RESUMO
A comprehensive understanding of carrier transport in photoisomeric molecular junctions is crucial for the rational design and delicate fabrication of single-molecule functional devices. It has been widely recognized that the conductance of azobenzene (a class of photoisomeric molecules) based molecular junctions is mainly determined by photoinduced conformational changes. In this study, it is demonstrated that the most probable conductance of amine-anchored azobenzene-based molecular junctions increases continuously upon UV irradiation. In contrast, the conductance of pyridyl-anchored molecular junctions with an identical azobenzene core exhibits a contrasting trend, highlighting the pivotal role that anchoring groups play, potentially overriding (even reversing) the effects of photoinduced conformational changes. It is further demonstrated that the molecule with cis-conformation cannot be fully mechanically stretched into the trans-conformation, clarifying that it is a great challenge to realize a reversible molecular switch by purely mechanical operation. Additionally, it is revealed that the coupling strength of pyridyl-anchored molecules is dramatically weakened when the UV irradiation time is prolonged, whereas it is not observed for amine-anchored molecules. The mechanisms for these observations are elucidated with the assistance of density functional theory calculations and UV-Vis spectra combined with flicker noise measurements which confirm the photoinduced conformational changes, providing insight into understanding the charge transport in photoisomeric molecular junctions and offering a routine for logical designing synchro opto-mechanical molecular switches.
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π-stacking interaction, as a fundamental type of intermolecular interaction, plays a crucial role in generating new functional molecules, altering the optoelectronic properties of materials, and maintaining protein structural stability. However, regulating intermolecular π-π interactions at the single-molecule level without altering the molecular conformation as well as the chemical properties remains a significant challenge. To this end, via conductance measurement with thousands of single molecular junctions employing a series of aromatic molecules, we demonstrate that the π-π coupling between neighboring aromatic molecules with rigid structures in a circuit can be greatly enhanced by increasing the bias voltage. We further reveal that this universal regulating effect of bias voltage without molecular conformational variation originates from the increases of the molecular dipole upon an applied electric field. These findings not only supply a non-destructive method to regulate the intermolecular interactions offering an approach to modulate the electron transport through a single molecular junction, but also deepen the understanding of the mechanism of π-π interactions.
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A new hypoxia-tolerant variety of blunt snout bream was obtained by successive breeding of the wild population, which markedly improved hypoxia tolerance. In this study, the hypoxia-tolerant variety was exposed to hypoxia (2.0 mg O2·L-1) for 4, 7 days. The contents of blood biochemical indicators including the number of red blood cells (RBC), total cholesterol (T-CHO), total protein (TP), triglyceride (TG), glucose (GLU), and lactic acid (LD) increased significantly (P < 0.05) under hypoxia. The glycogen content in the liver and muscle decreased significantly (P < 0.05) and the LD content in the brain, muscle and liver increased significantly (P < 0.05) under hypoxia. The levels of oxidative stress-related indicators i.e., superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T-AOC) also changed significantly (P < 0.05) in the heart, liver, and intestine of the new variety under hypoxia. Additionally, hypoxia has caused injuries to the heart, liver, and intestine, but it shows amazing repair ability during reoxygenation. The apoptotic cells and apoptosis rate in the heart, liver, and intestine increased under hypoxia. Under hypoxia, the expression of the B-cell lymphomas 2 (Bcl-2) gene in the heart, liver, and intestine was significantly (P < 0.05) down-regulated, while the expression of the BCL2-associated agonist of cell death (Bad) gene was significantly (P < 0.05) up-regulated. These results are of great significance for enriching the basic data of blunt snout bream new variety in response to hypoxia and promoting the healthy development of its culture industry.
Assuntos
Cyprinidae , Dieta , Animais , Cyprinidae/fisiologia , Antioxidantes/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Apoptose , Proteínas de Peixes/metabolismoRESUMO
A 66-year-old woman was admitted to our hospital due to chest distress and shortness of breath during 1 week. Transthoracic echocardiography (TTE) revealed massive pericardial effusion and multiple, irregular and high-density echo "tumor-like" masses on the heart, with the largest one on the apex. However, there were no masses found by computed tomography (CT) scan, except for increased lipids around the coronary artery. We performed emergency pericardiocentesis and drainage to relieve symptoms. The positron emission tomography/CT (PET/CT) also showed several ununiformly high accumulations in pericardial cavity. However, the high-density echo "tumor-like" masses cannot be seen by TTE after pericardiocentesis, and also cannot be detected when surgery. Pericardiotomy was performed due to severe pericardial adhesion. The diagnosis of tuberculosis (TB) was confirmed by pericardiotomy and pericardial biopsy.
