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The zinc dendrite growth generally relies upon a "positive-feedback" mode, where the fast-grown tips receive higher current densities and ion fluxes. In this study, a self-limiting polyacrylamide (PAM) hydrogel that presents negative feedback to dendrite growth is developed. The monomers are purposefully polymerized at the dendrite tips, then the hydrogel reduces the local current density and ion flux by limiting zinc ion diffusion with abundant functional groups. As a consequence, the accumulation at the dendrite tips is restricted, and the (002) facets-oriented deposition is achieved. Moreover, the refined porous structure of the gel enhances Coulombic Efficiency by reducing water activity. Due to the synergistic effects, the zinc anodes perform an ultralong lifetime of 5100 h at 0.5 mA cm-2 and 1500 h at 5 mA cm-2, which are among the best records for PAM-based gel electrolytes. Further, the hydrogel significantly prolongs the lifespan of zinc-ion batteries and capacitors by dozens of times. The developed in situ hydrogel presents a feasible and cost-effective way to commercialize zinc anodes and provides inspiration for future research on dendrite suppression using the negative-feedback mechanism.
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Aqueous Zn batteries (AZBs) are a promising energy storage technology, due to their high theoretical capacity, low redox potential, and safety. However, dendrite growth and parasitic reactions occurring at the surface of metallic Zn result in severe instability. Here we report a new method to achieve ultrafine Zn nanograin anodes by using ethylene glycol monomethyl ether (EGME) molecules to manipulate zinc nucleation and growth processes. It is demonstrated that EGME complexes with Zn2+ to moderately increase the driving force for nucleation, as well as adsorbs on the Zn surface to prevent H-corrosion and dendritic protuberances by refining the grains. As a result, the nanoscale anode delivers high Coulombic efficiency (ca. 99.5%), long-term cycle life (over 366 days and 8800 cycles), and outstanding compatibility with state-of-the-art cathodes (ZnVO and AC) in full cells. This work offers a new route for interfacial engineering in aqueous metal-ion batteries, with significant implications for the commercial future of AZBs.
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BACKGROUND: Rancidity causes unpleasant tastes and smells, and the degradation of fatty acids and natural antioxidants, so that an oil is unfit to be consumed. Natural antioxidants, including tocopherols, polyphenols (sesamol, canolol, ferulic acid, caffeic acid, etc.), ß-carotene, squalene and phytosterols, contribute to delay the oxidation of vegetable oils. However, studies on the combination of natural antioxidants to lengthen the shelf life of unsaturated fatty acid-rich blended oil have not been reported. RESULTS: All of the composite antioxidants had the potential to significantly improve the oxidation stability of blended oil. Blended oil G with 0.05 g kg-1 ß-carotene, 0.25 g kg-1 sesamol and 0.25 g kg-1 caffeic acid showed the best anti-autooxidation. It is also effective in improving the oxidative stability of vegetable oils containing various fatty acids. The oxidation stability index of the blended oil containing the optimum composition of natural antioxidants was 2.17-fold longer than that of the control sample. After the end of accelerated oxidation, the oil's peroxide value, p-anisidine value and total oxidation value were 6.59 times, 12.26 times and 6.65 times lower than those of the control sample, respectively. CONCLUSION: (1) The combination of natural antioxidants ß-carotene (0.05 g kg-1 ), sesamol (0.25 g kg-1 ) and caffeic acid (0.25 g kg-1 ) enhances the oxidative stability of unsaturated fatty acid-rich blended oils. (2) ß-Carotene is the main antioxidant in the early stages of oxidation. (3) Sesamol and caffeic acid are the main antioxidants in the middle and late stages of oxidation. © 2023 Society of Chemical Industry.
