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1.
J Colloid Interface Sci ; 663: 532-540, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38422978

ABSTRACT

The performance of thin lithium metal anodes is affected due to issues that weaken the electrode-electrolyte interphase. In this work, a coating layer serving as a Li+ traffic controller based on hexadecyl trimethyl ammonium bis(trifluoromethanesulphonyl)imide ([CTA][TFSI]) and poly (vinylidene difluoride co-hexafluoropropylene) (P(VDF-HFP)) is used to stabilize the thin lithium metal interface. The CTA+ ions in the coating layer can effectively regulate the distribution of Li+ concentration to promote uniform deposition of lithium. The anion of [CTA][TFSI] can optimize solid electrolyte interphase (SEI) with inorganic-rich components, which improve the ionic conductivity and reaction kinetics. Furthermore, the flexible polymer skeleton can fortify the fragile SEI, facilitating the consistent operation of the battery. Due to these improvements, a thin Li metal anode (4 mAh cm-2) with a coating layer in a Li||Li symmetric cell demonstrates a lifespan of 600 h at 1 mA cm-2 and 1 mAh cm-2. Notably, full cells with an ultra-low negative electrode/positive electrode = 1 (N/P = 1) demonstrate a stable performance over 200 cycles and 90 cycles at 0.5C and 1C (1C = 170 mA g-1), respectively.

2.
Nat Commun ; 15(1): 1354, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38355652

ABSTRACT

Exploiting thin Li metal anode is essential for high-energy-density battery, but is severely plagued by the poor processability of Li, as well as the uncontrollable Li plating/stripping behaviors and Li/electrolyte interface. Herein, a thickness/capacity-adjustable thin alloy-type Li/LiZn@Cu anode is fabricated for high-energy-density Li metal batteries. The as-formed lithophilic LiZn alloy in Li/LiZn@Cu anode can effectively regulate Li plating/stripping and stabilize the Li/electrolyte interface to deliver the hierarchical Li electrochemistry. Upon charging, the Li/LiZn@Cu anode firstly acts as Li source for homogeneous Li extraction. At the end of charging, the de-alloy of LiZn nanostructures further supplements the Li extraction, actually playing the Li compensation role in battery cycling. While upon discharging, the LiZn alloy forms just at the beginning, thereby regulating the following Li homogeneous deposition. The reversibility of such an interesting process is undoubtedly verified from the electrochemistry and in-situ XRD characterization. This work sheds light on the facile fabrication of practical Li metal anodes and useful Li compensation materials for high-energy-density Li metal batteries.

3.
Materials (Basel) ; 16(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37834606

ABSTRACT

In this study, our objective is to investigate the anisotropic deformation behavior and the indentation size effect (ISE) of monocrystalline barium fluoride (BaF2) using nanoindentation experiments with a diamond Berkovich indenter. BaF2 is known for its anisotropy, which results in significant variations in its mechanical properties. This anisotropy poses challenges in achieving high processing quality in ultra-precision machining. Through our experiments, we observed numerous pop-in events in the load-displacement curves, indicating the occurrence of plastic deformation in BaF2 crystals, specifically in the (100), (110), and (111) orientations; these pop-in events were observed as the indentation depth increased to 56.9 nm, 58.2 nm, and 57.8 nm, respectively. The hardness-displacement and elastic modulus-displacement curves were obtained from the tests exhibiting the ISE. The nanoindentation hardness of BaF2 is found to be highly dependent on its crystallographic orientation. Similarly, for BaF2 in the (100) orientation, the range is from 2.43 ± 0.74 and 1.24 ± 0.12 GPa. For BaF2 in the (110) orientation, the values range from 2.15 ± 0.66 to 1.18 ± 0.15 GPa. For BaF2 in the (111) orientation, the values range from 2.12 ± 0.53 GPa to 1.19 ± 0.12 GPa. These results highlight the significant influence of crystallographic orientation on the mechanical properties of BaF2. To better understand the ISE, we employed several models including Meyer's law, the Nix-Gao model, the proportional specimen resistance (PSR) model, and the modified PSR (mPSR) model, and compared them with our experimental results. Among these models, the mPSR model demonstrated the best level of correlation (R2>0.9999) with the experimental measurements, providing a reliable description of the ISE observed in BaF2. Our reports provide valuable insights into the anisotropic mechanical characteristics of BaF2 materials and serve as a theoretical guide for the ultra-precision machining of BaF2.

