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A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808â nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808â nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.
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Antineoplásicos , Complexos de Coordenação , Raios Infravermelhos , Fótons , Tiofenos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Tiofenos/química , Tiofenos/farmacologia , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Rutênio/química , Rutênio/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Terapia Fototérmica , Irídio/química , Estrutura Molecular , Apoptose/efeitos dos fármacosRESUMO
Carbon dioxide can be relatively easily reduced to organic matter in a bioelectrochemical system (BES). However, due to insufficient reduction force from in-situ hydrogen evolution, it is difficult for nitrogen reduction. In this study, MoS2 was firstly used as an electrocatalyst for the simultaneous reduction of CO2 and N2 to produce microbial protein (MP) in a BES. Cell dry weight (CDW) could reach 0.81±0.04â g/L after 14 d operation at -0.7â V (vs. RHE), which was 108±3 % higher than that from non-catalyst control group (0.39±0.01â g/L). The produced protein had a better amino acid profile in the BES than that in a direct hydrogen system (DHS), particularly for proline (Pro). Besides, MoS2 promoted the growth of bacterial cell on an electrode and improved the biofilm extracellular electron transfer (EET) by microscopic observation and electrochemical characterization of MoS2 biocathode. The composition of the microbial community and the relative abundance of functional enzymes revealed that MoS2 as an electrocatalyst was beneficial for enriching Xanthobacter and enhancing CO2 and N2 reduction by electrical energy. These results demonstrated that an efficient strategy to improve MP production of BES is to use MoS2 as an electrocatalyst to shift amino acid profile and microbial community.
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Dióxido de Carbono , Dissulfetos , Técnicas Eletroquímicas , Molibdênio , Molibdênio/química , Molibdênio/metabolismo , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Dissulfetos/química , Dissulfetos/metabolismo , Catálise , Ar , Proteínas de Bactérias/metabolismo , Nitrogênio/química , Nitrogênio/metabolismo , Fontes de Energia Bioelétrica , EletrodosRESUMO
We propose a polarization insensitive, flexible ultra-broadband terahertz (THz) metamaterial absorber. It consists of a chromium composite resonator on the top, a polyimide (PI) dielectric layer in the middle, and a chromium substrate. The simulation results show that the absorption achieves more than 90% ultra-wideband absorption in the range of 1.92-4.34 THz. The broadband absorption is produced by the combination of electric dipole resonance and magnetic resonance, as well as impedance matching with free space. Due to the rotational symmetry of the unit structure, the absorber is insensitive to polarization of the THz wave and has a larger range of incident angles. The total thickness of the absorber is only 13.4 µm, showing highly flexible and excellent high-temperature resistance characteristics. Therefore, it has potential applications in THz wave stealth and electromagnetic shielding.
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Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Irídio/farmacologia , Irídio/químicaRESUMO
Vasoactive intestinal peptide (VIP) is a neuropeptide that play an important role in immunoregulation and anti-inflammation. Numerous inflammatory/autoimmune disorders are associated with decreased VIP binding ability to receptors and diminished VIP activation of cAMP generation in immune cells. However, the mechanisms linking oxidative/nitrative stress to VIP immune dysfunction remain unknown. It has been reported that the elevated heme or Cu2+ in inflammatory diseases can cause oxidative and nitrative damage to nearby biological targets under high oxidative stress conditions, which affects the structure and activity of linked peptides or proteins. Thus, the VIP down-regulated immune response may be interfered by redox metal catalyzed VIP tyrosine nitration. To explore this, we systematically investigated the possibility of heme or Cu2+ to catalyze VIP tyrosine nitration. The results showed that Tyr10 and Tyr22 of VIP can both be nitrated in heme/H2O2/NO2- system as well as in Cu2+/H2O2/NO2- system. Then, we used synthetic mutant VIPs with tyrosine residues substituted by 3-nitrotyrosine to study the impact of tyrosine nitration on VIP activity in SHSY-5Y cells. Our findings demonstrated that VIP nitration dramatically decreased the content of its α-helix and random coil, suggesting that VIP nitration might reduce its affinity to the receptor. This was further confirmed in the cAMP assay. The results showed that 10 nM of these tyrosine nitrated VIPs could significantly (p < 0.01) decrease cAMP secretion compared to the wild type VIP. Our data reveal that the attenuation of the neuroprotective effect of VIP in inflammation-related diseases might be attributed to metal-catalyzed VIP tyrosine nitration.
