Publications by authors named "Yutong Wu"

38 Publications

Small extracellular vesicles deliver osteolytic effectors and mediate cancer-induced osteolysis in bone metastatic niche.

J Extracell Vesicles 2021 Feb 18;10(4):e12068. Epub 2021 Feb 18.

Department of Orthopedics Southwest Hospital Third Military Medical University Chongqing 400038 China.

Extracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular crosstalks. However, little is known about the contribution of EVs derived from cancer cells to the vicious cycle of bone metastasis. Here, we report a direct regulatory mode between tumour cells and osteoclasts in metastatic niche of prostate cancer via vesicular miRNAs transfer. Combined analysis of miRNAs profiles both in tumour-derived small EVs (sEVs) and osteoclasts identified miR-152-3p as a potential osteolytic molecule. sEVs were enriched in miR-152-3p, which targets osteoclastogenic regulator MAFB. Blocking miR-152-3p in sEVs upregulated the expression of MAFB and impaired osteoclastogenesis in vitro. In vivo experiments of xenograft mouse model found that blocking of miR-152-3p in sEVs significantly slowed down the loss of trabecular architecture, while systemic inhibition of miR-152-3p using antagomir-152-3p reduced the osteolytic lesions of cortical bone while preserving basic trabecular architecture. Our findings suggest that miR-152-3p carried by prostate cancer-derived sEVs deliver osteolytic signals from tumour cells to osteoclasts, facilitating osteolytic progression in bone metastasis.
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http://dx.doi.org/10.1002/jev2.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892803PMC
February 2021

Hybrid structure of PbS QDs and vertically-few-layer MoS nanosheets array for broadband photodetector.

Nanotechnology 2021 Jan 13;32(14):145602. Epub 2021 Jan 13.

Key Laboratory of In-Fiber Integrated Optics, Ministry Education of China, Harbin Engineering University, Harbin, 150001, People's Republic of China. Chongqing Key Laboratory of Multi-Scale Manufacturing Technology, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, People's Republic of China.

A novel three-dimensional (3D) vertically-few-layer MoS (V-MoS) nanosheets- zero-dimensional PbS quantum dots (QDs) hybrid structure based broadband photodetector was fabricated, and its photoelectric performance was investigated in detail. We synthesized the V-MoS nanosheets by chemical vapor deposition, using the TiO layer as the induced layer, and proposed a possible growth mechanism. The use of the TiO induction layer successfully changed the growth direction of MoS from parallel to vertical. The prepared V-MoS nanosheets have a large specific surface area, abundantly exposed edges and excellent light absorption capacity. The V-MoS nanosheets detector was then fabricated and investigated, which exhibits a high sensitivity for 635 nm light, a fast response time and an excellent photoelectric response. The V-MoS nanosheets with a height of approximately 1 μm successfully broke the light absorption limit caused by the atomic thickness. Finally, we fabricated the PbS QDs/V-MoS nanosheets hybrid detector and demonstrated their potential for high-performance broadband photodetectors. The response wavelength of the hybrid detector extends from the visible band to the near-infrared band. The responsivity of the hybrid detector reaches 1.46 A W under 1450 nm illumination. The combination of 3D MoS nanosheets and QDs further improves the performance of MoS-based photodetector devices. We believe that the proposed zero-dimensional QDs and 3D vertical nanosheets hybrid structure broadband photodetector provides a promising way for the next-generation optoelectronic devices.
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http://dx.doi.org/10.1088/1361-6528/abd57fDOI Listing
January 2021

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling.

Bone Res 2021 Jan 11;9(1). Epub 2021 Jan 11.

Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

Bone remodeling is precisely coordinated by bone resorption and formation. Apoptotic osteoclasts generate large amounts of apoptotic bodies (ABs) marking the end of the bone resorption phase, whereas the functions of osteoclast-derived ABs remain largely unknown. Here, we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions. ABs were isolated from apoptotic bone marrow macrophages, preosteoclasts, and mature osteoclasts induced by staurosporine. Proteomic signature analysis with liquid chromatography-tandem mass spectrometry suggested marked protein cargo differences among the different ABs. Further bioinformatic analysis showed that the proteomic signatures of the ABs were highly similar to those of their parental cells. Functionally, pOC-ABs induced endothelial progenitor cell differentiation and increased CD31Emcn endothelial cell formation in a murine bone defect model via their PDGF-BB cargo. mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling. In summary, we mapped the detailed proteomic landscapes of ABs derived from osteoclasts and showed that their potential biological roles are important in coupling bone formation with resorption during bone remodeling.
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http://dx.doi.org/10.1038/s41413-020-00121-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801485PMC
January 2021

Hybrid Structure of PbS QDs and Vertically-few-layer MoSNanosheets Array for Broadband Photodetector.

Nanotechnology 2020 Dec 21. Epub 2020 Dec 21.

Center for Nanofabrication and System Integration , Chongqing Institute of Green and Intelligent Technology,Chinese Academy of Sciences, No.266,Fangzheng Ave.Shuitu Hi-tech. Development Zone,BeiBei District, Chongqing, CHINA.

A novel three-dimensional (3D) vertically-few-layer MoS(V-MoS) nanosheets- zero-dimensional (0D) PbS quantum dots (QDs) hybrid structure based broadband photodetector was fabricated, and its photoelectric performance was investigated in detail. We synthesized the V-MoSnanosheets by chemical vapor deposition (CVD), using the TiOlayer as the induced layer, and proposed a possible growth mechanism. The use of the TiOinduction layer successfully changed the growth direction of MoSfrom parallel to vertical. The prepared V-MoSnanosheets have a large specific surface area, abundantly exposed edges and excellent light absorption capacity. The V-MoSnanosheets detector was then fabricated and investigated, which exhibits a high sensitivity for 635 nm light, a fast response time and an excellent photoelectric response. The V-MoS2 nanosheets with a height of approximately 1 μm successfully broke the light absorption limit caused by the atomic thickness. Finally, we fabricated the PbS QDs/V-MoSnanosheets hybrid detector and demonstrated their potential for high-performance broadband photodetectors. The response wavelength of the hybrid detector extends from the visible band to the near-infrared band. The responsivity of the hybrid detector reaches 1.46 A/W under 1450 nm illumination. The combination of 3D MoSnanosheets and QDs further improves the performance of MoS-based photodetector devices. We believe that the proposed zero-dimensional QDs and three-dimensional vertical nanosheets hybrid structure broadband photodetector provides a promising way for the next-generation optoelectronic devices.
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http://dx.doi.org/10.1088/1361-6528/abd57fDOI Listing
December 2020

Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis.

