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1.
Int J Mol Sci ; 20(19)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569360

RESUMO

The market success of any rice cultivar is exceedingly dependent on its grain appearance, as well as its grain yield, which define its demand by consumers as well as growers. The present study was undertaken to explore the contribution of nine major genes, qPE9~1, GW2, SLG7, GW5, GS3, GS7, GW8, GS5, and GS2, in regulating four size and weight related traits, i.e., grain length (GL), grain width (GW), grain thickness (GT), and thousand grain weight (TGW) in 204 diverse rice germplasms using Insertion/Deletion (InDel) markers. The studied germplasm displayed wide-ranging variability in the four studied traits. Except for three genes, all six genes showed considerable association with these traits with varying strengths. Whole germplasm of 204 genotypes could be categorized into three major clusters with different grain sizes and weights that could be utilized in rice breeding programs where grain appearance and weight are under consideration. The study revealed that TGW was 24.9% influenced by GL, 37.4% influenced by GW, and 49.1% influenced by GT. Hence, assuming the trend of trait selection, i.e., GT > GW > GL, for improving TGW in the rice yield enhancement programs. The InDel markers successfully identified a total of 38 alleles, out of which 27 alleles were major and were found in more than 20 genotypes. GL was associated with four genes (GS3, GS7, GW8, and GS2). GT was also found to be regulated by four different genes (GS3, GS7, GW8, and GS2) out of the nine studied genes. GW was found to be under the control of three studied genes (GW5, GW8, and GS2), whereas TGW was found to be under the influence of four genes (SLG7, GW5, GW8, and GS5) in the germplasm under study. The Unweighted Pair Group Method with Arithmetic means (UPGMA) tree based on the studied InDel marker loci segregated the whole germplasm into three distinct clusters with dissimilar grain sizes and weights. A two-dimensional scatter plot constructed using Principal Coordinate Analysis (PCoA) based on InDel markers further separated the 204 rice germplasms into four sub-populations with prominent demarcations of extra-long, long, medium, and short grain type germplasms that can be utilized in breeding programs accordingly. The present study could help rice breeders to select a suitable InDel marker and in formulation of breeding strategies for improving grain appearance, as well as weight, to develop rice varieties to compete international market demands with higher yield returns. This study also confirms the efficient application of InDel markers in studying diverse types of rice germplasm, allelic frequencies, multiple-gene allele contributions, marker-trait associations, and genetic variations that can be explored further.

2.
Apoptosis ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31583496

RESUMO

Our previous study revealed that Homeobox containing 1 (HMBOX1), essential for the survival of vascular endothelial cells (VECs), was involved in the progression of atherosclerosis. Knockdown of HMBOX1 promoted apoptosis and inhibited autophagy through regulating intracellular free zinc level in cultured VECs. In current study, in order to investigate the roles of HMBOX1 in vivo and in endothelium, we generated a knockout (KO) mouse for HMBOX1 by using transcription activator-like effector nucleases (TALENs) technology. Herein, we reported that the protein level of HMBOX1 was gradually increased during mouse development. The HMBOX1 KO mouse was viable and fertile. There existed no differences in apoptosis and autophagy of aortic endothelial cells between wild type and KO mouse. Whereas, loss of HMBOX1 promoted apoptosis and inhibited autophagy of aortic endothelial cells under lipopolysaccharide (LPS) stimulation in mouse. We also demonstrated that HMBOX1 deletion had no influence on the secretion of inflammatory cytokines TNF-α and IL-6. Moreover, overexpression or knockdown of HMBOX1 failed to regulate multiple pro-apoptotic genes expression in vitro. In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apoptosis and decreased autophagy with LPS treatment.