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Peróxido de Hidrogênio , Peptídeo Intestinal Vasoativo , Peróxido de Hidrogênio/metabolismo , Dióxido de Nitrogênio , Heme/metabolismo , Tirosina/metabolismoRESUMO
A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.
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Melanoma , Fotoquimioterapia , Humanos , Irídio/farmacologia , Irídio/química , Terapia Fototérmica , Luz , Fototerapia , Fármacos Fotossensibilizantes/química , Melanoma/tratamento farmacológico , Lasers , Linhagem Celular TumoralRESUMO
Actively controlling the phase of a terahertz (THz) wave is of great significance for beaming, tunable focusing, and holography. We present a THz phase modulator based on an electrically triggered vanadium dioxide (V O 2) reconfigurable metasurface. The unit cell of the device consists of two split-ring resonators embedded with a V O 2 ribbon. By electrically triggering the insulator-to-metal transition of V O 2, the resonance mode and resonance intensity of the unit cell can be dynamically controlled. The simulation results show that the structure can achieve a phase shift of about 360° in the range of 1.03-1.13 THz, and the reflection amplitude can reach 80%. The device has potential applications in THz imaging, radar, broadband wireless communications, and array phase control.
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We propose a method for diagnosis of cirrhosis and hepatocellular carcinoma (HCC) by using a terahertz (THz) metamaterial (MM) biosensor. The biosensor has a resonance frequency at about 0.801 THz and can measure the concentration of alpha-fetoprotein (AFP) in serum. The sensitivity of the sensor is 124 GHz/refractive index unit (RIU), and the quality-factor (Q) is 6.913, respectively. When the surface of the biosensor is covered with healthy serum (AFP≤7ng/mL), the maximum resonance frequency shift is 50 GHz. However, when it is covered with serum from patients with cirrhosis and early HCC (AFP>7ng/mL), the resonance frequency shift is more than 59 GHz. Positive correlation exists between the frequency shift of the biosensor and serum levels of the AFP in the HCC patients. This study provides a method for quick diagnosis and prediction of cirrhosis and HCC.
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Técnicas Biossensoriais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Cirrose Hepática , Biomarcadores TumoraisRESUMO
Owing to their stability in bodily fluids, exosomes have attracted increased attention as colorectal cancer (CRC) biomarkers for early diagnosis. To validate the potential of the plasma exosomes as a novel biomarker for the monitoring of CRC, we demonstrated a terahertz (THz) metamaterials (MMs) biosensor for the detection of exosomes in this work. The biosensor with two resonant frequencies is designed using full wave electromagnetic simulation software based on the finite integration time domain (FITD) method and fabricated by a surface micromachining process. The biosensor surface is first modified using Au nanoparticles (AuNPs), and then, anti-KRAS and anti-CD147, which are specific to the exosomes, are modified on the AuNPs assembled with HS-poly(ethylene glycol)-COOH (HS-PEG-COOH). Exosomes used in the experiment are extracted via the instructions in the exosomes isolation and purification kit and identified by using transmission electron microscopy (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). The biosensor covered with plasma-derived exosomes of CRC patients has a different resonance frequency shift compared to that with healthy-control-derived exosomes. This study proposes an emerging and quick method for diagnosing the CRC.
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Técnicas Biossensoriais , Exossomos , Nanopartículas Metálicas , Biomarcadores , Técnicas Biossensoriais/métodos , Ouro , Humanos , Microscopia Eletrônica de TransmissãoRESUMO
In this paper, a multi-parameter integrated detection photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) is proposed for its application in detecting temperature, magnetic field, and refractive index. The air holes on both sides of the fiber core were coated with gold film and introduced to the temperature-sensitive medium (PDMS) and magnetic fluid (MF), detecting temperature and magnetic field, respectively. The graphene layer is also presented on the gold film of the D-type side polished surface to improve the sensor sensitivity. The sensor's critical parameters' influence on its performance is investigated using a mode solver based on the finite element method (FEM). Simulation results show when the samples refractive index (RI) detection is a range of 1.36~1.43, magnetic field detection is a range of 20~550 Oe, and the temperature detection is a range of 5~55 °C; the maximum sensor's sensitivity obtains 76,000 nm/RIU, magnetic field intensity sensitivity produces 164.06 pm/Oe, and temperature sensitivity obtains -5001.31 pm/°C.