Aging (Albany NY) 2020 11 16;12(22):22656-22687. Epub 2020 Nov 16.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.

Increasing evidence supports long non-coding RNA-ZFAS1 as master protein regulators involved in a variety of human cancers. However, the molecular mechanism is not fully understood in colorectal cancer (CRC) and remains to be elucidated. Here, we uncovered a previously unreported mechanism linking RNA helicase DDX21 regulated by lncRNA ZFAS1 in control of POLR1B expression in CRC initiation and progression. Specifically, ZFAS1 exerted its oncogenic functions and was significantly up-regulated accompanied by elevated DDX21, POLR1B expression in CRC cells and tissues, which further closely associated with poor clinical outcomes. Notably, ZFAS1 knockdown dramatically suppressed CRC cell proliferation, invasion, migration, and increased cell apoptosis, which were contrary to the effect caused by ZFAS1 up-regulation. We further revealed that the inhibitory effect caused by ZFAS1 knockdown could be reversed by DDX21 overexpression and . Mechanistically, our research found that ZFAS1 could directly recruit DDX21 protein by harboring the specific motif (AAGA or CAGA). Finally, POLR1B was identified as the downstream target of DDX21 regulated by ZFAS1, which was also up-regulated in CRC cells and tissues and closely related to poor prognosis. The unrecognized ZFAS1/DDX21/POLR1B signaling regulation axis may provide new biomarkers and targets for CRC treatment and prognostic evaluation.
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http://dx.doi.org/10.18632/aging.103875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746388PMC
November 2020

A 5-Year Review of Invasive Fungal Infection at an Academic Medical Center.

Front Cell Infect Microbiol 2020 22;10:553648. Epub 2020 Oct 22.

Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.

Invasive fungal infection (IFI) is one of the most common nosocomial infections. However, data on the epidemiology of IFI and susceptibility to antifungal agents in China are quite limited, and in particular, no current data exist on the microbiological, and clinical characteristics of IFI patients in Northeast China. The purpose of this study was to provide a retrospective review of the clinical characteristics, laboratory test results, and risk factor predictions of inpatients diagnosed with IFI. Multivariate regression analysis was used to assess prognostic factors associated with the mortality of these patients. We retrospectively analyzed the results from 509 patients with IFI extracted from the First Hospital of China Medical University from January 2013 to January 2018. Neutrophil numbers, total bilirubin, length of stay in the ICU, renal failure, use of immunosuppressants within the past 30 days, stomach tube placement and septic shock were risk factors for death from IFI. Recent surgery (within 2 weeks) and drainage tube placement did not increase mortality in these IFI patients. Increased serum levels of PCT (AUC 0.601, 95% CI 0.536-0.665, = 0.003) and CRP (AUC 0.578, 95% CI 0.512-0.644, = 0.020) provided effective predictors of 30-day mortality rates. We report for the first time epidemiological data on invasive fungal infections in Northeast China over the past 5 years. Despite the limited available clinical data, these findings will greatly aid clinical health care workers with regard to the identification, prevention, and treatment of IFI in hospitalized patients.
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http://dx.doi.org/10.3389/fcimb.2020.553648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642834PMC
October 2020

Duck enteritis virus infection suppresses viability and induces apoptosis and endoplasmic reticulum stress in duck embryo fibroblast cells via the regulation of Ca.

J Vet Med Sci 2021 Apr 28;83(3):549-557. Epub 2020 Oct 28.

College of Animal Science, Guizhou University, Guiyang 550025, PR China.

Duck viral enteritis (DVE) is a lethal viral disease caused by duck enteritis virus (DEV) via an unknown mechanism. This study explores the relationship between Chinese standard challenge strain DEV (DEV-CSC)-induced apoptosis and endoplasmic reticulum stress (ERS) in duck embryo fibroblast (DEF) cells. Here we examined changes in Ca concentration, cell proliferation, apoptosis, and the differential expression of C/EBP homologous protein (CHOP), glucose regulatory protein 78 (GRP78), and activating transcription factor 6 (ATF6) in infected cells. The results revealed that DEV-CSC infection significantly decreased Ca concentration, suppressed cell viability, and induced apoptosis in DEF cells. Further experiments also demonstrated that DEV-CSC infection significantly upregulates CHOP, GRP78, and ATF6 expression. In addition, we show that the addition of ethylenediaminetetraacetic acid (EDTA) reverses the induction of apoptosis and the ERS mediated inhibition of cell viability in DEF cells associated with DEV-CSC infection. Therefore, we can conclude that infection with DEV-CSC induces apoptosis and ERS reducing the viability of DEF cells via the regulation of Ca. These findings may provide a new target for the treatment of DVE.
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http://dx.doi.org/10.1292/jvms.19-0584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025435PMC
April 2021

Current Advances on 3D-Bioprinted Liver Tissue Models.

Adv Healthc Mater 2020 12 19;9(24):e2001517. Epub 2020 Oct 19.

State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, P. R. China.

