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"Wan, Peng"
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IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader
The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.
Journal Article
Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer
Background
The conversion from estrogen-dependent to estrogen-independent state of ER+ breast cancer cells is the key step to promote resistance to endocrine therapies. Although the crucial role of MAPK/ERK signaling pathway in estrogen-independent breast cancer cell growth is well established, the underlying mechanism is not fully understood.
Methods
In this study, we profiled lncRNA expression against a focused group of lncRNAs selected from lncRNA database. CRISPR/Cas9 was employed to knockout (KO) linc-RoR in MCF-7 cells, while rescue experiments were carried out to re-express linc-RoR in KO cells. Colony formation and MTT assays were used to examine the role of linc-RoR in estrogen-independent growth and tamoxifen resistance. Western blot and qRT-PCR were used to determine the change of protein and lncRNA levels, respectively. The expression of DUSP7 in clinical specimens was downloaded from Oncomine (
www.oncomine.org
) and the dataset from Kaplan-Meier Plotter (
http://kmplot.com
) was used to analyze the clinical outcomes in relation to DUSP7.
Results
We identified that linc-RoR functions as an onco-lncRNA to promote estrogen-independent growth of ER+ breast cancer. Under estrogen deprivation, linc-RoR causes the upregulation of phosphorylated MAPK/ERK pathway which in turn activates ER signaling. Knockout of linc-RoR abrogates estrogen deprivation-induced ERK activation as well as ER phosphorylation, whereas re-expression of linc-RoR restores all above phenotypes. Moreover, we show that the ERK-specific phosphatase Dual Specificity Phosphatase 7 (DUSP7), also known as MKP-X, is involved in linc-RoR KO-induced repression of MAPK/ERK signaling. Interestingly, linc-RoR KO increases the protein stability of DUSP7, resulting in repression of ERK phosphorylation. Clinical data analysis reveal that DUSP7 expression is lower in ER+ breast cancer samples than that in ER- breast cancer. Moreover, downregulation of DUSP7 expression is associated with poor patient survival.
Conclusion
Taken together, these results suggest that linc-RoR promotes estrogen-independent growth and activation of MAPK/ERK pathway of breast cancer cells by regulating the ERK-specific phosphatase DUSP7. Thus, this study might help not only in establishing a role for linc-RoR in estrogen-independent and tamoxifen resistance of ER+ breast cancer, but also suggesting a link between linc-RoR and MAPK/ERK pathway.
Journal Article
Enhanced formation of methane hydrate from active ice with high gas uptake
Gas hydrates provide alternative solutions for gas storage & transportation and gas separation. However, slow formation rate of clathrate hydrate has hindered their commercial development. Here we report a form of porous ice containing an unfrozen solution layer of sodium dodecyl sulfate, here named active ice, which can significantly accelerate gas hydrate formation while generating little heat. It can be readily produced via forming gas hydrates with water containing very low dosage (0.06 wt% or 600 ppm) of surfactant like sodium dodecyl sulfate and dissociating it below the ice point, or by simply mixing ice powder or natural snow with the surfactant. We prove that the active ice can rapidly store gas with high storage capacity up to 185
V
g
V
w
−1
with heat release of ~18 kJ mol
−1
CH
4
and the active ice can be easily regenerated by depressurization below the ice point. The active ice undergoes cyclic ice−hydrate−ice phase changes during gas uptake/release, thus removing most critical drawbacks of hydrate-based technologies. Our work provides a green and economic approach to gas storage and gas separation and paves the way to industrial application of hydrate-based technologies.
Gas hydrates have promising energy storage applications, a main bottleneck being their slow formation kinetics. Here, the authors demonstrate that by dispersing kinetic promoters in porous ice as active ice for gas hydrate formation, a minute-level formation process can be achieved for hydrate-based technologies.
