Publications by authors named "Shaopeng Liu"

53 Publications

Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis.

Bone Joint Res 2020 Oct;9(10):689-700

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Aims: The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5).

Methods: TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.

Results: UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05).

Conclusion: MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: 2020;9(10):689-700.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1302/2046-3758.910.BJR-2020-0140.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572806PMC
October 2020

Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs.

Cell Stem Cell 2021 Jan 21;28(1):127-140.e9. Epub 2020 Sep 21.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Cell-fate conversion generally requires reprogramming effectors to both introduce fate programs of the target cell type and erase the identity of starting cell population. Here, we reveal insights into the activity of microRNAs miR-9/9 and miR-124 (miR-9/9-124) as reprogramming agents that orchestrate direct conversion of human fibroblasts into motor neurons by first eradicating fibroblast identity and promoting uniform transition to a neuronal state in sequence. We identify KLF-family transcription factors as direct target genes for miR-9/9-124 and show their repression is critical for erasing fibroblast fate. Subsequent gain of neuronal identity requires upregulation of a small nuclear RNA, RN7SK, which induces accessibilities of chromatin regions and neuronal gene activation to push cells to a neuronal state. Our study defines deterministic components in the microRNA-mediated reprogramming cascade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.stem.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796891PMC
January 2021

Chamber-specific transcriptional responses in atrial fibrillation.

JCI Insight 2020 09 17;5(18). Epub 2020 Sep 17.

Department of Medicine, Cardiovascular Division.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a murine genetic model is sufficient to increase ploidy in both atrial chambers. Notch activation within LA CMs generated a transcriptomic fingerprint resembling AF, with dysregulation of transcription factor and ion channel genes, including Pitx2, Tbx5, Kcnh2, Kcnq1, and Kcnip2. Notch activation also produced distinct cellular electrophysiologic responses in LA versus right atrial CMs, prolonging the action potential duration (APD) without altering the upstroke velocity in the left atrium and reducing the maximal upstroke velocity without altering the APD in the right atrium. Our results support a shared human/murine model of increased Notch pathway activity predisposing to AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.135319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526559PMC
September 2020

Comparison of differential accessibility analysis strategies for ATAC-seq data.

Sci Rep 2020 06 23;10(1):10150. Epub 2020 Jun 23.

Department of Developmental Biology, Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.

ATAC-seq is widely used to measure chromatin accessibility and identify open chromatin regions (OCRs). OCRs usually indicate active regulatory elements in the genome and are directly associated with the gene regulatory network. The identification of differential accessibility regions (DARs) between different biological conditions is critical in determining the differential activity of regulatory elements. Differential analysis of ATAC-seq shares many similarities with differential expression analysis of RNA-seq data. However, the distribution of ATAC-seq signal intensity is different from that of RNA-seq data, and higher sensitivity is required for DARs identification. Many different tools can be used to perform differential analysis of ATAC-seq data, but a comprehensive comparison and benchmarking of these methods is still lacking. Here, we used simulated datasets to systematically measure the sensitivity and specificity of six different methods. We further discussed the statistical and signal density cut-offs in the differential analysis of ATAC-seq by applying them to real data. Batch effects are very common in high-throughput sequencing experiments. We illustrated that batch-effect correction can dramatically improve sensitivity in the differential analysis of ATAC-seq data. Finally, we developed a user-friendly package, BeCorrect, to perform batch effect correction and visualization of corrected ATAC-seq signals in a genome browser.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-66998-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311460PMC
June 2020

MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1.

Arthritis Res Ther 2020 05 1;22(1):99. Epub 2020 May 1.

Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Number 44, Wen Hua Xi Lu, Jinan City, 250012, Shandong Province, China.

Background: Due to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1.

Methods: TMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB.

Results: In the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1β, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1β, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway.

Conclusion: This study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-2145-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195789PMC
May 2020

Estrogen-Related Receptor γ Induces Angiogenesis and Extracellular Matrix Degradation of Temporomandibular Joint Osteoarthritis in Rats.

Front Pharmacol 2019 6;10:1290. Epub 2019 Nov 6.

Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.

The main causes of cartilage destruction during temporomandibular joint osteoarthritis (TMJOA) are extracellular matrix degradation and angiogenesis, accompanied by an increased level of matrix-degrading enzymes and proangiogenic factors. Interleukin 6 and extracellular signal-regulated kinase (ERK) signaling pathways may play a critical role in these two processes simultaneously, but researchers have not clearly determined the mechanism. We hypothesized that estrogen-related receptor γ (ERRγ) is involved in both cartilage degeneration and angiogenesis in TMJOA. The interactions between ERRγ and the and promoter regions were investigated using a chromatin immunoprecipitation (ChIP) assay. A chick embryo chorioallantoic membrane (CAM) assay was performed to investigate the inhibitory effects of U0126 and GSK5182 on angiogenesis. Western blotting, reverse transcription-quantitative PCR (RT-qPCR), immunofluorescence staining, toluidine blue staining, and transfection with cDNAs or small interfering RNAs (siRNAs) were performed on primary mandibular condylar chondrocytes (MCCs). Unilateral anterior crossbite-induced TMJOA models were established in rats, and Western blotting, RT-qPCR, immunohistochemistry, and Safranin O-Fast Green staining were performed to evaluate changes . ERK1/2 activated matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor A (VEGFA), which are involved in cartilage destruction, through ERRγ. Based on the ChIP assay results, ERRγ directly activated the transcription of the and genes. In chick embryo CAM models, U0126 and GSK5182 significantly inhibited angiogenesis. In conclusion, ERRγ is a downstream transcription factor of ERK1/2, and its upregulation leads to extracellular matrix degradation and angiogenesis in TMJOA. This study identified a common factor between inflammation and vascularization in OA as well as a new therapeutic target for OA: ERRγ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.01290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851845PMC
November 2019

Regular Aerobic Exercise-Alleviated Dysregulation of CAMKIIα Carbonylation to Mitigate Parkinsonism via Homeostasis of Apoptosis With Autophagy.

