Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Analysis of carrier injection under high temperature AC operation in top gate IGZO TFTs

Abstract– With the development of high-quality displays, metal oxides gradually become a popular active layer in TFTs [1]. In this work, InGaZnO thin film transistors with double-layer oxide are investigated. The oxide layer is divided into top and bottom layers. We improve the characteristics and reliability of the device through the design of double-layer oxide stack structure. The bottom oxide layer is deposited with a lower SiH4 flow rate, and the top oxide layer is deposited with a higher SiH4 flow rate. By increasing the SiH4 flow rate of the top oxide layer, two effects can be achieved. Firstly, it is beneficial for speeding up the film deposition process. Furthermore, the hydrogen residue passivates the dangling bonds in the oxide layer and increases the bonding amount of silanol groups, SiO-H, and achieve hydrogen channel doping [2]. By modulating the SiH4 flow rate of the top oxide layer, the basic characteristics of the devices and the reliability under alternating current (AC) operation are improved. In this work, we use three waveform types of switch process to analyze the degradation under AC stress, and the physic mechanism is proposed subsequently [3-4]. After AC stress, the top oxide layer with higher SiH4 flow rate has a smaller threshold voltage right shift, and the reliability is significantly improved. Please click Download on the upper right corner to see the full abstract

Multidrug Resistant Acinetobacter baumannii: Risk Factors for Appearance of Imipenem Resistant Strains on Patients Formerly with Susceptible Strains

BACKGROUND: Multidrug resistant Acinetobacter baumannii (MDRAB) is an important nosocomial pathogen usually susceptible to carbapenems; however, growing number of imipenem resistant MDRAB (IR-MDRAB) poses further clinical challenge. The study was designed to identify the risk factors for appearance of IR-MDRAB on patients formerly with imipenem susceptible MDRAB (IS-MDRAB) and the impact on clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective case control study was carried out for 209 consecutive episodes of IS-MDRAB infection or colonization from August 2001 to March 2005. Forty-nine (23.4%) episodes with succeeding clinical isolates of IR-MDRAB were defined as the cases and 160 (76.6%) with all subsequent clinical isolates of IS-MDRAB were defined as the controls. Quantified antimicrobial selective pressure, "time at risk", severity of illness, comorbidity, and demographic data were incorporated for multivariate analysis, which revealed imipenem or meropenem as the only significant independent risk factor for the appearance of IR-MDRAB (adjusted OR, 1.18; 95% CI, 1.09 to 1.27). With selected cases and controls matched to exclude exogenous source of IR-MDRAB, multivariate analysis still identified carbapenem as the only independent risk factor (adjusted OR, 1.48; 95% CI, 1.14 to 1.92). Case patients had a higher crude mortality rate compared to control patients (57.1% vs. 31.3%, p = 0.001), and the mortality of case patients was associated with shorter duration of "time at risk", i.e., faster appearance of IR-MDRAB (adjusted OR, 0.9; 95% CI, 0.83 to 0.98). CONCLUSIONS/SIGNIFICANCE: Judicious use of carbapenem with deployment of antibiotics stewardship measures is critical for reducing IR-MDRAB and the associated unfavorable outcome