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Type I interferons (IFN-I) play pivotal roles in tumor therapy for three decades, underscoring the critical importance of maintaining the integrity of the IFN-1 signaling pathway in radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the specific mechanism by which IFN-I contributes to these therapies, particularly in terms of activating dendritic cells (DCs), remains unclear. Based on recent studies, aberrant DNA in the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway, which in turn produces IFN-I, which is essential for antiviral and anticancer immunity. Notably, STING can also enhance anticancer immunity by promoting autophagy, inflammation, and glycolysis in an IFN-I-independent manner. These research advancements contribute to our comprehension of the distinctions between IFN-I drugs and STING agonists in the context of oncology therapy and shed light on the challenges involved in developing STING agonist drugs. Thus, we aimed to summarize the novel mechanisms underlying cGAS-STING-IFN-I signal activation in DC-mediated antigen presentation and its role in the cancer immune cycle in this review.
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Interferon Tipo I , Neoplasias , Humanos , Nucleotidiltransferases/metabolismo , Transdução de Sinais , Interferon Tipo I/metabolismo , Neoplasias/metabolismo , Células Dendríticas/metabolismo , Imunidade InataRESUMO
As vitally prospective candidates for next-generation energy storage systems, room-temperature sodium-sulfur (RT-Na/S) batteries continue to face obstacles in practical implementation due to the severe shuttle effect of sodium polysulfides and sluggish S conversion kinetics. Herein, the study proposes a novel approach involving the design of a B, N co-doped carbon nanotube loaded with highly dispersed and electron-deficient cobalt (Co@BNC) as a highly conductive host for S, aiming to enhance adsorption and catalyze redox reactions. Crucially, the pivotal roles of the carbon substrate in prompting the electrocatalytic activity of Co are elucidated. The experiments and density functional theory (DFT) calculations both demonstrate that after B doping, stronger chemical adsorption toward polysulfides (NaPSs), lower polarization, faster S conversion kinetics, and more complete S transformation are achieved. Therefore, the as-assembled RT-Na/S batteries with S/Co@BNC deliver a high reversible capacity of 626 mAh g-1 over 100 cycles at 0.1 C and excellent durability (416 mAh g-1 over 600 cycles at 0.5 C). Even at 2 C, the capacity retention remains at 61.8%, exhibiting an outstanding rate performance. This work offers a systematic way to develop a novel Co electrocatalyst for RT-Na/S batteries, which can also be effectively applied to other transition metallic electrocatalysts.
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BACKGROUND: Our previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function by increasing SHP1 expression. We designed this study to further explore the influence of P5C on T cell metabolism, and produced an antibody for targeting P5C to restore the functions of T cells. METHOD: We co-immunoprecipated SHP1 from T cells and analyzed the proteins that were bound to it using liquid chromatography mass spectrometry (LC/MS-MS). The influence of P5C on T cells metabolism was also detected by LC/MS-MS. Seahorse XF96 analyzer was further used to identify the effect of P5C on T cells glycolysis. We subsequently designed and produced an antibody for targeting P5C by monoclonal technique and verified its effectiveness to restore the function of T cells in vitro and in vivo. RESULT: PKM2 and LDHB bind SHP1 in T cells, and P5C could increase the levels of p-PKM2 while having no effect on the levels of PKM2 and LDHB. We further found that P5C influences T cell energy metabolism and carbohydrate metabolism. P5C also inhibits the activity of PKM2 and decreases the content of intracellular lactic acid while increasing the activity of LDH. Using seahorse XF96 analyzer, we confirmed that P5C remarkably inhibits glycolysis in T cells. We produced an antibody for targeting P5C by monoclonal technique and verified that the antibody could oppose the influence of P5C to restore the process of glycolysis and function in T cells. Meanwhile, the antibody also inhibits the growth of prostate tumors in an animal model. CONCLUSION: Our study revealed that P5C inhibits the process of glycolysis in T cells by targeting SHP1/PKM2/LDHB complexes. Moreover, it is important that the antibody for targeting P5C could restore the function of T cells and inhibit the growth of prostate tumors.