J Neuropathol Exp Neurol 2020 01;79(1):46-61

Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha, Hunan, China (WL, RF, ZW, SL, CT, LL, DY); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota (WL); School of Health & Kinesiology, Georgia Southern University, Statesboro, Georgia (LL); and Qingyuan People's Hospital, The Sixth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China (DY).

This study investigated carbonylation of proteins with oxidative modification profiling in the striatum of aging and Parkinson disease (PD) rats, as well as the long-term effects of regular aerobic exercise on the carbonylation process and the damaging effects of PD vs habitual sedentary behavior. Regular aerobic exercise improved the PD rats' rotational behavior, increased tyrosine hydroxylase expression in both the striatum and substantia nigra pars compacta, and decreased α-synuclein expression significantly. Interestingly, apoptotic nuclei and autophagosomes were increased in the aerobic exercise PD rat striatum. Carbonylated protein Ca2+/calmodulin-dependent protein kinase alpha (CAMKIIα) was present in the middle-aged and aged groups but only in the sedentary, not the exercise, PD rat striatum. Notably, CAMKIIα was characterized by a 4-hydroxynonenal adduct. Regular aerobic exercise upregulated CAMKIIα expression level, activated the CAMK signaling pathway, and promoted the expression of autophagy markers Beclin1 and microtubule-associated proteins 1 A/1B light chain 3II. Aberrant carbonylation of CAMKII initiated age-related changes and might be useful as a potential biomarker of PD. Regular aerobic exercise alleviated protein carbonylation modification of CAMKIIα and regulated the CAMK signaling pathway, thereby affecting and regulating the homeostasis of apoptosis and autophagy in the striatum to alleviate the neurodegenerative process of PD lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnen/nlz106DOI Listing
January 2020

Joint optic disc and cup segmentation using semi-supervised conditional GANs.

Comput Biol Med 2019 12 10;115:103485. Epub 2019 Oct 10.

School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

Glaucoma is a chronic and widespread eye disease threatening humans' irreversible vision loss. The cup-to-disc ratio (CDR), one of the most important measurements used for glaucoma screening and diagnosis, requires accurate segmentation of optic disc and cup from fundus images. However, most existing techniques fail to obtain satisfactory segmentation performance because a significant number of pixel-level annotated data are often unavailable during training. To cope with this limitation, in this paper, we propose an effective joint optic disc and cup segmentation method based on semi-supervised conditional Generative Adversarial Nets (GANs). Our architecture consists of a segmentation net, a generator and a discriminator, to learn a mapping between the fundus images and the corresponding segmentation maps. Additionally, we employ both labeled and unlabeled data to improve the segmentation performance. The extensive experiments show that our method achieves state-of-the-art optic disc and cup segmentation results on both ORIGA and REFUGE datasets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2019.103485DOI Listing
December 2019

In vitro and in vivo assessment of the biocompatibility of an paclitaxel-eluting poly-l-lactide-coated Mg-Zn-Y-Nd alloy stent in the intestine.

Mater Sci Eng C Mater Biol Appl 2019 12 19;105:110087. Epub 2019 Aug 19.

Luoyang Central Hospital affiliated to Zhengzhou University, Luoyang 471000, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2019.110087DOI Listing
December 2019

Efficacy of secondary closure technique after extraction of third molars: a meta-analysis.

Br J Oral Maxillofac Surg 2019 12 17;57(10):977-984. Epub 2019 Sep 17.

Department of Oral and Maxillofacial Surgery, College of Stomatology, Shandong University, Number 44, Wen Hua Xi Lu, Jinan City, Shandong Province 250012, China. Electronic address:

The purpose of this study was to assess the influence of two suture methods on the postoperative complications of extraction of mandibular third molars (M3M). We searched the MEDLINE (PubMed), Cochrane Library, and Web of Science databases until 18 May 2018 for randomised controlled trials (RCT) that evaluated the influence of any suture techniques on postoperative complications after the removal of impacted M3M. Pain, facial swelling, and trismus were measured for both the early stage (2-3 days) and late stage (5-7 days) after extraction. We identified 655 records, of which five were assessed for eligibility. All trials included had a moderate risk of bias. The analysis showed that the patients whose wounds had been closed primarily had significantly more pain than those whose wounds were closed secondarily (a wedge of mucosa) during the early stage (standardised mean difference (SMD), -0.49; 95% CI -0.71 to -0.27; P<0.0001) and the late stage (SMD -0.36; 95% CI -0.54 to -0.19; P<0.0001) after the removal of impacted M3M. Patients whose wounds were closed secondarily had less swelling (mm) at the postoperative early stage (SMD -1.12; 95% CI -1.57 to -0.66; P<0.00001) and late stage (SMD -0.51; 95% CI -0.68 to -0.33; P<0.00001). There was more trismus in the primary closure group than in the secondary group during both stages. Our findings suggest that secondary closure causes less pain, facial swelling, and trismus in both early and late stages of surgical removal of impacted M3M, and therefore it improves the quality of life by reducing postoperative discomfort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjoms.2019.08.028DOI Listing
December 2019

MicroRNA Expression Profiling Screen miR-3557/324-Targeted in the Rat Striatum of Parkinson's Disease in Regular Aerobic Exercise.

