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1.
Mol Cell ; 81(16): 3339-3355.e8, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352206

RESUMO

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.


Assuntos
Colangiocarcinoma/genética , Proteínas de Ligação ao GTP/genética , Metiltransferases/genética , Biossíntese de Proteínas , Animais , Carcinogênese/genética , Colangiocarcinoma/patologia , Progressão da Doença , Receptores ErbB/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Camundongos , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
2.
Front Aging Neurosci ; 13: 644379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994995

RESUMO

Background: Although numerous studies have suggested that the gradually increasing selective preference for positive information over negative information in older adults depends on cognitive control processes, few have reported the characteristics of different attention stages in the emotional processing of older individuals. The present study used a real-time eye-tracking technique to disentangle the attentional engagement and disengagement processes involved in age-related positivity effect (PE). Methods: Eye movement data from a spatial-cueing task were obtained for 32 older and 32 younger healthy participants. The spatial-cueing task with varied cognitive loads appeared to be an effective way to explore the role of cognitive control during the attention engagement and disengagement stages of emotion processing. Results: Compared with younger adults, older participants showed more positive gaze preferences when cognitive resources were sufficient for face processing at the attention engagement stage. However, the age-related PE was not observed at the attention disengagement stage because older adults had more difficulty disengaging from fearful faces than did the younger adults due to the consumption of attention by the explicit target judgment. Conclusion: The present study highlights how cognitive control moderates positive gaze preferences at different attention processing stages. These findings may have far-reaching implications for understanding, preventing, and intervening in unsuccessful aging and, thus, in promoting active and healthy aging.

3.
Pharmaceuticals (Basel) ; 14(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922294

RESUMO

8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(-) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(-)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(-) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.

4.
Exp Neurol ; 341: 113700, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33741350

RESUMO

BACKGROUND: Pyroptosis mediated by NLRP3 inflammasome plays a critical role in the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Mounting evidences have verified the efficacy of exosomes by relieving the inflammatory response during cerebral I/R injury, but the specific mechanism has not been well elucidated. This study aimed to clarify whether the neuroprotective effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) are associated with the attenuation of NLPR3-mediated neuron pyroptosis by modulating microglial polarization. METHODS: Rats were initially subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion. Then, BMSC-Exos were administered intravenously 2 h after MCAO. The neuroprotective effects were measured using a modified neurological severity score(mNSS), triphenyltetrazolium chloride (TTC) staining, brain water content, Morris water maze,and CatWalk system. Western blotting and immunofluorescence staining were applied to detect NLRP3 inflammasome and pyroptosis. Microglial polarization was determined by real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining. To mimic cerebral I/R injury in vitro, BV2 and PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation. After treatment with PBS, BMSC-Exos, IL-4, or LPS, BV2 cells were co-cultured with PC12 cells in a Transwell system. RESULTS: BMSC-Exos reduced the brain infarct area and brain water content at 24 h dose dependently and improved the neurological function up to 5 weeks after stroke. In vivo, NLRP3 inflammasome- and pyroptosis-related proteins were mainly expressed on neurons and downregulated by BMSC-Exos. Furthermore, cerebral I/R injury-induced M1-polarized microglia could be shifted toward M2 phenotype by BMSC-Exos. In vitro, BMSC-Exos alleviated the neuron pyroptosis partially by modulating microglial polarization. CONCLUSION: BMSC-Exos could ameliorate cerebral I/R injury via suppression of NLRP3 inflammasome-mediated inflammation and pyroptosis by modulating microglial polarization.


Assuntos
Isquemia Encefálica/prevenção & controle , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Microglia , Piroptose/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Isquemia Encefálica/metabolismo , Linhagem Celular , Células Cultivadas , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Piroptose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
5.
Sci Total Environ ; 771: 144840, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33540165

