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Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands1-6. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gαq and the arrestin-biased ligand SBI-5537. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gαq protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling.
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Quinase 2 de Receptor Acoplado a Proteína G , Receptores Acoplados a Proteínas G , Transdução de Sinais , Arrestinas/metabolismo , Fosforilação , Receptores Acoplados a Proteínas G/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/biossíntese , Quinase 2 de Receptor Acoplado a Proteína G/química , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Ligantes , Ligação Proteica , Receptores de Neurotensina/metabolismoRESUMO
Most EML4-ALK rearrangement non-small cell lung cancer (NSCLC) patients inevitably develop acquired drug resistance after treatment. The main mechanism of drug resistance is the acquired secondary mutation of ALK kinase domain. L1196M and G1202R are classical mutation sites. We urgently need to understand the underlying molecular mechanism of drug resistance to study the therapeutic targets of mutant drug-resistant NSCLC cells. The silent information regulator sirtuin1 (SIRT1) can regulate the normal energy metabolism of cells, but its role in cancer is still unclear. In our report, it was found that the SIRT1 in EML4-ALK G1202R and EML4-ALK L1196M mutant drug-resistant cells was downregulated compared with EML4-ALK NSCLC cells. The high expression of SIRT1 was related to the longer survival time of patients with lung cancer. Activation of SIRT1 induced autophagy and suppressed the invasion and migration of mutant cells. Further experiments indicated that the activation of SIRT1 inhibited the phosphorylation level of mTOR and S6K by upregulating the expression of AMPK, thus activating autophagy. SIRT1 can significantly enhanced the sensitivity of mutant cells to crizotinib, improved its ability to promote apoptosis of mutant cells, and inhibited cell proliferation. In conclusion, SIRT1 is a key regulator of drug resistant in EML4-ALK L1196M and G1202R mutant cells. SIRT1 may be a novel therapeutic target for EML4-ALK drug resistant NSCLC.
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This study proposes an ultraviolet-visible composite optical target simulation technique based on a liquid crystal display (LCD) spatial light modulation device to solve the problem of not being able to satisfy the demand for optical target simulation for both ultraviolet and visible light operating spectral ranges in a single system when composite simulation of multi-source spatial targets is performed. We establish a composite light source model of an ultraviolet light emitting diode (LED) and a xenon lamp to enhance the energy simulation of the ultraviolet portion, and the light is mixed and homogenized by an integrating sphere. We analyze the light transmission principle of LCD display devices and derive the equation for the relationship between its working band and transmittance. We design a transmission-type projection system with a wide spectral range and simulate the transmittance of the whole system, and demonstrate the optical target simulator can realize the simulation requirements of a wide working spectral range, high interstellar angular distance accuracy, and high magnitude accuracy.
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Sudden jump of transmembrane pressure (TMP) in membrane bioreactors (MBRs), associated with abrupt aggravation of membrane fouling, limits practical applications of MBRs and calls for effective mitigation strategies. While the TMP jump is generally related to the bacterial activity of biocakes, the mechanisms underlying the TMP jump remain unclear. Herein, we conducted various backwash protocols with different nutrient (e.g., nitrate and sodium acetate) loadings on fouled membranes in MBRs to reveal the critical role of bacterial activity of biocakes for the TMP jump. The filtration tests showed a lower TMP jump rate for the membrane backwashed with a nutrient solution (a mixture of 180 mg/L NaNO3 and 200 mg/L NaAc, averaged at 1.40 kPa/d) than that backwashed with tap water (averaged at 3.56 kPa/d), implying that TMP jump could be efficiently mitigated by providing sufficient nutrients to biocake bacteria. The characterization of biocakes showed that high-nutrient solution backwash considerably increased bacterial viability and activity, while considerably reducing biomolecule accumulation on membranes. The keystone taxa (e.g., g_Aeromonas and o_Chitinophagaceae) in the network of nutrient-enriched biocake communities were involved in nitrate reduction and biomolecule degradation. Ecological null model analyses revealed that the deterministic manner mainly shaped biocake communities with high-nutrient availability. Overall, this study highlights the significance of the bacterial activity of biocakes for TMP development and provides potential alternatives for controlling membrane fouling.