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Antioxidantes , Benzodioxóis , Fenóis , beta Caroteno , Antioxidantes/química , Oxirredução , Ácidos Graxos Insaturados , Óleos de Plantas/química , Ácidos Graxos , Ácidos CafeicosRESUMO
BACKGROUND: Assessing the structure and function of left atrium (LA) is crucial in hypertrophic obstructive cardiomyopathy (HOCM) because LA remodeling correlates with atrial fibrillation. However, few studies have investigated the potential effect of myomectomy on LA phasic remodeling in HOCM after myectomy using cardiovascular magnetic resonance (CMR) feature tracking (FT). This study aims to evaluate the LA structural and functional remodeling with HOCM after myectomy by CMR-FT and to further investigate the determinants of LA reverse remodeling. METHODS: In this single-center study, we retrospectively studied 88 patients with HOCM who received CMR before and after myectomy between January 2011 and June 2021. Preoperative and postoperative LA parameters derived from CMR-FT were compared, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster function (booster EF, active strain [εa], late peak negative strain rate [SRa]). Eighty-six healthy participants were collected for comparison. Univariate and multivariate linear regression identified variables associated with the rate of change of εa. RESULTS: Compared with preoperative parameters, LA reservoir function (total EF, εs, SRs), booster function (booster EF, εa, SRa), and SRe were significantly improved after myectomy (all P < 0.05), while no significant differences were observed in passive EF and εe. Postoperative patients with HOCM still had larger LA and worse LA function than healthy controls (all P < 0.05). After analyzing the rates of change in LA parameters, LA boost function, especially εa, showed the most dramatic improvement beyond the improvements in reservoir function, conduit function, and volume. In multivariable regression analysis, minimum LA volume index (adjusted ß = - 0.39, P < 0.001) and Δleft ventricular outflow tract (LVOT) pressure gradient (adjusted ß = - 0.29, P = 0.003) were significantly related to the rate of change of εa. CONCLUSIONS: Patients with HOCM after septal myectomy showed LA reverse remodeling with a reduction in LA size and restoration in LA reservoir and booster function but unchanged LA conduit function. Among volumetric and functional changes, booster function had the greatest improvement postoperatively. Besides, preoperative LAVmin index and ΔLVOT might be potential factors associated with the degree of improvement in εa.
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Cardiomiopatia Hipertrófica , Átrios do Coração , Humanos , Estudos Retrospectivos , Valor Preditivo dos Testes , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Cardiomiopatia Hipertrófica/complicações , Espectroscopia de Ressonância MagnéticaRESUMO
Transition metal sulfides have exhibited remarkable advantages in gaseous elemental mercury (Hg0) capture under high SO2 atmosphere, whereas the weak thermal stability significantly inhibits their practical application. Herein, a novel N,N-dimethylformamide (DMF) insertion strategy via crystal growth engineering was developed to successfully enhance the Hg0 capture ability of MoS2 at an elevated temperature for the first time. The DMF-inserted MoS2 possesses an edge-enriched structure and an expanded interlayer spacing (9.8 Å) and can maintain structural stability at a temperature as high as 272 °C. The saturated Hg0 adsorption capacities of the DMF-inserted MoS2 were measured to be 46.91 mg·g-1 at 80 °C and 27.40 mg·g-1 at 160 °C under high SO2 atmosphere. The inserted DMF molecules chemically bond with MoS2, which prevents possible structural collapse at a high temperature. The strong interaction of DMF with MoS2 nanosheets facilitates the growth of abundant defects and edge sites and enhances the formation of Mo5+/Mo6+ and S22- species, thereby improving the Hg0 capture activity at a wide temperature range. Particularly, Mo atoms on the (100) plane represent the strongest active sites for Hg0 oxidation and adsorption. The molecule insertion strategy developed in this work provides new insights into the engineering of advanced environmental materials.