RESUMO

The efficient decontamination of pertechnetate (99TcO4-) is an essential task for managing radioactive 99Tc in nuclear wastes. Perrhenate, (ReO4-), as a nonradioactive analog, exhibits almost identical physicochemical properties as 99TcO4-. Herein, a novel magnetic amine-functionalized MIL-101(Cr) (NH2-MIL-101(Cr)@Fe3O4) was prepared and used to efficiently remove ReO4- from solution for the facile magnetic separation. A series of environmental parameters were considered to investigate the adsorption performance of NH2-MIL-101(Cr)@Fe3O4. Experimental results suggested that NH2-MIL-101(Cr)@Fe3O4 has reached a satisfied adsorption capacity (~401 mg/g) and a very fast adsorption kinetics at pH 7.0. The selectivity for ReO4- was maintained even in the presence of interfering anions with relatively high concentrations. ReO4- were mainly captured by N-donor sites of the surface-decorated amine via complexation and were trapped in the cavities of modified MIL-101(Cr). NH2-MIL-101(Cr)@Fe3O4 exhibits satisfactory adsorption performance for ReO4- and can be conveniently separated from wastewaters after adsorption.

6.
Acad Radiol ; 28(2): e27-e34, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32102748

RESUMO

RATIONALE AND OBJECTIVES: To explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) intensity histogram metrics, relative to time intensity curve (TIC)-derived metrics, in patients with suspected lung cancer. MATERIALS AND METHODS: This retrospective study enrolled 49 patients with suspected lung cancer on routine CT imaging who underwent DCE-MRI scans and had final histopathologic diagnosis. Three TIC-derived metrics (maximum enhancement ratio, peak time [Tmax] and slope) and eight intensity histogram metrics (volume, integral, maximum, minimum, median, coefficient of variation [CoV], skewness, and kurtosis) were extracted from DCE-MRI images. TIC-derived and intensity histogram metrics were compared between benignity versus malignancy using the Wilcoxon rank-sum test. Associations between imaging metrics and malignancy risk were assessed by univariate and multivariate logistic regression odds ratios (ORs). RESULTS: There were 33 malignant lesions and 16 benign lesions based on histopathology. Lower CoV (OR = 0.2 per 1-SD increase, p = 0.0006), lower Tmax (OR = 0.4 per 1-SD increase, p = 0.005), and steeper slope (OR = 2.4 per 1-SD increase, p = 0.010) were significantly associated with increased risk of malignancy. Under multivariate analysis, CoV was significantly independently associated with malignancy likelihood after accounting for either Tmax (OR = 0.3 per 1-SD increase, p = 0.007) or slope (OR = 0.3 per 1-SD increase, p = 0.011). CONCLUSION: This initial study found that DCE-MRI CoV was independently associated with malignancy in patients with suspected lung cancer. CoV has the potential to help diagnose indeterminate pulmonary lesions and may complement TIC-derived DCE-MRI metrics. Further studies are warranted to validate the diagnostic value of DCE-MRI intensity histogram analysis.


Assuntos
Neoplasias Pulmonares , Imageamento por Ressonância Magnética , Meios de Contraste , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos , Estatísticas não Paramétricas
7.
Adv Mater ; 33(1): e2005815, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33244822

RESUMO

Due to strong interlayer interaction and ease of oxidation issues of black phosphorus (BP), the domain size of artificial synthesized few-layer black phosphorus (FL-BP) crystals is often below 10 µm, which extremely limits its further applications in large-area thin-film devices and integrated circuits. Herein, a hydrogen-free electrochemical delamination strategy through weak Lewis acid intercalation enabled exfoliation is developed to produce ultralarge FL-BP single-crystalline domains with high quality. The interaction between the weak Lewis acid tetra-n-butylammonium acetate (CH3 COOTBA) and P atoms promotes the average domain size of FL-BP crystal up to 77.6 ± 15.0 µm and the largest domain size is found to be as large as 119 µm. The presence of H+ and H2 O is found to sharply decrease the size of as-exfoliated FL-BP flakes. The electronic transport measurements show that the delaminated FL-BP crystals exhibit a high hole mobility of 76 cm2 V-1 s-1 and an on/off ratio of 103 at 298 K. A broadband photoresponse from 532 to 1850 nm with ultrahigh responsivity is achieved. This work provides a scalable, simple, and low-cost approach for large-area BP films that meet industrial requirements for nanodevices applications.

