Comprehensive analysis of aberrantly expressed circRNAs, mRNAs and lncRNAs in patients with nasopharyngeal carcinoma.

BACKGROUND: The location of nasopharyngeal cancer is hidden, so it is difficult to diagnose at an early stage. In this study, we aimed to investigate the expression profiles of circRNAs, mRNAs and IncRNAs and to provide some basis for further studies. METHODS: Expression profiles of circRNAs, mRNAs, and lncRNAs were analyzed using microarray techniques. The differentially expressed ncRNA was calculated by bioinformatics. RESULTS: A total of 3048 circRNAs, 2179 lncRNAs, and 2015 mRNAs were detected to be significantly differentially expressed in NPC. The most upregulated circRNAs, lncRNAs, and mRNAs were hsa-circ-0067562, NONHSAT232922.1, and HOXB13, respectively. And, the most downregulated circRNAs, lncRNAs, and mRNAs were hsa_circ_0078837, lnc-TTC8-4:3, and LTF, respectively. The number of upregulated DE lncRNAs was more than twice than those downregulated. Our data showed that 80.44% of pairs of lncRNAs and cis-mRNAs demonstrated positive correlations. For lncRNAs and trans-mRNAs pairs, 53.7% of pairs showed positive correlation. LncRNA-mediated cis regulation is a prevalent regulatory mode in the development of nasopharyngeal carcinoma. CR1, LRMP and SORBS2 are predicted to be mediated not only by cis-acting lncRNA modes of action, but also by trans-acting lncRNA mechanisms. Additionally, we constructed a diagnostic prediction model with a high sensitivity and specificity. CONCLUSION: Our study characterized the landscape of circRNAs, mRNAs and lncRNAs in NPC tissue and provided novel insights into the molecular mechanisms of NPC.

Performance comparison of two nucleic acid amplification systems for SARS-CoV-2 detection: A multi-center study.

BACKGROUND: Many rapid nucleic acid testing systems have emerged to halt the development and spread of COVID-19. However, so far relatively few studies have compared the diagnostic performance between these testing systems and conventional detection systems. Here, we performed a retrospective analysis to evaluate the clinical detection performance between SARS-CoV-2 rapid and conventional nucleic acid detection system. METHODS: Clinical detection results of 63,352 oropharyngeal swabs by both systems were finally enrolled in this analysis. Sensitivity (SE), specificity (SP), and positive and negative predictive value (PPV, NPV) of both systems were calculated to evaluate their diagnostic accuracy. Concordance between these two systems were assessed by overall, positive, negative percent agreement (OPA, PPA, NPA) and κ value. Sensitivity of SARS-CoV-2 rapid nucleic acid detection system (Daan Gene) was further analyzed with respect to the viral load of clinical specimens. RESULTS: Sensitivity of Daan Gene was slightly lower than that of conventional detection system (0.86 vs. 0.979), but their specificity was equivalent. Daan Gene had ≥98.0% PPV and NPV for SARS-CoV-2. Moreover, Daan Gene demonstrated an excellent test agreement with conventional detection system (κ = 0.893, p = 0.000). Daan Gene was 99.31% sensitivity for specimens with high viral load (Ct < 35) and 50% for low viral load (Ct ≥ 35). CONCLUSIONS: While showing an analytical sensitivity slightly below than that of conventional detection system, rapid nucleic acid detection system may be a diagnostic alternative to rapidly identify SARS-CoV-2-infected individuals with high viral loads and a powerful complement to current detection methods.

Polydatin alleviated alcoholic liver injury in zebrafish larvae through ameliorating lipid metabolism and oxidative stress.