Biomed Res Int 2019 12;2019:7654798. Epub 2019 Jun 12.

The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha, Hunan, 410081, China.

This study aimed to screen the target miRNAs and to investigate the differential miR-3557/324-targeted signal mechanisms in the rats' model of Parkinson's disease (PD) with regular aerobic exercise. Rats were divided into sedentary control PD group (SED-PD, = 18) and aerobic exercise PD group (EX-PD, = 22). After 8 weeks of regular aerobic exercise, a 6-hydroxydopamine- (6-OHDA-) induced PD lesion model was constructed. Preregular aerobic exercises enhanced the injury resistance of rats with 6-OHDA-induced PD. The rotational behavior after injection of apomorphine hydrochloride was alleviated. Under the scanning electron microscopy, we found the neurons, axons, and villi of the striatum were clearly and tightly arranged, and neurons and axons significantly becoming larger. Tyrosine hydroxylase (TH) was increased significantly and -synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group. Screening from miRNA microarray chip, we further found upregulation of miR-3557 and downregulation of miR-324 were closely related to the calcium-modulating signaling pathway, remitting the progress of Parkinson's disease on aerobic exercise. Compared to the SED-PD group, Ca/calmodulin dependent protein kinase II () was upregulated, but and voltage-dependent anion-selective channel protein 1 () were significantly downregulated in the EX-PD group. Additionally, phosphatidylinositol-3-kinase ()/mammalian target of rapamycin () expression were activated, and ubiquitin carboxy-terminal hydrolase L1 () expression was upregulated in the EX-PD group. Conclusions: the adaptive mechanism of regular aerobic exercise delaying neurodegenerative diseases and lesions was that miR-3557/324 was activated to regulate one of its targets CaMKs signaling pathways. CaMKs, coordinated with mTOR pathway-related gene expression, improved UCH-L1 level to favor for delaying neurodegeneration or improving the pathogenesis of PD lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/7654798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594308PMC
December 2019

The balance of apoptosis and autophagy via regulation of the AMPK signal pathway in aging rat striatum during regular aerobic exercise.

Exp Gerontol 2019 09 27;124:110647. Epub 2019 Jun 27.

Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha, Hunan 410012, China; Qingyuan People's Hospital, the Sixth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511500, China. Electronic address:

The objective was to analyze the effects of aerobic exercise on aging striatum stress resistance, and the adaptive mechanisms related to neurodegenerative diseases, and the occurrence, and development of neural degeneration. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the aerobic exercise runner Sprague-Dawley rats. Apoptotic nuclei appeared in the striatum of aged rats, showing a tendency to relate to aging. The apoptotic index of the striatum in young, middle-aged, and old-aged rats of the aerobic exercise groups increased by 205.56%, 57%, and 68.24%. Autophagy markers Beclin l and LC 3-II expression, AMPKα1 and pAMPKα1 expression increased significantly in all age-exercise groups. The ratio of AMPKα1/pAMPKα1 increased after exercise, and the tendency of exercise to alter autophagy and cell apoptosis increased with aging. Then SirT2 mRNA was significantly upregulated in the aerobic exercise runner groups. In conclusion, we showed that the balance of autophagy and apoptosis were closely regulated by regular aerobic exercise, which affected the development of aging, and via regulation of the AMPK/SirT2 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2019.110647DOI Listing
September 2019

Conditional Activation of NF-κB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation.

J Bone Miner Res 2019 11 31;34(11):2087-2100. Epub 2019 Jul 31.

Musculoskeletal Research Center, Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Studies from global loss-of-function mutants suggest that alternative NF-κB downstream of NF-κB inducing kinase (NIK) is a cell-intrinsic negative regulator of osteogenesis. However, the interpretation of the osteoblast and/or osteocyte contribution to the bone phenotype is complicated by simultaneous osteoclast defects in these models. Therefore, we turned to a transgenic mouse model to investigate the direct role of NIK in the osteolineage. Osx-Cre;NT3 animals (NT3-Cre +), which bear a constitutively active NIK allele (NT3) driven by Osx-Cre, were compared with their Cre-negative, Control (Ctrl) littermates. NT3-Cre + mice had elevated serum P1NP and CTX levels. Despite this high turnover state, µCT showed that constitutive activation of NIK resulted in a net increase in basal bone mass in both cortical and cancellous compartments. Furthermore, NT3-Cre + mice exhibited a greater anabolic response following mechanical loading compared with controls. We next performed RNA-Seq on nonloaded and loaded tibias to elucidate possible mechanisms underlying the increased bone anabolism seen in NT3-Cre + mice. Hierarchical clustering revealed two main transcriptional programs: one loading-responsive and the other NT3 transgene-driven. Gene ontology (GO) analysis indicated a distinct upregulation of receptor, kinase, and growth factor activities including Wnts, as well as a calcium-response signature in NT3-Cre + limbs. The promoters of these GO-term associated genes, including many known to be bone-anabolic, were highly enriched for multiple κB recognition elements (κB-RE) relative to the background frequency in the genome. The loading response in NT3-Cre + mice substantially overlapped (>90%) with Ctrl. Surprisingly, control animals had 10-fold more DEGs in response to loading. However, most top DEGs shared between genotypes had a high incidence of multiple κB-RE in their promoters. Therefore, both transcriptional programs (loading-responsive and NT3 transgene-driven) are modulated by NF-κB. Our studies uncover a previously unrecognized role for NF-κB in the promotion of both basal and mechanically stimulated bone formation. © 2019 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854278PMC
November 2019

Proteomic Profile of Carbonylated Proteins Screen the Regulation of Calmodulin-Dependent Protein Kinases-AMPK-Beclin1 in Aerobic Exercise-Induced Autophagy in Middle-Aged Rat Hippocampus.

