scholarly journals Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Ying Liu ◽  
Ying Dong ◽  
Zhaojie Dong ◽  
Jiawei Song ◽  
Zhenzhou Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Heart Diseases ◽  
Ischemic Heart ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Vascular Tissues ◽  
Ischemic Heart Diseases ◽  
Wky Rats ◽  
Gene And Protein Expression

Background: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in heart and vasculature, thereby regulating their target gene and protein expression, via competitive endogenous RNA (ceRNA) mechanism. However, the exact roles and underlying mechanisms of circRNAs in hypertension and related cardiovascular diseases remain largely unknown.Methods and Results: High-throughput RNA sequencing (RNA-seq) was used to analyze the differentially expressed (DE) circRNAs in aortic vascular tissues of spontaneously hypertensive rats (SHR). Compared with the Wistar-Kyoto (WKY) rats, there were marked increases in the levels of systolic blood pressure, diastolic blood pressure and mean blood pressure in SHR under awake conditions via the tail-cuff methodology. Totally, compared with WKY rats, 485 DE circRNAs were found in aortic vascular tissues of SHR with 279 up-regulated circRNAs and 206 down-regulated circRNAs. Furthermore, circRNA-target microRNAs (miRNAs) and the target messenger RNAs (mRNAs) of miRNAs were predicted by the miRanda and Targetscan softwares, respectively. Additionally, real-time RT-PCR analysis verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005818, rno_circRNA_0005304, rno_circRNA_0005506, and rno_circRNA_0009301 were observed in aorta of SHR when compared with that of WKY rats. Then, the potential ceRNA regulatory mechanism was constructed via integrating 5 validated circRNAs, 31 predicted miRNAs, and 266 target mRNAs. More importantly, three hub genes (NOTCH1, FOXO3, and STAT3) were recognized according to PPI network and three promising circRNA-miRNA-mRNA regulatory axes were found in hypertensive rat aorta, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0009197/ miR-509-5p/FOXO3, and rno_circRNA_0005818/miR-10b-5p/STAT3, respectively.Conclusions: Our results demonstrated for the first time that circRNAs are expressed aberrantly in aortic vascular tissues of hypertensive rats and may serve as a sponge linking with relevant miRNAs participating in pathogenesis of hypertension and related ischemic heart diseases via the circRNA-miRNA-mRNA ceRNAnetwork mechanism.

Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ko Takesue ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Development Phase ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Activated Microglia ◽  
Wky Rats ◽  
Pressure Elevation ◽  
Hypertension Development

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.

scholarly journals Effect of a methionine-supplemented diet on the blood pressure of Wistar–Kyoto and spontaneously hypertensive rats

2003 ◽  
Vol 89 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Sophie Robin ◽  
Véronique Maupoil ◽  
Frédérique Groubatch ◽  
Pascal Laurant ◽  
Alain Jacqueson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Homocysteine ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Complex Interactions ◽  
Methionine Concentration ◽  
Wistar Kyoto

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0·01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.

scholarly journals Involvement of complement 3 in the salt-sensitive hypertension by activation of renal renin-angiotensin system in spontaneously hypertensive rats

2018 ◽  
Vol 315 (6) ◽  
pp. F1747-F1758 ◽  
Author(s):  
Eriko Negishi ◽  
Noboru Fukuda ◽  
Tomoyasu Otsuki ◽  
Mayumi Katakawa ◽  
Kazutoshi Komatsu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Complement 3 ◽  
Salt Sensitive Hypertension ◽  
E Cadherin

We previously showed that complement 3 (C3) is highly expressed in mesenchymal tissues in spontaneously hypertensive rats (SHR). We targeted C3 gene by zinc-finger nuclease (ZFN) gene-editing technology and investigated blood pressure and phenotype in SHR. Blood pressure was measured by tail-cuff and telemetry methods. Histology and expression of liver X receptor α (LXRα), renin, Krüppel-like factor 5 (KLF5), and E-cadherin were evaluated in kidneys. Mesangial cells (MCs) were removed from glomeruli from three strains, and we evaluated the phenotype in vitro. SHR showed the salt-sensitive hypertension that was abolished in C3 knockout (KO) SHR. Proliferation of MCs from SHR was higher than that from Wistar-Kyoto (WKY) rats and showed a synthetic phenotype. Renal injury scores were higher in SHR than in WKY rats and C3 KO SHR. Expression of E-cadherin was lower, and expression of renin was higher in the nephrotubulus from SHR than WKY rats and C3 KO SHR. Expression of C3 α-chain protein and α-smooth muscle actin protein was significantly higher in renal medulla from SHR than from WKY rats. Expression of angiotensinogen, LXRα, renin, and KLF5 mRNA was increased in kidney from SHR compared with C3 KO SHR. Intrarenal angiotensin II levels were significantly higher in kidney from SHR than WKY rats and C3 KO SHR. Urinary epinephrine and norepinephrine excretions were significantly higher in SHR than in WKY rats and C3 KO SHR. These findings showed that increased C3 induces salt-sensitive hypertension with increases in urinary catecholamine excretion and intrarenal activation of the renin-angiotensin system by the dedifferentiation of mesenchymal tissues in kidney from SHR.