4.
Front Immunol ; 14: 1227041, 2023.
Article in English | MEDLINE | ID: mdl-37662910

ABSTRACT

Retinoic acid-inducible gene-I (RIG-I) like receptor (RLR) pathway is one of the most significant pathways supervising aberrant RNA in cells. In predominant conditions, the RLR pathway initiates anti-infection function via activating inflammatory effects, while recently it is discovered to be involved in cancer development as well, acting as a virus-mimicry responder. On one hand, the product IFNs induces tumor elimination. On the other hand, the NF-κB pathway is activated which may lead to tumor progression. Emerging evidence demonstrates that a wide range of modifications are involved in regulating RLR pathways in cancer, which either boost tumor suppression effect or prompt tumor development. This review summarized current epigenetic modulations including DNA methylation, histone modification, and ncRNA interference, as well as post-transcriptional modification like m6A and A-to-I editing of the upstream ligand dsRNA in cancer cells. The post-translational modulations like phosphorylation and ubiquitylation of the pathway's key components were also discussed. Ultimately, we provided an overview of the current therapeutic strategies targeting the RLR pathway in cancers.


Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Phosphorylation , DNA Methylation , RNA, Double-Stranded , Tretinoin
5.
Front Plant Sci ; 14: 1149760, 2023.
Article in English | MEDLINE | ID: mdl-37008484

ABSTRACT

Introduction: Parameterizing the process of trees from the comfort zone to mortality during progressive drought is important for, but is not well represented in, vegetation models, given the lack of appropriate indices to gauge the response of trees to droughts. The objective of this study was to determine reliable and readily available tree drought stressindices and the thresholds at which droughts activate important physiological responses. Methods: We analyzed the changes in the transpiration (T), stomatal conductance, xylem conductance, and leaf health status due to a decrease in soil water availability (SWA), predawn xylem water potential (ψpd), and midday xylem water potential (ψmd) in Robinia pseudoacacia seedlings during progressive drought. Results: The results showed that ψmd was a better indicator of drought stress than SWA and ψpd, because ψmd was more closely related to the physiological response (defoliation and xylem embolization) during severe drought and could be measured more conveniently. We derived the following five stress levels from the observed responses to decreasing ψmd: comfort zone (ψmd > -0.9 MPa), wherein transpiration and stomatal conductance are not limited by SWA; moderate drought stress (-0.9 to -1.75 MPa), wherein transpiration and stomatal conductance are limited by drought; high drought stress (-1.75 to -2.59 MPa), wherein transpiration decreases significantly (T< 10%) and stomata closes completely; severe drought stress (-2.59 to -4.02 MPa), wherein transpiration ceases (T< 0.1%) and leaf shedding orwilting is > 50%; and extreme drought stress (< -4.02 MPa), leading to tree mortality due to xylem hydraulic failure. Discussion: To our knowledge, our scheme is the first to outline the quantitative thresholds for the downregulation of physiological processes in R. pseudoacacia during drought, therefore, can be used to synthesize valuable information for process-based vegetation models.

6.
Nanomicro Lett ; 13(1): 50, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-34138227

ABSTRACT

Rechargeable room temperature sodium-sulfur (RT Na-S) batteries are seriously limited by low sulfur utilization and sluggish electrochemical reaction activity of polysulfide intermediates. Herein, a 3D "branch-leaf" biomimetic design proposed for high performance Na-S batteries, where the leaves constructed from Co nanoparticles on carbon nanofibers (CNF) are fully to expose the active sites of Co. The CNF network acts as conductive "branches" to ensure adequate electron and electrolyte supply for the Co leaves. As an effective electrocatalytic battery system, the 3D "branch-leaf" conductive network with abundant active sites and voids can effectively trap polysulfides and provide plentiful electron/ions pathways for electrochemical reaction. DFT calculation reveals that the Co nanoparticles can induce the formation of a unique Co-S-Na molecular layer on the Co surface, which can enable a fast reduction reaction of the polysulfides. Therefore, the prepared "branch-leaf" CNF-L@Co/S electrode exhibits a high initial specific capacity of 1201 mAh g-1 at 0.1 C and superior rate performance.