Hepatic steatosis is the early stage of alcoholic liver disease (ALD), may progress to steatohepatitis, fibrosis even cirrhosis. Polydatin, the primary active component of Polygonum cuspidatum Sieb. et Zucc, has been recognized to possess hepatoprotective and anti-inflammatory properties. To investigate whether polydatin alleviates ethanol induced liver injury and to elucidate the underlying molecular mechanisms, zebrafish larvae at 4 days post-fertilization (dpf) were exposed to 350 mmol/L of ethanol for 32 h, then treated with polydatin for 48 h. Oil red O, Nile Red and H&E staining were used to analyze the pathological changes in liver. The mRNA levels were measured by quantitative PCR and the antioxidant capacity was detected using H2O2-specific fluorescent probe. Here, polydatin strongly alleviated hepatic steatosis and decreased the expression levels of alcohol and lipid metabolism-related genes, including CYP2Y3, CYP3A65, HMGCRa, HMGCRb and FASN. Additionally, polydatin inhibited oxidative stress in the liver according to fluorescent probe. Moreover, significantly up-regulated expression of DNA damage-related genes (CHOP, GADD45αa) revealed that polydatin attenuated hepatic apoptosis in larvae. In conclusion, polydatin may improve the liver function of zebrafish with acute alcoholic liver injury through attenuating hepatic fat accumulation, ameliorating lipid and ethanol metabolism and reducing oxidative stress and DNA damage.

Improved Thermal and Electrical Properties of P-I-N-Structured Perovskite Solar Cells Using ZnO-Added PCBM as Electron Transport Layer.

Not only can perovskite solar cells be exposed to high temperatures, up to 80 °C, depending on the operating environment, but absorbed energy is lost as heat, so it is important to have thermal stability for commercialization. However, in the case of the recently reported p-i-n structure solar cell, most of the electron and hole transport layers are composed of organic materials vulnerable to heat transfer, so the light absorption layer may be continuously exposed to high temperatures when the solar cell is operated. In this study, we attempted to improve the thermal conductivity of the electron transport layer using phenyl-C61-butyric acid methyl ester (PCBM) containing zinc oxide (ZnO). As a result, the thermal conductivity was improved by more than 7.4% and 23.5% by adding 6.57vol% and 22.38vol% of ZnO to PCBM, respectively. In addition, the insertion of ZnO resulted in changes in the electron transport behavior and energy level of the electron transport layer. As a result, it was confirmed that not only could the temperature stability of the perovskite thin film be improved, but the efficiency of the solar cell could also be improved from 14.12% to 17.97%.

Fabrication process and electromagnetic wave absorption characterization of a CNT/Ni/epoxy nanocomposite.

Since carbon nanotube (CNT) was first discovered in 1991, it has been considered as a viable type of conductive filler for electromagnetic wave absorption materials in the GHz range. In this paper, pearl-necklace-structure CNT/Ni nano-powders were fabricated by a polyol process as conductive fillers. Compared to synthesized CNT, pearl-necklace Ni-decorated CNT increased the electrical conductivity by an order of 1 due to the enhancement of the Ni-conductive network. Moreover, the decorated Ni particles prevented the agglomeration of CNTs by counterbalancing the Van der Walls interaction between the CNTs. A CNT/Ni nanocomposite showed a homogeneous dispersion in an epoxy-based matrix. This enhanced physical morphology and electrical properties lead to an increase in the loss tangent and reflection loss in the CNT/Ni/Epoxy nanocomposite compared to these characteristics of a CNT/Epoxy nanocomposite in range of 8-12 GHz. The electromagnetic wave absorption properties of CNT/Ni/epoxy nanocomposites will provide enormous opportunities for electronic applications where lightweight EMI shielding or electro-magnetic wave absorption properties are necessary.

Field emission behavior of carbon nanotube yarn for micro-resolution X-ray tube cathode.

