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Train traffic has recently been realized as a potential seismic source for imaging and monitoring shallow subsurface structures. High-speed trains usually move on viaducts and generate seismic wavefields through bridge piers. This kind of source is not randomly distributed in space and time and thus indicates the characteristic of self-correlation. We find that correlated sources of one high-speed train running over piers make time-delayed spurious signals in the crosscorrelation functions. The direct-wave interferometry with correlated sources is proposed and demonstrates that stacking of the interferometric responses from high-speed trains with different speeds may reduce the spurious imprint of source self-correlations, but it cannot remediate the problem. The influence of the source wavelet can be eliminated by using cross coherence. Stationary-phase segment selection and stacking can reduce the bias generated by trains moving out of the stationary-phase zone of station pairs. The validity is demonstrated by using synthetic data with inline and out-of-line linear arrays. We apply the proposed scheme to field data with nine high-speed train events. Multimodal Rayleigh waves were retrieved and shallow shear-wave velocities were inverted from multimodal dispersion data in a range of 4–25 Hz. The results bring a novel approach for the imaging and monitoring of the shallow subsurface using high-speed-train-induced vibrations.

Exercise training has been demonstrated as an effective therapy for insulin resistance (IR) to relieve skeletal muscle metabolic disorders. Physiologic protective autophagy was found blocked by IR induced severe endoplasmic reticulum (ER) stress, which may lead to progression of IR. However, the mechanisms are not fully understood. Therefore, this study sought to investigate that how exercise training act on IR through an exploration into the mechanism of ER stress and high-fat diet (HFD)-blocked autophagy. A rodent model was adopted in mice via a HFD and an 8-week swim exercise training intervention. The mouse IR model was successfully established through HFD treatment: body mass, adipose weight, HOMA-IR index increased, as well as IRS1, inhibited in the muscle of HFD mice. Moreover, the AMPK/PGC1α pathway was depressed and IRE1, PERK, ATF6-related ER stress signaling was activated in the muscle of HFD mice. While autophagy factors, including BNIP3, LC3II/LC3I, and PINK1, decreased. However, additional 8-week exercise training during HFD was found to reverse all these changes and alleviate IR. Thus, exercise training could facilitate HFD-blocked protective autophagy via the activation of the AMPK/PGC1α pathway to relieve insulin resistance in mice. Our study provides experimental data for the prevention of T2DM and insulin resistance.

Obesity induces skeletal muscle dysfunction. The pathogenesis of which appears to substantially involve mitochondrial dysfunction, arising from impaired quality control. Exercise is a major therapeutic strategy against muscle dysfunction. Trimetazidine, a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, the effects of Trimetazidine on regulating skeletal muscle function are largely unknown. Our present study used cell culture and obese mice models to test a novel hypothesis that Trimetazidine could improve muscle atrophy with similar results to exercise. In C2C12 cells, high palmitic acid-induced atrophy and mitochondrial dysfunction, which could be reversed by the treatment of Trimetazidine. In our animal models, with high-fat diet-induced obesity associated with skeletal muscle atrophy, Trimetazidine prevented muscle dysfunction, corrected metabolic abnormalities, and improved mitochondrial quality control and mitochondrial functions similarly to exercise. Thus, our study suggests that Trimetazidine successfully mimics exercise to enhance mitochondrial quality control leading to improved high-fat diet-induced muscle dysfunction.