The liver, the largest gland in the human body, plays a key role in metabolism, bile production, detoxification, and water and electrolyte regulation. The toxins or drugs that the gastrointestinal system absorbs reach the liver first before entering the bloodstream. Liver disease is one of the leading causes of death worldwide. Therefore, an in vitro liver tissue model that reproduces the main functions of the liver can be a reliable platform for investigating liver diseases and developing new drugs. In addition, the limitations in traditional, planar monolayer cell cultures and animal tests for evaluating the toxicity and efficacy of drug candidates can be overcome. Currently, the newly emerging 3D bioprinting technologies have the ability to construct in vitro liver tissue models both in static scaffolds and dynamic liver-on-chip manners. This review mainly focuses on the construction and applications of liver tissue models based on 3D bioprinting. Special attention is given to 3D bioprinting strategies and bioinks for constructing liver tissue models including the cell sources and hydrogel selection. In addition, the main advantages and limitations and the major challenges and future perspectives are discussed, paving the way for the next generation of in vitro liver tissue models.
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http://dx.doi.org/10.1002/adhm.202001517DOI Listing
December 2020

Metabolomics and correlation network analyses of core biomarkers in type 2 diabetes.

Amino Acids 2020 Sep 15;52(9):1307-1317. Epub 2020 Sep 15.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

The identification of metabolic pathways and the core metabolites provide novel molecular targets for the prevention and treatment of diseases. Diabetes is often accompanied with multiple metabolic disorders including hyperglycemia and dyslipidemia. Analysis of the variances of plasma metabolites is critical for identifying potential therapeutic targets for diabetes. In the current study, non-diabetic subjects with normal glucose tolerance and diabetics (age 40-60 years; n = 42 per group) were selected and plasma samples were analyzed by GC-MS for various metabolites profiling followed by network analysis. Our study identified 24 differential metabolites that were mainly enriched in protein synthesis, lipid and amino acid metabolism. Furthermore, we applied the correlation network analysis on these differential metabolites in fatty acid and amino acid metabolism and identified glycerol, alanine and serine as the hub metabolites in diabetic group. In addition, we measured the activities of enzymes in gluconeogenesis and amino acid metabolism and found significant higher activities of fructose 1,6-bisphosphatase, pyruvate carboxylase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in diabetic patients. In contrast, the enzyme activities of glycolysis pathway (e.g., hexokinase, phosphofructokinase and pyruvate kinase) and TCA cycle (e.g., isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase and malate dehydrogenase) were reduced in diabetes. Together, our studies showed that the linoleic acid and amino acid metabolism were the most affected metabolic pathways and glycerol, alanine and serine could play critical role in diabetes. The integration of network analysis and metabolic data could provide novel molecular targets or biomarkers for diabetes.
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http://dx.doi.org/10.1007/s00726-020-02891-8DOI Listing
September 2020

Judicious fabrication of bifunctionalized graphene oxide/MnFeO magnetic nanohybrids for enhanced removal of Pb(II) from water.

J Colloid Interface Sci 2020 Nov 4;579:815-822. Epub 2020 Jul 4.

School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China.

Novel ternary nanohybrids, bifunctionalized graphene oxide/MnFeO magnetic nanoparticles (PEHA-Phos-GO/MnFeO), were prepared by a facile method and applied for the removal of Pb(II) from aqueous solution. Attributing to the numerous amino and phosphate groups on the bifunctionalized GO nanosheets as well as the magnetic nanoparticles of MnFeO, PEHA-Phos-GO/MnFeO demonstrated high removal efficiency of Pb(II) and rapid magnetic separation. The 366.4 mg/g maximum adsorption capacity of Pb(II) on PEHA-Phos-GO/MnFeO was obtained at the optimal adsorption pH of 5.5, much higher than that on GO (212.1 mg/g). The kinetics and isotherm data indicated that the adsorption processes can be well described by the pseudo-second-order kinetics and the Langmuir model. For the adsorption of Pb(II) on PEHA-Phos-GO/MnFeO, thermodynamic studies revealed the endothermic nature of the spontaneous adsorption process. The exhibited adsorption capacity, easy magnetic separation and reusability make the PEHA-Phos-GO/MnFeO nanohybrids very promising adsorbents for efficacious removal of heavy metals from aqueous solutions in environmental pollution cleanup.
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http://dx.doi.org/10.1016/j.jcis.2020.06.085DOI Listing
November 2020

Comment on "Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus".

Diabetes Res Clin Pract 2020 08 12;166:108287. Epub 2020 Jul 12.

Department of Neurology Xinqiao Hospital, The Second Affiliated Hospital of the Army Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, China. Electronic address:

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http://dx.doi.org/10.1016/j.diabres.2020.108287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354265PMC
August 2020

Effects of a Reactive Phosphorus-Sulfur Containing Flame-Retardant Monomer on the Flame Retardancy and Thermal and Mechanical Properties of Unsaturated Polyester Resin.

Polymers (Basel) 2020 Jun 27;12(7). Epub 2020 Jun 27.

State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei 230000, China.

A novel reactive phosphorus and sulfur-containing monomer (bis(acryloxyethyldiphenylphosphate)sulfone, BADPS) was synthesized to enhance the comprehensive performance of unsaturated polyester resin (UPR),and corresponding flame-retardant unsaturated polyester resins (FR-UPRs) with various amounts of BADPS were prepared by radical bulk polymerization. The flame retardancy and thermal and mechanical properties of the UPR samples were investigated by limiting oxygen index (LOI) measurements, cone calorimetry, differential scanning calorimetry (DSC),a thermogravimetric analysis (TGA), and a tension test. The results showed that the introduction of BADPS remarkably enhanced the flame resistance and high-temperature stability, as well as the tensile performance of UPR. Scanning electron microscopy (SEM),Fourier transform infrared (FTIR), and Raman spectroscopy studies revealed that BADPS can efficaciously promote the formation of UPR char residue with an improved microstructure and increased graphitization degree, which enhancedthe high-temperature stability and char yield of UPR. Additionally, a thermogravimetry-Fourier transform infrared (TG-FTIR) analysis corroborated that the evolution of combustible volatiles from UPR decomposition was substantially restrained by the incorporation of BADPS, which is beneficial for the suppression of fire hazards in UPR.
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http://dx.doi.org/10.3390/polym12071441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407604PMC
June 2020

LNC942 promoting METTL14-mediated mA methylation in breast cancer cell proliferation and progression.

