4 results
The role of lncRNAKCNQ1OT1/miR-301b/Tcf7 axis in cardiac hypertrophy
- Mingyao E, Feifei Ren, Yanhua Yu, Haiyan Li, Chao Shen
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- Journal:
- Cardiology in the Young , First View
- Published online by Cambridge University Press:
- 08 March 2024, pp. 1-13
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Objective:
Cardiac hypertrophy, acting as a pathologic process of chronic hypertension and coronary disease, and its underlying mechanisms still need to be explored. Long non-coding RNA (LncRNA) potassium voltage-gated channel subfamily Q member 1 Transcript 1 (KCNQ1OT1) has been implicated in myocardial infarction. However, its role in cardiac hypertrophy remains reported.
Method:To explore the regulated effect of lncRNAKCNQ1OT1 and miR-301b in cardiac hypertrophy, gain-and-lose function assays were tested. The expression of lncRNAKCNQ1OT1 and miR-301b were tested by quantitative real time polymerase chain reaction (qRT-PCR). The levels of transcription factor 7 (Tcf7), Proto-oncogene c-myc (c-myc), Brainnatriureticpeptide (BNP) and β-myosin heavy chain (β-MHC) were detected by Western blot. Additionally, luciferase analysis revealed interaction between lncRNAKCNQ1OT1, BNPβ-MHCmiR-301b, and Tcf7.
Result:LncRNAKCNQ1OT1 overexpression significantly induced cardiac hypertrophy. Furthermore, lncRNAKCNQ1OT1 acts as a sponge for microRNA-301b, which exhibited lower expression in cardiac hypertrophy model, indicating an anti-hypertrophic role. Furthermore, the BNP and β-MHC expression increased, as well as cardiomyocyte surface area, with Ang II treatment, while the effect was repealed by miR-301b. Moreover, the protein expression of Tcf7 was inversely regulated by miR-301b and Antisense miRNA oligonucleotides (AMO)-301b.
Conclusion:Our study has shown that overexpression of lncRNAKCNQ1OT1 could promote the development of cardiac hypertrophy by regulating miR-301b and Tcf7. Therefore, inhibition of lncRNAKCNQ1OT1 might be a potential therapeutic strategy for cardiac hypertrophy.
Three-dimensional wake transitions of steady flow past two side-by-side cylinders
- Chengjiao Ren, Zinan Liu, Liang Cheng, Feifei Tong, Chengwang Xiong
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- Journal:
- Journal of Fluid Mechanics / Volume 972 / 10 October 2023
- Published online by Cambridge University Press:
- 29 September 2023, A17
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- Article
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Three-dimensional (3-D) wake transitions of a steady flow past two side-by-side circular cylinders are investigated through Floquet analysis and direct numerical simulations (DNS) over the gap-to-diameter ratio $g^*$ up to 3.5 and Reynolds number ${\textit {Re}}$ up to 400. When the flows behind two cylinders form in-phase and anti-phase wakes at large $g^*$, the wake transition is similar to the isolated cylinder counterpart, with the critical ${\textit {Re}}$ for the onset of 3-D transition (${\textit {Re}}_{cr-1}$) happens at around 180. At small $g^*$, 3-D transition becomes interestingly complex due to the distinct characteristics formed in base flows. The ${\textit {Re}}_{cr-1}$ suddenly drops to around 60–100 and forms distinct variation trends with $g^*$. Precisely, the ${\textit {Re}}_{cr-1}$ of the single symmetric wake (SS, $g^*\lessapprox 0.25$) is more than half of the isolated cylinder counterpart due to the large length scale of the SS wake. Only mode A is detected in SS. In the asymmetric single wake (ASS, $g^* \approx 0.25\unicode{x2013}0.6$) and flip-flop wake (FF, $g^* \approx 0.6\unicode{x2013}1.8$), the 3-D transition develops at ${\textit {Re}} \approx 103\unicode{x2013}60$ and 75–60, respectively. The decrease in ${\textit {Re}}_{cr-1}$ with increasing $g^*$ is because of the increased level of wake asymmetry in ASS and irregular vortex shedding in FF. Floquet analysis predicts two new unstable modes, namely mode A$'$ and subharmonic mode C$'$, of ASS. Both modes are transient features in 3-D DNS and the flow eventually saturates into a new 3-D mode, mode ASS. The gap flow of mode ASS is distinctly characterised by its time-independent spanwise waviness structure that is deflected towards different transverse directions with a long wavelength of about $14$ cylinder diameters. The 3-D mode of the FF is irregular both temporally and spatially. Variations of ${\textit {Re}}_{cr-1}$ with $g^*$, the characteristics and the physical mechanisms of each 3-D mode are discussed in this study.
