J-MISFET Hybrid Dual-Gate Switching Device for Multifunctional Optoelectronic Logic Gate Applications.

High-performance and low operating voltage are becoming increasingly significant device parameters to meet the needs of future integrated circuit (IC) processors and ensure their energy-efficient use in upcoming mobile devices. In this study, we suggest a hybrid dual-gate switching device consisting of the vertically stacked junction and metal-insulator-semiconductor (MIS) gate structure, named J-MISFET. It shows excellent device performances of low operating voltage (<0.5 V), drain current ON/OFF ratio (∼4.7 × 105), negligible hysteresis window (<0.5 mV), and near-ideal subthreshold slope (SS) (60 mV/dec), making it suitable for low-power switching operation. Furthermore, we investigated the switchable NAND/NOR logic gate operations and the photoresponse characteristics of the J-MISFET under the small supply voltage (0.5 V). To advance the applications further, we successfully demonstrated an integrated optoelectronic security logic system comprising 2-electric inputs (for encrypted data) and 1-photonic input signal (for password key) as a hardware security device for data protection. Thus, we believe that our J-MISFET, with its heterogeneous hybrid gate structures, will illuminate the path toward future device configurations for next-generation low-power electronics and multifunctional security logic systems in a data-driven society.

High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

Effect of thermal shock and sustained heat treatment on mainstream partial nitrification and microbial community in sequencing batch reactors.

In order to develop a promising means of achieving mainstream short-cut nitrification, this study evaluated the effect of thermal shock on nitrite accumulation using intermittent offline and continuous inline heat treatment of biomass in sequencing batch reactors (SBRs). The SBRs fed with municipal wastewater were operated at a solid retention time of 7 days and nitrogen loading rate of 0.04 gN/L·d to 0.08 gN/L·d without the application of pre-treatment. Contrary to literature studies that showed suppression of nitrite-oxidizing bacteria at temperature 60 to 80 °C, nitrite accumulation was achieved temporarily when 20% of the biomass was heated for 2 h at 47 °C, as well as in continuously heated SBRs at 37 °C and 42 °C. The continuously heated reactors at 37 °C and 42 °C produced a maximum nitrite accumulation ratio (NAR) of 0.59 and 0.79, respectively, whereas the intermittent offline heating at 47 °C-2 h produced a NAR of 0.37. Although nitrite accumulation was stable only for 10-12 days in all heated reactors, this study demonstrates the achievement of mainstream partial nitrification (PN) at lower temperature (42 °C) than that reported in literature and also highlights the potential for achieving PN by implementing heat treatment of a portion of the return activated sludge (RAS) in biological nitrogen removal (BNR) systems. During the time when full nitrification was achieved, Nitrospira was more dominant than Nitrosomonas in all reactors at ratios of 1.4:1, 2.4:1, 2.4:1, and 3.7:1 for the control SBR (22 °C), 47 °C -2 h offline heating SBR, 37 °C SBR, and 42 °C SBR, respectively, suggesting that it may have played a role as a comammox bacteria capable of degrading ammonia to nitrates at elevated temperature.

The Design of GNSS/IMU Loosely-Coupled Integration Filter for Wearable EPTS of Football Players.

This study presents the filter design of GNSS/IMU integration for wearable EPTS (Electronic Performance and Tracking System) of football players. EPTS has been widely used in sports fields recently, and GNSS (Global Navigation Satellite System) and IMU (Inertial Measurement Unit) in wearable EPTS have been used to measure and provide players' athletic performance data. A sensor fusion technique can be used to provide high-quality analysis data of athletic performance. For this reason, the integration filter of GNSS data and IMU data is designed in this study. The loosely-coupled strategy is considered to integrate GNSS and IMU data considering the specification of the wearable EPTS product. Quaternion is used to estimate a player's attitude to avoid the gimbal lock singularity in this study. Experiment results validate the performance of the proposed GNSS/IMU loosely-coupled integration filter for wearable EPTS of football players.

Effects of trace elements on digester performance and microbial community response in anaerobic digestion systems.

