DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways, it is characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 expression has a detrimental role in numerous disorders. However, its role in COPD remains understudied. This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated mice airway inflammation and lung function decline caused by CS, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion in 16 HBE cells after CSE simulation, respectively. Nuclear factor erythroid 2-related factor 2 (NRF2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking COPD patients when compared to nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typically characterized by chronic airway inflammation, with emerging evidence highlighting the driving role of cellular senescence-related lung aging. Accelerated lung aging and inflammation mutually reinforce each other, creating a detrimental cycle that contributes to disease progression. Growth arrest and DNA damage-inducible (GADD45) family has been reported to involve in multiple biological processes, including inflammation and senescence. However, the role of GADD45 family in COPD remains elusive. OBJECTIVES: To investigate the role and mechanism of GADD45 family in COPD pathogenesis. METHODS: Expressions of GADD45 family were evaluated by bioinformatic analysis combined with detections in clinical specimens. The effects of GADD45B on inflammation and senescence were investigated via constructing cell model with siRNA transfection or overexpression lentivirus infection and animal model with Gadd45b knockout. Targeted bisulfite sequencing was performed to probe the influence of DNA methylation in GADD45B expression in COPD. RESULTS: GADD45B expression was significantly increased in COPD patients and strongly associated with lung function, whereas other family members presented no changes. GADD45B upregulation was confirmed in mice exposed by cigarette smoke (CS) and HBE cells treated by CS extract as well. Moreover, experiments involving bidirectional modulation of GADD45B expression in HBE cells further substantiated its positive regulatory role in inflammatory response and cellular senescence. Mechanically, GADD45B-facilitated inflammation was directly mediated by p38 phosphorylation, while GADD45B interacted with FOS to promote cellular senescence in a p38 phosphorylation-independent manner. Furthermore, Gadd45b deficiency remarkably alleviated inflammation and senescence of lungs in CS-exposed mice, as well as improved emphysema and lung function. Eventually, in vivo and vitro experiments demonstrated that GADD45B overexpression was partially mediated by CS-induced DNA hypomethylation. CONCLUSION: Our findings have shed light on the impact of GADD45B in the pathogenesis of COPD, thereby offering a promising target for intervention in clinical settings.

Blood glucose and lipids are associated with sarcoidosis: findings from observational and mendelian randomization studies.

BACKGROUND: Several researches have demonstrated that patients with sarcoidosis accompanied with the abnormality in blood glucose and/or lipids, however, the causal relationship between them remains uncertain. To elucidate the potential association and causality of blood glucose and lipids with sarcoidosis, we conducted a propensity score matching (PSM)-based observational study combined with mendelian randomization (MR) analysis. METHODS: All subjects in this study were retrospectively collected from Tongji Hospital during 2010 and 2023. 1:1 PSM was employed to control the potential confounders as appropriate. Univariable and multivariable logistic regression analyses were performed to estimate the associations of sarcoidosis with fasting glucose, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and total triglyceride (TG). The further subtype analysis was also conducted. Afterwards, a bidirectional MR analysis based on public data deeply explored the causality among the 5 candidate traits and sarcoidosis, for which the inverse-variance weighted (IVW) method was utilized as the main inferring approach. RESULTS: In the observational study, a total number of 756 subjects were enrolled, with 162 sarcoidosis patients and 594 non-sarcoidosis participants, while 160 pairs of subjects were matched after PSM. Multivariable logistic regression analysis indicated that HDLC (OR: 0.151; 95% CI: 0.056-0.408; P < 0.001) and TC (OR: 3.942; 95% CI: 2.644-5.877; P < 0.001) were strongly associated with sarcoidosis. Subtype analysis showed that low HDLC was independently correlated to risk of lesions in bronchus and lungs, and mediastinal lymph nodes, while high TC was to cervical lymph nodes. In MR analysis, high fasting glucose, low HDLC, and high TC were identified as the causal factors of sarcoidosis. CONCLUSION: HDLC and TC had the potential to influence the risk of sarcoidosis, which could be regarded as predictors and may provide new diagnostic and therapeutic targets for sarcoidosis.

Highly Stable Garnet Fe2 Mo3 O12 Cathode Boosts the Lithium-Air Battery Performance Featuring a Polyhedral Framework and Cationic Vacancy Concentrated Surface.