Oncogene 2020 07 23;39(31):5358-5372. Epub 2020 Jun 23.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, PR China.

Increasing evidence supports that long noncoding RNAs (lncRNAs) act as master regulators involved in tumorigenesis and development at the N6-methyladenine (mA) epigenetic modification level. However, the underlying regulatory mechanism in breast cancer (BRCA) remains elusive. Here, we unveil that LINC00942 (LNC942) exerts its functions as an oncogene in promoting METTL14-mediated mA methylation and regulating the expression and stability of its target genes CXCR4 and CYP1B1 in BRCA initiation and progression. Specifically, LNC942 and METTL14 were significantly upregulated accompanied with the upregulation of mA levels in BRCA cells and our included BRCA cohorts (n = 150). Functionally, LNC942 elicits potent oncogenic effects on promoting cell proliferation and colony formation and inhibiting cell apoptosis, subsequently elevating METTL14-mediated mA methylation levels and its associated mRNA stability and protein expression of CXCR4 and CYP1B1 in BRCA cells. Mechanistically, LNC942 directly recruits METTL14 protein by harboring the specific recognize sequence (+176-+265), thereby stabilized the expression of downstream targets of LNC942 including CXCR4 and CYP1B1 through posttranscriptional mA methylation modification in vitro and in vivo. Therefore, our results uncover a novel LNC942-METTL14-CXCR4/CYP1B1 signaling axis, which provides new targets and crosstalk mA epigenetic modification mechanism for BRCA prevention and treatment.
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http://dx.doi.org/10.1038/s41388-020-1338-9DOI Listing
July 2020

System dynamics modelling of urbanization under energy constraints in China.

Sci Rep 2020 06 19;10(1):9956. Epub 2020 Jun 19.

School of Landscape Architecture and Planning, University of Florida, Gainesville, FL, 32611, USA.

The rapid urbanization in China has been associated with a growing hunger for energy consumption and steadily-increasing CO emissions. In this paper, an integrated system dynamics model composed of four sub-models is developed to simulate the urbanization and energy consumption in China from 1998 to 2050. Three scenarios are provided: accelerated economic development, emission reduction constraint, and low-carbon oriented. The result reveals that rapid economic growth and sufficient energy supply will foster China's urbanization in all three scenarios. Under the low carbon transition scenario, China's urbanization rate is expected to reach 76.41% in 2050, both reducing carbon emissions and promoting eco-friendly development. All three scenarios witness a dramatic growth of residential energy consumption and a steady increase of industrial energy consumption. China still has a long way to achieve the low-carbon transition goal. China should promote renewable resources and energy, pursue a low-carbon lifestyle, and reduce energy intensity over the next few decades.
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http://dx.doi.org/10.1038/s41598-020-66125-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305140PMC
June 2020

A Three-Dimensional Nano-web Scaffold of Ferroelectric Beta-PVDF Fibers for Lithium Metal Plating and Stripping.

ACS Appl Mater Interfaces 2020 Jul 23;12(26):29235-29241. Epub 2020 Jun 23.

School of Energy & Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

Lithium metal has been considered as an anode material to improve energy densities of lithium chemistry-based rechargeable batteries (that is to say, lithium metal batteries or LMBs). Higher capacities and cell voltages are ensured by replacing practically used anode materials such as graphite with lithium metal. However, lithium metal as the LMB anode material has been challenged by its dendritic growth, electrolyte decomposition on its fresh surface, and its serious volumetric change. To address the problems of lithium metal anodes, herein, we guided and facilitated lithium ion transport along a spontaneously polarized and highly dielectric material. A three-dimensional web of nanodiameter fibers of ferroelectric beta-phase polyvinylidene fluoride (beta-PVDF) was loaded on a copper foil by electrospinning (PVDF#Cu). The electric field applied between the nozzle and target copper foil forced the dipoles of PVDF to be oriented centro-asymmetrically and then the beta structure induced ferroelectric polarization. Three-fold benefits of the ferroelectric nano-web architecture guaranteed the plating/stripping reversibility especially at high rates: (1) three-dimensional scaffold to accommodate the volume change of lithium metal during plating and stripping, (2) electrolyte channels between fibers to allow lithium ions to move, and (3) ferroelectrically polarized or negatively charged surface of beta-PVDF fibers to encourage lithium ion hopping along the surface. Resultantly, the beta-PVDF web architecture drove dense and integrated growth of lithium metal within its structure. The kinetic benefit expected from the ferroelectric lithium ion transport of beta-PVDF as well as the porous architecture of PVDF#Cu was realized in a cell of LFP as a cathode and lithium-plated PVDF#Cu as an anode. Excellent plating/stripping reversibility along repeated cycles was successfully demonstrated in the cell even at a high current such as 2.3 mA cm, which was not obtained by the nonferroelectric polymer layer.
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http://dx.doi.org/10.1021/acsami.0c05065DOI Listing
July 2020

Identification and Validation of Prognostically Relevant Gene Signature in Melanoma.

Biomed Res Int 2020 8;2020:5323614. Epub 2020 May 8.

Department of Dermatology, The First Hospital of China Medical University, 110001 Shenyang, China.

Background: Currently, effective genetic markers are limited to predict the clinical outcome of melanoma. High-throughput multiomics sequencing data have provided a valuable approach for the identification of genes associated with cancer prognosis.

Method: The multidimensional data of melanoma patients, including clinical, genomic, and transcriptomic data, were obtained from The Cancer Genome Atlas (TCGA). These samples were then randomly divided into two groups, one for training dataset and the other for validation dataset. In order to select reliable biomarkers, we screened prognosis-related genes, copy number variation genes, and SNP variation genes and integrated these genes to further select features using random forests in the training dataset. We screened for robust biomarkers and established a gene-related prognostic model. Finally, we verified the selected biomarkers in the test sets (GSE19234 and GSE65904) and on clinical samples extracted from melanoma patients using qRT-PCR and immunohistochemistry analysis.

