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Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. The urgency of discovering new therapeutic options for the treatment of enterovirus infection is increasing. In the present study, we identified that trans-2-hexenoic acid (THA), a natural product from a dietary source, possesses antiviral activity against coxsackievirus B (CVB) and enterovirus A71 (EV-A71) in a dose-dependent manner. We found that THA possesses antiviral activity at 50% effective concentrations (EC50) of 2.9 µM and 3.21 µM against CVB3 and EV-A71 infections, respectively. The time of addition assay revealed that THA inhibits both CVB3 and EV-A71 replication at the entry stage of infection. Additional results from this study further suggest that THA inhibits viral replication by blocking viral entry. Given that THA has received approval as a food additive, treatment of enterovirus infections with THA might be a safe therapeutic option or could pave the way for semisynthetic manufacturing of more antiviral drugs in the future.
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Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Criança , Humanos , Antivirais/farmacologia , Infecções por Enterovirus/tratamento farmacológico , Replicação ViralRESUMO
Coxsackievirus B (CVB) is the major cause of human myocarditis and dilated cardiomyopathy. Toll-like receptor 3 (TLR3) is an intracellular sensor to detect pathogen's dsRNA. TLR3, along with TRAF6, triggers an inflammatory response through NF-κB signaling pathway. In the cells infected with CVB type 3 (CVB3), the abundance of miR-146a was significantly increased. The role of miR-146a in CVB infection is unclear. In this study, TLR3 and TRAF6 were identified as the targets of miR-146a. The elevated miR-146a inhibited NF-κB translocation and subsequently down-regulated proinflammatory cytokine expression in the CVB3-infected cells. Therefore, the NF-κB pathway can be doubly blocked by miR-146a through targeting of TLR3 and TRAF6. MiR-146a may be a negative regulator on inflammatory response and an intrinsic protective factor in CVB infection.
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Infecções por Coxsackievirus/imunologia , Enterovirus Humano B/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Animais , Infecções por Coxsackievirus/virologia , Citocinas/metabolismo , Regulação para Baixo , Enterovirus Humano B/genética , Fibroblastos/imunologia , Células HeLa , Humanos , Inflamação/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 3 Toll-Like/genéticaRESUMO
Wasted coal liquefaction residual was used to synthesize activated carbon fibers (ACFs) for CO2 capture, and the properties of the developed ACFs were optimized by adjusting the activation conditions, including the reaction temperature and soaking time. The yield, element distribution, pore structure, composition, functional group, morphology, and adsorption capacity of the as-synthesized ACFs were characterized by various apparatuses. In addition, static and dynamic adsorption experiments were conducted to investigate the adsorption capacity of CO2 in flue gas. The results revealed that the synthesized ACFs are mainly composed of carbon, accounting for more than 90% of the total elements. The specific surface area, pore volume, and pore width distribution of the prepared ACFs were optimized by changing the activation conditions, and ACFs with a specific surface area higher than 1400 m2/g were successfully developed by activation at 950 for 3 h. The amount of micropores occupied more than 90% of the total pore volume. The pore width distribution dominated by micropores is beneficial for CO2 adsorption since the diameter of CO2 is 0.33 nm. From FTIR and XPS analysis, it is found that the main structure of ACFs is a carbon skeleton composed of polycyclic aromatic hydrocarbons with a small number of oxygen-containing functional groups. The adsorption isotherm of ACFs for CO2 conforms to the Langmuir model, indicating that the adsorption process of CO2 by ACFs can be attributed to monolayer adsorption. Both the specific surface area and oxygen-containing functional groups have crucial effects on the adsorption capacity of CO2. The dynamic adsorption experiment determined that ACFs-920-3 had the highest adsorption capacity for CO2 in flue gas, and adsorption equilibrium was achieved after 7 min of adsorption. The adsorption process of CO2 in flue gas by the as-synthesized ACFs fits well with the pseudosecond kinetic model. The CO2 adsorption capacity of the obtained ACFs remained unchanged after 10 cycles of adsorption. A high-value-added route for synthesizing ACFs for CO2 capture using CLR as a raw material was developed.