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Herein, we propose a tunable plasmonic sensor with Fano resonators in an inverted U-shaped resonator. By manipulating the sharp asymmetric Fano resonance peaks, a high-sensitivity refractive index sensor can be realized. Using the multimode interference coupled-mode theory and the finite element method, we numerically simulate the influences of geometrical parameters on the plasmonic sensor. Optimizing the structure parameters, we can achieve a high plasmonic sensor with the maximum sensitivity for 840 nm/RIUand figure of merit for 3.9 × 105. The research results provide a reliable theoretical basis for designing high sensitivity to the next generation plasmonic nanosensor.
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Type 2 diabetes (T2D) is associated with pancreatic ß-cell dysfunction, which can be induced by oxidative stress or/and the aggregation of human islet amyloid polypeptide (hIAPP). Therefore, ONOO- and hIAPP become the crucial targets of T2D treatment. Previously, we found heme could be an effective inhibitor of hIAPP aggregation. However, heme causes serious toxic effects on cells, tissues and organs through oxidative stress, which block it as a potential drug candidate for T2D treatment. 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrinato iron(III) chloride (FeTPPS), a water-soluble derivative of heme, is recognized as a high-efficient ONOO- decomposition catalyst, which is reported to have a great therapeutic potential in ONOO- -related diseases, including T2D. Here, we explored the potentiality of FeTPPS to be an inhibitor of hIAPP aggregation and the protective effects on cytotoxicity of hIAPP aggregation. It was found that the interaction between FeTPPS and hIAPP remarkably affected hIAPP fibrillation by both stabilizing hIAPP monomers and disaggregating the long fibrils into small oligomeric species. Furthermore, unlike heme, the addition of FeTPPS completely reversed the cytotoxicity and ROS level induced by hIAPP, which was consistent with its strong inhibitory activity. These results implied that FeTPPS could be a promising agent for the treatment of T2D.
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Amiloide/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Metaloporfirinas/farmacologia , Ácido Peroxinitroso/farmacologia , Agregados Proteicos/efeitos dos fármacos , Animais , Humanos , Metaloporfirinas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Ácido Peroxinitroso/química , Agregação Patológica de Proteínas , Ratos , Espécies Reativas de Oxigênio , Análise Espectral , Relação Estrutura-AtividadeRESUMO
Cobalt-modified molybdenum dioxide nanoparticles highly dispersed on nitrogen-doped carbon nanorods (Co-MoO2/NCND), are synthesized from anilinium trimolybdate dihydrate nanorods, for the performance improvement of microbial fuel cell based on a mixed bacterial culture. Electrochemical measurements demonstrate that the as-synthesized Co-MoO2/NCND exhibits excellent electrocatalytic activity for the charge transfer on anode, providing the cell with a maximum power density of 2.06⯱â¯0.05â¯Wâ¯m-2, which is strikingly higher than the bare carbon felt anode (0.49⯱â¯0.04â¯Wâ¯m-2). The excellent performance of Co-MoO2/NCND is ascribed to the increased electronic conductivity of carbon nanorods by N-doping, the high ability of MoO2 to enrich electroactive bacteria, as demonstrated by high-throughput sequencing, and the enhanced activity of MoO2 by Co-modifying toward redox reactions in electroactive bacteria. This report provides a new concept of anode electrocatalyst fabrications for the application of microbial fuel cells in electricity generation and wastewater treatment.
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Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Separação Celular/métodos , Carbono/química , Cobalto/química , Molibdênio/química , Nanopartículas/química , Nanotubos/química , Nitrogênio/química , Óxidos/químicaRESUMO
We report a novel anode electrocatalyst, iron carbide nanoparticles dispersed in porous graphitized carbon (Nano-Fe3C@PGC), which is synthesized by facile approach involving a direct pyrolysis of ferrous gluconate and a following removal of free iron, but provides microbial fuel cells with superior performances. The physical characterizations confirm the unique configuration of iron carbide nanoparticles with porous graphitized carbon. Electrochemical measurements demonstrate that the as-synthesized Nano-Fe3C@PGC exhibits an outstanding electrocatalytic activity toward the charge transfer between bacteria and anode. Equipped with Nano-Fe3C@PGC, the microbial fuel cells based on a mixed bacterium culture yields a power density of 1856â¯mWâ¯m-2. The resulting excellent performance is attributed to the large electrochemical active area and the high electronic conductivity that porous graphitized carbon provides and the enriched electrochemically active microorganisms and enhanced activity towards the redox reactions in microorganisms by Fe3C nanoparticles.
