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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.
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Colangiocarcinoma/genética , Proteínas de Unión al GTP/genética , Metiltransferasas/genética , Biosíntesis de Proteínas , Animales , Carcinogénesis/genética , Colangiocarcinoma/patología , Progresión de la Enfermedad , Receptores ErbB/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Ratones , Procesamiento Postranscripcional del ARN/genética , ARN Mensajero/genética , ARN de Transferencia/genéticaRESUMEN
BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is an important curative therapy in hepatocellular carcinoma (HCC), but recurrence rate remains as high as all the other HCC therapeutic modalities. Methyltransferase 1 (METTL1), an enzyme for m 7 G tRNA modification, was reported to promote HCC development. Here, we assessed the role of METTL1 in shaping the immunosuppressive tumor microenvironment after insufficient RFA (iRFA). APPROACH AND RESULTS: By immunohistochemistry and multiplex immunofluorescence (mIF) staining, we showed that METTL1 expression was enhanced in post-RFA recurrent HCC, accompanied by increased CD11b + CD15 + polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and decreased CD8 + T cells. Mechanistically, heat-mediated METTL1 upregulation enhanced TGF-ß2 translation to form the immunosuppressive environment by induction of myeloid-derived suppressor cell. Liver-specific overexpression or knockdown of Mettl1 significantly affected the accumulation of PMN-MDSCs and subsequently affected CD8 + T cell infiltration. Complete RFA successfully eliminated the tumor, whereas iRFA-treated mice exhibited enhanced tumor growth and metastasis with increased PMN-MDSC accumulation and decreased CD8 + T cells compared to sham surgery. Interrupting METTL1-TGF-ß2-PMN-MDSC axis by anti-Ly6G antibody, or knockdown of hepatoma-intrinsic Mettl1 or Tgfb2 , or TGF-ß signaling blockade significantly mitigated tumor progression induced by iRFA and restored CD8 + T cell population. CONCLUSIONS: Our study sheds light on the pivotal role of METTL1 in modulating an immunosuppressive microenvironment and demonstrated that interrupting METTL1-TGF-ß2-PMN-MDSC axis could be a therapeutic strategy to restore antitumor immunity and prevent HCC recurrence after RFA treatment, meriting further clinical studies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supresoras de Origen Mieloide , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Células Supresoras de Origen Mieloide/metabolismo , Neoplasias Hepáticas/patología , Factor de Crecimiento Transformador beta2/metabolismo , Microambiente TumoralRESUMEN
Layered double hydroxides (LDHs) have garnered significant attention from researchers in the field of adsorption due to their unique laminated structures and ion exchange properties. LDHs with various anion intercalation showed different adsorption effects on adsorbing ions, but the corresponding adsorption mechanisms are ambiguous. In this study, three types of NiAl-LDHs were synthesized, utilizing NO3-, CO32-, or Cl- as the interlayer anions. Batch tests were conducted to study their adsorption performances for Br-. Among them, the LDH with a NO3- intercalation layer exhibited the highest adsorption capacity for Br-, reaching up to 1.40 mmol g-1. The adsorption kinetics, mechanism, and renewability of these NiAl-LDHs were systematically compared. As a result, the type of Br- adsorption by all three materials was single molecular layer chemisorption. Moreover, the thermodynamic results of adsorption suggested that the adsorption of Br- was a spontaneous exothermic process. X-ray photoelectron spectroscopy, X-ray diffraction, and point of zero charge analysis collectively indicated that the adsorption of Br- by LDHs primarily occurred through interlayer ion exchange and electrostatic interactions. Structural characterizations of the adsorbents revealed that Br- entered the interlayers of the three LDHs, causing varying degrees of reduction in the interlayer spacing. Density functional theory calculations indicated that the interlayer binding energy of LDH with NO3- intercalation was the lowest, thereby making it more susceptible NO3- to be exchanged with Br-. Finally, the stability of the NiAl-LDHs was studied. The NiAl-LDHs retains a high removal efficiency of Br- even after 5 cycles of adsorption and desorption.
