Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w.

MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3' UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3' UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA.

miR-564: A potential regulator of vascular smooth muscle cells and therapeutic target for aortic dissection.

BACKGROUND: Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation. METHODS: By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence. RESULTS: Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation. CONCLUSIONS: Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.

The association of demodex infestation with pediatric chalazia.

PURPOSE: This study aimed to investigate the association of Demodex infestation with pediatric chalazia. METHODS: In a prospective study, 446 children with chalazia and 50 children with non-inflammatory eye disease (controls) who underwent surgical treatment were enrolled from December 2018 to December 2019. Patient ages ranged from 7 months to 13 years old. All patients underwent eyelash sampling for light microscope examination, and statistical correlation analysis between Demodex infestation and chalazia, including the occurrence, recurrence, and course of disease, morphological characteristics, and meibomian gland dysfunction (MGD) in chalazia patients was performed. RESULTS: Demodex was found in 236 (52.91%) patients with chalazia and zero control patients. Demodicosis was significantly more prevalent in chalazia patients than the control group (P < 1 × 10- 14). Recurrent chalazia (P = 0.006) and skin surface involvement (P = 0.029) were highly correlated with Demodex infestation. Demodicosis was also associated with multiple chalazia (P = .023) and MGD(P = .024). However, Demodex infestation was comparable in the course of disease (P = 0.15), seasonal change (P = 0.68) and blepharitis subgroups (P = 0.15). Within the group of chalazia patients who underwent surgical removal of cysts, 4 (0.9%) patients with concurrent demodicosis experienced recurrence. CONCLUSIONS: Demodex infestation was more prevalent in pediatric chalazia patients than healthy children, and was associated with recurrent and multiple chalazia. Demodicosis should be considered as a risk factor of chalazia. In children with chalazia, Demodex examination and comprehensive treatment of Demodex mites should be applied to potentially prevent recurrence.

Reducing Geometric Uncertainty in Computational Hemodynamics by Deep Learning-Assisted Parallel-Chain MCMC.

Computational hemodynamic modeling has been widely used in cardiovascular research and healthcare. However, the reliability of model predictions is largely dependent on the uncertainties of modeling parameters and boundary conditions, which should be carefully quantified and further reduced with available measurements. In this work, we focus on propagating and reducing the uncertainty of vascular geometries within a Bayesian framework. A novel deep learning (DL)-assisted parallel Markov chain Monte Carlo (MCMC) method is presented to enable efficient Bayesian posterior sampling and geometric uncertainty reduction. A DL model is built to approximate the geometry-to-hemodynamic map, which is trained actively using online data collected from parallel MCMC chains and utilized for early rejection of unlikely proposals to facilitate convergence with less expensive full-order model evaluations. Numerical studies on two-dimensional aortic flows are conducted to demonstrate the effectiveness and merit of the proposed method.

Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5' end and 2'-O-methylation at the 3' end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

Noncoding RNAs in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets.

Anthracyclines, such as doxorubicin (DOX), are well known for their high efficacy in treating multiple cancers, but their clinical usage is limited due to their potential to induce fatal cardiotoxicity. Such detrimental effects significantly impact the overall physical condition or even induce the morbidity and mortality of cancer survivors. Therefore, it is extremely important to understand the mechanisms of DOX-induced cardiotoxicity to develop methods for the early detection of cytotoxicity and therapeutic applications. Studies have shown that many molecular events are involved in DOX-induced cardiotoxicity. However, the precise mechanisms are still not completely understood. Recently, noncoding RNAs (ncRNAs) have been extensively studied in a diverse range of regulatory roles in cellular physiological and pathological processes. With respect to their roles in DOX-induced cardiotoxicity, microRNAs (miRNAs) are the most widely studied, and studies have focused on the regulatory roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to have significant functions in the cardiovascular system. Recent discoveries on the roles of ncRNAs in DOX-induced cardiotoxicity have prompted extensive interest in exploring candidate ncRNAs for utilization as potential therapeutic targets and/or diagnostic biomarkers. This review presents the frontier studies on the roles of ncRNAs in DOX-induced cardiotoxicity, addresses the possibility and prospects of using ncRNAs as diagnostic biomarkers or therapeutic targets, and discusses the possible reasons for related discrepancies and limitations of their use.

Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes.

Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 µM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 µM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.

MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD.