3.
Sci Rep ; 9(1): 12048, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427624

RESUMO

In recent, the quantum yield (QY) and stability of green quantum dots (QDs) have been significantly improved. However, most of the progresses were achieved by using alloyed QDs, and the control of green emission QDs still remains challenging. Herein, we report a novel method for synthesizing thick-shell structure quantum dots (TSQDs) with saturated green-emitting where tri-n-octylphosphine (TOP) was used as both ligand and solvent to extract the redundant ions from the QDs surface and remove the lattice imperfections before any surface inorganic layer-by-layer coating. The as-prepared TSQDs demonstrate enhanced luminescent properties including high QY reaching up to 75%, full width at half maximum (FWHM) remaining close to 26 nm and tunable precise emission properties (532 nm), which can be utilized to perform 91% of the International Telecommunication Union (ITU) Recommendation BT. 2020 (Rec. 2020) for high definition and color gamut displays.

4.
Mikrochim Acta ; 186(8): 586, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363854

RESUMO

A dendrimer (termed G2) containing pyrene as the core and 9-phenylcarbazole (PCZ) on the periphery is shown to be a multi-functional fluorescent probe for iodide, iron(III) and mercury(II). It serves as the fluorometric/colorimetric dual-channel probe for these ions. As a fluorometric probe, the fluorescence of G2 is quenched both by iodide and iron(III). After that, the fluorescence of G2 which has been added iodide will recover when added mercury(II); as a colorimetric probe, the color of G2 solution can turn to yellow only by iodide which will change from yellow to colorless again when adding mercury(II). The color change is sensitive and observed visually at 0.1 mM for iodide. G2 also is an electroactive precursor for preparation of fluorescent films via electropolymerization. The resulting films can be used as the fluorescent films to sense the ions. This is attributed to the presence of a large specific surface, highly cross-linked microstructures and enhanced π conjugation. The electropolymerized film has blue fluorescence with excitation/emission maxima at 365/460 nm. The limits of detection (LOD) of G2 for iodide, iron(III) and mercury(II) were calculated to be 9.3, 37.1 and 22.0 nM in solution and 5.1, 12.0 and 6.1 nM in films, respectively. The linear range is from 2 to 10 µM for G2 electropolymerized films. The detection range is from 2 to 400 µM for iron(III) and mercury(II). The detection range is from 2 to 130 µM for iodide. For a third application, G2 displays compelling sensing performance in environmental systems and in living roundworms. Graphical abstractAs schematic presentation, after adding iodide, the fluorescence of G2 is quenched and the color changes to yellow. When adding Hg2+ to G2-iodide, the fluorescence and color of G2 recover. Iron(III) can also quench G2, but the color does not change.

5.
Obesity (Silver Spring) ; 27(9): 1482-1493, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328894

RESUMO

OBJECTIVE: Prepregnancy obesity is an epidemic disorder that seriously threatens both maternal and offspring health. This study investigated the effects of ß3-adrenergic receptor (ß3-AR) activation on the perinatal outcomes in a diet-induced prepregnancy obese (PPO) murine model. METHODS: Four-week-old female C57BL/6 mice were fed high-fat diet or chow diet for 16 weeks to yield PPO mice and chow-fed (CF) lean mice, respectively. After successful mating with CF males, the PPO and CF mice were both randomly divided into vehicle control- or CL316,243 (a highly selective ß3-AR agonist)-treated groups. On gestational day 7, subcutaneous infusion of CL316,243 or saline vehicle (1 mg/kg/d) was provided using osmotic pumps. The perinatal outcomes, adipose tissue morphology, and metabolic and inflammatory markers were examined. RESULTS: Chronic ß3-AR agonist infusion induced brown adipose tissue activation and white adipose tissue browning and countered obesity-induced alterations in lipid profiles, insulin resistance, and systemic and local inflammatory states. Moreover, ß3-AR activation was associated with improved placental perfusion and offspring outcomes. CONCLUSIONS: Our results provide proof-of-principle evidence that pharmacological ß3-AR activation may be of therapeutic potential in preventing prepregnancy-obesity-associated adverse maternal and offspring perinatal outcomes.