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Activated carbon (AC) is negatively charged in aqueous solution, which seriously restricts its application range. Quaternary ammonium salt as a common cationic surfactant was utilized to modify the surface charge distribution of materials. The evolution of the surface charge distribution of AC modified by benzalkonium chloride (BAC), diallyl dimethyl ammonium chloride (DDA) and 3-chloro-2-hydroxypropyl tri-methyl ammonium chloride (CTA) was investigated. Results showed that the surface charge of AC modified by CTA does not change significantly. BAC has a high molecular weight, low surface electrostatic potential and large steric hindrance due to its hydrophobic long-chain alkyl. The diffusion of BAC molecules from solution to AC changed its charge distribution. But these molecules were difficult to combine with AC surface, and most of them were adsorbed into the pores of AC to form aggregates, resulting in a significant reduction in the surface area. BAC modified AC could enhance the adsorption capacity of F- in aqueous solution through electrostatic attraction, but the improvement effect was limited due to the reduction of surface area, and the maximum adsorption capacity was only increased from 1.18 to 3.31 mg/g. DDA has a small molecular weight and high surface electrostatic potential and easily binds to the surface of AC. Some CC bonds in DDA combined with the ionized hydrogen ions derived from phenolic hydroxyl groups in AC to form carbonium-ions. Then, they could react with AC to form ether bonds, causing DDA to be closely bonded with the surface of AC. DDA realizes the targeted regulation of the surface charge distribution of AC, it has little effect on the porous structure of AC. The modified AC still maintained strong adsorption capacity, and the maximum adsorption capacity for F- was 54.98 mg/g. Meanwhile, a large number of zeolites were loaded on the modified AC and formed coating structures.
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Compostos de Amônio , Poluentes Químicos da Água , Adsorção , Cloreto de Amônio , Carvão Vegetal/química , Sais , Água/química , Poluentes Químicos da Água/químicaRESUMO
Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.
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Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Linfócitos T/citologia , Antígeno B7-H1/química , Linhagem Celular , Cristalografia por Raios X , Humanos , Interferon gama/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Cultura Primária de Células , Receptor de Morte Celular Programada 1/química , Ligação Proteica/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Ozone-biological activated carbon (O3-BAC) process has been proved to be an efficient and cost-effective technology in advanced treatment of drinking water. However, O3-BAC raises strict requirements in adsorption, hydrodynamic and regeneration performances, which one single activated carbon could hardly all-sided meet. Blending activated carbons seems to be an appropriate and economically feasible method to deal with the issue. Thus, the uniformity and stability of activated carbon blends during water treatment, especially in backwashing process are of great importance. In this paper, cyclic experiments of downward adsorption and upward backwash on 11 typical commercial granular coal-based activated carbons and their blends were carried out in column test. Hydrodynamic performances such as bed expansion rate and bed pressure drop were measured. The uniformity and stability of activated carbon blends were investigated by determining iodine number of samples collected from different heights of activated carbon bed. Then, both traditional regression methods and back-propagation neural network model were utilized to predict superficial velocity at 30% bed expansion rate and maximum bed pressure drop of activated carbon blends. The results indicate that water backwashing process has no effect on the composition proportion of activated carbon blends, and slightly changes the particle distribution of activated carbon bed regarding pore structure and adsorption capacity. A three-layer back-propagation neural network model for superficial velocity at 30% bed expansion rate yields mean relative errors of 2.17%, which is much lower than that given by traditional regression methods such as 5.53% (weighted average), 4.08% (linear) and 4.06% (polynomial). Moreover, the back-propagation neural network model for maximum bed pressure drop yields mean relative errors of 1.37%, which is much lower than that given by traditional regression methods such as 4.31% (weighted average), 4.28% (linear) and 4.22% (polynomial). The non-linear relationships can be accurately identified by the back-propagation neural network model.
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Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , HidrodinâmicaRESUMO
Apoptosis plays a crucial role in many biological processes, including development, cellular homeostasis and immune responses. The BCL-2 family is a key regulator of the mitochondrial response to apoptotic signals in the intrinsic pathway. In this study, we identified and characterized the cDNA and expression pattern of pufferfish BCL-2 (PfBCL-2). The full-length cDNA of PfBCL-2 was 1412 bp with an open reading frame of 657 bp encoding a putative protein of 219 amino acids (Accession no: KP898414). The calculated molecular mass of the PfBCL-2 was 24.2 kDa with a predicted isoelectric point of 5.27. The deduced PfBCL-2 protein exhibited four highly conserved BCL-2 homology domains, suggesting that PfBCL-2 may play a similar role in the apoptotic-signaling pathway as in other species. Real-time PCR results showed that PfBCL-2 transcript was expressed in a wide range of tissues but exhibited the greatest level of expression in blood. Transcriptional responses of PfBCL-2 exhibited different spatial and temporal expression profiles in liver and blood after bacterial infection. PfBcl-2 transcript was significantly up-regulated in liver at 6, 12, 24 and 48 h (with maximum induction at 48 h) and was up-regulated in blood at 3, 6, 12 and 24 h (with maximum induction at 12 h). Meanwhile, recombinant PfBCL-2 fused with His6 tag was efficiently expressed in Escherichia coli BL21 (DE3) and purified using Ni-nitrilotriacetic acid resin. Western blot analysis indicated that its protein level appeared to be elevated during the initial bacterial infection. These results suggest that PfBCL-2 plays important roles in immune responses against bacteria challenge.
