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1.
Dev Cell ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776924

RESUMO

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

2.
Entropy (Basel) ; 26(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539718

RESUMO

Sustainable development is a practical path to optimize industrial structures and enhance investment efficiency. Investigating risk contagion within ESG industries is a crucial step towards reducing systemic risks and fostering the green evolution of the economy. This research constructs ESG industry indices, taking into account the possibility of extreme tail risks, and employs VaR and CoVaR as measures of tail risk. The TENET network approach is integrated to to capture the structural evolution and direction of information flow among ESG industries, employing information entropy to quantify the topological characteristics of the network model, exploring the risk transmission paths and evolution patterns of ESG industries in an extreme tail risk event. Finally, Mantel tests are conducted to examine the existence of significant risk spillover effects between ESG and traditional industries. The research finds strong correlations among ESG industry indices during stock market crash, Sino-US trade frictions, and the COVID-19 pandemic, with industries such as the COAL, CMP, COM, RT, and RE playing key roles in risk transmission within the network, transmitting risks to other industries. Affected by systemic risk, the information entropy of the TENET network significantly decreases, reducing market information uncertainty and leading market participants to adopt more uniform investment strategies, thus diminishing the diversity of market behaviors. ESG industries show resilience in the face of extreme risks, demonstrating a lack of significant risk contagion with traditional industries.

3.
Nat Commun ; 15(1): 1497, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374257

RESUMO

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

4.
Sci Adv ; 9(48): eadi7375, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38019913

RESUMO

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.


Assuntos
Eritropoese , Síndromes Mielodisplásicas , Animais , Humanos , Camundongos , Eritropoese/genética , Síndromes Mielodisplásicas/genética , Proteínas do Tecido Nervoso/genética , Prognóstico , Receptores Imunológicos/genética , Proteínas Roundabout
5.
Blood ; 142(10): 903-917, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37319434

RESUMO

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.


Assuntos
Proteína 7 Semelhante a Angiopoietina , Proteína 1 Inibidora de Diferenciação , Leucemia Mieloide Aguda , Animais , Camundongos , Proteína 7 Semelhante a Angiopoietina/genética , Proteína 7 Semelhante a Angiopoietina/metabolismo , Medula Óssea/metabolismo , Modelos Animais de Doenças , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Microambiente Tumoral , Humanos , Proteína 1 Inibidora de Diferenciação/metabolismo
6.
Nanoscale ; 15(5): 2018-2035, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36648016

RESUMO

Ordered assemblies of inorganic nanoparticles (NPs) have shown tremendous potential for wide applications due to their unique collective properties, which differ from those of individual NPs. Various assembly methods, such as external field-directed assembly, interfacial assembly, template assembly, biomolecular recognition-mediated assembly, confined assembly, and others, have been employed to generate ordered inorganic NP assemblies with hierarchical structures. Among them, the external field-directed assembly method is particularly fascinating, as it can remotely assemble NPs into well-ordered superstructures. Moreover, external fields (e.g., electric, magnetic, and shear fields) can introduce a local and/or global field intensity gradient, resulting in an additional force on NPs to drive their rotation and/or translation. Therefore, the external field-directed assembly of NPs becomes a robust method to fabricate well-defined functional materials with the desired optical, electronic, and magnetic properties, which have various applications in catalysis, sensing, disease diagnosis, energy conversion/storage, photonics, nano-floating-gate memory, and others. In this review, the effects of an electric field, magnetic field, and shear field on the organization of inorganic NPs are highlighted. The methods for controlling the well-ordered organization of inorganic NPs at different scales and their advantages are reviewed. Finally, future challenges and perspectives in this field are discussed.

7.
Small ; 19(15): e2207206, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36604999

RESUMO

Dzyaloshinskii-Moriya interaction (DMI), one of antisymmetric exchanges, originates from the combination of low structural symmetry and large spin-orbit coupling and favors magnetization rotations with fixed chirality. Herein, this work reports a DMI-like behavior in permalloy via coupled vortices in confined structures. Under the in-plane magnetic fields, continuous reversals of different coupled vortices are directly observed by in situ Lorentz transmission electron microscopy, and reproduced by complementary micromagnetic simulations. The statistical results show that coupled vortices with opposite chirality appear more frequently with the frequency up to about 60%. Such an asymmetric phenomenon mainly arises from a DMI-like behavior, associated with the increased total energy difference between different ground-state coupled vortices. Moreover, in the reversal process, the junction between disks accelerates the annihilation of vortices moving toward it and is also the starting point of vortex nucleation. These results provide an effective method to generate a DMI-like behavior in magnetic systems with symmetry breaking surface and benefit the future development of vortex-based spintronic devices.