8.
ACS Appl Mater Interfaces ; 12(44): 49849-49856, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33103902

RESUMO

The fluorination/sulfofication-induced effect in the photovoltaic polymer solar cells (PSCs) needs to be paid much attention. In this work, a new donor polymer PBDB-PS2F was synthesized by heavily fluorinated and decorated S atom on the side chain of benzo[1,2-b:4,5-b']dithiophene (BDT) unit to explore the internal combined effect of F&S on the photoelectric performance. It was found that the heavy fluorination on the side chain could make PBDB-PS2F achieve a low highest occupied molecule orbital (HOMO) energy level of -5.72 eV and weaken the torsion of the main chain and effectively increase the intermolecular π-π* transition. Encouragingly, compared with the counterpart polymer PBDB-PS without the fluorination, PBDB-PS2F exhibited a much intense aggregation at room temperature but showed a tendency of reduced aggregation at high temperatures. This feature gives excellent solution processability and uniform morphology in the active layer of a PBDB-PS2F-based device, enabling an outstanding photovoltaic performance with the power conversion efficiency (PCE) of 13.56% (VOC = 0.90 V, JSC = 21.53 mA/cm2, FF = 69.68%). Compared with that of the counterpart polymer PBDB-PS with no heavy fluorination, the VOC of PBDB-PS2F increased by 15.4% and the PCE increased by 30.9%. Thus, the heavy-fluorination-induced effect to construct photovoltaic polymers could be used to improve the performance of polymer solar cells.

9.
Cancer Manag Res ; 12: 5713-5720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765074

RESUMO

Background: PLAC2 has been reported to participate in glioma, but its role in ovarian carcinoma (OC) is unclear. This study investigated the role of lncRNA PLAC2 in OC. Methods: A 5-year follow-up study of 64 patients was carried out in Weihai Municipal Hospital after the admission of patients. A total of 64 OC patients were selected from 178 OC patients admitted in the aforementioned hospital from August 2011 to January 2014. Cell transfections, cell cycle analysis, cell proliferation assay and Western blot were carried out during the research. Results: The expression levels of PLAC2 and CDK2 were both upregulated in OC and they were positively correlated. During the 5-year follow-up, patients with high levels of PLAC2 and CDK2 showed significantly lower overall survival rate. In OC cells, overexpression of PLAC2 resulted in upregulated, while silencing of PLAC2 resulted in downregulated expression of CDK2. Cell proliferation assay showed that overexpression of PLAC2 resulted in increased, while silencing of PLAC2 resulted in decreased proliferation rate of OC cells. In addition, overexpression of CDK2 attenuated the effects of silencing of PLAC2. Conclusion: PLAC2 positively regulates CDK2 to promote OC cell proliferation.

10.
ACS Nano ; 14(8): 10544-10551, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32806048

RESUMO

The recent discovery of van der Waals magnetic materials has attracted great attention in materials science and spintronics. The preparation of ultrathin magnetic layers down to atomic thickness is challenging and is mostly by mechanical exfoliation. Here, we report vapor deposition of magnetic van der Waals NiI2 crystals. Two-dimensional (2D) NiI2 flakes are grown on SiO2/Si substrates with a thickness of 5-40 nm and on hexagonal boron nitride (h-BN) down to monolayer thickness. Temperature-dependent Raman spectroscopy reveals robust magnetic phase transitions in the as-grown 2D NiI2 crystals down to trilayer. Electrical measurements show a semiconducting transport behavior with a high on/off ratio of 106 for the NiI2 flakes. Lastly, density functional theory calculation shows an intralayer ferromagnetic and interlayer antiferromagnetic ordering in 2D NiI2. This work provides a feasible approach to epitaxy 2D magnetic transition metal halides and also offers atomically thin materials for spintronic devices.

11.
Sensors (Basel) ; 20(13)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610586

RESUMO

Recent years have witnessed the development of the applications of machine learning technologies to well logging-based lithology identification. Most of the existing work assumes that the well loggings gathered from different wells share the same probability distribution; however, the variations in sedimentary environment and well-logging technique might cause the data drift problem; i.e., data of different wells have different probability distributions. Therefore, the model trained on old wells does not perform well in predicting the lithologies in newly-coming wells, which motivates us to propose a transfer learning method named the data drift joint adaptation extreme learning machine (DDJA-ELM) to increase the accuracy of the old model applying to new wells. In such a method, three key points, i.e., the project mean maximum mean discrepancy, joint distribution domain adaptation, and manifold regularization, are incorporated into extreme learning machine. As found experimentally in multiple wells in Jiyang Depression, Bohai Bay Basin, DDJA-ELM could significantly increase the accuracy of an old model when identifying the lithologies in new wells.