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Mercúrio , Molibdênio , Dissulfetos , SulfetosRESUMO
Parkinson's disease (PD) is a common neurodegenerative motor disorder characterized by a dramatic reduction in pars compacta of substantia nigra dopaminergic neurons and striatal dopamine (DA) levels. Mutations or deletions in the PARK7/DJ-1 gene are associated with an early-onset familial form of PD. DJ-1 protein prevents neurodegeneration via its regulation of oxidative stress and mitochondrial function as well as its roles in transcription and signal transduction. In this study, we investigated how loss of DJ-1 function affected DA degradation, ROS generation and mitochondrial dysfunction in neuronal cells. We showed that loss of DJ-1 significantly increased the expression of monoamine oxidase (MAO)-B but not MAO-A in both neuronal cells and primary astrocytes. In DJ-1-knockout (KO) mice, MAO-B protein levels in the substantia nigra (SN) and striatal regions were significantly increased. We demonstrated that the induction of MAO-B expression by DJ-1 deficiency depended on early growth response 1 (EGR1) in N2a cells. By coimmunoprecipitation omics analysis, we found that DJ-1 interacted with receptor of activated protein C kinase 1 (RACK1), a scaffolding protein, and thus inhibited the activity of the PKC/JNK/AP-1/EGR1 cascade. The PKC inhibitor sotrastaurin or the JNK inhibitor SP600125 completely inhibited DJ-1 deficiency-induced EGR1 and MAO-B expression in N2a cells. Moreover, the MAO-B inhibitor rasagiline inhibited mitochondrial ROS generation and rescued neuronal cell death caused by DJ-1 deficiency, especially in response to MPTP stimulation in vitro and in vivo. These results suggest that DJ-1 exerts neuroprotective effects by inhibiting the expression of MAO-B distributed at the mitochondrial outer membrane, which mediates DA degradation, ROS generation and mitochondrial dysfunction. This study reveals a mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the crosslinks among pathogenic factors, mitochondrial dysfunction and oxidative stress in PD pathogenesis.
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Doenças Neurodegenerativas , Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Monoaminoxidase/farmacologia , Regulação para Cima , Espécies Reativas de Oxigênio/metabolismo , Neurônios Dopaminérgicos/metabolismo , Transdução de Sinais , Doenças Neurodegenerativas/metabolismo , Receptores de Quinase C Ativada/genética , Receptores de Quinase C Ativada/metabolismo , Receptores de Quinase C Ativada/farmacologia , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismoRESUMO
BACKGROUND AND AIM: The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. METHODS AND RESULTS: A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016-2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P < 0.0001). There were significant positive correlations between BMI in each stage and ORs of MetS during lactation (P < 0.05). The best cut-off values for BMI in the four stages were 23.47, 30.49, 26.04 and 25.47 kg/m2. The non-linear spline test at BMI in 42 days postpartum, current and MetS in lactation was statistically significant (P non-linear = 0.0223, 0.0003). The mediation effect of all chains have to work through lactation BMI. The total indirect effect accounted for 80.95% of the total effect. CONCLUSIONS: The risk of MetS in lactating women is due to a high BMI base before pregnancy and postpartum. High BMI in all stages of pregnancy and postpartum were risk factors for MetS in lactation. BMI during lactation plays a key role in the risk of MetS.
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Síndrome Metabólica , Feminino , Humanos , Gravidez , Índice de Massa Corporal , Aleitamento Materno , População do Leste Asiático , Lactação , Síndrome Metabólica/epidemiologiaRESUMO
Although antibiotics are one of the most significant factors contributing to the propagation of antibiotic resistance genes (ARGs), studies on the dose-response relationship at sub-lethal concentrations of antibiotics remain scarce, despite their importance for assessing the risks of antibiotics in the environment. In this study, we constructed a series of microcosms to investigate the propagation of intracellular (iARGs) and extracellular (eARGs) ARGs in both water and biofilms when exposed to antibiotics at various concentrations (1-100 µg/L) and frequencies. Results showed that eARGs were more abundant than iARGs in water, while iARGs were the dominant ARGs form in biofilms. eARGs showed differentiated dose-response relationships from iARGs. The abundance of iARGs increased with the concentration of antibiotics as enhanced selective pressure overcame the metabolic burden of antibiotic-resistant bacteria carrying ARGs. However, the abundance of eARGs decreased with increasing antibiotic concentrations because less ARGs were secreted from bacterial hosts at higher concentrations (100 µg/L). Furthermore, combined exposure to two antibiotics (tetracycline & imipenem) showed a synergistic effect on the propagation of iARGs, but an antagonistic effect on the propagation of eARGs compared to exposure to a single antibiotic. When exposed to antibiotic at a fixed total dose, one-time dosing (1 time/10 d) favored the propagation of iARGs, while fractional dosing (5 times /10 d) favored the propagation of eARGs. This study sheds light on the propagation of antibiotic resistance in the environment and can help in assessing the risks associated with the use of antibiotics.