Effects of Bromocriptine on Blood Pressure and Plasma β-Endorphin in Spontaneously Hypertensive Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 343s-345s ◽  
Author(s):  
J. S. Hutchinson ◽  
R. Di Nicolantonio ◽  
A. Lim ◽  
J. Clements ◽  
J. W. Funder
Keyword(s):  
Blood Pressure ◽  
Plasma Levels ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intravenous Injections ◽  
Wky Rats ◽  
Wistar Kyoto

1. Immunoreactive β-endorphin (IR-βEP) was two- to three-fold higher in pituitary neuro-intermediate lobes (N-IL) of spontaneously hypertensive rats (SHR) than of normotensive Wistar—Kyoto (NT-WKY) controls. 2. Plasma levels of IR-βEP were lower in SHR than in NT-WKY rats. 3. Intravenous injections of morphine lowered blood pressure of both SHR and NT-WKY rats to the same level; naloxone restored blood pressure of both groups to pre-morphine values. 4. Infusion of bromocriptine in SHR for 1 week lowered blood pressure and N-IL IR-βEP concentration. 5. These results confirm and extend postulated dopaminergic defect in this model of hypertension.

Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats

1996 ◽  
Vol 271 (4) ◽  
pp. E658-E668 ◽  
Author(s):  
M. Pitre ◽  
A. Nadeau ◽  
H. Bachelard
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Insulin Sensitivity ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Hemodynamic Responses ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Vascular Beds ◽  
Wistar Kyoto

The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

scholarly journals Effects of hypertension on maternal adaptations to pregnancy: experimental study on spontaneously hypertensive rats

2001 ◽  
Vol 119 (2) ◽  
pp. 54-58 ◽  
Author(s):  
José Carlos Peraçoli ◽  
Marilza Vieira Cunha Rudge ◽  
Maria Salete Sartori ◽  
Roberto Jorge da Silva Franco
Keyword(s):  
Blood Pressure ◽  
Weight Gain ◽  
Spontaneously Hypertensive Rats ◽  
Sodium Retention ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Tail Cuff

CONTEXT: Animal models for essential hypertension have been used for understanding the human pathological conditions observed in pregnant hypertensive women. OBJECTIVE: To study the possible effects of pregnancy on hypertension and of hypertension on pregnancy in spontaneously hypertensive rats (SHR), and in their normotensive Wistar-Kyoto (WKY) counterparts. TYPE OF STUDY: Comparative study using laboratory animals. SETTING: Animal Research Laboratory of Clinical Medicine at the Medical School of Botucatu, São Paulo State University, Brazil. SAMPLE: Ten to twelve-week-old virgin female normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The animals were separated into four groups: 15 pregnant spontaneously hypertensive rats (SHR-P), 10 non-pregnant spontaneously hypertensive rats (SHR-NP), 15 pregnant normotensive rats (WKY-P), and 10 non-pregnant normotensive rats (WKY-NP). MAIN MEASUREMENTS: The blood pressure was evaluated by the tail cuff method, in rats either with or without prior training for the handling necessary for tail cuff measurements. The maternal volemia expansion was indirectly evaluated by weight gain, and by systemic parameters as hematocrit, hemoglobin, total protein, albumin and sodium retention. The perinatal outcome of pregnancy was evaluated by analysis of resorptions, litter size, rate of low weight and number of stillbirths. RESULTS: The late fall in blood pressure in the pregnant SHR strain and in the normotensive WKY strain can only be detected in rats previously trained to accept the handling necessary for the tail cuff measurement. During pregnancy the body weight gain was significantly higher in WKY than in SHR rats. Systemic parameters were significantly lower in pregnant WKY rats than in non-pregnant WKY rats, while no differences were observed between pregnant and non-pregnant SHR groups. In pregnant WKY rats the sodium retention was higher from the 13th day onwards, while in SHR rats this occurred only on the 21st day. The characteristics of reproductive function such as number and weight of fetus, perinatal mortality and the resorption rate were significantly affected in the SHR strain. CONCLUSION: The SHR strain may be considered as a model for chronic hypovolemic maternal hypertension, with the fetal growth retardation being determined by this hypovolemic state.

