ABSTRACT
BACKGROUND: Chemoresistance is associated with tumor relapse and unfavorable prognosis. Multiple mechanisms underlying chemoresistance have been elucidated, including stemness and DNA damage repair. Here, the involvement of the WNT receptor, FZD5, in ovarian cancer (OC) chemoresistance was investigated. METHODS: OC cells were analyzed using in vitro techniques including cell transfection, western blot, immunofluorescence and phalloidin staining, CCK8 assay, colony formation, flowcytometry, real-time PCR, and tumorisphere formation. Pearson correlation analysis of the expression levels of relevant genes was conducted using data from the CCLE database. Further, the behavior of OC cells in vivo was assessed by generation of a mouse xenograft model. RESULTS: Functional studies in OC cells showed that FZD5 contributes to epithelial phenotype maintenance, growth, stemness, HR repair, and chemoresistance. Mechanistically, FZD5 modulates the expression of ALDH1A1, a functional marker for cancer stem-like cells, in a ß-catenin-dependent manner. ALDH1A1 activates Akt signaling, further upregulating RAD51 and BRCA1, to promote HR repair. CONCLUSIONS: Taken together, these findings demonstrate that the FZD5-ALDH1A1-Akt pathway is responsible for OC cell survival, and targeting this pathway can sensitize OC cells to DNA damage-based therapy.
Subject(s)
Aldehyde Dehydrogenase , Ovarian Neoplasms , Humans , Animals , Mice , Female , Aldehyde Dehydrogenase/genetics , Drug Resistance, Neoplasm , Proto-Oncogene Proteins c-akt/metabolism , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Cell Line, Tumor , Neoplastic Stem Cells/metabolismABSTRACT
Nitrophenols, a versatile intermediate, have been widely used in leather, medicine, chemical synthesis, and other fields. Because these components are widely applied, they can enter the environment through various routes, leading to many hazards and toxicities. There has been a recent surge in the development of simple, rapid, environmentally friendly, and effective techniques for determining these environmental pollutants. This review provides a comprehensive overview of the latest research progress on the pretreatment and analysis methods of nitrophenols since 2017, with a focus on environmental samples. Pretreatment methods include liquid-liquid extraction, solid-phase extraction, dispersive extraction, and microextraction methods. Analysis methods mainly include liquid chromatography-based methods, gas chromatography-based methods, supercritical fluid chromatography. In addition, this review also discusses and compares the advantages/disadvantages and development prospects of different pretreatment and analysis methods to provide a reference for further research.
Subject(s)
Environmental Pollutants , Nitrophenols , Environmental Pollutants/analysis , Nitrophenols/analysis , Environmental Monitoring/methods , Liquid-Liquid Extraction/methods , Solid Phase Extraction , Chromatography, Liquid , Chromatography, Gas , Chromatography, Supercritical Fluid/methodsABSTRACT
X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12â times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92â nGy s-1 at 213â K and a detection limit of 196.31â nGy s-1 at 353â K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.
