Quorum sensing-based metabolic engineering of the precursor supply in Streptomyces coelicolor to improve heterologous production of neoaureothin.

Streptomyces are important industrial bacteria that produce pharmaceutically valuable polyketides. However, mass production on an industrial scale is limited by low productivity, which can be overcome through metabolic engineering and the synthetic biology of the host strain. Recently, the introduction of an auto-inducible expression system depending on microbial physiological state has been suggested as an important tool for the industrial-scale production of polyketides. In this study, titer improvement by enhancing the pool of CoA-derived precursors required for polyketide production was driven in a quorum sensing (QS)-dependent manner. A self-sustaining and inducer-independent regulatory system, named the QS-based metabolic engineering of precursor pool (QMP) system, was constructed, wherein the expression of genes involved in precursor biosynthesis was regulated by the QS-responsive promoter, scbAp. The QMP system was applied for neoaureothin production in a heterologous host, Streptomyces coelicolor M1152, and productivity increased by up to 4-fold. In particular, the engineered hyperproducers produced high levels of neoaureothin without adversely affecting cell growth. Overall, this study showed that self-regulated metabolic engineering mediated by QS has the potential to engineer strains for polyketide titer improvement.

One-Stop Strategy for Obtaining Controllable Sensitivity and Feasible Self-Patterning in Silver Nanowires/Elastomer Nanocomposite-Based Stretchable Ultrathin Strain Sensors.

In this study, selective photo-oxidation (SPO) is proposed as a simple, fast, and scalable one-stop strategy that enables simultaneous self-patterning and sensitivity adjustment of ultrathin stretchable strain sensors. The SPO of an elastic substrate through irradiation time-controlled ultraviolet treatment in a confined region enables precise tuning of both the surface energy and the elastic modulus. SPO induces the hydrophilization of the substrate, thereby allowing the self-patterning of silver nanowires (AgNWs). In addition, it promotes the formation of nonpermanent microcracks of AgNWs/elastomer nanocomposites under the action of strain by increasing the elastic modulus. This effect improves sensor sensitivity by suppressing the charge transport pathway. Consequently, AgNWs are directly patterned with a width of 100 µm or less on the elastic substrate, and AgNWs/elastomer-based ultrathin and stretchable strain sensors with controlled sensitivity work reliably in various operating frequencies and cyclic stretching. Sensitivity-controlled strain sensors successfully detect both small and large movements of the human hand.

Heterologous overproduction of oviedomycin by refactoring biosynthetic gene cluster and metabolic engineering of host strain Streptomyces coelicolor.

BACKGROUND: Oviedomycin is one among several polyketides known for their potential as anticancer agents. The biosynthetic gene cluster (BGC) for oviedomycin is primarily found in Streptomyces antibioticus. However, because this BGC is usually inactive under normal laboratory conditions, it is necessary to employ systematic metabolic engineering methods, such as heterologous expression, refactoring of BGCs, and optimization of precursor biosynthesis, to allow efficient production of these compounds. RESULTS: Oviedomycin BGC was captured from the genome of Streptomyces antibioticus by a newly constructed plasmid, pCBA, and conjugated into the heterologous strain, S. coelicolor M1152. To increase the production of oviedomycin, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system was utilized in an in vitro setting to refactor the native promoters within the ovm BGC. The target promoters of refactoring were selected based on examination of factors such as transcription levels and metabolite profiling. Furthermore, genome-scale metabolic simulation was applied to find overexpression targets that could enhance the biosynthesis of precursors or cofactors related to oviedomycin production. The combined approach led to a significant increase in oviedomycin production, reaching up to 670 mg/L, which is the highest titer reported to date. This demonstrates the potential of the approach undertaken in this study. CONCLUSIONS: The metabolic engineering approach used in this study led to the successful production of a valuable polyketide, oviedomycin, via BGC cloning, promoter refactoring, and gene manipulation of host metabolism aided by genome-scale metabolic simulation. This approach can be also useful for the efficient production of other secondary molecules encoded by 'silent' BGCs.

Perilla frutescens Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation.

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether Perilla frutescens leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.

Species sensitivity distributions for ethylparaben to derive protective concentrations for soil ecosystems.