RATIONALE: Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently. OBJECTIVE: The purpose of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through targeting FADD. METHODS AND RESULTS: Our results show that FADD participates in H2O2-induced necrosis by influencing the formation of RIPK1 and RIPK3 complexes in H9c2 cells. We further demonstrate that miR-103/107 target FADD directly. Knockdown of miR-103/107 antagonizes necrosis in the cellular model and also myocardial infarction in a mouse ischemia/reperfusion model. The miR-103/107-FADD pathway does not participate in tumor necrosis factor-α-induced necrosis. In exploring the molecular mechanism by which miR-103/107 are regulated, we show that long noncoding RNA H19 directly binds to miR-103/107 and regulates FADD expression and necrosis. CONCLUSIONS: Our results reveal a novel myocardial necrosis regulation model, which is composed of H19, miR-103/107, and FADD. Modulation of their levels may provide a new approach for preventing myocardial necrosis.

MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL), affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484) and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223.

AIMS: Sustained cardiac hypertrophy accompanied by maladaptive cardiac remodelling represents an early event in the clinical course leading to heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. However, the molecular mechanisms that regulate cardiac hypertrophy are largely unknown. METHODS AND RESULTS: Here we show that a circular RNA (circRNA), which we term heart-related circRNA (HRCR), acts as an endogenous miR-223 sponge to inhibit cardiac hypertrophy and heart failure. miR-223 transgenic mice developed cardiac hypertrophy and heart failure, whereas miR-223-deficient mice were protected from hypertrophic stimuli, indicating that miR-223 acts as a positive regulator of cardiac hypertrophy. We identified ARC as a miR-223 downstream target to mediate the function of miR-223 in cardiac hypertrophy. Apoptosis repressor with CARD domain transgenic mice showed reduced hypertrophic responses. Further, we found that a circRNA HRCR functions as an endogenous miR-223 sponge to sequester and inhibit miR-223 activity, which resulted in the increase of ARC expression. Heart-related circRNA directly bound to miR-223 in cytoplasm and enforced expression of HRCR in cardiomyocytes and in mice both exhibited attenuated hypertrophic responses. CONCLUSIONS: These findings disclose a novel regulatory pathway that is composed of HRCR, miR-223, and ARC. Modulation of their levels provides an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure.

The Role of MicroRNAs in Myocardial Infarction: From Molecular Mechanism to Clinical Application.

MicroRNAs (miRNAs) are a class of small single-stranded and highly conserved non-coding RNAs, which are closely linked to cardiac disorders such as myocardial infarction (MI), cardiomyocyte hypertrophy, and heart failure. A growing number of studies have demonstrated that miRNAs determine the fate of the heart by regulating cardiac cell death and regeneration after MI. A deep understanding of the pathophysiology of miRNA dependent regulatory pathways in these processes is required. The role of miRNAs as diagnostic, prognostic, and therapeutic targets also needs to be explored in order to utilize them in clinical settings. This review summarizes the role of miRNAs in myocardial infarction and focuses mainly on their influence on cardiomyocyte regeneration and cell death including apoptosis, necrosis, and autophagy. In addition, the targets of pro- and anti-MI miRNAs are comparatively described. In particular, the possibilities of miRNA-based diagnostic and therapeutic strategies for myocardial infarction are discussed in this review.

A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the Puma protein in apoptosis.

MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that function as negative regulators of gene expression. They are transcribed from endogenous DNA and form hairpin structures (termed as pre-miRNAs) that are processed to form mature miRNAs. It remains largely unknown as to the molecular consequences of the natural genetic variation in pre-miRNAs. Here, we report that an A→G polymorphism (rs71428439) is located in Homo sapiens miR-149 stem-loop region. This polymorphism results in a change in the structure of the miR-149 precursor. Our results showed that the genotype distribution of this polymorphism in myocardial infarction cases was significantly different from that in the control subjects. We examined the biological significance of this polymorphism on the production of mature miR-149, and we observed that the G-allelic miR-149 precursor displayed a lower production of mature miR-149 compared with the A-allelic one. Further investigations disclosed that miR-149 could withstand mitochondrial fission and apoptosis through targeting the pro-apoptotic factor p53-up-regulated modulator of apoptosis (Puma). Enforced expression of miR-149 promoted cell survival, whereas knockdown of miR-149 rendered cells to be sensitive to apoptotic stimulation. Intriguingly, the A to G variation led pre-miR-149 to elicit an attenuated effect on the inhibition of mitochondrial fission and apoptosis. Finally, this polymorphism exerts its influence on cardiac function in the mouse model of myocardial infarction. These data suggest that this polymorphism in the miR-149 precursor may result in important phenotypic traits of myocardial infarction. Our findings warrant further investigations on the relationship between miR-149 polymorphism and myocardial infarction.

A neural network-based algorithm for the reconstruction and filtering of single particle trajectory in magnetic particle tracking.