Lithium-air batteries (LABs), owing to their ultrahigh theoretical energy density, are recognized as one of the next-generation energy storage techniques. However, it remains a tricky problem to find highly active cathode catalyst operating within ambient air. In this contribution, a highly active Fe2 Mo3 O12 (FeMoO) garnet cathode catalyst for LABs is reported. The experimental and theoretical analysis demonstrate that the highly stable polyhedral framework, composed of FeO octahedrons and MO tetrahedrons, provides a highly effective air catalytic activity and long-term stability, and meanwhile keeps good structural stability. The FeMoO electrode delivers a cycle life of over 1800 h by applying a simple half-sealed condition in ambient air. It is found that surface-rich Fe vacancy can act as an O2 pump to accelerate the catalytic reaction. Furthermore, the FeMoO catalyst exhibits a superior catalytic capability for the decomposition of Li2 CO3 . H2 O in the air can be regarded as the main contribution to the anode corrosion and the deterioration of LAB cells could be attributed to the formation of LiOH·H2 O at the end of cycling. The present work provides in-depth insights to understand the catalytic mechanism in air and constitutes a conceptual breakthrough in catalyst design for efficient cell structure in practical LABs.

Metabolism-Related Gene TXNRD1 Regulates Inflammation and Oxidative Stress Induced by Cigarette Smoke through the Nrf2/HO-1 Pathway in the Small Airway Epithelium.

Chronic obstructive pulmonary disease (COPD), a small airway disease, is regarded as a metabolic disorder. To further uncover the metabolic profile of COPD patients, it is necessary to identify metabolism-related differential genes in small airway epithelium (SAE) of COPD. Metabolism-related differential genes in SAE between COPD patients and nonsmokers were screened from GSE128708 and GSE20257 datasets. KEGG, GO, and PPI analyses were performed to evaluate the pathway enrichment, term enrichment, and protein interaction of candidate metabolism-related differential genes, respectively. RT-PCR was used to verify the mRNA expression of the top ten differential genes. Western blotting was used to evaluate the protein expression of TXNRD1. TXNRD1 inhibitor auranofin (AUR) was used to assess the impact of TXNRD1 on oxidative stress and inflammation induced by cigarette smoke extraction (CSE). Twenty-four metabolism-related differential genes were selected. ALDH3A1, AKR1C3, CYP1A1, AKC1C1, CPY1B1, and TXNRD1 in the top ten genes were significantly upregulated after CSE simulation for 24 h in human bronchial epithelial (16HBE) cells. Among them, CYP1A1 and TXNRD1 also have a significant upregulation in primary SAE after simulation of CSE for 24 h. The overexpression of protein TXNRD1 has also been detected in 16HBE cells, primary SAE stimulated with CSE, and mouse lung exposed to cigarette smoke (CS). Additionally, inhibition of TXNRD1 with 0.1 µM AUR alleviated the expression of IL-6 and reactive oxygen species (ROS) induced by CSE by activating the Nrf2/HO-1 pathway in 16HBE cells. This study identified twenty-four metabolism-related differential genes associated with COPD. TXNRD1 might participate in the oxidative stress and inflammation induced by CS by regulating the activation of the Nrf2/HO-1 pathway.

Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

Safety and efficacy of COVID-19 vaccines in children and adolescents: A systematic review of randomized controlled trials.