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Rubidium (Rb) and cesium (Cs) have important applications in highly technical fields. Salt lakes contain huge reserves of Rb and Cs with industrial significance, which can be utilized after extraction. In this study, a composite magnetic adsorbent (Fe3O4@ZIF-8@AMP, AMP = ammonium phosphomolybdate) was prepared and its adsorption properties for Rb+ and Cs+ were studied in simulated and practical brine. The structure of the adsorbent was characterized by SEM, XRD, N2 adsorption-desorption, FT-IR, and vibrating sample magnetometer (VSM). The adsorbent had good adsorption affinity for Rb+ and Cs+. The Langmuir model and pseudo-second-order dynamics described the adsorbing isotherm and kinetic dates, respectively. The adsorption capacity and adsorption rate of Fe3O4@ZIF-8@AMP were increased by 1.86- and 2.5-fold compared with those of powdered crystal AMP, owing to the large specific surface area and high dispersibility of the adsorbent in the solution. The adsorbent was rapidly separated from the solution within 17 s using an applied magnetic field owing to the good magnetic properties. The composite adsorbent selectively adsorbed Rb+ and Cs+ from the practical brine even in the presence of a large number of coexisting ions. The promising adsorbent can be used to extract Rb+ and Cs+ from aqueous solutions.
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Intrahepatic cholangiocarcinoma (ICC) is a deadly cancer with rapid tumor progression. While hyperactive mRNA translation caused by mis-regulated mRNA or tRNA modifications promotes ICC development, the role of rRNA modifications remains elusive. Here, we found that 18S rRNA m6A modification and its methyltransferase METTL5 were aberrantly upregulated in ICC and associated with poorer survival (log rank test, p < 0.05). We further revealed the critical role of METTL5-mediated 18S rRNA m6A modification in regulation of ICC cell growth and metastasis using loss- and gain-of function assays in vitro and in vivo. The oncogenic function of METTL5 is corroborated using liver-specific knockout and overexpression ICC mouse models. Mechanistically, METTL5 depletion impairs 18S rRNA m6A modification that hampers ribosome synthesis and inhibits translation of G-quadruplex-containing mRNAs that are enriched in the transforming growth factor (TGF)-ß pathway. Our study uncovers the important role of METTL5-mediated 18S rRNA m6A modification in ICC and unravels the mechanism of rRNA m6A modification-mediated oncogenic mRNA translation control.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Animales , Ratones , ARN Ribosómico 18S/genética , ARN Ribosómico 18S/metabolismo , Colangiocarcinoma/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Biosíntesis de Proteínas , Línea Celular TumoralRESUMEN
OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC) exhibits very low response rate to immune checkpoint inhibitors (ICIs) and the underlying mechanism is largely unknown. We investigate the tumour immune microenvironment (TIME) of ICCs and the underlying regulatory mechanisms with the aim of developing new target to inhibit tumour growth and improve anti-programmed cell death protein-1 (PD-1) efficacy. DESIGN: Tumour tissues from patients with ICC together with hydrodynamic ICC mouse models were employed to identify the key cell population in TIME of ICCs. Functional analysis and mechanism studies were performed using cell culture, conditional knockout mouse model and hydrodynamic transfection ICC model. The efficacy of single or combined therapy with anti-PD-1 antibody, gene knockout and chemical inhibitor were evaluated in vivo. RESULTS: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in advanced ICCs and significantly correlated with N7-methylguanosine tRNA methyltransferase METTL1. Using diverse in vivo cancer models, we demonstrate the crucial immunomodulator function of METTL1 in regulation of PMN-MDSC accumulation in TIME and ICC progression. Mechanistically, CXCL8 in human and Cxcl5 in mouse are key translational targets of METTL1 that facilitate its function in promoting PMN-MDSC accumulation in TIME and ICC progression in vivo. Co-blockade of METTL1 and its downstream chemokine pathway enhances the anti-PD-1 efficacy in ICC preclinical mouse models. CONCLUSIONS: Our data uncover novel mechanisms underlying chemokine regulation and TIME shaping at the layer of messenger RNA translation level and provide new insights for development of efficient cancer immunotherapeutic strategies.
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Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Ratones , Animales , Guanosina/metabolismo , ARN de Transferencia/metabolismo , Microambiente Tumoral , Línea Celular TumoralRESUMEN
BACKGROUND: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. METHODS: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. RESULTS: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0-3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. CONCLUSIONS: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.
