Caenorhabditis elegans deep lipidome profiling by using integrative mass spectrometry acquisitions reveals significantly altered lipid networks.

Lipidomics coverage improvement is essential for functional lipid and pathway construction. A powerful approach to discovering organism lipidome is to combine various data acquisitions, such as full scan mass spectrometry (full MS), data-dependent acquisition (DDA), and data-independent acquisition (DIA). Caenorhabditis elegans (C. elegans) is a useful model for discovering toxic-induced metabolism, high-throughput drug screening, and a variety of human disease pathways. To determine the lipidome of C. elegans and investigate lipid disruption from the molecular level to the system biology level, we used integrative data acquisition. The methyl-tert-butyl ether method was used to extract L4 stage C. elegans after exposure to triclosan (TCS), perfluorooctanoic acid, and nanopolystyrene (nPS). Full MS, DDA, and DIA integrations were performed to comprehensively profile the C. elegans lipidome by Q-Exactive Plus MS. All annotated lipids were then analyzed using lipid ontology and pathway analysis. We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways. The biological investigations revealed that when C. elegans were exposed to nPS, lipid droplets were disrupted, whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group. The nPS treatment caused a significant disruption in lipid storage. Triacylglycerol, glycerophospholipid, and ether class lipids were those primarily hindered by toxicants. Finally, toxicant exposure frequently involved numerous lipid-related pathways, including the phosphoinositide 3-kinase/protein kinase B pathway. In conclusion, an integrative data acquisition strategy was used to characterize the C. elegans lipidome, providing valuable biological insights into hypothesis generation and validation.

Metabolic and Cardiovascular Benefits of Apple and Apple-Derived Products: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Quantitative evidence of the metabolic and cardiovascular effects of apples (Malus domestica) is lacking in interventional studies. This study aimed to summarize the available evidence of the beneficial effects of apples and apple-derived products (ADPs) on metabolic and cardiovascular markers. Methods: Peer-reviewed randomized controlled trials (RCTs) were identified from four databases on May 3, 2021 and regularly updated until the end of May 2021. Demographic characteristics, intervention types, and evaluation parameters were extracted. A meta-analysis on the mean difference of change scores was conducted on commonly presented outcomes in the RCTs. Results: The metabolic and cardiovascular effects of diverse regimens, including whole apple, apple extract, and apple juice, were examined in 18 eligible RCTs. Nine common evaluation outcomes were eventually introduced to the meta-analysis, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, glucose, insulin, C-reactive protein, and systolic/diastolic blood pressures. The levels of TC (-2.69 mg/dL; 95% CI: -5.43, 0.04 mg/dL) and LDL (-2.80 mg/dL; 95% CI: -5.78, 0.17 mg/dL) showed a non-significant decreasing tendency after at least a week of apple consumption. Further subgroup analysis, particularly, a comparison with placebo as a control, showed a significant reduction in TC and LDL levels. When stratified by the baseline level, subjects with high TC and LDL level were shown to have more benefits from the apple intake. Intriguingly, apple and ADPs significantly reduced HDL levels to a small extent (-1.04 mg/dL; 95% CI: -1.79, -0.29 mg/dL). The other markers were mostly unaffected by the intervention. Conclusion: Our investigation revealed that apples could improve blood cholesterol levels. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020215977].

Amodiaquine promotes testosterone production and de novo synthesis of cholesterol and triglycerides in Leydig cells.