Ethylparaben is used as an antifungal preservative. Although some countries have implemented regulations for human exposure to parabens, environmental regulations for ethylparaben have not been established. This study provides new toxicological data for ethylparaben, for which data regarding soil organisms were previously lacking. Although ethylparaben toxicity has been reported in other species, we present herein the first comprehensive study of its toxicity in soil organisms. We used 12 test species (Lycopersicon esculentum, Vigna radiata, Hordeum vulgare, Oryza sativa, Eisenia andrei, Folsomia candida, Lobella sokamensis, Caenorhabiditis elegans, Chlamydomonas reinhardtii, Chlorococcum infusionum, Chlorella sorokiniana, Chlorella vulgaris) from eight taxonomic groups for acute bioassays and nine test species (L. esculentum, V. radiata, H. vulgare, O. sativa, C. reinhardtii, C. infusionum, C. sorokiniana, and C. vulgaris) from five taxonomic groups for chronic bioassays. A suite of acute and chronic toxicity tests, using 21 soil species, was conducted to estimate EC50 values, which facilitated the construction of species sensitivity distributions (SSDs) and the calculation of protective concentrations (PCs). Acute and chronic PC95 values (protective concentration for 95% of species) for ethylparaben were estimated to be 14 and 5 mg/kg dry soil, respectively. To the best of our knowledge, this is the first study to evaluate the toxicity of ethylparaben to soil species and derive PCs for soil ecosystems based on SSDs. Therefore, the data presented in this study can be used as a basis for further investigations of paraben toxicity to the soil environment.

Theoretical Investigation of Excited-State Intramolecular Proton Transfer and Photoisomerization of 2-(Iminomethyl)phenol.

Time-dependent density functional theory and high-level ab initio calculations were performed to investigate the excited-state intramolecular proton transfer (ESIPT) and subsequent isomerization of 2-(iminomethyl)phenol (IMP). According to the results of the correlated theoretical methods, ESIPT is a barrierless process; subsequently, the isomerization (rotation of the torsion angle) of IMP also readily occurs. Fictitious intermediates are found due to an insufficient theoretical level. The molecular structure of the conical intersection (CI) during the isomerization process is optimized, and its branching plane is characterized. Both the gradient difference vector and the derivative coupling vector are significantly correlated to the C═O and H2N-C antiparallel stretching coordinates, and the dynamic electron correlation effect is crucial to optimize the molecular structure of the real CI of IMP. The relaxation pathway from the CI in the S0 state was examined; the dominant pathway proceeds to the trans-keto form of IMP. However, if the C═O and H2N-C antiparallel stretching mode is sufficiently populated, then the reaction proceeds to the cis-keto form of IMP and can eventually recover to the cis-enol form.

Effect of UV and Water on Electrical Properties at Pre- and Post-Annealing Processes in Solution-Processed InGaZnO Transistors.

There are some reports related to applications of ultraviolet (UV) and water to enhance the electrical performance of metal oxide thin-film transistors (TFTs). We recently discovered that treatment timing and treatment method are also important for a good metal oxide thin-film formation. There are different influences on the metal oxide TFTs' electrical properties based on the UV irradiation and water treatment timing. The field-effect mobility of TFTs treated with UV-irradiation and water, which was spin-coated on the UV-irradiated film after pre-annealing, increased to 4.71 cm²V-1s-1 and 6.41 cm²V-1s-1. This was higher than the 3.39 cm²V-1s-1 field-effect mobility of non-treated TFTs. On the other hands, TFTs which were fabricated by the same method, with only varying the treatment time, after post-annealing, exhibited the tendency to show a decrease in field-effect mobility to 1.93 cm²V-1s-1 and 1.32 cm²V-1s-1, gradually, showing a contrasting tendency with the former conditions.

The effects of pain on quadriceps strength, joint proprioception and dynamic balance among women aged 65 to 75 years with knee osteoarthritis.

BACKGROUND: Patients with knee osteoarthritis (OA) were reported to have quadriceps weakness, and impaired proprioception, both related to pain and swelling. It is unclear whether pain alone a causal factor to above findings over the knee joint. The purpose of this study was to assess the effects of knee pain alone on the quadriceps strength, proprioception and dynamic balance in subjects with bilateral knee OA without joint swelling. METHODS: Fourty females with mean age of 68.3 years were involved in this cross-sectional study. The inclusion criteria were bilateral knee OA without joint swelling, with a visual analogue pain scale difference (> 1) between each knee. Patients all underwent assessment of the isokinetic strength of knee muscles, knee proprioceptive acuity, and dynamic balance. RESULTS: Patients' more painful knee had weaker isokinetic quadriceps strength than less painful knee at both 60 °/s and 180 °/s (p = 0.01, p = 0.01, respectively). There were no differences in proprioceptive acuity between both knees in all three knee positions. Meanwhile, there was a significant difference in the dynamic balance index measurement between both knees (more painful versus less painful: 3.88 ± 1.15 vs. 3.30 ± 1.00, p = 0.01). Quadriceps strength was associated with dynamic balance stability (60 °/s, r = - 0.578, p <  0.01; 180 °/s, r = - 0.439, p <  0.01). CONCLUSIONS: For patients with knee OA, the more painful knee was associated with weaker quadriceps and poor balance ability. To improve lower limb function and balance stability of the older persons having knee OA, physicians should take the optimal pain management strategy.