Carbon nanotube (CNT) has excellent electrical and thermal conductivity and high aspect ratio for X-ray tube cathode. However, CNT field emission cathode has been shown unstable field emission and short life time due to field evaporation by high current density and detachment by electrostatic force. An alternative approach in this direction is the introduction of CNT yarn, which is a one dimensional assembly of individual carbon nanotubes bonded by the Van der Waals force. Because CNT yarn is composed with many CNTs, CNT yarns are expected to increase current density and life time for X-ray tube applications. In this research, CNT yarn was fabricated by spinning of a super-aligned CNT forest and was characterized for application to an X-ray tube cathode. CNT yarn showed a high field emission current density and a long lifetime of over 450 hours. Applying the CNT yarn field emitter to the X-ray tube cathode, it was possible to obtain micro-scale resolution images. The relationship between the field emission properties and the microstructure evolution was investigated and the unraveling effect of the CNT yarn was discussed.

Corrigendum: Xiaoyaosan exerts antidepressant effect by downregulating RAGE expression in cingulate gyrus of depressive-like mice.

[This corrects the article DOI: 10.3389/fphar.2021.703965.].

Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss. Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathway.

OBJECTIVE: To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo. METHODS: For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot. RESULTS: EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05). CONCLUSIONS: EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.

Isoliquiritigenin alleviates liver fibrosis through caveolin-1-mediated hepatic stellate cells ferroptosis in zebrafish and mice.

BACKGROUND: Liver fibrosis is a major disease that threatens people's health around the world. However, there is a lack of effective treatment to completely reverse liver fibrosis. Liver transplantation is currently the only curative option for patients with advanced cirrhosis. Ferroptosis is a newly discovered type of cell death and plays an important role in the process of liver fibrosis, but the specific mechanism needs to be clarified. HYPOTHESIS/PURPOSE: To explore the regulatory mechanism of isoliquiritigenin (ISL) in the process of liver fibrosis and the relationship between Cav-1 and ferroptosis. METHODS: In this research, zebrafish, HSC-T6 cells, and mice were used as the research object. Different ROS probes to visually detect the content and distribution of ROS in live zebrafish and cells. Lentivirus and siRNA-mediated transfection techniques were used for the construction of Cav-1 overexpression and knockdown cell lines to verify the important role of Cav-1 in vitro. RESULTS: Generally, we first elucidated that ISL relieved liver fibrosis by inducing hepatic stellate cells (HSCs) ferroptosis through repressing GPX4 expression and increasing the expression of TFR and DMT1, thus producing a large number of ROS, we also found that Cav-1 exerted its anti-hepatic fibrosis effect by promoting HSCs ferroptosis. CONCLUSION: Our results have shown that Cav-1-mediated HSCs ferroptosis is necessary for ISL to play an anti-fibrotic effect in vitro and in vivo.

Hepatic TGFßr1 Deficiency Attenuates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Inhibiting GSK3ß-Nrf2-Mediated Hepatocyte Apoptosis and Ferroptosis.

BACKGROUND & AIMS: Acute liver failure (ALF) is a condition with high mortality and morbidity, characterized by glutathione depletion, oxidative stress, and mitochondrial dysfunction. Ferroptosis may be involved in ALF. Indeed, emerging studies have shown that ferroptosis plays a significant role in ALF. However, the mechanism of ferroptosis in hepatocytes during ALF remains unknown. METHODS: Hepatic-specific transforming growth factor ß receptor 1 knockout (TGFßr1Δhep-CKO) mice and nuclear factor erythroid 2-related factor 2 knockout (Nrf2-/-) mice were generated and subjected to ALF. Electron microscopy was used to detect mitochondrial and other cell substructure changes during ALF. RESULTS: In this study, we noticed that lipopolysaccharide (LPS)/D-galactosamine (D-GalN) induced caspases-mediated apoptosis as current research reported, we also found lipid peroxidation, reactive oxygen species accumulation, and glutathione, co-enzyme Q10 system inhibition mediated ferroptosis during LPS/D-GalN-induced ALF. Rescue studies have shown that ferrostatin-1 (Fer-1) and deferoxamine mesylate (DFOM), the inhibitor of ferroptosis, could alleviate LPS/D-GalN-induced ALF. In addition, we noticed that TGFß1 was increased during ALF, while ALF was relieved in TGFßr1Δhep-CKO mice. We also noticed that liver TGFßr1 deficiency alleviated LPS/D-GalN-induced apoptosis and ferroptosis by affecting the phosphorylation of glycogen synthase kinase 3ß and Nrf2, a key antioxidant factor, by up-regulating the levels of glutathione peroxidase 4 (GPX4), glutamine antiporter xCT (XCT), dihydroorotate dehydrogenase (DHODH), and ferroptosis suppressor protein 1 (FSP1), and down-regulating transferrin receptor (TFR), prostaglandin-endoperoxide synthase (Ptgs2), chaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), and cytochrome P450 reductase (POR) expression. The further supplemental experiment showed that ferroptosis was aggravated significantly in Nrf2-/- mice compared with its wild-type controls and reversed by ferrostatin-1. CONCLUSIONS: This study shows that TGFßr1 plays a critical role in mediating LPS/D-GalN-induced ALF by promoting apoptosis and ferroptosis.