Background Reference values of cardiopulmonary exercise testing (CPX) vary with race/ethnicity. Chinese Americans are the fastest-growing racial/ethnic group in the United States. However, there is limited information about the reference values of cardiopulmonary exercise testing (CPX) variables in the Chinese population. Methods As part of the Xiangya Hospital Exercise Testing project (the X-ET project), this cross-sectional study screened 20,696 consecutive CPXs performed by 17,802 unique individuals at Xiangya Hospital of Central South University, China, from January 1, 2002, to December 31, 2019. A total of 964 unique healthy adults/tests (42% female) aged 49 ± 12 who completed a maximal ramp incremental CPX with cycle ergometry were included in this study. The reference values of primary CPX variables were expressed as the lower limit or upper limit of normal. Stepwise linear regression was used to fit the equations of key CPX variables. Predictive accuracy analysis for the equations with a comparison between present and previous studies were performed. Results Peak oxygen consumption ( V O2), carbon dioxide production, ventilation/min, work rate, and V O2 at the anaerobic threshold were regressed on age, height, weight, and sex. These predictive equations showed good in- and out-sample predictive accuracy. Comparison with prior research revealed that prediction equations of peak V O2 resultant from studies in which populations were entirely or primarily Caucasian had overestimated our subjects' actual values. Conclusion The reference values and predicted equations of CPX variables in this study may provide a more appropriate framework to interpret the response to maximal ramp incremental cycle ergometry in the Chinese adult population.

Myocardial infarction (MI) is the leading cause of death worldwide and can lead to the loss of cardiac function and heart failure. Reactive oxygen species (ROS) play a key role in the pathological progression of MI. The levels and effects of ROS are significantly different in three unique pathological stages of MI, and most antioxidants cannot make corresponding adjustments to eliminate ROS, which leads to a great compromise to treat MI with antioxidants. Herein, an innovative self-sustaining antioxidant strategy is developed to treat MI with self-sustaining selenium-embedded nanoparticles (SSSe NPs). SSSe NPs possess unique self-sustaining antioxidant effects at different pathological stages of MI. This strategy of on-demand ROS elimination during different pathological stages demonstrated excellent MI treatment efficacy and effectively reversed heart failure to normal heart function. The therapeutic mechanism of SSSe NPs is intensively investigated through a series of experiments and mainly involved five critical aspects of myocardial repair: protecting mitochondria, reducing cardiomyocyte apoptosis and ferroptosis, reducing inflammation and fibrosis, and promoting angiogenesis. This strategy not only provides a promising treatment option for MI but also offers inspiration for other ischemic diseases.

Rhodiola was found to be a potential treatment for nonalcoholic fatty liver disease (NAFLD). The macrophage migration inhibitory factor (MIF)-regulated lipophagy and lipid metabolism might be the therapeutic targets of Rhodiola.A 16-week high-fat diet (HFD) was used to simulate a NAFLD mouse model. Rhodiola extract or normal saline were administrated to mice. Blood was collected to assess blood glucose and insulin, and livers were harvested to assess lipid accumulation and metabolism. In cell experiments, the active ingredient of Rhodiola, salidroside, and recombinant MIF protein (rMIF) were used to treat palmitate (PA)-incubated HepG2 cells, with MIF-siRNA or NC-siRNA transfection. Then, the level of lipophagy and lipid metabolism was examined.Rhodiola improved lipid accumulation and metabolism disorder of HFD mice. The oil red O staining of the liver showed that increased lipid droplets in the NAFLD liver could be relieved by Rhodiola; Rhodiola also alleviated the increasing body weight, liver weight, and HOMA-IR index of HFD mice. Results in cell experiments were consistent: salidroside relieved the lipid droplet accumulation and triglyceride release in PA cells, as well as reduced lipophagosome and lipid metabolism disorder in PA cells. However, all these effects of salidroside were partially blocked by MIF-siRNA transfection.Rhodiola reduces lipid accumulation in the liver of NAFLD by facilitating the MIF pathway and the downstream lipophagy and lipid metabolism. MIF may be an endogenous regulator of liver lipophagy and lipid metabolism and a potential therapeutic target for NAFLD.