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Neoplasias da Próstata , Pirróis , Linfócitos T , Humanos , Masculino , Animais , Próstata , Microambiente Tumoral , Proliferação de Células , Glicólise , Linhagem Celular TumoralRESUMO
Room-temperature sodium-sulfur batteries are still hampered by severe shuttle effects and sluggish kinetics. Most of the sulfur hosts require high cost and complex synthesis process. Herein, a facile method is proposed to prepare a phosphorous doped porous carbon (CSBP) with abundant defect sites from camellia shell by oxidation pretreatment combined with H3PO4activation. The pretreatment can introduce pores and adjust the structure of biochar precursor, which facilitates the further activation of H3PO4and effectively avoids the occurrence of large agglomeration. Profiting from the synergistic effects of physical confinement and doping effect, the prepared CSBP/S cathode delivers a high reversible capacity of 804 mAh g-1after 100 cycles at 0.1 C and still maintains an outstanding capacity of 458 mAh g-1after 500 cycles at 0.5 C (1 C = 1675 mA g-1). This work provides new insights into the rational design of the microstructures of carbon hosts for high-performance room temperature sodium-sulfur batteries.
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Zigzag graphene nanoribbons (GNRs) were selected as electrodes, and the electron transport properties, optical properties, and thermoelectric properties of four fullerene cluster-based molecular devices were studied. By applying different voltages on them, their I-V curves exhibited the multiple negative differential resistance (NDR) effect and the platform effect, which are described in more detail using their density of states (DOS) and projected density of states (PDOS). The results of rotating two types of (C60)4 molecules verify that both the NDR and the platform effects are essential characteristics of them. Furthermore, an examination is conducted on the photocurrent of the devices at the point of maximum light absorption, revealing that α-(C60)4 connected by a [2+2] ring addition bond in the transport direction exhibits superior optical properties and works better as a photoelectric device than ß-(C60)4 connected via a C-C single bond in the transport direction. Finally, the thermoelectric current of the devices was studied. Our results contribute to the understanding and the potential application of single devices based on fullerene clusters in the area of molecular electronics.
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Cooking process can produce abundant volatile organic compounds (VOCs), which are harmful to environment and human health. Therefore, we conducted a comprehensive analysis in which VOCs emissions from multiple cuisines have been sampled based on the simulation and acquisition platform, involving concentration characteristics, ozone formation potential (OFP) and purification efficiency assessments. VOCs emissions varied from 1828.5 to 14,355.1 µg/m3, with the maximum and minimum values from Barbecue and Family cuisine, respectively. Alkanes and alcohol had higher contributions to VOCs from Sichuan and Hunan cuisine (64.1%), Family cuisine (66.3%), Shandong cuisine (69.1%) and Cantonese cuisine (69.8%), with the dominant VOCs species of ethanol, isobutane and n-butane. In comparison, alcohols (79.5%) were abundant for Huaiyang cuisine, while alkanes (19.7%), alkenes (35.9%) and haloalkanes (22.9%) accounted for higher proportions from Barbecue. Specially, carbon tetrachloride, n-hexylene and 1-butene were the most abundant VOCs species for Barbecue, ranging from 8.8% to 14.6%. The highest OFP occurred in Barbecue. The sensitive species of OFP for Huaiyang cuisine were alcohols, while other cuisines were alkenes. Purification efficiency assessments shed light on the removal differences of individual and synergistic control technologies. VOCs emissions exhibited a strong dependence on the photocatalytic oxidation, with the removal efficiencies of 29.0%-54.4%. However, the high voltage electrostatic, wet purification and mechanical separation techniques played a mediocre or even counterproductive role in the VOCs reduction, meanwhile collaborative control technologies could not significantly improve the removal efficiency. Our results identified more effective control technologies, which were conductive to alleviating air pollution from cooking emissions.
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Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Humanos , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental , Alcanos/análise , Alcenos , Ozônio/química , Culinária , ChinaRESUMO
Morphologies of evaporative deposition, which has been widely applied in potential fields, were induced by the competition between internal flows inside evaporating droplets. Controlling the pattern of deposition and suppressing the coffee-ring effect are essential issues of intense interest in the aspects of industrial technologies and scientific applications. Here, evaporative deposition of surfactant-laden nanofluid droplets over silicon was experimentally investigated. A ring-like deposition was formed after complete evaporation of sodium dodecyl sulfate (SDS)-laden nanofluid droplets with an initial SDS concentration ranging from 0 to 1.5 CMC. In the case of initial SDS concentrations above 1.3 CMC, no cracks were observed in the ring-like deposition, indicating that the deposition patterns of nanofluid droplets could be completely changed and cracks could be eliminated by sufficient addition of SDS. With the increase of the initial concentration of hexadecyl trimethylammonium bromide (CTAB), the width of the deposition ring gradually decreased until no ring-like structure was formed. On the contrary, with the increase of the initial Triton X-100 (TX-100) concentration, the width of the deposition ring gradually increased until a uniform deposition was generated. Moreover, when the initial TX-100 concentration was high, a "tree-ring-like" pattern was discovered. Besides, morphologies of evaporative pattern due to the addition of surfacants were qualitatively analyzed.
