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1.
FEBS Open Bio ; 10(5): 744-751, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32069381

RESUMO

Astrocytomas often recur after surgical resection, but the underlying mechanism remains enigmatic. Elucidation of clonal evolution in primary and relapse tumors may provide important information on tumor progression. Here, we examined genetic factors underlying recurrence in a patient with astrocytoma initially diagnosed with World Health Organization (WHO) grade II astrocytoma, who then relapsed with glioblastoma (WHO grade IV) complicated with local anaplastic astrocytoma (WHO grade III). We performed genomic DNA sequencing and data analysis of paired tumor tissue specimens and a peripheral blood sample (control), and used expands software for subclone analysis. A germline NOTCH1 missense mutation was identified in the peripheral blood sample, the primary tumor and the relapse tumor; in addition, we identified a tumor protein p53 (TP53) heterozygous nonsense mutation in the primary tumor and a TP53 homozygous nonsense mutation and an IDH1 heterozygous missense mutation in the relapse tumor. Clonal evolution trees indicated higher heterogeneity in the relapse tumor. Although germline mutations might contribute to the driving force of the primary tumor, aggressive chemotherapy and radiation may apply selective pressure for tumor clonal evolution; furthermore, a total loss of function of gatekeeping genes (TP53) may result in impaired DNA repair and catastrophic chromosomal aberrations.

2.
Proc Natl Acad Sci U S A ; 117(6): 2815-2823, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31996477

RESUMO

Existing lithium-ion battery technology is struggling to meet our increasing requirements for high energy density, long lifetime, and low-cost energy storage. Here, a hybrid electrode design is developed by a straightforward reengineering of commercial electrode materials, which has revolutionized the "rocking chair" mechanism by unlocking the role of anions in the electrolyte. Our proof-of-concept hybrid LiFePO4 (LFP)/graphite electrode works with a staged deintercalation/intercalation mechanism of Li+ cations and PF6 - anions in a broadened voltage range, which was thoroughly studied by ex situ X-ray diffraction, ex situ Raman spectroscopy, and operando neutron powder diffraction. Introducing graphite into the hybrid electrode accelerates its conductivity, facilitating the rapid extraction/insertion of Li+ from/into the LFP phase in 2.5 to 4.0 V. This charge/discharge process, in turn, triggers the in situ formation of the cathode/electrolyte interphase (CEI) layer, reinforcing the structural integrity of the whole electrode at high voltage. Consequently, this hybrid LFP/graphite-20% electrode displays a high capacity and long-term cycling stability over 3,500 cycles at 10 C, superior to LFP and graphite cathodes. Importantly, the broadened voltage range and high capacity of the hybrid electrode enhance its energy density, which is leveraged further in a full-cell configuration.

3.
Exp Eye Res ; 191: 107899, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866431

RESUMO

Retinal detachment (RD) induces ischemia and oxygen deficiency in the retina and results in multiple pathological events; photoreceptor cell degeneration and death is the eventual cause of vision decline. In this study, we investigated the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) in a rat retinal detachment (RD) model. The model was developed using a subretinal injection of 1% hyaluronic acid in male Sprague-Dawley rats. MSC-Exos were sub-retinally injected at the time of retinal separation to study their therapeutic function. The retinal expression levels of inflammatory cytokines TNF-α, IL-1ß, and MCP-1 were detected by RT-PCR, the autophagy-related protein 5 (Atg5) and microtubule-associated protein 1 light chain 3 beta (LC3) were detected by Western blot, and apoptosis was examined using TUNEL assays at 3 days following RD. Retinal structure was observed at 7 days post-RD. Proteomic analysis was also performed to detect proteins carried by MSC-Exos using iTRAQ-based technology combined with one-dimensional nano LC-nano-ESI- MS/MS. We found that expression of TNF-α and IL-1ß were significantly reduced, the LC3-II to LC3-I ratio was enhanced and cleavage of Atg5 was decreased after MSC-Exo treatment. Treatment with MSC-Exos also suppressed photoreceptor cell apoptosis and maintained normal retinal structure when compared to control groups. Proteomic analysis revealed that MSC-Exos contained proteins with anti-inflammatory, neuroprotective and anti-apoptotic effects. These results suggest that MSC-Exos have therapeutic effects on RD-induced retinal injury and can be used to reduce effects of retinal detachment on photoreceptor cell degeneration in patients.