ABSTRACT
BACKGROUND: Metastasis of malignant tumors accelerates systemic failure and hastens the deaths of pancreatic cancer patients. During the metastatic process, the physical translocation of cancer cells from the primary lesion to distant organs and is crucial. CSCs properties, such as self-renewal and multiple-direction differentiation capacity are essential for colonization in the microenvironment of distant organs and metastatic lesion formation. It is widely believed that EMT can cause cancer cells to penetrate blood vessels by undergoing phenotypic and cytoskeletal changes, so that they can infiltrate surrounding tissue and disseminate from the primary tumor to the blood circulation, where they are termed circulating tumor cells (CTCs), while CTCs often exhibit stemness properties. Accumulating evidence demonstrates that some EMT-related transcription factors are essential for CSCs self-renewal, so cancer cells that have undergone EMT typically acquire increased stemness properties. Abnormal activation of the WNT signaling pathway can drive a series of gene transcripts to promote EMT in multiple types of cancer, and among different Frizzled receptors of WNT signaling pathway, FZD7 expression is associated with distant organ metastasis, advanced clinical stages, and poor clinical prognosis. Objective of this study is to demonstrate that high FZD7 expression in pancreatic cancer can accelerate hepatic metastases and elucidate the related molecular mechanisms. METHODS: The expression of Frrizled receptor 7 (FZD7) in pancreatic ductal adenocarcinoma (PDAC) and relating survival rate were analyzed by bioinformatics, histochemistry assay and follow-up study. In vitro, FZD7 expression was silenced by lentiviral vectors carrying short hair RNA (shRNA) or upregulated by overexpression plasmid. Then, Wound-healing and Transwell experiment was used to analyze the abilities of migration and invasion; the levels of epithelial-to-mesenchymal transition (EMT) relating phenotype proteins, stemness relating phenotype proteins, and signaling molecular proteins were measured by Western-blot; cell stemness was evaluated by sphere forming ability of cells in suspension culture and detecting the proportion of CD24+CD44+ cells with flow cytometry. TGF-ß1 was used to induce EMT, and observe the effect of shRNA silencing FZD7 on which. RESULTS: High level of FZD7 expression in pancreatic cancer samples was associated with earlier hepatic metastasis. In vitro upregulation FZD7 can enable pancreatic cancer cells to obtain stronger migration and invasion ability and higher mesenchymal phenotype, and vice versa; the proportion of cancer stem cell (CSC) was also positively correlated with the level of FZD7; cells forming spheres in suspension culture showed stronger migration and invasion ability and higher level of mesenchymal phenotype than normal adherent cultured cells; the level of FZD7 was positively correlated with the level of activated ß-catenin. Silencing FZD7 expression can attenuate EMT induced by TGF-ß1 stimulating, and TGF-ß1 stimulating can also upregulate stemness phenotype expression, such as ABCG2, CD24, and CD44 by mediating of FZD7. CONCLUSIONS: High FZD7 expression in pancreatic cancer can accelerates hepatic metastases by promoting EMT and strengthening cell stemness, and FZD7 can work through the canonical Wingless-type (WNT) signaling pathway and participate in TGF-ß/SMAD3 signaling pathway also.
Subject(s)
Frizzled Receptors , Liver Neoplasms , Pancreatic Neoplasms , Smad3 Protein , Transforming Growth Factor beta1 , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Follow-Up Studies , Frizzled Receptors/genetics , Frizzled Receptors/metabolism , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Microenvironment , Wnt Signaling Pathway , Pancreatic NeoplasmsABSTRACT
BACKGROUND: Long noncoding RNA growth arrest-specific 5 (lnc-GAS5) is involved in the pathophysiology of acute ischemic stroke (AIS) by regulating vascular stenosis, inflammation, and neurocyte apoptosis. This study aimed to explore the clinical value of lnc-GAS5 in patients with AIS. METHODS: Plasma samples were collected from 120 patients with AIS at admission and 60 controls after enrollment, and lnc-GAS5 expression in the plasma of all participants was assessed by reverse transcription quantitative polymerase chain reaction. In patients with AIS, disease severity was evaluated using National Institute of Health Stroke Scale (NIHSS) score, and plasma inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Recurrence-free survival (RFS) was calculated during a 36-month follow-up period. RESULTS: Lnc-GAS5 expression levels were higher in patients with AIS than in the controls (p < 0.001), and it had the potential to discriminate the controls from patients with AIS (area under the curve: 0.893, 95% confidence interval: 0.849-0.938). In patients with AIS, elevated lnc-GAS5 levels were positively correlated with NIHSS score (r = 0.397, p < 0.001), diabetes mellitus (p = 0.046), and higher levels of tumor necrosis factor alpha (TNF-α; r = 0.374, p < 0.001), interleukin-6 (IL-6; r = 0.223, p < 0.001), and interleukin-17A (IL-17A; r = 0.222, p = 0.015). The expression levels of lnc-GAS5 were also negatively correlated with the levels of interleukin-10 (IL-10; r = -0.350, p < 0.001) and RFS (p = 0.036). CONCLUSION: Lnc-GAS5 is correlated with higher susceptibility to AIS, inflammation, and severity, and can predict an increased risk of AIS recurrence, indicating that monitoring of lnc-GAS5 might improve the management of AIS.