Synthetic control of the surface area in nickel cobalt oxide for glucose detection via additive-assisted wet chemical method.

We investigated the effect of specific surface area on the electrochemical properties of NiCo2O4 (NCO) for glucose detection. NCO nanomaterials with controlled specific surface areas were prepared by additive-assisted hydrothermal synthesis, and self-assembled nanostructures with urchin-, pine-needle-, tremella-, and flower-like morphologies were obtained. The novelty of this method is the systematic control of chemical reaction routes assisted by the addition of different additives during synthesis, which results in the spontaneous formation of various morphologies without any difference in the crystal structure and chemical states of the constituent elements. Such morphological control of NCO nanomaterials leads to considerable changes in the electrochemical performance for glucose detection. Combined with materials characterization, the relationship between the specific surface area and the electrochemical performance is discussed for glucose detection. This work can provide scientific insights for tailoring the surface area of nanostructures, which determines their functionality for potential applications in glucose biosensors.

Fabrication and characterization of a 3D-structured field emitter using carbon nanotube.

Carbon nanotube has good electrical properties and a high aspect ratio, which enable it to obtain a high current at a low voltage due to its high field. Due to the life and uniformity of their emission tips, carbon nanotube field emitters are hard to commercialize. A field emitter with a three-dimensional (3D) structure was fabricated in this study to overcome such problems. In the 3D-structured field emitter, the field emission tips are located only at the vertical plane, where an enlarged field emission area can be attained. To fabricate the tip of the 3D-structured field emitter, carbon nanotube/silver nanocomposite powders were fabricated via molecular-level mixing and were sprayed at a substrate with good attachment and homogeneous dispersion between the CNT tips and the silver. The field emission properties of the 3D-structured field emitter were then determined and compared with those of a flat field emitter. The field emission area of the 3D-structured field emitter was found to be 4.5 times larger than that of the flat field emitter, with six times higher current density. Moreover, the 3D-structured field emitter had better stability than the flat field emitter. At a high gate field, the emission images of the 3D-structured field emitter showed light spots expanded towards the gate direction.

Xiaoyaosan Exerts Antidepressant Effect by Downregulating RAGE Expression in Cingulate Gyrus of Depressive-Like Mice.

Xiaoyaosan (XYS), as a classic Chinese medicine compound, has been proven to have antidepressant effect in many studies, but its mechanism has not been clarified. In our previous studies, we found that chronic stress can induce depressive-like behavior and lead to emotion-related cingulate gyrus (Cg) dysfunction, as well as the decrease of neurotrophic factors and the increase of inflammatory-related proteins. Therefore, we speculated that XYS may play an antidepressant role by regulating the inflammation-related receptor of advanced glycation protein end product (RAGE) to affect the functional connectivity (FC) signal of the Cg and improve the depressive-like behavior. In order to verify this hypothesis, we analyzed the FC and RAGE expression in the Cg of depressive-like mice induced by chronic unpredictable mild stress (CUMS) and verified it with RAGE knockout mice. At the same time, we detected the effect of XYS on the depressive-like behavior, expression of RAGE, and the FC of the Cg of mice. The results showed that the FC of the Cg of depressive-like mice induced by CUMS was weakened, and the expression of RAGE was upregulated. The antidepressant effect of XYS is similar to that of fluoxetine hydrochloride, which can significantly reduce the depressive-like behavior of mice and inhibit the expression of the RAGE protein and mRNA in the Cg, and increase the FC of the Cg in mice. In conclusion, XYS may play an antidepressant role by downregulating the expression of RAGE in the Cg of depressive-like mice induced by CUMS, thereby affecting the functional signal and improving the depressive-like behavior.