Results: We obtained 1569 prognostic-related genes and 1101 copy-amplification, 1093 copy-deletions, and 92 significant mutations in genomic variants. These genomic variant genes were closely related to the development of tumors and genes that integrate genomic variation. A total of 141 candidate genes were obtained from prognosis-related genes. Six characteristic genes (, , , , , and ) were selected by random forest feature selection, many of which have been reported to be associated with tumor progression. Cox regression analysis was used to establish a 6-gene signature. Experimental verification with qRT-PCR and immunohistochemical staining proved that these selected genes were indeed expressed at a significantly higher level compared with the normal tissues. This signature comprised an independent prognostic factor for melanoma patients.

Conclusions: We constructed a 6-gene signature (, , , , , and ) as a novel prognostic marker for predicting the survival of melanoma patients.
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http://dx.doi.org/10.1155/2020/5323614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238332PMC
March 2021

Deeply Rechargeable and Hydrogen-Evolution-Suppressing Zinc Anode in Alkaline Aqueous Electrolyte.

Nano Lett 2020 Jun 29;20(6):4700-4707. Epub 2020 May 29.

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.

Metallic zinc as a rechargeable anode material for aqueous batteries has gained tremendous attention. Zn-air batteries, which operate in alkaline electrolytes, are promising with the highest theoretical volumetric energy density. However, rechargeable zinc anodes develop slowly in alkaline electrolytes due to passivation, dissolution, and hydrogen evolution issues. In this study, we report the design of a submicron zinc anode sealed with an ion-sieving coating that suppresses hydrogen evolution reaction. The design is demonstrated with ZnO nanorods coated by TiO, which overcomes passivation, dissolution, and hydrogen evolution issues simultaneously. It achieves superior reversible deep cycling performance with a high discharge capacity of 616 mAh/g and Coulombic efficiency of 93.5% when cycled with 100% depth of discharge at lean electrolyte. It can also deeply cycle ∼350 times in a beaker cell. The design principle of this work may potentially be applied to other battery electrode materials.
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http://dx.doi.org/10.1021/acs.nanolett.0c01776DOI Listing
June 2020

Shenzao jiannao oral liquid, an herbal formula, ameliorates cognitive impairments by rescuing neuronal death and triggering endogenous neurogenesis in AD-like mice induced by a combination of Aβ42 and scopolamine.

J Ethnopharmacol 2020 Sep 19;259:112957. Epub 2020 May 19.

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD Port, Dalian, 116600, PR China. Electronic address:

Ethnopharmacological Relevance: According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as "forgetfulness" or "dementia", and is mainly caused by "kidney essence deficiency" which ultimately induces "encephala reduction". Therefore, herbal formulas possessing the efficacy of nourishing kidney essence or replenishing brain marrow are commonly served as effective strategies for AD treatment. Shenzao jiannao oral liquid (SZJN), a traditional Chinese preparation approved by the China Food and Drug Administration (CFDA), is used for the treatment of insomnia and mind fatigue at present for its efficacy of nourishing kidneys. In present study, we found that SZJN could improve cognitive function of AD-like mice.

Aims Of Study: This study aims to investigate the effects of SJZN on ameliorating cognitive deficits of AD-like mouse model, and to illuminate the underlying mechanisms from the perspective of neuroprotection and neurogenesis.

Materials And Methods: Kunming mice (28 ± 2 g) were randomly allocated into seven groups: control, sham, model, donepezil and SZJN groups (low, middle and high). The AD mouse model was established by Aβ42 combined with scopolamine. SZJN were intragastrically administrated at doses of 0.3, 1.5 and 7.5 g/kg for 28 days. Morris water maze (MWM) test was applied to determine the cognitive function. Hematoxylin eosin (HE) and Nissl staining were carried out to evaluate pathological damages in the cortex and hippocampal tissues. To explore the protective effects of SZJN on multiple pathogenic factors of AD, protein levels of Aβ42, glial fibrillary acidic protein (GFAP), Bax, Bcl-2, Caspase-3, synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), and neurogenesis related proteins were assessed using Immunofluorescence (IF) and western blot analysis. In vitro, the AD cell model was established by transduction of APP genes into Neural stem cells (NSCs) isolated from the hippocampal tissues of neonatal C57BL/6 mice. Cell viability assay and neurosphere formation assay were carried out to verify the efficacy of SZJN on proliferation of NSCs.

Results: Our results demonstrated that SZJN (1.5 g/kg and 7.5 g/kg) treatment significantly ameliorated cognitive deficits of AD-like mice. SZJN (7.5 g/kg) treatment significantly retarded the pathological damages including neuronal degeneration, neuronal apoptosis, Aβ peptides aggregation and reaction of astrocytes in AD-like mice. In addition, SZJN (7.5 g/kg) increased the expression of BDNF and SYP, and restored the abnormal level of MDA and SOD in the brain of AD-like mice. Furthermore, SZJN treatment for 28 days remarkably increased the proliferation of NSCs evidenced by more Nestin and BrdU cells in the hippocampal DG regions, and increased the amount of mature neurons marked by NeuN both in the cortex and hippocampal DG regions. In vitro, SZJN treatement (16, 32, 64 mg/ml) promoted the proliferation of NSCs evidenced by the increased amount and enlarged size of the neurospheres (p < 0.05).

Conclusions: Our findings indicated that SZJN could ameliorate cognitive deficits by protecting neurons from death and triggering endogenous neurogenesis. Therefore, SZJN may be considered as a promising agent to restore neuronal loss and deter the deterioration in AD patients.
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http://dx.doi.org/10.1016/j.jep.2020.112957DOI Listing
September 2020

Osthole ameliorates cognitive impairments via augmenting neuronal population in APP / PS1 transgenic mice.

