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1.
IEEE Trans Vis Comput Graph ; 26(1): 759-769, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31443018

RESUMO

In this paper, we examine the robustness of scagnostics through a series of theoretical and empirical studies. First, we investigate the sensitivity of scagnostics by employing perturbing operations on more than 60M synthetic and real-world scatterplots. We found that two scagnostic measures, Outlying and Clumpy, are overly sensitive to data binning. To understand how these measures align with human judgments of visual features, we conducted a study with 24 participants, which reveals that i) humans are not sensitive to small perturbations of the data that cause large changes in both measures, and ii) the perception of clumpiness heavily depends on per-cluster topologies and structures. Motivated by these results, we propose Robust Scagnostics (RScag) by combining adaptive binning with a hierarchy-based form of scagnostics. An analysis shows that RScag improves on the robustness of original scagnostics, aligns better with human judgments, and is equally fast as the traditional scagnostic measures.

2.
J Clin Gastroenterol ; 54(1): 76-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30575631

RESUMO

GOALS: This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. BACKGROUND: Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. MATERIALS AND METHODS: In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. RESULTS: Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. CONCLUSIONS: Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.

3.
Life Sci ; 240: 117105, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786196

RESUMO

AIMS: To investigate whether Rac1 inhibition can alleviate radiation-induced intestinal injury (RIII), meanwhile exist no protection on tumors. MATERIALS AND METHODS: Rac1 inhibition was achieved by its specific inhibitor, NSC23766. Mice were pretreated with different intraperitoneal injections, which were normal saline for NS group (N = 9), and 2.5 mg/kg and 5 mg/kg of NSC23766 for Low-Dose group (N = 9) and High-Dose group (N = 9), respectively. After total body irritation (10Gy), small intestinal tissues were collected for Hematoxylin-Eosin (H&E) staining and Terminal-deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL). Intestinal epithelial and tumor cell lines, namely MODE-k and CT-26, were used to further study the role of Rac1 inhibition on radiation damage. Flow cytometry was used to detect changes in reactive oxygen species production, cell cycles and mitochondrial membrane potential, the latter was also checked by fluorescence microscope. Changes of protein-expression associated with apoptosis and cell cycles were detected by Western blotting to explain the possible molecular mechanism. KEY FINDINGS: Height of intestine villi and depth of crypt were higher (P < 0.01) and apoptosis ratio lower (P < 0.01) in High-Dose group compared with those in NS group. After radiation, Rac1 inhibition pre-treatment improved the vitality (P < 0.01) and reduced the apoptosis (P < 0.01) in MODE-k while yielded opposite results in CT-26, and reduced ROS production of MODE-k (P < 0.01) while had little effect on that of CT-26. Rac1 inhibition differently affected the cell cycles of normal cells and that of tumor cells. SIGNIFICANCE: Inhibition of Rac1 could alleviate RIII, meanwhile assist the killing effect of radiation on tumor cells.

4.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795136

RESUMO

An easily prepared benzothiazole-based probe (BHM) was prepared and characterized by general spectra, including 1H NMR, 13C NMR, HRMS, and single-crystal X-ray diffraction. Based on the synergistic mechanism of the inhabitation of intramolecular charge transfer (ICT), the BHM displayed high selectivity and sensitivity for Al3+ in DMF/H2O (v/v, 1/1) through an obvious blue-shift in the fluorescent spectrum and significant color change detected by the naked eye, respectively. The binding ratio of BHM with Al3+ was 1:1, as determined by the Job plot, and the binding details were investigated using FT-IR, 1H NMR titration, and ESI-MS analysis. Furthermore, the BHM was successfully applied in the detection of Al3+ in the Songhua River and on a test stripe. Fluorescence imaging experiments confirmed that the BHM could be used to monitor Al3+ in human stromal cells (HSC).

