Steroidogenic cytochrome P450 enzymes as drug target.

Human cytochrome P450 (CYP) enzymes are composed of 57 individual enzymes that perform monooxygenase activities. They have diverse physiological roles in metabolizing xenobiotics and producing important endogenous compounds, such as steroid hormones and vitamins. At least seven CYP enzymes are involved in steroid biosynthesis. Steroidogenesis primarily occurs in the adrenal glands and gonads, connecting each reaction to substrates and products. Steroids are essential for maintaining life and significantly contribute to sexual differentiation and reproductive functions within the body. Disorders in steroid biosynthesis can frequently cause serious health problems and lead to the development of diseases, such as prostate cancer, breast cancer, and Cushing's syndrome. In this review, we provide current updated knowledge on the major CYP enzymes involved in the biosynthetic process of steroids, with respect to their enzymatic mechanisms and clinical implications for the development of new drug candidates.

Structural Insights into the Interaction of Terpenoids with Streptomyces avermitilis CYP107P2.

Streptomyces avermitilis genome includes 33 genes encoding monooxygenation-catalyzing cytochrome P450 enzymes. We investigated the structure of CYP107P2 and its interactions with terpenoid compounds. The recombinant CYP107P2 protein was expressed in Escherichia coli and the purified enzyme exhibited a typical P450 spectrum upon CO-binding in its reduced state. Type-I substrate-binding spectral titrations were observed with various terpenoid compounds, including α-pinene, ß-pinene, α-terpinyl acetate, and (+)-3-carene. The calculated binding affinities (Kd) ranged from 15.9 to 50.8 µM. The X-ray crystal structure of CYP107P2 was determined at 1.99 Å resolution, with a well-conserved overall P450 folding conformation. The terpenoid compound docking models illustrated that the structural interaction between monoterpenes and CYP107P2, with the distance between heme and terpenes ranging from 3.4 to 5.4 Å, indicates potential substrate binding for P450 enzyme. This study suggests that CYP107P2 is a Streptomyces P450 enzyme capable of catalyzing terpenes as substrates, signifying noteworthy advancements in comprehending a novel P450 enzyme's involvement in terpene reactions.

NiAlFe LTH /MoS2 p-n junction heterostructure composite as an effective visible-light-driven photocatalyst for enhanced degradation of organic dye under high alkaline conditions.

Designing of an effectual heterostructure photocatalyst for catalytic organic pollutant exclusion has been the subject of rigorous research intended to resolve the related environmental aggravation. Fabricating p-n junctions is an effective strategy to promote electron-hole separation of semiconductor photocatalysts as well as enhance the organic toxin degradation performance. In this study, a series of n-type NiAlFe-layered triple hydroxide (LTH) loaded with various ratios of p-type MoS2 was synthesized for forming a heterostructure LTH/MoS2 (LMs) by an in situ hydrothermal strategy. The photocatalysts were characterized by XRD, SEM&EDX, TEM, FT-IR, XPS, as well as UV-vis DRS. The photoactivity of photocatalysts was tested by the degradation of Indigo Carmine (IC) dye. The optimized catalyst (LM1) degrades 100% of indigo dye in high alkaline pH under UV light for 100 min. Besides, the degradation rate of LM1 is 15 times higher than that of pristine NiAlFe-LTH. The enhanced photoactivity is attributed to the synergistic effect between NiAlFe-LTH and MoS2 as well as the p-n junction formation.

Non-destructive monitoring and prediction of fouling by organic matters and residual anionic coagulant during membrane process.