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Proteínas Proto-Oncogênicas c-bcl-2 , Aeromonas hydrophila , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/metabolismo , DNA Complementar/genética , Doenças dos Peixes/metabolismo , Brânquias/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Rim Cefálico/metabolismo , Fígado/metabolismo , Dados de Sequência Molecular , Músculos/metabolismo , Miocárdio/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Baço/metabolismo , TakifuguRESUMO
Efficient enrichment is crucial for the highly sensitive monitoring of phenylurea herbicides (PUHs) in various environmental waters. In this work, a stable core-shell spherically magnetic polyimide covalent organic framework (COF) was synthesized via a simple template-mediated precipitation polymerization method under mild conditions using tri(4-aminophenyl)amine (TAPA) and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA) as the building units (denoted as Fe3O4@TAPA-BPDA). The Fe3O4@TAPA-BPDA exhibits remarkable adsorption performance for PUHs with an optimized adsorption time of only 10 min. The adsorption of PUHs by Fe3O4@TAPA-BPDA followed the pseudo-second-order kinetic model and the Langmuir model. Furthermore, hydrogen bonding, halogen bonding, hydrophobic interaction, electro donor-acceptor interaction and π-π interactions are identified as the dominant mechanisms contributing to excellent adsorption performance. It was demonstrated that halogen bonds play an important role in the adsorption of substances containing chlorine atoms. The Fe3O4@TAPA-BPDA is easy to operate and highly regenerable. A simple magnetic solid-phase extraction (MSPE) method based on the Fe3O4@TAPA-BPDA was then developed for the rapid extraction of five PUHs in real samples, coupled with high-performance liquid chromatography (HPLC) determination. The analytical method developed has a linear range of 0.5-50 ng/mL, and the limit of detection (LOD) ranges from 0.06 to 0.10 ng/mL. The method exhibits good accuracy with recoveries ranged from 74.5 % to 111.4 %. The analytical method was successfully applied to the highly sensitive detection of PUHs in environmental water samples, which highlighting the potential application of the Fe3O4@TAPA-BPDA in the sample pretreatment.
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Neuro-symbolic artificial intelligence has garnered considerable attention amid increasing industry demands for high-performance neural networks that are interpretable and adaptable to previously unknown problem domains with minimal reconfiguration. However, implementing neuro-symbolic hardware is challenging due to the complexity in symbolic knowledge representation and calculation. We experimentally demonstrated a memristor-based neuro-fuzzy hardware based on TiN/TaOx/HfOx/TiN chips that is superior to its silicon-based counterpart in terms of throughput and energy efficiency by using array topological structure for knowledge representation and physical laws for computing. Intrinsic memristor variability is fully exploited to increase robustness in knowledge representation. A hybrid in situ training strategy is proposed for error minimizing in training. The hardware adapts easier to a previously unknown environment, achieving ~6.6 times faster convergence and ~6 times lower error than deep learning. The hardware energy efficiency is over two orders of magnitude greater than field-programmable gate arrays. This research greatly extends the capability of memristor-based neuromorphic computing systems in artificial intelligence.
