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1.
Cancer Res ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067266

RESUMO

Frontier evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)-MAPK-MMP-2/9 pathway. In addition, IGF2BP3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR-ACLY-PADI1-MAPK-MMP2/9 axis as a potential therapeutic target in NPC.

2.
Addict Biol ; : e12969, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047425

RESUMO

Internet gaming disorder (IGD), a worldwide mental health issue, has been widely studied using neuroimaging techniques during the last decade. Although dysfunctions in resting-state functional connectivity have been reported in IGD, mapping relationships from abnormal connectivity patterns to behavioral measures have not been fully investigated. Connectome-based predictive modeling (CPM)-a recently developed machine-learning approach-has been used to examine potential neural mechanisms in addictions and other psychiatric disorders. To identify the resting-state connections associated with IGD, we modified the CPM approach by replacing its core learning algorithm with a support vector machine. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 72 individuals with IGD and 41 healthy comparison participants. The modified CPM was conducted with respect to classification and regression. A comparison of whole-brain and network-based analyses showed that the default-mode network (DMN) is the most informative network in predicting IGD both in classification (individual identification accuracy = 78.76%) and regression (correspondence between predicted and actual psychometric scale score: r = 0.44, P < 0.001). To facilitate the characterization of the aberrant resting-state activity in the DMN, the identified networks have been mapped into a three-subsystem division of the DMN. Results suggest that individual differences in DMN function at rest could advance our understanding of IGD and variability in disorder etiology and intervention outcomes.

3.
Otolaryngol Head Neck Surg ; : 194599820965940, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048615

RESUMO

OBJECTIVE: To compare endoscopic myringoplasty using the cartilage-perichondrium complex as a graft (test group) with temporalis fascia microscopic myringoplasty (control group). STUDY DESIGN: A retrospective cohort study. SETTING: Department of Otorhinolaryngology in a tertiary Chinese hospital. METHODS: Data were collected on patients between 2017 and 2019. To balance the baseline characteristics between groups, we performed a propensity score-matched analysis, and 44 patients were included in each group. Hearing improvement and eardrum closure rates were compared, and risk factors affecting them were analyzed. RESULTS: In the control and test groups, 90.90% and 86.36% of patients had a mean air-bone gap ≤20 dB after the surgery, respectively (P = .843). The air conduction (AC) threshold gain at each frequency was similar in the 2 groups (P > .05). The closure rates were 95.45% and 93.18%, respectively (P = .645). The air-bone gap improved significantly after surgery, F(1, 61) = 6.729, P = .012. Age, group, middle ear mucosal status, and location of the perforation did not affect the change in air-bone gap or the drum closure rate (P > .05). However, there was an interaction between the change in air-bone gap and the size of the perforation, F(1, 61) = 11.067, P = 0001. CONCLUSION: Endoscopic myringoplasty using a cartilage-perichondrium complex graft is comparable with traditional surgery. Age, location of the perforation, and middle ear mucosal status did not significantly affect the change in air-bone gap or the drum closure rate. A perforation size ≥50% was always associated with a better air-bone gap improvement.

4.
J Mater Chem B ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030156

RESUMO

To enhance the efficacy of nanoparticle-based cancer therapy with reduced side effects and promote its clinical translation, a biocompatible nanocomposite based on mesoporous silica-coated gold nanorods (AuNR@MSN) for triple tumor therapy is reported in this study. The gold core served as a hyperthermia agent, while the MSN shell acted as a reservoir of chemotherapeutics owing to its excellent loading capacity. Cytochrome c with the apoptosis inducing function was anchored on the surface of AuNR@MSN to prevent drug leakage through redox-responsive disulfide bonds. The successful construction of a nanocomposite was confirmed by characterization of the physicochemical properties. In vitro and in vivo studies demonstrated that the nanocomposite displayed an optimizing anti-tumor effect with a synergistic strategy of excellent photothermal therapy, chemotherapy and protein therapy. Therefore, this cooperative strategy paves the way for high-efficiency oncotherapy with reduced side effects.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33043389

RESUMO

Several quorum sensing systems occurring in Bacillus subtilis, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in Bacillus velezensis NAU-B3. We found that the rapA4 and phrA4 genes were co-transcribed in NAU-B3. When rapA4 was expressed in the heterologous host Bacillus subtilis OKB105, surfactin production and sporulation were severely inhibited. However, when the phrA4 was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase srfA gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the srfA operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment. KEY POINTS: •Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42. •RapA4-PhrA4 regulates surfactin production and sporulation. •RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.