Magnetic particle tracking (MPT) is a recently developed non-invasive measurement technique that has gained popularity for studying dense particulate or granular flows. This method involves tracking the trajectory of a magnetically labeled particle, the field of which is modeled as a dipole. The nature of this method allows it to be used in opaque environments, which can be highly beneficial for the measurement of dense particle dynamics. However, since the magnetic field of the particle used is weak, the signal-to-noise ratio is usually low. The noise from the measuring devices contaminates the reconstruction of the magnetic tracer's trajectory. A filter is then needed to reduce the noise in the final trajectory results. In this work, we present a neural network-based framework for MPT trajectory reconstruction and filtering, which yields accurate results and operates at very high speed. The reconstruction derived from this framework is compared to the state-of-the-art extended Kalman filter-based reconstruction.

CircHIPK3 targets DRP1 to mediate hydrogen peroxide-induced necroptosis of vascular smooth muscle cells and atherosclerotic vulnerable plaque formation.

INTRODUCTION: Necroptosis triggered by H2O2 is hypothesized to be a critical factor in the rupture of atherosclerotic plaques, which may precipitate acute cardiovascular events. Nevertheless, the specific regulatory molecules of this development remain unclear. We aims to elucidate a mechanism from the perspective of circular RNA. OBJECTIVES: There are few studies on circRNA in VSMCs necroptosis. The objective of our research is to shed light on the intricate roles that circHIPK3 plays in the process of necroptosis in VSMCs and the development of atherosclerotic plaques that are prone to rupture. Our study elucidates the specific molecular mechanisms by which circHIPK3 regulates necroptosis and atherosclerotic vulnerable plaque formation through targeted proteins. Identifying this mechanism at the cellular level offers a molecular framework for understanding plaque progression and stability regulation, as well as a potential biomarker for the prognosis of susceptible atherosclerotic plaques. METHODS: We collected clinical vascular tissue for HE staining and Masson staining to determine the presence and stability of plaques. Then, NCBI database was used to screen out circRNA with elevated expression level in plaque tissue, and the up-regulated circRNA, circHIPK3, was verified by qRT-PCR and FISH. Further, we synthesized circHIPK3's small interference sequence and overexpressed plasmid in vitro, and verified its regulation effect on necroptosis of VSMCs under physiological and pathological conditions by WB, qRT-PCR and PI staining. Through RNA pull down, mass spectrometry and RNA immunoprecipitation, DRP1 was identified as circHIPK3 binding protein and was positively regulated by circHIPK3. Meanwhile, on the basis of silencing of DRP1, the regulation of circHIPK3 on necroptosis is verified to be mediated by DRP1. Finally, we validated the regulation of circHIPK3 on vulnerable plaque formation in ApoE-/- mice. RESULTS: We investigated that circHIPK3 was highly expressed in vulnerable plaques, and the increase in expression level promoted H2O2 induced necroptosis of VSMCs. CircHIPK3 targeted the protein DRP1, leading to an elevation in mitochondrial division rate, resulting in increased reactive oxygen species and impaired mitochondrial function, ultimately leading to necroptosis of VSMCs and vulnerable plaque formation. CONCLUSION: CircHIPK3 interact with DRP1 involve in H2O2 induced Mitochondrial damage and necroptosis of VSMCs, and Silencing circHIPK3 in vivo can reduce atherosclerotic vulnerable plaque formation. Our research findings may have applications in providing diagnostic biomarkers for vulnerable plaques.

Controlled arrays of self-assembled peptide nanostructures in solution and at interface.

Controlling the formation of large and homogeneous arrays of bionanostructures through the self-assembly approach is still a great challenge. Here, we report the spontaneous formation of highly ordered arrays based on aligned peptide nanostructures in a solution as well as at an interface by self-assembly. By controlling the time and temperature of self-assembly in the solution, parallel fibrous alignments and more sophisticated two-dimensional "knitted" fibrous arrays could be formed from aligned rod-like fibers. During the formation of such arrays, the "disorder-to-order" transitions are controlled by the temperature-responsible motile short hydrophobic tails of the gemini-like amphiphilic peptides (GAPs) with asymmetric molecular conformation. In addition, the resulting long-range-ordered "knitted" fibrous arrays are able to direct mineralization of calcium phosphate to form organic-inorganic composite materials. In this study, the self-assembly behavior of these peptide building blocks at an interface was also studied. Highly ordered spatial arrays with vertically or horizontally aligned nanostructures such as nanofibers, microfibers, and microtubes could be formed through interfacial assembly. The regular structures and their alignments on the interface are controlled by the alkyl chain length of building blocks and the hydrophilicity/hydrophobicity property of the interface.