12.
Dalton Trans ; 49(28): 9618-9631, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32584358

RESUMO

In this work, we perform an in-depth experimental and computational study about the structure-directing effect of two new chiral organic quaternary ammonium dications bearing two N-methyl-prolinol units linked by a xylene spacer in para or meta relative orientation, displaying four enantiopure stereogenic centers in (S) configuration. Synthesis results show that the para-xylene derivative is an efficient structure-directing agent, promoting the crystallization of ZSM-12 (in pure-silica composition), beta zeolite (as pure-silica, or in the presence of Al or Ge), and a mixture of polymorphs C, A and B of zeolite beta (in the presence of Ge). In contrast, the meta-xylene derivative showed a much poorer structure-directing activity, yielding only amorphous materials unless Ge is present in the gel, where beta and polymorph C (together with A and B) zeolites crystallized. Molecular simulations showed that the para-xylene dication displays a cylindrical shape suitable for confining in zeolite pores, while the meta-xylene derivative has an angular shape that shifts from the typical dimensions required for 12MR zeolite channels. Despite enantio-purity of the para-xylene dication with (S,S,S,S) configuration, no enrichment in polymorph A of the zeolite beta samples obtained was observed by Transmission Electron Microscopy. With the aid of molecular simulations, the failure in transferring chirality to the zeolite is explained by the loose fit of this SDA in the large-pores of zeolite beta, and a lack of close geometrical fit with the chiral element of polymorph A, as evidenced by the very similar interaction of the cation with the two enantiomorphic space groups of polymorph A. Nevertheless, the molecular-level knowledge gained in this work can provide insights for the future design of more efficient SDAs towards the synthesis of chiral zeolites.

13.
Am J Transl Res ; 12(5): 1928-1941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509188

RESUMO

Rs11614913 in pri-miR-196a-2 is involved in the occurrence of many diseases, especially in cancers. However, it remains unknown whether miR-196a-2 is associated with human recurrent spontaneous abortion (RSA) in Chinese Han population. Our study found that rs11614913 T/T in pri-miR-196a-2 was associated with the increase risk of human unexplained RSA (URSA) in recessive mode in Chinese Han population. The T allele of rs11614913 increased the production of mature miR-196a-3p. Rs11614913 T/T inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further investigation discovered that dihydrofolate reductase (DHFR) was the target of miR-196a-3p and inversely regulated by miR-196a-3p. Dual-luciferase assay indicated that T allele in miR-196a-2 rs11614913 could more effectively suppress DHFR expression than C allele. In addition, C to T substitution in miR-196a-2 rs11614913 attenuated the sensibility of cells to mifepristone. Collectively, our data suggest that miR-196a-2 rs11614913 T/T in pri-miR-196a-2 may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-196a-3p and reinforcing the expression of DHFR.

14.
Cancer Med ; 9(14): 5247-5257, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32463580

RESUMO

Transcription factors represent the crucial role of controlling gene transcription in cancer development and progression. However, their functions in gastric cancer have not been thoroughly characterized. For this study, we comprehensively evaluated the correlation between infiltration patterns of tumor microenvironment (TME) cells and TFs expression in the cohort of stomach adenocarcinoma (STAD) from TCGA database. We integrally explored differential expression panel and prognostic value of candidate TFs in TCGA-STAD cohort. Notably, we found a key transcription factor named HEYL, which its expression level was correlated with stromal component transformation of TME. HEYL was regularly high expressed in gastric cancer and correlated with patients' poor prognosis. Knockdown of HEYL prominently abrogated the tendency of cell proliferation, migration, and progression in gastric cancer. Consistently, overexpression of HEYL strikingly accelerated the gastric carcinoma development through activating oncogenic signaling pathways and transcriptional activation of cadherin 11 (CDH11). Our findings not only identified the close relationship between TFs and TME phenotype, but also emphasized the crucial importance of TFs, especially HEYL, which could be identified as a candidate biomarker to evaluate prognostic risk and therapeutic effect in gastric cancer.