ObjectivesTo observe the weight change in Chinese youth during a 4-month COVID-19 lockdown, and the association between weight change and mental health, physical activity and sedentary time changes, and dietary habits.DesignA retrospective observational study.SettingsTwo universities located in Zhejiang and Hunan provinces, China.ParticipantsThis study enrolled 12 889 college students whose body weight was measured before the lockdown (1 December 2019–20 January 2020) at the two universities, and reported their weight measured at home or community after the end of the lockdown (1–23 May 2020) via an online follow-up questionnaire.Primary and secondary outcome measuresThe primary outcome was the weight change in Chinese youth during a 4-month lockdown resulting from the COVID-19 pandemic. The secondary outcomes were the relationships of weight change to COVID-19-related stress, depression, anxiety, physical activity and sedentary time changes, and dietary habits.ResultsParticipants’ ages ranged from 17 to 27 years (M=19, SD=1) with 80.2% identified as female. The average absolute and relative changes in body weight were 2.6 (95% CI 2.0 to 3.2)) kg and 4.2% (95% CI 4.0% to 4.3%) for men, and 2.1 (1.9 to 2.4) kg and 4.2% (95% CI 3.9% to 4.4%) for women. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in men and women, respectively (PConclusionThe present study’s results suggest that the risk of weight gain in Chinese youth during the lockdown increased and that strategies to decrease sedentary time and improve mental health may be warranted to mitigate weight gain during and after the COVID-19 pandemic.

Background: The coronavirus disease-2019 (COVID-19) has resulted in nationwide lockdowns, cessation of school and work, and social distancing. Reducing the negative impacts, such as weight-gain, has garnered global attention.Methods: In this dual-center retrospective observational study of 12,889 students (aged 18-20), who performed a national student physical fitness battery between December 1, 2019, to January 20, 2020, and completed a follow-up online questionnaire beginning on May 1, 2020, and ending on May 23, 2020, and examined the associations between weight-gain and COVID-19 induced stress, depression and self-reported physical activity, dietary habits and sedentary time. Results: Participants gained an average of 2.6 kg (95% CI: 2.0 to 3.2 kg) for males and 2.1 kg (1.9 to 2.4 kg) for females. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in males and females respectively (PConclusion: These findings suggest that limiting sedentary time during lockdowns and strategies aimed t improve lifestyle habits and psychological health may be warranted to mitigate weight-gain during the pandemic.Registration: Registered with ChiCTR, registration no.: ChiCTR2000033514

Background: Acid sphingomyelinase (ASM) promotes atherogenesis and acute cardiovascular events. We previously demonstrated ASM inhibitor desipramine attenuated oxidized-LDL induced macrophage apoptosis in vitro. Here, we aim to determine whether ASM mediated apoptosis in plaque and improve stability in vivo. Methods: In this study, rabbits with abdominal aorta balloon injury and 12-week high-cholesterol diet (HCD) were used to simulate atherosclerotic plaque model. Atherosclerotic rabbits received oral administration of saline (Control group), atorvastatin (Ator group), or desipramine (DES group). ASM activity and ceramide level were measured by ultra-performance liquid chromatography (UPLC). Plaque morphology was assessed by histochemistry and immunohistochemistry. Apoptosis was evaluated by SPECT/CT imaging of 99mTc-duramycin uptake and TUNEL Results: We found that increasing ASM activity and ceramide level in atherosclerotic rabbits was abated by additional atorvastatin and desipramine treatment. Meanwhile, the DES and Ator groups were similar with regard to plaque stability, with smaller plaque size, areas of macrophages, higher smooth muscle cell content, and decreased apoptosis and matrix metalloproteinase (MMP) activities relative to the Control group. 99mTc-duramycin uptake of rabbit aorta was significantly higher in Control than in Normal group, while it was reduced by desipramine and atorvastatin administration. Moreover, uptake of 99mTc-duramycin positively correlated with apoptotic cell number, macrophage infiltration and plaque instability. Conclusion: The present study demonstrated that desipramine exerted plaque-stabilizing effects partially by suppressing apoptosis and MMP activity in rabbit model. And 99mTc-duramycin SPECT/CT imaging allowed noninvasively monitoring atherosclerotic disease and evaluating anti-atherosclerotic therapy. Funding Information: This work was supported by grants from the National Natural Science Foundation of China (No. 81901784 to ZM, No. 81170261 to ZGG). Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: All animal protocols were approved by the Committee of Animal Care and Use at Xiangya Hospital, Central South University, China. All procedures were conducted to minimize the number of animals used and their suffering.

