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1.
Biomed Pharmacother ; 121: 109553, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704611

RESUMO

OBJECTIVES: miRNAs in salivary exosomes are used as novel non-invasive biomarkers for detection strategies of human disease. Here, we aimed to investigate the diagnostic potential of salivary exosomal miRNAs as biomarkers for screening oral squamous cell carcinoma (OSCC) and to explore the underlying mechanisms of OSCC pathogenesis. MATERIALS AND METHODS: Differentially expressed miRNAs were obtained from salivary exosomes of four healthy controls and four OSCC patients using miRNA microarray analysis. The expression of miR-24-3p in the salivary exosomes was then verified by qRT-PCR. The diagnostic power was assessed by receiver operating characteristic (ROC) analysis. Cell proliferation was measured using CCK-8 cell viability assay and colony formation assay. The target gene of miR-24-3p was confirmed by dual luciferase reporter assay. RESULTS: A total of 109 miRNAs were found to be more than 2-fold altered in the salivary of patients and healthy individuals by miRNA microarray. qRT-PCR analysis further confirmed a significant increase of miR-24-3p in the salivary exosomes from 45 preoperative OSCC patients compared to 10 normal controls. ROC analysis showed that miR-24-3p has excellent diagnostic accuracy for OSCC (area under the ROC curve [AUC] = 0.738; P = 0.02). Similarly, we found that miR-24-3p expressed a higher level in OSCC neoplastic tissues, suggesting that circulating miR-24-3p may originate from tumor cells. Furthermore, exogenous exosomal miR-24-3p increased proliferation of recipient malignant cells. Additionally, overexpression of miR-24-3p promoted the proliferation of OSCC cells and regulated the expression of cell cycle-related genes. Dual luciferase reporter assay indicated that miR-24-3p can interact with PER1 directly. CONCLUSIONS: Salivary exosomal miR-24-3p is a potential novel diagnostic biomarker for OSCC, and miR-24-3p can maintain the proliferation of OSCC cells through targeting PER1.

2.
J Cell Biochem ; 121(1): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31081181

RESUMO

Porphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP-binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real-time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg- and Lys-gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin-1ß (IL-1ß) and IL-6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild-type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis.

3.
Methods Mol Biol ; 2061: 259-265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31583665

RESUMO

Proteomics analysis was a powerful technology for characterizing proteins and protein posttranslational modification (PTMs). Recently, many anther and pollen-related proteomic analyses have been reported, which have expanded our understanding of anther and pollen development and regulation. In this chapter, we describe a detailed, optimized protocol for the separation, digestion, tagging, and subsequent mass spectrometry-based identification and quantification of proteins and phosphoproteins from anther and pollen.

4.
Clin Chim Acta ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794767

RESUMO

Atherosclerosis is an arterial disease associated with dyslipidemia, abnormal arterial calcification and oxidative stress. It has been shown that a continued chronic inflammatory state of the arterial wall contributes to the development of atherosclerosis. The inflammatory stimulation, recruitment of inflammatory cells and production of pro-inflammatory cytokines enhances vascular inflammation. Some members of the S100 proteins family bind with their receptors, such as advanced glycation end products (RAGE), scavenger receptors (CD36) and toll-like receptor 4 (TLR-4), contributing to the cellular response in atherosclerotic progression. This review summarizes the roles of S100 proteins (S100A8, S100A9 and S100A12) in the vascular inflammation, vascular calcification and vascular oxidative stress. S100 proteins are released from monocytes, smooth muscle cells and endothelial cells in response to cellular stress stimuli, and then the binding of S100 proteins to RAGE activate downstream signaling such as transcription factor kappa B (NF-κB) translocation and reactive oxygen species (ROS) production, which act as a positive feedback loop for inducing pro-inflammatory phenotype in a wide variety of cell types including endothelial cells, vascular smooth muscle cells and leukocytes. Thus, it suggests that the inhibition of S100 proteins-mediated RAGE and TLR4 activation appears to be a promising approach to treat atherosclerosis. In addition, recent study showed that serum S100A12 can predict future cardiovascular events, highlighting that S100A12 is likely to be a potential biomarker of therapeutic efficacy and disease progression in coronary heart disease. Future studies of patients with coronary heart disease may provide more evidences supporting that S100 proteins is promising drug target in the prevention and therapy of atherosclerosis.