Assuntos
Neoplasias , Derrame Pericárdico , Pericardite Tuberculosa , Feminino , Humanos , Idoso , Pericardite Tuberculosa/complicações , Pericardite Tuberculosa/diagnóstico por imagem , Pericardite Tuberculosa/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pericárdio/diagnóstico por imagem , Derrame Pericárdico/diagnóstico por imagem , Neoplasias/patologiaRESUMO
Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD-fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin-treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin-induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.
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Tecido Adiposo/efeitos dos fármacos , Emodina/farmacologia , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Macrófagos/efeitos dos fármacos , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Linhagem Celular , Dieta Hiperlipídica , Inflamação/metabolismo , Insulina/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismoRESUMO
The microRNA miR-30a has been reported to mitigate podocyte damage and resist injurious factors in lupus nephritis (LN), but the precise molecular mechanisms underlying these effects remain elusive. We hypothesized that miR-30a can ameliorate podocyte injury by downregulating the Notch1 signaling pathway and investigated the role of miR-30a in the pathogenesis of podocyte-treated with Immunoglobulin G from patients with LN (IgG-LN). The study enrolled 30 patients from new-onset systemic lupus erythematosus and 28 healthy individuals, then evaluated the levels of their serum miR-30a using RT-qPCR. Additionally, MPC5 cells were transfected with NICD-vector to overexpress Notch1, then with miR-30a mimics or inhibitors to determine miR-30a effects on Notch1. Analysis of function and regulatory mechanisms were performed with RT-qPCR, Western blotting, and CCK8 assays. Furthermore, we verified the candidate sequence targeted by miR-30a using a luciferase reporter gene assay. We observed a significant decrease in the serum miR-30a levels in patients with LN. Also, in IgG-LN-treated podocytes, miR-30a decreased and Notch1 expression was elevated. Bioinformatic analysis and transfection experiments revealed that Notch1 is a direct target of miR-30a. Further supporting this finding, miR-30a upregulation appeared to alleviate IgG-LN-treated podocyte injury, and Notch1 overexpression reversed this effect. To conclude, miR-30a can ameliorate podocyte injury via suppression of the Notch1 signaling pathway.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , MicroRNAs , Podócitos , Humanos , Imunoglobulina G/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMO
Seasonal changes, diurnal variations, and eutrophication result in periodic hypoxia in fish habitats, thus affecting the success of commercial aquaculture. In this study, the grass carp (Ctenopharyngodon idella) presented moderate hypoxia tolerance; they showed a medium critical oxygen tension during the loss of equilibrium. In response to 7 d of hypoxic exposure, the erythrocyte count and hemoglobin (Hb) concentration significantly increased (p < 0.01). To cope with the hypoxic environment, the grass carp underwent gill remodeling marked by reduction in the interlamellar cell mass (ILCM) and an increase in respiratory surface area. The gill remodeling under hypoxia was enabled by apoptosis induction. Although apoptotic signals were not found on ILCM cells, transferase dUTP nick end labeling (TUNEL) assay results indicated that after 1 d of hypoxic exposure, the number of TUNEL-positive cells per lamella increased until 4 d and then began to decrease. Consistent with the results of the TUNEL assay, the mRNA expression of apoptosis-related genes, caspase-3, Bax, and Bcl-2, increased at 1, 4, and 7 d of the hypoxia treatment. In addition, gill remodeling significantly (p < 0.01) decreased the concentration of sodium and chloride ions in the fish serum. These findings provide evidence that grass carps increase their respiratory surface area through gill remodeling by apoptosis in the gill filaments to acclimate to a hypoxic environment. This study expands our understanding of the morphological and physiological changes in grass carp in response to a hypoxic environment; therefore, it could be useful for maintaining grass carp production.