The COVID-19 (coronavirus disease-19) has resulted in nationwide lockdowns, cessation of school and work, and social distancing. Reducing the negative impacts, such as weight-gain, has garnered global attention. In this dual-center prospective cohort study of 12,889 students, we assessed weight-gain in a youth during the 4-month COVID-19 lockdown, and examined the associations between weight-gain and COVID-19 induced stress, depression and self-reported physical activity, dietary habits and sedentary time. Participants gained an average of 2.6 kg (95% CI: 2.0 to 3.2 kg) for males and 2.1 kg (1.9 to 2.4 kg) for females. An increase in overweight and obese individuals as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in males and females respectively (P

Highlights • Study on the immunological changes in COVID-19 patients during 3-Month Follow-up; • Antibiotics use during hospital stay was related to a decrease in IgG after discharge; • Glucocorticoid intake was associated with an increase in CD4+T cell after discharge., Background Understanding the immunological responses in COVID-19 patients during their recovery period is essential to the development of a vaccine and herd immunity. Methods This retrospective cohort study screened 233 patients admitted to the First Hospital of Changsha, China with COVID-19 from January 17th to February 29th, 2020. After completion of SARS-CoV2-specific immunoglobulins, and T cells tests at 2-week and 3-month follow-up points after discharge, 87 were enrolled. Wilcoxon signed-rank test was performed to assess changes in the values of IgG and IgM, the number of CD3+, CD4+ and CD8+ T cells, and CD4+/CD8+ ratio during the 3-month follow-up. Linear regressions were used to evaluate the associations of immunological changes and medications during hospitalization. Results The positive rate of IgG decreased from 98.6% (40/41) to 85.4% (35/41) in men and 100% (43/43) to 76.7% (33/43) in women, whereas IgM declined from 34.1% (14/41) to 12.2% (5/41) in men and 37.2% (16/43) to 27.9% (12/43) in women during the follow-up. CD4+ T cells increased from (median (IQR), 484 (384-635)) cells/ul to 543 (414-657) cells/ul (P=0.01). Antibiotic use was negatively associated with IgG change (mean change [95%CI], 8.08 [0.80 to 15.37] U, P=0.03), and glucocorticoid use was positively related to increased CD4+ T cells (100.85 [16.56 to 185.15] cells/ul, P=0.02). Conclusion This study demonstrated that the positive rates and values of IgG and IgM decreased in COVID-19 patients over a 3-month follow-up, while CD4+ T cells significantly increased. Moreover, we found that antibiotic use during hospitalization was associated with IgG decrease, and glucocorticoid use was associated with increases in CD4+ T cells.

Recently, coronary microthrombosis has received attention owing to its involvement in the pathophysiological process of no-reflow after acute myocardial ischemia/reperfusion. Due to the small size of coronary microthrombi, there are no precise detection and treatment methods available in the clinic so far. In experimental study, bimodal molecular probes for both detecting and dissolving coronary microthrombi have not yet been reported. In this study, multimodal and multifunctional PLGA-cRGD-PFH-ICG NPs (PLGA: poly(lactic-co-glycolic) acid, cRGD: cyclic arginine-glycine-aspartic acid, PFH: perfluorohexane, ICG: indocyanine green, NPs: nanoparticles) were constructed through a three-step emulsification process, and the corresponding physical and chemical characteristics of the NPs were also tested. The in vitro and in vivo experiments showed that PLGA-cRGD-PFH-ICG NPs could bind to the activated platelets of coronary microthrombi through cRGD and could achieve bimodal molecular imaging (photoacoustic and near-infrared fluorescence) through ICG. Moreover, the PLGA-cRGD-PFH-ICG NPs could permeate more deeply into the thrombus than other common NPs before being triggered by low-intensity focused ultrasound (LIFU), and thrombolysis was carried out through the cavitation effect of PFH after triggering by LIFU. In summary, PLGA-cRGD-PFH-ICG NPs, constructed with safe and approved materials, serve as an excellent theranostic contrast agent that paves the way for the clinical diagnosis and treatment of coronary microthrombosis.