Ginsenoside-Rg1 acts as an IDO1 inhibitor, protects against liver fibrosis via alleviating IDO1-mediated the inhibition of DCs maturation.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) has been reported as a hallmark of hepatic fibrosis. Ginseng Rg1(G-Rg1) is a characterized bioactive component isolated from a traditional Chinese medicinal herb Panax ginseng C. A. Meyer (Ginseng) that used in China widely. However, the anti-hepatic fibrosis property of G-Rg1 and the underlying mechanisms of action are poorly reported. PURPOSE: Here, we researched the effect of G-Rg1 on experimental liver fibrosis in vivo and in vitro. STUDY DESIGN AND METHODS: We applied a CCL4-induced liver fibrosis in mice (wild-type and those overexpressing IDO1 by in vivo AAV9 vector) and HSC-T6 cells to detect the anti-hepatic fibrosis effect of G-Rg1 in vivo and in vitro. RESULTS: We found that G-Rg1 reduced serum levels of AST and ALT markedly. Histologic examination indicated that G-Rg1 dramatically improved the extent of liver fibrosis and suppressed the hepatic levels of fibrotic marker α-SMA in vivo and in vitro. The proliferation of HSC-T6 was significantly inhibited by G-Rg1 in vitro. Both TUNEL staining and flow cytometry demonstrated that G-Rg1 attenuated the levels of hepatocyte apoptosis in fibrotic mice. Additionally, G-Rg1 up-regulated the maturation of hepatic DCs via reducing the expression level of hepatic IDO1, which played an inverse role in the maturation of DCs. Furthermore, oral administration of G-Rg1 ameliorated IDO1 overexpression-induced worsen liver fibrosis as well as IDO1 overexpression-mediated more apparent inhibition of maturation of DCs. CONCLUSION: These results suggest that G-Rg1, which exerts its antifibrotic properties via alleviating IDO1-mediated the inhibition of DCs maturation, may be a potential therapeutic drug in treating liver fibrosis.

Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis.

Liver fibrosis is a course of chronic liver dysfunction, can develop into cirrhosis and hepatocellular carcinoma. Inflammatory insult owing to pathogenic factors plays a crucial role in the pathogenesis of liver fibrosis. Indoleamine 2,3-dioxygenase 1 (IDO1) can affect the infiltration of immune cells in many pathology processes of diseases, but its role in liver fibrosis has not been elucidated completely. Here, the markedly elevated protein IDO1 in livers was identified, and dendritic cells (DCs) immune-phenotypes were significantly altered after BDL challenge. A distinct hepatic population of CD11c+DCs was decreased and presented an immature immune-phenotype, reflected by lower expression levels of co-stimulatory molecules (CD40, MHCII). Frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+MHCII+, and CD11c+CD40+ cells in splenic leukocytes were reduced significantly. Notably, IDO1 overexpression inhibited hepatic, splenic CD11c+DCs maturation, mature DCs-mediated T-cell proliferation and worsened liver fibrosis, whereas above pathological phenomena were reversed in IDO1-/- mice. Our data demonstrate that IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis. Thus, amelioration of immune responses in hepatic and splenic microenvironment by targeting IDO1 might be essential for the therapeutic effects on liver fibrosis.