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Antibacterianos , Genes Bacterianos , Antibacterianos/farmacologia , Tetraciclina , Resistência Microbiana a Medicamentos/genética , Bactérias , ÁguaRESUMO
Hepatocellular carcinoma (HCC), the major type of liver cancer, causes a high annual mortality worldwide. RAD51 is the critical recombinase responsible for homologous recombination (HR) repair in DNA damage. In this study, we identified that RAD51 was upregulated in HCC and that RAD51 silencing or inhibition reduced the proliferation, migration, and invasion of HCC cells and enhanced cell apoptosis and DNA damage. HCC cells with the combinatorial treatments of RAD51 siRNA or inhibitor and sorafenib demonstrated a synergistic effect in inhibiting HCC cell proliferation, migration, and invasion, as well as inducing cell apoptosis and DNA damage. Single RAD51 silencing or sorafenib reduced RAD51 protein expression and weakened HR efficiency, and their combination almost eliminated RAD51 protein expression and inhibited HR efficiency further. An in vivo tumor model confirmed the RAD51 inhibitor's antitumor activity and synergistic antitumor activity with sorafenib in HCC. RNA-Seq and gene set enrichment analysis (GSEA) in RAD51-inactivated Huh7 cells indicated that RAD51 knockdown upregulated cell apoptosis and G1/S DNA damage checkpoint pathways while downregulating mitotic spindle and homologous recombination pathways. Our findings suggest that RAD51 inhibition exhibits antitumor activities in HCC and synergizes with sorafenib. Targeting RAD51 may provide a novel therapeutic approach in HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Rad51 Recombinase/genética , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: Drug-Drug interactions (DDIs) are a challenging problem in drug research. Drug combination therapy is an effective solution to treat diseases, but it can also cause serious side effects. Therefore, DDIs prediction is critical in pharmacology. Recently, researchers have been using deep learning techniques to predict DDIs. However, these methods only consider single information of the drug and have shortcomings in robustness and scalability. RESULTS: In this paper, we propose a multi-type feature fusion based on graph neural network model (MFFGNN) for DDI prediction, which can effectively fuse the topological information in molecular graphs, the interaction information between drugs and the local chemical context in SMILES sequences. In MFFGNN, to fully learn the topological information of drugs, we propose a novel feature extraction module to capture the global features for the molecular graph and the local features for each atom of the molecular graph. In addition, in the multi-type feature fusion module, we use the gating mechanism in each graph convolution layer to solve the over-smoothing problem during information delivery. We perform extensive experiments on multiple real datasets. The results show that MFFGNN outperforms some state-of-the-art models for DDI prediction. Moreover, the cross-dataset experiment results further show that MFFGNN has good generalization performance. CONCLUSIONS: Our proposed model can efficiently integrate the information from SMILES sequences, molecular graphs and drug-drug interaction networks. We find that a multi-type feature fusion model can accurately predict DDIs. It may contribute to discovering novel DDIs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Redes Neurais de Computação , Interações Medicamentosas , Fusão Gênica , HumanosRESUMO
Enzyme-linked immunosorbent assay (ELISA) is one of the most common methods in biological studies, and enzyme-linked immunospot (ELISpot) is a method to measure specific cell numbers by detecting protein secretion at a single-cell level. However, these two current methods can only detect one signal at one time and the sensitivity is not high enough to test low-concentration samples, which are major shortcomings in systematically analyzing the samples of interest. Herein, we demonstrated fluorescence-based oligo-linked immunosorbent assay (FOLISA) and fluorescence-based oligo-linked immunospot (FOLISPOT), which utilized DNA-barcoded antibodies to provide a highly multiplexed method with signal amplification. Signal amplification and simultaneous multiple-target detection were achieved by DNA complementary pairing and modular orthogonal DNA concatemers. By comparing FOLISA with traditional ELISA and comparing FOLISPOT with traditional ELISPOT, we found that the detection sensitivities of FOLISA and FOLISPOT are much higher than those of traditional ELISA and ELISPOT. The detection limit of ELISA is around 3 pg/mL, and the detection limit of FOLISA is below 0.06 pg/mL. FOLISPOT can detect more spots than ELISPOT and can detect targets that are undetectable for ELISPOT. Furthermore, FOLISA and FOLISPOT allowed sequential detection of multiple targets by using a single dye or multiple dyes in one round and sequential detection in multiple rounds. Thus, FOLISA and FOLISPOT enabled simultaneous detection of a large number of targets, significantly improved the detection sensitivity, and overcame the shortcomings of ELISA and ELISPOT. Overall, FOLISA and FOLISPOT presented effective and general platforms for rapid and multiplexed detection of antigens or antibodies with high sensitivity, either in laboratory tests or potentially in clinic tests.