Background Integrin α2β1 inhibitor BTT-3033 (1-(4-fluorophenyl)-N-methyl-N-[4[[(phenylamino)carbonyl]amino]phenyl]-1H-pyrazole-4-sulfonamide) was recently reported to inhibit neurogenic and thromboxane A2-induced human prostate smooth muscle contraction, and thus represents a target with a different inhibition spectrum than that of α1-blockers in benign prostate hyperplasia (BPH) treatments. Clarifying the underlying mechanisms of the inhibition effects will provide insights into the role of integrin α2β1 in prostate contraction and enable new intracellular targets for smooth muscle contraction to be explored. Methods ProteomeHD was used to predict and enrich the top co-regulated proteins of integrin α2 (ITGA2). A phosphoproteomic analysis was conducted on human prostate stromal cells (WPMY-1) treated with 1 or 10 µM of BTT-3033 or solvent for controls. A clustering analysis was conducted to identify the intracellular targets that were inhibited in a dose-dependent manner. Gene ontology (GO) and annotation enrichments were conducted to examine any functional alterations and identify possible downstream targets. A Kinase-substrate enrichment analysis (KSEA) was conducted to identify kinases-substrate relationships. Results Enrichments of the actin cytoskeleton and guanosine triphosphatases (GTPases) signaling were predicted from the co-regulated proteins with ITGA2. LIM domain kinases, including LIM domain and actin-binding 1 (LIMA1), zyxin (ZYX), and thyroid receptor-interacting protein 6 (TRIP6), which are functionally associated with focal adhesions and the cytoskeleton, were present in the clusters with dose-dependent phosphorylation inhibition pattern. 15 substrates were dose-dependently inhibited according to the KSEA, including polo-like kinase 1 (PLK1), and GTPases signaling proteins, such as disheveled segment polarity protein 2 (DVL2). Conclusions In this study, we proposed that the mechanisms underlying the contractile and proliferative effects of integrin α2β1 are the LIM domain kinases, including the ZYX family, and substrates, including PLK1 and DVL2.

AimsReactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling.Methods and resultsThe vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague–Dawley (SD) rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1 expression and HOCl production were significantly increased in hypoxic rats, which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced PH model was generated by exposing primary rat pulmonary artery smooth muscle cells (PASMCs) to hypoxic conditions (3% O2, 48 h), which significantly increased the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes were accompanied by enhanced proliferation, apoptosis resistance, and migration. In PASMCs, hypoxia-induced changes, including effects on the expression of cell cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl-2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and 9), and NF-κB expression, as well as the production of HOCl, were all inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with HOCl under hypoxic conditions upregulated NF-κB expression and enhanced proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082 (an inhibitor of NF-κB) significantly inhibited these effects.ConclusionCollectively, these results demonstrate that VPO1 promotes hypoxia-induced proliferation, apoptosis resistance, and migration in PASMCs via the NOX4/VPO1/HOCl/NF-κB signalling pathway.

Vascular peroxidase 1 (VPO1) has been proved to be associated with vascular endothelial cell apoptosis by producing reactive oxygen species. However, the contribution of VPO1 to the development of vascular remodeling (VR) remains to be fully characterized. We explored the role of VPO1 in VR in spontaneously hypertensive rats (SHRs) and the underlying mechanism of losartan in inhibiting VR. Compared to Wistar-Kyoto (WKY) rats, the SHR showed remodeling of their vascular walls. The level of VPO1 and the hydrogen peroxide (H2O2) concentration were increased in the SHRs. However, the SHRs pretreated with losartan showed significant inhibition of blood pressure and VR and decreased levels of VPO1 and H2O2 compared to the non-treated SHRs. Angiotensin II significantly increased the expressions of MMP-2, MMP-9 and the concentrations of H2O2 and hypochlorous acid (HOCl) in vascular smooth muscle cells (VSMCs). However, only the H2O2 level increased in VSMCs when transfected with VPO1 shRNA. These results support a critical but previously unrecognized role of VPO1 in VR and suggest that therapies to reduce VPO1 may be novel approaches for VR.