7.
J Colloid Interface Sci ; 599: 190-197, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33933793

ABSTRACT

The irreversible consumption of active sodium in sodium-ion full-cells (SIFCs) becomes particularly serious due to the existence of unavoidable interface or side reaction, which has become the key to restrict the development of high-performance sodium-ion batteries (SIBs). Interface design and electrolyte optimization have been proved to be effective strategies to improve or solve this problem. In this work, on the basis of traditional organic liquid electrolytes, a novel gel polymer electrolyte with high ionic conductivity (1.13 × 10-3 S cm-1) and wide electrochemical stability window (~4.7 V) was designed and synthesized using bacterial cellulose film as precursor. Compared with the liquid electrolyte, the obtained electrolyte can endow better sodium storage performance in both half- and full-cells. When coupled with sodium hexacyanoferrate cathode and hard carbon anode, a capacity of 94.2 mA h g-1 can be obtained with a capacity retention of 75% after 100 cycles at a current density of 100 mA g-1, while those of with conventional liquid electrolyte can deliver a capacity of 99.0 mA h g-1 but only accompany 58% capacity retention under the same conditions. Significantly, when the current density increases to 800 mA g-1, their capacity difference reaches 23.4 mA h g-1.

8.
ACS Appl Mater Interfaces ; 13(10): 11852-11860, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33656849

ABSTRACT

Room-temperature (RT) sodium-sulfur batteries hold great promise for the development of efficient, low-cost, and environmentally friendly energy storage systems. Nevertheless, the dissolution of long-chain polysulfides is a huge obstacle. In this work, a composite cathode which integrates Ni/Co bimetal nanoparticles as the catalyst and carbon spheres with abundant channels as the host is prepared for RT Na-S batteries. Moreover, a valuable strategy to reduce the dissolution of polysulfides by accurately regulating the two-step reaction kinetics of polysulfide transformation (from Na2S to long-chain polysulfides and then from polysulfides to sulfur) is presented. Through adjusting the ratio of Ni and Co, the optimal cathode with a Ni/Co ratio of 1:2 can retard the first conversion of Na2S to polysulfides and simultaneously accelerate the subsequent transformation of polysulfides to sulfur. In this case, the soluble polysulfides can immediately transform to solid sulfur as soon as it appears, thus avoiding the shuttle of polysulfides. The galvanostatic intermittent titration method and in situ Raman are employed to supervise the transformation of polysulfides during the discharge/charge process. As a result, the composite shows excellent performance as the cathode of RT liquid/quasi-solid-state Na-S batteries in terms of specific capacities, rate capability, and cycle stability.

9.
J Colloid Interface Sci ; 582(Pt B): 932-939, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-32927173

ABSTRACT

Quasi-solid-state potassium-ion batteries (QSPIBs) are regarded as one of the most promising safety-enhanced energy storage devices. Herein, a facile method for preparing a potassium-ion composite electrolyte membrane on a large scale is presented for the first time. The as-synthesized membrane displays excellent electrochemical stability, good mechanical flexibility, and high ionic conductivity (9.31 × 10-5 S cm-1 at 25 °C). Furthermore, QSPIBs prepared with this membrane and commercial raw material-based electrodes show superior electrochemical performance even at low temperatures (99.7 mAh g-1 at -20 °C for half QSPIBs and 90.7 mAh g-1 at -15 °C for full QSPIBs), and a promising rate performance (115.6 mAh g-1 for half QSPIBs and 90.9 mAh g-1 for full QSPIBs at 800 mA g-1). The reaction mechanism and structure evolution of a 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (PTCDA) cathode is also systematically studied. The promising characteristics of the prepared low-cost quasi-solid-state potassium-ion batteries in this work open up new possibilities for safer and more durable batteries and a wide range of practical applications in the electronics industry.

10.
Front Chem ; 8: 577582, 2020.
Article in English | MEDLINE | ID: mdl-33363104

ABSTRACT

CdS nanostep-structured arrays were grown on F-doped tin oxide-coated glasses using a two-step hydrothermal method. The CdS arrays consisted of a straight rod acting as backbone and a nanostep-structured morphology on the surface. The morphology of the samples can be tuned by varying the reaction parameters. The phase purity, morphology, and structure of the CdS nanostep-structured arrays were characterized by X-ray diffraction and field emission scanning electron microscopy. The light and photoelectrochemical properties of the samples were estimated by a UV-Vis absorption spectrum and photoelectrochemical cells. The experimental results confirmed that the special nanostep structure is crucial for the remarkable enhancement of the photoelectrochemical performance. Compared with CdS rod arrays, the CdS nanostep-structured arrays showed increased absorption ability and dramatically improved photocurrent and energy conversion efficiency. This work may provide a new approach for improving the properties of photoelectrodes in the future.

