Publications by authors named "Xuejian Wu"

44 Publications

LncRNA X inactive-specific transcript promotes osteoclast differentiation through Tgif2 by acting as a ceRNA of miR-590-3p in a murine model.

Regen Med 2021 Jul 30;16(7):643-653. Epub 2021 Jun 30.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

This study aims to investigate whether  can regulate osteoclast differentiation in osteoporosis and the mechanism. The mouse model of osteoporosis was established by ovariectomy surgery. Osteoclast differentiation from RAW264.7 cells was induced . The relationships between associated genes were assessed. and Tgif2 were upregulated, but was downregulated in ovariectomy mouse femurs and cell models. knockdown or overexpression inhibited Tgif2 expression and osteoclast differentiation. Tgif2 and were the targets of . Increased expression inhibited Tgif2 level and osteoclast differentiation, while overexpression reversed these effects. serves as a ceRNA of to promote Tgif2 level; thereby, contributing to osteoclast differentiation.
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http://dx.doi.org/10.2217/rme-2020-0174DOI Listing
July 2021

Punicalagin attenuates osteoarthritis progression via regulating Foxo1/Prg4/HIF3α axis.

Bone 2021 Nov 23;152:116070. Epub 2021 Jun 23.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.. Electronic address:

Background: Punicalagin (PUN) is a common anti-inflammatory polyphenol. However, the function and mechanism of PUN in osteoarthritis remains unknown.

Methods: Chondrocytes were isolated from rats, and confirmed by toluidine blue staining and immunofluorescence. Chondrocytes were challenged by lipopolysaccharide (LPS), and rat osteoarthritis model was established by Hulth method. The secretion of inflammatory factors, cell viability and apoptosis were tested via enzyme linked immunosorbent assay (ELISA), MTT and flow cytometry. The levels of forkhead box O1 (Foxo1), proteoglycan 4 (Prg4), hypoxia-inducible factor-3α (HIF3α), autophagy-related genes or extracellular matrix (ECM)-related proteins were examined via quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot or immunohistochemistry. The cartilage tissue damage was assessed via hematoxylin-eosin (HE) staining, toluidine blue staining and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick and labeling (TUNEL) staining.

Results: LPS triggered inflammatory injury in chondrocytes. PUN promoted autophagy to mitigate LPS-induced inflammatory injury. Foxo1 silence attenuated the effect of PUN on LPS-mediated autophagy inhibition and inflammatory injury. Promotion of Prg4/HIF3α axis abolished the influence of Foxo1 knockdown on LPS-mediated chondrocytes injury. PUN mitigated the inflammatory injury in rat osteoarthritis model by promoting autophagy and inhibiting inflammation and ECM degradation via Foxo1/Prg4/HIF3α axis.

Conclusion: PUN attenuates LPS-induced chondrocyte injury and osteoarthritis progression by regulating Foxo1/Prg4/HIF3α axis.
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http://dx.doi.org/10.1016/j.bone.2021.116070DOI Listing
November 2021

Down-regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR-524/RASSF6 axis.

J Gene Med 2021 Jun 20:e3373. Epub 2021 Jun 20.

Department of Orthopedics, Zhengzhou University First Affiliated Hospital, China.

Background: Osteosarcoma (OS) is a malignant bone cancer, in which circular RNAs (circRNAs) act as important modulators. The present study aimed to explore the functional role of circRNA itchy E3 ubiquitin protein ligase (circITCH) in the development and doxorubicin (DXR) resistance of OS and the possible mechanistic pathway.

Methods: A quantitative real-time polymerase chain reaction or western blot assays were exploited to analyze the expression of circITCH, miR-524 and Ras association domain family member 6 (RASSF6). Cell viability and half-maximal inhibitory concentration (IC ) value of DXR were monitored using a cell counting kit-8 assay. Cell migration, invasion and apoptosis were determined via a transwell assay and flow cytometry. The target interaction among circITCH, miR-524 and RASSF6 was validated by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model of MG-63/DXR cells stably expressing circITCH in nude mice was established for assessing the role of circITCH in vivo.

Results: Down-regulation of circITCH and RASSF6, as well as the up-regulation of miR-524, was revealed in OS by investigating 40 paired OS tissue and normal tissue samples. Overexpression of circITCH lowered the cell viability, IC value of DXR, migration and invasion, whereas it facilitated apoptosis of OS cells. circITCH sponged miR-524 to up-regulate RASSF6, causing OS progression inhibition and DXR resistance reduction. Additionally, circITCH up-regulation reduced tumor growth in vivo.

Conclusions: Transduction with circITCH represses OS progression and promotes DXR sensitivity by the miR-524/RASSF6 axis, providing a new perspective for therapeutic intervention.
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http://dx.doi.org/10.1002/jgm.3373DOI Listing
June 2021

Cartilage tissue miR-214-3p regulates the TrkB/ShcB pathway paracrine VEGF to promote endothelial cell migration and angiogenesis.

Bone 2021 10 6;151:116034. Epub 2021 Jun 6.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, China. Electronic address:

Background: This study was designed to explore the mechanisms through which chondrocytes regulated endothelial cell migration and angiogenesis in osteoarthritis (OA).

Methods: The expressions of related genes of OA were detected by Western blot and real-time quantitative PCR. Chondrocytes were co-cultured with endothelial cells, and migration as well as angiogenesis rates, and vascular endothelial growth factor (VEGF) secretion of the cells were detected. The relationship between miRNA and TrkB were analyzed by bioinformatics analysis, RNA immunoprecipitation and dual-luciferase assays. The effects of miRNA on the histopathology of the OA mice were determined.