Neurosci Res 2021 Mar 14;164:33-45. Epub 2020 Apr 14.

School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disorder with notable factors of dysfunction in multiple neurological changes, encompassing neuronal loss in the frontal cortex and hippocampal regions. Dysfunction of proliferation and self-renewal of neural stem cells (NSCs) was observed in AD patients and animals. Thereby, mobilizing endogenous neurogenesis by pharmacological agents would provide a promising route for neurodegeneration. Osthole (Ost), a natural coumarin derivative, has been reported to exert extensive neuroprotective effects in AD. However, whether ost can facilitate endogenous neurogenesis against AD in vivo is still unknown. In this study, by using Morris water maze (MWM) test, hematoxylin-eosin (HE) staining, Nissl staining, immunofluorescence analysis and western blot, we demonstrated that oral administration of ost could improve the learning and memory function, inhibit neuronal apoptosis, elevate the expression of glial cell line derived neurotrophic factor (GDNF), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95). Moreover, ost could remarkably enhance proliferation of NSCs and increase the amount of mature neurons in APP/PS1 transgenic mice. Together, our findings demonstrated that ost possessed the ability of promoting endogenous neurogenesis and ost could be served as a plausible agent to reverse or slow down the progress of AD.
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http://dx.doi.org/10.1016/j.neures.2020.04.001DOI Listing
March 2021

Selection and validation of appropriate reference genes for gene expression studies in .

Physiol Mol Biol Plants 2020 Jan 9;26(1):173-188. Epub 2019 Dec 9.

Beijing Key Laboratory of Ornamental Plants Germplasm Innovation and Molecular Breeding, Beijing, China.

The qRT-PCR method has been widely used to detect gene expression level in plants, helping to understand the molecular mechanisms. However, there are few researches which focus on the selection of the internal reference genes in . To select the appropriate reference genes of aimed at qRT-PCR normalization, twelve candidate reference genes were selected from our transcriptome data. Their expression was assessed by RT-PCR analysis in 47 samples, including 12 species cultivars, different organs and tissues. GeNorm, NormFinder, and BestKeeper software were used to select the appropriate reference genes, and were used to verify the accuracy of the outcome. The results showed that was a stable reference gene in leaves of twelve germplasms and in different developmental stages of fruits. , + , and + +  were stable reference genes in different organs. and were stable reference genes in different flower tissues and different developmental stages of the flower buds. When plants were stressed with PEG or ABA, + +  was the stable reference gene group for qRT-PCR. The results provided the basis for investigating the physiological and biochemical processes of related to medicinal and ornamental properties, and drought-resistance in the level of gene expression.
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http://dx.doi.org/10.1007/s12298-019-00731-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036397PMC
January 2020

A sp. NEAU-HV9: Isolation, Identification, and Potential as a Biocontrol Agent against of Tomato Plants.

Microorganisms 2020 Mar 1;8(3). Epub 2020 Mar 1.

Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin 150030, China.

is an important soil-borne bacterial plant pathogen. In this study, an actinomycete strain named NEAU-HV9 that showed strong antibacterial activity against was isolated from soil using an in vitro screening technique. Based on physiological and morphological characteristics and 98.90% of 16S rRNA gene sequence similarity with 1MR-8, the strain was identified as a member of the genus . Tomato seedling and pot culture experiments showed that after pre-inoculation with the strain NEAU-HV9, the disease occurrence of tomato seedlings was effectively prevented for . Then, a bioactivity-guided approach was employed to isolate and determine the chemical identity of bioactive constituents with antibacterial activity from strain NEAU-HV9. The structure of the antibacterial metabolite was determined as actinomycin D on the basis of extensive spectroscopic analysis. To our knowledge, this is the first report that actinomycin D has strong antibacterial activity against with a MIC (minimum inhibitory concentration) of 0.6 mg L (0.48 μmol L). The in vivo antibacterial activity experiment showed that actinomycin D possessed significant preventive efficacy against in tomato seedlings. Thus, strain NEAU-HV9 could be used as BCA (biological control agent) against , and actinomycin D might be a promising candidate for a new antibacterial agent against .
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http://dx.doi.org/10.3390/microorganisms8030351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142955PMC
March 2020

Identification of functional circRNA/miRNA/mRNA regulatory network for exploring prospective therapy strategy of colorectal cancer.

J Cell Biochem 2020 Mar 1. Epub 2020 Mar 1.

Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, China.

Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.
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http://dx.doi.org/10.1002/jcb.29703DOI Listing
March 2020

Non-coenzyme role of vitamin B1 in RANKL-induced osteoclastogenesis and ovariectomy induced osteoporosis.

J Cell Biochem 2020 07 26;121(7):3526-3536. Epub 2020 Feb 26.

Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.

Vitamins B are co-enzymes participating in energy metabolic pathways. While some vitamins B are known affecting bone homeostasis, the effects of vitamin B1 (thiamine) on bone health remains unclear. In our study, we used cell counting kit-8, tartrate-resistant acid phosphatase stain, actin cytoskeleton stain, and pit formation assay to evaluate the effect of thiamine on osteoclast differentiation, formation, and function, respectively. Then we used dichloro-dihydro-fluorescein diacetate assay to investigate reactive oxygen species (ROS) generation and removal. Osteoporosis model by ovariectomy was established for animal experiments. We found that thiamine had inhibitory effect on osteoclast differentiation. And its inhibitory role on osteoclast differentiation is in a dose-dependent way. Mechanistically, ThDP suppresses intracellular ROS accumulation and unfolded protein response signaling during osteoclastogenesis via inhibiting Rac-Nox1/2/4 and intracellular inositol-requiring protein-1α/X-box-binding protein pathways, respectively. Osteoporotic mice treated with thiamine rich dietary showed better bone strength relative to thiamine deficient dietary. Our study explored the non-coenzyme inhibitory functions of B1 vitamin in receptor activator of nuclear factor κB ligand induced osteoclastogenesis and uncovered the significance of B1 vitamin in bone health.
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http://dx.doi.org/10.1002/jcb.29632DOI Listing
July 2020

Anterior gradient 2-derived peptide upregulates major histocompatibility complex class I-related chains A/B in hepatocellular carcinoma cells.