Physical fouling characteristics on silicon carbide (SiC) membranes induced by various organic matter compounds vary depending on the presence of calcium ions (Ca2+). Both destructive techniques (morphological surface analysis) and non-destructive techniques (fouling properties monitoring) were used to determine the fouling mechanisms and behavior during the membrane filtration systems. Destructive analysis and a modified Hermia model were employed to assess the fouling mechanisms. Fouling behavior was also analyzed through non-destructive monitoring techniques including optical coherence tomography (OCT) and three-dimensional laser scanning confocal microscopy (3D-LSM). At concentrations of 10, 30, and 100 mg/L without Ca2+, the flux decreased by 57-95% for humic acid (HA) and anionic polyacrylamide (APAM). APAM exhibited a notable removal rate of up to 56% without Ca2+. At concentration of 10, 30, and 100 mg/L in the absence of Ca2+, the flux decreased by 6-8% for sodium alginate (SA). However, the addition of Ca2+ led to a reduction in the flux for SA by up to 91% and resulted in a removal rate of 40%. Furthermore, addition of Ca2+ led to an alteration of the fouling characteristics of HA and SA. In the case of HA, higher concentrations resulted in elevated thickness and roughness with correlation coefficients of 0.991 and 0.992, respectively. For SA, increased SA concentration led to a thicker (correlation coefficient of 0.999) but smoother surfaces (correlation coefficients of 0.502). Monitoring of these physical characteristics of the fouling layer through non-destructive analysis is crucial for effective fouling management, optimization of the system performance and extending the lifespan of the membrane. By continuously assessing the fouling layer thickness and surface roughness, we expect to be able to provide insights on the fouling behavior, identify trends, that can help scientists and engineers to make informed decisions regarding fouling control strategies in future.

Catalytic enhancements in cytochrome P450 2C19 by cytochrome b5.

Human cytochrome P450 2C19 catalyzes P450 enzyme reactions of various substrates, including steroids and clinical drugs. Recombinant P450 2C19 enzyme with histidine tag was successfully expressed in Escherichia coli and purified using affinity column chromatography. Ultra-performance liquid chromatography-tandem mass (UPLC-MS/MS) spectrometry showed that the purified P450 2C19 enzyme catalyzed 5-hydroxylation reaction of omeprazole. The purified enzyme displayed typical type I binding spectra to progesterone with a Kd value of 4.5 ± 0.2 µM, indicating a tight substrate binding. P450 2C19 catalyzed the hydroxylation of progesterone to produce 21-hydroxy (OH) as a major and 17-OH product as a minor product. Steady-state kinetic analysis of progesterone 21-hydroxylation indicated that the addition of cytochrome b5 stimulated a five-times catalytic turnover number of P450 2C19 with a kcat value of 1.07 ± 0.08 min-1. The molecular docking model of progesterone in the active site of P450 2C19 displayed that the 21-carbon of progesterone was located close to the heme with a distance of 4.7 Å, suggesting 21-hydroxylation of progesterone is the optimal reaction of P450 2C19 enzyme for a productive orientation of the substrate. Our findings will help investigate the extent to which cytochrome b5 affects the metabolism of P450 2C19 to drugs and steroids. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00219-8.

Stable and High-performance Flow H2-O2 Fuel Cells with Coupled Acidic Oxygen Reduction and Alkaline Hydrogen Oxidation Reactions.

Conventional H2-O2 fuel cells suffer from the low output voltage, insufficient durability, and high-cost catalysts (e.g., noble metals). Herein, this work reports a conceptually new coupled flow fuel cell (CF-FC) by coupling asymmetric electrolytes for acidic oxygen reduction reaction and alkaline hydrogen oxidation reaction. By introducing an electrochemical neutralization energy, the newly-developed CF-FCs possess a significantly increased theoretical open-circuit voltage. Specifically, a CF-FC based on a typical transition metal single-atom Fe-N-C cathode catalyst demonstrates a high electricity output up to 1.81 V and durability with an ultrahigh retention of 91% over 110 h, far superior to the conventional fuel cells (usually, < 1.0 V, < 50% retention over 20 h). The output performance can even be significantly enhanced easily by connecting multiple CF-FCs into the parallel, series, or combined parallel-series connections at a fractional cost of that for the conventional H2-O2 fuel cells, showing great potential for large-scale practical applications. Thus, this study provides a platform to transform conventional fuel cell technology through the rational design and development of advanced energy conversion and storage devices by coupling different electrocatalytic reactions.

Machine learning analysis to interpret the effect of the photocatalytic reaction rate constant (k) of semiconductor-based photocatalysts on dye removal.