4.
Nanoscale ; 11(42): 20194-20198, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31617548

RESUMO

Here, we propose a novel nanotip microstructure which can be easily fabricated through a simply Reactive Ion Etching (RIE) process combined with anodic aluminum oxide (AAO) membranes. When combined with Ag coating and annealing on the surface of micro-sized nanotip arrays, the as-formed Ag-nanoparticles (Ag-NPs)/Si-nanotip hybrid structure exhibited a significantly high enhancement factor and highly sensitive surface enhanced Raman scattering (SERS) for rhodamine 6G molecules. The nanotip microstructure showed a sharp curvature with an apex diameter which significantly affected the SERS results. The Ag-NPs/Si-nanotip hybrid structure verified a very prominent "hot spot" effect that exists around the nanotip structures, which contributed mainly to an enhanced SERS signal with an enhancement factor (EF) of 1.6 × 106. Moreover, the Ag-NPs/Si-nanotip hybrid structure demonstrated superior sensitivity, with obvious featured Raman peaks even when the concentration was as low as 10-10 M. Our work demonstrated a feasible way to prepare a novel nanotip microstructure with a highly localized surface plasmon resonance response which could be feasibly applied for highly sensitive and reproducible SERS applications.

5.
Micromachines (Basel) ; 10(9)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489954

RESUMO

In this paper, we report a novel aluminum nitride (AlN) thin-film piezoelectric resonant accelerometer. Different from the ordinary MEMS (micro-electro-mechanical systems) resonant accelerometers, the entire structure of the accelerometer, including the mass and the springs, is excited to resonate in-plane, and the resonance frequency is sensitive to the out-plane acceleration. The structure is centrosymmetrical with serpentine electrodes laid on supporting beams for driving and sensing. The stiffness of the supporting beams changes when an out-plane inertial force is applied on the structure. Therefore, the resonance frequency of the accelerometer will also change under the inertial force. The working principle is analyzed and the properties are simulated in the paper. The proposed AlN accelerometer is fabricated by the MEMS technology, and the structure is released by an ICP isotropic etching. The resonance frequency is 24.66 kHz at a static state. The quality factor is 1868. The relative sensitivity of this accelerometer, defined as the shift in the resonance frequency per gravity unit (1 g = 9.8 m/s2) is 346 ppm/g. The linearity of the accelerometer is 0.9988. The temperature coefficient of frequency (TCF) of this accelerometer is -2.628 Hz/°C (i.e., -106 ppm/°C), tested from -40 °C to 85 °C.

6.
Sensors (Basel) ; 19(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362399

RESUMO

A novel microcantilever sensor was batch fabricated for Yersinia detection. The microcantilever surface modification method was optimized by introducing a secondary antibody to increase the number of binding sites. A novel microfluidic platform was designed and fabricated successfully. A 30 µL solution could fully react with the microcantilever surface. Those routines enhanced the binding efficiency between the target and receptor on the microcantilever. With this novel designed microfluidic platform, the specific adsorption of 107 Yersinia on the beam surface with modified F1 antibody was significantly enhanced.


Assuntos
Anticorpos/química , Técnicas Biossensoriais , Yersiniose/diagnóstico , Yersinia/isolamento & purificação , Anticorpos/imunologia , Sítios de Ligação , Humanos , Microfluídica/métodos , Propriedades de Superfície , Yersinia/química , Yersinia/imunologia , Yersiniose/imunologia , Yersiniose/microbiologia
7.
Sci Rep ; 9(1): 6854, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048730

RESUMO

Fine particulate matter 2.5 (PM2.5) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM2.5-induced inflammatory responses in mother rats, and PM2.5-induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM2.5-induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM2.5-induced modulation.