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Activated carbon (AC) is a broad-spectrum adsorbent but is flammable and has low adsorption capacities for polar and/or high-boiling volatile organic compounds (VOCs), while zeolites exhibit high thermal stability but poor adsorption of macromolecular and nonpolar VOCs. In this study, zeolite/AC composites were synthesized with the aim of obtaining broad-spectrum, efficient, and safe adsorbents for VOCs. Dimethyldiallylammonium chloride (DDA)-modified AC was used as a carrier for an in situ hydrothermal reaction enabling assembly with zeolites due to electrostatic attraction. Interface models were constructed for their phases, which revealed the binding force and simulated the binding process. The adsorption and flame resistance of the composites were evaluated. The results showed that DDA effectively modified AC to give it a long-lasting positive charge in solutions. High-silicon and pure-silicon zeolites exhibited low negative charges or were even neutral; it was difficult to combine with the modified AC via electrostatic attractions. Instead, LTA zeolites with high aluminum contents and negative charges were used, and the seed-induction method was used. Ethanol and ultrasonic dispersion were used to prevent agglomeration of the seeds and modified AC powder, so they were self-assembled electrostatically. Moreover, the crystallization time was extended and composites with high zeolite loadings were successfully prepared. According to the model calculation, the binding energy between the zeolite and AC before and after the DDA modification were 324.97 and 1076.46 kcal mol-1, respectively, and the distance between them was shortened by 2.7 Å after DDA treatment. As a result, AC and zeolite combined more closely and exhibited a stronger binding energy. The adsorption capacity for highly polar dichloromethane was improved by zeolite loading on the AC, and the bed penetration time was doubled. However, impregnation with inorganic sodium enhanced the reactivities of the organic components in the composite, and the ignition point was slightly reduced. Furthermore, the electrostatic self-assembly method can expand to prepare the LTA zeolite/columnar AC composite from shaped AC, greatly improving its application prospects.
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Electrochemical bacteria Shewanella oneidensis MR-4 (MR-4) was used to biologically generate cadmium sulfide (bio-CdS) nanocrystals and construct a self-assembled intimately coupled photocatalysis-biodegradation system (SA-ICPB) to remove cadmium (Cd) and tetracycline hydrochloride (TCH) from wastewater. The characterization using EDS, TEM, XRD, XPS, and UV-vis confirmed the successful CdS bio-synthesis and its visible-light response capacity (520 nm). 98.4% of Cd2+ (2 mM) was removed during bio-CdS generation within 30 min. The electrochemical analysis confirmed the photoelectric response capability of the bio-CdS as well as its photocatalytic efficiency. Under visible light, SA-ICPB entirely eliminated TCH (30 mg/L). In 2 h, 87.2% and 43.0% of TCH were removed separately with and without oxygen. 55.7% more chemical oxygen demand (COD) was removed with oxygen participation, indicating the degradation intermediates elimination by SA-ICPB required oxygen participation. Biodegradation dominated the process under aerobic circumstances. Electron paramagnetic resonance analysis indicated that h+ and ·O2- played a decisive role in photocatalytic degradation. Mass spectrometry analysis proved that TCH was dehydrated, dealkylated, and ring-opened before mineralizing. In conclusion, MR-4 can spontaneously generate SA-ICPB and rapidly-deeply eliminate antibiotics by coupling photocatalytic and microbial degradation. Such an approach was efficient for the deep degradation of persistent organic pollutants with antimicrobial properties.
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Cádmio , Tetraciclina , Tetraciclina/metabolismo , Cádmio/metabolismo , Antibacterianos/química , Luz , Bactérias/metabolismo , Oxigênio/metabolismo , CatáliseRESUMO
OBJECTIVE: To study the changes of macular retinal thickness and microvascular system in children with monocular hyperopic anisometropia and severe amblyopia using optical coherence tomography angiography (OCTA) and to explore the value of OCTA in the diagnosis and treatment of amblyopia. METHODS: Thirty-two children with monocular hyperopic anisometropia and severe amblyopia who were treated in the Department of Ophthalmology of the First Affiliated Hospital of Gannan Medical College from January 2020 to December 2020 were included in the study. Eyes with amblyopia (n = 32) served as the experimental group, and the contralateral healthy eyes (n = 32 eyes) served as the control group. All children underwent comprehensive ophthalmological examination including slit lamp, eye position, visual acuity, optometry, eye movement, intraocular pressure, ocular axis, and fundus examination to rule out organic lesions. Macular 6 mm × 6 mm scans were performed on both eyes of all subjects by the same experienced clinician using an OCTA instrument. After ImageJ processing, the vessel density, inner layer, and full-layer retinal thickness (RT) of superficial retinal capillary plexus (SCP) were obtained. All data were analyzed by SPSS21.0 software, and a paired t-test was used for comparison between groups. P < 0.05 was considered to indicate statistical significance. RESULTS: The vessel densities of macular SCP in the amblyopia and control groups were 47.66 ± 2.36% and 50.37 ± 2.24% in the outer superior, 49.19 ± 2.64% and 51.44 ± 2.44% in the inner inferior, 49.63 ± 2.51% and 51.41 ± 3.03% in the outer