Photocatalytic reactions with semiconductor-based photocatalysts have been investigated extensively for application to wastewater treatment, especially dye degradation, yet the interactions between different process parameters have rarely been reported due to their complicated reaction mechanisms. Hence, this study aims to discern the impact of each factor, and each interaction between multiple factors on reaction rate constant (k) using a decision tree model. The dyes selected as target pollutants were indigo and malachite green, and 5 different semiconductor-based photocatalysts with 17 different compositions were tested, which generated 34 input features and 1527 data points. The Boruta Shapley Additive exPlanations (SHAP) feature selection for the 34 inputs found that 11 inputs were significantly important. The decision tree model exhibited for 11 input features with an R2 value of 0.94. The SHAP feature importance analysis suggested that photocatalytic experimental conditions, with an importance of 59%, was the most important input category, followed by atomic composition (39%) and physicochemical properties (2%). Additionally, the effects on k of the synergy between the metal cocatalysts and important experimental conditions were confirmed by two feature SHAP dependence plots, regardless of importance order. This work provides insight into the single and multiple factors that affect reaction rate and mechanism.

Concurrent oxygen reduction and water oxidation at high ionic strength for scalable electrosynthesis of hydrogen peroxide.

Electrosynthesis of hydrogen peroxide via selective two-electron transfer oxygen reduction or water oxidation reactions offers a cleaner, cost-effective alternative to anthraquinone processes. However, it remains a challenge to achieve high Faradaic efficiencies at elevated current densities. Herein, we report that oxygen-deficient Pr1.0Sr1.0Fe0.75Zn0.25O4-δ perovskite oxides rich of oxygen vacancies can favorably bind the reaction intermediates to facilitate selective and efficient two-electron transfer pathways. These oxides exhibited superior Faradic efficiencies (~99%) for oxygen reduction over a wide potential range (0.05 to 0.45 V versus reversible hydrogen electrode) and current densities surpassing 50 mA cm-2 under high ionic strengths. We further found that the oxides perform a high selectivity (~80%) for two-electron transfer water oxidation reaction at a low overpotential (0.39 V). Lastly, we devised a membrane-free electrolyser employing bifunctional electrocatalysts, achieving a record-high Faradaic efficiency of 163.0% at 2.10 V and 50 mA cm-2. This marks the first report of the concurrent oxygen reduction and water oxidation catalysed by efficient bifunctional oxides in a novel membrane-free electrolyser for scalable hydrogen peroxide electrosynthesis.

Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Near-surface termination of upward-propagating strike-slip ruptures on the Yangsan Fault, Korea.

We present a new example of the termination of strike-slip paleoearthquake ruptures in near-surface regions on the Yangsan Fault, Korea, based on multi-scale structural observations. Paleoearthquake ruptures occur mostly along the boundary between the inherited fault core and damage zone (N10-20°E/> 75°SE). The ruptures propagated upward to the shallow subsurface along a < 3-cm-wide specific slip zone with dextral-slip sense, along which the deformation mechanism is characterized mainly by granular flow in near-surface region. The ruptures either reach the surface or are terminated in unconsolidated sediment below the surface. In the latter case, the rupture splays show westward bifurcation, and their geometry and kinematics show a change to NNW-strike with low-angle dip and dextral-reverse oblique-slip sense in the strata. We suggest that the upward termination of the contractional strike-slip ruptures is controlled by the inherited fault geometry that is unfavorable with respect to the stress field (ENE-WSW σHmax) at basement depths in terms of movement on the fault, and the lack of extension of the fault into shallow subsurface; a depth-dependent change in stress from σHmax > σv > σHmin to σHmax > σHmin > σv at depth of a ~ 200 m; and the physical properties of unconsolidated sediment, which have low inter-granular cohesion, resulting in distributed deformation.

Functional Characterization of Allelic Variations of Human Cytochrome P450 2C8 (V181I, I244V, I331T, and L361F).

The human cytochrome P450 2C8 is responsible for the metabolism of various clinical drugs as well as endogenous fatty acids. Allelic variations can significantly influence the metabolic outcomes. In this study, we characterize the functional effects of four nonsynonymous single nucleotide polymorphisms *15, *16, *17, and *18 alleles recently identified in cytochrome P450 2C8. The recombinant allelic variant enzymes V181I, I244V, I331T, and L361F were successfully expressed in Escherichia coli and purified. The steady-state kinetic analysis of paclitaxel 6-hydroxylation revealed a significant reduction in the catalytic activities of the V181I, I244V, and L361F variants. The calculated catalytic efficiency (kcat/Km) of these variants was 5-26% of that of the wild-type enzyme. The reduced activities were due to both decreased kcat values and increased Km values of the variants. The epoxidation of arachidonic acid by the variants was analyzed. The L361F variant only exhibited 4-6% of the wild-type catalytic efficiency in ω-9- and ω-6-epoxidation reactions to produce 11,12-epoxyeicosatrienoic acid (EET) and 14,15-EET, respectively. These reductions were mainly due to a decrease in the kcat value of the L361F variant. The binding titration analysis of paclitaxel and arachidonic acid showed that all variants had similar affinities to those of the wild-type (10-14 µM for paclitaxel and 20-49 µM for arachidonic acid). The constructed paclitaxel docking model of the variant enzyme suggests that the L361F substitution leads to the incorrect orientation of paclitaxel in the active site, with the 6'C of paclitaxel displaced from the productive catalytic location. This study suggests that individuals carrying the newly identified P450 2C8 allelic variations are likely to have an altered metabolism of clinical medicines and production of fatty acid-derived signal molecules.