Trace elements (TE), as micronutrients for microorganisms, have a significant impact on the stability of anaerobic digestion (AD). Studies have been conducted on process stability and performance of the AD of food waste (FW) by supplementing TEs. In this study, mesophilic batch biomethane potential (BMP) tests using FW were conducted to investigate the effect of TEs (Fe, Ni, Co, Se, and Mo) as single and mixed ions. In view of their scarcity, correlations between the microbial community and digester performance such as first-order hydrolysis coefficient (Kh), volatile fatty acids (VFA), methane yield, and methane production rate (MPR) have been developed. Ni2+ at 1 and 1.5 mg/L increased the methane yield by 27% and 23% respectively. Similarly, Co2+ at 0.1 and 0.5 mg/L increased the yield by 21% and 23% respectively, compared to control. Although Se4+ at all concentrations enhanced the methane yield, Fe2+ at only 50 mg/L increased methane yield by 22%. For mixed TEs, the combination of Ni2+ [1 mg/L] +Co2+ was the best and increased methane for all Co2+ concentrations (0.1, 0.4 and 0.5 mg/L) by 16%, 14% and 12% respectively. Firmicutes and Methanosaeta were the most abundant phyla among hydrolytic and methanogenic microbial groups, respectively, constituting 42%-61% and 60-80% of their respective microbial groups. The most significant positive correlations were observed between aceto/acidogenic microorganisms and final VFA concentrations with Pearson correlation factors of 0.91.

Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production.

BACKGROUND: Lipid emulsion (LE) is effective in treating intractable cardiac depression induced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine (CQ)-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by CQ in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism. METHODS: The effects of CQ (1 × 10-4 M), LE, and the reactive oxygen species (ROS) scavengers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane potential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by CQ were assessed. RESULTS: Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migration and viability, mitochondrial membrane potential, and ATP levels evoked by CQ, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by CQ. LE inhibited the increase in Bax expression, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by CQ. CQ did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect CQ concentration. CONCLUSIONS: Collectively, these results suggest that LE (Lipofundin MCT/LCT) inhibits the cardiotoxicity and late apoptosis induced by CQ toxicity via the intrinsic mitochondrial apoptotic pathway that is associated with direct inhibition of ROS production.

Graphene Bridge Heterostructure Devices for Negative Differential Transconductance Circuit Applications.

Two-dimensional van der Waals (2D vdW) material-based heterostructure devices have been widely studied for high-end electronic applications owing to their heterojunction properties. In this study, we demonstrate graphene (Gr)-bridge heterostructure devices consisting of laterally series-connected ambipolar semiconductor/Gr-bridge/n-type molybdenum disulfide as a channel material for field-effect transistors (FET). Unlike conventional FET operation, our Gr-bridge devices exhibit non-classical transfer characteristics (humped transfer curve), thus possessing a negative differential transconductance. These phenomena are interpreted as the operating behavior in two series-connected FETs, and they result from the gate-tunable contact capacity of the Gr-bridge layer. Multi-value logic inverters and frequency tripler circuits are successfully demonstrated using ambipolar semiconductors with narrow- and wide-bandgap materials as more advanced circuit applications based on non-classical transfer characteristics. Thus, we believe that our innovative and straightforward device structure engineering will be a promising technique for future multi-functional circuit applications of 2D nanoelectronics.

A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells.

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1-4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.

Dexmedetomidine-Induced Aortic Contraction Involves Transactivation of the Epidermal Growth Factor Receptor in Rats.

In this study, we examined whether aortic contraction, induced by the alpha-2 adrenoceptor agonist dexmedetomidine, is involved in the transactivation of the epidermal growth factor receptor (EGFR) in isolated endothelium-denuded rat aortas. Additionally, we aimed to elucidate the associated underlying cellular mechanisms. The effects of the alpha-2 adrenoceptor inhibitor rauwolscine, EGFR tyrosine kinase inhibitor AG1478, Src kinase inhibitors PP1 and PP2, and matrix metalloproteinase inhibitor GM6001 on EGFR tyrosine phosphorylation and c-Jun NH2-terminal kinase (JNK) phosphorylation induced by dexmedetomidine in rat aortic smooth muscles were examined. In addition, the effects of these inhibitors on dexmedetomidine-induced contraction in isolated endothelium-denuded rat aorta were examined. Dexmedetomidine-induced contraction was inhibited by the alpha-1 adrenoceptor inhibitor prazosin, rauwolscine, AG1478, PP1, PP2, and GM6001 alone or by a combined treatment with prazosin and AG1478. AG1478 (3 × 10-6 M) inhibited dexmedetomidine-induced contraction in isolated endothelium-denuded rat aortas pretreated with rauwolscine. Dexmedetomidine-induced EGFR tyrosine and JNK phosphorylation were inhibited by rauwolscine, PP1, PP2, GM6001, and AG1478. Furthermore, dexmedetomidine-induced JNK phosphorylation reduced upon EGFR siRNA treatment. Therefore, these results suggested that the transactivation of EGFR associated with dexmedetomidine-induced contraction, mediated by the alpha-2 adrenoceptor, Src kinase, and matrix metalloproteinase, caused JNK phosphorylation and increased calcium levels.