inferior, and 45.56 ± 3.44% and 50.44 ± 3.52% in the outer temporal regions, respectively. The vessel density of macular SCP in the amblyopia group was significantly lower than that in contralateral healthy eyes in the outer superior, inner inferior, outer inferior, outer temporal, and central regions. There was no significant difference between the two groups in the inner superior, inner nasal, outer nasal, and inner temporal regions. The macular RT in the amblyopia group and the control group is 90.38 ± 6.09 µm and 87.56 ± 5.55 µm in the outer temporal, respectively. The RT in the macular inner layer in the outer temporal region of the amblyopia group was thicker than that of the control group (P < 0.05). There was no significant difference in the other eight regions between the two groups. The whole macular RT in the amblyopia group was thicker than that in the control group in nine regions, and the central area of macular RT in the amblyopia and control groups was 229.06 ± 6.70 µm and 214.50 ± 10.36 µm, respectively. CONCLUSION: The OCTA results showed the overall RT of macula in 9 areas in the amblyopia group was thicker than that in the control group, which could show that the macular retinal thickness can be a potential way to distinguish the children with monocular hyperopic anisometropia and severe amblyopia.
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Ambliopia/patologia , Anisometropia/patologia , Macula Lutea/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Macula Lutea/irrigação sanguínea , MasculinoRESUMO
The preparation of activated carbon (AC) is a promising approach for the efficient utilization of Zhundong high-alkali coal. The volatilization and release of alkali and alkaline earth metal (AAEM) species can be effectively inhibited by using a lower operating temperature and a carbon matrix. However, the long time of the pyrolysis and activation process may promote the release of the AAEM from the coal during the process. Therefore, it is necessary to explore the transformation of AAEM during the preparation of AC from Zhundong high-alkali coal, and the cleanness of this process is evaluated accurately. In this study, the evolution of AAEM, distribution, and chemical speciation is characterized before and after the preparation of AC from the coal, and then thermodynamic calculations were performed using FactSage to simulate the transformation of AAEM in the coupled process of pyrolysis and activation. The results showed that in the process of AC preparation, the AAEM species inside the carbon matrix moved towards the surface of the AC with the aid of released volatiles and the activation reaction. Some Na and K species were released due to their weak binding with the carbon matrix and this resulted in the loss of Na and K content, whereas Mg and Ca were closely combined with the carbon matrix and were enriched in the AC. Furthermore, the defects and amorphous structure of the AC prepared with H2O activation were more than that of the AC prepared with CO2 activation, which meant that more of the AAEM species were exposed to the high temperature environment. As a result, the loss of AAEM content in the AC with H2O activation was higher than that in the AC with CO2 activation. In this process, a small amount of highly volatile and corrosive AAEM was produced, and the release of volatile matter and the consumption of the carbon matrix were the main factors for the AAEM loss. Therefore, the preparation of AC from Zhundong high-alkali coal is a viable method for its clean use.
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Stroke is a major public health problem leading to high rates of death and disability worldwide, but no effective pharmacological therapy is currently available except for the use of PLAT (plasminogen activator, tissue). Here we show that PARP14 (poly (ADP-ribose) polymerase family, member 14) level was significantly increased in the peri-infarct zone of photothrombotic stroke (PT) mice. Genetic knockdown and pharmacological inhibition of PARP14 aggravated functional impairment and increased infarct volume in PT mice, while overexpression of PARP14 displayed the opposite effects. Furthermore, PARP14 was abundant in microglia, and downregulation of PARP14 increased post-stroke microglial activation, whereas overexpression of PARP14 alleviated microglial activation, possibly through microglial macroautophagy/autophagy modulation. Mechanistically, overexpression of PARP14 suppressed Lpar5 (lysophosphatidic acid receptor 5) gene transcription to inhibit microglial activation post stroke. Taken together, PARP14 is a stroke-induced signal that restricts microglial activation and promotes functional recovery, and can serve as a novel target to develop new therapeutic agents for stroke. Moreover, these findings may be conducive to proper use of various PARP inhibitors.Abbreviations: 3-MA: 3-methyladenine; AIF1/Iba-1: allograft inflammatory factor 1; CNS: central nervous system; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; ELISA: enzyme-linked immunosorbent assay; FBS: fetal bovine serum; GFAP: glial fibrillary acidic protein; IL1B/IL-1ß: interleukin 1 beta; IL6/IL-6: interleukin 6; LPAR5: lysophosphatidic acid receptor 5; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; NOS2/iNOS: nitric oxide synthase 2, inducible; OGD: oxygen glucose deprivation; PAR: polymer of poly (ADP ribose); PARP: poly (ADP-ribose) polymerase family; PBS: phosphate-buffered saline; PLAT/tPA: plasminogen activator, tissue; PT: photothrombotic stroke; qPCR: quantitative polymerase chain reaction; Rap: rapamycin; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; SQSTM1: sequestosome 1; TNF/TNF-α: tumor necrosis factor.