6.
J Am Heart Assoc ; 8(14): e012027, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31267796

RESUMO

Background In contrast to the general population, outcome-derived thresholds for diagnosing ambulatory hypertension in pregnancy are not yet available. We aimed to identify and compare outcome-derived ambulatory blood pressure (BP) monitoring thresholds for adverse perinatal outcomes by using approaches related and not related to clinic BP in a southern Chinese population. Methods and Results Ambulatory BP monitoring was performed in a cohort of 1768 high-risk participants in late pregnancy who were not taking antihypertensive medications. Participants were followed for composite maternal (severe complications) and neonatal (pregnancy loss, advanced neonatal care, and small for gestational age) outcomes. Modeling of clinic BP-unrelated approaches revealed a nonlinear threshold effect of ambulatory diastolic BP on the composite outcome, with increased risk for daytime ≥79 mm Hg and 24-hour measurement ≥76 mm Hg. For other ambulatory BP components showing linear associations with outcome, the following thresholds were identified: 131 mm Hg for daytime systolic, 121 mm Hg for nighttime systolic, 130 mm Hg for 24-hour systolic, and 73 mm Hg for night-time diastolic BP. These thresholds unrelated to clinic BP were lower than the equivalents yielding a similar probability of outcome to clinic BP of 140/90 mm Hg and were comparable with equivalents to clinic BP of 130/80 mm Hg. Conclusions Using an outcome-derived approach unrelated to clinic BP, we identified rounded thresholds to define ambulatory hypertension in at-risk women in late pregnancy in a southern Chinese population as follows: 130/80 mm Hg for daytime, 120/75 mm Hg for nighttime, and 130/75 mm Hg for 24-hour measurement. For wider clinical applicability and to align both nonpregnancy and pregnancy ambulatory BP monitoring with an outcomes-based approach, prospective, multiethnic, international studies from early pregnancy onward will be required.

7.
Plant Sci ; 286: 17-27, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300138

RESUMO

The plant-specific gibberellic acid (GA)-stimulated transcript gene family is critical for plant growth and development. There are 10 family members in rice (Oryza sativa), known as OsGASRs. However, few have been functionally characterized. Here, we investigated the function of OsGASR9 in rice. OsGASR9 transcripts were detected in various tissues, with the lowest and highest levels in leaves and panicles, respectively. Greater mRNA levels accumulated in young, compared with in old, panicles and spikelets. OsGASR9 localized to the plasma membrane, cytoplasm and nucleus. Transgenic RNA interference-derived lines in the Zhonghua 11 background exhibited reduced plant height, grain size and yield compared with the wild-type. The two osgasr9 mutants in the Nipponbare background showed similar phenotypes. Conversely, the overexpression of OsGASR9 in the two backgrounds increased plant height and grain size. A significantly increased grain yield per plant was also observed in the overexpression lines having a Nipponbare background. Furthermore, by measuring the GA-induced lengths of the second leaf sheaths and α-amylase activity levels of seeds, we concluded that OsGASR9 is a positive regulator of responses to GA in rice. Thus, OsGASR9 may regulate plant height, grain size and yield through the GA pathway and could have an application value in breeding.


Assuntos
Giberelinas/metabolismo , Oryza/genética , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Sequência de Aminoácidos , Sequência de Bases , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Família Multigênica , Oryza/crescimento & desenvolvimento , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Interferência de RNA
8.
9.
Talanta ; 201: 330-334, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122431