Gerontology 2019 26;65(6):620-633. Epub 2019 Jun 26.

Qingyuan People's Hospital, The Sixth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Background: Carbonylation is an oxidative modification of the proteins and a marker of oxidative stress. The accumulation of toxic carbonylated proteins might be one of the onsets of pathogenesis in hippocampal aging or neurodegeneration. Enormous evidence indicates that regular aerobic exercise might alleviate the dysfunction of carbonylated proteins, but the adaptational mechanisms in response to exercise are unclear.

Objective: This study explored the carbonyl stress mechanism in the hippocampus using proteomics and the role of calmodulin-dependent protein kinases (CAMK)-AMP-activated protein kinase (AMPK)-Beclin1 signaling pathways in alleviating aging or improving function with regular aerobic exercise.

Methods: Twenty-four healthy 13-month-old male Sprague-Dawley rats (average 693.21 ± 68.85 g) were randomly divided into middle-aged sedentary control group (M-SED, n = 12) and middle-aged aerobic exercise runner group (M-EX, n = 12). The M-EX group participated in regular aerobic exercise - treadmill running - with exercise intensity increasing gradually from 50-55% to 65-70% of maximum oxygen consumption (V˙O2max) over 10 weeks. The targeted proteins of oxidative modification were profiled by avidin magnetic beads and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS). Western blots were used to test for molecular targets.

Results: Regular aerobic exercise restores the intersessional habituation and rescues the hippocampus morphological structure in middle-aged rats. -ESI-Q-TOF-MS screened 56 carbonylated proteins only found in M-SED and 16 carbonylated proteins only found in M-EX, indicating aerobic exercise decreased carbonyl stress. Intriguingly, Ca2+/CAMK II alpha (CAMKIIα) was carbonylated only in the M-SED group at the oxidative modification site of 4-hydroxynonenal adducts, while regular aerobic exercise alleviated CAMKIIα carbonylation. Regular aerobic exercise significantly increased the expression and phosphorylated, active levels of CAMKIIα and AMPKα1. It also upregulated the expression of Beclin1 and microtubule-associated protein1-light chain 3 in the hippocampus.

Conclusion: Quantification of CAMKIIα carbonylation may be a potential biomarker of the hippocampal senescence. Additionally, regular aerobic exercise-induced autophagy via the activation of CAMK-AMPK-Beclin1 signaling pathway may mitigate the hippocampal neurodegeneration or pathological changes by alleviating protein carbonylation (carbonyl stress).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000500742DOI Listing
April 2020

Safety and sedative effect of intranasal dexmedetomidine in mandibular third molar surgery: a systematic review and meta-analysis.

Drug Des Devel Ther 2019 23;13:1301-1310. Epub 2019 Apr 23.

Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, People's Republic of China,

Objective: The focus of this meta-analysis was to assess the sedative effect and safety of intranasal dexmedetomidine (Dex) in mandibular third molar surgery.

Methods: The PubMed/Medline, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases were searched for studies published until May 1, 2018. Eligible studies were restricted to randomized controlled trials (RCTs) and controlled clinical trials. The evaluation indicators mainly included the bispectral index, observer assessment of alertness/sedation scale, systolic blood pressure, and heart rate. Data for each period in the Dex and control groups were pooled to evaluate its sedative effect and safety.

Results: Five RCTs met the inclusion criteria. This study included 363 patients: 158 patients received intranasal inhalation of Dex before surgery, and 158 patients were negative controls. The pooled results showed a good sedative effect during tooth extraction when intranasal inhalation of Dex was performed 30 minutes before third molar extraction (assessment of alertness/sedation, Dex vs control SMD -1.20, 95% CI -1.73 to -0.67, =0, =0.95; bispectral index, Dex vs control SMD -11.68, 95% CI -19.49 to -3.87, =89%; =0.0001), and parameters returned to normal within 90 minutes after inhalation. During the operation, blood pressure and heart rate decreased to some extent, but the decreases did not exceed 20% of the baseline, and all patients returned to normal conditions within 90 minutes after inhalation.

Conclusion: Intranasal inhalation of Dex 30 minutes before third molar extraction can provide a good sedative effect, and large-sample multicenter RCTs are needed to evaluate the analgesic effect of Dex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S194894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485320PMC
December 2019

The effect of hydrodynamic forcing on the transport and deposition of polybrominated diphenyl ethers (PBDEs) in Hangzhou Bay.

Ecotoxicol Environ Saf 2019 Sep 24;179:111-118. Epub 2019 Apr 24.