11.
Biomaterials ; 257: 120279, 2020 10.
Article in English | MEDLINE | ID: mdl-32763613

ABSTRACT

Chemodynamic therapy (CDT), an emerging therapeutic strategy, has been recently exploited for in situ treatment through Fenton or Fenton-like reactions to generate cytotoxic reactive oxygen species (ROS). However, current systems rely significantly on the high local oxygen levels and strongly acidic conditions (pH = 3.0-5.0). Simultaneously, the produced ROS can be rapidly consumed by intracellular glutathione (GSH) in the electron transport chain. Herein, an original and biomimetic CoO@AuPt nanocatalyst was prepared based on the assembly of Au and Pt nanoparticles (NPs) on the surface of hollow CoO nanocapsules. The as-synthesized nanozyme exhibits extremely high stability under physiological conditions, whereas it undergoes spontaneous disintegration in the unique tumor microenvironment (TME). Subsequently, the decomposition products can catalyze a cascade of biochemical reactions to produce abundant ROS without any external stimuli. Thus, the present nanoplatform can increase intracellular ROS levels through continuous supply of H2O2, relief of local hypoxia and depletion of GSH, which result in remarkable and specific tumor damage both in vitro and in vivo. The findings of this study highlight the promising potential of CoO@AuPt nanocatalyst as a TME-responsive CDT nanomagnet for highly efficient tumor therapy.


Subject(s)
Antineoplastic Agents , Tumor Microenvironment , Antineoplastic Agents/pharmacology , Biomimetics , Cell Line, Tumor , Hydrogen Peroxide/pharmacology
12.
J Colloid Interface Sci ; 578: 710-716, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32570141

ABSTRACT

Room-temperature sodium/sulfur battery has raised concern due to the superiority of high theoretical capacity and low cost that promise for large-scale application. However, the sluggish electrochemical activity and "shuttle effect" limits the progress of practical application. This work designs a template method for constructing metal/carbon sulfur host, which possesses metal (Co, Ni) nanoparticles highly distributed in large amounts of porous channels in carbon sphere. The metal nanoparticles assist in sulfur immobilization, electric conductivity and catalyze reaction kinetics, meanwhile the hollow channels can buffer the volume change of sulfur. When testing as the liquid/solid-state room-temperature Na/S batteries, the S@Co/C and S@Ni/C electrodes deliver high capacities and rate capability. This template method possesses utility potential in developing high-powered RT Na/S batteries, which provides possibility to for the preparation of various electrode materials in battery technology.

13.
J Cell Physiol ; 235(10): 6711-6724, 2020 10.
Article in English | MEDLINE | ID: mdl-31994732

ABSTRACT

Hypermethylation of gene promoter has been indicated for the contribution of gene silencing, and DNA demethylating drugs, such as 5-aza-2'-deoxycytidine (DAC), has been used clinically for cancer treatment. However, the reason why a proportion of genes with hypermethylated promoter exhibit high expression levels remains unclear and this drug is not much successful as expected in use. Furthermore, CpG islands (CGIs) are found to be located in not only promotors, but also in gene bodies. By RNA-seq and reduced representation bisulfite sequencing, we found the mismatch between the level of promoter methylation and gene expression. By chromatin Immunoprecipitation-quantitative polymerase chain reaction and luciferase reporter assay, we identified putative promoters in gene body, and proved the activities of putative promoters were affected by the methylation level of the CGI nearby. DAC can reverse the DNA hypermethylation at promoter CGIs effectively but not the CGIs in gene body. We also found that TET1 could demethylate CGIs both in promoter and gene body. Furthermore, we revealed a novel mechanism that H3K36me3 could affect the activity of putative promoter, and 5hmC recruited MeCP2 and CREB1 as a coactivator to SETD2 promoter, to enhance its gene expression and result in increased H3K36me3 in gene body. Our results concluded that putative promoters existed in the gene bodies, and TET1 could influence the transcriptional activity of putative promoters by intragenic demethylation.


Subject(s)
DNA Methylation/genetics , Exons/genetics , Histones/genetics , Mixed Function Oxygenases/genetics , Promoter Regions, Genetic/genetics , Proto-Oncogene Proteins/genetics , A549 Cells , Cell Line, Tumor , Chromatin Immunoprecipitation/methods , CpG Islands/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Gene Silencing/physiology , Histone-Lysine N-Methyltransferase/genetics , Humans , Methyl-CpG-Binding Protein 2/genetics , Transcription, Genetic/genetics
14.
J Cell Mol Med ; 23(5): 3451-3463, 2019 05.
Article in English | MEDLINE | ID: mdl-30809937