Results: The expressions of NGF, TrkA, TrkB, and ShcB were increased significantly in OA patients. IL-1β promoted the expressions of TrkA, TrkB, and ShcB in chondrocytes and inhibited the expressions of chondrogenic differentiation markers, but shTrkB partially reversed IL-1β-mediated chondrogenic differentiation. Overexpression of TrkB promoted cell migration, angiogenesis, and VEGF levels, while silencing ShcB reversed the regulation of TrkB. Moreover, chondrocytes miR-214-3p regulated endothelial cell migration and angiogenesis by targeting TrkB paracrine VEGF to activate PI3K/Akt pathway proteins. In addition, overexpressed miR-214-3p improved collagenase-induced cartilage and synovial damage in OA mice.

Conclusion: The activation of TrkB/ShcB signaling pathway paracrine VEGF is mediated by miR-214-3p in chondrocytes and it regulates endothelial cell migration and angiogenesis in the development of OA.
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http://dx.doi.org/10.1016/j.bone.2021.116034DOI Listing
October 2021

Circular RNA hsa_circ_0032463 Acts as the Tumor Promoter in Osteosarcoma by Regulating the MicroRNA 498/LEF1 Axis.

Mol Cell Biol 2021 07 23;41(8):e0010021. Epub 2021 Jul 23.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Several studies have examined the relationship between osteosarcoma (OS) and microRNAs (miRNAs). However, only a few researchers have investigated the underlying mechanism of circular RNAs (circRNAs) in OS development. Our paper aimed to assess how hsa_circ_0032463 (abbreviated "circ_0032463" here) initiates and regulates OS progression. We detected circ_0032463 expression in OS tissues and cell lines by using reverse transcription-quantitative PCR (RT-qPCR) analysis and then investigated the interaction between circ_0032463, miRNA 489 (miR-498), and using RNA pulldown, RNA immunoprecipitation (RIP), and luciferase assays. The effect of the circ_0032463/miR-498/LEF1 axis on the migration, proliferation, and apoptosis levels of OS cells was explored using CCK-8, bromodeoxyuridine (BrdU), wound healing, and fluorescein isothiocyanate (FITC) assays. Our findings revealed that circ_0032463 expression was upregulated in OS tissues and cell lines. We also found that circ_0032463 interacted with miR-498, thereby reducing the expression of miR-498 in OS cells. Experimental results indicated that miR-498 could directly target in OS cells and that circ_0032463 could abrogate the tumor-inhibitory effect of miR-498 by upregulating in OS. More specifically, by binding to miR-498 and inhibiting expression, circ_0032463 promoted the migration and proliferation abilities of OS cells and suppressed the apoptosis ability of OS cells. Overall, this research suggested that circ_0032463 could promote OS development by regulating the miR-498/LEF1 axis.
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http://dx.doi.org/10.1128/MCB.00100-21DOI Listing
July 2021

Hsa_circ_0032463 acts as the tumor promoter in osteosarcoma by regulating the miR‑330‑3p/PNN axis.

Int J Mol Med 2021 05 31;47(5). Epub 2021 Mar 31.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.

Osteosarcoma (OS), also known as bone cancer, is a threat to the lives of millions of adolescents worldwide. Although dedicated efforts have been invested in reducing the mortality rate of this bone cancer, the research community is yet to find the exact causes of OS. Thus, the present research aimed to study the association between circular RNA circ_0032463 and OS progression. The impact of circ_0032463 on cells with OS was first evaluated using reverse transcription‑quantitative PCR. This evaluation was followed by the assessment of cell proliferation, viability, apoptosis, invasion and adhesion using BrdU, Cell Counting Kit‑8, flow cytometry, Transwell and cell adhesion assays, respectively. RNA pull‑down, RNA immunoprecipitation chip and dual‑luciferase reporter systems were utilized to investigate the relationship between circ_0032463, microRNA (miR)‑330‑3p and Pinin desmosome associated protein (PNN) in OS. The findings indicated that circ_0032463 and PNN were highly expressed in OS tissues and OS cell lines, and that they facilitated cell proliferation, viability, invasion and adhesion, but attenuated cell apoptosis in OS cells. The low expression of miR‑330‑3p suppressed OS development. It was also noted that circ_0032463 inhibited miR‑330‑3p to upregulate PNN expression. In conclusion, this study confirmed that by regulating the miR‑330‑3p/PNN axis, circular RNA circ_0032463 could function as a tumor enhancer in cells with OS.
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http://dx.doi.org/10.3892/ijmm.2021.4925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012025PMC
May 2021

Downregulation of long non-coding RNA UCA1 represses tumorigenesis and metastasis of osteosarcoma via miR-513b-5p/E2F5 axis.

Anticancer Drugs 2021 06;32(6):602-613

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Long non-coding RNAs have the regulatory roles in different kinds of human cancers. The key point of this study was to research the functional mechanisms of urothelial carcinoma associated 1 (UCA1) in the development of osteosarcoma. Quantitative real-time PCR was adopted for the expression detection of UCA1, microRNA-513b-5p (miR-513b-5p) and E2F transcription factor 5 (E2F5). The target relation was verified via dual-luciferase reporter assay and RNA pull-down assay. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Transwell assay was applied to assess cell migration and invasion. Western blot was performed for protein examination. Xenograft experiment was used to explore the effect of UCA1 on osteosarcoma in vivo. UCA1 expression was enhanced while miR-513b-5p was refrained in osteosarcoma tissues and cells. MiR-513b-5p was a target of UCA1. Inhibition of UCA1 or overexpression of miR-513b-5p suppressed osteosarcoma cell proliferation, migration and invasion. E2F5 was identified as a downstream gene of miR-513b-5p. MiR-513b-5p inhibitor or E2F5 overexpression rescued the progression inhibition of osteosarcoma by UCA1 knockdown, and UCA1 regulated E2F5 and Cyclin E expression by targeting miR-513b-5p. Downregulation of UCA1 restrained the tumorigenesis of osteosarcoma in vivo through the miR-513b-5p/E2F5 axis. Collectively, knockdown of UCA1 inhibited tumorigenesis and metastasis of osteosarcoma via regulating the miR-513b-5p/E2F5 axis. UCA1 might be a biological indicator in the progression and treatment of osteosarcoma.
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http://dx.doi.org/10.1097/CAD.0000000000001034DOI Listing
June 2021

ROS-Mediated Necroptosis Is Involved in Iron Overload-Induced Osteoblastic Cell Death.