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Edema Encefálico , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Humanos , Animales , Ratas , Análisis de Expresión Génica de una Sola Célula , Corteza Cerebral , Infarto de la Arteria Cerebral MediaRESUMEN
Compared with their younger counterparts, older adults are inclined to allocate more attentional resources to positive over negative materials. This age-related positivity effect has been reported in various experimental paradigms; however, studies have not investigated the attention stage at which it appears or its potential neural mechanism. Thus, we investigated the time and frequency domain dynamics of younger and older adults during emotional attention processes. We obtained electroencephalography oscillation and event-related potential data for 20 older and 20 younger participants while they performed an emotional dot-probe task. We focused our time and frequency domain dynamics analyses on the posterior regions as a key structure for facial emotion perception and the frontal regions as a crucial structure for cognitive control. In the time domain, older adults showed an initial attentional shift to happy-related stimuli, whereas their younger counterparts did not demonstrate emotional modulation, as reflected by the N2pc component. The time-frequency decomposition was analyzed for the N2pc time window. The results showed that compared with younger adults, older adults showed an increased alpha power for happy faces in the right-posterior regions. Moreover, a parallel pattern was seen in frontal theta activity. The current findings highlight how electrocortical activity of the brain might moderate the tendency to prioritize positive information among healthy older adults. The emergence of an age-related positivity effect may be related to frontal cognitive control processing. These findings provide insight into the prevention and treatment of unsuccessful aging, such as late-life depression and anxiety.
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Atención , Emociones , Humanos , Anciano , Felicidad , Ansiedad/psicología , Envejecimiento/psicología , Expresión FacialRESUMEN
BACKGROUND AND AIM: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive disease with the underlying mechanisms poorly understood. YTHDF1, an N6 -methyladenosine (m6 A) reader protein, has important physiological functions in regulation of tumor development. However, the effect of YTHDF1 on ICC progression remains unknown yet. METHODS: The expression level of YTHDF1 in human ICC tissue was examined in The Cancer Genome Atlas database and our cohort. The role of YTHDF1 was detected using two human ICC cell lines in vitro. An ICC tumorigenesis mouse model was established via hydrodynamic transfection of AKT/YAP plasmids. m6 A sequencing, RNA immunoprecipitation sequencing, and RNA sequencing were carried out to explore the mechanism of YTHDF1 modulating ICC progression. RESULTS: Here, we find that YTHDF1 is upregulated in ICC and associated with shorter survival of ICC patients. Depletion of YTHDF1 inhibits cell proliferation, migration, and invasion, while overexpression of wild-type YTHDF1, but not m6 A reader domain mutant YTHDF1, significantly enhances tumor cell growth and aggressive abilities in vitro. Moreover, overexpression of YTHDF1 promotes the AKT/YAP transfection-induced orthotopic ICC tumorigenesis and progression in vivo. Mechanistically, we identify that YTHDF1 regulates the translation of epidermal growth factor receptor (EGFR) mRNA via binding m6 A sites in the 3'-UTR of EGFR transcript, thus leading to aberrant activities of downstream signal pathways that impact tumor progression. CONCLUSIONS: Our data uncover the oncogenic function and m6 A reader-dependent mechanism of YTHDF1 in regulation of ICC progression. Restricting abnormal oncogenic mRNA translation by targeting YTHDF1 may be a novel and promising strategy for ICC treatment.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Animales , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Carcinogénesis , Línea Celular Tumoral , Colangiocarcinoma/patología , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Ratones , Biosíntesis de Proteínas , Proteínas Proto-Oncogénicas c-akt , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
The cotton bollworm, Helicoverpa armigera, is one of the most destructive agricultural pests in the world, infesting cotton, maize, soybean, and many other crops. In recent years, H. armigera has been observed damaging walnuts, Juglans regia, in Xinjiang China. Here we examine the chemical perception by H. armigera of the marginal host J. regia. In Y-tube olfactometer tests, we found H. armigera females and males both showed significant behavioral responses to odors from walnut branches. Furthermore, nine electrophysiologically active volatiles (α-pinene, ß-pinene, myrcene, limonene, eucalyptol, ocimene, ß-caryophyllene, (E)-ß-farnesene, and germacrene D) were identified from walnuts with gas chromatography coupled with electroantennography (GC-EAD) and gas chromatography-mass spectrometry (GC-MS). Among these volatiles, ß-pinene and eucalyptol were released in relatively higher amounts. In electroantennogram (EAG) dose-dependent trials, all compounds evoked responses in H. armigera adults when tested at high concentrations, with germacrene D evoking the greatest response. In wind tunnel tests, H. armigera females preferred eight of the electrophysiologically active volatile dilutions compared with clean air, while males showed preference for only five compounds. As such we describe the chemical recognition of H. armigera for walnut, a marginal host. This study contributes to understanding the interaction between polyphagous pests and their host plants.