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Reatores Biológicos , Membranas Artificiais , Pressão , Filtração , Bactérias/metabolismoRESUMO
Life and death are 2 fundamental concepts regarding existence of organisms. People often signify these concepts using symbols to facilitate communications, but how the brain learns and represents these symbols remains unclear. In the present study, we quantified behavioral and brain responses during learning associations between words ("life" or "death") with shapes as concrete referents. Behavioral responses to word-shape pairs showed an affirmative response bias to life-shape pairs but a denial response bias to death-shape pairs. Multimodal brain imaging results revealed that the right frontal and dorsal cingulate cortices monitored these response biases, respectively. Moreover, relative to unlearned shapes, life-related shapes induced increased alpha (9-14 Hz) oscillations in the right parietal cortex and precuneus, whereas death-related shapes enhanced beta (15-30 Hz) oscillations in the left parietal cortex, superior temporal sulcus, and precuneus. Our findings unraveled distinct neurocognitive mechanisms underlying learning and representations of concrete referents of life and death concepts.
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Imageamento por Ressonância Magnética , Lobo Parietal , Humanos , Imageamento por Ressonância Magnética/métodos , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Aprendizagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Lobo Temporal/fisiologia , Mapeamento EncefálicoRESUMO
Outgroup aggression characterizes intergroup conflicts in human societies. Previous research on relationships between cultural traits and outgroup aggression behavior showed inconsistent results, leaving open questions regarding whether cultural traits predict individual differences in outgroup aggression and related neural underpinnings. We conducted 2 studies to address this issue by collecting self-construal scores, EEG signals in response to Asian and White faces with painful or neutral expressions, and decisions to apply electric shocks to other-race individuals in a context of interracial conflict. We found that interdependent self-construals were well explained by 2 subcomponents, including esteem for group (EG) and relational interdependence (RI), which are related to focus on group collectives and harmonious relationships, respectively. Moreover, EG was positively associated with the decisions to punish racial outgroup targets, whereas RI was negatively related to the decisions. These opposite relationships were mediated by neural representations of perceived race at 120-160 ms after face onset. Our findings highlight the multifaceted nature of interdependent self-construal and the key role of neural representations of race in mediating the relationships of different subcomponents of cultural traits with racial outgroup punishment decisions in a context of interracial conflict.
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Agressão , Punição , Humanos , DorRESUMO
In laser direct writing lithography, there is not any image information from the sample surface, which makes it difficult to find the position of the focal plane. To overcome the problem, an autofocusing through the crosshair projection method is proposed in this work. The crosshair on the reticle is inserted into the lighting path and imaged onto the sample surface. The addition of the crosshair projection increases the image information from the sample surface, meeting the requirement for the image information in focusing and improving the focusing environment. Furthermore, this work presents what we believe to be a new division of the focusing curve based on the range of the perpendicular feature extracted from the crosshair projection during the focusing process. The perpendicular feature can be extracted from the crosshair projection in the focusing zone but not in the flat zone. Compared with the traditional division, this new division enables the use of the perpendicular feature to directly determine the zone of the current sample position and to find the focusing zone during the focusing process. This can completely filter out the interference of local fluctuations in the flat zone, greatly facilitating the sample focusing. The autofocusing process was designed based on this division, and experiments were carried out accordingly. The focusing accuracy is about 0.15 µm, which is in the range of the depth of focus of the optical system. The results show that the proposed method provides a good solution to achieve accurate focusing based on the crosshair projection image from the sample surface in laser lithography.
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In this work, complex Chinese micropatterns are experimentally inscribed in AgInSbTe thin films through laser writing technique. The overlapping inscription strategy is introduced to reduce the size of complex Chinese micropatterns, and the erosion algorithm is used to eliminate sticking effects among fine strokes in complex Chinese micropatterns. The results show that the size of complex Chinese micropatterns can be reduced to around 15.41µm×15.41µm. The width of the finest stroke is only 0.45 µm. This method can achieve a fidelity of 95%. This work helps with the long-term preservation of massive Chinese character archives.
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While amber suppression is the most common approach to introduce noncanonical amino acids into proteins in live cells, quadruplet codon decoding has potential to enable a greatly expanded genetic code with up to 256 new codons for protein biosynthesis. Since triplet codons are the predominant form of genetic code in nature, quadruplet codon decoding often displays limited efficiency. In this work, we exploited a new approach to significantly improve quadruplet UAGN and AGGN (N = A, U, G, C) codon decoding efficiency by using recoding signals imbedded in mRNA. With representative recoding signals, the expression level of mutant proteins containing UAGN and AGGN codons reached 48% and 98% of that of the wild-type protein, respectively. Furthermore, this strategy mitigates a common concern of reading-through endogenous stop codons with amber suppression-based system. Since synthetic recoding signals are rarely found near the endogenous UAGN and AGGN sequences, a low level of undesirable suppression is expected. Our strategy will greatly enhance the utility of noncanonical amino acid mutagenesis in live-cell studies.