scholarly journals Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats

2020 ◽  
Author(s):  
Yusuke Murata ◽  
Takahiro Ueno ◽  
Sho Tanaka ◽  
Hiroki Kobayashi ◽  
Masahiro Okamura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Microarray Analysis ◽  
Pressure Fluctuation ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Distal Tubules ◽  
Blood Pressure Fluctuation

Abstract Background There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsible for blood pressure circadian rhythm formation under the control of the kidney biological clock in hypertension. Methods DNA microarray analysis was performed in kidneys from 5-week-old spontaneously hypertensive rats (SHRs)/Izm, stroke-prone SHR rats (SHRSP)/Izm, and Wistar Kyoto (WKY)/Izm rats. To detect variation, mouse tubular epithelial cells (TCMK-1) were stimulated with dexamethasone. We performed immunostaining and western blot analysis in the renal medulla of kidney from 5-week-old WKY rats and SHRs. Results We extracted 1,032 genes with E-box, a binding sequence for BMAL1 and CLOCK using a Gene Set Enrichment Analysis. In a microarray analysis, we identified 12 genes increased as more than 2-fold in the kidneys of SHRs and SHRSP in comparison to WKY rats. In a periodic regression analysis, phosphoribosyl pyrophosphate amidotransferase (Ppat) and fragile X mental retardation, autosomal homolog 1 (Fxr1) showed circadian rhythm. Immunocytochemistry revealed PPAT-positivity in nuclei and cytoplasm in the tubules, and FXR1-positivity in the cytoplasm of TCMK-1. In 5-week-old WKY rat and SHR kidneys, PPAT was localized in the nucleus and cytoplasm of the proximal and distal tubules, and FXR1 was localized to the cytoplasm of the proximal and distal tubules. Conclusions PPAT and FXR1 are pivotal molecules in the control of blood pressure circadian rhythm by the kidney in hypertension.

Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II

1993 ◽  
Vol 264 (2) ◽  
pp. R388-R395 ◽  
Author(s):  
H. Muratani ◽  
C. M. Ferrario ◽  
D. B. Averill
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Gamma Aminobutyric Acid ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats

We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/- 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma-aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Differential Antihypertensive Effects of Oral Doses of Acetylcholine between Spontaneously Hypertensive Rats and Normotensive Rats

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2107
Author(s):  
Yamaguchi Shohei ◽  
Matsumoto Kento ◽  
Wang Wenhao ◽  
Nakamura Kozo
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Hypertensive Rats ◽  
Food Component ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Oral Doses

Acetylcholine (ACh) is a novel antihypertensive food component. Here, we demonstrate the differential effects of oral ACh on high and normal blood pressure in rats. Spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats were administered ACh orally. The blood pressure and heart rate of SHRs were significantly lowered with ACh doses of 10−5 and 10−3 mol/kg body weight (b.w.), and the urinary catecholamine levels were significantly decreased with 10−3 mol/kg b.w. In contrast, oral ACh administration had no effect on WKY rats. This difference was likely caused by differences in sympathetic nervous activity and the baroreflex between strains. Comparison of gene sequences between the two strains revealed Chga mutations, suggesting that changes in the expression of chromogranin A might be involved in the baroreflex in SHRs. Oral ACh had an antihypertensive effect under hypertension but not normotension, indicating that this may be used safely to prevent hypertension.

scholarly journals Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats

2012 ◽  
Vol 302 (3) ◽  
pp. H837-H844 ◽  
Author(s):  
Mahmoud M. El-Mas ◽  
Abdel A. Abdel-Rahman
Keyword(s):  
Blood Pressure ◽  
Catalase Activity ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Critical Role ◽  
Ventrolateral Medulla ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Strain Dependent

We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.

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