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Juglans , Mariposas Nocturnas , Animales , Productos Agrícolas , Eucaliptol , Femenino , Cromatografía de Gases y Espectrometría de Masas , Masculino , Mariposas Nocturnas/fisiología , Odorantes/análisis , PercepciónRESUMEN
Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.
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Antimaláricos/farmacología , Artemisininas/farmacología , Resistencia a Medicamentos/efectos de los fármacos , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Resistencia a Medicamentos/genética , Estudio de Asociación del Genoma Completo , Modelos Moleculares , Mutación , Fosfatidilinositol 3-Quinasa/química , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Protozoarias/antagonistas & inhibidores , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
Metal halide perovskite has attracted enhanced interest for its diverse electronic and optoelectronic applications. However, the fabrication of micro- or nanoscale crystalline perovskite functional devices remains a great challenge due to the fragility, solvent, and heat sensitivity of perovskite crystals. Here, a strategy is proposed to fabricate electronic and optoelectronic devices by directly growing perovskite crystals on microscale metallic structures in liquid phase. The well-contacted perovskite/metal interfaces ensure these heterostructures serve as high-performance field effect transistors (FETs) and excellent photodetector devices. When serving as an FET, the on/off ratio is as large as 106 and the mobility reaches up to ≈2.3 cm2 V-1 s-1 . A photodetector is displayed with high photoconductive switching ratio of ≈106 and short response time of ≈4 ms. Furthermore, the photoconductive response is proved to be band-bending-assisted separation of photoexcited carriers at the Schottky barrier of the silver and p-type perovskites.
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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.
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Imagen por Resonancia Magnética , Agua , Aumento de la Imagen , Interpretación de Imagen Asistida por Computador , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Relación Señal-RuidoRESUMEN
MicroRNAs (miRNAs) regulate diverse cellular processes such as cell differentiation, proliferation and apoptosis. Mutation in miRNAs results in various pathological conditions such as inflammation, viral infections, neurodegeneration, and autoimmunity. We have evaluated the association of miR-423 rs6505162C>A and rs8067576 A>T among patients with recurrent pregnancy loss (RPL) and controls from North China. Our study found that one SNP rs6505162C>A in miR-423 coding region was associated with the increase risk of humanunexplained RPL (URPL), but no differences were found in another SNP rs8067576 A>T. However, in two-locus haplotype analysis, miR-423-CC/TT haplotype was associated with an increased risk of URPL. The level of mature miR-423 was obviously down-regulated in cells transfected with miR-423-CC/TT haplotype. miR-423-CC/TT haplotype inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that mesoderm development candidate 1 (MESDC1) was a functionally relevant target of miR-423, and its expression was reversely regulated by miR-423. More importantly, dual-luciferase assay indicated miR-423-CC/TT haplotype decreasing miR-423 expression, could up-regulate MESDC1 expression. Collectively, our data suggest that miR-423-CC/TT haplotype in pre-miR-423 may aggravate the risk of developing URPL by influencing the level of mature miR-423 and its target gene MESDC1.
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Aborto Habitual/genética , Pueblo Asiatico/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Regiones no Traducidas 3'/genética , Apoptosis/genética , Secuencia de Bases , Línea Celular , Movimiento Celular/genética , Proliferación Celular , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/química , MicroARNs/metabolismo , Mifepristona/farmacología , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Conformación de Ácido Nucleico , Embarazo , Progesterona/farmacología , Factores de RiesgoRESUMEN
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.
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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.