Qingdao Institute of Marine Geology, China Geological Survey, Qingdao, 266071, China. Electronic address:

Surface sediment samples (n = 92) were collected from Hangzhou Bay to investigate the transport and deposition of polybrominated diphenyl ethers (PBDEs) and to assess the ecological risks in Hangzhou Bay. The concentrations of ∑PBDEs (sum of BDE-28, 47, 99, 100, 153, 154, 183) and BDE-209 ranged from 3.61 to 91.09 pg g and from non-detectable to 2007.52 pg g (dry weight), respectively. The high values of ∑PBDEs and BDE-209 were commonly occurred at the northeast of Hangzhou Bay and the Nanhui Spit coast of Shanghai. Compared with the south part of the bay, the dominance of BDE-209 was more prominent and the linear correlations between PBDEs concentrations and TOCs as well as median grain size were more significant in the northern Hangzhou Bay. Hydrodynamic forcing on the transport and deposition of PBDEs is primarily responsible for the discrepancy of this spatial distribution in these two parts. In addition to BDE-209, BDEs-153, 99, 47, and 100 were also the abundant congeners. Three principal components were extracted using principal component analysis (PCA), mainly attributed to human activities, erosion of polluted soils via surface runoff and release from products for PC1, PC2 and PC3, respectively. The calculation results of mass inventories, hazard quotients (HQs) and risk quotients (RQs) indicated that the ecological risk of PBDEs in Hangzhou Bay was low. The multiple effect of hydrodynamic forcing with complicated and large-scope tidal currents made it hard to deposit for organic matters and contaminants in Hangzhou Bay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.04.026DOI Listing
September 2019

Oral Bromelain for the Control of Facial Swelling, Trismus, and Pain After Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.

J Oral Maxillofac Surg 2019 Aug 21;77(8):1566-1574. Epub 2019 Mar 21.

Lecturer, College of Stomatology, Shandong University, Jinan, Shandong Province, China. Electronic address:

Purpose: The purpose of this study was to evaluate whether bromelain can decrease trismus, pain, and facial swelling in patients undergoing impacted third molar surgery.

Materials And Methods: Three databases were searched to identify relevant studies through November 1, 2017. Randomized controlled trials (RCTs) that compared the effect of bromelain versus placebo after mandibular third molar surgery were included. The main outcome measures, pain, facial swelling, and trismus, were assessed in the early stage (2 to 3 days) and the late stage (7 days) after surgery. Standardized mean differences (SMDs) and weighted mean differences (WMDs) were calculated using fixed-effect models. All statistical analyses were implemented using Review Manager 5.3.

Result: Six RCTs were included in this meta-analysis. The pooled results suggested that bromelain appears to be effective for decreasing facial swelling in the early and late stages after surgery (early-stage SMD, -0.24; 95% confidence interval [CI], -0.46 to -0.02; P = .03; late-stage SMD, -0.54; 95% CI, -0.84 to -0.24; P = .0004). Bromelain alleviated postoperative pain 7 days after surgery (SMD, -0.54; 95% CI, -0.87 to -0.20; P = .002), but there was no significant difference in pain levels at the early stage. For trismus, analyses showed that bromelain had no apparent effect on early or late trismus.

Conclusion: Bromelain conferred moderate relief of postoperative discomfort after third molar surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2019.02.044DOI Listing
August 2019

Highly sensitive mass detection based on nonlinear sum-sideband in a dispersive optomechanical system.

Opt Express 2019 Feb;27(4):3909-3919

We present a theoretical scheme to realize high-sensitive mass detection in a dispersive optomechanical system (DOMS) via nonlinear sum-sideband. In this scheme, DOMS assisted by a degenerate parametric amplifier (DPA) provides a well-established optomechanical circumstance, where nonlinear optomechanical interaction between cavity mode and mechanical mode of dielectric membrane is expected for creating the frequency components at optical sum-sideband. Such a scheme for mass detection mainly relies on monitoring the conversion efficiency of generated sum-sideband after the added mass is absorbed on the dielectric membrane. Using experimentally achievable parameters, we find that the conversion efficiency of sum-sideband and the sensitivity of mass detection can be simultaneously improved when the nonlinear gain of DPA increases. Furthermore, our results also demonstrate that this mass detection of DOMS can reach femtogram (fg) level resolution, when the method of mass detection relies on a direct relationship between maximum efficiency of sum-sideband and mass-change of membrane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.27.003909DOI Listing
February 2019

Comprehensive assessment of tranexamic acid during orthognathic surgery: A systematic review and meta-analysis of randomized, controlled trials.

J Craniomaxillofac Surg 2019 Apr 21;47(4):592-601. Epub 2019 Jan 21.

School of Stomatology, Shandong University, 250012, Jinan City, Shandong Province, PR China; Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan City, Shandong Province, PR China. Electronic address:

The objective of this study was to comprehensively assess the use of tranexamic acid (TXA) during orthognathic surgery. A systematic review and meta-analysis of randomized controlled trials addressing these issues were carried out. Three electronic databases, included PubMed, Web of Science, and Cochrane Library, were searched until April 30, 2018. Eligible studies were restricted to randomized, controlled trials (RCTs). Weighted mean differences (WMD) for blood loss, operation time, haematocrit, quality of surgical field, and odds ratio (OR) for transfusion rates were pooled for the included studies. Eight randomized, controlled trials were included for analysis. Compared with the control group, the TXA group showed a reduction in intraoperative blood loss of 165.03 ml (p < 0.00001; 95% CI, -200.93 to -129.13 ml), a reduction in the drop of haematocrit of 2.32 g/dl (p < 0.00001; 95% CI, -3.38 to -1.26 g/dl), and an improved quality of surgical field (p < 0.00001; MD, -1.01; 95% CI, -1.23 to -0.80). Tranexamic acid has a limited effect on reducing operative time (p < 0.00001; MD, -16.18 min; 95% CI, -19.60 to -12.75 min) and on decreasing the transfusion rates (p = 0.02; OR = 0.33; 95% CI, 0.13 to 0.83).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcms.2019.01.021DOI Listing
April 2019

Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise.