Subject(s)
Cytokines/blood , Genetic Predisposition to Disease , Ischemic Stroke/genetics , RNA, Long Noncoding/metabolism , Aged , Case-Control Studies , Female , Humans , Inflammation , Interleukin-17/blood , Interleukin-6/blood , Male , Middle Aged , Prognosis , Recurrence , Severity of Illness Index , Tumor Necrosis Factor-alpha/bloodABSTRACT
Mesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes and a panel of stemness-related genes. Fzd7 knockdown in mesenchymal-like MDA-MB-231 and Hs578T cells reduced expression of Vimentin, Slug and Zeb1, induced an epithelial-like morphology, inhibited cell motility, impaired mammosphere formation and decreased Lgr5+ subpopulation. In contrast, Fzd7 overexpression in MCF7 cells resulted in opposite changes. Fzd7 knockdown delayed xenograft tumor formation, suppressed tumor growth, and impaired lung metastasis. Mechanistically, Fzd7 combined with Wnt5a/b and modulated expression of phosphorylated Stat3 (p-STAT3), Smad3 and Yes-associated protein 1 (Yap1). Moreover, Fzd7-Wnt5b modulated expression of collagen, type VI, alpha 1 (Col6a1). Both Wnt5b knockdown and Col6a1 knockdown disrupted BC cell mesenchymal phenotype and stemness. Taken together, Fzd7 contributes to BC cell EMT and stemness, inducing tumorigenesis and metastasis, mainly through a non-canonical Wnt5b pathway. Col6a1 is implicated in Fzd7-Wnt5b signaling, and mediates Fzd7-Wnt5b -induced mesenchymal-like stemness. Video Abstract.
Subject(s)
Breast Neoplasms/pathology , Collagen Type VI/metabolism , Frizzled Receptors/metabolism , Neoplastic Stem Cells/pathology , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Line, Tumor , Collagen Type VI/genetics , Epithelial-Mesenchymal Transition , Female , Frizzled Receptors/genetics , Gene Expression Regulation, Neoplastic , Humans , Mice, Inbred NOD , Mice, SCID , Neoplastic Stem Cells/metabolism , Signal TransductionABSTRACT
Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or low-density-lipoprotein receptor-related proteins 5/6 (LRP5/6), initiating ß-catenin-dependent and -independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled-related proteins (SFRP) and dickkopf-related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on human clinical breast cancer patients and studies on in vitro cultured human breast cancer cells. This review focuses on the roles of Wnt ligands, receptors and antagonists in breast cancer development instead of molecules or signaling transactivating ß-catenin independent on Wnt upstream components.
Subject(s)
Breast Neoplasms/metabolism , Mammary Neoplasms, Animal/metabolism , Wnt Signaling Pathway , Animals , Breast Neoplasms/genetics , Disease Progression , Female , Frizzled Receptors/metabolism , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , LDL-Receptor Related Proteins/metabolism , Mammary Neoplasms, Animal/genetics , Mice , Mice, Transgenic , Wnt Proteins/genetics , Wnt Proteins/metabolismABSTRACT
A new class of high-temperature dipolar polymers based on sulfonylated poly(2,6-dimethyl-1,4-phenylene oxide) (SO2 -PPO) was synthesized by post-polymer functionalization. Owing to the efficient rotation of highly polar methylsulfonyl side groups below the glass transition temperature (Tg ≈220 °C), the dipolar polarization of these SO2 -PPOs was enhanced, and thus the dielectric constant was high. Consequently, the discharge energy density reached up to 22â J cm-3 . Owing to its high Tg , the SO2 -PPO25 sample also exhibited a low dielectric loss. For example, the dissipation factor (tan δ) was 0.003, and the discharge efficiency at 800â MV m-1 was 92 %. Therefore, these dipolar glass polymers are promising for high-temperature, high-energy-density, and low-loss electrical energy storage applications.