8.
Leukemia ; 37(1): 164-177, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36352191

RESUMO

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Animais , Camundongos , Humanos , Rituximab/uso terapêutico , Pimozida/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Proteases Específicas de Ubiquitina/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
9.
Cell Res ; 32(12): 1105-1123, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36302855

RESUMO

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A-associated protein 30 (SAP30) through two critical amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Further knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, our study reveals the mechanisms for altered epigenetic programs in AML and provides a promising targeted therapeutic strategy against AML.


Assuntos
Leucemia Mieloide Aguda , Humanos , Carcinogênese , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Histona Desacetilases , Leucemia Mieloide Aguda/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
10.
Phys Chem Chem Phys ; 24(15): 9018-9028, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35381056

RESUMO

Aptamers have been widely used in the detection, diagnosis, and treatment of cancer. Owing to their special binding affinity toward cancer-related biomarkers, aptamers can be used for targeted drug delivery or bio-sensing/bio-imaging in various scenarios. The interfacial properties of aptamers play important roles in controlling the surface charge, recognition efficiency, and binding affinity of drug-delivering lipid-based carriers. In this research, the interfacial behaviors, such as surface orientation, molecular conformation, and adsorption kinetics of conjugated AS1411 molecules at different cationic lipid bilayer interfaces were investigated by sum frequency generation vibrational spectroscopy (SFG-VS) in situ and in real-time. It is shown that the conjugated AS1411 molecules at the DMTAP bilayer interface show a higher binding affinity but with slower binding kinetics compared to the DMDAP bilayer interface. The analysis results also reveal that the thymine residues of cholesteryl conjugated AS1411 molecules show higher conformational ordering compared to the thymine residues of the alkyl chain conjugated AS1411 molecules. These understandings provide unique molecular insight into the aptamer-lipid membrane interactions, which may help researchers to improve the efficiency and safety of aptamer-related drug delivery systems.


Assuntos
Aptâmeros de Nucleotídeos , Bicamadas Lipídicas , Aptâmeros de Nucleotídeos/química , Conformação Molecular , Oligodesoxirribonucleotídeos/química , Timina
11.
ACS Nano ; 16(4): 6565-6577, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35344331

RESUMO

Carbon aerogels (CAs) are attractive candidates for the thermal protection of aerospace vehicles due to their excellent thermostability and thermal insulation. However, the brittleness and low mechanical strength severely limits their practical applications, and no significant breakthroughs in large CAs with a high strength have been made. We report a high-pressure-assisted polymerization method combined with ambient pressure drying to fabricate large, strong, crack-free carbon/carbon (C/C) composites with an excellent load-bearing capacity, thermal stability, and thermal insulation. The composites are comprised of an aerogel-like carbon matrix and a low carbon crystallinity fiber reinforcement, featuring overlapping nanoparticles, macro-mesopores, large particle contact necks, and strong fiber/matrix interfacial bonding. The resulting C/C composites with a medium density of 0.6 g cm-3 have a very high compressive strength (80 MPa), in-plane shear strength (20 MPa), and specific strength (133 MPa g-1 cm3). Moreover, the C/C composites of 7.5-12.0 mm in thickness exposed to an oxyacetylene flame at 1800 °C for 900 s display very low back-side temperatures of 778-685 °C and even better mechanical properties after the heating. This performance makes the composites ideal for the ultrahigh temperature thermal protection of aerospace vehicles where both excellent thermal-insulating and load-bearing capacities are required.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 273: 121030, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35189488

RESUMO

Silver nanowires (AgNWs) as a promising surface-enhanced Raman spectroscopy (SERS) substrate could be used in the analytical science due to its high sensitivity. However, it is difficult for the randomly-distributed silver nanowires to offer uniform "hot spots" to achieve the SERS signal reproducibility of small molecules detection. Herein, the evaporation-induced aggregation had been used to assemble long silver nanowires into highly aligned structure to achieve uniform "hot spots" for SERS detection. The normal glass slide with well-aligned silver nanowires could act as a high sensitivity and excellent reproducibility SERS substrate to provide a versatile platform for detecting analytes. Rhodamine 6G (R6G) is used to evaluate the sensitivity and reproducibility of these AgNWs SERS substrates. Even the low concentration of the R6G was 10-10 mol/L, the SERS features of R6G could be still observed clearly, and the uniform distribution of enhancement factor (EF) was higher than 0.8 × 104 accounting for about 75 % in the observed mapping area. Moreover, the relative standard deviation (RSD) of SERS intensity at the band of 610 cm-1 was used to estimate the signal reproducibility, and the calculated RSD value of aligned AgNWs substrate was about 3.6%, which was much higher than that of the randomly distributed AgNWs (26.8%) because of the highly aligned structure of silver nanowires with abundant and uniform inherent "hot spots". In addition, potential SERS detection of other small molecule, e.g. melamine was also demonstrated in the micromolar range.