Life Sci 2020 Apr 5;246:117396. Epub 2020 Feb 5.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China; Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation; Liaoning Cancer immune peptide drug Engineering Technology Research Center; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education; China Medical University, Shenyang, Liaoning Province, China.. Electronic address:

Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Decrease in NKG2D ligand levels and exhaustion of NK cells in HCC patients are major causes of immune escape, high recurrence, poor prognosis, and low overall survival. Enhancing the susceptibility of HCC to NK cells by upregulating NKG2DLs on tumor cells is an effective treatment strategy. This study aimed to identify the effect of the Anterior gradient 2 (AGR2)-derived peptide P1, which was reported to bind to HLA-A*0201 as an epitope, on both the expression of major histocompatibility complex class I-related chains A/B (MICA/B) on HCC cells and the cytotoxicity of NK cells.

Main Methods: The effect of P1 on MICA/B expression on HCC cells was determined by qRT-PCR, western blotting, and flow cytometry analysis. HCC cells were pre-treated with various pathway inhibitors to identify the molecular pathways associated with P1 treatment. The cytotoxicity of NK cells toward HCC was investigated by LDH cytotoxicity assay. The tumor-suppression effect of P1 was determined in vivo using a NOD/SCID mice HCC model.

Key Findings: P1 significantly increased MICA/B expression on HCC cells, thereby enhancing their susceptibility to the cytotoxicity of NK cells in vitro and in vivo. Further, p38 MAPK cell signaling pathway inhibitor SB203580 significantly attenuated the effects of P1 in vivo and in vitro.

Significance: P1 upregulates MICA and MICB expression on HCC cells, thereby promoting their recognition and elimination by NK cells, which makes P1 an attractive novel immunotherapy agent.
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http://dx.doi.org/10.1016/j.lfs.2020.117396DOI Listing
April 2020

JsrNet: A Joint Sampling-Reconstruction Framework for Distributed Compressive Video Sensing.

Sensors (Basel) 2019 Dec 30;20(1). Epub 2019 Dec 30.

College of Internet of Things, Nanjing University of Posts and Telecommunications, Nanjing 210003, China.

Huge video data has posed great challenges on computing power and storage space, triggering the emergence of distributed compressive video sensing (DCVS). Hardware-friendly characteristics of this technique have consolidated its position as one of the most powerful architectures in source-limited scenarios, namely, wireless video sensor networks (WVSNs). Recently, deep convolutional neural networks (DCNNs) are successfully applied in DCVS because traditional optimization-based methods are computationally elaborate and hard to meet the requirements of real-time applications. In this paper, we propose a joint sampling-reconstruction framework for DCVS, named "JsrNet". JsrNet utilizes the whole group of frames as the reference to reconstruct each frame, regardless of key frames and non-key frames, while the existing frameworks only utilize key frames as the reference to reconstruct non-key frames. Moreover, different from the existing frameworks which only focus on exploiting complementary information between frames in joint reconstruction, JsrNet also applies this conception in joint sampling by adopting learnable convolutions to sample multiple frames jointly and simultaneously in an encoder. JsrNet fully exploits spatial-temporal correlation in both sampling and reconstruction, and achieves a competitive performance in both the quality of reconstruction and computational complexity, making it a promising candidate in source-limited, real-time scenarios.
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http://dx.doi.org/10.3390/s20010206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983164PMC
December 2019

In Operando Visualization of the Electrochemical Formation of Liquid Polybromide Microdroplets.

Angew Chem Int Ed Engl 2019 Oct 5;58(43):15228-15234. Epub 2019 Sep 5.

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Zinc-bromine flow batteries are promising for stationary energy storage, and bromine-complexing agents have been used to form phase-separated liquid polybromide products. However, an understanding of the dynamics of polybromide nucleation is limited due to the beam sensitivity and complexity of polybromides. Here we report an in operando platform composed of dark-field light microscopy and a transparent electrochemical cell to reveal the dynamics of polybromide formation in their native environment. Using our platform, we confirm and reveal the liquid nature, chemical composition, pinning effect (strong interaction with Pt), residual effect (residual charge products on the surface), self-discharging, and over-oxidation of the polybromide products. The results provide insights into the role of complexing agents and guide the future design of zinc-bromine flow batteries. Furthermore, our in operando platform can potentially be used to study sensitive species and phases in other electrochemical reactions.
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http://dx.doi.org/10.1002/anie.201906980DOI Listing
October 2019

Polypropylene Carbonate-Based Adaptive Buffer Layer for Stable Interfaces of Solid Polymer Lithium Metal Batteries.

ACS Appl Mater Interfaces 2019 Aug 24;11(31):27906-27912. Epub 2019 Jul 24.

Department of Condensed Matter Physics , University of Barcelona , Barcelona 08028 , Spain.

Solid polymer electrolytes (SPEs) have the potential to enhance the safety and energy density of lithium batteries. However, poor interfacial contact between the lithium metal anode and SPE leads to high interfacial resistance and low specific capacity of the battery. In this work, we present a novel strategy to improve this solid-solid interface problem and maintain good interfacial contact during battery cycling by introducing an adaptive buffer layer (ABL) between the Li metal anode and SPE. The ABL consists of low molecular-weight polypropylene carbonate , poly(ethylene oxide) (PEO), and lithium salt. Rheological experiments indicate that ABL is viscoelastic and that it flows with a higher viscosity compared to PEO-only SPE. ABL also has higher ionic conductivity than PEO-only SPE. In the presence of ABL, the interface resistance of the Li/ABL/SPE/LiFePO battery only increased 20% after 150 cycles, whereas that of the battery without ABL increased by 117%. In addition, because ABL makes a good solid-solid interface contact between the Li metal anode and SPE, the battery with ABL delivered an initial discharge specific capacity of >110 mA·h/g, which is nearly twice that of the battery without ABL, which is 60 mA·h/g. Moreover, ABL is able to maintain electrode-electrolyte interfacial contact during battery cycling, which stabilizes the battery Coulombic efficiency.
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http://dx.doi.org/10.1021/acsami.9b08285DOI Listing
August 2019

Mature osteoclast-derived apoptotic bodies promote osteogenic differentiation via RANKL-mediated reverse signaling.