6.
Phys Chem Chem Phys ; 21(45): 25035-25046, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31690917

RESUMO

Hydrocarbons confined in porous media find applications in a wide variety of industries and therefore their diffusive behavior is widely studied. Most of the porous media found in natural environments are laden with water, which might affect the confined hydrocarbons. To quantify the effect of hydration, we report here a combined quasielastic neutron scattering (QENS) and molecular dynamics (MD) simulation study on the dynamics of propane confined in the 1.5 nm-wide micropores of MCM-41-S in the presence of water at 230 and 250 K. To eliminate the strong incoherent signal from water and emphasize the propane signal we have used heavy water (D2O). QENS data show two dynamically different populations of propane in MCM-41-S and suggest that the presence of water hinders the diffusion of propane. Weak elastic contributions to the QENS spectra suggest that only long-range translational motion of propane molecules contributes to the quasielastic broadening. MD simulations carried out using a model cylindrical silica pore of 1.6 nm diameter filled with water and propane agree with the experimental finding of water hindering the diffusion of propane. Further, the simulation results suggest that the slowing down of propane motions is a function of the water content within the pore and is stronger at higher water contents. At high water content, the structure and the dynamics, both translational and rotational, of propane are severely impacted. Simulation data suggest that the rotational motion of the propane molecule occurs on time scales much faster than those accessible with the QENS instrument used, and thus explain the weak elastic contribution to the QENS spectra measured in the experiments. This study shows the effects of hydration on the structure and dynamics of volatiles in porous media, which are of interest for fundamental understanding and applied studies of confined fluids.

7.
Biomed Chromatogr ; : e4741, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743479

RESUMO

Duzhong Jiangya Tablet (DJT) composed of Eucommia ulmoides Oliv and several other traditional Chinese medicines is a Chinese herbal compound, which is clinically used to treat hypertension. The aim of this study was to evaluate the antihypertensive effect of DJT and amlodipine besylate (AB) on the synergistic treatment of spontaneously hypertensive rats (SHR), and to explore its antihypertensive mechanism. The synergistic therapeutic effect of DJT in combination with AB on SHR was studied using two metabolomics methods based on MS and NMR. Metabolomics analysis of plasma, urine, liver and kidney and the combination of OPLS-DA to expose potential biomarkers. Then the overall metabolic characteristics and related abnormal metabolic pathways in hypertensive rats were constructed. Blood pressure measurements showed that DJT combined with AB has better effects in treating hypertension than it being alone. A total of 30 biomarkers were identified, indicating that hypertension disrupted the balance of multiple metabolic pathways in the body, and that combined administration restored metabolite levels better than administration alone. The changes of biomarkers revealed the synergistic therapeutic mechanism of DJT combined with AB, which provided a reference for the combination of Chinese and Western medicines.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31740123

RESUMO

A dual-function probe NAHH based on naphthalene was synthesized and characterized. Based on the combination effects derived from the inhabitation of photo-induced electron transfer (PET) and CN isomerization, probe NAHH achieved in the recognition of Zn2+ and Al3+ both through obvious fluorescence enhancement and color changes detected by naked eye, respectively. Probe NAHH showed high sensitivity with the limit of detection as low as 3.02 × 10-7 M for Zn2+ and 7.55 × 10-8 M for Al3+, indicated the capability of probe NAHH in trace detection for Zn2+ and Al3+. The binding ratio of NAHH with Zn2+ and Al3+ were all 1:1 determined by Job plot, and the corresponding association constant was calculated as 8.48 × 104 M-1 and 4.45 × 105 M-1, respectively. The mechanism was further confirmed by FT-IR, 1H NMR titration and ESI-MS analysis. Furthermore, probe NAHH was successfully applied in logic gate construction and the detection of Zn2+ and Al3+ in Songhua River and test stripe. Fluorescence imaging experiments confirmed that NAHH could be used to monitor Zn2+ in plant root.