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Código Genético , Técnicas Genéticas , Mutagênese , Aminoácidos/genética , Aminoácidos/metabolismo , Biossíntese de Proteínas , Proteínas/genéticaRESUMO
BACKGROUND: Patients receiving epidural or intrathecal opioids administration for neuraxial analgesia frequently suffer from an irritating itch. STING (stimulator of interferon genes), an innate immune modulator, is strongly implicated in pain pathogenesis via neuron-immune modulation. Given that pain and itch share some common neurocircuits, we evaluate the therapeutic potential of STING agonists in opioid-induced itch and chronic itch. METHODS: Opioids (morphine, fentanyl and sufentanil) were intrathecally injected to induce acute itch. Chronic itch was induced by dry skin and contact dermatitis. Opioids analgesic effect, itch-induced scratching behavior, spinal expression of STING, phosphorylation of TBK1 (tank-binding kinase 1), IRF3 (interferon regulatory factor-3) and ERK (extracellular signal-regulated kinase), as well as production of IFN-α and IFN-ß were examined. STING agonists (DMXAA and ADU-S100), TBK1 inhibitor, recombinant IFN-α and IFN-ß elucidated the mechanism and treatment of itch. Whole-brain functional connectivity was evaluated using resting-state fMRI. RESULTS: We report the primary expression of STING protein by the spinal dorsal horn neurons. Intraperitoneal injection of DMXAA dose-dependently reduces morphine-induced scratch bouts, without impairing morphine antinociception. Simultaneously, DMXAA alleviates fentanyl- and sufentanil-induced itching-like behavior, and chronic scratching behavior caused by dry skin and contact dermatitis. Furthermore, DMXAA drastically increases spinal phosphorylation of TBK1 and IRF3 following morphine exposure, dry skin and contact dermatitis. DMXAA-induced anti-pruritus effects and spinal productions of IFN-α and IFN-ß are compensated by intrathecal delivery of the TBK1 inhibitor. Also, ADU-S100, recombinant IFN-α and IFN-ß exhibits remarkable attenuation in scratching behaviors after morphine injection and dermatitis. Recombinant IFN-α inhibits morphine-induced spinal phosphorylation of ERK. Finally, DMXAA prevents dermatitis-induced the increase of cerebral functional connectivity between regions of interests such as primary somatosensory cortex, piriform cortex, retrosplenial cortex, colliculus and ventral thalamus. CONCLUSIONS: STING activation confers protection against opioid-induced itch and chronic itch through spinal up-regulation of TBK1-IRF3-type I interferon cascades in mice, suggesting that STING agonists are promising candidates in translational development for pruritus relief.
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Dermatite de Contato , Dermatite , Interferon Tipo I , Animais , Camundongos , Analgésicos Opioides/farmacologia , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Morfina , Dor , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Sufentanil/efeitos adversosRESUMO
Producing stable nitrite is a necessity for anaerobic ammonium oxidation (anammox) but remains a huge challenge. Here, we describe the design and operation of a hydrogenotrophic denitratation system that stably reduced >90% nitrate to nitrite under self-alkaline conditions of pH up to 10.80. Manually lowering the pH to a range of 9.00-10.00 dramatically decreased the nitrate-to-nitrite transformation ratio to <20%, showing a significant role of high pH in denitratation. Metagenomics combined with metatranscriptomics indicated that six microorganisms, including a Thauera member, dominated the community and encoded the various genes responsible for hydrogen oxidation and the complete denitrification process. During denitratation at high pH, transcription of periplasmic genes napA, nirS, and nirK, whose products perform nitrate and nitrite reduction, decreased sharply compared to that under neutral conditions, while narG, encoding a membrane-associated nitrate reductase, remained transcriptionally active, as were genes involved in intracellular proton homeostasis. Together with no reduction in only nitrite-amended samples, these results disproved the electron competition between reductions of nitrate and nitrite but highlighted a lack of protons outside cells constraining biological nitrite reduction. Overall, our study presents a stably efficient strategy for nitrite production and provides a major advance in the understanding of denitratation.