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Proteínas de Caenorhabditis elegans , Acidente Vascular Cerebral , Animais , Autofagia/fisiologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Regulação para Baixo , Camundongos , Microglia/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Proteínas de Ligação a RNA/metabolismo , Acidente Vascular Cerebral/genéticaRESUMO
Zhundong coal can significantly reduce the preparation temperature of activated carbon (AC) due to the high contents of alkali and alkaline earth metals (AAEMs) present in it. Moreover, because of its lower operating temperature and the presence of carbon matrix, Zhundong coal can effectively inhibit the release of AAEM during the preparation of AC. For these reasons, the preparation of AC from Zhundong coal is a promising approach for the clean utilization of Zhundong coal. Accordingly, this study was aimed to investigate optimum conditions for the preparation of AC from Zhundong coal. For this purpose, at first, Raman spectroscopy was used to determine the conditions for an optimal carbonization process using a coal sample; then, the evolution of the pore structure of AC under different conditions was examined by small-angle X-ray scattering (SAXS) and the N2 adsorption analyser. Furthermore, environmental scanning electron microscopy (ESEM) was performed to analyze the surface morphology of AC. Finally, by dividing the activation process into gas-solid diffusion and activation reactions, a mechanism for the evolution of pore structure during the preparation of AC was proposed. The results showed that the char with an amorphous structure and less graphite-like carbon, which was obtained by heating Zhundong coal from room temperature to 600 °C at 5 °C min-1 under the protection of N2 and then maintaining it at this temperature for 60 min, is suitable for the subsequent activation process. At low temperatures, the diffusion of H2O was dominant in the activation process, and the weak gas-solid reaction resulted in poor development of the pore structure; on the other hand, the CO2 activation reaction mainly occurred on the surface of the char due to the poor diffusion of CO2, and then, the produced pores could improve the diffusion of CO2; this led to significant development of the pore structure. With an increase in temperature, the H2O diffusion reaction was enhanced, and the pore structure of AC was completely developed; however, the diffusion of CO2 reduced with an enhancement in the CO2 activation reaction, leading to the consumption of carbon matrix by CO2 gasification instead of pore formation by the CO2 activation reaction. Therefore, proper utilization of the unique characteristics of H2O and CO2 during pore formation is important to control the activation process.
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In this work, isotropic pitch precursors are synthesized by the bromination-debromination method with ethylene bottom oil (EO) as the raw material and bromine as the initiator for pitch formation and condensation reactions. The aggregation structure, molecular weight distribution, and molecular structure of isotropic pitch precursors are characterized by thermal mechanical analyzer (TMA), MALDI TOF-MS, and 13C NMR, respectively, for revealing the mechanism of synthesis of isotropic pitch precursors. The results show that at low bromine concentrations, polycyclic aromatic hydrocarbons (PAHs) were mainly ordered in cross-linked structures by bromination-debromination through substitution reactions of side chains. The condensed reactivity can be improved by the effect of bromine, meaning that condensation reaction was aggravated by the method of bromination-dehydrobromination. In the presence of excess bromine, the cross-linked stereo structure of PAHs changed to the planar structure of condensed PAHs, which was not conducive to the subsequent spinning and preparation of carbon fibers.