9.
Food Funct ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696185

RESUMO

Natural polyphenols showing a variety of beneficial effects will interact with multiple proteases after administration. The interactions of oxyresveratrol and piceatannol with trypsin and lysozyme were investigated using fluorescence spectroscopy, UV-vis absorption spectroscopy, circular dichroism spectroscopy, differential scanning calorimetry and molecular docking. Fluorescence quenching results and UV-vis absorption difference spectra revealed that the quenching process was a static mode initiated by ground-state complex formation. The different binding ability of oxyresveratrol and piceatannol with trypsin and lysozyme was discussed based on their different molecular structures. Moreover, the major driving force for the binding process was elucidated as hydrogen bonding and van der Waals forces by the negative enthalpy and entropy changes. Synchronous fluorescence, three-dimensional fluorescence and circular dichroism spectral analysis suggested that the binding of oxyresveratrol and piceatannol to trypsin and lysozyme induced some microenvironmental and conformational changes of the two enzymes. The thermal stability of the enzymes in the presence of polyphenols was studied based on the change in melting temperature by differential scanning calorimetry. The above experimental results were validated by the protein-ligand docking studies which showed the location of the two ligands in the enzymes and the surrounding amino acid residues. Furthermore, enzyme activity assays indicated that the enzymatic activity of trypsin and lysozyme was inhibited by oxyresveratrol and piceatannol. The effect of trypsin and lysozyme on the antioxidant activity and stability of oxyresveratrol and piceatannol was also investigated. In conclusion, the comparative study on the interaction of oxyresveratrol and piceatannol with trypsin and lysozyme showed that the positions of hydroxyl groups of the polyphenols had an important influence on their interaction with enzymes and their antioxidant activity and stability as well as the enzyme activities. The obtained results are expected to provide a theoretical basis for the application of polyphenols in functional foods and pharmaceuticals.

10.
Genes (Basel) ; 10(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766424

RESUMO

miR319 was the first plant miRNA discovered via forward genetic mutation screening. In this study, we found that miR319 family members had similar sequences but different expression patterns in Brassica campestris and Arabidopsis thaliana. RT-PCR analysis revealed that Bra-MIR319a and Bra-MIR319c had similar expression patterns and were widely expressed in plant development, whereas Bra-MIR319b could only be detected in stems. The overexpression of each Bra-MIR319 family member in Arabidopsis could inhibit cell division and function in leaf and petal morphogenesis. Bra-miR319a formed a new regulatory relationship after whole genome triplication, and Bra-MIR319a overexpressing in Arabidopsis led to the degradation of pollen content and affected the formation of intine, thereby causing pollen abortion. Our results suggest that Bra-MIR319 family members have functional similarity and difference in plant development.

11.
Int J Biol Macromol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759012

RESUMO

In this paper, the structural characteristics and bioactivity of a novel polysaccharide from H. erinaceus (HEPN) were investigated, wherein, physico-chemical characterization demonstrated that HEPN with an average molecular weightof 12.713 kDa was composed of mannose (5.13%), glucose (43.02%), and galactose (51.85%). The models in vitro for preventing oxidative damage of human gastric epithelium (GES-1) cells were established and used to investigate the preventive effects of HEPN from oxidative damage. It was found that HEPN could significantly prevent GES-1 cells against H2O2-induced oxidative damage by promoting cell proliferation, inhibiting cell necrosis, reducing ROS levels, regulating mitochondrial membrane potential and maintaining mitochondrial membrane permeability. These results indicated HEPN can effectively prevent gastric cell damage in vitro and suggested the potential application of HEPN as bioactive ingredient for healthy foods.