Kinetics of aerobic cellulose degradation in raw municipal wastewater.

Cellulose contributes approximately one third of the influent suspended solids to wastewater treatment plants and is a key target for resource recovery. This study investigated the temperature impact on biological aerobic degradation of cellulose in laboratory-scale sequencing batch reactors (SBR) at four different temperatures (10-33 °C) and two different solids retention times (SRT) of 15 days and 3 days. The degradation efficiency of cellulose was observed to increase with temperature and was slightly dependent on SRT (80%-90% at an SRT of 15 days, and 78%-85% at an SRT of 3 days). Hydrolysis followed 1st order kinetics, rather than the biomass dependent Contois kinetics (default in the activated sludge models), with a hydrolysis coefficient at 20 °C of 1.14 ± 0.01 day-1.

Preparation of Polydimethylsiloxane-Modified Waterborne Polyurethane Coatings for Marine Applications.

A series of waterborne polyurethane dispersions (WPUs) modified with hydroxyl-terminated polydimethylsiloxane (PDMS) were prepared by incorporating PDMS into the soft segments of polyurethane chains. The structural characteristics of the prepared samples were analyzed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and particle size analysis (PSA). The effect of PDMS content on the thermal and mechanical properties of PDMS-modified waterborne polyurethanes (PS-WPU) was investigated. In addition, the water resistance and dimensional stability of the PS-WPU were investigated by measuring its water absorption ratio and water contact angle along with universal testing machine measurements.

Post-surgical wireless monitoring of arterial health progression.

Early detection of limb ischemia, strokes, and heart attacks may be enabled via long-term monitoring of arterial health. Early stenosis, decreased blood flow, and clots are common after surgical vascular bypass or plaque removal from a diseased vessel and can lead to the above diseases. Continuous arterial monitoring for the early diagnosis of such complications is possible by implanting a sensor during surgery that is wirelessly monitored by patients after surgery. Here, we report the design of a wireless capacitive sensor wrapped around the artery during surgery for continuous post-operative monitoring of arterial health. The sensor responds to diverse artery sizes and extents of occlusion in vitro to at least 20 cm upstream and downstream of the sensor. It demonstrated strong capability to monitor progression of arterial occlusion in human cadaver and small animal models. This technology is promising for wireless monitoring of arterial health for pre-symptomatic disease detection and prevention.

The effect of autogenous tooth bone graft material without organic matter and type I collagen treatment on bone regeneration.

OBJECTIVES: The aim of this study is to examine the effect of particulate autogenous tooth graft removed with organic matter and type I collagen addition on bone regeneration and to validate the possibility of useful allograft material for jaw defects. MATERIAL AND METHODS: Autogenous tooth bone maker (Korean Dental Solution® KOREA) made particulate autogenous tooth not including organic matter. We used to the developed tooth grafts for experiment. Cell adhesion test with hemacytometer and energy dispersive X-ray spectroscopy (Supra40 VP®, Carl Zeiss, Germany) analysis about the particulate autogenous tooth and type I collagen were performed. Rabbits were divided into three groups: bone graft with organic matter (OM) removing particulate autogenous tooth group, bone graft with OM removing particulate autogenous tooth and type I collagen group, and a control group. Bone grafting was performed in rabbit's calvaria. The rabbits were sacrificed at different interval at 1, 2, 4, and 6 weeks after bone grafting for the histopathologic observation and observed the effect of bone regeneration by SEM, H-E & Masson stains, osteocalcin IHC staining. RESULT: In vitro cytopathological study showed affinity for cells, cell attachment pattern, and cell proliferation in the order of control group, OM-removed and collagen-treated group, OM-removed particulate autogenous tooth group. The results of the degree of mineralization were opposite to those of the previous cell experimental results, and the OM-removed group, OM-removed group and collagen-treated group were relatively higher than the control group. Histopathologic analysis showed that vascularization and neonatal bone formation were higher in particulate autogenous tooth group with removing OM and with addition of collagen than control group and group of OM removed only. Immunohistochemical analysis showed that osteocalcin (OSC) expression was not observed in the control group, but at 4 weeks groups, OSC expression was observed the OM removed and OM-removed-collagen-treated particulate autogenous tooth, and the degree of expression was somewhat stronger in group of the OM removed and collagen additionally treated particulate autogenous tooth. CONCLUSION: Particles that do not contain organic matter, the saint tooth, was responsible for sufficient bone graft material through the role of space maintenance and bone conduction, and further improved bone formation ability through additional collagen treatment. Therefore, research on various extracellular substrates and autologous bone grafting materials is necessary, and through this, it is possible to lay the foundation for a new type of autologous bone grafting material with excellent academic and technical utility.