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Carpas , Doenças dos Peixes , Ração Animal/análise , Animais , Carpas/metabolismo , Doenças dos Peixes/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Brânquias/metabolismo , Hipóxia/metabolismo , Sistema RespiratórioRESUMO
Bisphenol S (BPS) is associated with neurotoxicity, but its molecular mechanisms are unclear. Our aim was to investigate the role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cAMP-response element-binding protein (CREB) signaling pathway in BPS-induced cytotoxicity in SK-N-SH cells. The cells were treated with various concentrations of BPS, and cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and the BDNF, cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TrkB, CREB, and phospho-CREB (p-CREB) levels were determined. The effects of pretreatment with the TrkB activator 7,8-dihydroxyflavone (7,8-DHF) were also explored. BPS decreased SK-N-SH cell viability and altered their morphology. Their apoptosis rate was increased, as were the levels of the proapoptotic proteins Bax and cleaved-caspase-3, but MMP was decreased. Thus, BPS may induce mitochondria-dependent apoptosis pathways. BPS also reduced the BDNF, TrkB, and p-CREB levels, and pretreatment with 7,8-DHF alleviated its cytotoxic effects. Thus, BPS-induced cytotoxicity might be mediated by the BDNF/TrkB/CREB signaling pathway.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citotoxinas/farmacologia , Glicoproteínas de Membrana/metabolismo , Fenóis/farmacologia , Receptor trkB/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , HumanosRESUMO
OBJECTIVE: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. METHODS: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. RESULTS: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. CONCLUSION: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.
Assuntos
Encéfalo/metabolismo , Doença da Descompressão/complicações , Oxigenoterapia Hiperbárica/métodos , Animais , Apoptose , Encéfalo/patologia , Química Encefálica , Caspase 3/análise , Catalase/análise , Catalase/metabolismo , Descompressão , Doença da Descompressão/metabolismo , Hipóxia-Isquemia Encefálica/etiologia , Ferro/análise , Ferro/metabolismo , Magnésio/análise , Magnésio/metabolismo , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Manganês/análise , Manganês/metabolismo , Necrose , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Zinco/análise , Zinco/metabolismo , Proteína X Associada a bcl-2/análiseRESUMO
We report a novel solid-state molecular device structure based on double self-assembled monolayers (D-SAM) incorporated into the suspended nanowire architecture to form a "Au|SAM-1||SAM-2|Au" junction. Using commercially available thiol molecules that are devoid of synthetic difficulty, we constructed a "Au|S-(CH2)6-ferrocene||SAM-2|Au" junction with various lengths and chemical structures of SAM-2 to tune the coupling between the ferrocene conductive molecular orbital and electrode of the junction. Combining low noise and a wide temperature range measurement, we demonstrated systematically modulated conduction depending on the length and chemical nature of SAM-2. Meanwhile, the transport mechanism transition from tunneling to hopping and the intermediate state accompanied by the current fluctuation due to the coexistence of the hopping and tunneling transport channels were observed. Considering the versatility of this solid-state D-SAM in modulating the electrode-molecule interface and electroactive groups, this strategy thus provides a novel facile strategy for tailorable nanoscale charge transport studies and functional molecular devices.
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One of the most globally prevalent supraventricular arrhythmias is atrial fibrillation (AF). Knowledge of the structures and functions of messenger RNA (mRNA) has recently increased. It is no longer viewed as solely an intermediate molecule between DNA and proteins but has come to be seen as a dynamic and modifiable gene regulator. This new perspective on mRNA has led to rising interest in it and its presence in research into new therapeutic schemes. This paper, therefore, focuses on microRNAs (miRNAs), which are small noncoding RNAs that regulate posttranscriptional gene expression and play a vital role in the physiology and normative development of cardiovascular systems. This means they play an equally vital role in the development and progression of cardiovascular diseases. In recent years, multiple studies have pinpointed particular miRNA expression profiles as being associated with varying histological features of AF. These studies have been carried out in both animal models and AF patients. The emergence of miRNAs as biomarkers and their therapeutic potential in AF patients will be discussed in the body of this paper.