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Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/cirugía , MicroARNs/genética , ARN Largo no Codificante/genética , Anciano , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Expresión Génica , Humanos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/sangreRESUMEN
BACKGROUND: This study aimed to explore the associations of common inflammatory cytokine levels with restenosis and rapid angiographic stenotic progression (RASP) risk in coronary artery disease (CAD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: Two hundred and ten CAD patients underwent PCI with DES were consecutively recruited, then pre-operative serum levels of TNF-α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, and IL-23 were determined by ELISA. The 12-month in-stent restenosis and RASP of non-intervened lesion were assessed by quantitative coronary angiography analysis. RESULTS: The pre-operative TNF-α, IL-6, IL-17A, and IL-23 expressions were increased while IL-4 expression was decreased in restenosis patients compared with non-restenosis patients. Further analysis revealed that IL-6, IL-8, hypercholesteremia, diabetes mellitus, and HsCRP could independently predict restenosis risk, and subsequent ROC curve revealed that their combination was able to differentiate restenosis patients from non-restenosis patients with an AUC of 0.951 (95%CI: 0.925-0.978). Meanwhile, the pre-operative TNF-α, IL-6, IL-17A, IL-21, and IL-23 expressions were increased whereas IL-4 level was decreased in RASP patients compared with non-RASP patients. Further analysis revealed that TNF-α, IL-6, IL-23, hypercholesteremia, SUA, HsCRP, and multivessel artery lesions could independently predict RASP risk, and subsequent ROC curve disclosed that their combination could discriminate RASP patients from non-RASP patients with an AUC of 0.886 (95%CI: 0.841-0.931). CONCLUSIONS: This study unveils the potentiality of pre-operative circulating inflammatory cytokines as markers for predicting restenosis and RASP risk in CAD patients underwent PCI with DES.
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Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/sangre , Citocinas/sangre , Progresión de la Enfermedad , Stents Liberadores de Fármacos , Mediadores de Inflamación/sangre , Intervención Coronaria Percutánea , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Reestenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Curva ROC , Factores de RiesgoRESUMEN
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.
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PURPOSE: To compare the ability of radiological semantic and quantitative texture features in lung cancer diagnosis of pulmonary nodules. MATERIALS AND METHODS: A total of N = 121 subjects with confirmed non-small-cell lung cancer were matched with 117 controls based on age and gender. Radiological semantic and quantitative texture features were extracted from CT images with or without contrast enhancement. Three different models were compared using LASSO logistic regression: "CS" using clinical and semantic variables, "T" using texture features, and "CST" using clinical, semantic, and texture variables. For each model, we performed 100 trials of fivefold cross-validation and the average receiver operating curve was accessed. The AUC of the cross-validation study (AUCCV) was calculated together with its 95% confidence interval. RESULTS: The AUCCV (and 95% confidence interval) for models T, CS, and CST was 0.85 (0.71-0.96), 0.88 (0.77-0.96), and 0.88 (0.77-0.97), respectively. After separating the data into two groups with or without contrast enhancement, the AUC (without cross-validation) of the model T was 0.86 both for images with and without contrast enhancement, suggesting that contrast enhancement did not impact the utility of texture analysis. CONCLUSIONS: The models with semantic and texture features provided cross-validated AUCs of 0.85-0.88 for classification of benign versus cancerous nodules, showing potential in aiding the management of patients. KEY POINTS: ⢠Pretest probability of cancer can aid and direct the physician in the diagnosis and management of pulmonary nodules in a cost-effective way. ⢠Semantic features (qualitative features reported by radiologists to characterize lung lesions) and radiomic (e.g., texture) features can be extracted from CT images. ⢠Input of these variables into a model can generate a pretest likelihood of cancer to aid clinical decision and management of pulmonary nodules.
Asunto(s)
Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmón/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Semántica , Tomografía Computarizada por Rayos X/métodos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
Photodetectors have widespread applications in fields including telecommunications, thermal imaging and bio-medical imaging. The photogating effect, arising from charge trapping at defects and/or interfaces, can have extremely high photoelectric gain which can be a benefit to high-sensitivity room temperature photodetection. Here, we introduce thin layered organic charge transfer complexes (CPXs) integrated on graphene transistors for the development of hybrid phototransistors with ultra-high photoresponsivity of â¼106 A W-1 in the near infrared (NIR) region at room temperature. Our study has demonstrated a graphene-organic CPX with a broadband photoresponse ranging from the visible to the NIR region. The high photoelectric gain was from the photogating effect at the graphene/CPX interface. In addition, the photoresponse properties of the graphene-organic CPX can be regulated by electrical gating of graphene.