Decursin Alleviates Mechanical Allodynia in a Paclitaxel-Induced Neuropathic Pain Mouse Model.

Chemotherapy-induced neuropathic pain (CINP) is a severe adverse effect of platinum- and taxane-derived anticancer drugs. The pathophysiology of CINP includes damage to neuronal networks and dysregulation of signal transduction due to abnormal Ca2+ levels. Therefore, methods that aid the recovery of neuronal networks could represent a potential treatment for CINP. We developed a mouse model of paclitaxel-induced peripheral neuropathy, representing CINP, to examine whether intrathecal injection of decursin could be effective in treating CINP. We found that decursin reduced capsaicin-induced intracellular Ca2+ levels in F11 cells and stimulated neurite outgrowth in a concentration-dependent manner. Decursin directly reduced mechanical allodynia, and this improvement was even greater with a higher frequency of injections. Subsequently, we investigated whether decursin interacts with the transient receptor potential vanilloid 1 (TRPV1). The web server SwissTargetPrediction predicted that TRPV1 is one of the target proteins that may enable the effective treatment of CINP. Furthermore, we discovered that decursin acts as a TRPV1 antagonist. Therefore, we demonstrated that decursin may be an important compound for the treatment of paclitaxel-induced neuropathic pain that functions via TRPV1 inhibition and recovery of damaged neuronal networks.

A Study on User Recognition Using the Generated Synthetic Electrocardiogram Signal.

Electrocardiogram (ECG) signals are time series data that are acquired by time change. A problem with these signals is that comparison data that have the same size as the registration data must be acquired every time. A network model of an auxiliary classifier based generative adversarial neural network that is capable of generating synthetic ECG signals is proposed to resolve the data size inconsistency problem. After constructing comparison data with various combinations of the real and generated synthetic ECG signal cycles, a user recognition experiment was performed by applying them to an ensemble network of parallel structure. Recognition performance of 98.5% was demonstrated when five cycles of real ECG signals were used. Moreover, 98.7% and 97% accuracies were provided when the first cycle of synthetic ECG signals and the fourth cycle of real ECG signals were repetitively used as the last cycle, respectively, in addition to the four cycles of real ECG. When two cycles of synthetic ECG signals were used with three cycles of real ECG signals, 97.2% accuracy was shown. When the last third cycle was repeatedly used with the three cycles of real ECG signals, the accuracy was 96%, which was 1.2% lower than the performance obtained while using the synthetic ECG. Therefore, even if the size of the registration data and that of the comparison data are not consistent, the generated synthetic ECG signals can be applied to a real life environment, because a high recognition performance is demonstrated when they are applied to an ensemble network of parallel structure.

Simultaneous nitrification-denitrifying phosphorus removal (SNDPR) at low DO for treating carbon-limited municipal wastewater.