ABSTRACT

Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF-E2-related factor 2 (Nrf2) is of great significance. Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch-like ECH-associated protein 1 (Keap1) reduced the expression of glucose-6-phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia-inducing factor 1α (HIF-1α) in MCF-7 and MDA-MB-231 cells. Overexpression of Nrf2 up-regulated the expression of Notch1 via G6PD/HIF-1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES-1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2-driven breast cancer metastasis.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Movement , Glucosephosphate Dehydrogenase/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , NF-E2-Related Factor 2/metabolism , Receptor, Notch1/metabolism , Up-Regulation , Cell Line, Tumor , Cell Proliferation , Female , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Models, Biological , Pentose Phosphate Pathway , Signal Transduction
15.
Physiol Plant ; 165(4): 701-710, 2019 Apr.
Article in English | MEDLINE | ID: mdl-29602179

ABSTRACT

A vulnerability curve (VC) describes the extent of xylem cavitation resistance. Centrifuges have been used to generate VCs for decades via static- and flow-centrifuge methods. Recently, the validity of the centrifuge techniques has been questioned. Researchers have hypothesized that the centrifuge techniques might yield unreliable VCs due to the open-vessel artifact. However, other researchers reject this hypothesis. The focus of the dispute is centered on whether exponential VCs are more reliable when the static-centrifuge method is used rather than the flow-centrifuge method. To further test the reliability of the centrifuge technique, two centrifuges were manufactured to simulate the static- and flow-centrifuge methods. VCs of three species with open vessels of known lengths were constructed using the two centrifuges. The results showed that both centrifuge techniques produced invalid VCs for Robinia because the water flow through stems under mild tension in centrifuges led to an increasing loss of water conductivity. In addition, the injection of water in the flow-centrifuge exacerbated the loss of water conductivity. However, both centrifuge techniques yielded reliable VCs for Prunus, regardless of the presence of open vessels in the tested samples. We conclude that centrifuge techniques can be used in species with open vessels only when the centrifuge produces a VC that matches the bench-dehydration VC.


Subject(s)
Centrifugation/methods , Artifacts , Prunus/physiology , Water/metabolism , Xylem/physiology
16.
Tree Physiol ; 39(1): 156-165, 2019 01 01.
Article in English | MEDLINE | ID: mdl-29788216

ABSTRACT

Cavitation resistance is a key trait for characterizing the drought adaption in plants and is usually presented in terms of vulnerability curves. Three principal techniques have been developed to produce vulnerability curves, but curves generated with centrifugation are reported to suffer from artifacts when applied to long-vesseled species. The main cause of this artifact is the issue of open vessels, resulting in a nano-particle effect that may seed premature embolism. We used two methods to test the potential mechanism behind the nano-particle effect in centrifuge-based vulnerability curves. A four-cuvette rotor system based on a traditional Cochard rotor was designed to inhibit effervescence while injecting water, but the recalcitrant vulnerability curves in Robinia could not be eliminated. There may be multiple sources, besides effervescence, of hypothetical nano-particles: they may arise from cut surfaces or they may be always present in the injected water, leading to the premature embolisms. To prevent the entry of the hypothetical nano-particles, water extraction curves in terms of PLV (percentage loss volume of extracted water from stems) vs tensions were constructed. The PLV curves of Robinia showed s-shaped characteristics after subtracting the first Weibull components from water extraction curves, which were not related to the water loss from vessels according to dye staining experiments. The differences between T50 (xylem tension at which 50% of hydraulic conductivity is lost) in mean PLV curve and T50 in percentage loss of conductivity curves determined by the four-cuvette rotor system and by the bench dehydration method were 3.9 MPa and 0.7 MPa, respectively. Hence, PLV curves may be a valid way to measure the cavitation resistance in long-vesseled species with centrifugation. Keeping bark intact in the process of measurement is recommended, otherwise it would increase evaporation from the entire system.


Subject(s)
Acclimatization , Centrifugation/methods , Nanoparticles , Plant Diseases , Robinia/physiology , Calibration , Centrifugation/instrumentation , Disease Resistance , Droughts , Plant Stems/physiology , Water
17.
Int J Biochem Cell Biol ; 95: 85-92, 2018 02.
Article in English | MEDLINE | ID: mdl-29275212

ABSTRACT

High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells. Down-regulation of NRF2 decreased MCF7 and MBA-DA-231 breast cell proliferation, while it reversed by hypoxia inducible factor 1α (HIF1α). Knockdown of NRF2 inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including HK2, PFKFB3, PKM2 and LDHA. Our results further indicated that the AKT activation and AMPK inhibition were required for NRF2-mediated up-regulation of glycolytic enzymes. Consistent with these results, a positive correlation existed between NRF2 or HIF1α and several key glycolytic genes in human breast cancer cell samples and breast cancer patients with high NRF2 or HIF1α expression had poorer overall survival. In conclusion, our study demonstrates that NRF2 promotes breast cancer progression by enhancing glycolysis through coactivation of HIF1α, implicating that NRF2 is a potential molecular target for breast cancer treatment.