Assuntos
Fibrilação Atrial/metabolismo , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , MicroRNAs/metabolismo , Animais , Fibrilação Atrial/patologia , Doenças Cardiovasculares/patologia , Humanos , RNA Mensageiro/metabolismo , Pequeno RNA não Traduzido/metabolismoRESUMO
OBJECTIVE: Atrial fibrillation (AF) represents the most common arrhythmia encountered in cardiology department. The purpose of this study was designed to investigate whether cilostazol, an oral phosphodiesterase 3 inhibitor (PDE3) could have protective effects on atrial remodeling in a canine model of AF and explore the potential molecular mechanisms. METHODS: Dogs were randomly assigned to Sham, Paced, Paced + cilostazol group, 7 dogs in each group. In Sham group, pacemaker was instrumented but without pacing. Rapid atrial pacing (RAP) at 600 or 500 bpm/min was maintained in Paced group and Paced + cilo group for 2 h or 2 weeks in acute or chronic experiment, respectively. The Paced + cilo group of dogs were pretreated with cilostazol orally (10 mg·kg-1·d-1, cilo) for 1 h or 2 days prior RAP induction and served as treatment group. Atrial effective refractory periods (AERP) at different basic cycle lengths (BCLs), inducibility, and duration time of AF were measured after pacing for 2 h. The blood sample, echocardiography, histopathology, inflammation and oxidative stress makers, protein and mRNA expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected after 2 weeks pacing in each group. RESULTS: Significant changes in electrophysiological parameters were observed in the acute RAP canine model, the AERPs shortened with increased inducibility and duration of AF, which was attenuated by cilostazol (P < 0.05). The serum inflammation makers as interleukin-8 (IL-8) and toll like receptor 4 (TLR 4) levels and oxidative stress indicators like xanthine oxidative (XO) and reactive oxygen species (ROS) in the Paced group was significantly higher than that in Sham group (P < 0.01), and was significantly reduced by cilostazol treatment (P < 0.01). The level of mean platelet volume (MPV) which is one of the platelet indices was significantly elevated in Paced group (P < 0.01). While after cilostazol treated for 2 weeks, the level of MPV was obviously decreased than Paced group (P < 0.01). Pathology and echocardiography studies showed that cilostazol can also prevent RAP induced cardiac fibrosis and structural remodeling. The MPV level has close correlations with IL-8, TLR4, XO and ROS (all P < 0.01). MMP-2 and MMP-9 expression were significantly increased in Paced group (all P < 0.01), which can be attenuated by cilostazol. CONCLUSIONS: Cilostazol may have protective effects on RAP-induced atrial remodeling by anti-inflammatory, anti-oxidative stress action and regulate the extracellular collagen matrix in a canine model. Moreover, MPV level is associated with inflammation and oxidative stress response of RAP, which might be an important predictors of new-onset and recurrent AF.
Assuntos
Fibrilação Atrial , Animais , Fibrilação Atrial/tratamento farmacológico , Estimulação Cardíaca Artificial , Cilostazol , Modelos Animais de Doenças , Cães , Eletrocardiografia , Átrios do Coração , Metaloproteinase 2 da Matriz , Diester Fosfórico HidrolasesRESUMO
Marine actinobacterium Streptomyces xinghaiensis NRRL B-24674T has been characterized as a novel species, but thus far, its biosynthetic potential remains unexplored. In this study, the high-quality genome sequence of S. xinghaiensis NRRL B-24674T was obtained, and the production of anticomplement agents, xiamycin analogs, and siderophores was investigated by genome mining. Anticomplement compounds are valuable for combating numerous diseases caused by the abnormal activation of the human complement system. The biosynthetic gene cluster (BGC) nrps1 resembles that of complestatins, which are potent microbial-derived anticomplement agents. The identification of the nrps1 BGC revealed a core peptide that differed from that in complestatin; thus, we studied the anticomplement activity of this strain. The culture broth of S. xinghaiensis NRRL B-24674T displayed good anticomplement activity. Subsequently, the disruption of the genes in the nrps1 BGC resulted in the loss of anticomplement activity, confirming the involvement of this BGC in the biosynthesis of anticomplement agents. In addition, the mining of the BGC tep5, which resembles that of the antiviral pentacyclic indolosesquiterpene xiamycin, resulted in the discovery of nine xiamycin analogs, including three novel compounds. In addition to the BGCs responsible for desferrioxamine B, neomycin, ectoine, and carotenoid, 18 BGCs present in the genome are predicted to be novel. The results of this study unveil the potential of S. xinghaiensis as a producer of novel anticomplement agents and provide a basis for further exploration of the biosynthetic potential of S. xinghaiensis NRRL B-24674T for the discovery of novel bioactive compounds by genome mining.