This study investigated simultaneous nitrification-denitrifying phosphorus removal in a sequencing batch reactor (SBR) activated sludge process. The process consisted of an extended anaerobic period (180 min) followed by a low DO (0.3 ± 0.05 mg/L) simultaneous nitrification-denitrifying phosphorus removal. The reactor was operated within a wide range of COD/N ratio (5-10) without any volatile fatty acids (VFA) supplementation. N and P removal efficiencies were as high as 91% and 96%, respectively. The process was efficient even at a very low COD /N ratio of 5, with N and P removal efficiencies of 70% and 90%, respectively. The N and P removal efficiencies improved to more than 90% at a COD/N ratio 8. It was found that the initial filtered flocculated COD (ffCOD)/[total oxidized Kjeldahl Nitrogen (TKNoxidized) + NOx-Nintitial] ratio in the reactor played a significant role in the process efficiency. It was observed that N-removal efficiency decreased with a decrease of [ffCODinitial/ (TKNoxidized + NOx-Ninitial)] ratio even at high COD/N ratio of 10. Simultaneous nitrification denitrification (SND) efficiencies varied between 60%-88% depending on the influent COD/N ratio and [ffCODinitial/ (TKNoxidized + NOx-Ninitial)] ratio in the reactor. Cyclic studies showed a distinct two step phosphorus release in the extended anaerobic period in contrast to the more conventional single step phosphorus release. During the aerobic period, low DO favored denitrifying P-removal without significant accumulation of NO3-N, and NO2-N until all endogenous carbon was consumed. Denitrifying phosphorus accumulating organisms (DPAOs) played a vital role in simultaneous denitrification and phosphorus removal. Aerobic and anoxic P-removal represented about 55% and 45% of the overall phosphorus removal, respectively. Cycle tests showed that DPAOs have a competitive advantage over NOB for nitrite consumption at low DO. The process was found to be carbon efficient as evidenced by the COD/NOx-N ratio of 4.2 for denitrification. Compared to traditional enhanced biological phosphorus removal (EBPR) coupled with exogenous denitrification, this process reduces carbon and oxygen demand for combined N and P removal from municipal wastewater by about 45%, and 35% respectively.

3,4,5-Trihydroxycinnamic acid exerts anti-asthmatic effects in vitro and in vivo.

3,4,5-Trihydroxycinnamic acid (THCA) has been reported to possess anti-inflammatory activity. However, the effect of THCA for treating allergic asthma was unknown. Therefore, in the present study, the anti-asthmatic effects of THCA were studied in both in vitro and in vivo studies. In phorbol 12-myristate 13-acetate (PMA)-stimulated A549 airway epithelial cells, THCA pretreatment decreased the mRNA expression and secretion of interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecules 1 (ICAM-1), and reduced the mRNA expression of matrix metalloproteinase 9 (MMP-9). THCA also inhibited PMA-induced protein kinase B (AKT), mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation in A549 cells. In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, THCA pretreatment suppressed the mRNA expression of ICAM-1 and MMP-9. In addition, THCA suppressed the adhesion of EOL and A549 cells. In ovalbumin (OVA)-administered asthmatic mice, THCA exerted inhibitory activity on IL-5, IL-13, and MCP-1 in bronchoalveolar lavage fluid (BALF) and on OVA-specific immunoglobulin E (IgE) in serum. THCA attenuated the numbers of inflammatory cells in BALF and the influx of inflammatory cell in lung tissues. Furthermore, THCA downregulated the levels of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), and leukotriene B4 (LTB4) expression, mucus production and CREB phosphorylation as well as Penh value. These effects were accompanied by suppression of AKT, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB activation. Therefore, the results of the current study suggest that THCA may be a valuable adjuvant or therapeutic in the prevention or treatment of allergic asthma.

The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice.

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1ß, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

3,4,5-Trihydroxycinnamic acid exerts a protective effect on pulmonary inflammation in an experimental animal model of COPD.

3,4,5-Trihydroxycinnamic acid (THCA), a derivative of hydroxycinnamic acid, has been reported to exert anti-inflammatory and antioxidant activities. However, its anti-inflammatory effects in chronic obstructive pulmonary disease (COPD) have not yet been elucidated. Therefore, we explored the protective effects of THCA on pulmonary inflammation in an experimental COPD model elicited by cigarette smoke (CS) and lipopolysaccharide (LPS). Oral administration of THCA significantly inhibited the activity of elastase, the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO) and the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) of experimental COPD mice. THCA also exerted inhibitory effects on the recruitment of inflammatory cells, the levels of PAS positive cells and cAMP-response-element-binding protein (CREB) activation, and the expression of phosphodiesterase 4 (PDE4) in the lungs of experimental COPD mice. In addition, THCA exerted a regulatory effect on the activation of p38, ERK and nuclear factor-κB (NF-κB) in the lungs of experimental COPD mice. THCA also significantly upregulated the expression of NAD(P)H dehydrogenase (quinone 1) 1 (NQO1) and the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in the lungs of mice. Furthermore, THC restored the reduction of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in the lungs of experimental COPD mice. In phorbol myristate acetate (PMA)-stimulated A549 or H292 airway epithelial cells, pretreatment of THCA dose-dependently inhibited the generation of IL-6. THCA also led to increased NQO1 expression in H292 cells. Collectively, these protective effects of antioxidant THCA were notably excellent and are thought to be associated with the downregulation of MAPK (partial)/NF-κB signaling and upregulation of NQO1 and SIRT1 expression.