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1.
Prostate ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32941694

RESUMO

BACKGROUND: Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor ß (ERß), activation of which has anti-inflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation. METHODS: Male Sprague-Dawley rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (control, n = 5). Rats with prostatic inflammation were divided into dutasteride therapy (dutasteride, n = 5) and placebo groups (placebo, n = 5). Dutasteride was administrated at a dose of 0.5 mg/kg daily from 2 days before induction of prostatic inflammation whereas placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of messenger RNA (mRNA) expression levels of ERα, ERß, interleukin-1ß (IL-1ß), and IL-18 by quantitative polymerase chain reaction. RESULTS: The mean number of NVCs was significantly greater in placebo group than that of control group without prostatic inflammation (p < .05), and ICI were significantly decreased in placebo group compared with control group (p < .05). On the contrary, there was no significant change in NVCs or ICI between control and dutasteride groups. RV was not significantly different among three groups. Gene expression levels of ERα, IL-1ß, and IL-18 was significantly increased in placebo rats compared with control rats (p < .05), but not significantly different between control and dutasteride rats. On the other hand, the mRNA expression level of ERß was significantly decreased in placebo rats (p < .05), but not in dutasteride rats, compared with control rats. CONCLUSION: Dutasteride treatment improved not only prostatic inflammation evident as increased gene expression levels in IL-1ß and IL-18, but also bladder overactivity shown by increased NVCs during bladder filling. These therapeutic effects were associated with the restored expression of anti-inflammatory ERß. Therefore, dutasteride might be effective via ERß modulation for the treatment of prostatic inflammation in addition to its previously known, anti-androgenic effects on benign prostatic hyperplasia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32872106

RESUMO

Low-carbon tourism is an effective solution to cope with the goal conflict between developing tourist economy and responding to carbon emission reduction and ecological environment protection. Tourism scenic spots are important carriers of tourist activities and play a crucial role in low-carbon tourism. There are multiple factors affecting the low-carbon performance of a tourism scenic spot, and thus the performance evaluation and ranking of low-carbon tourism scenic spots can be framed as a hierarchical multi-criteria decision making (MCDM) problem. This paper develops a novel method to tackle hierarchical MCDM problems, in which the importance preferences of criteria over the decision goal and sub-criteria with respect to the upper-level criterion are provided by linguistic-term-based pairwise comparisons and the assessments of alternatives over each of sub-criteria at the lowest level are furnished by positive interval values. The linguistic-term-based pairwise comparison matrices are converted into intuitionistic fuzzy preference relations and an approach is developed to obtain the global importance weights of the lowest level sub-criteria. A multiplicatively normalized intuitionistic fuzzy decision matrix is established from the interval-value-based assessments of alternatives and a method is proposed to determine the intuitionistic fuzzy value based comprehensive scores of alternatives. A case study is offered to illustrate how to build a performance evaluation index system of low-carbon tourism scenic spots located at Zhejiang Province of China and show the use of the proposed intuitionistic fuzzy hierarchical MCDM method.

3.
Cancer Manag Res ; 12: 5527-5536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765064

RESUMO

Purpose: Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells. Materials and Methods: We screened differentially expressed lncRNAs between high- and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting. Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1. Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32748301

RESUMO

Dietary potentially toxic elements (PTEs) exposure in developing countries is of great concern. Probabilistic estimation exhibits great superiority in risk assessment by dealing with the variability and uncertainty of the parameters. Here, a probabilistic estimation based on two dimensions, PTEs in foods and food intake, was conducted. A total of 13 foods were collected from Shenzhen markets during 2005-2017, and the concentrations of Pb, Cd, Hg, and As were detected. A total of 853 residents from 245 households participated in a total diet study. The mean concentrations of Pb, Cd, Hg and As were 0.046, 0.0196, 0.0038, and 0.029 mg kg-1 in cereals, 0.042, 0.0174, 0.0027, and 0.014 mg kg-1 in vegetables, 0.044, 0.0237, 0.0056, and 0.021 mg kg-1 in meat, and 0.081, 0.1035, 0.0257, and 0.680 mg kg-1 in aquatic products, respectively. The probability density function showed that the 95th percentiles of the Pb, Cd, Hg, As hazard quotients (HQ) and the hazard index (HI) were 0.68, 1.57, 0.38, 5.81 and 7.51, respectively. Cumulative probability and sensitivity analysis showed that cereals and vegetables contributed most to Pb and Cd exposure; aquatic products to Hg exposure; and cereals and aquatic products to As exposure. The results showed that Shenzhen residents were at risk of exposure to Cd, As, and four PTEs in combination, although a temporal decreasing trend was observed. The probabilistic estimation used here reveals a complete picture of multiple PTEs exposure risk and identifies major contributing food categories, providing a valuable means for risk assessment.