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Antígenos , Imunoadsorventes , Anticorpos , Ensaio de Imunoadsorção Enzimática/métodos , ELISPOT/métodosRESUMO
Background Myocardial replacement fibrosis is one of the major histologic features of hypertrophic cardiomyopathy (HCM), but its characteristics have not been well delineated. Purpose To clarify the characteristics of replacement fibrosis in HCM and to evaluate the prognostic value of the regional extent of fibrosis. Materials and Methods This prospective study evaluated participants with HCM who underwent contrast-enhanced cardiac MRI from March 2011 to April 2019. For each participant, global and 16-segment extent of late gadolinium enhancement (LGE) in the left ventricle (LV) at cardiac MRI was analyzed. The primary end point was all-cause death. Results Among the 798 study participants enrolled (median age, 49 years [interquartile range {IQR}: 38-59 years]; 508 men), 588 (74%) underwent whole-exome sequencing. Thirty-five participants (4%) experienced death from any cause during a median follow-up of 2.9 years (IQR: 1.5-4.7 years). Spearman analysis showed weak correlations between the extent of LGE and wall thickness (LGE of global LV and maximal LV wall thickness, r = 0.35 [P < .001]; LGE and thickness of septum, r = 0.30 [P < .001]). In the 16-segment model, the distribution of LGE was visually inhomogeneous and higher in the basal anterior, basal septal, midanterior, and midseptal regions (P < .001). This similar distribution of LGE was observed in participants with asymmetric septal hypertrophy, those with apical HCM, participants positive for mutation and those negative for mutation, and participants with MYH7 and MYBPC3 mutations. Cox analysis indicated that both the global extent of LGE (adjusted hazard ratio = 1.68 per 10% increase in LGE; P < .001) and the regional extent of LGE (ie, basal, midventricular, and apical regions of LV when on the short-axis view; septum, anterior free wall, inferior free wall, and lateral free wall when on the long-axis view) were associated with adverse outcomes. Conclusion In hypertrophic cardiomyopathy, myocardial replacement fibrosis weakly correlated with hypertrophy, was inhomogeneous and asymmetric, and was predominantly distributed in the interventricular septal wall and anterior free wall at the basal and mid levels. Greater extent of fibrosis was associated with poor prognosis, regardless of its location in the left ventricle. © RSNA, 2021 See also the editorial by Hanneman in this issue.