To systematically review and synthesize the safety and efficacy of coronavirus disease-2019 (COVID-19) vaccines in children and adolescents. PubMed, EMBASE, Web of Science, Cochrane Library databases, the International Clinical Trials Registry Platform (ICTRP), the Chinese Clinical Trials Registry (ChiCTR), and ClinicalTrials.gov website were searched to collect accessible randomized controlled trials (RCTs) about the safety and efficacy of human COVID-19 vaccines in children and adolescents until May 1, 2022. Three steps, including duplicate removal, title and abstract screening, and full-text review, were used to screen the studies. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. Microsoft Excel 16.57 (2021) software was used for data extraction and analysis. (PROSPERO Code No: CRD42021295422). COVID-19 vaccines were evaluated in a total of 10 950 children and adolescents in seven published studies and over 49 530 participants in 26 ongoing randomized controlled trials. Descriptive findings of the included published studies were reported stratified by vaccine type. The overall, local, and systemic adverse events following immunization (AEFIs) reported in most trials were similar between the vaccine and placebo groups. Most of the reactions reported were mild to moderate, whereas a few were severe. The common adverse events were injection-site pain, fever, headache, cough, fatigue, and muscle pain. Few clinical trials reported serious adverse events, but most of them were unrelated to vaccination. In terms of efficacy, the investigated messenger RNA (mRNA) vaccine was found to be 90.7%-100% efficacious in preventing COVID-19 among children and adolescents, revealing good efficacy profiles in this age group. Among children and adolescents, the safety of current COVID-19 vaccines is acceptable, and studies have suggested that mRNA vaccines can provide high protection against COVID-19 infection in pediatric age groups.

Prescription of Potentially Inappropriate Medication Use in Older Cancer Outpatients With Multimorbidity: Concordance Among the Chinese, AGS/Beers, and STOPP Criteria.

Objectives: Age-related multimorbidity is a general problem in older patients, which increases the prevalence of potentially inappropriate medication (PIM) use. This study aimed to examine the prevalence and predictors of PIM use in older Chinese cancer outpatients with multimorbidity based on the 2017 Chinese criteria, 2019 AGS/Beers criteria, and 2014 STOPP criteria. Methods: A cross-sectional study was conducted using electronic medical data from nine tertiary hospitals in Chengdu from January 2018 to December 2018. The 2017 Chinese criteria, 2019 AGS/Beers criteria, and 2014 STOPP criteria were used to evaluate the PIM status of older cancer outpatients (age ≥65 years), the concordance among the three PIM criteria was calculated using kappa tests, and multivariate logistic regression was used to identify the risk factors associated with PIM use. Results: A total of 6,160 cancer outpatient prescriptions were included in the study. The prevalence of PIM use was 34.37, 32.65, and 15.96%, according to the 2017 Chinese criteria, 2019 AGS/Beers criteria, and 2014 STOPP criteria, respectively. Furthermore, 62.43% of PIMs met table 2, 0.27% of PIMs met table 3, 34.68% of PIMs met table 4, 2.62% of PIMs met table 5 of 2019 AGS/Beers criteria, respectively. According to the three criteria, 84.93%, 82.25%, and 94.61% of older cancer outpatients had one PIM. The most frequently used PIM in cancer outpatients was estazolam. The Chinese criteria and the STOPP criteria indicated poor concordance, whereas the 2019 AGS/Beers criteria showed moderate concordance with the other two criteria. Logistic regression demonstrated that age ≥ 80, more diseases, polypharmacy, irrational use of drugs, and lung cancer were positively associated with PIM use in older cancer outpatients. Conclusion: The prevalence of PIM use in Chinese older cancer outpatients with multimorbidity is high in China, and poor-to-moderate concordance among the three criteria was observed. Research on building PIM criteria for the older cancer population is necessary in the future.

The prevalence and factors associated with potentially inappropriate medication use in Chinese older outpatients with cancer with multimorbidity.

BACKGROUND: Multimorbidity and polypharmacy is a general problem in older patients; they increase the prevalence of potentially inappropriate medication (PIM) use. But PIM use in patients with cancer is less clear. This study aimed to examine the prevalence and the predictors of PIM use in Chinese older outpatients with cancer with multimorbidity in Chengdu based on the 2019 Beers Criteria. METHODS: A cross-sectional study was conducted using electronic medical data from nine tertiary hospitals in Chengdu from January 2018 to December 2018. The 2019 AGS Beers Criteria were used to evaluate the PIM status of older outpatients with cancer (age ≥ 65 years), and multivariate logistic regression was used to identify the risk factors associated with PIM use. RESULTS: A total of 6160 cancer outpatient prescriptions were included in the study. The prevalence of PIM use based on the 2019 AGS Beers Criteria was 32.65%. The most frequently used PIMs in outpatients with cancer were benzodiazepines and benzodiazepine receptor agonist hypnotics, diuretics, tramadol, non-steroidal anti-inflammatory drugs, and glimepiride. Logistic regression demonstrated that age ≥ 80 (odds ratio [OR]: 1.238, 95% confidence interval [CI]: 1.071, 1.431, P = 0.004), more diseases (OR: 1.193, 95% CI: 1.017, 1.399, P = 0.03), polypharmacy (OR: 2.520, 95% CI: 2.169, 2.927, P<0.001), and irrational use of drugs (OR: 1.762, 95% CI: 1.408, 2.205, P<0.001) were positively associated with PIM use in older outpatients with cancer. CONCLUSIONS: The prevalence of PIM use in Chinese older outpatients with cancer and multimorbidity is high in China. The increased prescription complexity caused by cancer will further increase the prevalence of PIM use. Research on interventions rationing PIM use in the older cancer population are necessary in the future.