Testosterone is a hormone essential for male reproductive function. It is produced primarily by Leydig cells in the testicle through activation of steroidogenic acute regulatory protein and a series of steroidogenic enzymes, including a cytochrome P450 side-chain cleavage enzyme (cytochome P450 family 11 subfamily A member 1), 17α-hydroxylase (cytochrome P450 family 17 subfamily A member 1), and 3ß-hydroxysteroid dehydrogenase. These steroidogenic enzymes are mainly regulated at the transcriptional level, and their expression is increased by the nuclear receptor 4A1. However, the effect on Leydig cell function of a small molecule-activating ligand, amodiaquine (AQ), is unknown. We found that AQ effectively and significantly increased testosterone production in TM3 and primary Leydig cells through enhanced expression of steroidogenic acute regulatory protein, cytochome P450 family 11 subfamily A member 1, cytochrome P450 family 17 subfamily A member 1, and 3ß-hydroxysteroid dehydrogenase. Concurrently, AQ dose-dependently increased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in the cholesterol synthesis pathway, through induction of the transcriptional and DNA-binding activities of nuclear receptor 4A1, contributing to increased cholesterol synthesis in Leydig cells. Furthermore, AQ increased the expression of fatty acid synthase and diacylglycerol acyltransferase and potentiated de novo synthesis of fatty acids and triglycerides (TGs). Lipidomics profiling further confirmed a significant elevation of intracellular lipid and TG levels by AQ in Leydig cells. These results demonstrated that AQ effectively promotes testosterone production and de novo synthesis of cholesterol and TG in Leydig cells, indicating that AQ may be beneficial for treating patients with Leydig cell dysfunction and subsequent testosterone deficiency.

Analysis of Interface Phenomena for High-Performance Dual-Stacked Oxide Thin-Film Transistors via Equivalent Circuit Modeling.

Oxide thin-film transistors (TFTs) have attracted much attention because they can be applied to flexible and large-scaled switching devices. Especially, oxide semiconductors (OSs) have been developed as active layers of TFTs. Among them, indium-gallium-zinc oxide (IGZO) is actively used in the organic light-emitting diode display field. However, despite their superior off-state properties, IGZO TFTs are limited by low field-effect mobility, which critically affects display resolution and power consumption. Herein, we determine new working mechanisms in dual-stacked OS, and based on this, we develop a dual-stacked OS-based TFT with improved performance: high field-effect mobility (∼80 cm2/V·s), ideal threshold voltage near 0 V, high on-off current ratio (>109), and good stability at bias stress. Induced areas are formed at the interface by the band offset: band offset-induced area (BOIA) and BOIA-induced area (BIA). They connect the gate bias-induced area (GBIA) and electrode bias-induced area (EBIA), resulting in high current flow. Equivalent circuit modeling and the transmission line method are also introduced for more precise verification. By verifying current change with gate voltage in the single OS layer, the current flowing direction in the dual-stacked OS is calculated and estimated. This is powerful evidence to understand the conduction mechanism in a dual-stacked OS-based TFT, and it will provide new design rules for high-performance OS-based TFTs.

Systematic Review of Recent Lipidomics Approaches Toward Inflammatory Bowel Disease.

Researchers have endeavored to identify the etiology of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Though the pathogenesis of inflammatory bowel diseases remains unknown, dysregulation of the immune system in the host gastrointestinal tract is believed to be the major causative factor. Omics is a powerful methodological tool that can reveal biochemical information stored in clinical samples. Lipidomics is a subset of omics that explores the lipid classes associated with inflammation. One objective of the present systematic review was to facilitate the identification of biochemical targets for use in future lipidomic studies on inflammatory bowel diseases. The use of high-resolution mass spectrometry to observe alterations in global lipidomics might help elucidate the immunoregulatory mechanisms involved in inflammatory bowel diseases and discover novel biomarkers for them. Assessment of the characteristics of previous clinical trials on inflammatory bowel diseases could help researchers design and establish patient selection and analytical method criteria for future studies on these conditions. In this study, we curated literature exclusively from four databases and extracted lipidomics-related data from literature, considering criteria. This paper suggests that the lipidomics approach toward research in inflammatory bowel diseases can clarify their pathogenesis and identify clinically valuable biomarkers to predict and monitor their progression.

N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application.