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Fontes de Energia Bioelétrica , Compostos Inorgânicos de Carbono/química , Grafite/química , Compostos de Ferro/química , Nanoestruturas/química , Fontes de Energia Bioelétrica/economia , Fontes de Energia Bioelétrica/microbiologia , Compostos Inorgânicos de Carbono/economia , Catálise , Condutividade Elétrica , Eletrodos , Desenho de Equipamento , Grafite/economia , Compostos de Ferro/economia , Nanopartículas/química , Nanopartículas/economia , Nanopartículas/ultraestrutura , Nanoestruturas/economia , Nanoestruturas/ultraestrutura , PorosidadeRESUMO
BACKGROUND: Recent evidence suggests early screening of preeclampsia and small-for-gestational-age (SGA) would benefit pregnancies followed by subsequent prophylactic use of aspirin. Multi-marker models have shown capability of predicting preeclampsia and SGA in first trimester. Yet the clinical feasibility of combined screening model for Chinese pregnancies has not been fully assessed. The aim of this study is to evaluate the applicability of a multi-marker screening model to the prediction of preeclampsia and SGA in first trimester particularly among Chinese population. METHODS: Three thousand two hundred seventy pregnancies meeting the inclusion criteria took first-trimester screening of preeclampsia and SGA. A prior risk based on maternal characteristics was evaluated, and a posterior risk was assessed by combining prior risk with multiple of median (MoM) values of mean arterial pressure (MAP), serum placental growth factor (PLGF) and pregnancy associated plasma protein A (PAPP-A). Both risks were calculated by Preeclampsia PREDICTOR™ software, Perkin Elmer. Screening performance of prior and posterior risks for early and late preeclampsia by using PREDICTOR software was shown by Receiver Operating Characteristics (ROC) curves. The estimation of detection rates and false positive rates of delivery with both preeclampsia and SGA was made. RESULTS: Eight cases developed early preeclampsia (0.24%) and 35 were diagnosed as late preeclampsia (1.07%). Five with early preeclampsia and ten with late preeclampsia later delivered SGA newborns (0.46%); 84 without preeclampsia gave birth to the SGAs (2.57%). According to ROC curves, posterior risks performed better than prior risks in terms of preeclampsia, especially in early preeclampsia. At 10% false positive rate, detection rates of early and late preeclampsia were 87.50 and 48.57%, detection rates of early and late SGA were 41.67 and 28.00%, respectively. For SGA, detection rates in cases with preeclampsia were much higher than those in absence of it. CONCLUSIONS: This study demonstrates that combined screening model could be useful for predicting early preeclampsia in Chinese pregnancies. Furthermore, the performance of SGA screening by same protocol is strongly associated with preeclampsia.
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Recém-Nascido Pequeno para a Idade Gestacional/sangue , Pré-Eclâmpsia/diagnóstico , Proteínas da Gravidez/sangue , Primeiro Trimestre da Gravidez/sangue , Diagnóstico Pré-Natal/métodos , Adulto , Biomarcadores/sangue , China , Reações Falso-Positivas , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido , Fator de Crescimento Placentário/análise , Valor Preditivo dos Testes , Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Estudos Prospectivos , Curva ROCRESUMO
A novel bi-component composite of porous self-assembled micro-/nanostructured Ni0.1Mn0.9O1.45 microellipsoids as high-performance anode electrocatalyst for microbial fuel cells (MFCs) is successfully synthesized via a simple coprecipitation reaction in microemulsion and calcination method in air atmosphere. The morphology and structural characterization indicate that the as-fabricated Ni0.1Mn0.9O1.45 product is consist of Mn2O3 and NiMn2O4 (n(Mn2O3): n(NiMn2O4) = 0.35: 0.1) and has a porous microellipsoidal morphology. The microellipsoids are compose of numerous layered micro-/nanostructured blocks and the special porous microellipsoids structure of Ni0.1Mn0.9O1.45 offers a large specific surface area for bacteria adhesion. The porous Ni0.1Mn0.9O1.45 microellipsoids as anode electrocatalyst for MFCs exhibits excellent electrocatalytic activity to promote the extracellular electron transfer (EET) between the anode and bacteria, hence improves the performance of MFC. The MFC equipped with Ni0.1Mn0.9O1.45/CF anode achieves a maximum power density of 1.39 ± 0.02Wm-2, is significantly higher than that of commercial carbon felt anode. This work proposes a new method for the synthesis of high-performance and environmentally friendly anode electrocatalyst for MFCs.