Effects of fluorine on crops, soil exoenzyme activities, and earthworms in terrestrial ecosystems.

Fluorine can flow into the environment after leakage or spill accidents and these excessive amounts can cause adverse effects on terrestrial ecosystems. Using three media (filter paper, soil, and filter-paper-on-soil), we investigated the toxic effects of fluorine on the germination and growth of crops (barley, mung bean, sorghum, and wheat), on the activities of soil exoenzymes (acid phosphatase, arylsulfatase, fluorescein diacetate hydrolase, and urease) and on the survival, abnormality, and cytotoxicity of Eisenia andrei earthworms. The germination and growth of crops were affected by fluorine as exposure concentration increased. The activities of the four enzymes after 0-, 3-, 10-, and 20-day periods varied as exposure concentration increased. According to in vivo and in vitro earthworm assays, E. andrei mortality, abnormality, and cytotoxicity increased with increasing fluorine concentration. Overall, fluorine significantly affected each tested species in the concentration ranges used in this study. The activities of soil exoenzymes were also affected by soil fluorine concentration, although in an inconsistent manner. Albeit the abnormally high concentrations of fluorine in soil compared to that observed under natural conditions, its toxicity was much restrained possibly due to the adsorption of fluorine on soil particles and its combination with soil cations.

Mixture Toxicity of Nickel and Microplastics with Different Functional Groups on Daphnia magna.

In recent years, discarded plastic has become an increasingly prevalent pollutant in aquatic ecosystems. These plastic wastes decompose into microplastics, which pose not only a direct threat to aquatic organisms but also an indirect threat via adsorption of other aquatic pollutants. In this study, we investigated the toxicities of variable and fixed combinations of two types of microplastics [one coated with a carboxyl group (PS-COOH) and the other lacking this functional group (PS)] with the heavy metal nickel (Ni) on Daphnia magna and calculated mixture toxicity using a toxic unit model. We found that toxicity of Ni in combination with either of the two microplastics differed from that of Ni alone. Furthermore, in general, we observed that immobilization of D. magna exposed to Ni combined with PS-COOH was higher than that of D. magna exposed to Ni combined with PS. Collectively, the results of our study indicate that the toxic effects of microplastics and pollutants may vary depending on the specific properties of the pollutant and microplastic functional groups, and further research on the mixture toxicity of various combinations of microplastics and pollutants is warranted.

Species Sensitivity Distributions for Nonylphenol to Estimate Soil Hazardous Concentration.

Nonylphenol is an endocrine-disrupting chemical that mimics estrogenic activity. Few studies have investigated the soil ecotoxicity of nonylphenol in the environment, based on probabilistic approaches. The present study generated soil toxicity data for nonylphenol through bioassays that determined the acute and chronic species sensitivity distributions and estimated the hazardous concentrations of nonylphenol in soil in order to protect soil ecosystems. We used eight soil-based organisms from six taxonomic groups for acute assays and five soil-based organisms from four taxonomic groups for chronic assays. The hazardous concentration values of nonylphenol in soil, based on acute and chronic species sensitivity distributions, were estimated using compiled data from the present study, as well as previous studies. This is the first study that generated sufficient data to develop species sensitivity distributions for nonylphenol in soil, and to determine hazardous concentrations of nonylphenol for soil environments.

The Inverse Relationship between Cardiorespiratory Fitness and Intima-Media Thickness with Prehypertensive Middle-Aged Women.