Assuntos
Proteínas de Bactérias/genética , Proteínas Inativadoras do Complemento/biossíntese , Genoma Bacteriano , Família Multigênica , Sesquiterpenos/metabolismo , Streptomyces/genética , Sequência de Aminoácidos , Proteínas de Bactérias/metabolismo , Proteínas Inativadoras do Complemento/química , Dados de Sequência Molecular , Estrutura Molecular , Filogenia , Alinhamento de Sequência , Sesquiterpenos/química , Streptomyces/química , Streptomyces/classificação , Streptomyces/metabolismoRESUMO
A sensitive and reliable LC-ESI-MS method for the determination of salvianolic acid C in rat plasma has been developed and validated. Plasma samples were prepared by liquid-liquid extraction with ethyl acetate and separated on a Zorbax SB-C18 column (3.5 µm, 2.1 × 100 mm) at a flow rate of 0.3 mL/min using acetonitrile-water as mobile phase. The detection was carried out by a single quadrupole mass spectrometer with electrospray ionization source and selected ion monitoring mode. Linearity was obtained for salvianolic acid C ranging from 5 to 1000 ng/mL. The intra- and inter-day precisions (RSD, %) didn't exceed 9.96%, and the accuracy (RE, %) were all within ±3.64%. The average recoveries of the analyte and internal standard were >89.13%. Salvianolic acid C was proved to be stable during all sample storage, preparation and analytic procedures. The validated method was successfully applied to pharmacokinetic study after oral and intravenous administration of salvianolic acid C to rats. The absolute oral bioavailability of salvianolic acid C was 0.29 ± 0.05%. This method was further applied to simultaneous determination of salvianolic acid A, salvianolic acid B and salvianolic acid C in rat plasma and showed good practicability.
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Alcenos/sangue , Alcenos/farmacocinética , Cromatografia Líquida/métodos , Polifenóis/sangue , Polifenóis/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Alcenos/química , Animais , Estabilidade de Medicamentos , Feminino , Modelos Lineares , Masculino , Polifenóis/química , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A new label-free resonance light scattering method for the highly selective and sensitive detection of mercury ion was designed. This strategy makes use of the target-induced DNA conformational change to enhance the resonance light scattering intensity leading to an amplified optical signal. The Hg²âº ion, which possesses a unique property to bind specifically to two DNA thymine (T) bases, in the presence of Hg²âº, the specific oligonucleotide probes form a conformational reorganization of the oligonucleotide probes from single-chain structure to duplex-like complexes, which can greatly enhance the resonance light scattering intensity. Under the optimum experimental conditions, the enhanced resonance light scattering intensity at 566 nm was in proportion of mercury ion concentration in the range 7.2 x 10â»9 x 10â»8 mol · L⻹ with the linear regression equation was ΔI = 5.12c+3.55 (r = 0.999 5). This method was successfully applied to detection of Hg²âº in enviro nmental water samples, the RSD were less than 1.9% and recoveries were 99.4%-104.3%. This label-free strategy uses the mercury specific oligonucleotide probes as recognition elements and control the strength of resonance light scattering by changing the concentration of Hg²âº. It translating the small molecule detection into the DNA hybridization behavior leading to an amplified resonance light scattering signal can well enhance the sensitive detection of Hg²âº. With amplification by DNA hybridization behavior, the sensitivity for the detection of Hg²âº can achieve 2.16 x 10â»9 mol · L(⻹). In this study, the stacked T-Hg²âº-Tfunctioned not only as amplification property but also as an selective recognition. The highly specific detection of Hg²âº is attributed to the formation of a stable T-Hg²âº-T complex.
Assuntos
Técnicas Biossensoriais , DNA/química , Mercúrio/análise , Timina/química , Hibridização de Ácido Nucleico , Sondas de OligonucleotídeosRESUMO
Folding-induced folding for the construction of artificial hybrid helices from two different kinds of aromatic sequences is described. Linear compounds 1 a, 1 b, and 2, containing one aromatic amide trimer or pentamer and one or two aromatic 1,2,3-triazole tetramers, have been designed and synthesized. The trimeric and pentameric amide segments are driven by intramolecluar N-Hâ â â F hydrogen bonding to adopt a folded or helical conformation, whereas the triazole segment is intrinsically disordered. In organic solvents of low polarity, the amide foldamer segment induces the attached triazole segment(s) to fold through intramolecular stacking, leading to the formation of hybrid helices. The helical conformation of these hybrid sequences has been confirmed by (1)H and (19)Fâ NMR spectroscopy, UV/Vis spectroscopy, circular dichroism (CD) experiments, and theoretical calculations. It was found that the amide pentamer exhibits a stronger ability to induce the folding of the attached triazole segment(s) compared with that of the shorter trimer. Enantiomers (R)-3 and (S)-3, which contain an R- or S-(1-naphthyl)ethylamino group at the end of a tetraamide segment, have also been synthesized. CD experiments showed that introduction of a chiral group caused the whole framework to produce a strong helicity bias. Density-functional-theory calculations on (S)-3 suggested that this compound exists as a right-handed (P) helix.
