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We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.

We evaluated the 3-year clinical outcomes following early invasive (EI) and delayed invasive (DI) strategies in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing successful new-generation drug-eluting stents (DESs) implantation to reflect current real-world practice. Overall, 2437 older adults (age, ≥ 65 years) with NSTEMI were recruited from the Korea Acute Myocardial Infarction Registry-National Institute of Health. They were divided into two groups: EI (n = 1750) and DI (n = 687). The primary clinical outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), defined by all-cause death, recurrent MI, any repeat coronary revascularization, and stroke. The secondary clinical outcome was stent thrombosis (ST). After multivariable-adjusted and propensity score-matched analyses, the primary and secondary clinical outcomes were not significantly different between the EI and DI groups. Even after the analysis was confined to those having complex lesions, these major clinical outcomes were similar between these two groups. The EI and DI strategies in older adults with NSTEMI receiving new-generation DES showed comparable results.Clinical Trial Registration: URL: http://cris.nih.go.kr/cris/en/; Unique identifier: KCT0000863.

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.Trial registration: NCT02707445 (https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1).

We investigated the effects of stent generation on 2-year clinical outcomes between prediabetes and diabetes patients after acute myocardial infarction (AMI). A total of 13,895 AMI patients were classified into normoglycemia (group A: 3673), prediabetes (group B: 5205), and diabetes (group C: 5017). Thereafter, all three groups were further divided into first-generation (1G)-drug-eluting stent (DES) and second-generation (2G)-DES groups. Patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcome. Stent thrombosis (ST) was the secondary outcome. In both prediabetes and diabetes groups, the cumulative incidences of POCOs, any repeat revascularization, and ST were higher in the 1G-DES than that in the 2G-DES. In the diabetes group, all-cause death and cardiac death rates were higher in the 1G-DES than that in the 2G-DES. In both stent generations, the cumulative incidence of POCOs was similar between the prediabetes and diabetes groups. However, in the 2G-DES group, the cumulative incidences of Re-MI and all-cause death or MI were significantly higher in the diabetes group than that in the prediabetes group. To conclude, 2G-DES was more effective than 1G-DES in reducing the primary and secondary outcomes for both prediabetes and diabetes groups.

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

Amorphous metal-oxide semiconductors (AOSs) such as indium-gallium-zinc-oxide (IGZO) as an active channel have attracted substantial interests with regard to high-performance thin-film transistors (TFTs). Recently, intensive and extensive studies of flexible and/or wearable AOS-based TFTs fabricated by solution-process have been reported for emerging approaches based on device configuration and fabrication process. However, several challenges pertaining to practical and effective solution-process technologies remain to be resolved before low-power consuming AOS-based TFTs for wearable electronics can be realized. In this paper, we investigate the non-thermal annealing processes for sol-gel based metal-oxide semiconductor and dielectric films fabricated by deep ultraviolet (DUV) photo and microwave annealing at low temperature, compared to the conventional thermal annealing at high temperature. A comprehensive investigation including a comparative analysis of the effects of DUV photo and microwave annealing on the degree of metal-oxide-metal networks in amorphous IGZO and high-dielectric-constant (high-k) aluminum oxide (Al2O3) films and device performance of IGZO-TFTs in a comparison with conventional thermal annealing at 400 °C was conducted. We also demonstrate the feasibility of wearable IGZO-TFTs with Al2O3 dielectrics on solution-processed polyimide films exhibiting a high on/off current ratio of 5 × 104 and field effect mobility up to 1.5 cm2/V-s operating at 1 V. In order to reduce the health risk and power consumption during the operation of wearable electronics, the operating voltage of IGZO-TFTs fabricated by non-thermal annealing at low temperature was set below ~1 V. The mechanical stability of wearable IGZO-TFTs fabricated by an all-solution-process except metal electrodes, against cyclic bending tests with diverse radius of curvatures in real-time was investigated. Highly stable and robust flexible IGZO-TFTs without passivation films were achieved even under continuous flexing with a curvature radius of 12 mm.

Recently, we reported that orphan nuclear receptor small heterodimer partner (SHP) is involved in neutrophil recruitment through the regulation of C-X-C motif chemokine ligand 2 (CXCL2) expression in a concanavalin A (ConA)-induced hepatitis model. In the present study, we examined the mechanisms underlying CXCL2 regulation by SHP and the cell types involved in liver inflammation. To this end, either Shp knockout (KO) or wild-type (WT) bone marrow cells were transferred into sublethally-irradiated WT (KO → WT or WT → WT) or Shp KO (KO → KO or WT → KO) recipients, followed by intravenous injection of ConA (20–30 mg/kg) 8 weeks later. The KO recipient groups showed higher ConA-induced lethality than the WT recipient groups. Accordingly, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory cytokine expressions were significantly higher in the KO recipients than in the WT recipients regardless of donor genotype. Massively increased hepatocyte death in KO recipients, as determined by H&E and TUNEL staining, was observed after ConA challenge. Bone marrow chimera experiments and in vitro chemotaxis assay also showed that SHP-deficient hepatocytes have an enhanced ability to recruit neutrophils to the injured liver. In vitro promoter assays showed that SHP is a negative regulator of Cxcl2 transcription by interfering with c-Jun binding to the AP-1 site within the Cxcl2 promoter. Collectively, SHP regulates Cxcl2 transcription in hepatocytes, playing a pivotal role in the recruitment of neutrophils. SHP-targeting strategies may represent alternative approaches to control fulminant hepatitis.