New Methylene Blue Covalently Functionalized Graphene Oxide Nanocomposite as Interfacial Material for the Electroanalysis of Hydrogen Peroxide.

New methylene blue (NMB), a phenothiazine dye, was covalently bonded to graphene oxide (GO) using glutaraldehyde as a crosslinking agent, which was characterized by spectroscopic techniques and electrochemistry. The obtained GO-NMB nanocomposite was used as interface material to construct a novel electrochemical sensor for the determination of hydrogen peroxide (H2O2). The electrochemical sensor based on GO-NMB nanocomposite exhibited excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2), which was also enhanced by GO within the GO-NMB nanocomposite. With the optimized experimental conditions, the developed sensor showed high sensitivity (79.4 µA mM-1 cm-2) for electrocatalytic determination of H2O2 at the applied potential of -0.50 V in the concentration range of 0.000333 to 2.28 mΜ. The low limit of detection (1.35 µM), good reproducibility, and high stability of the sensor suggests that the electrochemical sensor based on the GO-NMB nanocomposite possesses obvious advantages, which paves a new avenue to functionalize GO for obtaining electrode interface materials.

Optimization extraction of rosemary essential oils using hydrodistillation with extraction kinetics analysis.

Rosemary (Rosmarinus officinales L. (Labiatae)) is one of the major economic crops in the world, and rosemary essential oil (REO) is one of the top products derived from rosemary and has excellent commercial prospects. Many factors affect the yield of REO extracted by hydrodistillation (HY). This study was proposed to identify and analyze these factors to maximize the yield of essential oils and reduce the cost. First, two different single-factor extraction experiments were conducted, (1) adding NaCl and (2) using various organs of the plant, to determine the influence of each factor on the oil yield. Based on single-factor experiments, the orthogonal experiments (L9, 33) were designed to determine the optimal conditions for the extraction of rosemary oil. Meanwhile, the kinetic extraction analysis of the test data was carried out. The results revealed that the highest oil yield was achieved when rosemary leaves were crushed to 2 cm, the ratio of water to the material was 1:3, and NaCl concentration was 5%. A simple first-order kinetic model has also proved to be an acceptable general choice and allows to predict the output of extraction operations overtime accurately and robustly in practice. This study provides a reference scheme for using hydrodistillation to extract rosemary essential oil.

KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP.

Hepatocellular carcinoma (HCC) is a prevalent solid cancer worldwide and sorafenib is a common treatment. Nevertheless, sorafenib resistance is a severe clinical problem. In the present study, we identified that epigenetic regulator, KAT6A, was overexpressed in clinical HCC tissues and sorafenib-resistant HCC samples. The depletion of KAT6A repressed the cell viability and Edu-positive cell numbers of HCC cells. The IC50 value of sorafenib was increased in sorafenib-resistant HCC cells. In addition, the expression of KAT6A was induced in sorafenib-resistant HCC cells. The depletion of KAT6A suppressed the IC50 of sorafenib. Mechanically, YAP was decreased by the depletion of KAT6A. KAT6A was able to enrich in the promoter of YAP. The silencing of KAT6A reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) and RNA polymerase II (RNA pol II) on the promoter of YAP in sorafenib-resistant HCC cells. KAT6A inhibitor WM-1119 repressed the cell proliferation of sorafenib-resistant HCC cells, while overexpression of KAT6A or YAP could reverse the effect in the cells. Meanwhile, the treatment of sorafenib inhibited the viability of sorafenib-resistant HCC cells, while the co-treatment of WM-1119 could improve the effect of sorafenib. Collectively, KAT6A was associated with sorafenib resistance and contributes to progression of HCC by targeting YAP. Targeting KAT6A may be served as a promising therapeutic approach for HCC.