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Nitratos , Nitritos , Nitritos/química , Desnitrificação , Oxirredução , Concentração de Íons de Hidrogênio , Reatores Biológicos , NitrogênioRESUMO
Believing as a fundamental mental process influences other cognitive/affective processes and behavior. However, it is unclear whether believing engages distinct neurocognitive mechanisms in people with different cultural experiences. We addressed this issue by scanning Chinese and Danish adults using functional MRI during believing judgments on personality traits of oneself and a celebrity. Drift diffusion model analyses of behavioral performances revealed that speed/quality of information acquisition varied between believing judgments on positive and negative personality traits in Chinese but not in Danes. Chinese adopted a more conservative strategy of decision-making during celebrity- than self-believing judgments whereas an opposite pattern was observed in Danes. Non-decisional processes were longer for celebrity- than for self-believing in Danes but not in Chinese. Believing judgments activated the medial prefrontal cortex (mPFC) in both cultural groups but elicited stronger left anterior insular and ventral frontal activations in Chinese. Greater mPFC activity in Chinese was associated with longer duration of non-decision processes during believing-judgments, which predicted slower retrieval of self-related information in a memory test. Greater mPFC activity in Danes, however, was associated with a less degree of adopting a conservative strategy during believing judgments, which predicted faster retrieval of self-related information. Our findings highlight different neurocognitive processes engaged in believing between individuals from East Asian and Western cultures.
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Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Comparação Transcultural , Cultura , Tomada de Decisões/fisiologia , Julgamento/fisiologia , Imageamento por Ressonância Magnética/métodos , Personalidade/fisiologia , Adulto , China , Dinamarca , Feminino , Humanos , MasculinoRESUMO
Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca2+ oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3ß activator of pyrvinium. Moreover, an IP3 receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca2+ oscillation/Calcineurin/GSK-3ß and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.
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Calcineurina , Microglia , Anti-Inflamatórios/farmacologia , Calcineurina/metabolismo , Linhagem Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores sigma , Fator de Necrose Tumoral alfa/metabolismo , Receptor Sigma-1RESUMO
A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice. In addition, co-culture with exosomes from depression models or patients instead of from controls prevented LPS-induced inflammation responses in microglial BV2 cells. Moreover, Sig-1R was demonstrated for the first time to significantly be enriched in exosomes from depression models or patients compared with that from normal controls. However, Sig-1R null exosomes no longer emerged antidepressant-like action in LPS-challenged mice. Thus, we demonstrated that plasma exosomes from depression exerted antidepressant-like effects in a Sig-1R dependent manner in the LPS-induced depression. This work improves our understanding of the exosomes in depression, suggesting a novel exosomes-based approach for MDD treatment.
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Transtorno Depressivo Maior , Exossomos , Animais , Depressão , Células HEK293 , Humanos , Inflamação , Camundongos , Receptores sigma , Receptor Sigma-1RESUMO
Graphene has been used as a conductive substrate to improve the electrochemical performance of layered VS2 as an anode material for lithium-ion batteries. However, there is still a lack of in-depth understanding of the synergistic effect between the layered VS2 and graphene, which contributes to the enhanced performance of Li/Na-ion batteries. In this work, using first-principles calculations, we have systematically studied the VS2/graphene heterostructure as an anode material for Li/Na-ion batteries. Our results show that the VS2/graphene heterostructure is a promising anode material with good structural stability, high adsorption strength, high stiffness, intrinsic metallic characteristic after Li/Na adsorption, high theoretical specific capacity, shallow averaged open-circuit voltage and ultra-low ion diffusion barriers. The diffusion barriers are found to be 0.03 eV (Li) and 0.08 eV (Na), superior to that of the widely studied heterostructure materials, which guarantees an extremely fast Li/Na diffusion rate during charge/discharge cycling. The anode overall open-circuit voltages for the Li/Na-ion batteries are calculated to be as low as 0.65 and 0.46 V, and the maximum theoretical storage capacity is 771 and 578 mA h g-1, respectively. The above results provide valuable insights into the experimental set-up of the VS2/graphene nanocomposite anode material for ultra-high rate and high-specific capacity Li/Na-ion batteries.
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Despite sigma-1 receptor (Sig-1R) is a promising therapeutic target in depression, little is known regarding the cellular mechanisms underlying its antidepressant responses. Here, we demonstrated that astrocyte can be a direct cellular target of Sig-1R exerting antidepressant-like effect. In multiple behavioral models including forced swimming test (FST), tail suspension test (TST), open field test (OFT), and chronic unpredictable mild stress (CUMS), inhibition of astrocyte function blocked pharmacological Sig-1R activation-induced antidepressant-like effect, while specific activation of astrocytc Sig-1R by adeno-associated virus (AAV) was sufficient to produce antidepressant-like effect. In depression-related cellular tests, Sig-1R agonist or lentivirus-stimulated astrocyte conditioned medium (ACM) promoted neuronal neurite outgrowth, dendritic branch, and survival. Mechanismly, stimulation of Sig-1R enhanced the expression of CD38 via activation of extracellular regulated protein kinases 1/2 (ERK1/2), resulting in facilitating mitochondrial transfer from astrocyte. Furthermore, blockage of CD38-driven astrocyte transferring mitochondria in vivo and in vitro reversed the antidepressant-like effect of pharmacological Sig-1R activation. Thus, this study sheds light on the cellular mechanism of Sig-1R activation producing antidepressant-like effect. These data present the first evidence that enhancement of Sig-1R action on astrocytes entirely exerts antidepressant-like effect, indicating that specific activation of astrocytic Sig-1R may provide a new approach for antidepressant drug development.