RESUMO

A novel ratiometric fluorescence probe for hypochlorous acid was constructed by coumarin and pyridinium fluorophore based on the Forster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) platform. In this ICT/FRET system, the energy transfer efficiency is high to 94.3%. Moreover, the probe could respond to hypochlorous acid with high selectivity and sensitivity, and exhibited a large Stokes shift. It was interesting to find that the probe could recognize hypochlorous acid via a new mechanism, in which the α-position of carbonyl group was oxidized to form a diketone derivative. More importantly, the probe was successfully applied to the ratiometric imaging of both exogenous and endogenous hypochlorous acid in living RAW 264.7 cells, with low toxicity and high photo-stability.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Compostos de Piridínio/química , Animais , Cumarínicos/síntese química , Cumarínicos/efeitos da radiação , Desenho de Drogas , Fluorescência , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Concentração de Íons de Hidrogênio , Luz , Limite de Detecção , Camundongos , Imagem Óptica/métodos , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Células RAW 264.7
10.
Bioorg Med Chem ; 27(13): 2845-2856, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103402

RESUMO

Biological activities of a series of fluorescent compounds against human lung cancer cell line A549 were investigated. The results showed that (E)-1,3,3-trimethyl-2-(4-(piperidin-1-yl)styryl)-3H-indol-1-ium iodide (8) and (E)-2-(5,5-dimethyl-3-(4-(piperazin-1-yl)styryl)cyclohex-2-en-1-ylidene) malononitrile (11) could inhibit the growth of A549 cancer cells in a dose and time-dependent manner. Furthermore, compound 8 could trigger autophagy and apoptosis, but not obviously induce necrosis under the stimulatory condition. Therefore, 8 can be used as autophagy activator to investigate the regulatory mechanism of autophagy and may offer a new candidate for the treatment of lung cancer.

11.
Mol Med Rep ; 19(5): 4514-4522, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942410

RESUMO

Thyroid stimulating hormone (TSH) consists of an α­subunit and a unique ß­subunit. The first in­frame TSHß splice variant produced by the cells of immune system was identified in 2009. The TSHß splice variant and native TSHß exhibit different expression profiles, and research has been conducted to elucidate the role of the TSHß splice variant in different diseases. However, understanding of the fundamental physiological characteristics of the TSHß splice variant is currently limited. To verify whether the TSHß splice variant has the potential to induce thyroid follicular cells to synthesize thyroid hormone, in vivo and in vitro stimulation experiments were conducted in the present study. A total of 60 C57BL/6 mice were divided into control­, 5 and 10 µg TSHß splice variant­treated groups at random. Mice were sacrificed at 0.5, 1 and 4 h after intraperitoneal injection, and serum levels of tri­iodothyronine (T3) and thyroxine (T4) were determined using a radioimmunoassay. Thyroid follicular cells were isolated from the thyroids of mice, and stimulated with 2 µg/ml TSHß splice variant. Supernatants were collected, and the levels of T3 and T4 were detected. The protein expression levels of the sodium­iodide symporter, thyroperoxidase and thyroglobulin in thyroid follicular cells were quantified using western blot analysis. To verify whether the TSHß splice variant expression was regulated by the hypothalamus­pituitary­thyroid (HPT) axis, similar to native TSHß, a total of 60 C57BL/6 mice were equally divided into control, 2 mg/kg T3 intraperitoneal injection and 0.05 mg/kg thyroid­releasing hormone intraperitoneal injection groups at random. Mice were sacrificed at 1 and 4 h after injection. Alterations in the expression of the TSHß splice variant in the pituitary, thyroid, peripheral blood leukocytes and spleen tissues were detected using western blot analysis. The present study demonstrated that the TSHß splice variant is not regulated by the HPT axis and may affect thyroid hormone synthesis. Modifications in the expression of the TSHß splice variant may occur in a uniquely regulated manner to provide peripheral immunological compartments with a source of activated cells, particularly under immune stress.