Oxid Med Cell Longev 2020 16;2020:1295382. Epub 2020 Oct 16.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Excess iron has been reported to lead to osteoblastic cell damage, which is a crucial pathogenesis of iron overload-related osteoporosis. However, the cytotoxic mechanisms have not been fully documented. In the present study, we focused on whether necroptosis contributes to iron overload-induced osteoblastic cell death and related underlying mechanisms. Here, we showed that the cytotoxicity of iron overload in osteoblastic cells was mainly due to necrosis, as evidenced by the Hoechst 33258/PI staining, Annexin-V/PI staining, and transmission electronic microscopy. Furthermore, we revealed that iron overload-induced osteoblastic necrosis might be mediated via the RIPK1/RIPK3/MLKL necroptotic pathway. In addition, we also found that iron overload was able to trigger mitochondrial permeability transition pore (mPTP) opening, which is a critical downstream event in the execution of necroptosis. The key finding of our experiment was that iron overload-induced necroptotic cell death might depend on reactive oxygen species (ROS) generation, as N-acetylcysteine effectively rescued mPTP opening and necroptotic cell death. ROS induced by iron overload promote necroptosis via a positive feedback mechanism, as on the one hand N-acetylcysteine attenuates the upregulation of RIPK1 and RIPK3 and phosphorylation of RIPK1, RIPK3, and MLKL and on the other hand Nec-1, siRIPK1, or siRIPK3 reduced ROS generation. In summary, iron overload induced necroptosis of osteoblastic cells in vitro, which is mediated, at least in part, through the RIPK1/RIPK3/MLKL pathway. We also highlight the critical role of ROS in the regulation of iron overload-induced necroptosis in osteoblastic cells.
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http://dx.doi.org/10.1155/2020/1295382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586162PMC
May 2021

MicroRNA-613 alleviates IL-1β-induced injury in chondrogenic CHON-001 cells by targeting fibronectin 1.

Am J Transl Res 2020 15;12(9):5308-5319. Epub 2020 Sep 15.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, P. R. China.

Background: Osteoarthritis (OA) is an aging-related chronic degenerative joint disease. A number of miRNAs have been found to be involved in the development of OA, but the role of miR-613 in OA remains unclear. Thus, this study aimed to investigate the role of miR-613 during the progression of OA.

Methods: CHON-001 cells were transfected with miR-613 agonist for 48 h, and then exposed to 10 ng/mL IL-1β for 24 h. Cell viability, cell proliferation and cell apoptosis in CHON-001 cells were assessed by CCK-8, immunofluorescence, and flow cytometry assays, respectively. In addition, the dual luciferase reporter system assay was used to determine the interaction of miR-613 and fibronectin 1 in CHON-001 cells.

Results: The level of miR-613 was significantly decreased in IL-1β-treated CHON-001 cells. Overexpression of miR-613 markedly inhibited IL-1β-induced apoptosis in CHON-001 cells. In addition, upregulation of miR-613 obviously alleviated IL-1β-induced inflammatory response and cartilage matrix degradation in CHON-001 cells. Meanwhile, fibronectin 1 was identified as a direct binding target of miR-613 in CHON-001 cells. Overexpression of miR-613 alleviated IL-1β-induced injury in CHON-001 cells via downregulating the expression of fibronectin 1. Furthermore, overexpression of miR-613 alleviated cartilage degradation, and reduced OARSI scores and subchondral bone thickness in a mouse model of OA.

Conclusion: Our data indicated that overexpression of miR-613 could inhibit IL-1β-induced injury in CHON-001 cells via decreasing the level fibronectin 1 , and alleviate the symptoms of OA . Therefore, miR-613 might be a potential therapeutic option for the treatment of OA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540165PMC
September 2020

LncRNA NEAT1 regulates chondrocyte proliferation and apoptosis via targeting miR-543/PLA2G4A axis.

Hum Cell 2021 Jan 10;34(1):60-75. Epub 2020 Oct 10.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No.1, East Jianshe Road, Zhengzhou, 450000, Henan Province, China.

Osteoarthritis (OA), which is characterized by articular cartilage degeneration, shows a gradually increasing incidence with age. This study explored the molecular mechanism underlying the proliferation and apoptosis of chondrocytes during OA progression. In this study, chondrocytes were isolated from human knee cartilages. The targeted relationship among nuclear enriched abundant transcript 1 (NEAT1), microRNA-543 (miR-543) and PLA2G4A was predicted on TargetScan V7.2 and starBase and validated by performing dual-luciferase reporter assay. High-expressed NEAT1 was detected in OA cartilage and chondrocytes. NEAT1 was negatively correlated with miR-543 and was low-expressed in OA cartilage and PLA2G4A was negatively correlated with miR-543 and was high-expressed in OA cartilage. In OA chondrocytes, the overexpressed NEAT1 inhibited the expressions of p-Akt1 and Bcl-2 and upregulated that of matrix metalloprotease (MMP)-3, MMP-9, MMP-13, interleukin (IL)-6 and IL-8, but such effects of overexpressed NEAT1 were reversed by miR-543 mimic. SiRNA-NEAT1 exerted an opposite effect to NEAT1 overexpression on OA chondrocytes, but this could be reversed by miR-543 inhibitor. The effect of PLA2G4A overexpression was the opposite to miR-543 mimic on OA chondrocytes. In conclusion, NEAT1 could sponge miR-543 to induce PLA2G4A expression, inhibit chondrocyte proliferation and promote apoptosis.
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http://dx.doi.org/10.1007/s13577-020-00433-8DOI Listing
January 2021

Ubiquitin-specific protease 49 attenuates IL-1β-induced rat primary chondrocyte apoptosis by facilitating Axin deubiquitination and subsequent Wnt/β-catenin signaling cascade inhibition.