5.
Insect Biochem Mol Biol ; 126: 103452, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32822817

RESUMO

Although the mechanisms that control growth are now well understood, the mechanism by which animals assess their body size remains one of the great puzzles in biology. The final larval instar of holometabolous insects, after which growth stops and metamorphosis begins, is specified by a threshold size. We investigated the mechanism of threshold size assessment in the tobacco hornworm, Manduca sexta. The threshold size was found to change depending on the amount of exposure to poor nutrient conditions whereas hypoxia treatment consistently led to a lower threshold size. Under these various conditions, the mass of the muscles plus integuments was correlated with the threshold size. Furthermore, the expression of myoglianin (myo) increased at the threshold size in both M. sexta and Tribolium castaneum. Knockdown of myo in T. castaneum led to larvae that underwent supernumerary larval molts and stayed in the larval stage permanently even after passing the threshold size. We propose that increasing levels of Myo produced by the growing tissues allow larvae to assess their body size and trigger metamorphosis at the threshold size.

6.
Prostate ; 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32692865

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF-ß1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin-1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin-1 in the prostatic epithelial barrier and its regulation by TGF-ß1 in prostatic epithelial cells are not clear. METHODS: The expression of claudin-1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH-1 and BHPrE1 were treated with TGF-ß1 and transfected with small interfering RNAs specific to claudin-1. Epithelial monolayer permeability changes in the treated cells were measured using trans-epithelial electrical resistance (TEER). The expression of claudin-1, E-cadherin, N-cadherin, snail, slug, and activation of mitogen-activated proteins kinases (MAPKs) and AKT was assessed following TGF-ß1 treatment using Western blot analysis. RESULTS: Claudin-1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF-ß1 treatment or claudin-1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF-ß1 decreased levels of claudin-1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal-regulated kinase-1/2 (ERK-1/2) in both BPH-1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin-1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK-1/2 (ie, MEK-1/2) restored claudin-1 expression level as well as the epithelial barrier. CONCLUSION: Our findings suggest that downregulation of claudin-1 by TGF-ß1 acting through the noncanonical MEK-1/2/ERK-1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF-ß1 may contribute to claudin-1 downregulation and compromised epithelial barrier in clinical BPH specimens.

7.
Dalton Trans ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32613994

RESUMO

Asymmetric supercapacitors (ASCs) show promising potential for electrochemical energy storage applications. However, the energy density of ASCs is limited by the poor electrochemical performance of anodes. To achieve high-performance ASCs, herein, Fe2O3 nanotubes constructed from Fe2O3 nanoneedles were fabricated by employing MnO2 nanotubes as a self-sacrificing template, and then a layer of polypyrrole (PPy) was coated through an in situ chemical oxidative polymerization method to enhance their performance. The electrochemical tests indicate that the resultant PPy-coated Fe2O3 nanotubes (Fe2O3@PPy) exhibit a high areal capacitance of 530 mF cm-2 at 1 mA cm-2 and good cycling stability, which are superior to those of the Fe2O3 nanotubes. The superior performance of the Fe2O3@PPy nanotubes can be attributed to the synergistic effect between the PPy shell and Fe2O3 core, in which the conducting PPy shell not only works as a superhighway for charge transport, but also stabilizes the Fe2O3 nanotubes during charge-discharge processes. When the Fe2O3@PPy nanotubes were assembled with MnO2 nanotubes, the as-assembled ASCs possess a high cell voltage of 2.0 V and deliver a high energy density of up to 51.2 Wh kg-1 at a power density of 285.4 W kg-1 with an excellent cycling stability (83.5% capacitance retention over 5000 cycles).