Biomed Res Int 2018 18;2018:2828143. Epub 2018 Dec 18.

Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha, Hunan 410012, China.

To research carbonylated proteins and screen molecular targets in the rat striatum on regular aerobic exercise, male Sprague-Dawley rats (13 months old, n = 24) were randomly divided into middle-aged sedentary control (M-SED) and aerobic exercise (M-EX) groups (n = 12 each). Maximum oxygen consumption (VO) gradually increased from 50%-55% to 65%-70% for a total of 10 weeks. A total of 36 carbonylated proteins with modified oxidative sites were identified by Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometer (ESI-Q-TOF-MS), including 17 carbonylated proteins unique to the M-SED group, calcium/calmodulin-dependent protein kinase type II subunit beta (CaMKII), and heterogeneous nuclear ribonucleoprotein A2/B1 (Hnrnpa2b1), among others, and 19 specific to the M-EX group, ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), and malic enzyme, among others. Regular aerobic exercise improved behavioral and stereological indicators, promoted normal apoptosis (P < 0.01), alleviated carbonylation of the CaMKII and Hnrnpa2b1, but induced carbonylation of the UCH-L1, and significantly upregulated the expression levels of CaMKII, CaMKII, and Vdac1 ( < 0.01) and Hnrnpa2b1 and UCH-L1 ( < 0.01), as well as the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways (PI3K/Akt/mTOR) pathway-related genes Akt and mTOR. Regular aerobic exercise for 10 weeks (incremental for the first 6 weeks followed by constant loading for 4 weeks) enhanced carbonylation of CaMKII, Hnrnpa2b1, and modulated apoptosis via activation of CaMK and phosphoinositide 3-kinase/protein kinase B/mTOR signaling. It also promoted normal apoptosis in the rat striatum, which may have protective effects in neurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/2828143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312609PMC
May 2019

Biofunctional magnetic hybrid nanomaterials for theranostic applications.

Nanotechnology 2019 Jan 16;30(3):032002. Epub 2018 Nov 16.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) & Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, People's Republic of China.

Cancer is a major disease that seriously threatens human health and is a leading cause of human death. At present, the commonly used cancer treatment methods are surgical therapy, chemical drug therapy and radiation therapy (RT). However, these treatments all have their own shortcomings and cannot perfectly meet the needs of clinical diagnosis and treatment. It is of great significance to improve the diagnosis and treatment level, so that the curative effect and quality of life of tumor patients can be improved. The rapid development of nanotechnology has brought hope to the diagnosis and treatment of cancer and the appearance of biofunctional magnetic hybrid nanomaterials (MHNs) has provided a new possibilities for the integration of cancer diagnosis and treatment. As a promising research direction, the multifunctional nanoplatform integrates imaging diagnosis, drug therapy and drug delivery. Better treatment effects and fewer side effects can be achieved by optimizing materials to build stable, efficient, and safe MHNs with combined functions of multimodal imaging and various treatments. This review focuses on not only the research progress of MHNs but also their applications and development trend in the integration of cancer diagnosis and treatment. A description of the applications of MHN structure optimization for both magnetic resonance imaging-based multimodal diagnosis and cancer therapy is given. Furthermore, RT is introduced and the development of MHNs for diagnosis and treatment system is investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/aaebccDOI Listing
January 2019

Anesthetic Efficiency of Articaine Versus Lidocaine in the Extraction of Lower Third Molars: A Meta-Analysis and Systematic Review.

J Oral Maxillofac Surg 2019 Jan 5;77(1):18-28. Epub 2018 Sep 5.

Professor, College of Stomatology, Shandong University, Jinan, China. Electronic address:

Purpose: The purpose of this study was to evaluate whether the anesthetic efficiency of articaine is superior to that of lidocaine during lower third molar extraction (LTME).

Materials And Methods: Three electronic databases (PubMed, Cochrane, and Web of Science) were searched to identify randomized controlled trials up to December, 31 2017. Five evaluation indexes were extracted, namely success rate of anesthesia, subjective onset time of anesthesia, objective onset time of anesthesia, duration time of anesthesia, and intraoperative pain assessment, to assess the anesthesia efficiency of the 2 solutions. All data analyses were conducted using Review Manager (version 5.3; The Cochrane Collaboration, London, United Kingdom).

Results: Nine studies were included in this review. The sample was composed of 770 LTMEs from 493 patients, with 382 LTMEs in the lidocaine group and 388 LTMEs in the articaine group. Compared with lidocaine, 4% articaine with 1:100,000 epinephrine showed a higher success rate of anesthesia (risk ratio, 1.10; 95% confidence interval [CI], 1.01 to 1.21; P = .03), shorter subjective onset time of anesthesia (standardized mean difference, 1.20; 95% CI, 0.50 to 1.89; P = .0007), and longer duration time of anesthesia (mean difference, 0.83 hours; 95% CI, 0.59 to 1.07 hours; P < .00001); however, for intraoperative pain assessment (mean difference, 3.12 mm; 95% CI, -0.13 to 6.37 mm; P = .06) and objective onset time of anesthesia (standardized mean difference, 0.44; 95% CI, -0.39 to 1.26; P = .30), there was no significant difference between the 2 solutions.