Mol Cell Biochem 2020 Nov 31;474(1-2):263-275. Epub 2020 Jul 31.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

Osteoarthritis (OA) is an age-related chronic joint degenerative disease. Interleukin 1 beta (IL-1β) is considered a marker for the progression of OA. In this study, we found that Ubiquitin-Specific Peptidase 49 (USP49) was significantly less expressed in OA patients compared with healthy individuals. Treating primary rat chondrocytes with different concentrations of IL-1β resulted in decreased Usp49 expression, while Usp49 overexpression could attenuate IL-1β-induced chondrocyte apoptosis by promoting Axin deubiquitination. The deubiquitination of Axin led to the accumulation of the protein, which in turn resulted in β-catenin degradation and Wnt/β-catenin signaling cascade inhibition. Interestingly, we also found that [6]-gingerol, an anti-OA drug, could upregulate the protein level of Usp49 and suppress the Wnt/β-catenin signaling cascade in primary rat chondrocytes. Taken together, our study not only demonstrates that Usp49 can negatively regulate the progression of OA by inhibiting the Wnt/β-catenin signaling cascade, but also elucidates the underlying molecular mechanisms.
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http://dx.doi.org/10.1007/s11010-020-03850-3DOI Listing
November 2020

Long non-coding RNA H19 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating microRNA-140-5p/SATB2 axis.

J Biosci 2020 ;45

Department of Orthopedics, WuWei People's Hospital, Wuwei, China.

The osteogenic differentiation of mesenchymal stem cells (MSCs) has potential clinical values in the treatment of bone-related diseases. Long non-coding RNA H19 and microRNA-140-5p (miR-140-5p) have attracted much attention of researchers by virtue of their biological importance in cell differentiation and bone formation. Moreover, bioinformatics analyses suggest that miR-140-5p have the potential to bind with H19 and SATB homeobox 2 (SATB2). In this study, we further explored whether H19 could regulate osteogenic differentiation of human bone marrow-derived MSCs (BM-MSCs) by miR-140-5p/SATB2 axis. RT-qPCR assay was conducted to examine the expression of H19, miR-140-5p and SATB2. The osteogenic differentiation capacity of BM-MSCs was assessed through alkaline phosphatase (ALP) activity and osteogenic marker expression. The relationships among H19, miR-140-5p and SATB2 were examined through bioinformatics analyses, luciferase reporter assay, RIP assay and RNA pull-down assay. H19 expression was remarkably increased and miR-140-5p expression was dramatically reduced during osteogenic differentiation of BMMSCs. Functional analyses revealed that H19 overexpression or miR-140-5p depletion accelerated osteogenic differentiation of BM-MSCs. Conversely, H19 loss or miR-140-5p increase suppressed osteogenic differentiation of BM-MSCs. MiR-140-5p was confirmed as a target of H19, and miR-140-5p could bind to SATB2 as well. Moreover, H19 knockdown reduced SATB2 expression by upregulating miR-140-5p. Additionally, miR140-5p depletion antagonized the inhibitory effect of H19 knockdown on osteogenic differentiation of BMMSCs. And, miR-140-5p inhibited osteogenic differentiation of BM-MSCs by targeting SATB2. In conclusion, H19 promoted osteogenic differentiation of BM-MSCs through regulating miR-140-5p/SATB2 axis, deepening our understanding on the molecular mechanisms of H19 in coordinating osteogenesis.
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January 2021

Upregulation of miRNA-154-5p prevents the tumorigenesis of osteosarcoma.

Biomed Pharmacother 2020 Apr 27;124:109884. Epub 2020 Jan 27.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address:

Background: Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS.

Methods: The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5.

Results: The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model.

Conclusion: These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.
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http://dx.doi.org/10.1016/j.biopha.2020.109884DOI Listing
April 2020

Upregulation Of miR-149-3p Suppresses Spinal Chordoma Malignancy By Targeting Smad3.

Authors:
Jie Yao Xuejian Wu

Onco Targets Ther 2019 19;12:9987-9997. Epub 2019 Nov 19.

Department of Orthopaedics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.

Purpose: Dysregulation of miRNAs plays an important role in the malignancy of different tumors including chordoma. Expression of miR-149-3p was earlier reported to be downregulated in chordoma tissue. However, its biological role remains to be unrevealed in chordoma, especially in spinal chordoma.

Methods: Expression of miR-149-3p and Smad3 was detected by RT-qPCR and Western blot. Chordoma malignancy was evaluated by cell proliferation, migration, invasion, and apoptosis using MTT assay, transwell assay, flow cytometry analyzing apoptosis rate, and Western blot-determined expression of Bcl-2, Bax, and cleaved caspase 3, respectively. The target binding between miR-149-3p and Smad3 was predicted by TargetScan Human website and confirmed by luciferase reporter assay and RNA immunoprecipitation. Xenograft tumors were generated, and expression of miR-149-3p and Smad3 was investigated in vivo.

Results: miR-149-3p was downregulated in spinal chordoma tissues and cells, and its overexpression promoted chordoma cell apoptosis and inhibited proliferation, migration, and invasion in U-CH1 and MUG-Chor1 cells. Unexpectedly, Smad3 was a downstream target of miR-149-3p and negatively correlated with miR-149-3p expression in chordoma tissues. Besides, Smad3 was upregulated in chordoma tissues and its silencing had a similar effect as miR-149-3p overexpression in U-CH1 and MUG-Chor1 cells. Moreover, Smad3 upregulation could partially reverse the tumor-suppressive effect of miR-149-3p in chordoma cells. In vivo, the tumorigenesis of U-CH1 and MUG-Chor1 cells was impaired by upregulated miR-149-3p through decreasing Smad3 expression.