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Electrochemical sodium-ion storage has come out as a promising technology for energy storage, where the development of electrode material that affords high volumetric capacity and long-term cycling stability remains highly desired yet a challenge. Herein, Ti3 C2 Tx (MXene)-based films are prepared by using sulfur (S) as the mediator to modulate the surface chemistry and microstructure, generating S-doped mesoporous Ti3 C2 Tx films with high flexibility. The mesoporous architecture offers desirable surface accessibility without significantly sacrificing the high density of Ti3 C2 Tx film. Meanwhile, the surface sulfur doping of Ti3 C2 Tx favors the diffusion of sodium ions. These merits are of critical importance to realize high volumetric capacity of the electrode material. As a consequence, as the freestanding electrode material for electrochemical sodium-ion storage, the S-doped mesoporous Ti3 C2 Tx film exhibits a high volumetric capacity of 625.6 mAh cm-3 at 0.1 A g-1 , which outperforms that of many reported electrodes. Moreover, outstanding rate capability and excellent long-term cycling stability extending 5000 cycles are achieved. The work opens the door for innovative design and rational fabrication of MXene-based films with ultrahigh volumetric capacity for sodium-ion storage.
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Capture of circulating tumor cells (CTCs) with high efficiency and high purity holds great value for potential clinical applications. Besides the existing problems of contamination from blood cells and plasma proteins, unknown/down-regulated expression of targeting markers (e.g., antigen, receptor, etc.) of CTCs have questioned the reliability and general applicability of current CTCs capture methodologies based on immune/aptamer-affinity. Herein, a cell-engineered strategy is designed to break down such barriers by employing the cell metabolism as the leading force to solve key problems. Generally, through an extracellular vesicle generation way, the cell-released magnetic vesicles inherited parent cellular membrane characteristics are produced, and then functionalized with dibenzoazacyclooctyne to target and isolate the metabolic labeled rare CTCs. This strategy offers good reliability and broader possibilities to capture different types of tumor cells, as proven by the capture efficiency above 84% and 82% for A549 and HepG2 cell lines as well as an extremely low detection limitation of 5 cells. Moreover, it enabled high purity enrichment of CTCs from 1 mL blood samples of tumor-bearing mice, only ≈5-757 white blood cells are non-specific caught, ignoring the potential phenotypic fluctuation associated with the cancer progression.
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Células Neoplásicas Circulantes , Animais , Contagem de Células , Linhagem Celular Tumoral , Separação Celular , Fenômenos Magnéticos , Magnetismo , Camundongos , Reprodutibilidade dos TestesRESUMO
In recent years, there have been a number of studies on bioretention during hot summer, with only few studies reported during low-temperature winters. The application of bioretention in cold areas still lacks effective guidance. In this study, runoff simulation experiments were conducted to explore the influence of wood chips filler and water treatment residue on the removal of runoff pollutants under different packing gradations and low temperature conditions. Under low temperature, nitrate nitrogen removal rate of wood chips filler decreased from 70% to 90% in autumn to -23%- 35% in winter, the total nitrogen removal rate decreased from 75 to 90% in autumn to 20%-50% in winter, the removal rate of ammonia nitrogen and total phosphorus exceeded 70% during the entire experiment. Water treatment residue filler maintained a high ammonia nitrogen and total phosphorus removal rate during the experiment, with the total phosphorus removal rate above 90% and ammonia nitrogen removal rate above 80%. The bioretention effluent concentration of nitrate and total nitrogen was higher than 7.3 mg/L and 8.5 mg/L, respectively, most of the time. However, at low temperature, the COD removal rate of the two fillers was 25%-50%, which was very poor. Therefore, wood chips filler was observed to be better suited for the removal of nitrate and total nitrogen from the runoff, while water treatment residue had a better effect on the removal of ammonia nitrogen and total phosphorus in winter. Thus, for the application of bioretention in northern China, appropriate fillers should be selected considering the water quality characteristics of the area.