12.
J Biol Chem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722967

RESUMO

Interferons inhibit viruses by inducing antiviral protein expression. One of the interferon-induced antiviral proteins, human Moloney leukemia virus 10 (MOV10), a superfamily 1 RNA helicase, has been shown to inhibit retroviruses and several RNA viruses. However, it remains undetermined whether MOV10 also inhibits DNA viruses, including hepatitis B virus (HBV). Here, we report that MOV10 dramatically reduces the levels of intracellular HBV DNA, resulting in significant inhibition of both the HBV experimental strain and the clinical isolates. Mechanistic experiments revealed that MOV10 interacts with HBV RNA and blocks the early step of viral reverse transcription, thereby impairing viral DNA synthesis, without affecting viral gene expression and pregenomic RNA encapsidation. Moreover, mutation of the helicase domain of MOV10 caused loss of binding to HBV RNA and of the anti-HBV activity. Together, our results indicate that MOV10 restricts HBV replication, insights that may open new avenues to the development of anti-HBV therapeutics.

13.
Plant Mol Biol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776846

RESUMO

KEY MESSAGE: Conserved motif, gene structure, expression and interaction analysis of C2H2-ZFPs in Brassica rapa, and identified types of genes may play essential roles in flower development, and BrZFP38 was proved to function in flower development by affecting pollen formation. Flower development plays a central role in determining the reproduction of higher plants, and Cys2/His2 zinc-finger proteins (C2H2-ZFPs) widely participate in the transcriptional regulation of flower development. C2H2-ZFPs with various structures are the most widespread DNA-binding transcription factors in plants. In this study, conserved protein motif and gene structures were analyzed to investigate systematically the molecular features of Brassica rapa C2H2-ZFP genes. Expression of B. rapa C2H2-ZFPs in multiple tissues showed that more than half of the family members with different types ZFs were expressed in flowers. The specific expression profiles of these C2H2-ZFPs in different B. rapa floral bud stages were further evaluated to identify their potential roles in flower development. Interaction networks were constructed in B. rapa based on the orthology of flower-related C2H2-ZFP genes in Arabidopsis. The putative cis-regulatory elements in the promoter regions of these C2H2-ZFP genes were thoroughly analyzed to elucidate their transcriptional regulation. Results showed that the orthologs of known-function flower-related C2H2-ZFP genes were conserved and differentiated in B. rapa. A C2H2-ZFP was proved to function in B. rapa flower development. Our study provides a systematic investigation of the molecular characteristics and expression profiles of C2H2-ZFPs in B. rapa and promotes further work in function and transcriptional regulation of flower development.

14.
Opt Express ; 27(20): 27618-27627, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684526

RESUMO

Black phosphorus (BP), an emerging two-dimensional (2D) material with intriguing optical properties, forms a promising building block in optical and photonic devices. In this work, we propose a simple structure composed of a monolayer BP sandwiched by polymer and dielectric materials with low index contrast, and numerically demonstrate the perfect absorption mechanism via the critical coupling of guided resonances in the mid-infrared. Due to the inherent in-plane anisotropic feature of BP, the proposed structure exhibits highly polarization-dependent absorption characteristics, i.e., the optical absorption of the structure reaches 99.9% for TM polarization and only 3.2% for TE polarization at the same wavelength. Furthermore, the absorption peak and resonance wavelength can be flexibly tuned by adjusting the electron doping of BP, the geometrical parameters of the structure and the incident angles of light. Finally, the perfect absorption is also realized with the multilayer BP by simply adjusting the geometrical parameters. With high efficiency absorption, the remarkable anisotropy, flexible tunability, and easy-to-fabricate advantages, the proposed structure shows promising prospects in the design of polarization-selective and tunable high-performance devices in the mid-infrared, such as polarizers, modulators and photodetectors.