Assuntos
Hormônios Tireóideos/biossíntese , Tireotropina Subunidade beta/genética , Animais , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Processamento de RNA , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/farmacologia , Simportadores/metabolismo , Tireoglobulina/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo , Tireotropina Subunidade beta/metabolismo , Tiroxina/sangue , Tri-Iodotironina/sangue
12.
Anal Chim Acta ; 1064: 87-93, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30982522

RESUMO

A ratiometric fluorescence probe (named ZOC) for the fast detection of HClO/ClO- was constructed by coumarin (donor) and pyridinium (acceptor) based on Forster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) platform. ZOC possessed red emission signal (610 nm), large Stocks shift (190 nm), high energy transfer efficiency (95.3%), high selectivity and sensitivity, low detection limit (25 nM), wider detection range (from 25 nM to 30 µM), rapid response (within 13 S), and good biocompatibility. It was very interesting that the recognition mechanism involved a new organic reaction in which olefin double bond reacted first with HClO/ClO- regioselectively, followed by cyclization. ZOC was successfully used to the real time detection of endogenous HClO/ClO- in RAW 264.7 cells.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Imagem Óptica , Animais , Camundongos , Estrutura Molecular , Células RAW 264.7
13.
Artigo em Inglês | MEDLINE | ID: mdl-31009824

RESUMO

Mutations in the Kelch domain of the K13 gene (PF3D7_1343700) were previously associated with artemisinin resistance in Plasmodium falciparum. This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007-2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). The 50% effective concentration (EC5072h) values of 133 culture-adapted field isolates to AS and DHA, measured by the conventional 72 h SYBR Green I-based assay, varied significantly among the parasites from different years; all were significantly higher than that of the reference strain 3D7. Compared with parasites from 2007 to 2008, ring survival rates almost doubled in parasites obtained in later years. Sequencing the full-length K13 genes identified 11 point mutations present in 85 (63.9%) parasite isolates. F446I was the predominant (55/133) variant, and its frequency was increased from 17.6% (3/17) in 2007 to 55.9% (19/34) in 2014-2016. No wild-type (WT) Kelch domain sequences were found in the 34 samples obtained from 2014 to 2016. In the 2014-2016 samples, a new mutation (G533S) appeared and reached 44.1% (15/34). Collectively, parasites with the Kelch domain mutations (after amino acid 440) had significantly higher ring survival rates than the WT parasites. Individually, F446I, G533S and A676D showed significantly higher ring survival rates than the WT. Although the drug sensitivity phenotypes measured by the RSA6h and EC5072h assays may be intrinsically linked to the in vivo clinical efficacy data, the values determined by these two assays were not significantly correlated. This study identified the trend of K13 mutations in parasite populations from the China-Myanmar border area, confirmed an overall correlation of Kelch domain mutations with elevated ring-stage survival rates, and emphasized the importance of monitoring the evolution and spread of parasites with reduced artemisinin sensitivity along the malaria elimination course.

14.
Apoptosis ; 24(7-8): 552-561, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30911960

RESUMO

More and more studies reported that diverse biological roles of long noncoding RNAs were usually dependent on their subcellular location. In our previous study, long noncoding RNA CERNA1 was identified both located in cytoplasm and nucleus of vascular endothelial cells (VECs). And CERNA1 in cytoplasm, which functioned as competitive endogenous RNA (ceRNA), alleviated the apoptosis of VECs. However, the function of CERNA1 in nucleus was still unclear. In this study, we found that nuclear CERNA1 positively regulated BCL2L10, which accelerated the serum and FGF-2 starvation-induced apoptosis of VECs, by enhancing the histone modification level of H3K9ac and H3K4me3 in BCL2L10 promoter region. Furthermore, due to the paradoxical function, we investigated the variation of CERNA1 subcellular location in VECs. The results showed that, as the change of apoptosis status, CERNA1 altered the cellular distribution in VECs. And the annexin A7 inhibitor, ABO (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine), not only increased the expression of CERNA1 by TIA-1, but also specifically improved its cytoplasm distribution proportion so as to inhibit the apoptosis of VECs. This evidence suggested that the subcellular location of CERNA1 played an important role in the VECs apoptosis and ABO might be a potential chemical molecule for therapy of VECs apoptosis related cardiovascular diseases.