Active c-Src non-receptor tyrosine kinase localizes to the plasma membrane via N-terminal lipid modification. Membranous c-Src causes cancer initiation and progression. Even though transmembrane 4 L six family member 5 (TM4SF5), a tetraspan(in), can be involved in this mechanism, the molecular and structural influence of TM4SF5 on c-Src remains unknown. Methods: Here, we investigated molecular and structural details by which TM4SF5 regulated c-Src devoid of its N-terminus and how cell-penetrating peptides were able to interrupt c-Src activation via interference of c-Src-TM4SF5 interaction in hepatocellular carcinoma models. Results: The TM4SF5 C-terminus efficiently bound the c-Src SH1 kinase domain, efficiently to the inactively-closed form. The complex involved protein tyrosine phosphatase 1B able to dephosphorylate Tyr530. The c-Src SH1 domain alone, even in a closed form, bound TM4SF5 to cause c-Src Tyr419 and FAK Y861 phosphorylation. Homology modeling and molecular dynamics simulation studies predicted the directly interfacing residues, which were further validated by mutational studies. Cell penetration of TM4SF5 C-terminal peptides blocked the interaction of TM4SF5 with c-Src and prevented c-Src-dependent tumor initiation and progression in vivo. Conclusions: Collectively, these data demonstrate that binding of the TM4SF5 C-terminus to the kinase domain of inactive c-Src leads to its activation. Because this binding can be abolished by cell-penetrating peptides containing the TM4SF5 C-terminus, targeting this direct interaction may be an effective strategy for developing therapeutics that block the development and progression of hepatocellular carcinoma.

Conductive Polymer-Assisted Metal Oxide Hybrid Semiconductors for High-Performance Thin-Film Transistors.

Metal oxide semiconductors doped with additional inorganic cations have insufficient electron mobility for next-generation electronic devices so strategies to realize the semiconductors exhibiting stability and high performance are required. To overcome the limitations of conventional inorganic cation doping to improve the electrical characteristics and stability of metal oxide semiconductors, we propose solution-processed high-performance metal oxide thin-film transistors (TFTs) by incorporating polyaniline (PANI), a conductive polymer, in a metal oxide matrix. The chemical interaction between the metal oxide and PANI demonstrated that the defect sites and crystallinity of the semiconductor layer are controllable. In addition, the change in oxygen-related chemical bonding of PANI-doped indium oxide (InOx) TFTs induces superior electrical characteristics compared to pristine InOx TFTs, even though trace amounts of PANI are doped in the semiconductor. In particular, the average field-effect mobility remarkably enhanced from 15.02 to 26.58 cm2 V-1 s-1, the on/off current ratio improved from 108 to 109, and the threshold voltage became close to 0 V actually from -7.9 to -1.4 V.

The effect of surface energy characterized functional groups of self-assembled monolayers for enhancing the electrical stability of oxide semiconductor thin film transistors.

The exact direction of the surface energy characterized functional groups of self-assembled monolayers (SAMs) is proposed for achieving enhanced electrical stability of indium gallium zinc oxide (IGZO) semiconductor thin film transistors (TFTs). The SAM treatment, particularly with the SAM functional group having lower surface energy, makes it difficult to adsorb oxygen molecules difficult onto IGZO. Such an effect greatly improves the positive bias stability (PBS) and clockwise hysteresis stability. For NH2 and CF3 functional groups, SAMs with surface energies of 49.4 mJ m-2 and 23.5 mJ m-2, respectively, improved the IGZO TFT PBS from 2.47 V to 0.32 V after the SAM treatment and the IGZO TFT clockwise hysteresis was also enhanced from 0.23 V to 0.11 V without any deterioration of TFT characteristics. Employing lower surface energy functional groups to the SAM, of the same head and body groups, passivates and protects the IGZO backchannel region from oxygen molecules in the atmosphere. Consequently, the enhanced electrical stability of IGZO TFTs can be achieved by the simple and economic SAM treatment.

The effect of Surface energy characterized functional group of self-assembled monolayer for enhancing electrical stability of oxide semiconductor thin film transistor.