Conclusion: miR-149-3p could serve as a tumor suppressor in spinal chordoma through targeting and downregulating Smad3.
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http://dx.doi.org/10.2147/OTT.S222380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875263PMC
November 2019

Gravity surveys using a mobile atom interferometer.

Sci Adv 2019 Sep 6;5(9):eaax0800. Epub 2019 Sep 6.

Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA.

Mobile gravimetry is important in metrology, navigation, geodesy, and geophysics. Atomic gravimeters could be among the most accurate mobile gravimeters but are currently constrained by being complex and fragile. Here, we demonstrate a mobile atomic gravimeter, measuring tidal gravity variations in the laboratory and surveying gravity in the field. The tidal gravity measurements achieve a sensitivity of 37 μGal/ (1 μGal = 10 nm/s) and a long-term stability of better than 2 μGal, revealing ocean tidal loading effects and recording several distant earthquakes. We survey gravity in the Berkeley Hills with an uncertainty of around 0.04 mGal and determine the density of the subsurface rocks from the vertical gravity gradient. With simplicity and sensitivity, our instrument paves the way for bringing atomic gravimeters to field applications.
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http://dx.doi.org/10.1126/sciadv.aax0800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731071PMC
September 2019

MiR-33b-3p promotes chondrocyte proliferation and inhibits chondrocyte apoptosis and cartilage ECM degradation by targeting DNMT3A in osteoarthritis.

Biochem Biophys Res Commun 2019 11 13;519(2):430-437. Epub 2019 Sep 13.

The Department of Orthopaedics, The First Affilicated Hospital of Zhengzhou University, China. Electronic address:

Osteoarthritis (OA) is a common and frequently-occurring disease in middle-aged and older people. A growing number of studies have shown that microRNAs (miRNAs) are involved in the development of OA. However, the role and mechanism of miR-33b-3p in OA remain ill-defined. The levels of miR-33b-3p and DNA methyltransferase 3A (DNMT3A) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of DNMT3A protein, matrix metalloprotein 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), collagen II, aggrecan, cleaved Caspase-3, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) were measured by Western blot assay. Cell proliferation and cell apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The targeting relationship between miR-33b-3p and DNMT3A was verified by dual-luciferase reporter assay. The expression of miR-33b-3p was decreased and the expression of DNMT3A was increased in OA cartilage tissues and IL-1β-induced chondrocytes. There was an inverse correlation between miR-33b-3p and DNMT3A in OA cartilage tissues. MiR-33b-3p overexpression or DNMT3A knockdown inhibited extracellular matrix (ECM) degradation and cell apoptosis and promoted cell proliferation in IL-1β-induced chondrocytes. Moreover, DNMT3A was confirmed to be a direct target of miR-33b-3p. Upregulation of DNMT3A weakened the effects of miR-33b-3p overexpression on cartilage ECM degradation, cell proliferation and apoptosis in IL-1β-activated chondrocytes. MiR-33b-3p overexpression suppressed cartilage ECM degradation and cell apoptosis, and promoted cell proliferation by directly targeting DNMT3A in IL-1β-stimulated chondrocytes.
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http://dx.doi.org/10.1016/j.bbrc.2019.09.022DOI Listing
November 2019

Embedded control system for mobile atom interferometers.

Rev Sci Instrum 2019 Jul;90(7):073103

Department of Physics, University of California, Berkeley, California 94720, USA.

Atom interferometers require precise control of digital, analog, and radio frequency signals for effective operation. In this paper, we propose and implement a control system for mobile atom interferometers. The system consists of a microcontroller and peripherals to synthesize radio frequency signals and to read or write analog signals. We use the system to operate a mobile atomic gravimeter by controlling 7 analog outputs, 16 digital outputs, 2 radio frequency channels, and 1 analog input. Our control system eliminates dead time between repetitions of the measurement and, consequently, improves the sampling rate of our atomic gravimeter, while maintaining the sensitivity per repetition compared to the system based on a desktop computer.
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http://dx.doi.org/10.1063/1.5083981DOI Listing
July 2019

CBX2 is a functional target of miRNA let-7a and acts as a tumor promoter in osteosarcoma.

Cancer Med 2019 07 31;8(8):3981-3991. Epub 2019 May 31.

Department of Bone and Soft Tissue, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Osteosarcoma is the most common type of primary malignant tumor of skeletal with poor prognosis in children and adolescents. Accumulating evidence indicates that CBX2 is overexpressed in multiple human neoplasm and play a critical role in tumorigenesis and progression. However, its functional role and upstream regulation mechanism in osteosarcoma remain unknown. In the present study, tissue microarray (TMA) analysis was performed to determine the association between CBX2 expression and clinical prognosis of osteosarcoma patients by immunohistochemistry. We also investigated the functional role of CBX2 using small interfering RNA (siRNA) in vitro and in vivo. Additionally, we confirmed the direct binding between CBX2 and let-7a via qPCR, western blot and luciferase reporter assay. We found that CBX2 is dramatically upregulated in osteosarcoma tissues and high CBX2 expression was correlated with metastasis, recurrence, and chemotherapy response, as well as unfavorable prognosis in patients with osteosarcoma. Similar results were observed in a sarcoma cohort from The Cancer Genome Atlas (TCGA) dataset. Further experiments revealed that CBX2 knockdown significantly impeded osteosarcoma cell proliferation and invasion ability in vitro, and suppressed the tumor growth in tumor xenografts model. Mechanistically, we confirmed that CBX2 is a functional target of miRNA let-7a. Overexpression of let-7a inhibits osteosarcoma cell proliferation, which was reversed by CBX2 overexpression. Taken together, our study demonstrates that let-7a/CBX2 plays a crucial role in osteosarcoma progression. CBX2 could serve as a promising prognostic biomarker and potential therapeutic target for osteosarcoma patients.
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http://dx.doi.org/10.1002/cam4.2320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639449PMC
July 2019

A Causal Relationship in Spinal Cord Injury Rat Model Between Microglia Activation and EGFR/MAPK Detected by Overexpression of MicroRNA-325-3p.