ABSTRACT
BACKGROUND: High content of (1,3;1,4)-ß-d-glucan in barley grains is regarded as an undesirable factor affecting malting potential, brewing yield and feed utilization. Production of thermostable bacterial (1,3;1,4)-ß-glucanase in transgenic barley grain or supplementation of exogenous bacterial (1,3;1,4)-ß-glucanase has been used to improve malt and feed quality. The aim of the present study was to investigate the effect of over-expression of an endogenous (1,3;1,4)-ß-glucanase on ß-glucan content and grain composition in barley. RESULTS: A construct containing full-length HvGlb2 cDNA encoding barley (1,3;1,4)-ß-glucanase isoenzyme EII under the control of a promoter of barley D-Hordein gene Hor3-1 was introduced into barley cultivar Golden Promise via Agrobacterium-mediated transformation, and transgenic plants were regenerated after hygromycin selection. The T2 generation of proHor3:HvGlb2 transgenic lines showed increased activity of (1,3;1,4)-ß-glucanase in grains. Total ß-glucan content was reduced by more than 95.73% in transgenic grains compared with the wild-type control. Meanwhile, over-expression of (1,3;1,4)-ß-glucanase led to an increase in 1000-grain weight, which might be due to elevated amounts of starch in the grain. CONCLUSION: Manipulating the expression of (1,3;1,4)-ß-glucanase EII can control the ß-glucan content in grain with no apparent harmful effects on grain quality of transgenic plants. © 2016 Society of Chemical Industry.
Subject(s)
Glucans/metabolism , Glycoside Hydrolases/genetics , Hordeum/metabolism , Plant Proteins/genetics , Plants, Genetically Modified/metabolism , Starch/metabolism , Glucans/chemistry , Glycoside Hydrolases/metabolism , Hordeum/chemistry , Hordeum/enzymology , Hordeum/genetics , Isoenzymes/genetics , Isoenzymes/metabolism , Plant Proteins/metabolism , Plants, Genetically Modified/enzymology , Plants, Genetically Modified/genetics , Seeds/chemistry , Seeds/enzymology , Seeds/metabolismABSTRACT
The effects of temperature on nitrous oxide (N2O) accumulation during denitrification and denitritation were investigated. Batch experiments were performed to measure N2O accumulation at 25 and 35 °C. More N2O accumulation was observed during denitritation at the higher temperature as compared with full denitrification and low temperature tests. The highest nitrite concentration tested in this study (25 mg/L NO2 (-)N and pH 8.0) did not show inhibitory effect on N2O reduction. It was found that the major cause of more N2O accumulation during denitrification at higher temperature was due to higher N2O production rate and lower N2O solubility. Specific nitrate, nitrite, and N2O reduction rates increased 62, 61, and 41 %, respectively, when temperature rose from 25 to 35 °C. The decrease of N2O solubility in mixed liquor at 35 °C (when compared to 25 °C) resulted in faster diffusing rate of N2O from liquid to gas phase. It was also more difficult for gas phase N2O to be re-dissolved. The diffused N2O was then accumulated in the headspace, which was not available for denitrification by denitrifiers. The results of this study suggest higher temperature may worsen N2O emission from wastewater treatment plants (WWTPs).
Subject(s)
Denitrification , Nitrous Oxide/analysis , Wastewater/chemistry , Hydrogen-Ion Concentration , Nitrates/metabolism , Nitrites/metabolism , Oxidation-Reduction , Temperature , Wastewater/microbiology , Water PurificationABSTRACT
Jun dimerization protein 2 (JDP2) is a repressor of transcription factor AP-1. To investigate the transcriptional regulation of the JDP2 gene, we cloned the 5'-flanking region of the mouse JDP2 gene. Primer extension analysis revealed a new transcription start site (+1). Promoter analysis showed that the region from nt -343 to nt +177 contains basal transcriptional activity. Interestingly, the tumor suppressor p53 significantly repressed the transcriptional activity of the JDP2 promoter. Given that JDP2 inhibits expression of p53, our results suggest a negative feedback loop between JDP2 and p53, and a direct link between JDP2 and a key oncogenic pathway.