Subject(s)
Breast Neoplasms/metabolism , Breast/metabolism , Cellular Reprogramming , Gene Expression Regulation, Neoplastic , Glycolysis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , NF-E2-Related Factor 2/metabolism , Breast/cytology , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Line , Cell Line, Tumor , Cell Proliferation , Electronic Health Records , Female , Gene Knockdown Techniques , HEK293 Cells , Humans , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Neoplasm/metabolism , Survival Analysis
18.
J Cell Physiol ; 233(2): 1359-1369, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28513825

ABSTRACT

Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri-methylation causing repression of the target gene E-cadherin. Ectopic expression of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression.


Subject(s)
Cadherins/metabolism , Cell Movement , Colonic Neoplasms/metabolism , Histones/metabolism , Mixed Function Oxygenases/metabolism , Proto-Oncogene Proteins/metabolism , Antigens, CD , Cadherins/genetics , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , DNA Methylation , Down-Regulation , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Histone Demethylases/genetics , Histone Demethylases/metabolism , Humans , Mixed Function Oxygenases/genetics , Neoplasm Invasiveness , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Promoter Regions, Genetic , Proto-Oncogene Proteins/genetics , RNA Interference , Signal Transduction , Time Factors , Transfection
19.
Arch Biochem Biophys ; 625-626: 17-23, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28583828

ABSTRACT

Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression. In addition, we showed that PI3K/AKT activation and AMPK inhibtion was required for the PKM2-mediated inhibition of autophagy in Tat-treated TZM-bl cells. In conclusion, our data reveals that PKM2-mediated autophagy inhibition is required for Tat-mediated HIV-1 transactivation. Metabolism-related autophagic pathway may act as a promising diagnostic and therapeutic tool for HIV-1 infection in the future.


Subject(s)
Autophagy , Carrier Proteins/metabolism , HIV Infections/metabolism , HIV-1/physiology , Membrane Proteins/metabolism , Thyroid Hormones/metabolism , Transcriptional Activation , tat Gene Products, Human Immunodeficiency Virus/metabolism , AMP-Activated Protein Kinases/metabolism , Carrier Proteins/genetics , Cell Line , Gene Expression Regulation , HIV Infections/genetics , HIV Infections/pathology , HIV Infections/virology , HIV-1/genetics , Humans , Membrane Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Thyroid Hormones/genetics , Thyroid Hormone-Binding Proteins
20.
Int J Biochem Cell Biol ; 80: 51-56, 2016 11.
Article in English | MEDLINE | ID: mdl-27671333

ABSTRACT

Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymatic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down-regulation of H3K27 methylation on the specific regions of HIV-1 LTR. The increase in H3K27me3 and the decrease in H3K4me3 induced by UTX-1 knockdown was detected on the HIV-1 LTR, but not by control siRNA. Additionally, UTX-1 promotes HIV-1 gene expression by enhancing both the NF-κB p65's nuclear translocation and its p65 binding to HIV-1 LTR. And we further demonstrated that H3K27 demethylase activity was required for increased HIV-1 transactivation induced by UTX-1. Together, our data reveal key roles for UTX-1 in a timely transition from poised to active chromatin in HIV-1 LTR during HIV-1 transcription and a fundamental mechanism by which a H3K27 demethylase triggers tissue-specific chromatin changes. Our findings provide a mechanistic link between UTX-1 and enhanced HIV-1 replication, and suggest that targeting at epigenetic mechanism may have a therapeutic benefit for HIV-1 patients.


Subject(s)
HIV-1/genetics , Histone Demethylases/metabolism , Histones/metabolism , Nuclear Proteins/metabolism , Transcriptional Activation , tat Gene Products, Human Immunodeficiency Virus/metabolism , Active Transport, Cell Nucleus , Cell Nucleus/metabolism , HeLa Cells , Histones/chemistry , Humans , Lysine/metabolism , Methylation , NF-kappa B/metabolism , Transcription Factor RelA/metabolism , Up-Regulation
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