5.
BMJ Open ; 9(12): e028518, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796472

RESUMO

INTRODUCTION: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics. METHODS AND ANALYSIS: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPGBFM)model in the original cohort and assess the model in the validation cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03470389.

6.
J Mol Endocrinol ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794424

RESUMO

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known, how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested these hypotheses: 1) a sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion; and 2) dopamine, via the D1R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist, FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D1-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells, via the D1R, because the D5R, the other D1-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate, acutely, an oral sodium load. Dopamine, via the D1R, by interacting with PPAR-α, is involved in this process.

7.
Sci China Life Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31784935

RESUMO

Gonorrhea is one of the most common sexually transmitted diseases worldwide. To cure infection and prevent transmission, timely and appropriate antimicrobial therapy is necessary. Unfortunately, Neisseria gonorrhoeae, the etiological agent of gonorrhea, has acquired nearly all known mechanisms of antimicrobial resistance (AMR), thereby compromising the efficacy of antimicrobial therapy. Treatment failure resulting from AMR has become a global public health concern. Whole-genome sequencing is an effective method to determine the AMR characteristics of N. gonorrhoeae. Compared with next-generation sequencing, the MinION sequencer (Oxford Nanopore Technologies (ONT)) has the advantages of long read length and portability. Based on a pilot study using MinION to sequence the genome of N. gonorrhoeae, we optimized the workflow of sequencing and data analysis in the current study. Here we sequenced nine isolates within one flow cell using a multiplexed sequencing strategy. After hybrid assembly with Illumina reads, nine integral circular chromosomes were obtained. By using the online tool Pathogenwatch and a BLAST-based workflow, we acquired complete AMR profiles related to seven classes of antibiotics. We also evaluated the performance of ONT-only assemblies. Most AMR determinants identified by ONT-only assemblies were the same as those identified by hybrid assemblies. Moreover, one of the nine assemblies indicated a potentially novel antimicrobial-related mutation located in mtrR which results in a frame-shift, premature stop codon, and truncated peptide. In addition, this is the first study using the MinION sequencer to obtain complete genome sequences of N. gonorrhoeae strains which are epidemic in China. This study shows that complete genome sequences and antimicrobial characteristics of N. gonorrhoeae can be obtained using the MinION sequencer in a simple and cost-effective manner, with hardly any knowledge of bioinformatics required. More importantly, this strategy provides us with a potential approach to discover new AMR determinants.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 725-730, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762245

RESUMO

OBJECTIVE: To understand the relationship between obesity and depression in the elderly in China, and to explore whether there are differences between the genders. METHODS: The data were collected from the 2015 China Health and Retirement National Investigation (China Health and Retirement Longitudinal Study, CHARLS). The respondents were grouped according to depressive status. The difference of depressive status between the elderly male and female groups was examined by Chi-square test. The relationship between depression, obesity and the other sociological factors was analyzed by binary logistic regression. RESULTS: There were 4 019 valid cases, including 2 109 males (52.48%) and 1 910 females (47.52%). All the respondents were aged 60 years and over. There were 474 cases of central obesity (11.79%) and 2 418 cases of abdominal obesity (60.16%). There were significant differences in central obesity and abdominal obesity between the elderly male and female groups (P < 0.001). 1 304 cases suffered from depression, accounting for 32.45%, of which 539 cases were male (41.33%) and 765 cases were female (58.67%). Different groups of gender, central obesity and abdominal obesity had significant differences in depressive status (P < 0.001). The results of univariate analysis indicated that the characteristics of female, divorced/widowed/unmarried, in rural areas, having chronic diseases and functional loss were the risk factors for depression. The results of multivariate logistic regression analysis indicated that, in terms of the total sample, after adjustment for the confounding factors, both central obesity and abdominal obesity groups were less likely to suffer from depression. After stratified by gender, both central obesity and abdominal obesity were negatively correlated with depression. CONCLUSIONS: The elderly with central obesity or abdominal obesity are less likely to suffer from depression, regardless of gender.