Bistabilities in two parallel Kármán wakes
- Chengjiao Ren, Liang Cheng, Chengwang Xiong, Feifei Tong, Tingguo Chen
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- Journal:
- Journal of Fluid Mechanics / Volume 929 / 25 December 2021
- Published online by Cambridge University Press:
- 19 October 2021, A5
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Bistabilities of two equilibrium states discovered in the coupled side-by-side Kármán wakes are investigated through Floquet analysis and direct numerical simulation (DNS) with different initial conditions over a range of gap-to-diameter ratio ($g^*= 0.2\text {--}3.5$) and Reynolds number ($Re = 47\text {--}100$). Two bistabilities are found in the transitional $g^*-Re$ regions from in-phase (IP) to anti-phase (AP) vortex shedding states. By initialising the flow in DNS with zero initial conditions, the flow in the first bistable region (i.e. bistable IP/FF$_C$ at $g^*= 1.4 \text {--} 2.0$, where FF$_C$ denotes the conditional flip-flop flow) attains flip-flop (FF) flow, it settles into the IP state by initialising the flow with an IP flow. The second bistability is observed between cylinder-scale IP and AP states at large $g^*$ ($=$ 2.0–3.5). The transition from the FF$_C$ to IP is dependent on initial conditions and irreversible over the parameter space, meaning that the flow cannot revert back to the FF$_C$ state once it jumps to the IP state irrespective of the direction of $Re$ variations. Its counterpart for the bistable IP/AP state is reversible. We also found that the FF$_C$ flow in the first bistable region is primarily bifurcated from synchronised AP with cluster-scale features, possibly because the cluster-scale AP flow is inherently unstable to FF flow instabilities. It is demonstrated that the irreversible bistability exists in other interacting wakes around multiple cylinders. A good understanding of flow bistabilities is pivotal to flow control applications and the interpretation of desynchronised flow features observed at high $Re$ values.
Oscillatory flow regimes around four cylinders in a diamond arrangement
- Chengjiao Ren, Liang Cheng, Feifei Tong, Chengwang Xiong, Tingguo Chen
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- Journal:
- Journal of Fluid Mechanics / Volume 877 / 25 October 2019
- Published online by Cambridge University Press:
- 02 September 2019, pp. 955-1006
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Oscillatory flow around a cluster of four circular cylinders in a diamond arrangement is investigated using two-dimensional direct numerical simulation over Keulegan–Carpenter numbers (KC) ranging from 4 to 12 and Reynolds numbers (Re) from 40 to 230 at four gap-to-diameter ratios (G) of 0.5, 1, 2 and 4. Three types of flows, namely synchronous, quasi-periodic and desynchronized flows (along with 14 flow regimes) are mapped out in the (G, KC, Re)-parameter space. The observed flow characteristics around four cylinders in a diamond arrangement show a few unique features that are absent in the flow around four cylinders in a square arrangement reported by Tong et al. (J. Fluid Mech., vol. 769, 2015, pp. 298–336). These include (i) the dominance of flow around the cluster-scale structure at $G=0.5$ and 1, (ii) a substantial reduction of regime D flows in the regime maps, (iii) new quasi-periodic (phase trapping) $\text{D}^{\prime }$ (at $G=0.5$ and 1) and period-doubling $\text{A}^{\prime }$ flows (at $G=1$) and most noteworthily (iv) abnormal behaviours at ($G\leqslant 2$) (referred to as holes hereafter) such as the appearance of spatio-temporal synchronized flows in an area surrounded by a single type of synchronized flow in the regime map ($G=0.5$). The mode competition between the cluster-scale and cylinder-scale flows is identified as the key flow mechanism responsible for those unique flow features, with the support of evidence derived from quantitative analysis. Phase dynamics is introduced for the first time in bluff-body flows, to the best knowledge of the authors, to quantitatively interpret the flow response (e.g. quasi-periodic flow features) around the cluster. It is instrumental in revealing the nature of regime $\text{D}^{\prime }$ flows where the cluster-scale flow features are largely synchronized with the forcing of incoming oscillatory flow (phase trapping) but are modulated by localized flow features.