J Mol Neurosci 2019 Jun 25;68(2):181-190. Epub 2019 Mar 25.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Erqi District, Zhengzhou, 450003, Henan Province, China.

Microglial activation and inflammatory response played an important role in the secondary injury of spinal cord injury (SCI). Several microRNAs were associated with this procedure, but the underlying molecular mechanism was poorly understood. Sprague-Dawley (SD) rats were divided into four groups: SCI group (n = 7), agomiR-325-3p group (n = 7), and their control groups. Expression of miR-325-3p and proteins in epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway was evaluated in microglia from SCI rats and primary microglia/BV2 cells activated by lipopolysaccharide (LPS). Concentrations of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in supernatants were measured by ELISA. Low expression of miR-325-3p and activation of EGFR/MAPK was observed in microglia of SCI and LPS-induced primary microglia. Overexpression of miR-325-3p in LPS-induced BV2 cells inhibited microglial activation and release of TNF-α and IL-1β. Luciferase reporter assay confirmed that miR-325-3p negatively regulated EGFR by targeting its 3'-untranslated regions. Additionally, agomiR-325-3p inhibited the activation of microglia and EGFR/MAPK, alleviating the inflammatory response. These results indicated that miR-325-3p attenuated secondary injury after SCI through inhibition of EGFR/MAPK signaling pathway, the microglial activation, and the release of inflammatory cytokines, suggesting that miR-325-3p may be employed as a therapeutic target for SCI.
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http://dx.doi.org/10.1007/s12031-019-01297-wDOI Listing
June 2019

miR-134 inhibits chondrogenic differentiation of bone marrow mesenchymal stem cells by targetting SMAD6.

Biosci Rep 2019 01 30;39(1). Epub 2019 Jan 30.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, Henan Province, China

Various miRNAs have been reported to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs); however, whether miR-134 plays a role in this biological process remains undetermined. In the present study, we first evaluated the chondrogenic differentiation of BMSCs by Alcian blue staining, and examined the miR-134 expression by quantitative real-time PCR (qRT-PCR) during this process. And miR-134 inhibitor was used to investigate the functions of miR-134 in chondrogenic differentiation of BMSCs by Alcian blue staining, qRT-PCR, and Western blot. Subsequently, the correlation between miR-134 and SMAD6 was assessed via bioinformatics analysis and dual-luciferase reporter assay. Finally, the role of SMAD6 in chondrogenic differentiation of BMSCs was also determined through Alcian blue staining, qRT-PCR, and Western blot. As results showed that miR-134 expression was significantly down-regulated during chondrogenic differentiation, and inhibition of miR-134 obviously promoted chondrogenic differentiation. Dual-luciferase reporter assay indicated that miR-134 could directly target the 3'-UTRs of SMAD6, inhibit miR-134 expression in BMSCs, and up-regulate SMAD6 expression. Moreover, we found that overexpression of SMAD6 significantly promoted chondrogenic differentiation, and that SMAD6-induced promotion of chondrogenic differentiation could be reversed by miR-134 mimics. In conclusion, our findings suggest that miR-134 may act as a negative regulator during chondrogenic differentiation of BMSCs by interacting with SMAD6.
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http://dx.doi.org/10.1042/BSR20180921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356013PMC
January 2019

Knockdown of long non-coding RNA TP73-AS1 inhibits osteosarcoma cell proliferation and invasion through sponging miR-142.

Biomed Pharmacother 2018 Jul 7;103:1238-1245. Epub 2018 May 7.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address:

Long non-coding RNA P73 antisense RNA 1 T (lncRNA TP73-AS1) has been shown to involve in the progression of numerous tumors. Nevertheless, the expression as well as the functional mechanisms of TP73-AS1 in osteosarcoma (OS) are still largely unknown. This study aimed to explore the roles and underlying mechanism of TP73-AS1 in OS progression. In thye present study, TP73-AS1 expression was significantly increased in OS tissues and cell lines. High TP73-AS1 expression was associated with poor overall survival of OS patients. TP73-AS1 knockdown suppressed OS cells proliferation and invasion in vitro as well as tumor growth in vivo. Furthermore, we identified that miR-142 could act as a direct target for TP73-AS1 and miR-142 inhibition reversed the suppression of OS cells proliferation and invasion induced by TP73-AS1 knockdown. In addition, we showed that TP73-AS1 could function as a sponge of miR-142 to positively regulate Rac1 in OS cells. Thus, our data suggested that TP73-AS1 served as an oncogenic lncRNA in OS progression, and could be regarded as an efficient therapeutic target in the treatment of OS.
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http://dx.doi.org/10.1016/j.biopha.2018.04.146DOI Listing
July 2018

[Ilizarov technique combined with limited surgery for correction of spastic clubfoot in adolescents with cerebral palsy].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2018 02;32(2):182-186

Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou Henan, 450052,

Objective: To evaluate the effectiveness of Ilizarov technique combined with soft tissue release and muscle strength balance in the treatment of spastic clubfoot in adolescents with cerebral palsy.

Methods: A retrospective analysis of clinical data of 29 cases (33 feet) of cerebral palsy spastic clubfoot deformity conformed to the selection criteria between June 2011 and September 2016. Among them, 17 were male (20 feet) and 12 were female (13 feet) with an age range from 13 to 28 years (mean, 17.6 years). According to Diméglio classification, 19 feet were rated as gradeⅡ and 14 feet as grade Ⅲ. All patients were treated with soft tissue release and muscle balance, while using Ilizarov technique to correct varus deformity. Began to gradually adjust the external fixator after 5-7 days of operation, until to reach satisfactory foot ankle form. Orthopedic brace was used after removal of external fixator, and the wearing time gradually reduced to completely abandon the brace.