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Pure, highly chlorinated polyvinyl chloride (CPVC), with a 63 wt % of chlorine, showed a unique-thermal-pyrolytic-phenomenon that meant it could be converted to carbon material through solid-phase carbonisation rather than liquid-phase carbonisation. The CPVC began to decompose at 270 °C, with a rapid loss in mass due to dehydrochlorination and novel aromatisation and polycondensation up to 400 °C. In this study, we attempted to prepare carbon fibre (CF) without oxidative stabilisation, using the aforementioned CPVC as a novel precursor. Through the processes of solution spinning and solid-state carbonisation, the spun CPVC fibre was directly converted to CF, with a carbonisation yield of 26.2 wt %. The CPVC-derived CF exhibited a relatively smooth surface; however, it still demonstrated a low mechanical performance. This was because the spun fibre was not stretched during the heat treatment. Tensile strength, Young's modulus and elongation values of 590 ± 84 MPa, 50 ± 8 GPa, and 1.2 ± 0.2%, respectively, were obtained from the CPVC spun fibre, with an average diameter of 19.4 µm, following carbonisation at 1600 °C for 5 min.
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ETHNOPHARMACOLOGY RELEVANCE: Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. AIM OF THE STUDY: The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity. MATERIALS AND METHODS: After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells. RESULTS: In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100µM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2). CONCLUSION: Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2.
Assuntos
Dioscorea , Diosgenina/análogos & derivados , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Eliminação Renal/efeitos dos fármacos , Espirostanos/farmacologia , Ácido Úrico/sangue , Uricosúricos/farmacologia , Adenina , Animais , Biomarcadores/sangue , Creatinina/sangue , Dioscorea/química , Diosgenina/isolamento & purificação , Diosgenina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Células HCT116 , Humanos , Hiperuricemia/sangue , Hiperuricemia/induzido quimicamente , Eliminação Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ácido Oxônico , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Sprague-Dawley , Espirostanos/isolamento & purificação , Fatores de Tempo , Uricosúricos/isolamento & purificaçãoRESUMO
Triboelectric nanogenerators (TENGs) are highly promising because they can scavenge energy from their working environment to sustainably power wearable/mobile electronics. In this work, we propose a novel and straightforward strategy for six-axis force detection and object controlling by using a self-powered sensor based on TENG. The self-powered sensor can be used in diversified tactile sensing and energy saving applications, which has been demonstrated to be able to detect normal force in the range of 0â»18 N. Using the vector properties of external force, six-axis directions in three-dimensional (3D) space is detected. Additionally, it is fabricated with environmental friendly materials, i.e., galinstan and polydimethylsiloxane (PDMS), promoting its applications in more diversified situations. Because of the available and high output voltage as well as the low internal impedance, the self-powered sensor is readily compatible with commercial signal processing and management circuits. The device presented in this work shows robust structure and stable output performance, enabling itself as an ideal human machine interface in self-powered, batteryless, and electric energy saving applications.
RESUMO
Nickel has been found a key pollutant in farmlands of central and south China, and understanding of Ni toxicity in rice is of great significance in safety production of rice and remediation of Ni polluted paddy soils. The present study aimed to investigate the uptake and subcellular distribution of Ni, antioxidant production, and osmolyte accumulation of rice (Oryza sativa L., cv. yangliangyou 6) plants exposed to excessive Ni concentrations to gain an insight into Ni-induced phytotoxicity. Results revealed that exposure of rice seedlings to high Ni concentrations resulted a decline in root and shoot lengths and fresh weight (FW) and dry weight (DW) of rice plants, which are in connection with the depletion of the contents of photosynthetic pigments. Measurement of Ni concentrations in the roots and shoots showed that Ni was mainly accumulated in roots followed by shoots. Moreover, Ni was mainly deposited in soluble fraction and cell wall, than cell organelle, which suggests that both compartments act as crucial defensive barriers against Ni toxicity in rice plants. Ni also induced its toxicity by damaging oxidative metabolism, as indicated by increased level of hydrogen peroxide and malondialdehyde content. Furthermore, Ni stress also showed a desynchronized antioxidant system by increasing the activities of catalase, peroxidase, and the contents of ascorbic acid and glutathione, whereas decreasing the activity of superoxide dismutase in the roots and shoots of rice plants. Ni stress also triggered the rate of proline accumulation and decreasing the contents of soluble protein and soluble sugar. In crux, our results suggests that excessive Ni inhibited rice growth and induced oxidative stress through inducing ROS formation, while stimulated enzymatic and non-enzymatic antioxidants system appeared as adaptive mechanisms of rice plants against Ni-induced oxidative stress. Furthermore, majority of Ni was located in soluble fraction and modulation in osmolyte accumulation under Ni stress seemed to provide additional defense against oxidative stress.