Assuntos
Depressão/complicações , Obesidade Abdominal/complicações , Idoso , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
9.
Environ Toxicol Pharmacol ; 74: 103296, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31783317

RESUMO

In vitro to in vivo extrapolation (IVIVE) for next-generation risk assessment (NGRA) of chemicals requires computational modeling and faces unique challenges. Using mitochondria-related toxicity data of troglitazone (TGZ), a prototype drug known for liver toxicity, from HepaRG, HepG2, HC-04, and primary human hepatocytes, we explored inherent uncertainties in IVIVE, including cell models, cellular response endpoints, and dose metrics. A human population physiologically-based pharmacokinetic (PBPK) model for TGZ was developed to predict in vivo doses from in vitro point-of-departure (POD) concentrations. Compared to the 200-800 mg/d dose range of TGZ where liver injury was observed clinically, the predicted POD doses for the mean and top one percentile of the PBPK population were 28-372 and 15-178 mg/d respectively based on Cmax dosimetry, and 185-2552 and 83-1010 mg/d respectively based on AUC. In conclusion, although with many uncertainties, integrating in vitro assays and PBPK modeling is promising in informing liver toxicity-inducing TGZ doses.

10.
Mol Med Rep ; 20(5): 4059-4066, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702028

RESUMO

The present study aimed to explore the role of the PTEN/Akt/mTOR signaling pathway in the neurite outgrowth and apoptosis of cortical neurons. Cortical neurons were seeded on or adjacent to chondroitin sulfate proteoglycans. The length, number and crossing behavior of the neurites were calculated. Immunohistochemical staining and TUNEL data were analyzed. Neurites treated with PTEN inhibitor exhibited significant enhancements in elongation, initiation and crossing abilities when they encountered chondroitin sulfate proteoglycans in vitro. These effects disappeared when the PTEN/Akt/mTOR signaling pathway was blocked. Neurons exhibited significant enhancements in survival ability following PTEN inhibition. The present study demonstrated that PTEN inhibition can promote axonal elongation and initiation in cerebral cortical neurons, as well as the ability to cross the chondroitin sulfate proteoglycan border. In addition, PTEN inhibition is useful for protecting the neuron from apoptosis. The PTEN/Akt/mTOR signaling pathway is an important signaling pathway.

11.
Opt Express ; 27(21): 30441-30448, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684291

RESUMO

Parametric spectro-temporal analyzer (PASTA) has been demonstrated as a powerful tool for ultrafast spectrum measurement with superior frame rate and resolution. Compared with other time-stretch-based counterparts, the temporal focusing mechanism enlarges the initial condition and enables the observation of arbitrary waveform, especially the emission spectrum. However, due to the limited conversion bandwidth of the parametric mixing-based time-lens, the observation bandwidth of PASTA is constrained within the C (conventional) band, which hinders its practical applications. To overcome this constraint, both stokes and anti-stokes conversions of the parametric mixing process are leveraged, and the concept of time division multiplexing (TDM) is introduced to ensure their separability. Therefore, the TDM-based PASTA system successfully demultiplexes the C band and L (long) band spectra in two adjacent temporal frames. It is capable of reconstructing the wavelength-to-time sequence for arbitrary waveform over a record 58-nm observation bandwidth, which can be further improved by optimizing the filters and amplifiers. Meanwhile, both of these two bands achieve 20-pm resolution, 10-MHz frame rate, and -30-dBm sensitivity. Moreover, this TDM concept can also be applied to other parametric mixing-based temporal imaging systems to enlarge the working wavelength band, such as temporal magnification.

12.
Curr Pharm Des ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696803

RESUMO

ß thalassemia is a common monogenic genetic disease that is very harmful to human health. The disease arises is due to the deletion of or defects in ß-globin, which reduces synthesis of the ß-globin chain, resulting in a relatively excess number of α-chains. The formation of inclusion bodies deposited on the cell membrane causes a decrease in the ability of red blood cells to deform and a group of hereditary haemolytic diseases caused by massive destruction in the spleen. In this work, machine learning algorithms were employed to build a prediction model for inhibitors against K562 based on 117 inhibitors and 190 non-inhibitors. The overall accuracy (ACC) of a 10-fold cross-validation test and an independent set test using Adaboost were 83.1% and 78.0%, respectively, surpassing Bayes Net, Random Forest, Random Tree, C4.5, SVM, KNN and Bagging. It was determined that Adaboost could be applied to build a learning model in the prediction of inhibitors against K526 cells.

13.
Genome Biol ; 20(1): 254, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779641

RESUMO

Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis.