Results: All 29 patients (33 feet) were followed up 12-22 months with an average of 18 months. All patients restored line plantar foot without needle infection and nerve or vessel injury. One foot had a mild relapse of deformity at 6 months after removal of external fixator, and the gait restored to normal after symptomatic treatment. The rest of 32 feet had no deformity recurrence during the follow-up. At last follow-up, International Club Foot Study Group (ICFSG) score (5.21±3.91) was significantly lower than the preoperative score (36.73±4.80), and the difference was significant ( =47.227, =0.000). The results were excellent in 27 feet, good in 3 feet, and fair in 3 feet, and the excellent and good rate was 90.91%. The patients were very satisfied in 27 feet and satisfied in 6 feet by self-evaluation of effectiveness.

Conclusion: Ilizarov technique is effective in treatment of clubfoot. And it is also a feasible method to treat spastic clubfoot in adolescents with cerebral palsy when combined with appropriate soft tissue surgery according to the patient's symptoms and signs.
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http://dx.doi.org/10.7507/1002-1892.201710045DOI Listing
February 2018

Magnesium Lithospermate B Protects against Lipopolysaccharide-Induced Bone Loss by Inhibiting RANKL/RANK Pathway.

Front Pharmacol 2018 6;9:64. Epub 2018 Feb 6.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhenghou, China.

Lipopolysaccharide (LPS) can induce bone loss by stimulating bone resorption. Natural compounds have great potential for the treatment of osteolytic bone diseases. Magnesium lithospermate B (MLB) plays an important role in protecting against oxidative damage and also has potential anti-inflammatory pharmacological properties. However, its role in LPS-induced bone loss is still unknown. In the present study, we observed the effects of MLB on LPS-induced bone damage and investigated the possible mechanisms. The bone loss models were established by LPS administration in male Sprague-Dawley rats. MLB (200 mg/kg body weight) was given by subcutaneous injection. MicroCT analysis, biomarker assay, histological examination and immunohistochemical staining were performed at the 8th weeks. In addition, RAW264.7 cells were treated with LPS in the presence or absence of MLB. The osteoclast formation, resorption activity and differentiation-related genes [(receptor activator of nuclear factor kappa-B (RANK), Traf6, Fra-1, and c-src)] expression were evaluated. LPS induced bone loss shown as the decrease in bone volume fraction and trabecular number, and increase in trabecular separation. LPS also markedly enhanced the osteoclast formation and resorption activity compared with the control. MLB significantly abolished the LPS-induced bone microstructure damage ( < 0.05) and osteoclast formation. MLB also inhibited the increases of serum tartrate-resistant acid phosphatase 5b, RANK ligand (RANKL) and TNF-α level enhanced by LPS ( < 0.05). Immunohistochemical staining indicated that MLB attenuated the high expression of RANKL and RANK stimulated by LPS. In addition, MLB significantly abolished the LPS-enhanced osteoclast formation, resorption activity, RANK, Traf6, Fra-1, and c-src expression . Our data demonstrate that MLB can suppress LPS-induced bone loss via inhibiting RANKL/RANK related osteoclast formation.
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http://dx.doi.org/10.3389/fphar.2018.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810254PMC
February 2018

Comb-referenced frequency-sweeping interferometry for precisely measuring large stepped structures.

Appl Opt 2018 Feb;57(5):1247-1253

A precise 3D surface measurement method for large stepped structures without height ambiguity is proposed based on optical-frequency-comb-referenced frequency-sweeping interferometry and Fourier-transformed fractional phase retrieval. Unlike other interferometry that depends on the absolute phase value for several certain wavelengths, this method obtains results from the phase change during frequency sweeping and thus remains free from the confined non-ambiguity range. By reference to an optical frequency comb, the relative uncertainty from the tunable laser frequency was reduced by three orders of magnitude, and the sweeping frequency range can be precisely determined. Besides, the fractional phase can be rapidly retrieved in only one step using a Fourier transform method, with advantages of high accuracy and immunity to light intensity fluctuation and mechanical vibration noise. Samples of step heights from 1 μm to 1 mm were measured, and the standard uncertainty was 45 nm. This permits applications such as quality assurance in microelectronics production and micro-electro-mechanical system (MEMS) manufacture.
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http://dx.doi.org/10.1364/AO.57.001247DOI Listing
February 2018

Lipoxin A4 protects against spinal cord injury via regulating Akt/nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 signaling.

Biomed Pharmacother 2018 Jan 7;97:905-910. Epub 2017 Nov 7.

The Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, Henan, China.

Spinal cord injury (SCI) is a devastating physical trauma worldwide. The mechanisms of SCI are still not clear and the effective treatment is limited. Lipoxin A4 (LXA4) possesses anti-inflammatory and neuroprotective effects. The present study was designed to further evaluate the molecular mechanisms of LXA4-induced protective effects in a rat model of SCI. We found that LXA4 increased Basso, Beattie and Bresnahan (BBB) scores, increased mechanical paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) to a radiant heat, reduced the lesion volume, decreased Bax mRNA expression and increased Bcl-2 expression after SCI. The phosphorylation of Akt and protein expression of Nrf2 and HO-1 were reduced after SCI. LXA4 treatment significantly inhibited the reduction of Akt phosphorylation and Nrf2 and HO-1 protein expression. Injection of LY294002 notably inhibited the phosphorylation of Akt, and the expression of total Akt and Nrf2 and HO-1 after SCI in LXA4-treated rats. LY294002 prohibited LXA4-induced effects after SCI. shNrf2 injection markedly decreased both Nrf2 and HO-1 expression in LXA4-treated rats after SCI. ZnPP notably decreased HO-1 expression but did not markedly affect Nrf2 expression. shNrf2 and ZnPP prohibited LXA4-induced increase of BBB scores, and PWT and PWL, decrease of lesion volume of spinal cord, reduction of Bax expression and increase of Bcl-2 expression. The results indicate that LXA4 protects against SCI through Akt/Nrf2/HO-1 signaling. The data provide novel insights into the mechanisms of LXA4-mediated neuprotective effects against SCI and suggest that LXA4 may be a potential therapeutic agent for SCI and its associated complications.
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http://dx.doi.org/10.1016/j.biopha.2017.10.092DOI Listing
January 2018

RSF1 functions as an oncogene in osteosarcoma and is regulated by XIST/miR-193a-3p axis.