Subject(s)
Gene Expression Regulation/physiology , Promoter Regions, Genetic , Repressor Proteins/genetics , Tumor Suppressor Protein p53/physiology , Animals , Base Sequence , Cell Line, Tumor , Cloning, Molecular , DNA/genetics , Mice , Molecular Sequence Data , Transcription, GeneticABSTRACT
In this paper, we propose a new dictionary learning approach for image deconvolution, which effectively integrates the Fourier regularization and dictionary learning technique into the deconvolution framework. Specifically, we propose an iterative algorithm with the decoupling of the deblurring and denoising steps in the restoration process. In the deblurring step, we involve a regularized inversion of the blur in the Fourier domain. Then we remove the colored noise using a dictionary learning method in the denoising step. In the denoising step, we propose an approach to update the estimation of noise variance for dictionary learning. We will show that this approach outperforms several state-of-the-art image deconvolution methods in terms of improvement in signal-to-noise ratio and visual quality.
Subject(s)
Algorithms , Artifacts , Artificial Intelligence , Data Interpretation, Statistical , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Analysis of Variance , Fourier Analysis , Regression Analysis , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Most studies on the acceleration process of electric vehicle focus on reducing energy consumption, but do not consider the impact of the power battery discharge current and its change rate on the battery life. Therefore, this paper studied the interaction between electric vehicle energy consumption and power battery capacity attenuation during acceleration. First, a power battery life model for electric vehicle under driving conditions is established, and the percentage of battery capacity loss per kilometer is used to measure the capacity loss under different acceleration conditions. Then, the relationship between the percentage of battery capacity loss per kilometer and velocity and acceleration is explored, and the capacity attenuation mechanism of power battery under different acceleration processes is analyzed. Finally, the energy consumption and battery capacity attenuation is studied when the electric vehicle accelerated with multiple accelerations curves, and the interaction of the first acceleration and acceleration time on the electric vehicle energy consumption and the power battery capacity attenuation characteristics is discussed. The research results indicate that when the electric vehicle accelerates with different multiple accelerations curves, the change of energy consumption per kilometer and percentage of battery capacity loss per kilometer with acceleration and acceleration time is different, and the change of the two is basically opposite.
ABSTRACT
The phenomenon of high-temperature oxidation in magnesium alloys constitutes a significant obstacle to their application in the aerospace field. However, the incorporation of active elements such as alloys and rare earth elements into magnesium alloys alters the organization and properties of the oxide film, resulting in an enhancement of their antioxidation capabilities. This paper comprehensively reviews the impact of alloying elements, solubility, intermetallic compounds (second phase), and multiple rare earth elements on the antioxidation and flame-retardant effects of magnesium alloys. The research progress of flame-retardant magnesium alloys containing multiple rare earth elements is summarized from two aspects: the oxide film and the matrix structure. Additionally, the existing flame-retardancy models for magnesium alloys and the flame-retardant mechanisms of various flame-retardant elements are discussed. The results indicate that the oxidation of rare earth magnesium alloys is a complex process determined by internal properties such as the structure and properties of the oxide film, the type and amount of rare earth elements added, the proportion of multiple rare earth elements, synergistic element effects, as well as external properties like heat treatment, oxygen concentration, and partial pressure. Finally, some issues in the development of multi-rare earth magnesium alloys are raised and the potential directions for the future development of rare earth flame-retardant magnesium alloys are discussed. This paper aims to promote an understanding of the oxidation behavior of flame-retardant magnesium alloys and provide references for the development of rare earth flame-retardant magnesium alloys with excellent comprehensive performance.