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Astrócitos , Antidepressivos/farmacologia , Mitocôndrias , Receptores sigma , Receptor Sigma-1RESUMO
Aiming at the fault diagnosis issue of rotating machinery, a novel method based on the deep learning theory is presented in this paper. By combining one-dimensional convolutional neural networks (1D-CNN) with self-normalizing neural networks (SNN), the proposed method can achieve high fault identification accuracy in a simple and compact architecture configuration. By taking advantage of the self-normalizing properties of the activation function SeLU, the stability and convergence of the fault diagnosis model are maintained. By introducing α -dropout mechanism twice to regularize the training process, the overfitting problem is resolved and the generalization capability of the model is further improved. The experimental results on the benchmark dataset show that the proposed method possesses high fault identification accuracy and excellent cross-load fault diagnosis capability.
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BACKGROUND: /Objective: To evaluate the factor structure of the simplified Chinese version of "Perceived Physical Literacy Instrument" (PPLI) among Chinese undergraduates. METHODS: The PPLI scale (simplified Chinese version) is based on the original 18-item Cantonese version of PPLI scale, which was first constructed and validated to measure the perceived physical literacy (PL) of physical education (PE) teachers and adolescents in Hong Kong. In this study, 622 undergraduates were randomly split into two subsets. Exploratory factor analysis (EFA) was conducted on the first subset (n = 311) and then confirmatory factor analysis (CFA) was conducted on the second subset (n = 311) for the adapted version based upon the first EFA result. RESULTS: EFA led to an 8-item, 3-factor scale and item loadings ranged from 0.68 to 0.93, Cronbach's alpha ranged from 0.79 to 0.83. CFA showed that the construct factor loading ranged from 0.60 to 0.92, which further confirmed the satisfactory factor validity. CONCLUSION: The PPLI (simplified Chinese version) is a reliable and valid instrument to examine the perceived PL for Chinese undergraduates. Unlike the original Cantonese version of PPLI, PPLI (simplified Chinese version) exactly explore the kernel attributes, namely, motivation, confidence and physical competence, and interaction with the environment, of the concept of PL. Build from this instrument, more studies could explore the potential factors that influence the physical activity level, as well as structure appropriate intervention programs to utilize PL as a standard to evaluate the quality of PE courses or foster lifelong physical activity level, among Chinese young generation.
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N-doped and double-walled carbon nanotube-modified TiO2 (DWCNT-N/TiO2) hybrid was synthesized using a two-step hydrothermal method and characterized using X-ray diffraction, UV-vis diffuse reflectance spectroscopy, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. DWCNT-N/TiO2 photocatalytic activities were investigated on the basis of the photocatalytic degradation of sulfathiazole under visible light irradiation. Experimental results showed that DWCNTs in the hybrid were coated with N/TiO2 nanoparticles, which facilitated close contact between the DWCNTs and N/TiO2. Modification with DWCNTs contributed to the separation of photo-generated carriers and the absorption of visible light. N-doping provided the DWCNT-N/TiO2 hybrid with enhanced absorption of visible light. The significant visible-light-driven photo-catalytic activity of the DWCNT-N/TiO2 hybrid was caused by the synergetic effects of DWCNT modification and N-doping.
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Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5 ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM2.5 exposure. However, the mechanisms underlying PM2.5 -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM2.5 -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)-1ß, and IL-18 in BALF were determined using ELISA. mRNA levels of IL-6, IL-1ß, IL-18, CXCL1, IL-10, NLRP3, Caspase-1, and NLRP12 in lung tissues were determined by RT-PCR. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase-1, NLRP3, NF-κB-p52/p100, and NF-κB-p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM2.5 exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM2.5 were markedly elevated relative to the control. mRNA levels of CXCL1, IL-1ß, and IL-18 in lung tissues of PM2.5 -exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM2.5 -exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM2.5 -instilled mice were higher than those in the lungs of the control. The protein levels of NF-κB-p52/p100 and NF-κB-p65 in bronchial epithelium of PM2.5 -exposed mice were also increased compared with the control. This study suggests that EGF-EGFR-Akt-NF-κB signaling and NLRP12 inflammasome may be associated with PM2.5 -induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017.