14.
J Orthop Surg Res ; 14(1): 395, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779651

RESUMO

BACKGROUND: The relationship between preoperative hip measurements and dislocation after bipolar hemiarthroplasty is presently unclear. In the current study, we investigated the morphological risk factors associated with dislocation after bipolar hemiarthroplasty of the hip in patients with femoral neck fractures. METHODS: Between January 2011 and June 2017, a nested case-control design study was used to analyze the risk factors for dislocation in 348 patients who had undergone bipolar hemiarthroplasty because of femoral neck fractures. Twelve patients underwent at least one dislocation postoperatively. Sixty patients without dislocation were selected as controls matched in terms of time of surgery, age, and sex, at a ratio of 1:5. Patient acetabular measurements were compared between the dislocation group and the control group, including the center-edge angle, abduction angle, acetabular width and depth, depth-to-width ratio, femoral neck offset, leg length discrepancy, and femoral head coverage ratio. A multivariate logistic regression model was used to evaluate the morphological risk factors of dislocation. RESULTS: Postoperatively, the incidence of dislocation was 3.4%. A smaller center-edge angle was found to be a risk factor associated with dislocation after bipolar hemiarthroplasty of the hip. Patients with small acetabular depth and a small acetabular depth-width ratio were prone to dislocation. Patients with a center-edge angle of ≤ 45.4° or an acetabular depth of ≤ 19.12 mm were more likely to suffer dislocation. CONCLUSIONS: Careful preoperative measurements before bipolar hemiarthroplasty of the hip are important. Surgical intervention for femoral neck fracture patients with a shallow acetabulum should be carefully planned and total hip arthroplasty should be considered when necessary.

15.
Mol Ther Nucleic Acids ; 18: 831-840, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31739208

RESUMO

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC.

16.
Biomed Res Int ; 2019: 4506876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737663

RESUMO

Inflammation plays a central role in knee osteoarthritis (OA) pathogenesis (C. R. Scanzello, 2017). The synovial membrane inflammation is associated with disease progression and represents a primary source of agony in knee OA (L. A. Stoppiello et al., 2014). Many inflammatory mediators may have biomarker utility. To identify synovium related to knee OA pain biomarkers, we used canonical correlation analysis to analyze the miRNA-mRNA dual expression profiling data and extracted the miRNAs and mRNAs. After identifying miRNAs and mRNAs, we built an interaction network by integrating miRWalk2.0. Then, we extended the network by increasing miRNA-mRNA pairs and identified five miRNAs and four genes (TGFBR2, DST, TBXAS1, and FHLI) through the Spearman rank correlation test. For miRNAs involved in the network, we further performed the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, whereafter only those mRNAs overlapped with the Online Mendelian Inheritance in Man (OMIM) genetic database were analyzed. Receiver operating characteristic (ROC) curve and support vector machine (SVM) classification were taken into the analysis. The results demonstrated that all the recognized miRNAs and their gene targets in the network might be potential biomarkers for synovial-associated pain in knee OA. This study predicts the underlying risk biomarkers of synovium pain in knee OA.

17.
Oncol Rep ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31746408

RESUMO

Mutation of the isocitrate dehydrogenase (IDH) gene is regarded a novel indicator for the prognosis of patients with glioma. However, the role of the IDH1 gene mutations in carcinogenesis and the mechanisms underlying their function in glioblastoma multiforme (GBM) remain unknown. The present study aimed to determine whether the association of RLIP76 with the different IDH1 mutational status could serve as a putative biomarker for improving disease prognosis. Quantitative PCR, western blotting and immunohistochemical staining assays were used to investigate the expression levels of RLIP76 in 124 patients with GBM with different IDH1 mutational status. In addition, the association between RLIP76 expression, IDH1 mutational status and clinicopathological characteristics was investigated. The effects of RLIP76 expression and IDH1 mutational status on cell proliferation, cell apoptosis, and cell signaling were examined by Cell Counting Kit­8, flow cytometry and western blot assays, respectively. The data demonstrated that IDH1 wild­type (IDH1Wt) patients with low RLIP76 expression exhibited improved overall and progression­free survival. This effect was not observed in patients with IDH1 mutant (IDH1Mut) GBM. In vitro assays demonstrated that knockdown of IDH1 or overexpression of the IDH1 R132H mutation suppressed cell proliferation and promoted cell apoptosis in U87 glioma cells. Mechanistic studies further indicated that although the IDH1 R132H mutant phenotype exhibited similar antitumor effects on GBM cells as those observed with the IDH1 knockdown, it acted via a different mechanism with regard to the regulation of the apoptosis signaling pathway. IDH1 R132H mutant cells promoted p53­induced apoptosis, while the IDH1 knockdown inhibited the RLIP76­dependent apoptotic pathway in glioma cells. The findings of the present study provided insight to the contribution of IDH1 mutation in the development of GBM and indicated that RLIP76 may be considered as a prognostic biomarker of IDH1Wt GBM.