Conclusions: The results of this study suggest that 4% articaine with 1:100,000 epinephrine possesses superior anesthetic efficiency relative to lidocaine for inferior alveolar nerve blocks during LTME.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2018.08.020DOI Listing
January 2019

The role of Twist1 in mutant huntingtin-induced transcriptional alterations and neurotoxicity.

J Biol Chem 2018 07 11;293(30):11850-11866. Epub 2018 Jun 11.

From the Department of Neurological Surgery,

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the huntingtin protein (Htt). Transcriptional dysregulation is an early event in the course of HD progression and is thought to contribute to disease pathogenesis, but how mutant Htt causes transcriptional alterations and subsequent cell death in neurons is not well understood. RNA-Seq analysis revealed that expression of a mutant Htt fragment in primary cortical neurons leads to robust gene expression changes before neuronal death. Basic helix-loop-helix transcription factor Twist1, which is essential for embryogenesis and is normally expressed at low levels in mature neurons, was substantially up-regulated in mutant Htt-expressing neurons in culture and in the brains of HD mouse models. Knockdown of Twist1 by RNAi in mutant Htt-expressing primary cortical neurons reversed the altered expression of a subset of genes involved in neuronal function and, importantly, abrogated neurotoxicity. Using brain-derived neurotrophic factor (), which is known to be involved in HD pathogenesis, as a model gene, we found that Twist1 knockdown could reverse mutant Htt-induced DNA hypermethylation at the regulatory region and reactivate expression. Together, these results suggest that Twist1 is an important upstream mediator of mutant Htt-induced neuronal death and may in part operate through epigenetic mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA117.001211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066321PMC
July 2018

Effectiveness of Drainage in Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.

J Oral Maxillofac Surg 2018 Aug 15;76(8):1640-1650. Epub 2018 Mar 15.

Professor, College of Stomatology, Shandong University, Jinan, Shandong, China. Electronic address:

Purpose: The purpose of this study was to provide an evidence-based evaluation of the impact of surgical drainage after the removal of mandibular third molars.

Materials And Methods: The Medline (PubMed), Cochrane Library, and Web of Science databases were searched to identify randomized controlled trials up to September 1, 2017. Postoperative variables, including facial swelling, trismus, and pain, were calculated early (2 to 3 days) and late (5 to 7 days) after the removal of impacted mandibular third molars. Weighted mean differences for trismus and standardized mean differences (SMDs) for swelling and pain were pooled for the included studies.

Results: The samples consisted of 592 extractions (297 with surgical drainage and 295 controls) in 409 participants. The included studies were published from 1988 to 2016. Participants who received surgical drainage had significantly less facial swelling during the early stage (SMD, -0.46; 95% confidence interval [CI], -0.67 to -0.26; P < .0001) and the late stage (SMD, -0.36; 95% CI, -0.55 to -0.16; P = .0004) after the removal of an impacted mandibular third molar. They also had better mouth opening than controls during the early and late stages (early MD, 5.55 mm; 95% CI, 2.31-8.79; P = .0008; late MD, 2.38 mm; 95% CI, 1.47-3.29; P < .0001). The level of pain was significantly different between the 2 groups in the early stage (SMD, -0.55; 95% CI, -1.00 to -0.10; P = .01); however, there were no significant differences in the late stage (SMD, -0.13; 95% CI, -0.38 to 0.12; P = .30).

Conclusion: The use of surgical drainage has an obviously positive effect on postoperative reactions after the removal of a mandibular third molar. Given the need for additional time for clinic visits, surgical drainage presents an alternative for the perioperative management of impacted mandibular third molar surgery, especially in cases of a fully bony tooth with poor drainage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2018.03.004DOI Listing
August 2018

Quadrature squeezing of a higher-order sideband spectrum in cavity optomechanics.

Opt Lett 2018 Jan;43(1):9-12

We propose an efficient scheme to generate quadrature squeezing of a higher-order sideband spectrum in an optomechanical system. This is achieved by exploiting a well-established optomechanical circumstance, where a second-order nonlinearity is embedded into the optomechanical cavity driven by a strong control field and a weak probe pulse. Using experimentally achievable parameters, we demonstrate that the second-order nonlinearity intensity and the frequency detuning of a control field allow us to modify the amplitude of higher-order sidebands and improve the amount of squeezing of a higher-order sideband spectrum. Furthermore, in the presence of a strong second-order nonlinearity, an optimizing quadrature squeezing of a higher-order sideband spectrum can be achieved, which provides a practical opportunity to design the squeezed frequency combs and other precision measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.43.000009DOI Listing
January 2018

Tunable two-phonon higher-order sideband amplification in a quadratically coupled optomechanical system.

Sci Rep 2017 12 15;7(1):17637. Epub 2017 Dec 15.

Department of Physics, Zhejiang Sci-Tech University, Hangzhou, 310018, China.

We propose an efficient scheme for the controllable amplification of two-phonon higher-order sidebands in a quadratically coupled optomechanical system. In this scheme, a strong control field and a weak probe pulse are injected into the cavity, and the membrane located at the middle position of the cavity is driven resonantly by a weak coherent mechanical pump. Beyond the conventional linearized approximation, we derive analytical expressions for the output transmission of probe pulse and the amplitude of second-order sideband by adding the nonlinear coefficients into the Heisenberg-Langevin formalism. Using experimentally achievable parameters, we identify the conditions under which the mechanical pump and the frequency detuning of control field allow us to modify the transmission of probe pulse and improve the amplitude of two-phonon higher-order sideband generation beyond what is achievable in absence of the mechanical pump. Furthermore, we also find that the higher-order sideband generation depends sensitively on the phase of mechanical pump when the control field becomes strong. The present proposal offers a practical opportunity to design chip-scale optical communications and optical frequency combs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-17974-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732222PMC
December 2017

Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development.