6.
World J Gastroenterol ; 26(36): 5408-5419, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33024393

RESUMO

Gastric cancer is the fourth leading cause of cancer-related mortality across the globe, with a 5-year survival rate of less than 40%. In recent years, several applications of artificial intelligence (AI) have emerged in the gastric cancer field based on its efficient computational power and learning capacities, such as image-based diagnosis and prognosis prediction. AI-assisted diagnosis includes pathology, endoscopy, and computerized tomography, while researchers in the prognosis circle focus on recurrence, metastasis, and survival prediction. In this review, a comprehensive literature search was performed on articles published up to April 2020 from the databases of PubMed, Embase, Web of Science, and the Cochrane Library. Thereby the current status of AI-applications was systematically summarized in gastric cancer. Moreover, future directions that target this field were also analyzed to overcome the risk of overfitting AI models and enhance their accuracy as well as the applicability in clinical practice.

7.
Acupunct Med ; : 964528420958714, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33032445

RESUMO

OBJECTIVES: The objectives of this study were to identify the mean safe needling depth and angle at BL40 between subjects, taking into account variables including sex and body mass index (BMI). METHODS: One hundred and twenty-four participants who had undergone magnetic resonance imaging (MRI) examination of the knee region for clinical indications were included in this study. BL40 needling sites were localized by World Health Organization (WHO) standards and were measured by MRI. As much as 70% of the value of AN (from the needle insertion point to the popliteal artery) was considered to represent the safe depth, and angle alpha between the BL40 straight line and the AN line was regarded as the safe angle. RESULTS: Overall, mean safe depth regardless of BMI and sex was 18.51 ± 3.56 mm (95% confidence interval (CI), 17.88%-19.14%). Mean safe depth was 17.24 ± 3.14 mm in the low and normal BMI group, 18.76 ± 2.90 mm in the overweight group, and 22.01 ± 3.71 mm in the obese group. Thirteen patients (10.5%) had internal deviation of angle alpha (95% CI, 5.6%-15.3%), while 111 patients (89.5%) had external deviation (95% CI, 84.7%-94.4%). The mean internal and external deviations of angle alpha were 8.78° ± 2.92° (95% CI, 7.01°-10.55°) and 9.75° ± 3.46° (95% CI, 9.10°-10.41°), respectively. CONCLUSION: We would suggest that, when using a straight needle insertion at BL40, it is safe to advance a 25-mm needle approximately 12.5 mm, and 17.5 mm should be safe for patients with BMI greater than 28 kg/m2. Practitioners should decrease the depth of penetration when treating patients of low body weight or height.

8.
Int J Biol Macromol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038405

RESUMO

The structure of extracted condensed tannin (CT) from the fruit of Sour jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow) and the molecular mechanisms by which CT inhibits the activity of mushroom tyrosinase were investigated. The structure of CT was characterized by high performance liquid chromatography electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The kinetic assays were used to detect inhibition effect, type and mechanism. UV scanning, fluorescence quenching, copper interacting, o-quinone interaction and molecular docking assays were also used to reveal the molecular mechanisms by which CT inhibit tyrosinase. The results showed the main structural units of CT contain afzelechin/epiafzelechin, catechin/epicatechin, and atechin/epicatechin. Kinetic analysis showed that CT inhibits both the monophenolase and diphenolase activities of tyrosinase and exhibits reversible, mixed type mechanism. The fruit CT interacts primarily with the copper ions and specific amino acid residue (Asn191, Thr203, Ala202, Ser206, Met201, His194, His54, Glu182 and Ile42) in the active site of tyrosinase to disturb oxidation of substrates by tyrosinase. These results suggested the sour jujube fruit is a potential natural source of tyrosinase inhibitors, and has a potential to be used in food preservation, whitening cosmetics.

9.
Planta ; 252(5): 75, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026530

RESUMO

MAIN CONCLUSION: Exogenous SA treatment at appropriate concentrations promotes adventitious root formation in cucumber hypocotyls, via competitive inhibiting the IAA-Asp synthetase activity of CsGH3.5, and increasing the local free IAA level. Adventitious root formation is critical for the cutting propagation of horticultural plants. Indole-3-acetic acid (IAA) has been shown to play a central role in regulating this process, while for salicylic acid (SA), its exact effects and regulatory mechanism have not been elucidated. In this study, we showed that exogenous SA treatment at the concentrations of both 50 and 100 µM promoted adventitious root formation at the base of the hypocotyl of cucumber seedlings. At these concentrations, SA could induce the expression of CYCLIN and Cyclin-dependent Kinase (CDK) genes during adventitious rooting. IAA was shown to be involved in SA-induced adventitious root formation in cucumber hypocotyls. Exposure to exogenous SA led to a slight increase in the free IAA content, and pre-treatment with the auxin transport inhibitor 1-naphthylphthalamic acid (NPA) almost completely abolished the inducible effects of SA on adventitious root number. SA-induced IAA accumulation was also associated with the enhanced expression of Gretchen Hagen3.5 (CsGH3.5). The in vitro enzymatic assay indicated that CsGH3.5 has both IAA- and SA-amido synthetase activity and prefers aspartate (Asp) as the amino acid conjugate. The Asp concentration dictated the functional activity of CsGH3.5 on IAA. Both affinity and catalytic efficiency (Kcat/Km) increased when the Asp concentration increased from 0.3 to 1 mM. In contrast, CsGH3.5 showed equal catalytic efficiency for SA at low and high Asp concentrations. Furthermore, SA functioned as a competitive inhibitor of the IAA-Asp synthetase activity of CsGH3.5. During adventitious formation, SA application indeed repressed the IAA-Asp levels in the rooting zone. These data show that SA plays an inducible role in adventitious root formation in cucumber through competitive inhibition of the auxin conjugation enzyme CsGH3.5. SA reduces the IAA conjugate levels, thereby increasing the local free IAA level and ultimately enhancing adventitious root formation.