J Biol Chem 2019 07 5;294(29):11240-11247. Epub 2019 Jun 5.

Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

In bone remodeling, after a lifespan of ∼2 weeks, osteoclasts undergo apoptosis in each bone turnover cycle, resulting in generation of a large number of apoptotic bodies (ABs). However, the biological roles of osteoclast-derived ABs (OC-ABs) in bone remodeling have not been investigated and remain unknown. In this study, we stimulated bone marrow macrophages with receptor activator of NF-κB ligand (RANKL) to obtain both preosteoclasts and mature osteoclasts (mOCs). We then used alendronate to induce apoptosis in preosteoclasts and mOCs and generate the respective ABs and used flow cytometry and immunoblotting to characterize the sizes and immunogenic characteristics of the extracted ABs. We show that mOC-ABs are engulfed by preosteoblastic MC3T3-E1 cells and promote the viability of these cells. Among all osteoclast-derived extracellular vesicles, mOC-ABs had the highest osteogenic potency. We further observed that mOC-ABs had the highest vesicular receptor activator of NF-κB (RANK) levels among all types of osteoclast-derived extracellular vesicles. Of note, masking of vesicular RANK by soluble RANKL strongly abolished the osteogenic potency of osteoclast-derived ABs. Mechanistically, we found that mOC-ABs induce osteoblast differentiation by activatingPI3K/AKT/mechanistic target of rapamycin (mTOR)/ribosomal protein S6 kinase signaling. In conclusion, OC-ABs promote osteogenic differentiation by stimulating osteoblast differentiation via activation of RANKL reverse signaling. These findings provide important insights into the reversal phase between the bone resorption and formation stages during bone remodeling and identify an AB-dependent cellular signaling mechanism in osteoclast-osteoblast coupling.
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http://dx.doi.org/10.1074/jbc.RA119.007625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643026PMC
July 2019

Experimental study of rhBMP-2 chitosan nano-sustained release carrier-loaded PLGA/nHA scaffolds to construct mandibular tissue-engineered bone.

Arch Oral Biol 2019 Jun 28;102:16-25. Epub 2019 Mar 28.

Department of Oral & Maxillofacial Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; School of Stomatology, Qingdao University, Qingdao, Shandong, China.

Objectives: To develop PLGA/nHA scaffold containing BMP-2 cell growth factor chitosan sustained release system as tissue engineered bone for repairing large jaw defects, test its sustained release rhBMP-2 efficiency in vitro, and evaluate its Osteogenesis in rabbit mandibular defects.

Methods: Tissue engineered bone scaffold complexes were prepared by complexing rhBMP-2 loaded chitosan (CS / rhBMP-2) nano sustained release carrier with PLGA / nHA scaffold carrier by 3D printing. In vitro, the porosity, pore size and degradation rate and the dose-time effect relationship of cytokine release were examined. Micro-CT, hematoxylin/eosin staining, Masson staining and immunohistochemistry were determined at week 4, week 8 and week 12 in 18 rabbits.

Results: In vitro, the porosity was (73.64 ± 1.82)%, and the average pore diameter was (431.31 ± 18.40) μm. The cumulative release was only 9.54 ± 0.86% within 48 h and 61.38 ± 2.39% on the 30th day. In vivo, Micro-CT examination showed that the BMD and the bone volume fraction at 4, 8, and 12 weeks were higher in the implantation group than in the control group. In the 12th week, Masson staining showed that new bone occupied 19.2% of the defect area in the control group, whereas the proportion of new bone reached 45.5% in the experimental group.

Conclusions: PLGA/nHA/CS/rhBMP-2 scaffold complex effectively controlled the early burst effect of rhBMP-2. The bone tissue engineering scaffold complex had good biocompatibility and induced osteogenic effects. It successfully repaired the experimental bone defect area of the rabbit mandible.
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http://dx.doi.org/10.1016/j.archoralbio.2019.03.023DOI Listing
June 2019

[Osthole suppresses amyloid precursor protein expression by up-regulating miRNA-101a-3p in Alzheimer's disease cell model].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2018 May;47(5):473-479

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, Liaoning Province, China.

Objective: To investigate the effect of osthole on the expression of amyloid precursor protein (APP) in Alzheimer's disease (AD) cell model and its mechanism.

Methods: The SH-SY5Y cell with over expression of APP was established by transfection by liposome 2000. The cells were treated with different concentrations of osthole, and the cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The differentially expressed miRNAs with and without osthole treatment were detected by miRNA array, and the target genes binding to the differentially expressed miRNAs were identified and verified by databases and Cytoscape. After the inhibitor of the differentially expressed miRNA was transduced into cells, the changes of APP and amyloid β (Aβ) protein were determined by immunofluorescence cytochemistry, and the mRNA expression of APP was determined by RT-PCR.

Results: The AD cell model with over expression of APP was established successfully. The results of MTT and LDH assay showed that osthole had a protective effect on cells and alleviated cell damage. miR-101a-3p was identified as the differentially expressed miRNA, which was binding to the 3'-UTR of APP. Compared with APP group, the expression of APP and Aβ protein and APP mRNA increased in the miR-101a-3p inhibitor group (all <0.01), while the expression of APP and Aβ protein and APP mRNA decreased in the cells with osthole treatment (all <0.01).

Conclusions: Osthole inhibits the expression of APP by up-regulating miR-101a-3p in AD cell model.
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May 2018