High-efficient and rapid removal of anionic and cationic dyes using a facile synthesized sole adsorbent NiAlFe-layered triple hydroxide (LTH).

It would be extremely momentous to familiarize a low-cost sole adsorbent NiAlFe-layered triple hydroxides (LTHs) having a strong sorption affinity towards both anionic and cationic dyes. Using the urea hydrolysis hydrothermal method LTHs were fabricated and by altering the ratio of participant metal cations the adsorbent was optimized. BET analysis revealed that the optimized LTHs possess an elevated surface area (160.04 m2/g) while TEM and FESEM analysis portrayed the stacked sheets-like 2D morphology. LTHs were employed for the amputation of anionic congo red (CR) and cationic brilliant green (BG) dye. The adsorption study showed that within 20 and 60 min, respectively, maximum adsorption capacities were achieved at 57.47 mg/g and 192.30 mg/g for CR and BG dye. Adsorption isotherm, kinetics, and thermodynamics study revealed that both chemisorptions with physisorptions were the assertive factor for the dye encapsulation. This enhanced adsorption performance of the optimized LTH for the anionic dye is attributed to its inherent anions exchange properties and new bond formation with the adsorbent skeleton. Whereas for the cationic dye, it was because of the formation of strong hydrogen bonds, and electrostatic interaction. Morphological manipulation of LTHs, formulates the optimized adsorbent LTH111, provokes the adsorbent for this elevated adsorption performance. Overall, this study revealed that LTHs have a high potential for the effectual remediation of dyes from wastewater as a sole adsorbent at a low cost.

Hydroxylation and lyase reactions of steroids catalyzed by mouse cytochrome P450 17A1 (Cyp17a1).

Cytochrome P450 17A1 (CYP17A1) catalyzes 17α-hydroxylation and 17,20-lyase reactions with steroid hormones. Mice contain an orthologous Cyp17a1 enzyme in the genome, and its amino acid sequence has high similarity with human CYP17A1. We purified recombinant mouse Cyp17a1 and characterized its oxidation reactions with progesterone and pregnenolone. The open reading frame of the mouse Cyp17a1 gene was inserted and successfully expressed in Escherichia coli and then purified using Ni2+-nitrilotriacetic acid (NTA) affinity column chromatography. Purified mouse Cyp17a1 displayed typical Type I binding titration spectral changes upon the addition of progesterone, 17α-OH progesterone, pregnenolone, and 17α-OH pregnenolone, with similar binding affinities to those of human CYP17A1. Catalytic activities for 17α-hydroxylation and 17,20-lyase reactions were studied using ultra-performance liquid chromatography (UPLC)-mass spectrometry analysis. Mouse Cyp17a1 showed cytochrome b5 stimulation in catalysis. In comparison to human enzyme, much higher specificity constants (kcat/Km) were observed with mouse Cyp17a1. In the reactions of Δ4-steroids (progesterone and 17α-OH progesterone), the specificity constants were 2100 times higher than the human enzyme. The addition of cytochrome b5 produced significant stimulation of 17,20-lyase activities of mouse Cyp17a1. Two Arg mutants of mouse Cyp17a1 (R347H and R358Q) displayed a larger decrease in 17,20-lyase reaction (from 17α-OH pregnenolone to dehydroepiandrosterone, DHEA) than 17α-hydroxylation, indicating that -as in human CYP17A1-these basic residues in mouse Cyp17a1 are important in interacting with the cytochrome b5 protein in the lyase reactions.

Economic benefits of preventing bird collisions in South Korea: findings from a choice experiment survey.