Assuntos
Neoplasias Gástricas/genética , Fatores de Transcrição/metabolismo , Carcinogênese , Feminino , Humanos , Masculino , Neoplasias Gástricas/patologia , Microambiente Tumoral
15.
Appl Opt ; 59(2): 324-332, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32225310

RESUMO

Anamorphic lenses, with different optical powers along the tangential plane and the sagittal plane, are calibrated in this paper. The imaging model for anamorphic lenses is introduced. Compared with the pinhole model, it has two more intrinsic parameters: the anamorphic distance and the anamorphic angle. The anamorphic lens has two optical centers: one is in the tangential plane and the other is in the sagittal plane. The distance between the two optical centers is the anamorphic distance. The anamorphic angle refers to the angle between the camera coordinates and the pixel coordinates in the CCD plane. Formulas determining the initial value of the anamorphic distance are provided. Two experiments are conducted for the anamorphic lens calibration. As a comparison, the anamorphic lens is calibrated using the anamorphic imaging model and the pinhole model, respectively. The calibration accuracy can be improved remarkably if the anamorphic imaging model is applied, and calibrated results for the anamorphic distance and the anamorphic angle are very stable for different positions of the calibration target, which shows the validity and effectiveness of the anamorphic imaging model for anamorphic lens calibration.

16.
J Clin Lab Anal ; 34(7): e23299, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32185824

RESUMO

BACKGROUND: The study aimed to investigate the long noncoding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) and microRNA-125a (miR-125a) expressions, and further explore the role of lnc-NEAT1/miR-125a axis in predicting major adverse cardiac and cerebrovascular event (MACCE) risk in patients with unprotected left main coronary artery disease (ULMCAD) underwent coronary artery bypass grafting (CABG). METHODS: A total of 280 patients with ULMCAD underwent CABG were consecutively enrolled in our prospective study, and their plasma samples were collected before CABG for the detection of lnc-NEAT1 and miR-125a expressions by reverse transcription quantitative polymerase chain reaction. Lnc-NEAT1/miR-125a axis was calculated via dividing lnc-NEAT1 by miR-125a. After CABG, regular follow-up was continued until MACCE occurrence or 36 months. RESULTS: Lnc-NEAT1 expression, miR-125a expression, and lnc-NEAT1/miR-125a axis were 0.998 (IQR: 0.440-1.720, range: 0.116-5.771), 0.997 (IQR: 0.461-1.650, range: 0.055-3.621), and 1.018 (IQR: 0.384-2.782, range: 0.041-52.832), respectively. And lnc-NEAT1 was negatively associated with miR-125a. The 1-, 2-, and 3-year MACCE occurrence was 19 (6.8%), 29 (10.4%), and 38 (13.6%), respectively. Lnc-NEAT1/miR-125a axis (χ2  = 11.207, P = .001) and lnc-NEAT1 expression (χ2  = 5.345, P = .021) positively associated with accumulating MACCE occurrence, while miR-125a expression (χ2  = 5.869, P = .015) negatively correlated with accumulating MACCE occurrence. Notably, lnc-NEAT1/miR-125a axis presented numerically better predictive value compared with lnc-NEAT1 or miR-125a alone for MACCE risk. Furthermore, lnc-NEAT1/miR-125a axis high, elderly age, increased BMI, diabetes, previous stroke, LVEF, and higher disease extent (all P < .05) were independent predictive factors for increased accumulating MACCE occurrence. CONCLUSION: Lnc-NEAT1/miR-125a axis, as a combined index, presents potential value to be a prognostic biomarker for MACCE risk in ULMCAD management.

17.
Front Oncol ; 10: 33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117710

RESUMO

Background: Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. However, their roles in gastric cancer (GC) remain unclear. Methods: We analyzed the differential expressions of TFs and, using GC cells and tissues, investigated plexin C1 (PLXNC1) RNA levels, as well as PLXNC1's clinical relevance and functional mechanisms. The molecular function of PLXNC1 was evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS). Results: PLXNC1 was frequently up-regulated in GC and associated with poor prognosis. The expression level of PLXNC1 could serve as an independent biomarker to predict a patient's overall survival. Notably, knockdown of PLXNC1 significantly abolished GC cell proliferation, and migration, and overexpression of PLXNC1 accelerated carcinogenesis in GC. The gene set enrichment analysis (GSEA) indicated that high-expression of PLXNC1 was positively correlated with the activation of epithelial-mesenchymal transition (EMT), TNF-α, and IL-6/STAT3 signaling pathways. PLXNC1 promoted proliferation and migration of GC cells through transcriptional activation of the interleukin 6 signal transducer (IL6ST), which could rescue the malignant behavior of PLXNC1-deficient GC cells. Conclusions: Our study demonstrated that the PLXNC1 plays an oncogenic role in GC patients. The PLXNC1-IL6ST axis represents a novel potential therapeutic target for GC.