There is an increasing demand in the flexible electronics industry for highly robust flexible/transparent conductors that can withstand high temperatures and corrosive environments. In this work, outstanding thermal and ambient stability is demonstrated for a highly transparent Ag nanowire electrode with a low electrical resistivity, by encapsulating it with an ultra-thin Al2O3 film (around 5.3 nm) via low-temperature (100 °C) atomic layer deposition. The Al2O3-encapsulated Ag nanowire (Al2O3/Ag) electrodes are stable even after annealing at 380 °C for 100 min and maintain their electrical and optical properties. The Al2O3 encapsulation layer also effectively blocks the permeation of H2O molecules and thereby enhances the ambient stability to greater than 1,080 h in an atmosphere with a relative humidity of 85% at 85 °C. Results from the cyclic bending test of up to 500,000 cycles (under an effective strain of 2.5%) confirm that the Al2O3/Ag nanowire electrode has a superior mechanical reliability to that of the conventional indium tin oxide film electrode. Moreover, the Al2O3 encapsulation significantly improves the mechanical durability of the Ag nanowire electrode, as confirmed by performing wiping tests using isopropyl alcohol.

There is an increasing demand in the flexible electronics industry for highly robust flexible/transparent conductors that can withstand high temperatures and corrosive environments. In this work, outstanding thermal and ambient stability is demonstrated for a highly transparent Ag nanowire electrode with a low electrical resistivity, by encapsulating it with an ultra-thin Al2O3 film (around 5.3 nm) via low-temperature (100 °C) atomic layer deposition. The Al2O3-encapsulated Ag nanowire (Al2O3/Ag) electrodes are stable even after annealing at 380 °C for 100 min and maintain their electrical and optical properties. The Al2O3 encapsulation layer also effectively blocks the permeation of H2O molecules and thereby enhances the ambient stability to greater than 1,080 h in an atmosphere with a relative humidity of 85% at 85 °C. Results from the cyclic bending test of up to 500,000 cycles (under an effective strain of 2.5%) confirm that the Al2O3/Ag nanowire electrode has a superior mechanical reliability to that of the conventional indium tin oxide film electrode. Moreover, the Al2O3 encapsulation significantly improves the mechanical durability of the Ag nanowire electrode, as confirmed by performing wiping tests using isopropyl alcohol.

Small heterodimer partner (SHP) is a transcriptional corepressor regulating diverse metabolic processes. Here, we show that SHP acts as an intrinsic negative regulator of iron homeostasis. SHP-deficient mice maintained on a high-iron diet showed increased serum hepcidin levels, decreased expression of the iron exporter ferroportin as well as iron accumulation compared to WT mice. Conversely, overexpression of either SHP or AMP-activated protein kinase (AMPK), a metabolic sensor inducing SHP expression, suppressed BMP6-induced hepcidin expression. In addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6-mediated hepcidin gene expression was significantly attenuated by ablation of SHP expression. Interestingly, SHP physically interacted with SMAD1 and suppressed BMP6-mediated recruitment of the SMAD complex to the hepcidin gene promoter by inhibiting the formation of SMAD1 and SMAD4 complex. Finally, overexpression of SHP and metformin treatment of BMP6 stimulated mice substantially restored hepcidin expression and serum iron to baseline levels. These results reveal a previously unrecognized role for SHP in the transcriptional control of iron homeostasis.

We have demonstrated that photo-thin film transistors (photo-TFTs) fabricated via a simple defect-generating process could achieve fast recovery, a high signal to noise (S/N) ratio, and high sensitivity. The photo-TFTs are inverted-staggered bottom-gate type indium-gallium-zinc-oxide (IGZO) TFTs fabricated using atomic layer deposition (ALD)-derived Al2O3 gate insulators. The surfaces of the Al2O3 gate insulators are damaged by ion bombardment during the deposition of the IGZO channel layers by sputtering and the damage results in the hysteresis behavior of the photo-TFTs. The hysteresis loops broaden as the deposition power density increases. This implies that we can easily control the amount of the interface trap sites and/or trap sites in the gate insulator near the interface. The photo-TFTs with large hysteresis-related defects have high S/N ratio and fast recovery in spite of the low operation voltages including a drain voltage of 1 V, positive gate bias pulse voltage of 3 V, and gate voltage pulse width of 3 V (0 to 3 V). In addition, through the hysteresis-related defect-generating process, we have achieved a high responsivity since the bulk defects that can be photo-excited and eject electrons also increase with increasing deposition power density.