8.
Toxicol Sci ; 170(1): 95-108, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30985903

RESUMO

The bile salt export pump (BSEP, ABCB11) mediates bile acid efflux from hepatocytes into bile. Although the inhibition of BSEP has been implicated as an important mechanism of drug-induced liver injury (DILI), liver injury caused by BSEP-inhibiting drugs is rarely reproduced in experimental animals, probably due to species differences in bile acid composition between humans and rodents. In this study, we tested whether supplementation with chenodeoxycholic acid (CDCA) sodium, a hydrophobic bile salt, could sensitize rats to liver injury caused by a BSEP-inhibiting drug. A potent BSEP inhibitor, ketoconazole (KTZ), which is associated with clinical DILI, was intragastrically administered simultaneously with CDCA at a nontoxic dose once a day for 3 days. Plasma transaminase levels significantly increased in rats receiving CDCA+KTZ, whereas neither treatment with CDCA alone, KTZ alone nor a combination of CDCA and miconazole, a safe analog to KTZ, induced liver injury. In CDCA+KTZ-treated rats, most bile acid species in the liver significantly increased compared with treatment with vehicle or CDCA alone, suggesting that KTZ administration inhibited bile acid excretion. Furthermore, hepatic mRNA expression levels of a bile acid synthesis enzyme, Cyp7a1, and a basolateral bile salt influx transporter, Ntcp, decreased, whereas a canalicular phosphatidylcholine flippase, Mdr2, increased in the CDCA+KTZ group to compensate for hepatic bile acid accumulation. In conclusion, we found that oral CDCA supplementation predisposed rats to KTZ-induced liver injury due to the hepatic accumulation of bile acids. This method may be useful for assessing the potential of BSEP-inhibiting drugs inducing liver injury in vivo.

9.
Oral Dis ; 25(6): 1581-1588, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31009146

RESUMO

OBJECTIVES: Mitophagy is an important mitochondrial quality control mechanism. In this study, we investigated the mitochondrial damage and mitophagy occurred in inflammatory human dental pulp and lipopolysaccharide-stimulated preodontoblasts. MATERIALS AND METHODS: In dental pulp tissues and lipopolysaccharide-stimulated preodontoblasts, immunofluorescences and Western blot were performed to detect the expression of mitochondrial and mitophagy-related proteins, and autophagy markers were also examined. Reactive oxygen species generated by mitochondria were examined by MitoSOX. Transmission electron microscope (TEM) was used to examine the morphology of mitochondria in lipopolysaccharide-stimulated preodontoblasts. RESULTS: The active fission activity of mitochondria and mitophagy in inflammatory dental pulp was observed. In lipopolysaccharide-treated preodontoblasts, mitophagy-related proteins were also upregulated. Moreover, increased reactive oxygen species in the inflamed preodontoblasts were observed. Additionally, single-membrane autolysosomes containing partially degraded mitochondria with swollen inner membranes in lipopolysaccharide-treated preodontoblasts were observed by TEM. CONCLUSIONS: These results indicate that mitochondria were damaged and mitophagy might be activated to degrade impaired mitochondria in inflamed odontoblasts.