15.
EBioMedicine ; 48: 289-300, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31648989

RESUMO

BACKGROUND: Thymidylate synthase (TYMS) is a successful chemotherapeutic target for anticancer therapy. Numerous TYMS inhibitors have been developed and used for treating gastrointestinal cancer now, but they have limited clinical benefits due to the prevalent unresponsiveness and toxicity. It is urgent to identify a predictive biomarker to guide the precise clinical use of TYMS inhibitors. METHODS: Genome-scale CRISPR-Cas9 knockout screening was performed to identify potential therapeutic targets for treating gastrointestinal tumours as well as key regulators of raltitrexed (RTX) sensitivity. Cell-based functional assays were used to investigate how MYC regulates TYMS transcription. Cancer patient data were used to verify the correlation between drug response and MYC and/or TYMS mRNA levels. Finally, the role of NIPBL inactivation in gastrointestinal cancer was evaluated in vitro and in vivo. FINDINGS: TYMS is essential for maintaining the viability of gastrointestinal cancer cells, and is selectively inhibited by RTX. Mechanistically, MYC presets gastrointestinal cancer sensitivity to RTX through upregulating TYMS transcription, supported by TCGA data showing that complete response cases to TYMS inhibitors had significantly higher MYC and TYMS mRNA levels than those of progressive diseases. NIPBL inactivation decreases the therapeutic responses of gastrointestinal cancer to RTX through blocking MYC. INTERPRETATION: Our study unveils a mechanism of how TYMS is transcriptionally regulated by MYC, and provides rationales for the precise use of TYMS inhibitors in the clinic. FUNDING: This work was financially supported by grants of NKRDP (2016YFC1302400), STCSM (16JC1406200), NSFC (81872890, 81322034, 81372346) and CAS (QYZDB-SSW-SMC034, XDA12020210).

16.
Exp Appl Acarol ; 79(2): 221-231, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31587112

RESUMO

The tick Haemaphysalis longicornis (Neumann) (Acari, Ixodidae) is distributed throughout China and is the most notorious blood feeding ectoparasite of livestock. Haemaphysalis longicornis can transmit a large number of pathogens that cause human infectious diseases, such as Rickettsia spp. Here, we characterized the genetic structure of H. longicornis and tested for the presence of Rickettsia spp. from five regions in China. Analysis of the two mitochondrial marker sequences (16S rRNA and COI) and the nuclear sequence (ITS2) showed that the overall level of nucleotide diversity was low and the variability did not differ among the five regions. From the five locations, the infection rates of Rickettsia species ranged from 0 to 65%. The nucleotide diversities of the high-infected group were lower than those of the low- and uninfected group. And in neutrality tests for the high-infected group based on COI sequences, the Tajima's D and Fu's FS were coincidentally < 0 and significant, whereas they were closer to zero and non-significant in low- and uninfected groups.

17.
PLoS One ; 14(10): e0223530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581247

RESUMO

BACKGROUND: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. METHODS: PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: 25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22-0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39-0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43-0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57-0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70-0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. CONCLUSIONS: Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered.

18.
BMC Anesthesiol ; 19(1): 181, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604428

RESUMO

BACKGROUND: Intravenous dexmedetomidine is known to attenuate stress response in patients undergoing laparoscopic surgery. We investigated whether the addition of the highly selective alpha-2 adrenergic agonist dexmedetomidine into ropivacaine for ultrasound-guided transversus abdominis plane block could inhibit stress response during laparoscopic surgery, and determined the optimal dose of dexmedetomidine in it. METHODS: One hundred and twenty-five patients undergoing laparoscopic gynecological surgery were included in this prospective and randomized double-blind study. Patients received general anesthesia with or without a total of 60 ml of 0.2% ropivacaine in combination with low (0.25 µg/kg), medium (0.50 µg/kg) or high dose (1.0 µg/kg) of dexmedetomidine for the four-quadrant transversus abdominis plane block (n = 25). The primary outcomes were stress marker levels during the operation. RESULTS: One hundred and twenty patients completed the study protocol. Dexmedetomidine added to ropivacaine for transversus abdominis plane block significantly reduced serum levels of cortisol, norepinephrine, epinephrine, interleukin-6, blood glucose, mean arterial pressure and heart rate in a dose-dependent manner (P < 0.05), accompanied with decreased anesthetic and opioid consumption during the operation (P < 0.05), but the high dose of dexmedetomidine induced higher incidences of bradycardia than low or medium dose of dexmedetomidine (P < 0.05). CONCLUSION: The addition of dexmedetomidine at the dose of 0.5 µg/kg into ropivacaine for ultrasound-guided transversus abdominis plane block is the optimal dose to inhibit stress response with limited impact on blood pressure and heart rate in patients undergoing laparoscopy gynecological surgery. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn on November 6th, 2016 (ChiCTR-IOR-16009753).