Journal Article
An Easy-to-Use Airborne LiDAR Data Filtering Method Based on Cloth Simulation
Separating point clouds into ground and non-ground measurements is an essential step to generate digital terrain models (DTMs) from airborne LiDAR (light detection and ranging) data. However, most filtering algorithms need to carefully set up a number of complicated parameters to achieve high accuracy. In this paper, we present a new filtering method which only needs a few easy-to-set integer and Boolean parameters. Within the proposed approach, a LiDAR point cloud is inverted, and then a rigid cloth is used to cover the inverted surface. By analyzing the interactions between the cloth nodes and the corresponding LiDAR points, the locations of the cloth nodes can be determined to generate an approximation of the ground surface. Finally, the ground points can be extracted from the LiDAR point cloud by comparing the original LiDAR points and the generated surface. Benchmark datasets provided by ISPRS (International Society for Photogrammetry and Remote Sensing) working Group III/3 are used to validate the proposed filtering method, and the experimental results yield an average total error of 4.58%, which is comparable with most of the state-of-the-art filtering algorithms. The proposed easy-to-use filtering method may help the users without much experience to use LiDAR data and related technology in their own applications more easily.
Journal Article
New Copper Complex on Fe3O4 Nanoparticles as a Highly Efficient Reusable Nanocatalyst for Synthesis of Polyhydroquinolines in Water
In this work, we present a simple, environmentally friendly and economical route for the preparation of a novel copper-Schiff-base organometallic complex on Fe
3
O
4
nanoparticles (Fe
3
O
4
@Schiff-base-Cu) using an inexpensive and simple method and available materials. This magnetic nanocatalyst was comprehensively characterized using Fourier transform infrared spectroscopy (FT-IR), X-Ray Diffractometer (XRD), inductively coupled plasma atomic emission spectroscopy (ICP), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), X-ray mapping, thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM) analysis. In the second stage, the catalytic activity of this catalyst was studied in the synthesis of polyhydroquinoline derivatives via Hantzsch reaction in water as a green solvent. In this sense, simple preparation of the catalyst from the commercially available materials, high catalytic activity, simple operation, short reaction times, high yields and use of green solvent can be regarded as some advantages of this protocol. In addition, it is worth mentioning that this nanocatalyst was easily recovered using external magnet and reused for several times without significant loss of its catalytic efficiency. Finally, the leaching, heterogeneity and stability of Fe
3
O
4
@Schiff-base-Cu were studied by hot filtration test and ICP technique.
Graphic Abstract
A green and novel Fe
3
O
4
@Schiff-base-Cu catalyst sucssesfully was prepared and characterized. This catalyst can be used for the Synthesis of polyhydroquinolines in water as the green solvent. This catalyst could be recovered easily and reused many times without important decrease in efficiency.
Journal Article
Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy
Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm
3
), entire gastrocnemius and tibialis muscles (~200 mm
3
) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.
High resolution imaging of large biological volumes typically takes a long time from hours to days. Here the authors use a Bessel light-sheet approach combined with a content-aware compressed sensing computational pipeline to image whole mouse organs at subcellular resolution in a few minutes.
Journal Article
A Novel Approach for the Detection of Standing Tree Stems from Plot-Level Terrestrial Laser Scanning Data
Tree stem detection is a key step toward retrieving detailed stem attributes from terrestrial laser scanning (TLS) data. Various point-based methods have been proposed for the stem point extraction at both individual tree and plot levels. The main limitation of the point-based methods is their high computing demand when dealing with plot-level TLS data. Although segment-based methods can reduce the computational burden and uncertainties of point cloud classification, its application is largely limited to urban scenes due to the complexity of the algorithm, as well as the conditions of natural forests. Here we propose a novel and simple segment-based method for efficient stem detection at the plot level, which is based on the curvature feature of the points and connected component segmentation. We tested our method using a public TLS dataset with six forest plots that were collected for the international TLS benchmarking project in Evo, Finland. Results showed that the mean accuracies of the stem point extraction were comparable to the state-of-art methods (>95%). The accuracies of the stem mappings were also comparable to the methods tested in the international TLS benchmarking project. Additionally, our method was applicable to a wide range of stem forms. In short, the proposed method is accurate and simple; it is a sensible solution for the stem detection of standing trees using TLS data.