Assuntos
Amidas/química , Triazóis/química , Dicroísmo Circular , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Conformação MolecularRESUMO
PURPOSE: In the present study, we investigated the vasodilatory effect of a novel scaffold Rho-kinase inhibitor, DL0805-2, on isolated rat arterial rings including mesenteric, ventral tail, and renal arteries. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings. METHODS: A DMT multiwire myograph system was used to test the tension of isolated small arteries. Several drugs were employed to verify the underlying mechanisms. RESULTS: DL0805-2 (10(-7)-10(-4) M) inhibited KCl (60 mM)-induced vasoconstriction in three types of small artery rings (pEC50: 5.84 ± 0.03, 5.39 ± 0.03, and 5.67 ± 0.02 for mesenteric, renal, and ventral tail artery rings, respectively). Pre-incubation with DL0805-2 (1, 3, or 10 µM) attenuated KCl (10-60 mM) and angiotensin II (AngII; 10(-6) M)-induced vasoconstriction in mesenteric artery rings. The relaxant effect on the rat mesenteric artery was partially endothelium-dependent (pEC50: 6.02 ± 0.05 for endothelium-intact and 5.72 ± 0.06 for endothelium-denuded). The influx and release of Ca(2+) were inhibited by DL0805-2. In addition, the increased phosphorylation levels of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by AngII were blocked by DL0805-2. However, DL0805-2 had little effect on K(+) channels. CONCLUSIONS: The present results demonstrate that DL0805-2 has a vasorelaxant effect on isolated rat small arteries and may exert its action through the endothelium, Ca(2+) channels, and the Rho/ROCK pathway.
Assuntos
Artérias/efeitos dos fármacos , Indazóis/farmacologia , Vasodilatadores/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Artérias/metabolismo , Artérias/fisiologia , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Técnicas In Vitro , Cadeias Leves de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Fosforilação/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Cloreto de Potássio/antagonistas & inibidores , Cloreto de Potássio/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Ratos , Vasoconstritores/antagonistas & inibidores , Vasoconstritores/farmacologiaRESUMO
This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.
Assuntos
Boraginaceae/química , Flavonoides/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Apoptose , Proteínas Reguladoras de Apoptose , Coração , Interleucina-6 , Infarto do Miocárdio , Miocárdio , Fosfatidilinositol 3-Quinases , Fosforilação , Substâncias Protetoras , Proteínas Proto-Oncogênicas c-akt , Ratos , Transdução de Sinais , Fator de Necrose Tumoral alfa , Proteína X Associada a bcl-2RESUMO
This study introduces a modified DF2016 criterion to model a ductile fracture of sheet metals from shear to equibiaxial tension. The DF2016 criterion is modified so that a material constant is equal to the fracture strain at equibiaxial tension, which can be easily measured by the bulging experiments. To evaluate the performance of the modified DF2016 criterion, experiments are conducted for QP980 with five different specimens with stress states from shear to equibiaxial tension. The plasticity of the steel is characterized by the Swift-Voce hardening law and the pDrucker function, which is calibrated with the inverse engineering approach. A fracture strain is measured by the XTOP digital image correlation system for all the specimens, including the bulging test. The modified DF2016 criterion is also calibrated with the inverse engineering approach. The predicted force-stroke curves are compared with experimental results to evaluate the performance of the modified DF2016 criterion on the fracture prediction from shear to equibiaxial tension. The comparison shows that the modified DF2016 criterion can model the onset of the ductile fracture with high accuracy in wide stress states from shear to plane strain tension. Moreover, the calibration of the modified DF2016 criterion is comparatively easier than the original DF2016 criterion.