8.
J Int Med Res ; 48(7): 300060520943070, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32720541

RESUMO

OBJECTIVE: We aimed to investigate the diagnostic value of microRNA-155 (miR-155) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) in patients with sepsis. METHODS: In this prospective study, we used Spearman correlation analysis to investigate relationships between miR-155 expression and inflammatory factors, oxygenation ratio (PaO2/FiO2), and ALI/ARDS score, and used area under the receiver operating characteristic curve (AU-ROC) to evaluate miR-155's diagnostic accuracy for ALI/ARDS in patients with sepsis. RESULTS: In total, 156 patients with sepsis were enrolled in our study, of which 41 had ALI and 32 had ARDS. miR-155 expression in plasma of patients with sepsis and ALI/ARDS was significantly higher than that of patients with sepsis but no ALI/ARDS. The miR-155 level in patients with sepsis and ALI/ARDS was positively correlated with interleukin (IL)-1ß and tumor necrosis factor (TNF)-α levels and ALI/ARDS score, but negatively correlated with PaO2/FiO2. The AU-ROC of plasma miR-155 for diagnosis of sepsis with ALI/ARDS was 0.87, and plasma miR-155, IL-1ß, and TNF-α had high sensitivity and specificity for the diagnosis of sepsis with ALI/ARDS. CONCLUSION: miR-155 is highly expressed in plasma of patients with septic ALI/ARDS; it is positively correlated with lung function and can be used for early diagnosis.

9.
Huan Jing Ke Xue ; 41(6): 2635-2645, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608778

RESUMO

The chromophoric dissolved organic matter (CDOM), the main component of dissolved organic matter, affects the morphological characteristics, migration, and conversion of pollutants in water. Based on UV-vis spectra and excitation emission matrix spectroscopy (EEMs) combined with the parallel factor analysis (PARAFAC), the spatial distribution and spectral characteristics were investigated and source analysis of CDOM was performed. Thus, the spatiotemporal differences in the CDOM in Gangnan Reservoir were analyzed. Results showed that a254, a260, a280, and a355 exhibited significant seasonal differences in Gangnan Reservoir, and the order of CDOM concentrations was summer > spring > autumn > winter. There are significant seasonal differences in the E2/E3, E3/E4, E4/E6, and SR of interstitial water CDOM. The concentrations of E2/E3, E3/E4, E4/E6, and SR were high in winter and low in summer. E2/E3 and E3/E4 in autumn and winter were significantly higher than those in spring and summer, and the E3/E4 in autumn and winter was greater than 3.5, which indicates that the CDOM of the autumn and winter sediments has a smaller molecular weight and a lower degree of humification. Protein-like substances (C1), short-wave fulvic acid (C2), and degraded humic substances (C3) were identified by the PARAFAC model, and there was a significant positive correlation among the three fluorescent components (P<0.001). The total fluorescence intensity of CDOM and the fluorescence intensity of each fluorescent component show significant seasonal differences. The total fluorescence intensity and the fluorescence intensity of each component show the highest levels in spring, followed by autumn and winter, and the lowest levels in summer. The proportion of each fluorescent component in autumn and winter and that of each fluorescent component in spring and summer showed no significant difference. There was a significant difference in the proportion of each fluorescent component between autumn/winter and spring/summer. The BIX and FI of CDOM for autumn and winter were higher than those for spring and summer, indicating that the autogenous source of CDOM in autumn and winter is stronger than that in spring and summer, which was consistent with the result of HIX. PCA and Adonis analysis showed that the spectral characteristics of CDOM exhibited obvious seasonal differences (P<0.001). Moreover, the C1, C2, and C3 and water quality parameters (NH4+, NO3-, NO2-, TDN, and TDP) exhibited significant correlation based on linear regression. The results could provide technical support for the control of organic carbon pollution sources and water quality management in Gangnan Reservoir.