The exact direction, of the surface energy characterized functional group of self-assembled monolayer (SAM), is proposed for achieving the enhanced electrical stability of indium gallium zinc oxide (IGZO) semiconductor thin film transistor (TFT). The SAM treatment, particularly at the SAM functional group having lower surface energy, makes oxygen molecules difficult to be adsorbed onto IGZO. And such an effect much improves positive bias stability (PBS) and clockwise hysteresis stability to the same tendency. For NH2 and CF3 functional group SAMs with surface energies of 49.4 mJ/m2 and 23.5 mJ/m2, respectively, the IGZO TFT PBS was improved from 2.47 V to 0.32 V after the SAM treatment and the IGZO TFT clockwise hysteresis was also enhanced from 0.23 V to 0.11 V without any deterioration of TFT characteristics. Employing lower surface energy functional group to the SAM, of same head group and body group, does passivate and protect the IGZO backchannel region from oxygen molecules in the atmosphere. Consequently, the enhanced electrical stability of IGZO TFT can be achieved by the simple and economic SAM treatment.

Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials.

Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention. This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline, randomized controlled trials on the effects of ginger were investigated. Accordingly, 109 eligible papers were fully extracted in terms of study design, population characteristics, evaluation systems, adverse effects, and main outcomes. The reporting quality of the included studies was assessed based on the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials and integrated together with studies that investigated the same subjects. The included studies that examined the improvement of nausea and vomiting in pregnancy, inflammation, metabolic syndromes, digestive function, and colorectal cancer's markers were consistently supported, whereas other expected functions were relatively controversial. Nevertheless, only 43 clinical trials (39.4%) met the criterion of having a 'high quality of evidence.' In addition to the quality assessment result, small populations and unstandardized evaluation systems were the observed shortcomings in ginger clinical trials. Further studies with adequate designs are warranted to validate the reported clinical functions of ginger.

Atmospheric-pressure plasma treatment toward high-quality solution-processed aluminum oxide gate dielectric films in thin-film transistors.

We present an atmospheric-pressure plasma (APP) treatment technique to improve the electrical performance of solution-processed dielectric films. This technique can successfully reduce leakage current and frequency dependence of solution-processed dielectric films. The APP treatment contributes to the conversion of metal hydroxide to metal oxide, and in the case of a solution-treated AlO x dielectric thin film, it effectively ascribes to the formation of high-quality AlO x dielectric thin films. The capacitance of the untreated AlO x dielectric thin film varies up to 9.9% with frequency change, but the capacitance of the APP treated AlO x dielectric thin film varies within 1.5%. When the solution-processed InO x thin-film transistors (TFTs) were fabricated using these dielectric films, the field-effect mobility of TFTs with the APP-treated AlO x dielectric film was increased significantly from 9.77 to 26.79 cm2 V-1 s-1 in comparison to that of TFTs with the untreated AlO x dielectric film. We also have confirmed that these results are similar to the properties of the sample prepared at high annealing temperature including electrical performance, conduction mechanism and chemical structure. The APP treatment technique provides a new opportunity to effectively improve the electrical performance of solution-processed dielectrics in the atmosphere at low temperature.

Solution-Grown Homojunction Oxide Thin-Film Transistors.

Growing attention has been given to low temperature, solution-processed metal oxide thin-film transistors because they can be applied in the emerging sector of flexible and large-scale electronics. However, major obstacles of solution-grown devices, such as their relatively low field-effect mobility and the difficulty of controlling carrier concentration, limit the further advancement of the electronics. Here, we overcome these constraints through a newly renovated structure, called a "homojunction", consisting of double-stacked semiconductors with same material. The homojunction oxide thin-film transistor has remarkable electrical performance with controllability, for example, tunable turn-on voltage (-80 V to -8 V) and high average field-effect mobility (∼50 cm2/V·s) are obtained via a low annealing temperature process (250 °C). Furthermore, notable achievements associated with stability, reliability, and uniformity are verified. These results are attributed to the unique phenomena of solution-grown thin films: the change of both chemical and physical properties of thin films. Our findings highlight that the thin films of high quality can be yielded through the solution process at low annealing temperatures, and thus solution-grown transistors hold great promise for widespread industrial applications.