Using visual and/or kinesthetic information to stabilize intrinsic bimanual coordination patterns is a function of movement frequency.

Coordination dynamics suggest that both in-phase and anti-phase movements are intrinsic and can be readily performed without practice. As movement frequency increases, individuals performing anti-phase movement inevitably switch to perform in-phase movement. However, due to different frames of reference used to define intrinsic coordination patterns in visual and kinesthetic domains, the perception of intrinsic coordination patterns could be ambiguous, which leads to the question whether the visually or kinesthetically perceived information is used to maintain the intrinsic coordination patterns. The current study explored how the consistency between visual and kinesthetic information would impact the performance and the associated metabolic energy consumption of intrinsic bimanual coordination patterns as movement frequency increased. Thirty participants were recruited and randomly assigned to one of three groups ("Info + Spatial +", "Info + Spatial -", and "Info-Spatial +") to perform intrinsic bimanual coordination tasks using a computer-joystick system at low, high, and self-selected frequencies. The visual and kinesthetic information were manipulated to be either consistent or inconsistent by changing the spatial mapping between the motion of display and motion of joysticks. The results showed that the kinesthetic information was largely used to maintain the stability of intrinsic coordination patterns at high frequency, which could be an energy-conserving solution. However, spatial mapping alone seemed to be beneficial for keeping the visually perceived in-phase and anti-phase coordination patterns equally stable at low movement frequency, and spatially mapping the visual information to be consistent with kinesthetic information greatly enhanced the stability of anti-phase coordination. The dynamical use of visual and kinesthetic information for control of bimanual coordination is discussed.

Enhanced electrochemical performance by nickel-iron layered double hydroxides (LDH) coated on Fe3O4 as a cathode catalyst for single-chamber microbial fuel cells.

The improvement of cathode performance has always been the bottleneck and research hot spot for microbial fuel cells (MFCs). An Fe3O4@NiFe-LDH composite with a nanoscale core-shell structure containing an Fe3O4 magnetic core and a layered double hydroxide (LDH) shell was prepared by the hydrothermal method. The Fe3O4@NiFe-LDH was characterized by FT-IR, XRD, SEM and EDS. The characterization results showed that the composite had a unique cauliflower-like nanoflake structure and special pore size distribution, which greatly improved the ORR performance. Moreover, the use of the synthesized Fe3O4@NiFe-LDH core-shell structure as an electrode in an MFC was characterized by CV and LSV, which showed that the Fe3O4@NiFe-LDH exhibited excellent ORR catalytic properties. The voltage output of the Fe3O4@NiFe-LDH MFC was maintained at approximately 0.39 V, with insignificant variations over 110 h. The maximum power density was 211.40 ± 2.27 mW/m2, which was 34 times that of the blank control group MFC and was caused by the many electroactive sites, good rate capability and remarkable cycling stability of LDH. This study provides the possibility for using Fe3O4@NiFe-LDH in cathodes to operate continuously and at low cost in fuel cells.

Dual-beam potassium Voigt filter for atomic line imaging.

Spectrally narrowband imaging in remote sensing applications can be advantageous for detecting atomic emission features. This is especially useful in detecting specific constituents within rocket plumes, which are challenging to discern from naturally occurring sunglints. In this paper, we demonstrate a dual-beam technique, implemented with a Wollaston prism, for calibrating a Voigt magneto-optical filter for a linear polarizer's finite extinction ratio, as well as optical misalignment between the linear polarizers' transmission axes. Such a strategy would be key towards expanding the filter's field of view while maintaining its classification capabilities. Validation of the potassium Voigt filter is demonstrated using the simulation tool ElecSus in combination with a potassium hollow cathode lamp. RMS error between the filter's temperature response and that of the simulation was approximately 2%. We then demonstrate the detection of a potassium model rocket motor outdoors alongside a sunglint. Results indicate a 20-fold increase in contrast when using our dual-beam calibration strategy.

Optical crosstalk and off-axis modeling of an intrinsic coincident polarimeter.