10.
Sci Rep ; 10(1): 16127, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999311

RESUMO

Foveated near-eye display is one of the most promising approaches to deliver immersive experience of mixed reality. However, it is challenged to conceive a compact optical system. Here, we introduce a method to use polarization optics via liquid crystal photonics to improve the foveated display performance. We demonstrate a benchtop prototype of this idea. We implement and combine two display modules for peripheral and foveal visions. A peripheral display consists of a polarization selective lens (PSL) module, a polarization selective diffuser (PSD), and a slanted projection system. An 80[Formula: see text] diagonal field of view is achieved by on-axis optical configuration of the PSL module and the PSD. A foveal holographic display is composed of a spatial light modulator (SLM), a volume grating lens, and a microelectromechanical system mirror possibly in combination with a switchable polarization selective grating module. The holographic reconstruction using the SLM enables accurate focus cue generation and high resolution above 30 cycles per degree within 15[Formula: see text] by 15[Formula: see text] field of view. We explore and discuss the liquid crystal photonics in the prototype that has a novel optical design using volume gratings with polarization selectivity.

11.
Gene ; : 145194, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007376

RESUMO

The low laying performance of geese seriously damages the growth of the poultry industry, and is related to the development of pre- hierarchical follicles. Our previous studies have revealed that FAR1 and TGFBRAP1 were involved in follicular development, but the exact regulation mechanism still kept unclear. In recent studies, the expression of FAR1 and TGFBRAP1 mRNA were detected, and we found that their expression levels were relatively higher in hierarchical follicles than in pre- hierarchical follicles (P < 0.05). Moreover, generally the level of FAR1 and TGFBRAP1 mRNA gradually increased in hierarchical follicles. In addition, the proliferation and apoptosis of granulosa cells were assayed with overexpression or knockdown technology. The results showed that by the knockdown of FAR1 mRNA level, the proliferation rate of follicular granulosa cells increased significantly, the apoptosis rate decreased (P < 0.05), and the apoptosis rate also reduced obviously by transfecting TGFBRAP1-siRNA (P< 0.05). Finally, the overexpression of FAR1 or TGFBRAP1 resulted in the inhabitation to the secretion of E2 and P4 in granulosa cells, while the knockdown of FAR1 or TGFBRAP1 enhanced the secretion of E2 and P4. In conclusion, the results indicated that FAR1 and TGFBRAP1 regulated the apoptosis of follicular granulosa cells and cut the secretion of E2 and P4 in geese, which provided basic data for the understanding of the regulating process of goose reproduction.

12.
Mediators Inflamm ; 2020: 2960517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013197

RESUMO

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33020276

RESUMO

Genomes of all characterized higher eukaryotes harbor examples of transposable element (TE) bursts-the rapid amplification of TE copies throughout a genome. Despite their prevalence, understanding how bursts diversify genomes requires the characterization of actively transposing TEs before insertion sites and structural rearrangements have been obscured by selection acting over evolutionary time. In this study, rice recombinant inbred lines (RILs), generated by crossing a bursting accession and the reference Nipponbare accession, were exploited to characterize the spread of the very active Ping/mPing family through a small population and the resulting impact on genome diversity. Comparative sequence analysis of 272 individuals led to the identification of over 14,000 new insertions of the mPing miniature inverted-repeat transposable element (MITE), with no evidence for silencing of the transposase-encoding Ping element. In addition to new insertions, Ping-encoded transposase was found to preferentially catalyze the excision of mPing loci tightly linked to a second mPing insertion. Similarly, structural variations, including deletion of rice exons or regulatory regions, were enriched for those with break points at one or both ends of linked mPing elements. Taken together, these results indicate that structural variations are generated during a TE burst as transposase catalyzes both the high copy numbers needed to distribute linked elements throughout the genome and the DNA cuts at the TE ends known to dramatically increase the frequency of recombination.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33024017