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Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Imagem Cinética por Ressonância Magnética/métodos , Adulto , Cardiomiopatia Hipertrófica/genética , Meios de Contraste , Feminino , Fibrose/diagnóstico por imagem , Fibrose/patologia , Gadolínio DTPA , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sequenciamento do ExomaRESUMO
The unique capitulum of Asteraceae has important ornamental and research value. Few studies have described the complex molecular mechanism of flower development. In this study, SvGLOBOSA(SvGLO), the MADS-box gene of Senecio vulgaris, was identified by screening the transcriptome data, and its function was examined. The gene structure was analyzed and its function was predicted through bioinformatics. The relative expression levels in different tissues of wild-type S. vulgaris were analyzed by qRT-PCR. SvGLO was overexpressed in Solanum nigrum and morphological observations were made. Histological staining was used in analyzing the histological changes in the ovary of transgenic S. nigrum. The results showed that the open reading frame of SvGLO was 591 bp long, encoding 196 amino acids. It has typical MADS-box and K-box domains and contains a PI motif at the C-terminal. SvGLO belongs to the PI/GLO subfamily of class B MADS-box genes. qRT-PCR results showed that SvGLO was highly expressed in inflorescence tissues but not in vegetative organs. In SvGLO-overexpressed S. nigrum, the sepals showed some characteristics of petals, carpels transformed into stamen-like organs, and fruit development was abnormal. Histological staining revealed that the morphology of ovary wall cells of transgenic S. nigrum was similar to that of anther wall cells of the stamen of wild-type S. vulgaris. Therefore, SvGLO may be involved in the regulation of petal and stamen development in S. vulgaris.
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Proteínas de Domínio MADS , Senécio , Flores/genética , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Senécio/metabolismoRESUMO
Acute kidney injury has a high global morbidity associated with an increased risk of death and chronic kidney disease. Renal tubular epithelial cell regeneration following injury may be a decisive factor in renal repair or the progression of acute kidney injury to chronic kidney disease, but the underlying mechanism of abnormal renal tubular repair remains unclear. In the present study, we investigated the role of heterotrimeric G stimulatory protein α-subunit (Gsa) in renal tubular epithelial cell regeneration. We generated renal tubule epithelium-specific Gsa knockout (GsaKspKO) mice to show the essential role of Gsa in renal tubular epithelial cell regeneration in two AKI models: acute aristolochic acid nephropathy (AAN) and unilateral ischemia-reperfusion injury (UIRI). GsaKspKO mice developed more severe renal impairment after AAN and UIRI, higher serum creatinine levels, and more substantial tubular necrosis than wild-type mice. More importantly, Gsa inactivation impaired renal tubular epithelial cell proliferation by reducing bromodeoxyuridine+ cell numbers in the AAN model and inhibiting cyclin-dependent kinase 2/cyclin E1 expression in the UIRI model. This reduced proliferation was further supported in vitro with Gsa-targeting siRNA. Downregulation of Gsa inhibited tubular epithelial cell proliferation in HK-2 and mIMCD-3 cells. Furthermore, Gsa downregulation inhibited cyclin-dependent kinase 2/cyclin E1 expression, which was dependent on the Raf-MEK-ERK signaling pathway. In conclusion, Gsa is required for tubular epithelial cell regeneration during kidney repair after AKI. Loss of Gsa impairs renal tubular epithelial cell regeneration by blocking the Raf-MEK-ERK pathway.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Nefropatias/etiologia , Animais , Ácidos Aristolóquicos , Linhagem Celular , Proliferação de Células , Proteínas Quinases Dependentes de AMP Cíclico/genética , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Regulação para Baixo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Nefropatias/metabolismo , Túbulos Renais/citologia , Camundongos , Camundongos Knockout , Traumatismo por ReperfusãoRESUMO
Protein tyrosine (Tyr) nitration, the covalent addition of a nitro group (â¢NO2) to Tyr residues, is emerging as a candidate mechanism of endothelial dysfunction. Previous studies have shown that Tyr nitration is primarily induced by nitrosative stress, a process characterized by the production of reactive nitrogen species, especially peroxynitrite anion (ONOO-), which is considered a secondary product of NO in the presence of superoxide radicals (O2â¢-). However, the impact of nitrosative stress-induced Tyr nitration on endothelial dysfunction has not been thoroughly elucidated to date. We developed an endothelial dysfunction model, a process called "endothelial-to-mesenchymal transition (EndMT)," and evaluated the production of NO, O2â¢-, and protein nitration during EndMT. The results showed that TGF-ß1 stimulation induced EndMT and elevated endothelial NO and O2â¢- production as well as nitration of the catalytic subunit of protein phosphatase (PP)2A. Mass spectrometry analysis showed that Tyr265 was the nitration site in the catalytic subunit of protein phosphatase (PP)2A, and this Tyr nitration increased PP2A activity and disrupted endothelial integrity. To devise an endothelial-targeted anti-PP2Ac nitration strategy, a mimic peptide, tyrosine 265 wild type (Y265WT), conjugated with the cell-penetrating peptide HIV-1 TAT protein (TAT) was synthesized. PP2Ac nitration and PP2A activity were significantly inhibited by pretreatment with TAT-265WT, and the integrity of endothelial cells was maintained. Furthermore, injection of TAT-265WT attenuated renal nitration formation and caused anticapillary rarefaction in a unilateral urethral obstructive nephropathy model. Taken together, these results offer preclinical proof of concept for TAT-265WT as a tractable agent to protect against nitrosative stress-induced endothelial dysfunction in renal microvessels.-Deng,Y., Cai, Y., Liu, L., Lin, X., Lu, P., Guo, Y., Han, M., Xu, G. Blocking Tyr265 nitration of protein phosphatase 2A attenuates nitrosative stress-induced endothelial dysfunction in renal microvessels.