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Poluentes Químicos da Água , Purificação da Água , China , Nitrogênio/análise , Fósforo/análise , Chuva , TemperaturaRESUMO
Improving our understanding of air pollutant emissions from the asphalt industry is critical for the development and implementation of pollution control policies. In this study, the spatial distribution of potential maximum emissions of volatile organic compounds (VOCs) in the complete life cycle of asphalt mixtures, as well as the particulate matter (PM), asphalt fume, nonmethane hydrocarbons (NMHCs), VOCs, and benzoapyrene (BaP) emissions from typical processes (e.g., asphalt and concrete mixing stations, asphalt heating boilers, and asphalt storage tanks) in asphalt mixing plants, were determined in Beijing in 2017. The results indicated that the potential maximum emissions of VOCs in the complete life cycle of asphalt mixtures were 18,001 ton, with a large contribution from the districts of Daxing, Changping, and Tongzhou. The total emissions of PM, asphalt fume, NMHC, VOCs, and BaP from asphalt mixing plants were 3.1, 12.6, 3.1, 23.5, and 1.9 × 10-3 ton, respectively. The emissions of PM from asphalt and concrete mixing stations contributed the most to the total emissions. The asphalt storage tank was the dominant emission source of VOCs, accounting for 96.1% of the total VOCs emissions in asphalt mixing plants, followed by asphalt heating boilers. The districts of Daxing, Changping, and Shunyi were the dominant regions for the emissions of PM, asphalt fume, NMHC, and BaP, while the districts of Shunyi, Tongzhou, and Changping contributed the most emissions of VOCs.
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Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Pequim , China , Monitoramento Ambiental , Hidrocarbonetos , Compostos Orgânicos Voláteis/análiseRESUMO
The development of high-performance anode materials for potassium-based energy storage devices with long-term cyclability requires combined innovations from rational material design to electrolyte optimization. A three-dimensional K+ -pre-intercalated Ti3 C2 Tx MXene with enlarged interlayer distance was constructed for efficient electrochemical potassium-ion storage. We found that the optimized solvation structure of the concentrated ether-based electrolyte leads to the formation of a thin and inorganic-rich solid electrolyte interphase (SEI) on the K+ -pre-intercalated Ti3 C2 Tx electrode, which is beneficial for interfacial stability and reaction kinetics. As a proof of concept, 3D K+ -Ti3 C2 Tx //activated carbon (AC) potassium-ion hybrid capacitors (PIHCs) were assembled, which exhibited promising electrochemical performances. These results highlight the significant roles of both rational structure design and electrolyte optimization for highly reactive MXene-based anode materials in energy storage devices.
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OBJECTIVE: To increase the in vivo stability of bioactive proteins via optimized loading methods. RESULTS: ß-Glucosidase (ß-Glu), as a model protein, was immobilized on magnetic nanoparticles(denoted as MNP-ß-Glu) by chemical coupling methods and was further modified by poly(ethylene glycol) (PEG) molecules (denoted as MNP-ß-Glu-PEG) to increase its stability. The physicochemical properties of the as-prepared nanohybrids, including the particle size, zeta potential, and enzyme activity, were well characterized. The proper MNP/ß-Glu feed ratio was important for optimizing the particle size. Analysis of enzyme activity showed that the stability of immobilized ß-Glu compared with free ß-Glu was lower in deionized water and higher in blood serum at 37 °C. MNP-ß-Glu-PEG retained 77.9% of the initial activity within 30 days at 4 °C, whereas the free enzyme retained only 58.2%. Pharmacokinetic studies of Sprague-Dawley (SD) rats showed that the MNP-ß-Glu-PEG group retained a higher enzyme activity in vivo (41.46% after 50 min) than the MNP-ß-Glu group (0.03% after 50 min) and the ß-Glu group (0.37% after 50 min). Moreover, in contrast to the MNP-ß-Glu group, the enzyme activity was not fully synchronous with the decrease in the Fe concentration in the MNP-ß-Glu-PEG group. CONCLUSIONS: All findings indicated that the method of immobilization on magnetic nanoparticles and PEG modification is promising for the application of bioactive proteins in vivo.
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Enzimas Imobilizadas , Nanopartículas de Magnetita/química , Polietilenoglicóis/química , Animais , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/farmacocinética , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , beta-Glucosidase/química , beta-Glucosidase/metabolismo , beta-Glucosidase/farmacocinéticaRESUMO
BACKGROUND: This study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer. METHODS: The mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p. RESULTS: Our results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells' viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction. CONCLUSION: Our results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial-mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.
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Proteínas Ativadoras de GTPase/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Proteínas Supressoras de Tumor/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.