RESUMO

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

15.
Food Funct ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026021

RESUMO

The effect of short-term intake of high- and low-concentrations of sucrose solution on the neurochemistry of male and female mice was studied. The body weight, feed intake, sucrose solution consumption and brain monoamine neurotransmitters were determined after 34 days' intake of 1% and 8% sucrose solutions. The gene expression and protein levels related to dopamine and opioids were also determined. The results showed that the intake of 1% and 8% sucrose solution for 34 days did not cause significant changes in the weight development of both male and female mice. The preference for sucrose varies with sex. Both males and females had greater preference for the high concentration sucrose solution than the low concentration sucrose solution. The continuous intake of sucrose stimulated the release of monoamine neurotransmitters (DA, 5-HT, NE) in the brains of mice, and the reward effect of 8% sucrose solution is significantly higher than that of 1% sucrose solution. The sex of mice did not affect the release of neurotransmitters. The gene expressions of D1 and D2 were up-regulated in the 1% sucrose group of male mice, while the OPRM1 gene expression was down-regulated. The expression of these three genes in the 8% sucrose group of male mice was all down-regulated, while the gene expressions of D1 and D2 in the 1% and 8% sucrose group (p < 0.05) of female mice were both up-regulated.

16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1165-1168, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018194

RESUMO

Osteosarcoma is a prominent bone cancer that typically affects adolescents or people in late adulthood. Early recognition of this disease relies on imaging technologies such as x-ray radiography to detect tumor size and location. This paper aims to differentiate osteosarcoma from benign tumors by analyzing both imaging and RNA-seq data through a combination of image processing and machine learning. In experimental results, the proposed method achieved an Area Under the Receiver Operator Characteristic Curve (AUC) of 0.7272 in three-fold cross-validation, and an AUC of 0.9015 using leave-one-out cross-validation.

17.
Shanghai Kou Qiang Yi Xue ; 29(3): 257-261, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043341

RESUMO

PURPOSE: To preliminarily explore the cytotoxicological responses of keratinocytes derived from human embryonic stem cells(K-hESCs) to drugs, and to provide a basis for the establishment of a new biosafety evaluation model. METHODS: CCK-8 assay was used to detect cell viability and cytotoxicity. The detection of pharmacological response was observed and compared when K-hESCs directly derived from human embryonic stem cells, human gingival epithelial cells (HGECs), and human immortalized oral epithelial cells (HIOECs) were treated with retinoic acid (RA), 5-fluorouracil(5-FU), dexamethasone(DEX), and penicillin G(PG). Statistical analysis was performed using SPSS 16.0 software package. RESULTS: After drugs were applied to HGECs, HIOEC and K-hESCs, the half inhibitory concentrations (IC50) of RA was 6.1±0.03, 5.62±0.05 and 6.58±0.02, respectively. The IC50 of 5-FU was 1.65±0.02,3.00±0.02 and 1.72±0.04, respectively. The IC50 of DEX was 113.67±0.014,328±0.002 and 126.17±0.05, respectively. The IC50 of PG was 2200±1.34,3795±2.42 and 2880±1.5, respectively. The IC50 of the four drugs between HIOEC and HGECs had significant differences(P<0.05), but there was no significant difference in IC50 between K-hESCs and HGECs(P>0.05). The IC50 of K-hESCs and HIOEC also had significant differences(P<0.05). CONCLUSIONS: IC50 of K-hESCs was closer to HGECs than HIOEC. It was speculated that K-hESCs could simulate the response of normal human cells in cytotoxicity study.


Assuntos
Células-Tronco Embrionárias , Células-Tronco Embrionárias Humanas , Diferenciação Celular , Células Epiteliais , Humanos , Queratinócitos
19.
J Cell Mol Med ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32969198

RESUMO

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.

20.
Stat Med ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969528

RESUMO

The probability of agreement has been used as an effective strategy for quantifying the similarity between the reliability of two populations. By contrast to hypothesis testing approaches based on P-values, the probability of agreement provides a more realistic assessment of similarity by emphasizing practically important differences. In this article, we propose the use of the probability of agreement to evaluate the similarity of two Kaplan-Meier curves, which estimate the survival functions in two populations. This article extends the probability of agreement paradigm to right censored data and explores three different methods of quantifying uncertainty in the probability of agreement estimate. The first approach provides a convenient assessment based on large-sample normal-theory (LSNT), while the other two approaches are nonparametric alternatives based on ordinary and fractional random-weight bootstrap (FRWB) techniques. All methods are illustrated with examples for which comparing the survival curves of related populations is of interest and the efficacy of the methods are also evaluated through simulation studies. Based on these simulations we recommend point estimation using the proposed LSNT calculation and confidence interval estimation via the FRWB approach. We also provide a Shiny app that facilitates an automated implementation of the methodology.

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