Assuntos
Dilatação Mitocondrial , Odontoblastos , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
10.
ACS Appl Mater Interfaces ; 11(5): 5373-5379, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30632744

RESUMO

An ingeniously designed porous structure can synergistically optimize the desired properties and maximize the advantages of a material as an electrode for a high-performance energy storage system. The active material with a porous nanostructure could reduce the ion diffusion path and buffer the strain caused by the volume changes during cycling. Furthermore, combining the active material with a three-dimensional (3D) graphene aerogel (GA) matrix is an ideal way to maintain the structural integrity, improve the conductivity, and overcome the aggregation problem of the nanomaterials. Herein, we adopted a facile template-based strategy to derive a composite of 3D hierarchically porous cobalt phosphide nanocubes with a graphene aerogel (CoP@GA). The as-prepared CoP@GA features porous cobalt phosphide nanocubes that are firmly encapsulated and uniformly distributed in the well-defined graphene aerogel skeleton. Benefiting from the hierarchical porosity, structural integrity, and conductive network, the CoP@GA electrode manifests an ultrahigh initial Coulombic efficiency (88.6%), outstanding lithium storage performance in terms of excellent cycling performance (805.3 mAh·g-1 after 200 cycles at 200 mA·g-1), superior high-energy performance (351.8 mAh·g-1 after 4000 cycles at 10 A·g-1), and exceptional rate capability. Moreover, this synthesis protocol could be an instructive precedent for fabricating transition-metal-phosphide-based 3D porous composites with excellent electrochemical performances.

11.
Micromachines (Basel) ; 9(2)2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30393357

RESUMO

A novel design of piezoelectric aluminum nitride (AlN)-Si composite cantilever gyroscope is proposed in this paper. The cantilever is stimulated to oscillate in plane by two inverse voltages which are applied on the two paralleled drive electrodes, respectively. The whole working principles are deduced, which based on the piezoelectric equation and elastic vibration equation. In this work, a cantilever gyroscope has been simulated and optimized by COMSOL Multiphysics 5.2a. The drive mode frequency is 87.422 kHz, and the sense mode frequency is 87.414 kHz. The theoretical sensitivity of this gyroscope is 0.145 pm/◦/s. This gyroscope has a small size and simple structure. It will be a better choice for the consumer electronics.

12.
Nanoscale Res Lett ; 13(1): 332, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30353230

RESUMO

As three-dimensional (3D) nanostructures can significantly improve the absorption capacity of photons, it is widely used in various photovoltaic devices. However, the high-cost and complex preparation process of traditional 3D nanostructures restricted its development greatly. In this paper, a new type of nanocone cluster microstructure was prepared on polydimethylsiloxane (PDMS) substrate by using a simple template process. This novel nanocone cluster microstructure can significantly improve the light transmittance and reduce the light reflection, showing superior anti-reflection property. In the whole range of visible band, the nanocone cluster microstructure effectively reduces the reflectivity of the light, so that it remains below 3.5%. In addition, this kind of cluster microstructure showed excellent superhydrophobic property and self-cleaning ability with the contact angle of 151°.

13.
Am J Transl Res ; 10(8): 2677-2684, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210704

RESUMO

Periapical lesions are the distinct result of chronic root canal infection and could generate severe bone resorption surrounding apical regions. Despite the local cytokine and cell-mediated immune responses, periapical lesions are also characterized by its auto-restrict inflammation. However, the detailed mechanism related to its auto-restriction of immune response is still unclear. Co-inhibitory immune checkpoints are important molecules which could negatively modulate immune response especially in T cell function. In this study we detected the expressional pattern of PD-1/LAG-3 in periapical lesions. Immunohistochemical staining showed that the inflammatory response including up-regulation of TNF-α and the infiltration of T cells, was severe in granuloma and restricted in periapical cyst. PD-1 and LAG-3 both could be detected in granuloma and cyst, while scarcely observed in control group. Exhausted T cells, characterized by PD-1 or LAG-3 positive, accumulated within granuloma and reduced in cyst. Our study revealed that in periapical lesions, T cell exhaustion characterized by PD-1 or LAG-3 positive, might contribute to the auto-restriction of inflammatory response in periapical lesions.