Polarimeters have broad applications in remote sensing, astronomy, and biomedical imaging to measure the emitted, reflected, or transmitted state of polarization. An intrinsic coincident (IC) full-Stokes polarimeter was previously demonstrated by our group, in a free space configuration, by using stain-aligned polymer-based organic photovoltaics. To minimize the model's complexity, these were tilted to avoid crosstalk from back-reflections. We present a theoretical model of a monolithic IC polarimeter that considers the back-reflection's influence for on-axis light. The model was validated using a monolithic four-detector polarimeter, which achieved an error of less than 3%. Additionally, an off-axis model was produced and validated for a simpler two detector polarimeter, demonstrating an error between the TM and TE polarized components of less than 3% for angles spanning an 18° incidence cone.

An effective approach to achieve high energy storage density and efficiency in BNT-based ceramics by doping AgNbO3.

Perovskite dielectric materials for capacitors have received wide attention in recent years because of their fast charge/discharge rates and high power densities. In this work, lead-free relaxor ferroelectric ceramics of (1 -x)[(Bi0.55Na0.45)0.94Ba0.06]0.98La0.02TiO3-xAgNbO3 were synthesized by a conventional sintering method. All ceramics are situated at the morphotropic phase boundary (MPB) of rhombohedral and tetragonal phases, suggesting that a small amount of AgNbO3 (abbreviated as AN) doping does not affect this phase-coexistence structure. The added AN not only improves the dielectric breakdown strength (DBS) from 84.11 kV cm-1 (x = 0) to 137.89 kV cm-1 (x = 0.01), but also broadens the phase transition peak and enhances the relaxation behavior of ceramics. Moreover, when x = 0.01, the ceramic demonstrates a high saturation polarization (Ps) of 25.54 µC cm-2 and a low remanent polarization (Pr) of 0.65 µC cm-2 at an electric field of 130 kV cm-1. More importantly, an optimal energy storage density (Ws) of 1.697 J cm-3 and energy efficiency (η) of 82.3% are simultaneously achieved in the BNBLT-0.01AN ceramic with excellent thermal stability (∼25-175 °C) and frequency stability (∼10-80 Hz).

Bioinspired genetic engineering of supramolecular assembled formate dehydrogenase with enhanced biocatalysis activities.

A bioinspired strategy for the synthesis of supramolecular and biocatalytical materials was developed base on protein-protein supramolecular interaction and genetic engineering. Formate dehydrogenase (FDH) and its functional fragments were separately fused to form a multi-function domain. The fusion proteins and functional fragments self-assembled into the expanded and controllable supramolecular interaction networks. Morphology characterization by scanning-electron microscopy showed that the assembled functional fragments and fusion proteins formed multi-dimensional (3D) and two-dimensional (2D) layer-like structures. Moreover, the oligomeric biocatalysts exhibited higher structural stability and NAD(H) recycling efficiency than the unassembled structures when they were applied to a co-enzyme regeneration system. These results suggest that the bioinspired strategy provides a promising approach for the fabrication of supramolecular FDH materials via genetic engineering and self-assembly. The significant improvement on the biocatalytical activity reveals the essential role of supramolecular interface design in their biocatalysis applications.

The role of IDO, IL-10, and TGF-ß in the HCV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10, and TGF-ß were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST, and total bilirubin (TBil) were collected from clinical databases. HCV-related liver cirrhosis (HC-Cirr) and HCV-related Hepatocellular carcinoma (HCV-HCC) had significantly high plasma levels of IDO compared to other patient groups and healthy controls. Plasma IL-10 level were significantly greater in all chronic liver disease groups and with respect to TGF-ß, the level was high in all the selected patients with HCV infection compare with controls. Moreover, HCV-HCC patients showed highest values for both IL-10 and TGF-ß, with significant difference compared with other groups. In addition, plasma IDO was positively correlated with TGF-ß among all patients with HCV infection (r = 0.4509, P < 0.0001), with IL-10 in CHC patients (r = 0.4787, P = 0.0047), with TBil in HCV-Cirr patients (r = 0.4671; P = 0.0093). High level of IDO and TGF-ß is associated with hepatocyte necrosis and intrahepatic inflammation, and may be used as an index of disease progression for patients with chronic HCV infection.