18.
Rev Sci Instrum ; 90(11): 115005, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31779450

RESUMO

Research on the multi-degree-of-freedom and large-displacement motion control of the levitated object makes a contribution to broadening the application field of the Maglev technology. A one-dimensional motion control system and method of the Maglev ball are investigated in this paper. The Maglev ball motion control system is required to have a large operating range. In order to meet this requirement, a novel Maglev system based on double linear hall sensors is designed and implemented. The step-by-step control based on the Proportional-Integral-Derivative (PID) controller is proposed as one method to realize the large step response of the levitated object. The controlled object responds to the successive small step input rather than the large step input. Then, the mathematical model of the system is set up based on the electromagnetic force equation and controller parameters are tuned by following the mathematical model of the Maglev system at different positions. The experimental data show that the position accuracy of the Maglev control system using the PID controller reaches ±0.02 mm. Moreover, step-by-step control can not only safely realize large-displacement motion of the levitated object but also effectively reduce the overshoot of the step response and make the step response process smoother.

19.
BMC Cardiovasc Disord ; 19(1): 261, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771529

RESUMO

BACKGROUND: High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). VKAs, represented by warfarin, have been widely used as traditional anticoagulants, whereas NOACs have been used in clinical practice, but their anticoagulant effects and side effects are still the focus of research. We used a meta-analysis to compare the incidence of left atrial thrombi (LAT) between different anticoagulants. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases for observational studies that compared the transesophageal echocardiography (TEE) findings for patients treated with NOACs and VKAs. The incidence of LAT and dense spontaneous echocardiographic contrast (dense SEC) were extracted as the basis of the meta-analysis. RESULTS: Fifteen studies were included in the meta-analysis. We found that patients anticoagulated with NOACs and VKAs had similar incidence of LAT (OR = 0.74, 95%CI: 0.55-1.00). After excluding the heterogeneous article by sensitivity analysis, we found the incidence of LAT in patients anticoagulated with NOACs is lower than VKAs (OR = 0.59, 95%CI: 0.42-0.84). The results of subgroup analysis showed that the incidence of LAT among three types of NOACs have no significant difference (dabigatran vs. rivaroxaban, OR = 1.16 [0.75, 1.81]; rivaroxaban vs. apixaban, OR = 0.97 [0.54, 1.74]; dabigatran vs. apixaban, OR = 1.09 [0.55, 2.16]). CONCLUSION: Patients anticoagulated with NOACs may have lower incidence of LAT than VKAs. The incidence of LAT among different type of NOACs are similar.

20.
J Clin Invest ; 129(12): 5468-5473, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31682240

RESUMO

In patients with acute myeloid leukemia (AML), 10% to 30% with the normal karyotype express mutations in regulators of DNA methylation, such as TET2 or DNMT3A, in conjunction with activating mutation in the receptor tyrosine kinase FLT3. These patients have a poor prognosis because they do not respond well to established therapies. Here, utilizing mouse models of AML that recapitulate cardinal features of the human disease and bear a combination of loss-of-function mutations in either Tet2 or Dnmt3a along with expression of Flt3ITD, we show that inhibition of the protein tyrosine phosphatase SHP2, which is essential for cytokine receptor signaling (including FLT3), by the small molecule allosteric inhibitor SHP099 impairs growth and induces differentiation of leukemic cells without impacting normal hematopoietic cells. We also show that SHP099 normalizes the gene expression program associated with increased cell proliferation and self-renewal in leukemic cells by downregulating the Myc signature. Our results provide a new and more effective target for treating a subset of patients with AML who bear a combination of genetic and epigenetic mutations.

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