Proc Natl Acad Sci U S A 2017 12 11;114(52):E11180-E11189. Epub 2017 Dec 11.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110;

Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties. We defined transcriptome changes accompanying this process and integrated these data with direct transcriptional targets of NKX2-1, a transcription factor controlling MGE specification. This analysis defined NKX2-1-associated genes with enriched expression during MGE specification and cIN differentiation, including known and previously unreported transcription factor targets with likely roles in MGE specification, and other target classes regulating cIN migration and function. NKX2-1-associated peaks were enriched for consensus binding motifs for NKX2-1, LHX, and SOX transcription factors, suggesting roles in coregulating MGE gene expression. Among the NKX2-1 direct target genes with cIN-enriched expression was , which encodes a chromatin remodeling protein mutated to cause human epilepsies. Accordingly, CHD2 deficiency impaired cIN specification and altered later electrophysiological function, while CHD2 coassociated with NKX2-1 at -regulatory elements and was required for their transactivation by NKX2-1 in MGE-like progenitors. This analysis identified several aspects of gene-regulatory networks underlying human MGE specification and suggested mechanisms by which NKX2-1 acts with chromatin remodeling activities to regulate gene expression programs underlying cIN development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1712365115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748186PMC
December 2017

Dynamic control of coherent pulses via destructive interference in graphene under Landau quantization.

Sci Rep 2017 05 31;7(1):2513. Epub 2017 May 31.

Department of Physics, Southeast University, Nanjing, 211189, China.

We analyze the destructive interference in monolayer graphene under Landau quantization in a time-dependent way by using the Bloch-Maxwell formalism. Based on this analysis, we investigate the dynamics control of an infrared probe and a terahertz (THz) switch pulses in graphene. In presence of the THz switch pulse, the destructive interference take places and can be optimized so that the monolayer graphene is completely transparent to the infrared probe pulse. In absence of the THz switch pulse, however, the infrared probe pulse is absorbed due to such a interference does not take place. Furthermore, we provide a clear physics insight of this destructive interference by using the classical dressed-state theory. Conversely, the present model may be rendered either absorbing or transparent to the THz switch pulse. By choosing appropriate wave form of the probe and switch pulses, we show that both infrared probe and THz switch pulses exhibit the steplike transitions between absorption and transparency. Such steplike transitions can be used to devise a versatile quantum interference-based solid-state optical switching with distinct wave-lengths for optical communication devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-02740-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451483PMC
May 2017

Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells.

Stem Cells Int 2017 17;2017:7168687. Epub 2017 Jan 17.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.

Hypoxia is an important and influential factor in development. The embryonic kidney is exposed to a hypoxic environment throughout its development. The Wnt/-catenin pathway plays vital roles in the differentiation and self-renewal of metanephrogenic mesenchymal stem cells (MMSCs) from which the kidney is derived. Thus, we hypothesized that hypoxia can regulate the differentiation and pluripotency of MMSCs through the Wnt/-catenin pathway. To test this hypothesis, MMSCs from rats at embryonic day 18.5 were cultured in normoxic (21% O) and hypoxic (1% O) conditions. The effects of hypoxia on differentiation, stemness, proliferation, and apoptosis of cultured MMSCs and on the activity of the Wnt/-catenin pathway were tested. Our results revealed that the hypoxic condition increased the number of epithelial cells (E-cadherin or CK18) as well the expression of markers of renal tubule epithelia cells (CDH6, Aqp1, and OPN), decreased the number and proliferation of stem cells (SIX-2 or CITED1), and induced apoptosis. Additionally, hypoxia reduced the expression of Wnt4 as well as its downstream molecules -catenin, LEF-1, and Axin2. Activation of the Wnt/-catenin pathway by LiCl or BIO modified the effects of hypoxia on the differentiation and self-renewal of MMSCs. Thus, we concluded that hypoxia induces the differentiation and inhibits the self-renewal of MMSCs by inhibiting the Wnt/-catenin pathway. The observations further our understanding of the effects of hypoxia on kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/7168687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282446PMC
January 2017

Extrinsic parameter calibration of stereo vision sensors using spot laser projector.

Appl Opt 2016 Sep;55(25):7098-105

The on-site calibration of stereo vision sensors plays an important role in the measurement field. Image coordinate extraction of feature points of existing targets is difficult under complex light conditions in outdoor environments, such as strong light and backlight. This paper proposes an on-site calibration method for stereo vision sensors based on a spot laser projector for solving the above-mentioned problem. The proposed method is used to mediate the laser spots on the parallel planes for the purpose of calibrating the coordinate transformation matrix between two cameras. The optimal solution of a coordinate transformation matrix is then solved by nonlinear optimization. Simulation experiments and physical experiments are conducted to validate the performance of the proposed method. Under the condition that the field of view is approximately 400  mm×300  mm, the proposed method can reach a calibration accuracy of 0.02 mm. This accuracy value is comparable to that of the method using a planar target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.55.007098DOI Listing
September 2016