18.
Reprod Sci ; 27(1): 152-162, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046397

RESUMO

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.


Assuntos
Aborto Habitual/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Proliferação de Células/fisiologia , MicroRNAs/metabolismo , Trofoblastos/metabolismo , Adulto , Linhagem Celular , Feminino , Humanos , Gravidez , Trofoblastos/citologia , Regulação para Cima
19.
Biomolecules ; 10(2)2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033048

RESUMO

SMAD ubiquitination regulatory factor 1 (Smurf1) is a Nedd4 family E3 ubiquitin ligase that regulates cell motility, polarity and TGFß signaling. Smurf1 contains an N-terminal protein kinase C conserved 2 (C2) domain that targets cell membranes and is required for interactions with membrane-localized substrates such as RhoA. Here, we investigated the lipid-binding mechanism of Smurf1 C2, revealing a general affinity for anionic membranes in addition to a selective affinity for phosphoinositides (PIPs). We found that Smurf1 C2 localizes not only to the plasma membrane but also to negatively charged intracellular sites, acting as an anionic charge sensor and selective PIP-binding domain. Site-directed mutagenesis combined with docking/molecular dynamics simulations revealed that the Smurf1 C2 domain loop region primarily interacts with PIPs and cell membranes, as opposed to the ß-surface cationic patch employed by other C2 domains. By depleting PIPs from the inner leaflet of the plasma membrane, we found that PIP binding is necessary for plasma membrane localization. Finally, we used a Smurf1 cellular ubiquitination assay to show that the amount of ubiquitin at the plasma membrane interface depends on the lipid-binding properties of Smurf1. This study shows the mechanism by which Smurf1 C2 targets membrane-based substrates and reveals a novel interaction for non-calcium-dependent C2 domains and membrane lipids.


Assuntos
Membrana Celular/metabolismo , Fosfatidilinositóis/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Células A549 , Animais , Domínios C2 , Células COS , Chlorocebus aethiops , Células HEK293 , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Ubiquitina-Proteína Ligases/análise , Ubiquitinação
20.
Magn Reson Med ; 83(5): 1810-1824, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31605554

RESUMO

PURPOSE: Without explicit coil sensitivity information acquired by means of a reference body coil, multi-channel signal combination for water-fat separation (WFS) can be challenging due to channel-dependent phase offsets and chemical-shift dependent phase shifts. This study aims to develop a referenceless, robust, accurate, and fast channel combination method for WFS. THEORY AND METHODS: A dual-step multi-channel combination method is proposed. In the first step, channel-dependent phase offsets are estimated with a preliminary WFS estimation. In the second step, the multi-channel data are combined after removing phase offsets. Thereafter, WFS is performed to obtain final results. Numerical simulations (4-64 coils) and in vivo experiments (8, 16, 28 coils) at 3T field strength are conducted to compare the proposed method to previous methods. Channel combination with a body-coil scan serves as the reference for in vivo experiments. RESULTS: The proposed method estimates channel-dependent phase offsets accurately. It shows improved robustness to phase singularities than weighted mean and adaptive reconstruction. It is faster than adaptive reconstruction (e.g., 25.45 versus 46.34 s with 28 coils) and the channel-by-channel WFS method (e.g., 21.77 versus 50.04 s with 8 coils). It provides comparable fat quantification accuracy to the reference under various reasonable signal-to-noise ratio conditions (e.g., Pearson correlation coefficient r = 0.981 with P < 0.01, for in vivo fat fractions using flip angle = 10°). CONCLUSION: The proposed referenceless channel combination method may be beneficial to both qualitative and quantitative water-fat imaging.


Assuntos
Imageamento por Ressonância Magnética , Água , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Razão Sinal-Ruído
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