10.
Prostate ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32659026

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease characterized by nonmalignant abnormal growth of the prostate, which is also frequently associated with lower urinary tract symptoms. The prostate with BPH exhibits enhanced growth not only in the epithelium but also in the stroma, and stromal-epithelial interactions are thought to play an important role in BPH pathogenesis. However, our understanding of the mechanisms of stromal-epithelial interactions in the development and progression of BPH is very limited. METHODS: Matched pairs of glandular BPH and normal adjacent prostate specimens were obtained from BPH patients undergoing simple prostatectomy for symptomatic BPH. Tissues were divided further into fresh specimens for culture of primary prostatic stromal cells, and specimens were embedded in paraffin for immunohistochemical analyses. Proliferation assays, immunohistochemistry, and immunoblotting were used to characterize the primary prostate stromal cells and tissue sections. Coculture of the primary stromal cells with benign human prostate epithelial cell lines BHPrE1 or BPH-1 was performed in three-dimensional (3D) Matrigel to determine the impact of primary stromal cells derived from BPH on epithelial proliferation. The effect of stromal-conditioned medium (CM) on BHPrE1 and BPH-1 cell growth was tested in 3D Matrigel as well. RESULTS: BPH stromal cells expressed less smooth muscle actin and calponin and increased vimentin, exhibiting a more fibroblast and myofibroblast phenotype compared with normal adjacent stromal cells both in culture and in corresponding paraffin sections. Epithelial spheroids formed in 3D cocultures with primary BPH stromal cells were larger than those formed in coculture with primary normal stromal cells. Furthermore, CM from BPH stromal cells stimulated epithelial cell growth while CM from normal primary stromal cells did not in 3D culture. CONCLUSIONS: These findings suggest that the stromal cells in BPH tissues are different from normal adjacent stromal cells and could promote epithelial cell proliferation, potentially contributing to the development and progression of BPH.

11.
J Nanosci Nanotechnol ; 20(12): 7601-7609, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711632

RESUMO

Magnetic magnesium ferrite nanoparticles were fabricated via the ethanol-assisted solution combustion and gel calcination route. The scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectrometer, Brunauer-Emmett-Teller (BET) surface area measurement, vibrating sample magnetometer (VSM) and X-ray diffraction (XRD) were applied to characterize magnetic magnesium ferrite nanoparticles which were prepared under the condition of 20 mL absolute alcohol and calcined at 600 °C for two hours. The results showed that the nanoparticles were spinel structure with the saturation magnetization of 183 emu·g-1, the average grain size of 52 nm, the specific surface area of 33.2 m² · g-1. In addition, the electrochemical property and adsorption mechanism of neutral red (NR) onto the magnetic MgFe2O4 nanoparticles were investigated. The adsorption results were conformed to the pseudo-second-order adsorption kinetic and Temkin model, which implied that the multimolecular layer chemical adsorption had occurred. Moreover, the pH had little effect on the process of the adsorption, and the value of the magnetic magnesium ferrite nanoparticles for NR adsorption was up to 555 mg · g-1.

13.
Huan Jing Ke Xue ; 41(5): 2177-2187, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608835

RESUMO

To isolate the aerobic denitrification bacteria suitable for water quality in the low-temperature period of Baiyangdian Lake, a water quality investigation and bioinformatics analysis of the aerobic denitrification bacterial community were carried out using a MiSeq high-throughput sequencing technique based on napA. Moreover, α-diversity, ß-diversity, and network analyses were also carried out. The results showed significant differences in the water quality of different sampling sites in Baiyangdian Lake, and the estuary area exhibited the highest nitrogen concentration. α-diversity exhibited significant differences (P<0.05), and the abundance and diversity of ZZD and BH were the lowest. The operational taxonomic units of the water body mainly belonged to Proteobacteria (α-Proteobacteria, ß-Proteobacteria, and γ-Proteobacteria). Meanwhile, Venn diagram analysis indicated the community of aerobic denitrification bacteria exhibited significant differences, and variance inflation factor and redundancy analysis showed that temperature, dissolved oxygen, ammonia, nitrate, dissolved total phosphorus, and redox potential were the main environmental factors. Network analysis showed that symbiotic relationships accounted for a major proportion of the microbial network. Mantel test analysis shows that temperature, redox potential, nitrate, ammonia, dissolved total phosphorus, and iron and manganese are the key factors affecting the evolution of modular community structure. From all the results, the MiSeq high-throughput sequencing technique based on the napA gene was an effective tool to explore the changes of aerobic denitrification bacterial community structure, which could supply a reference to isolate the "directional-accurate-efficient" aerobic denitrification bacterial agent in the future.


