluminum oxide (AlOx) and poly(4-vinylphenol) (PVP), exhibited high dielectric constant (ε~8.15) and high-frequency-stable characteristics (1 MHz). Using the ionic-type HGD as a gate dielectric layer, an minimal electron-double-layer (EDL) can be formed at the gate dielectric/InOx interface, enhancing the field-effect mobility of the TFTs. Particularly, using the ionic-type HGD gate dielectrics annealed at 350 °C, InOx TFTs having an average field-effect mobility of 16.1 cm2/Vs were achieved (maximum mobility of 24 cm2/Vs). Furthermore, the ionic-type HGD gate dielectrics can be processed at a low temperature of 150 °C, which may enable their applications in low-thermal-budget plastic and elastomeric substrates. In addition, we systematically studied the operational stability of the InOx TFTs using the HGD gate dielectric, and it was observed that the HGD gate dielectric effectively suppressed the negative threshold voltage shift during the negative-illumination-bias stress possibly owing to the recombination of hole carriers injected in the gate dielectric with the negatively charged ionic species in the HGD gate dielectric. [ABSTRACT FROM AUTHOR]

Estrogen-related receptor γ (ERRγ) is a major positive regulator of hepatic gluconeogenesis. Its transcriptional activity is suppressed by phosphorylation signaled by insulin in the fed state, but whether posttranslational modification alters its gluconeogenic activity in the fasted state is not known. Metabolically active hepatocytes direct a small amount of glucose into the hexosamine biosynthetic pathway, leading to protein O-GlcNAcylation. In this study, we demonstrate that ERRγ is O-GlcNAcylated by O-GlcNAc transferase in the fasted state. This stabilizes the protein by inhibiting proteasome-mediated protein degradation, increasing ERRγ recruitment to gluconeogenic gene promoters. Mass spectrometry identifies two serine residues (S317, S319) present in the ERRγ ligand-binding domain that are O-GlcNAcylated. Mutation of these residues destabilizes ERRγ protein and blocks the ability of ERRγ to induce gluconeogenesis in vivo. The impact of this pathway on gluconeogenesis in vivo was confirmed by the observation that decreasing the amount of O-GlcNAcylated ERRγ by overexpressing the deglycosylating enzyme O-GlcNAcase decreases ERRγ-dependent glucose production in fasted mice. We conclude that O-GlcNAcylation of ERRγ serves as a major signal to promote hepatic gluconeogenesis. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. [ABSTRACT FROM AUTHOR]

Background: Actual differences of long term outcome of extrahepatic cholangiocarcinoma according to the location of the tumor have not yet been studied. The aim of this study was to evaluate the prognosis and optimal surgical procedure for middle (BD) cancer.Methods: Among 109 patients with carcinoma of the extrahepatic BD underwent surgical resection, curative resection of extrahepatic BD cancer was performed in 90 patients. They were classified into three groups according to the location of tumors: DISTAL (n = 32), tumor was confined to the intrapancreatic bile duct; MID (n = 20), tumor was located between below the confluence of the hepatic duct bifurcation and suprapancreatic portion of the BD; and DIFFUSE (n = 38), tumor was located diffusely.Results: Tumor involving the middle BD (MID or DIFFUSE) had a higher rate of perineural invasion as compared to the DISTAL group. The overall and disease-free survival rate for the MID or DIFFUSE group was significantly worse than that of DISTAL. In the MID/DIFFUSE group, there was no significant difference of survival according to the type of the operation (pancreaticoduodenectomy or segmental BD resection). The multivariate analysis showed that tumor involving middle BD (MID or DIFFUSE group) and node metastasis were independently poor prognostic factors for the disease free and overall survival.Conclusion: Extrahepatic cholangiocarcinoma involving the extrapancreatic BD has a worse prognosis than those confined to the intrapancreatic BD. In patients with tumors confined to the middle BD, BD resection can be considered as an alternative surgical procedure to pancreaticoduodenectomy, if an R0 resection can be accomplished. [ABSTRACT FROM AUTHOR]

We report a derivative spectroscopic method for determining insulator-to-semiconductor transition during sol-gel metal-oxide semiconductor formation. When an as-spun sol-gel precursor film is photochemically activated and changes to semiconducting state, the light absorption characteristics of the metal-oxide film is considerable changed particularly in the ultraviolet region. As a result, a peak is generated in the first-order derivatives of light absorption (A') vs. wavelength (λ) plots, and by tracing the peak center shift and peak intensity, transition from insulating-to-semiconducting state of the film can be monitored. The peak generation and peak center shift are described based on photon-energy-dependent absorption coefficient of metal-oxide films. We discuss detailed analysis method for metal-oxide semiconductor films and its application in thin-film transistor fabrication. We believe this derivative spectroscopy based determination can be beneficial for a non-destructive and a rapid monitoring of the insulator-to-semiconductor transition in sol-gel oxide semiconductor formation. [ABSTRACT FROM AUTHOR]

Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sexmatched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions.Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Opentype atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05).Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation. [ABSTRACT FROM AUTHOR]

The hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose. [ABSTRACT FROM AUTHOR]

Objective: Home blood pressure (HBP) measurements are known as an important adjunct to office blood pressure (OBP) measurements in clinical practice. But little is known about the relationship between HBP and subclinical target organ damage (TOD) other than left ventricular hypertrophy (LVH). So we investigated the relationship of HBP measurements with subclinical TOD in untreated hypertensive patients. Methods: We measured ambulatory blood pressure (ABP), HBP and OBP of 93 untreated hypertensive patients (men: 60 and women: 33, mean age, 49±13 years). The ABP was recorded for 24 hours, HBP was measured for one week, and OBP was measured at least in two visits. All BP measurements were taken using automatic BP measuring device. The parameters indicating subclinical TOD were the left-ventricular mass index (LVMI) by transthoracic echocardiography, urinary albumin excretion rate (AER), brachial ankle pulse-wave velocity (PWV), and carotid intima-media thickness (IMT). Results: The LVMI was significantly correlated with systolic HBP and 24 hours systolic ABP but not with OBP The AER, PWV and IMT were also significantly correlated with systolic HBP and 24 hours systolic ABP In a binary logistic regression analysis, systolic HBP 24 hours systolic and diastolic ABP were the predictors of LVMI, AER and PWV (all p<0.05). Conclusion: Our data suggest that HBP is as good as ABP monitoring and superior to OBP measurements in regard to their association with subclinical TOD. Therefore, HBP measurements give valuable information on the subclinical TOD in hypertensive patients in addition to ABP monitoring. [ABSTRACT FROM AUTHOR]