Lupeol ameliorates LPS/D-GalN induced acute hepatic damage by suppressing inflammation and oxidative stress through TGFß1-Nrf2 signal pathway.

Acute hepatic damage is a severe condition characterized by inflammation and oxidative stress, which is a serious threat to people's life and health. But there are few effective treatments for acute liver injury. Therefore, safe and effective therapeutic approaches for preventing acute liver damage are urgently needed. Lupeol is a natural compound, which has significant antioxidant and anti-inflammatory properties in liver disease. However, the protective mechanism of lupeol against acute liver injury remains unclear. Here, zebrafish and mutant mice were utilized to investigate the protective effects of lupeol against lipopolysaccharide (LPS)/ D-galactosamine(D-GalN) -induced liver injury and the underlying mechanisms. We found that pretreatment with lupeol attenuated the LPS/D-GalN-induced liver injury by decreasing the infiltration of inflammatory cells and reducing pro-inflammatory cytokines. We also demonstrated that lupeol could protect injured liver from oxidative stress by downregulating the expression of TGFß1 and upregulating Nrf2. Notably, our experimental results provided the support that lupeol effectively protected against LPS/D-GalN-induced acute liver injury via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via downregulating TGFß1.

Ginsenoside Rb1 Alleviates Alcohol-Induced Liver Injury by Inhibiting Steatosis, Oxidative Stress, and Inflammation.

Alcoholic liver disease (ALD) has become a heavy burden on health worldwide. Ginsenoside Rb1 (GRb1), extracted from Panax quinquefolium L., has protective effects on many diseases, but the effect and mechanisms of GRb1 on ALD remain unknown. This study aimed to investigate the protective effects of GRb1 on ALD and to discover the potential mechanisms. Zebrafish larvae were exposed to 350 mM ethanol for 32 h to establish a model of acute alcoholic liver injury, and the larvae were then treated with 6.25, 12.5, or 25 µM GRb1 for 48 h. The human hepatocyte cell line was stimulated by 100 mM ethanol and meanwhile incubated with 6.25, 12.5, and 25 µM GRb1 for 24 h. The lipid changes were detected by Oil Red O staining, Nile Red staining, and triglyceride determination. The antioxidant capacity was assessed by fluorescent probes in vivo, and the expression levels of inflammatory cytokines were detected by immunohistochemistry, immunofluorescence, and quantitative real-time PCR. The results showed that GRb1 alleviated lipid deposition in hepatocytes at an optimal concentration of 12.5 µM in vivo. GRb1 reversed the reactive oxygen species accumulation caused by alcohol consumption and partially restored the level of glutathione. Furthermore, GRb1 ameliorated liver inflammation by inhibiting neutrophil infiltration in the liver parenchyma and downregulating the expression of nuclear factor-kappa B pathway-associated proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß. This study revealed that GRb1 has a protective effect on alcohol-induced liver injury due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions. These findings suggest that GRb1 may be a promising candidate against ALD.

Mechanical and electrical properties of carbon nanotube/Cu nanocomposites by molecular-level mixing and controlled oxidation process.

A molecular-level mixing and controlled oxidation process is proposed as a novel fabrication technique for the production of CNT/Cu nanocomposite powders. The fabricated CNT/Cu2O nanocomposite powders showed microstructures with homogeneous dispersion of implanted CNTs in a Cu2O matrix. The CNT/Cu2O nanocomposite powders were reduced to CNT/Cu nanocomposite powders with H2 gas and then the as-prepared CNT/Cu nanocomposite powders were spark plasma sintered to fabricate CNT/Cu nanocomposites. The mechanical properties of the Cu and the CNT/Cu nanocomposites were characterized by tensile testing before and after hot compression. Before hot compression, the CNT/Cu nanocomposites were brittle, but after hot compression both yield strength and elongation were increased, while the yield strength of the Cu was decreased after hot compression. Hot compression enhanced the ductility and strength of the CNT/Cu nanocomposites due to alignment of Cu grains and CNTs. Electrical conductivity was also enhanced due to a reduced scattering of electrons because of the alignment of the CNTs and Cu grains as well as the annealing effects of the Cu matrix.