19.
J Cell Mol Med ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642192

RESUMO

Vascular endothelial growth factor receptors (VEGFRs) are major contributors to angiogenesis and lymphangiogenesis through the binding of VEGF ligands. We have previously shown that the bone marrow tyrosine kinase BMX is critical for inflammatory angiogenesis via its direct transactivation of VEGFR2. In the present study, we show that siRNA-mediated silencing of BMX led to a significant decrease in the total levels of VEGFR2 mRNA and protein, without affecting their stability, in human endothelial cells (ECs). Interestingly, BMX was detected in the nuclei of ECs, and the SH3 domain of BMX was necessary for its nuclear localization. Luciferase assays showed a significant decrease in the Vegfr2 (kdr) gene promoter activity in ECs after BMX silencing, indicating that BMX is necessary for Vegfr2 transcription. In addition, we found that wild-type BMX, but not a catalytic inactive mutant BMX-K445R, promoted Vegfr2 promoter activity and VEGF-induced EC migration and tube sprouting. Mechanistically, we show that the enhancement of Vegfr2 promoter activity by BMX was mediated by Sp1, a transcription factor critical for the Vegfr2 promoter. Loss of BMX significantly reduced Sp1 binding to the Vegfr2 promoter as assayed by chromatin immunoprecipitation assays. Wild-type BMX, but not a kinase-inactive form of BMX, associated with and potentially phosphorylated Sp1. Moreover, a nuclear-targeted BMX (NLS-BMX), but not cytoplasm-localized form (NES-BMX), bound to Sp1 and augmented VEGFR2 expression. In conclusion, we uncovered a novel function of nuclear-localized BMX in regulating VEGFR2 expression and angiogenesis, suggesting that BMX is a therapeutic target for angiogenesis-related diseases.

20.
Harmful Algae ; 88: 101658, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31582162

RESUMO

The typical musty/earthy odor-causing compound, 2-methylisoborneol (MIB), is usually associated with the occurrence and proliferation of benthic/subsurface-living cyanobacteria in source water. Control of MIB-producing cyanobacteria in source water may greatly reduce the processing burden for drinking water treatment plants. We explored the mechanism and feasibility of restricting the growth of subsurface-living Planktothrix sp. by reducing underwater light availability. The effects of light intensity (5, 17, 36, 85, and 250 µmol photons m-2 s-1) on the growth and MIB production of Planktothrix sp. were first determined using batch culture, followed by an in-situ experiment deployed at different depths (0.5, 1.5, 3.5, and 5.0 m) in a drinking source water reservoir (Miyun Reservoir, China) to verify the laboratory results. The optimum conditions for growth (7.5 × 108 cells L-1) and MIB production ((1300 ±â€¯29) µg L-1) of Planktothrix sp. were achieved at 85 µmol photons m-2 s-1 in the laboratory and at 1.5 m (the corresponding average light intensity of 66 µmol photons m-2 s-1) in the field. The minimum light requirement for the growth of Planktothrix sp. (4.4 µmol photons m-2 s-1) was determined according to the laboratory data. While the in-situ experiment further indicated that Planktothrix sp. could not successfully grow at depths of 5 m where light intensity was below the minimum light requirement. In addition, the history data also verified the negative relationships between underwater light availability and MIB concentration.

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