14.
Nanomaterials (Basel) ; 8(6)2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891767

RESUMO

With high power density, fast charging-discharging speed, and a long cycling life, supercapacitors are a kind of highly developed novel energy-storage device that has shown a growing performance and various unconventional shapes such as flexible, linear-type, stretchable, self-healing, etc. Here, we proposed a rational design of thin film, flexible micro-supercapacitors with in-plane interdigital electrodes, where the electrodes were fabricated using the oblique angle deposition technique to grow oblique Ni/NiO nanowire arrays directly on polyimide film. The obtained electrodes have a high specific surface area and good adhesion to the substrate compared with other in-plane micro-supercapacitors. Meanwhile, the as-fabricated micro-supercapacitors have good flexibility and satisfactory energy-storage performance, exhibiting a high specific capacity of 37.1 F/cm³, a high energy density of 5.14 mWh/cm³, a power density of up to 0.5 W/cm³, and good stability during charge-discharge cycles and repeated bending-recovery cycles, respectively. Our micro-supercapacitors can be used as ingenious energy storage devices for future portable and wearable electronic applications.

15.
Sensors (Basel) ; 18(4)2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29597284

RESUMO

With an aim to reduce the cost of prototype development, this paper establishes a PSPICE hybrid model for the simulation of capacitive microelectromechanical systems (MEMS) gyroscopes. This is achieved by modeling gyroscopes in different modules, then connecting them in accordance with the corresponding principle diagram. Systematic simulations of this model are implemented along with a consideration of details of MEMS gyroscopes, including a capacitance model without approximation, mechanical thermal noise, and the effect of ambient temperature. The temperature compensation scheme and optimization of interface circuits are achieved based on the hybrid closed-loop simulation of MEMS gyroscopes. The simulation results show that the final output voltage is proportional to the angular rate input, which verifies the validity of this model.

16.
Nanomaterials (Basel) ; 8(2)2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29385759

RESUMO

Heavily boron-doped silicon layers and boron etch-stop techniques have been widely used in the fabrication of microelectromechanical systems (MEMS). This paper provides an introduction to the fabrication process of nanoscale silicon thermoelectric devices. Low-dimensional structures such as silicon nanowire (SiNW) have been considered as a promising alternative for thermoelectric applications in order to achieve a higher thermoelectric figure of merit (ZT) than bulk silicon. Here, heavily boron-doped silicon layers and boron etch-stop processes for the fabrication of suspended SiNWs will be discussed in detail, including boron diffusion, electron beam lithography, inductively coupled plasma (ICP) etching and tetramethylammonium hydroxide (TMAH) etch-stop processes. A 7 µm long nanowire structure with a height of 280 nm and a width of 55 nm was achieved, indicating that the proposed technique is useful for nanoscale fabrication. Furthermore, a SiNW thermoelectric device has also been demonstrated, and its performance shows an obvious reduction in thermal conductivity.

17.
Micromachines (Basel) ; 10(1)2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30597830

RESUMO

A MEMS fabrication process with through-glass vias (TGVs) by laser drilling was presented, and reliability concerns about MEMS packaging with TGV, likes debris and via metallization, were overcome. The via drilling process on Pyrex 7740 glasses was studied using a picosecond laser with a wavelength of 532 nm. TGVs were tapered, the minimum inlet diameter of via holes on 300 µm glasses was 90 µm, and the relative outlet diameter is 48 µm. It took about 9 h and 58 min for drilling 4874 via holes on a four-inch wafer. Debris in ablation was collected only on the laser inlet side, and the outlet side was clean enough for bonding. The glass with TGVs was anodically bonded to silicon structures of MEMS sensors for packaging, electron beam evaporated metal was used to cover the bottom, the side, and the surface of via holes for vertical electrical interconnections. The metal was directly contacted to silicon with low contact resistance. A MEMS gyroscope was made in this way, and the getter was used for vacuum maintenance. The vacuum degree maintained under 1 Pa for more than two years. The proposed MEMS fabrication flow with a simple process and low cost is very suitable for mass production in industry.