15.
Nanoscale ; 11(19): 9327-9334, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-30911741

RESUMO

As opposed to traditional photoluminescence and ultra-violet based optical sensing, we present here a sensing system based on resolved optically active polarization with promising applications. It is based on the ultrathin CdSe nanoplatelets (NPLs) when modified with either l or d-cysteine molecules (l/d-cys) as bio-to-nano ligands. The chiral ligand transfers its chiroptical activity to the achiral nanoplatelets with an anisotropy factor of ∼10-4, which unlocks the chiral excitonic transitions and allows lead ion detection with a limit of detection (LOD) as low as 4.9 nM. Simulations and modelling based on time-dependent density functional theory (TD-DFT) reveal the chiral mechanism of l/d-cys capped CdSe NPLs. The presented CD-based sensing system illustrates an alternative possibility of using chiral CdSe NPLs as competitive chiral sensors for heavy metal ion detection.

16.
Endocr J ; 66(5): 431-441, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30814439

RESUMO

Forty-five pregnant women who underwent cesarean section, including 30 cases of gestational diabetes mellitus (GDM) and 15 normal pregnant women, were enrolled in this study to examine the differential expression of circular RNAs (circRNAs) in the placentas of women with GDM by RNA sequencing (RNA-seq) analysis. The differentially expressed circRNAs were analyzed bioinformatically using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and circRNA-microRNA (miRNA) interaction prediction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the results. A total of 8,321 circRNAs were identified in the human placenta, among which 46 were differentially expressed (fold change ≥2 and p < 0.05), including three that were upregulated and 43 that were downregulated. According to the GO and KEGG enrichment results, these circRNAs may be associated with vital biological processes, cellular components, molecular functions, and signaling pathways. In particular, KEGG analysis shown they may be involved in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, indicating that these circRNAs might participate in the occurrence and pathogenesis of GDM. qRT-PCR verified that the expression of circ_5824, circ_3636, and circ_0395 was consistent with RNA-seq analysis; their expression levels were significantly lower in the GDM group than in the control group. The circRNA-miRNA interaction was analyzed according to the molecular sponge mechanism, and its potential function is discussed. These results shed light on future functional studies of circRNAs related to GDM.

17.
Biochem Biophys Res Commun ; 511(1): 92-98, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30770100

RESUMO

Vascular endothelial cell (VEC) apoptosis takes part in the development of various cardiovascular diseases. Heat shock protein 90 (HSP90) regulates apoptosis through various apoptosis associated client proteins. In previous study, we identified a novel HSP90 inhibitor HCP1 induced apoptosis in A549 human lung cancer cells. Here, we found that low-concentration HCP1 (1 µM, 2 µM) suppressed VEC apoptosis caused by serum and fibroblast growth factor 2 (FGF-2) deprivation. HCP1 directly bound to glucose-regulated protein 94 (Grp94), an isoform of HSP90 located in endoplasmic reticulum, and HCP1 selectively inhibited Grp94 activity via binding to site 3. Overexpression of Grp94 inhibited the anti-apoptotic effect of HCP1 in human umbilical vein endothelial cells. Therefore, we provided HCP1 as a new VEC apoptosis inhibitor which might be a potential compound in the treatment of VEC apoptosis related vascular diseases. And we provided new pieces of evidence to understand the role of Grp94 in VEC apoptosis.