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Células Endoteliais/metabolismo , Rim/metabolismo , Microvasos/metabolismo , Estresse Nitrosativo/fisiologia , Proteína Fosfatase 2/metabolismo , Tirosina/metabolismo , Doenças Vasculares/metabolismo , Animais , Linhagem Celular , Endotélio/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Peroxinitroso/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Superóxidos/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
In designing organic semiconductors for organic devices, halogenation is a very popular strategy for tuning the electronic properties and packing arrangement in the solid state. Herein, we report the synthesis and characterization of halogenated dibenzo[a,j]perylene (DBP) with triethylsilyl (TES)-ethynyl substituents at the 8- and 16-positions (TES-DBP). The resulting compounds are characterized by optical, electrochemical, crystallographic, and computational studies to clarify the effect of halogenation on the optoelectronic properties and charge-carrier transport. It is found that the halogen atoms, the degree of halogenation, and their positional locations can alter the electronic properties and crystal packing of the compounds. In contrast to fluorinated TES-DBP, the chlorinated counterpart has red-shifted maximum absorption and lower electron affinity owing to the electron delocalization between DBP core and the unoccupied 3d orbitals of Cl atom. Organic field-effect transistor measurements demonstrate that TES-2ClDBP shows a hole mobility of 0.25 cm2 V-1 s-1, which is higher than TES-2FDBP and TES-DBP. On the other hand, TES-4ClDBP exhibits ambipolar transport characteristics with electron and hole mobilities up to 0.02 and 0.07 cm2 V-1 s-1, respectively.
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Root-knot nematode, Meloidogyne mali can cause damage in trees, shrubs, and herbaceous plants, and was placed on the EPPO Alert List in 2014. In the present study, we report a population isolated from Japanese maple. The recovered population is described by detailed morphological and molecular approaches. The molecular phylogentic analysis based on 28S rRNA, ITS, and mitochondrial COI genes places the population in the clade together with other M. mali sequences available in GenBank. The cloned sequences of the 28S rRNA gene revealed a high intragenomic rRNA polymorphism where the polymorphic copies are spread across M. mali clade. Similarly, we also found high variation in the mitochondrial COI gene. Among four haplotypes in M. mali, three occur in the newly found population. Our study provides the first report of intragenomic polymorphism in M. mali, and the results suggest that intragenomic polymorphism maybe widespread in Meloidogyne.