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Bactérias/isolamento & purificação , Aderência Bacteriana , Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Bactérias/química , Carbono/química , Manganês/química , Nanoestruturas/química , Níquel/química , PorosidadeRESUMO
A novel macroscale porous structure electrode, molybdenum carbide nanoparticles-modified carbonized cotton textile (Mo2C/CCT), was synthesized by a facile two-step method and used as an anode material for high-performance microbial fuel cells (MFCs). The characterization results show that the carbonized cotton textile modified with Mo2C nanoparticles offers a great specific surface area (832.17 m2 g-1) for bacterial adhesion. The MFC using Mo2C/CCT anode delivers the maximum power density of 1.12 W m-2, which is 51% and 116% higher than that of CCT and unmodified carbon felt anodes under the same conditions. The high power density is mainly due to the Mo2C nanoparticles with good biocompatibility and high conductivity and superior electrochemical activity, as well as the macroscale porous structure of carbonized cotton textile, which facilitate the formation of electroactive biofilm and improve the electron transfer. This paper introduces a feasible way to synthesize cost-effective and high-performance anode materials for MFCs.
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BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).
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Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Idoso , Broncodilatadores/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Brometo de Tiotrópio/efeitos adversosRESUMO
This study demonstrated the inhibitory effect of 6-benzylaminopurine (BAP), the first generation synthetic cytokinin, on the invasion of Monilinia fructicola in peach fruit and the possible mechanism involved for the first time. Our results suggested that BAP treatment had a 63% lower disease incidence and approximately 10 times lower lesion diameter compared to the control throughout the incubation period. In vitro BAP showed a direct inhibitory effect on M. fructicola spore germination. BAP could prevent fruit texture deterioration and protect the cell membrane from oxidative stress, while no adverse effects were observed on fruit quality maintenance. Analysis of defense-related enzymes activities indicated that the use of BAP induced higher specific polyphenol oxidase and peroxidase activities which triggered stronger host defensive responses. Thus, our results verified the proposed mechanism of BAP in controlling M. fructicola by direct inhibitory effect, delay peach senescence and activation of defensive enzymes.
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Ascomicetos/efeitos dos fármacos , Frutas/microbiologia , Fungicidas Industriais/farmacologia , Cinetina/farmacologia , Prunus persica/microbiologia , Ascomicetos/crescimento & desenvolvimento , Compostos de Benzil , Catecol Oxidase/genética , Catecol Oxidase/imunologia , Frutas/enzimologia , Frutas/genética , Frutas/imunologia , Peroxidase/genética , Peroxidase/imunologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Prunus persica/enzimologia , Prunus persica/genética , Prunus persica/imunologia , PurinasRESUMO
In this paper, Ni/ß-Mo2C(S) and Ni/ß-Mo2C(G) were prepared from solution-derived precursor with two different carbon sources (starch and glucose) and tested as anodic noble-metal-free catalysts in air-cathode microbial fuel cells (MFCs). The carburized catalyst samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the electrocatalyst towards the oxidation of several common microbial fermentation products (formate, lactate, and ethanol) was studied for MFC based on Klebsiella pneumoniae conditions. The composite MFC anodes were fabricated, and their catalytic behavior was investigated. With different carbon sources, the crystalline structure does not change and the crystallinity and surface area increase. The electrocatalytic experiments show that the Ni/ß-Mo2C(G) gives the better bio- and electrocatalytic performance than Ni/ß-Mo2C(S) due to its higher crystallinity and BET surface area.