Biomed Pharmacother 2017 Nov 12;95:207-214. Epub 2017 Sep 12.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address:

RSF1 (HBXAP), is a member of ATP-dependent chromatin remodeling factor. Dysregulated RSF1 has been reported to be related to tumor progression. However, the function of RSF1 in osteosarcoma (OS) remains unclear. In this study, we showed that RSF1 expression was upregulated in OS cells. RSF1 inhibition suppressed OS cell proliferation and invasion. We further showed that MAPK/Erk signaling pathway was inactivated by RSF1 suppression. In addition, RSF1 was identified as a direct target of miR-193a-3p. Clinically, RSF1 was increased and associated with advanced clinical features and poor overall survival of OS patients. MiR-193a-3p expression was decreased and associated with advanced clinical features and poor overall survival of OS patients. In addition, we found that miR-193a-3p was negatively correlated with RSF1 expression in OS tissues. Moreover, our data showed that XIST could function as competing endogenous RNA to repress miR-193a-3p, which regulated its downstream target RSF1. In conclusion, our findings demonstrated that the XIST/miR-193a-3p/RSF1 axis might contribute to the progression and act as a therapeutic target of OS patients.
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http://dx.doi.org/10.1016/j.biopha.2017.08.068DOI Listing
November 2017

Frequency comb calibrated frequency-sweeping interferometry for absolute group refractive index measurement of air.

Appl Opt 2017 Apr;56(11):3109-3115

The absolute group refractive index of air at 194061.02 GHz is measured in real time using frequency-sweeping interferometry calibrated by an optical frequency comb. The group refractive index of air is calculated from the calibration peaks of the laser frequency variation and the interference signal of the two beams passing through the inner and outer regions of a vacuum cell when the frequency of a tunable external cavity diode laser is scanned. We continuously measure the refractive index of air for 2 h, which shows that the difference between measured results and Ciddor's equation is less than 9.6×10-8, and the standard deviation of that difference is 5.9×10-8. The relative uncertainty of the measured refractive index of air is estimated to be 8.6×10-8. The data update rate is 0.2 Hz, making it applicable under conditions in which air refractive index fluctuates fast.
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http://dx.doi.org/10.1364/AO.56.003109DOI Listing
April 2017

Laser frequency stabilization by combining modulation transfer and frequency modulation spectroscopy.

Appl Opt 2017 Apr;56(10):2649-2652

We present a hybrid laser frequency stabilization method combining modulation transfer spectroscopy (MTS) and frequency modulation spectroscopy (FMS) for the cesium D2 transition. In a typical pump-probe setup, the error signal is a combination of the DC-coupled MTS error signal and the AC-coupled FMS error signal. This combines the long-term stability of the former with the high signal-to-noise ratio of the latter. In addition, we enhance the long-term frequency stability with laser intensity stabilization. By measuring the frequency difference between two independent hybrid spectroscopies, we investigate the short-and long-term stability. We find a long-term stability of 7.8 kHz characterized by a standard deviation of the beating frequency drift over the course of 10 h and a short-term stability of 1.9 kHz characterized by an Allan deviation of that at 2 s of integration time.
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http://dx.doi.org/10.1364/AO.56.002649DOI Listing
April 2017

MiRTDL: A Deep Learning Approach for miRNA Target Prediction.

IEEE/ACM Trans Comput Biol Bioinform 2016 11 22;13(6):1161-1169. Epub 2015 Dec 22.

MicroRNAs (miRNAs) regulate genes that are associated with various diseases. To better understand miRNAs, the miRNA regulatory mechanism needs to be investigated and the real targets identified. Here, we present miRTDL, a new miRNA target prediction algorithm based on convolutional neural network (CNN). The CNN automatically extracts essential information from the input data rather than completely relying on the input dataset generated artificially when the precise miRNA target mechanisms are poorly known. In this work, the constraint relaxing method is first used to construct a balanced training dataset to avoid inaccurate predictions caused by the existing unbalanced dataset. The miRTDL is then applied to 1,606 experimentally validated miRNA target pairs. Finally, the results show that our miRTDL outperforms the existing target prediction algorithms and achieves significantly higher sensitivity, specificity and accuracy of 88.43, 96.44, and 89.98 percent, respectively. We also investigate the miRNA target mechanism, and the results show that the complementation features are more important than the others.
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http://dx.doi.org/10.1109/TCBB.2015.2510002DOI Listing
November 2016

Optically stabilized Erbium fiber frequency comb with hybrid mode-locking and a broad tunable range of repetition rate.

Appl Opt 2016 Dec;55(34):D29-D34

We present an optically stabilized Erbium fiber frequency comb with a broad repetition rate tuning range based on a hybrid mode-locked oscillator. We lock two comb modes to narrow-linewidth reference lasers in turn to investigate the best performance of control loops. The control bandwidth of fast and slow piezoelectric transducers reaches 70 kHz, while that of pump current modulation with phase-lead compensation is extended to 32 kHz, exceeding laser intrinsic response. Eventually, simultaneous lock of both loops is realized to totally phase-stabilize the comb, which will facilitate precision dual-comb spectroscopy, laser ranging, and timing distribution. In addition, a 1.8-MHz span of the repetition rate is achieved by an automatic optical delay line that is helpful in manufacturing a secondary comb with a similar repetition rate. The oscillator is housed in a homemade temperature-controlled box with an accuracy of ±0.02  K, which not only keeps high signal-to-noise ratio of the beat notes with reference lasers, but also guarantees self-starting at the same mode-locking every time.
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http://dx.doi.org/10.1364/AO.55.000D29DOI Listing
December 2016
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