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Disfunção Erétil/etiologia , Ereção Peniana/fisiologia , Induração Peniana/patologia , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Fibronectinas/metabolismo , Masculino , Pênis/cirurgia , Proteína-Lisina 6-Oxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismos do Sistema Nervoso/complicaçõesRESUMO
In China, volatile organic compound (VOC) control directives have been continuously released and implemented for important sources and regions to tackle air pollution. The corresponding control requirements were based on VOC emission amounts (EA), but never considered the significant differentiation of VOC species in terms of atmospheric chemical reactivity. This will adversely influence the effect of VOC reduction on air quality improvement. Therefore, this study attempted to develop a comprehensive classification method for typical VOC sources in the Beijing-Tianjin-Hebei region (BTH), by combining the VOC emission amounts with the chemical reactivities of VOC species. Firstly, we obtained the VOC chemical profiles by measuring 5 key sources in the BTH region and referencing another 10 key sources, and estimated the ozone formation potential (OFP) per ton VOC emission for these sources by using the maximum incremental reactivity (MIR) index as the characteristic of source reactivity (SR). Then, we applied the data normalization method to respectively convert EA and SR to normalized EA (NEA) and normalized SR (NSR) for various sources in the BTH region. Finally, the control index (CI) was calculated, and these sources were further classified into four grades based on the normalized CI (NCI). The study results showed that in the BTH region, furniture coating, automobile coating, and road vehicles are characterized by high NCI and need to be given more attention; however, the petro-chemical industry, which was designated as an important control source by air quality managers, has a lower NCI.
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Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental/métodos , Compostos Orgânicos Voláteis/análise , Poluentes Atmosféricos/classificação , Indústria Química , China , Ozônio , Compostos Orgânicos Voláteis/classificaçãoRESUMO
A substrate-controlled regioselective arylation of 2-indolylmethanols with indoles has been established, which efficiently afforded bis(indolyl)methane and 3,3'-bisindole derivatives in high yields and with a broad substrate scope (up to 98% yield, 36 examples). This approach will not only provide an important strategy for the diversified synthesis of bis(indolyl)methane and 3,3'-bisindole derivatives but also serve as a good example for substrate-controlled regioselective reactions.
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The first catalytic asymmetric cycloaddition using 2-indolylmethanols as 3C building blocks has been established by a chiral phosphoric acid-catalyzed enantioselective and regioselective [3+3] cycloaddition of 2-indolylmethanols with azomethine ylides, which constructed biologically important tetrahydro-γ-carboline frameworks in high yields and excellent enantioselectivities (up to 83 % yield, 99:1 e.r.). This reaction not only represents the first application of 2-indolylmethanols as 3C building blocks in catalytic asymmetric cycloadditions, but also has established an abnormal regioselectivity in indolylmethanol-involved transformations.
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Reação de Cicloadição , Indóis/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
INTRODUCTION: Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury. MATERIALS AND METHODS: Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-ß1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry. RESULTS: Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-ß1/Smad2 and collagen expression in corpus cavernosum. CONCLUSIONS: Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.
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Calpaína/antagonistas & inibidores , Disfunção Erétil/tratamento farmacológico , Fibras Parassimpáticas Pós-Ganglionares/lesões , Ereção Peniana/efeitos dos fármacos , Animais , Calpaína/metabolismo , Dipeptídeos/uso terapêutico , Modelos Animais de Doenças , Glicoproteínas/uso terapêutico , Imuno-Histoquímica , Masculino , Compressão Nervosa , Óxido Nítrico Sintase Tipo I/metabolismo , Pênis/patologia , Prostatectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Proteína Smad2/metabolismo , Espectrina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Resultado do TratamentoRESUMO
The local-scale relationship between ambient ozone (O3) and its precursors was examined around a coking plant in northern China. The upwind, plant boundary, and downwind locations were selected for investigation during the summer and autumn seasons in 2012. It was found that propene, toluene, and benzene were the top three non-methane hydrocarbon (NMHC) species for O3 formation at plant boundary, while propene, toluene, and m/p-xylene were the top three NMHC species at downwind location. Isoprene was the dominant species for O3 formation at upwind location. It was also found that an O3 depressing process occurred at plant boundary as a result of high NO emissions. Both local photochemistry and transport led to O3 accumulation at the downwind locations. The variation of NMHC concentration during O3 polluted and non-polluted episodes was investigated, and it indicated that NMHC concentration was higher during non-polluted episodes than polluted episodes. The impacts of precursors on O3 formation under different meteorological conditions were also examined.