18.
Proc Natl Acad Sci U S A ; 116(8): 3177-3182, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30728298

RESUMO

The Plasmodium falciparum var gene family encodes ∼60 surface antigens by which parasites escape the host immune responses via clonal expression of var genes. However, the mechanism controlling this mutual exclusivity, associated with alterations in chromatin assembly, is not understood. Here, we determined how expression of the var gene family is regulated by two RecQ DNA helicase family members, PfRecQ1 and PfWRN, in P. falciparum Through genetic manipulation, we found that the complete var repertoire was silenced on PfRecQ1 knockout, whereas their expression did not show noticeable changes when PfWRN was knocked out. More important, mutually exclusive expression of var genes could be rescued by complementation of PfRecQ1. In addition, knocking out either of these two helicase genes changed the perinuclear cluster distribution of subtelomeres and subtelomeric var genes. Whereas deletion of PfRecQ1 increased the heterochromatin mark trimethylated (H3K9me3) at the transcription start site (TSS) of the var gene upsC1, that deletion had no effect on the global distribution of H3K9me3 over gene bodies, including those for the var genes. ChIP-seq assay showed that PfRecQ1 was enriched globally at the TSSs of all genes, whereas PfWRN-enriched regions occurred at the gene bodies of the var gene family, but not of other genes or at TSSs of all genes. On PfRecQ1 deletion, the upsC1 var gene moved from the active perinuclear transcription region to a silenced region of the upsC type. These findings imply that PfRecQ1, but not PfWRN, is essential for maintaining the clonal expression of var genes.


Assuntos
DNA Helicases/genética , Interações Hospedeiro-Parasita/genética , Malária Falciparum/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Animais , Montagem e Desmontagem da Cromatina/genética , Regulação da Expressão Gênica/genética , Inativação Gênica , Heterocromatina/genética , Histonas/genética , Malária Falciparum/parasitologia , Plasmodium falciparum/patogenicidade , Regiões Promotoras Genéticas/genética
19.
ACS Nano ; 13(2): 1625-1634, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30673271

RESUMO

High-efficiency hole transport layer free perovskite solar cells (HTL-free PSCs) with economical and simplified device structure can greatly facilitate the commercialization of PSCs. However, eliminating the key HTL in PSCs results usually in a severe efficiency loss and poor carrier transfer due to the energy-level mismatching at the indium tin oxide (ITO)/perovskite interface. In this study, we solve this issue by introducing an organic monomolecular layer (ML) to raise the effective work function of ITO with the assistance of an interface dipole created by Sn-N bonds. The energy-level alignment at the ITO/perovskite interface is optimized with a barrier-free contact, which favors efficient charge transfer and suppressed nonradiative carrier recombination. The HTL-free PSCs based on the ML-modified ITO yield an efficiency of 19.4%, much higher than those of HTL-free PSCs on bare ITO (10.26%), comparable to state-of-the-art PSCs with a HTL. This study provides an in-depth understanding of the mechanism of interfacial energy-level alignment and facilitates the design of advanced interfacial materials for simplified and efficient PSC devices.

20.
Talanta ; 194: 308-313, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609535

RESUMO

Lipid droplets were found to be involved in many organism activities. Here, a lipid droplets-targeted near-infrared fluorescence probe (named XHZ) for ratiometric detection of endogenous hypochlorous acid/hypochlorite (HClO/ClO-) in living cells was developed, which was constructed by a coumarin moiety and a malononitrile derivative. XHZ could detect HClO/ClO- with high selectivity and sensitivity in a ratiometric manner based on FRET (Förster Resonance Energy Transfer) mechanism. The two well-resolved emission (470/672 nm) bands could ensure accurate detection of HClO/ClO- in vitro as well as in vivo. XHZ was successfully used for ratiometric fluorescence imaging of exogenous and endogenous HClO/ClO- in RAW264.7 cells. A good linear relationship between the fluorescence intensity ratios of the two emissions and HClO/ClO- concentrations from 0 to 40 µM was obtained. Importantly, XHZ could localize mainly in lipid droplets of RAW264.7 cells. To the best of our knowledge, XHZ is the first lipid droplets-targeted ratiometric fluorescence probe for HClO/ClO-.


Assuntos
Corantes Fluorescentes/metabolismo , Ácido Hipocloroso/metabolismo , Gotículas Lipídicas/metabolismo , Animais , Sobrevivência Celular , Cumarínicos/química , Corantes Fluorescentes/química , Gotículas Lipídicas/química , Camundongos , Imagem Óptica , Células RAW 264.7
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