Assuntos
Nanofios , Prata , Vidro , Nanofios/química , Reprodutibilidade dos Testes , Prata/química , Análise Espectral Raman/métodos
13.
Small ; 18(4): e2107265, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34908242

RESUMO

Designing heterogeneous interfaces and components at the nanoscale is proven effective for optimizing electromagnetic wave absorption and shielding properties, which can achieve desirable dielectric polarization and ferromagnetic resonances. However, it remains a challenge for the precise control of components and microstructures via an efficient synthesis approach. Here, the arc-discharged plasma method is proposed to synthesize core@shell structural high-entropy-alloy@graphite nanocapsules (HEA@C-NPs), in which the HEA nanoparticles are in situ encapsulated within a few layers of graphite through the decomposition of methane. In particular, the HEA cores can be designed via combinations of various transition elements, presenting the optimized interfacial impedance matching. As an example, the FeCoNiTiMn HEA@C-NPs obtain the minimum reflection loss (RLmin ) of -33.4 dB at 7.0 GHz (3.34 mm) and the efficient absorption bandwidth (≤-10 dB) of 5.45 GHz ranging from 12.55 to 18.00 GHz with an absorber thickness of 1.9 mm. The present approach can be extended to other carbon-coated complex components systems for various applications.

14.
ACS Omega ; 7(51): 48320-48331, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36591178

RESUMO

In this work, manganese dioxide (MnO2) nanosheets in situ loaded on a high-purity graphite flake (GF) were prepared by one-step hydrothermal deposition. It was found that the specific capacitance value of a single MnO2/GF electrode was 882 F/g at a current density of 1.0 A/g in a KOH electrolyte, and the specific capacitance retention of the MnO2/GF electrode can reach about 90.1% after 5000 charge-discharge cycles at a current density of 10 A/g. Furthermore, a MnO2/GF∥MnO2/GF symmetric supercapacitor device was fabricated with two pieces of MnO2/GF electrodes and ordinary filter paper with a 1 M KOH/PVA gel electrolyte as a separator. The single symmetric device displayed a high energy density of 64.2 Wh/kg at a power density of 400 W/kg within an applied voltage of 1.6 V, and this value was superior to those of previously reported MnO2-based systems. A tandem device consisting of a five-series tandem device (the applied voltage of a single device was 0.7 V) and a three-series tandem device (the applied voltage of a single device was 1.6 V) was prepared to drive a red light-emitting diode (LED). These findings open up application prospects for MnO2-based composite electrode materials for high-performance supercapacitors.

15.
Nanotechnology ; 33(7)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34663763

RESUMO

Here, we report an improved synthesis strategy for 3D nitrogen-doped graphene to increase the specific capacity of supercapacitors. Ethanol replaces the strong oxidant hydrogen peroxide in the improved Hummers method, and the loose porous structure is conducive to charge transfer. N-doped porous 3D graphene was synthesized from RGO-C prepared by ethanol secondary intercalation modification of functional groups. Ammonia was selected as the dopant; the microstructure and electrochemical performance of samples synthesized at different temperatures were examined. The results demonstrate that the 3D nitrogen-doped graphene (N-RGO-5) had a layered tuple shape with a sheet thickness of 0.612 nm.The specific surface area of the 3D N-RGO-5, which was prepared at 190°C, was 258.371 m2g-1, which was higher than that (5.877 m2g-1) of the original graphite. The 3D N-RGO-5 exhibited a specific capacitance of 236 F g-1and an energy density of 32.78 Wh kg-1at a current density of 1 A g-1, which is 27% higher than the specific capacitance of RGO. The 3D N-RGO-5 demonstrated an excellent capacity retention rate of 93.6% after 5000 cycles at a current density of 1 A g-1. This study demonstrates that the unique 3D structure and N-doping of N-RGO considerably improved the overall energy storage performance of graphene-based nanomaterials.

16.
J Phys Condens Matter ; 33(42)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-33503606

RESUMO

The manipulation of magnetic skyrmion has been attracting considerable attention for the fundamental physical perspective and promising applications in spintronics, ascribed to their nontrivial topology and emergent electrodynamics. However, there is a hindrance to the transmission of a skyrmion in the racetrack memory due to the skyrmion Hall effect (SHE). Antiferromagnetic (AFM) materials provide a possibility to overcome the SHE in high-velocity data writing. Herein, we systematically investigate the generation and motion of an AFM target skyrmion under the spin-polarized current. We found that the AFM target skyrmion can reach a velocity of 1088.4 m s-1under the current density of 8 × 1012 A m-2, which is lower than 1269.8 m s-1for the AFM skyrmion. This slowdown can be ascribed to the deformation of AFM target skyrmion in the process of motion on a nanotrack. In addition, we observed a transformation from AFM target skyrmion to AFM skyrmion by the unzipping process through a constricted nanostructure which is mediated by the formation of AFM domain wall. Two energy barriers need to be overcome in this dynamic process, i.e. 2.93 × 104 eV from AFM target skyrmion to AFM domain wall, and 7.625 × 103 eV from AFM domain wall to AFM skyrmion. Our results provide guidance for future target skyrmion-based devices.