Individuals with prehypertension have a greater risk of developing hypertension and cardiovascular disease than those with normal blood pressure. Good cardiorespiratory fitness has been associated with a reduced risk for cardiovascular diseases, but whether it is related to slower progression of early atherosclerosis is unclear. We evaluated 442 women, aged 40-60 years, with resting systolic blood pressure 120-139 mmHg and diastolic blood pressure 80-89 mmHg, defined as prehypertension in cross-sectional study. Blood glucose, blood lipids and carotid intima-media thickness (CIMT) were measured at rest. Cardiorespiratory fitness (VO2peak) was measured by respiratory gas exchange during a treadmill exercise test. Participants were divided into three cardiorespiratory fitness levels: low, moderate, and high. The prevalence of subclinical carotid atherosclerosis was defined as a mean carotid intima-media thickness greater than the 75th percentile. After adjustment for various confounders, a high cardiorespiratory fitness level was associated with significantly lower SBP, DBP and CIMT compared with low and moderate fitness (p < 0.05). After adjustment for established risk factors, high and moderate fitness were each associated with significantly lower odds ratios for carotid atherosclerosis 0.74 (95% CI 0.45-0.92) and 0.70 (95% CI 0.46-0.95), respectively, compared with low fitness. Our results indicate that good cardiorespiratory fitness is associated with a slower progression of early atherosclerosis in middle-aged women. These findings are important, because they emphasize that middle-aged women can be evaluated for cardiorespiratory fitness to estimate their future risk for atherosclerotic vascular diseases.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Nonlinear Transport in Organic Thin Film Transistors with Soluble Small Molecule Semiconductor.

Nonlinear transport is intensively explained through Poole-Frenkel (PF) transport mechanism in organic thin film transistors with solution-processed small molecules, which is, 6,13-bis(triisopropylsilylethynyl) (TIPS) pentacene. We outline a detailed electrical study that identifies the source to drain field dependent mobility. Devices with diverse channel lengths enable the extensive exhibition of field dependent mobility due to thermal activation of carriers among traps.

Cardiorespiratory fitness and incident metabolic syndrome in middle-aged Korean men.

This study investigated the relationship of cardiorespiratory fitness (CRF) with incident metabolic syndrome in 810 middle aged Korean men. All subjects were free of metabolic syndrome at baseline examination. The metabolic syndrome was defined by NCEP criteria and CRF was directly measured by peak oxygen uptake during a treadmill test. During an average of 3.3 years of follow-up, 155 (19.1%) men developed the metabolic syndrome. The incidence of metabolic syndrome was inversely associated with CRF quartiles (p < 0.05). The relative risk (RR) of incident metabolic syndrome in the lowest CRF quartile vs the highest CRF quartile was 1.67 (95% CI = 1.07-2.60) after adjustment for covariates. Each metabolic equivalent (MET) increment in peak oxygen consumption was associated with a 17% (RR = 0.83, 95% CI = 0.73-0.94) lower incidence of metabolic syndrome. These results demonstrate that cardiorespiratory fitness was associated with the incidence of metabolic syndrome independent of covariates in middle aged Korean men.

Evidence of soil particle-induced ecotoxicity in old abandoned mining area.

Ecotoxicity of heavy metals in soil is primarily associated with their bioaccessibility and bioavailability in the soil media. However, in some exceptional cases, soil ecotoxicity has been observed despite high total metal concentrations and low extractable metal concentrations in contaminated field sites; therefore, other exposure pathways must be considered. Therefore, the aim of this study was to evaluate the soil-particle induced ecotoxicity in an old mining area. We hypothesized that heavy metals, strongly adsorbed onto soil particles of consumable size for soil organisms, exhibit ecotoxicity, especially on soil particles ∼1 µm to 300 µm in size. A plant seedling assay, in vivo cytotoxicity assay using earthworm immune cells, and a metal bioconcentration assessment were performed. The results of soil particle toxicity revealed that the soil from the study area (A1-A4) had a low contribution to the soil ecotoxicity of extractable metals. For instance, the concentration of extractable arsenic was only 1.9 mg/kg soil, despite the total arsenic concentration reaching 36,982 mg/kg soil at the A1 site. The qualitative and quantitative analyses using SEM-EDX and ICP-OES, as well as principal component analyses, supported the hypothesis of the present study. Overall, the study results emphasize the importance of soil particle-induced ecotoxicity in long-term contaminated field soils. Our study results can inform on effective site-specific soil ecological risk assessment as they suggest the inclusion of soil particle-induced ecotoxicity as an important criterion in old, contaminated field sites, even when the extractable metal fraction in the field soil is low. ENVIRONMENTAL IMPLICATION: Bioaccessibility and bioavailability are primary factors contributing to the soil ecotoxicity of heavy metals. However, in some cases, such as long-term contaminated field sites, soil ecotoxicity has been confirmed even when low extractable metal concentrations were detected alongside high total metal concentrations. The findings of this study reveal that soil particles of edible size could be sources of soil ecotoxicity in the case of long-term contaminated fields with low extractable metal concentrations. The results of this study would contribute to the area of site-specific soil ecological risk assessment.

Analyzing species sensitivity distribution of evidently edible microplastics for freshwater biota.