Assuntos
Desnitrificação , Lagos , Bactérias , Congelamento , Nitrogênio
14.
Enzyme Microb Technol ; 138: 109583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32527527

RESUMO

The enzyme 1, 4-dihydroxy-2-naphthoic acid (DHNA) prenyltransferase (MenA) is a critical player in determining the efficiency of the menaquinone (MK) synthesis pathway and is an attractive target for the development of novel chemotherapeutics against pathogenic Gram-positive bacteria. However, there has been no report on structural properties or active region of MenA. To solve this challenge, we predicted the three-dimensiona structure and critical amino acid sites of MenA by bioinformatics analysis. Six amino acid sites were chosen by alligning the amino acid sequence of MenA from Bacillus subtilis natto with 4-hydroxybenzoate octaprenyl transferase (UbiA) from Escherichia coli, Aeropyrum pernix and Archaeoglobus fulgidus. Among them, four Asp sites located in two Asp-rich motifs (D78XXXXXD84 and D208XXXD212) were found to be indispensable amino acid residues in maintaining MenA activity. Site-directed mutagenesis of two other sites (Q67th, N74th) positively affected the catalytic activity of MenA and the MK titer. Q67R resulted in more than a 5-fold increase in specific 2-demethylmenaquinone (DMK) content (YP1/x) compared to wild-type, and the hydrophobic interaction between Cys63 and Arg67 could be the main reason according to the three-dimensional structure analysis. Moreover, a dramatic increase in specific MK content (YP2/x) was realized by co-expressing menG in EcMenA (Q67R). The results obtained could be useful not only in developing novel chemotherapeutics to combat potentially pathogenic Gram-positive bacteria, but also in regulating and optimizating E. coli mutant cultures for the efficient production of MK metabolites.

15.
Int J Cancer ; 147(8): 2210-2224, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32573785

RESUMO

Enhancer can transcribe RNAs, however, most of them were neglected in traditional RNA-seq analysis workflow. Here, we developed a Pipeline for Enhancer Transcription (PET, http://fun-science.club/PET) for quantifying enhancer RNAs (eRNAs) from RNA-seq. By applying this pipeline on lung cancer samples and cell lines, we showed that the transcribed enhancers are enriched with histone marks and transcription factor motifs (JUNB, Hand1-Tcf3 and GATA4). By training a machine learning model, we demonstrate that enhancers can predict prognosis better than their nearby genes. Integrating the Hi-C, ChIP-seq and RNA-seq data, we observe that transcribed enhancers associate with cancer hallmarks or oncogenes, among which LcsMYC-1 (Lung cancer-specific MYC eRNA-1) potentially supports MYC expression. Surprisingly, a significant proportion of transcribed enhancers contain small protein-coding open reading frames (sORFs) and can be translated into microproteins. Our study provides a computational method for eRNA quantification and deepens our understandings of the DNA, RNA and protein nature of enhancers.

16.
Acta Biomater ; 113: 554-569, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569637

RESUMO

As a breast cancer subtype with high mortality in women, the efficient treatment of Triple-negative breast cancer (TNBC) is still a challenge due to its unique metastatic mode and poor prognosis. In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. In vitro assay indicated good biocompatibility, prolonged blood circulation time (3-fold longer than GT NPs), and effectively enhanced cell and nucleus targeting capability of this nanosystem. Fluorescence activated cell sorter (FACS) analysis indicated that the combination of DOX and CS-6 induced TNBC cell apoptosis more than 89 % under the ratio of 10:1. In vivo assay indicated that the accumulation of GTDC@M-R NPs in tumor sites increased about 2-fold compared to naked GTDC NPs, which was accompanied by high tumor apoptosis rates through blocking chemotherapy-activated cyclooxygenase-2 (COX-2) and enhancing DOX's anti-tumor activity of chemical drugs (85%). Moreover, comparing with the control, the average number of lung metastatic nodules in tumor-bearing mice reduced 84%, the molecular mechanism of which is related to the down expression of COX-2, matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF). Taken together, our results proved that the developed GTDC@M-R NPs can inhibit the growth and suppress metastasis of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy. STATEMENT OF SIGNIFICANCE: In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. These GTDC@M-R NPs indicated synergistic chemotherapy against TNBC cells through the precise cell and nuclear targeting, immune escape, and improved DOX sensitivity. A effective inhibition of tumor growth and metastasis was achieved by inhibiting Bcl-2/BAX, COX-2 and VEGF related signal pathways. Our finding suggests that the developed GTDC@M-R NPs present great treating effects in the preclinical models of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy.