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Seinura italiensis n. sp. isolated from the medium soil imported from Italy is described and illustrated using morphological and molecular data. The new species is characterized by having short body (477 (407-565) µm and 522 (469-590) µm for males and females, respectively), three lateral lines, stylet lacking swellings at the base, and excretory pore at the base or slightly anterior to base of metacorpus; females have 58.8 (51.1-69.3) µm long post-uterine sac (PUS), elongate conical tail with its anterior half conoid, dorsally convex, and ventrally slightly concave and the posterior half elongated, narrower, with finely rounded to pointed tip and males having seven caudal papillae and 14.1 (12.6-15.0) µm long spicules. Morphologically, the new species is similar to S. caverna, S. chertkovi, S. christiei, S. hyrcania, S. longicaudata, S. persica, S. steineri, and S. tenuicaudata. The differences of the new species with aforementioned species are discussed. In molecular phylogenetic analyses using near full-length small and large subunit ribosomal DNA (SSU and LSU rDNA D2-D3 expansion segments) sequences, the new species fell into a clade including three previously described/sequenced species of the genus in both SSU and LSU Bayesian phylogenetic trees.Seinura italiensis n. sp. isolated from the medium soil imported from Italy is described and illustrated using morphological and molecular data. The new species is characterized by having short body (477 (407-565) µm and 522 (469-590) µm for males and females, respectively), three lateral lines, stylet lacking swellings at the base, and excretory pore at the base or slightly anterior to base of metacorpus; females have 58.8 (51.1-69.3) µm long post-uterine sac (PUS), elongate conical tail with its anterior half conoid, dorsally convex, and ventrally slightly concave and the posterior half elongated, narrower, with finely rounded to pointed tip and males having seven caudal papillae and 14.1 (12.6-15.0) µm long spicules. Morphologically, the new species is similar to S. caverna, S. chertkovi, S. christiei, S. hyrcania, S. longicaudata, S. persica, S. steineri, and S. tenuicaudata. The differences of the new species with aforementioned species are discussed. In molecular phylogenetic analyses using near full-length small and large subunit ribosomal DNA (SSU and LSU rDNA D2-D3 expansion segments) sequences, the new species fell into a clade including three previously described/sequenced species of the genus in both SSU and LSU Bayesian phylogenetic trees.
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Laimaphelenchus sinensis n. sp. isolated from declining Chinese pine, Pinus tabuliformis Carrière, is described and characterized morphologically and molecularly. The new species has four incisures in the lateral field and the excretory pore situated posterior to the nerve ring; the female has a vulval flap and vaginal sclerotization is quite prominent in majority of specimens. The female tail is conoid, ventrally curved having a single stalk-like terminus with 8 to 10 projections. The male spicules are 14.0 (13.2-15) µm long along curved median line and tail is ventrally curved typical of the genus; however, the projections are less prominent as compared to those of female. The male has two pairs of caudal papillae and Bursa is absent. Phylogenetically, the ribosomal DNA sequences of the new species placed it within Laimaphelenchus clade and are morphologically similar to L. persicus, L. preissii, L. simlaensis and L. unituberculus.Laimaphelenchus sinensis n. sp. isolated from declining Chinese pine, Pinus tabuliformis Carrière, is described and characterized morphologically and molecularly. The new species has four incisures in the lateral field and the excretory pore situated posterior to the nerve ring; the female has a vulval flap and vaginal sclerotization is quite prominent in majority of specimens. The female tail is conoid, ventrally curved having a single stalk-like terminus with 8 to 10 projections. The male spicules are 14.0 (13.2-15) µm long along curved median line and tail is ventrally curved typical of the genus; however, the projections are less prominent as compared to those of female. The male has two pairs of caudal papillae and Bursa is absent. Phylogenetically, the ribosomal DNA sequences of the new species placed it within Laimaphelenchus clade and are morphologically similar to L. persicus, L. preissii, L. simlaensis and L. unituberculus.
RESUMO
Two isomeric pyrenodithiophenediones and their triisopropylsilyl(TIPS)-ethynyl-functionalized derivatives were synthesized and characterized. With treatment of excess lithium TIPS-acetylide, the isomeric diones could undergo Michael and carbonyl additions to form three derivatives with four, three, and two TIPS-ethynyl groups, respectively. The isomeric TIPS-ethynyl-functionalized derivatives show different physicochemical properties. The single-crystalline transistors based on TIPS-ethynyl-functionalized derivatives exhibit a promising p-type transport behavior, with hole mobilities up to 0.51 cm2 V-1 s-1.