Journal Article
Regulation of osteogenesis and osteoclastogenesis by zoledronic acid loaded on biodegradable magnesium-strontium alloy
Inhibiting osteoclasts and osteoclast precursors to reduce bone resorption is an important strategy to treat osteoclast-related diseases, such as peri-prosthetic osteolysis. In this study, our objective was to study the role of zoledronic acid (ZA), as a highly potent and nitrogen-containing bisphosphonate, in promoting osteogenesis and inhibiting osteoclastogenesis properties of magnesium (Mg)-based implants. ZA was chemically associated with calcium phosphate (CaP) deposited on magnesium-strontium (Mg-Sr) alloy, which was confirmed by the morphological observation, phase composition and drug releasing via SEM, XRD spectrum and High Performance Liquid Chromatography (HPLC), respectively. The
in vitro
performances indicated that ZA-CaP bilayer coating Mg-Sr alloy could enhance the proliferation and the osteogenic differentiation as well as the mineralization of pre-osteoblasts, however, induce the apoptosis and inhibit the osteoclast differentiation. We further investigated the possible molecular mechanisms by using Quantitative real-time PCR (qRT-PCR) and Western Blotting, and the results showed that ZA-CaP bilayer coating Mg-Sr alloy could regulate the osteogenesis and osteoclastogenesis through the Estrogen Receptor α (ERα) and NF-κB signaling pathway. Moreover, ZA-CaP bilayer coating Mg-Sr alloy could regulate the cross talk of osteoblast-osteoclast and increase the ratio of OPG: RANKL in the co-culture system through OPG/RANKL/RANK signaling pathway, which promoting the balance of bone remodeling process. Therefore, these promising results suggest the potential clinical applications of ZA pretreated Mg-Sr alloys for bone defect repairs and periprosthetical osteolysis due to the excessive differentitation and maturation of osteoclasts.
Journal Article
Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway
Folic acid- (FA-) induced kidney injury is characterized by the tubule damage due to the disturbance of the antioxidant system and subsequent interstitial fibrosis. FG-4592 is an inhibitor of prolyl hydroxylase of hypoxia-inducible factor (HIF), an antioxidant factor. The present study investigated the protective role of FG-4592 pretreatment at the early stage of the kidney injury and long-term impact on the progression of renal fibrosis. FG-4592 was administrated two days before FA injection in mice. On the second day after FA injection, the mice with FG-4592 pretreatment showed an improved renal function, compared with those without FG-4592 pretreatment, indicated by biochemical and histological parameters; meanwhile, the cellular content of iron, malondialdehyde, and 4-hydroxynonenal histologically decreased, implying the suppression of iron accumulation and lipid peroxidation. Simultaneously, upregulation of HIF-1α was found, along with Nrf2 activation, which was reflected by increased nuclear translocation and high-expression of downstream proteins, including heme-oxygenase1, glutathione peroxidase4, and cystine/glutamate transporter, as well as ferroportin. Correspondingly, the elevated levels of antioxidative enzymes and glutathione, as well as reduced iron accumulation, were observed, suggesting a lower risk of occurrence of ferroptosis with FG-4592 pretreatment. This was confirmed by reversed pathological parameters and improved renal function in FA-treated mice with the administration of ferrostatin-1, a specific ferroptosis inhibitor. Furthermore, a signal pathway study indicated that Nrf2 activation was associated with increased phosphorylation of Akt and GSK-3β, verified by the use of an inhibitor of the PI3K that phosphorylates Akt. Moreover, FG-4592 pretreatment also decreased macrophage infiltration and expression of inflammatory factors TNF-α and IL-1β. On the 14th day after FA injection, FG-4592 pretreatment decreased collagen deposition and expression of fibrosis biomarkers. These findings suggest that the protective role of FG-4592 pretreatment is achieved mainly by decreasing ferroptosis at the early stage of FA-induced kidney injury via Akt/GSK-3β-mediated Nrf2 activation, which retards the fibrosis progression.
Journal Article