Mutual antagonism between indoleamine 2,3-dioxygenase 1 and nuclear factor E2-related factor 2 regulates the maturation status of DCs in liver fibrosis.

Liver fibrosis can develop into liver cirrhosis and hepatocellular carcinoma substantially without effective available treatment currently due to rarely characterized molecular pathogenesis. Indoleamine 2,3-dioxygenase 1(IDO1) can be detected on antigen-presenting cells (APCs) and modulates various immune responses. However, the role of IDO1 in the regulation of dendritic cells (DCs) during liver fibrosis is rarely reported. Here, we found that hepatic IDO1 was up-regulated during CCL4-induced liver fibrosis, which accompanied by a significant decrease in the frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+CD40+ and CD11c+MHCII+ cells and a reduction in the subsequent T cell proliferation rate, whereas these changes were reversed significantly in IDO1-/- mice. Overexpressing IDO1 by adeno-associated viral vector serotype 9 (AAV9) significantly inhibited the maturation status of DCs, worsened fibrosis. In vitro studies showed that significantly elevated CD80, CD86, CD40 and MHCII expression were observed in BMDCs derived from IDO1-/- mice. Moreover, the maturation of BMDCs derived from WT mice were significantly increased after stimulated with IDO1 inhibitor (1-methyl- D -tryptophan). Nuclear factor E2-related factor 2 (Nrf2), a key regulator of the cellular adaptive response to oxidative insults and inflammation, exhibited a markedly decrease in the liver of WT fibrotic mice, nevertheless, knockout of IDO1 enhanced the protein level of Nrf2. Moreover, the expression of IDO1 and Nrf2 exhibited inverse colocalization pattern suggesting that ectopically expressed IDO1 down-regulated Nrf2. Additionally, up-regulation of IDO1 was also observed in the livers of Nrf2-/- fibrotic mice. Taken together, these data uncovered mutual antagonism between IDO1 and Nrf2 on the maturation status of DCs during hepatic fibrosis.

Indoleamine 2, 3-dioxygenase 1enhanceshepatocytes ferroptosis in acute immune hepatitis associated with excess nitrative stress.

Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms of ferroptosis in acute immune hepatitis (AIH) are largely unknown. In this study, we investigated the classical ferroptotic events in the livers of mice with concanavalin A (ConA) to induce AIH. The dramatically upregulated gene indoleamine 2, 3-dioxygenase 1 (IDO1) was identified with AIH, and its role in generation of ferroptosis and reactive nitrogen species (RNS) was assessed both in vitro and in vivo by genetic deletion or pharmacologic inhibition of IDO1. We observed that ferroptosis contributed to the ConA-induced hepatic damage, which was confirmed by the therapeutical effects of ferroptosis inhibitor (ferrostatin-1). Noteworthy, upregulation of hepatic IDO1 and nitrative stress in ConA-induced hepatic damage were also remarkably inhibited by the ferroptosis abolishment. Additionally, IDO1 deficiency contributed to ferroptosis resistance by activating solute carrier family 7 member 11 (SLC7A11; also known as xCT) expression, accompanied with the reductions of murine liver lesions and RNS. Meanwhile, IDO inhibitor 1-methyl tryptophan alleviated murine liver damage with the reduction of inducible nitric oxide synthase and 3-nitrotyrosine expression. Consistent with the results in vivo, hepatocytes-specific knockdown of IDO1 led to ferroptosis resistance upon exposure to ferroptosis-inducing compound (Erastin) in vitro, whereas IDO1 overexpression aggravated the classical ferroptotic events, and the RNS stress. Overall, these results revealed a novel molecular mechanism of ferroptosis with the key feature of nitrative stress in ConA-induced liver injury, and also identified IDO1-dependent ferroptosis as a potential target for the treatment of AIH.