Bird deaths due to collisions with artificial structures, such as glass windows of buildings and transparent noise barriers, are continuing to occur in South Korea. The government is trying to prevent bird collisions by increasing the attachment of specially designed tapes to help birds avoid windows. This article estimates the economic benefits arising from the prevention of collisions by applying a choice experiment (CE). For this purpose, a CE survey of 1000 South Korean interviewees was conducted. The four attributes to be attached with the tapes for the CE application were a transparent soundproof wall window on an expressway, a transparent soundproof wall window on a general road, a glass window in a public building, and a glass window in a private building. The unit was the percentage of each structure with the tapes attached to the window. The marginal values of a one-unit (1%p) increase in each attribute were computed to be KRW 534 (USD 0.46), KRW 233 (USD 0.20), KRW 1,318 (USD 1.13), and KRW 12,930 (USD 11.05), respectively. This quantitative information will be an important reference for implementing the prevention policy. For example, based on the collision prevention of 1000 birds per structure, the priority for attaching tapes can be placed in the order of expressways, public buildings, private buildings, and general roads.

Current Advances in Regenerative Strategies for Dry Eye Diseases: A Comprehensive Review.

Dry eye disease (DED) is an emerging health issue affecting millions of individuals annually. Ocular surface disorders, such as DED, are characterized by inflammation triggered by various factors. This condition can lead to tear deficiencies, resulting in the desiccation of the ocular surface, corneal ulceration/perforation, increased susceptibility to infections, and a higher risk of severe visual impairment and blindness. Currently, the clinical management of DED primarily relies on supportive and palliative measures, including the frequent and lifelong use of different lubricating agents. While some advancements like punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts have been attempted, they have shown limited effectiveness. Recently, there have been promising developments in the treatment of DED, including biomaterials such as nano-systems, hydrogels, and contact lenses for drug delivery, cell-based therapies, biological approaches, and tissue-based regenerative therapy. This article specifically explores the different strategies reported so far for treating DED. The aim is to discuss their potential as long-term cures for DED while also considering the factors that limit their feasibility and effectiveness. These advancements offer hope for more effective and sustainable treatment options in the future.

Chromism-Integrated Sensors and Devices for Visual Indicators.

The bifunctionality of chromism-integrated sensors and devices has been highlighted because of their reversibility, fast response, and visual indication. For example, one of the representative chromism electrochromic materials exhibits optical modulation under ion insertion/extraction by applying a potential. This operation mechanism can be integrated with various sensors (pressure, strain, biomolecules, gas, etc.) and devices (energy conversion/storage systems) as visual indicators for user-friendly operation. In this review, recent advances in the field of chromism-integrated systems for visual indicators are categorized for various chromism-integrated sensors and devices. This review can provide insights for researchers working on chromism, sensors, or devices. The integrated chromic devices are evaluated in terms of coloration-bleach operation, cycling stability, and coloration efficiency. In addition, the existing challenges and prospects for chromism-integrated sensors and devices are summarized for further research.

Studies on Preformulation and Formulation of JIN-001 Liquisolid Tablet with Enhanced Solubility.

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in vivo antitumor activity; however, JIN-001 was a crystalline solid with very low solubility in an aqueous solution, and therefore, Capryol 90, which has excellent solubilization ability, was selected as an optimal liquid vehicle based on solubility studies. JIN-001 liquisolid (JLS) powder was successfully prepared by dissolving JIN-001 in Capryol 90 and mixing colloidal silicon dioxide (CSD) used as an oil adsorption agent. The prepared JLS was confirmed to be amorphous. Based on the result of the solubility test of JLS, compared to JIN-001, the solubility of the former was significantly improved in all solvents regardless of pH. JLS tablets were prepared through wet granulation using JIN-001 and stable excipients based on the compatibility test. The developed JLS tablet significantly increased the drug release rate in all tested solutions; however, the liquisolid method had no significant effect on bioavailability in the pharmacokinetics study in beagle dogs. In conclusion, the liquisolid system influenced the solubility and dissolution rate of JIN-001.

Better survival of patients with hepatitis B virus-related hepatocellular carcinoma in South Korea: Changes in 16-years cohorts.

AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) have decreased over time in South Korea, where hepatitis B virus (HBV) in endemic. This study investigated the changes in the characteristics and clinical outcomes of HCC patients in Korea. METHODS: Patients initially diagnosed with HCC and treated at the National Cancer Center, Korea between 2000 and 2015 (n = 4,291) were followed up until February 2017. Differences in patient characteristics and outcomes were compared between chronological cohorts: cohort A (2000-2004, n = 1,157) vs. B (2005-2009, n = 1,678) vs. C (2010-2015, n = 1,456). RESULTS: The median age of the patient cohort was 57 years (range, 13-98 years), and male predominance was noted (81.6%). HBV infection was the most common etiology (74.8%). The proportion of patients diagnosed with good liver function and small tumors (<2 cm) increased significantly over time: 74.6%, 79.9%, and 87.4% for Child-Pugh class A (p<0.001) and 8.0%, 8.5%, and 12.0% for modified UICC stage I (p<0.001) in cohorts A, B, and C, respectively. Median overall survival improved significantly over time: 14.4 months (95% confidence interval [CI], 12.0-16.8 months), 22.9 months (95% CI, 20.3-25.5 months), and 53.6 months (95% CI, 45.7-61.5 months) in cohorts A, B, and C, respectively. HBV-related patients showed significantly improved survival (12.7 vs. 20.4 vs. 64.5 months, p<0.001) associated with the use of antiviral treatments (adjusted hazard ratio, 0.72; 95% CI, 0.64-0.80). CONCLUSIONS: The survival of patients with HCC, especially HBV-related HCC, has improved significantly over time in Korea.

A Unique Immune-Related Gene Signature Represents Advanced Liver Fibrosis and Reveals Potential Therapeutic Targets.

Innate and adaptive immune responses are critically associated with the progression of fibrosis in chronic liver diseases. In this study, we aim to identify a unique immune-related gene signature representing advanced liver fibrosis and to reveal potential therapeutic targets. Seventy-seven snap-frozen liver tissues with various chronic liver diseases at different fibrosis stages (1: n = 12, 2: n = 12, 3: n = 25, 4: n = 28) were subjected to expression analyses. Gene expression analysis was performed using the nCounter PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA). Biological meta-analysis was performed using the CBS Probe PINGSTM (CbsBioscience, Daejeon, Korea). Using non-tumor tissues from surgically resected specimens, we identified the immune-related, five-gene signature (CHIT1_FCER1G_OSM_VEGFA_ZAP70) that reliably differentiated patients with low- (F1 and F2) and high-grade fibrosis (F3 and F4; accuracy = 94.8%, specificity = 91.7%, sensitivity = 96.23%). The signature was independent of all pathological and clinical features and was independently associated with high-grade fibrosis using multivariate analysis. Among these genes, the expression of inflammation-associated FCER1G, OSM, VEGFA, and ZAP70 was lower in high-grade fibrosis than in low-grade fibrosis, whereas CHIT1 expression, which is associated with fibrogenic activity of macrophages, was higher in high-grade fibrosis. Meta-analysis revealed that STAT3, a potential druggable target, highly interacts with the five-gene signature. Overall, we identified an immune gene signature that reliably predicts advanced fibrosis in chronic liver disease. This signature revealed potential immune therapeutic targets to ameliorate liver fibrosis.

Concurrent and Selective Determination of Dopamine and Serotonin with Flexible WS2 /Graphene/Polyimide Electrode Using Cold Plasma.

Makers of point-of-care devices and wearable diagnostics prefer flexible electrodes over conventional electrodes. In this study, a flexible electrode platform is introduced with a WS2 /graphene heterostructure on polyimide (WGP) for the concurrent and selective determination of dopamine and serotonin. The WGP is fabricated directly via plasma-enhanced chemical vapor deposition (PECVD) at 150 °C on a flexible polyimide substrate. Owing to the limitations of existing fabrication methods from physical transfer or hydrothermal methods, many studies are not conducted despite excellent graphene-based heterostructures. The PECVD synthesis method can provide an innovative WS2 /graphene heterostructure of uniform quality and sufficient size (4 in.). This unique heterostructure affords excellent electrical conductivity in graphene and numerous electrochemically active sites in WS2 . A large number of uniform qualities of WGP electrodes show reproducible and highly sensitive electrochemical results. The synergistic effect enabled well-separated voltammetric signals for dopamine and serotonin with a potential gap of 188 mV. Moreover, the practical application of the flexible sensor is successfully evaluated by using artificial cerebrospinal fluid.