ABSTRACT
Almonds are a commonly consumed nut. They possess significantof nutritional and health benefitsand are commonly processed by roasting. This study aimed to investigatthe effects of roasting on the compound composition and antioxidant activity of almonds. Metabolomics analysis, performed via UPLC-QTOF/MS, and fatty acid analysis, conducted via GC-MS, employed, and the results demonstrated a significant increase in antioxidant activity of post-roasting and in vitro digestion, ranging from 1.16 to 3.44 times. Untargeted metabolomics identified a total of 172 compounds, with notable differences observed in organic oxides, fatty acids, and their derivatives. Correlation analysis identified fatty acids as the primary influencers of changes in antioxidant activity following roasting. Taken together, these findings suggest that roasting enhances the antioxidant activity of almonds, primarily due to alterations in fatty acid analogs, thereby providing valuable insights into optimizing almond consumption for health benefits.
Subject(s)
Antioxidants , Fatty Acids , Gas Chromatography-Mass Spectrometry , Metabolomics , Prunus dulcis , Antioxidants/analysis , Antioxidants/metabolism , Metabolomics/methods , Prunus dulcis/chemistry , Chromatography, High Pressure Liquid , Fatty Acids/analysis , Cooking/methods , Nuts/chemistry , Hot Temperature , Food Handling/methods , Tandem Mass SpectrometryABSTRACT
Chemoresistance poses a significant obstacle to the treatment of breast cancer patients. The increased capacity of DNA damage repair is one of the mechanisms underlying chemoresistance. Bioinformatic analyses showed that E2F8 was associated with cell cycle progression and homologous recombination (HR) repair of DNA double-strand breaks (DSBs) in breast cancer. E2F8 knockdown suppressed cell growth and attenuated HR repair. Accordingly, E2F8 knockdown sensitized cancer cells to Adriamycin and Cisplatin. Centromere protein L (CENPL) is a transcriptional target by E2F8. CENPL overexpression in E2F8-knockdowned cells recovered at least in part the effect of E2F8 on DNA damage repair and chemotherapy sensitivity. Consistently, CENPL knockdown impaired DNA damage repair and sensitized cancer cells to DNA-damaging drugs. These findings demonstrate that targeting E2F8-CENPL pathway is a potential approach to overcoming chemoresistance.
Subject(s)
Breast Neoplasms , Recombinational DNA Repair , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , DNA Repair , DNA , Repressor Proteins/genetics , Chromosomal Proteins, Non-Histone , Cell Cycle Proteins/geneticsABSTRACT
In this paper we propose an approach for handling noise in deconvolution algorithm based on multidirectional filters. Most image deconvolution techniques are sensitive to the noise. Even a small amount of noise will degrade the quality of image estimation dramatically. We found that by applying a directional low-pass filter to the blurred image, we can reduce the noise level while preserving the blur information in the orthogonal direction to the filter. So we apply a series of directional filters at different orientations to the blurred image, and a guided filter based edge-preserving image deconvolution is used to estimate an accurate Radon transform of the clear image from each filtered image. Finally, we reconstruct the original image using the inverse Radon transform. We compare our deconvolution algorithm with many competitive deconvolution techniques in terms of the improvement in signal-to-noise ratio and visual quality.