17.
ACS Omega ; 5(50): 32395-32402, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33376876

RESUMO

Polyaniline with oriented nanorod arrays could provide high surface area and relaxed nanostructure to optimize ion diffusion paths, thus enhancing the performance of the device. In this paper, we designed an all-solid symmetrical supercapacitor with good performance based on polyaniline nanorod arrays in situ-grown on a graphite flake free-standing substrate. The specific capacitance, cycle stability, and energy density of the prepared supercapacitor device were 135 F/g, 75.4% retention after 1500 cycles, and the energy density is 18.75 W h/kg at a power density of 500 W/kg. The good performance of the supercapacitor device was obviously related to the oriented nanorod arrays of polyaniline/graphite flakes. In order to find the application of the prepared supercapacitor device, the tandem device consisting of three single supercapacitor devices connected in series had been used to drive small electronic equipment. The red light-emitting diode and chronograph could be easily driven by the 3-series supercapacitor devices. These results indicated that the prepared supercapacitor device based on the polyaniline/graphite flake electrode had potential applications in energy storage devices.

18.
Blood ; 135(25): 2271-2285, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32202636

RESUMO

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.


Assuntos
Anemia Refratária com Excesso de Blastos/patologia , Calgranulina B/fisiologia , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/fisiologia , Leucemia Mieloide Aguda/etiologia , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/metabolismo , Animais , Calgranulina B/biossíntese , Calgranulina B/genética , Transformação Celular Neoplásica , Células Cultivadas , Decitabina/farmacologia , Regulação para Baixo , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Código das Histonas/efeitos dos fármacos , Histona-Lisina N-Metiltransferase/biossíntese , Histona-Lisina N-Metiltransferase/genética , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Síndromes Mielodisplásicas/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Análise Serial de Tecidos , Transcriptoma
19.
RSC Adv ; 10(46): 27401-27406, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35516951

RESUMO

Due to the shortage of freshwater, seawater has been widely considered for mineral flotation. However, the presence of Mg2+ in seawater plays an apparently negative role. In this work, two dispersants (i.e., sodium silicate (SS) and sodium hexametaphosphate (SH)) were applied to reduce the detrimental effects of Mg2+ on the flotation of molybdenite (MoS2). Various measurements including contact angle, zeta potential, FTIR and XPS were carried out to understand the impacts of these two dispersants on MoS2 flotation. Results indicate that both dispersants prevented the adsorption of colloidal Mg(OH)2 onto MoS2 surface under alkaline conditions, thereby improving MoS2 floatability. In addition, both dispersants are physically adsorbed on MoS2 surface, but chemically adsorbed on Mg(OH)2 surface. In addition, the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) calculation suggests that both SS and SH reverse the total interaction energies between MoS2 and colloidal Mg(OH)2 from negative (attraction force) to positive (repulsive force), with the impact of SH being more significant.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 228: 117733, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31753654

RESUMO

Silver nanowires (i.e., AgNWs) can act as effective surface-enhanced Raman spectroscopy (i.e., SERS) substrates to detect small molecules. However, a lot of prepared AgNWs were often wrapped by polyvinylpyrrolidone (i.e., PVP) thin film to form an insulating layer to produce ill-defined AgNWs-PVP-AgNWs interface, limiting the plasmonic coupling among the stacked AgNWs. Herein, we reported a facile method in removal of PVP ligands from AgNWs for high performance and reusable SERS substrate. Sodium borohydride (NaBH4) was used to completely remove the PVP ligands from the surface of AgNWs and produce a clean AgNWs-AgNWs interface that effectively enhances the localized surface plasmon resonance (i.e., LSPR) was produced, greatly improving the SERS activity of the AgNWs thin film. The SERS detection of rhodamine 6G (i.e., R6G) used with PVP AgNWs and without PVP AgNWs is 1.0 × 10-9 and 1.0 × 10-15 M, and the average enhancement factor (EF) is about 0.86 × 104 and 9.35 × 104, respectively. Moreover, the recyclable behavior of the AgNWs with several analyte molecules is much more interesting than that of the PVP@AgNWs. The SERS detection of AgNWs for R6G, the 3-mercaptopropionic acid (i.e., 3-MPA) and melamine with good recyclability in nanomolar and millimolar concentration can be easily detected.

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