17.
Invest New Drugs ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32468271

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and most patients die within one year after diagnosis. This cancer is resistant to almost all current therapies, so there is an urgent need to identify novel druggable targets. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that functions in carcinogenesis, but its role in PDAC is unknown. Our experiments indicated that several subtypes of PDAC cells are sensitive to USP7 inhibition. In particular, pharmaceutical inhibition of USP7 by the small molecule P22077 attenuated PDAC cell growth and induced cell death in vitro and in vivo. Pharmaceutical inhibition of USP7 in P22077-resistant PDAC cells allowed them to overcome chemoresistance. Genetic silencing experiments supported the importance of USP7 in the pathogenesis of PDAC. In particular, genetic disruption of USP7 greatly reduced cell proliferation and chemoresistance in vitro and prevented PDAC growth in vivo. Protein profiling by mass spectrometry (MS) indicated USP7 was associated 4 ontology terms: translation, localization and protein transporting, nucleotide or ribonucleotide binding, and ubiquitin-dependent catabolic processes. Puromycin labeling indicated that P22077 greatly reduced protein synthesis, and transcriptional analysis indicated that P22077 significantly altered the extracellular space matrix. In summary, we provided multiple lines of evidence which indicate that USP7 plays a critical role in PDAC, and may therefore be a suitable target for treatment of this cancer.

18.
Phys Rev Lett ; 124(17): 173201, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412259

RESUMO

Rescattering by electrons on classical trajectories is central to understand photoelectron and high-harmonic emission from isolated atoms or molecules in intense laser pulses. By controlling the cluster size and the quiver amplitude of electrons, we demonstrate how rescattering influences the energy distribution of photoelectrons emitted from noble gas nanoclusters. Our experiments reveal a universal dependence of photoelectron energy distributions on the cluster size when scaled by the field driven electron excursion, establishing a unified rescattering picture for extended systems with the known atomic dynamics as the limit of zero extension. The result is supported by molecular dynamics calculations and rationalized with a one-dimensional classical model.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32356747

RESUMO

Rate-distortion (RD) theory is at the heart of lossy data compression. Here we aim to model the generalized RD (GRD) trade-off between the visual quality of a compressed video and its encoding profiles (e.g., bitrate and spatial resolution). We first define the theoretical functional space W of the GRD function by analyzing its mathematical properties. We show that W is a convex set in a Hilbert space, inspiring a computational model of the GRD function, and a method of estimating model parameters from sparse measurements. To demonstrate the feasibility of our idea, we collect a large-scale database of real-world GRD functions, which turn out to live in a low-dimensional subspace of W. Combining the GRD reconstruction framework and the learned low-dimensional space, we create a low-parameter eigen GRD method to accurately estimate the GRD function of a source video content from only a few queries. Experimental results on the database show that the learned GRD method significantly outperforms state-of-the-art empirical RD estimation methods both in accuracy and efficiency. Last, we demonstrate the promise of the proposed model in video codec comparison.

20.
Nat Plants ; 6(6): 686-698, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32451448

RESUMO

Organ size and shape are precisely regulated to ensure proper function. The four sepals in each Arabidopsis thaliana flower must maintain the same size throughout their growth to continuously enclose and protect the developing bud. Here we show that DEVELOPMENT RELATED MYB-LIKE 1 (DRMY1) is required for both timing of organ initiation and proper growth, leading to robust sepal size in Arabidopsis. Within each drmy1 flower, the initiation of some sepals is variably delayed. Late-initiating sepals in drmy1 mutants remain smaller throughout development, resulting in variability in sepal size. DRMY1 focuses the spatiotemporal signalling patterns of the plant hormones auxin and cytokinin, which jointly control the timing of sepal initiation. Our findings demonstrate that timing of organ initiation, together with growth and maturation, contribute to robust organ size.

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