Laser direct patterning of indium tin oxide for defining a channel of thin film transistor.

In this work, using a Q-switched diode-pumped neodymium-doped yttrium vanadate (Nd:YVO4, lambda = 1064 nm) laser, a direct patterning of indium tin oxide (ITO) channel was realized on glass substrates and the results were compared and analyzed in terms of the effect of repetition rate, scanning speed on etching characteristics. The results showed that the laser conditions of 40 kHz repetition rate with a scanning speed of 500 mm/s were appropriate for the channeling of ITO electrodes. The length of laser-patterned channel was maintained at about 55 microm. However, residual spikes (about 50 nm in height) of ITO were found to be formed at the edges of the laser ablated area and a few ITO residues remained on the glass substrate after laser scanning. By dipping the laser-ablated ITO film in ITO diluted etchant (ITO etchant/DI water: 1/10) at 50 degrees C for 3 min, the spikes and residual ITO were effectively removed. At last, using the laser direct patterning, a bottom-source-drain indium gallium zinc oxide thin film transistor (IGZO-TFT) was fabricated. It is successfully demonstrated that the laser direct patterning can be utilized instead of photolithography to simplify the fabrication process of TFT channel, resulting in the increase of productivity and reduction of cost.

Nd:YVO4 laser direct ablation of indium tin oxide films deposited on glass and polyethylene terephthalate substrates.

A Q-switched diode-pumped neodymium-doped yttrium vanadate (Nd:YVO4, lambda = 1064 nm) laser was applied to obtain the indium tin oxide (ITO) patterns on flexible polyethylene terephthalate (PET) substrate by a direct etching method. After the ITO films were deposited on a soda-lime glass and PET substrate, laser ablations were carried out on the ITO films for various conditions and the laser ablated results on the ITO films were investigated and analyzed considering the effects of substrates on the laser etching. The laser ablated widths on ITO deposited on glass were found to be much narrower than those on ITO deposited on PET substrate, especially, at a higher scanning speed of laser beam such as 1000 mm/s and 2000 mm/s. As the thermal conductivity of glass substrate is about 7.5 times higher than that of PET, more thermal energy would be spread and transferred to lateral direction in the ITO film in case of PET substrate.

Semi-transparent a-IGZO thin-film transistors with polymeric gate dielectric.

We report the fabrication of semi-transparent a-IGZO-based thin-film transistors (TFTs) with crosslinked poly-4-vinylphenol (PVP) gate dielectric layers on PET substrate and thermally-evaporated Al/Ag/Al source and drain (S&D) electrodes, which showed a transmittance of 64% at a 500-nm wavelength and sheet resistance of 16.8 omega/square. The semi-transparent a-IGZO TFTs with a PVP layer exhibited decent saturation mobilities (maximum approximately 5.8 cm2Ns) and on/off current ratios of approximately 10(6).

Predicting 3D soft tissue dynamics from 2D imaging using physics informed neural networks.

Tissue dynamics play critical roles in many physiological functions and provide important metrics for clinical diagnosis. Capturing real-time high-resolution 3D images of tissue dynamics, however, remains a challenge. This study presents a hybrid physics-informed neural network algorithm that infers 3D flow-induced tissue dynamics and other physical quantities from sparse 2D images. The algorithm combines a recurrent neural network model of soft tissue with a differentiable fluid solver, leveraging prior knowledge in solid mechanics to project the governing equation on a discrete eigen space. The algorithm uses a Long-short-term memory-based recurrent encoder-decoder connected with a fully connected neural network to capture the temporal dependence of flow-structure-interaction. The effectiveness and merit of the proposed algorithm is demonstrated on synthetic data from a canine vocal fold model and experimental data from excised pigeon syringes. The results showed that the algorithm accurately reconstructs 3D vocal dynamics, aerodynamics, and acoustics from sparse 2D vibration profiles.

Effect of organic buffer layer in the electrical properties of amorphous-indium gallium zinc oxide thin film transistor.

In this research, we reported on the fabrication of top-contact amorphous-indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) with an organic buffer layer between inorganic gate dielectric and active layer in order to improve the electrical properties of devices. By inserting an organic buffer layer, it was possible to make an affirmation of the improvements in the electrical characteristics of a-IGZO TFTs such as subthreshold slope (SS), on/off current ratio (I(ON/OFF)), off-state current, and saturation field-effect mobility (muFE). The a-IGZO TFTs with the cross-linked polyvinyl alcohol (c-PVA) buffer layer exhibited the pronounced improvements of the muFE (17.4 cm2/Vs), SS (0.9 V/decade), and I(ON/OFF) (8.9 x 10(6)).