18.
Sensors (Basel) ; 19(1)2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30597879

RESUMO

A novel three-dimensional (3D) hermetic packaging technique suitable for capacitive microelectromechanical systems (MEMS) sensors is studied. The composite substrate with through silicon via (TSV) is used as the encapsulation cap fabricated by a glass-in-silicon (GIS) reflow process. In particular, the low-resistivity silicon pillars embedded in the glass cap are designed to serve as the electrical feedthrough and the fixed capacitance plate at the same time to simplify the fabrication process and improve the reliability. The fabrication process and the properties of the encapsulation cap were studied systematically. The resistance of the silicon vertical feedthrough was measured to be as low as 263.5 mΩ, indicating a good electrical interconnection property. Furthermore, the surface root-mean-square (RMS) roughnesses of glass and silicon were measured to be 1.12 nm and 0.814 nm, respectively, which were small enough for the final wafer bonding process. Anodic bonding between the encapsulation cap and the silicon wafer with sensing structures was conducted in a vacuum to complete the hermetic encapsulation. The proposed packaging scheme was successfully applied to a capacitive gyroscope. The quality factor of the packaged gyroscope achieved above 220,000, which was at least one order of magnitude larger than that of the unpackaged. The validity of the proposed packaging scheme could be verified. Furthermore, the packaging failure was less than 1%, which demonstrated the feasibility and reliability of the technique for high-performance MEMS vacuum packaging.

19.
Biomed Microdevices ; 18(6): 110, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27834053

RESUMO

Early liver cancer diagnosis has clinical significance in treating cancer. Joint detection of multiple biomarkers has been considered as an effective and reliable method for early cancer diagnosis. In this work, a novel biosensor based on microcantilever array was batch-fabricated for multiple liver cancer biomarkers detection with high sensitivity, high accuracy, high throughput, and high specification. A micro-cavity was designed in the free end of the cantilever for local reaction between antibody and antigen, which can dramatically reduce the effect of adsorption-induced stiffness coefficient k variation. Furthermore,the pillar arrays in the micro-cavity were designed for increasing detection upper limit. A linear relationship between the relative frequency shift and the antigen concentration was observed for three liver cancer biomarkers, alpha-fetoprotein (AFP), γ-glutamyltranspeptidase II (GGT-2), and hepatocyte growth factor (HGF). Slight cross-reaction response to different antigens ensures high specificity of the sensor. These features will promote clinical application of the cantilever sensors in early cancer diagnosis.


Assuntos
Detecção Precoce de Câncer/instrumentação , Neoplasias Hepáticas/diagnóstico , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/metabolismo , Reações Cruzadas , Humanos , Neoplasias Hepáticas/sangue , Microtecnologia , Sensibilidade e Especificidade
20.
Tumour Biol ; 37(9): 12609-12618, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27405564

RESUMO

Unlike genetic aberrations, epigenetic alterations do not modify the deoxyribonucleic acid (DNA) coding sequence and can be reversed pharmacologically. Identifying a particular epigenetic alteration such as abnormal DNA methylation may provide better understanding of cancers and improve current therapy. In a Chinese pedigree with colorectal carcinoma and acute myeloid leukemia, we examined the genome-wide DNA methylation level of cases and explored the role of methylation in pathogenesis and progression. DNA methylation status in the four cases, which all harbor a MLL3 germline mutation, differed from that of the normal control, and hypermethylation was more prevalent. Also, more CpG sites were hypermethylated in the acute-phase AML patient than in the AML patient in remission. Fifty-nine hyper- or hypomethylated genes were identified as common to all four cases. Genome-wide DNA methylation analysis demonstrated that differentially methylated sites among acute myeloid leukemia and colorectal carcinoma cases and the control were in both promoters (CpG island) and gene body regions (shelf/shore areas). Hypermethylation was more prevalent in cancer cases. The study supports the suggestion that the level of DNA methylation changes in AML progression.


Assuntos
Neoplasias Colorretais/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Leucemia Mieloide Aguda/genética , Linhagem , Adulto , Ilhas de CpG , Humanos , Masculino
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