ABSTRACT
BACKGROUND: Recently, aberrant expression of PIWI-interacting RNAs (piRNAs) has been discovered in a variety of cancer cells. However, the roles of PIWI proteins and piRNAs in papillary thyroid carcinoma (PTC) are still elusive. METHODS: RT-qPCR and Northern blotting were used to evaluate piR-13643 levels in PTC and para-carcinoma tissues, as well as in PTC cell lines. piR-13643 mimic and piR-13643 inhibitor were transfected into K-1 and B-CPAP cells. CCK-8, Transwell, annexin V-FITC/PI, flow cytometry and Western blot assays were performed to measure cell proliferation, invasion, apoptosis, cell cycle and E-cadherin and Vimentin proteins, respectively. Total RNA from B-CPAP cells was pulled down with PIWIL1, PIWIL2, or PIWIL3 specific antibodies or IgG as a control, respectively, followed by detection of piR-13643 expression with RT-qPCR. Immunoblotting of PRMT1 was detected in piR-13643 / PIWIL1 complex immune-precipitates by Co-IP assay. Subsequently, PRMT1 protein expression was detected by stably transfection of Flag tagged GLI1 (Flag-GLI1) into B-CPAP cells. Methylation assay with PRMT1 and wild-type or R597 lysine (R597K)-mutant GLI1. Then rescue experiments were applied to explore effects of piR-13643 and GLI1 on the malignant behavior of PTC cells. B-CPAP cells transfected with piR-13643 inhibitor were subcutaneously injected into nude mice to evaluate the effect of piR-13643 knockdown on the xenograft tumor growth of PTC. RESULTS: piR-13643 was elevated in PTC patient specimens and cell lines. piR-13643 overexpression facilitated cell proliferation, invasion and Vimentin level, and restrained apoptosis and E-cadherin expression, whereas piR-13643 knockdown showed the opposite results. Mechanically, piR-13643 could bind to PIWIL1 to form the PIWIL1/piR-13643 complex, and PRMT1 enhanced GLI1 transcription by methylating GLI1 at R597. Further, PIWIL1/piR-13643 promoted PRMT1-mediated GLI1 methylation. GLI1 knockdown countered the effects of piR-13643 mimic on cell malignant behaviors. piR-13643 knockdown preeminently prevented the xenograft tumor growth of PTC in vivo. CONCLUSIONS: This study confirmed that piR-13643 facilitates PTC malignant behaviors in vitro and in vivo by promoting PRMT1-mediated GLI1 methylation via forming a complex with PIWIL1, which may provide a novel insight for PTC treatment.
ABSTRACT
While the synthesis of nanographenes has advanced greatly in the past few years, development of their atomically precise functionalization strategies remains rare. The ability to modify the carbon scaffold translates to controlling, adjusting, and adapting molecular properties. Towards this end, here, we show that mechanochemistry is capable of transforming graphitization precursors directly into chlorinated curved nanographenes through a Scholl reaction. The halogenation occurs in a regioselective, high-yielding, and general manner. Density Functional Theory (DFT) calculations suggest that graphitization activates specific edge-positions for chlorination. The chlorine atoms allow for precise chemical modification of the nanographenes through a Suzuki or a nucleophilic aromatic substitution reaction. The edge modification enables modulation of material properties. Among the molecules prepared, corannulene-coronene hybrids and laterally fully π-extended helicenes, heptabenzo[5]superhelicenes, are particularly noteworthy.
ABSTRACT
Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a ß-integrin-related extracellular matrix protein and is reported to promote progression of some types of cancer. Nevertheless, the function of ITGBL1 in PC is still not clear. Herein, we found that ITGBL1 was highly expressed in PC tissues compared to normal tissues (P<0.05) and PC patients with higher TGBL1 expression showed worse prognosis. PANC-1 and AsPC-1 cells were used for gain/loss-of-function experiments. We found that ITGBL1-silenced cells exhibited decreased proliferation, migration, and invasion abilities and delayed cell cycle, whereas ITGBL1 overexpression reversed these malignant behaviors. ITGBL1 was also demonstrated to activate the TGF-ß/Smad pathway, a key signaling pathway in PC progression. Additionally, ITGBL1 expression was found to be suppressed by a suppressor of PC progression, c-Jun dimerization protein 2 (JDP2). Results of dual-luciferase assay indicated that transcription factor JDP2 could inhibit TGBL1 promoter activity. ITGBL1 overexpression inversed the effects of JDP2 up-regulation on cell function. Collectively, we concluded that ITGBL1 may be transcriptionally suppressed by JDP2 and promote PC progression through the TGF-ß/Smad pathway, indicating that ITGBL1 may have therapeutic potential for the treatment of PC.