Assessing the ecological risks of microplastics is difficult because of the limited availability of reliable ecotoxicity data. Although freshwater is a valuable sink for microplastics, the current framework for ecological risk assessment using traditional toxicity data is not applicable to freshwater ecosystems. Herein, species sensitivity distribution (SSD) curves were compared for edible and all microplastics exposed to aquatic organisms based on traditional endpoint-based and all-endpoint-based databases. Freshwater toxicity data for microplastics were screened after verifying microplastic presence in test species (56 toxicity datapoints for one microalga, three water fleas, one fish, and one crab; 0.02-100 µm-sized microplastics). SSD and curve parameters were compared with or without non-traditional toxicity endpoints. The HC50 in all endpoint databases was more sensitive than that in the traditional endpoint database and showed a good fit. SSD curves derived from the database for all microplastics were compared and analyzed with edible microplastics. HCx increased for edible microplastics (0.02-100 µm-sized) than for all microplastics (0.02-200 µm-sized), and the size of edible microplastics was lower than of all microplastics. Thus, using non-traditional toxicity data, the SSD approach compensates for the limited ecotoxicity data on microplastics while considering the internalization of microplastics in biota.

Evidence of parental transfer of nanoplastics in pea (Pisum sativum) plants.

The increasing abundance of nanoplastics in the environment is a cause of serious concern and its acute and chronic effects on ecosystems need to be thoroughly investigated. Toward this end, this study investigated the parental transfer of nanoplastics by chronically exposing Pisum sativum (pea) plants to nanoplastics through soil medium. We observed the presence of nanoplastics in harvested fruits and a subsequent generation of plants replanted in uncontaminated soil using confocal laser scanning microscopy. The fluorescence was located in the cell wall of the vascular bundles, but not in the epidermis, indicating the parental transfer of nanoplastics. In addition, we determined the effects of nanoplastics on the health of subsequent plant generations by estimating the reproductive factors and measuring the content of individual nutrients in peas. Decreases in crop yield and fruit biomass, in addition to changes in nutrient content and composition, were noted. The transgenerational effects of nanoplastics on plants can profoundly impact terrestrial ecosystems, including both plant species and their predators, raising critical safety concerns. Our findings highlight the evidence of parental transfer of nanoplastics in the soil through plants and shows that the chronic effects of nanoplastics on plants may pose a threat to the food supply.

Microplastic ingestion in aquatic and soil biota: A comprehensive review of laboratory studies on edible size and intake pattern.

Microplastic contamination is ubiquitous and can be transferred through the food chain to humans. However, studies on microplastic size have mainly focused on large animals with a body length >20 mm. To address this gap, we conducted a comprehensive review of 169 laboratory studies to determine the edible size of microplastics for macrofauna and flora in aquatic and soil biota. Our findings indicate that microplastics with a size of <300 µm and 1 µm, respectively, are edible for these organisms, which are positioned at the base of the food chain. We also analyzed intake and depuration patterns and identified factors affecting microplastic ingestion. Our study fills an important knowledge gap by identifying the range of microplastic sizes that can enter the food chain and be transferred to humans. The study findings have strong implications for the ecological risk assessment of microplastics and suggest a starting point for mitigating this threat.

Dependence of Positive Bias Stress Instability on Threshold Voltage and Its Origin in Solution-Processed Aluminum-Doped Indium Oxide Thin-Film Transistors.

The initial electrical characteristics and bias stabilities of thin-film transistors (TFTs) are vital factors regarding the practical use of electronic devices. In this study, the dependence of positive bias stress (PBS) instability on an initial threshold voltage (VTH) and its origin were analyzed by understanding the roles of slow and fast traps in solution-processed oxide TFTs. To control the initial VTH of oxide TFTs, the indium oxide (InOx) semiconductor was doped with aluminum (Al), which functioned as a carrier suppressor. The concentration of oxygen vacancies decreased as the Al doping concentration increased, causing a positive VTH shift in the InOx TFTs. The VTH shift (∆VTH) caused by PBS increased exponentially when VTH was increased, and a distinct tendency was observed as the gate bias stress increased due to a high vertical electric field in the oxide dielectric. In addition, the recovery behavior was analyzed to reveal the influence of fast and slow traps on ∆VTH by PBS. Results revealed that the effect of the slow trap increased as the VTH moved in the positive direction; this occured because the main electron trap location moved away from the interface as the Fermi level approached the conduction band minimum. Understanding the correlation between VTH and PBS instability can contribute to optimizing the fabrication of oxide TFT-based circuits for electronic applications.