Mitochondrial quality control (MQC) and function are determinants for cellular energy metabolism, and their disorders are reported to play an important role in the development of insulin resistance (IR). Salidroside was reported to have beneficial effects on MQC through AMPK pathway; however, it is unknown whether salidroside exerts anti-IR effect with this action. This study sought to investigate the effects of salidroside on IR with an exploration of the mechanisms of its action. Experimental IR models were adopted in high-fat-diet (HFD)-fed mice and palmitate-treated C2C12 myotubes, respectively. Blood levels of glucose and insulin as well as cellular glucose uptake were determined, and mitochondrial function and MQC-associated parameters and reactive oxygen species (ROS) production were analyzed based on treatments with the activator (AICAR), inhibitors (compound C and EX-527) or specific siRNA of Ampk/Sirt1 and mitochondrial ROS scavenger (mito-TEMPO). Protein expression level was determined by Western blot, cellular observation by transmission electron microscope and ROS production by functional analysis kits. Salidroside reduced IR and activated insulin signaling along with the stimulation of AMPK/SIRT1 signaling and downstream regulation of MQC and ROS production. These salidroside effects were comparable to those of AICAR and could be prevented by AMPK/SIRT1 inhibitors or siRNAs, respectively. Salidroside reduces IR and regulates MQC and ROS production by activating AMPK/SIRT1 signaling pathway. Since IR is a critical issue for public health, to explore a potent agent against IR is of high interest. The anti-IR effects of salidroside warrant further experimental and clinical studies.

Aim To emphasize the mechanism of the effect of exercise on lipid droplet (LD) metabolism disorder in nonalcoholic fatty liver disease (NAFLD). Main methods C57BL/6J mice were randomly divided into three groups: The first group was fed with a normal diet (CON), the second group was fed a high-fat diet (HF), and finally group with a high-fat diet intervention and swim training (HF-EX). The total intervention period was 16 weeks. RT-PCR and Western blot were performed to evaluate the effect of exercise on LDs metabolism and the AMPK pathway. Histopathological examinations and immunofluorescence were performed to evaluate the lipid deposition and lipophagy in the liver. Key findings Exercise reduced liver steatosis and insulin resistance along with the stimulation of AMPK/SIRT1 signaling and downstream regulation of lipid metabolism. In addition, exercise increased the expression of autophagy marker and colocalization of LC3 and LAMP1 with LDs. Significance Exercise stimulated AMPK/SIRT1 and activated lipophagy in NAFLD. Enhancing lipophagy may be one of the key mechanisms of regulation and resolution of NAFLD by exercise.

Background Hydrogen peroxide (H 2 O 2 ) is a critical molecular signal in the development of abdominal aortic aneurysm ( AAA ) formation. Vascular peroxidase 1 ( VPO 1) catalyzes the production of hypochlorous acid ( HOC l) from H 2 O 2 and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells ( VSMC s) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO 1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch. Methods and Results VPO 1 is upregulated in human and elastase‐induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF 4, a nuclear transcriptional factor, is upregulated in aneurysmatic tissues along with a concomitant downregulation of differentiated smooth muscle cell markers and an increase of synthetic phenotypic markers, indicating VSMC phenotypic switch in these diseased tissues. In cultured VSMC s from rat abdominal aorta, H 2 O 2 treatment significantly increases VPO 1 expression and HOC l levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO 1 significantly attenuates the effects of H 2 O 2 and HOC l treatment. Furthermore, HOC l treatment promotes VSMC phenotypic switch and ERK 1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK 1/2) significantly attenuates HOC l‐induced VSMC phenotypic switch. Conclusions Our results demonstrate that VPO 1 modulates VSMC phenotypic switch through the H 2 O 2 / VPO 1/ HOC l/ ERK 1/2 signaling pathway and plays a key role in the development of AAA . Our findings also implicate VPO 1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA . Clinical Trial Registration URL : www.chictr.org.cn . Unique identifier: Chi CTR 1800016922.

Vascular peroxidase 1 (VPO1) has been proved to be associated with vascular endothelial cell apoptosis by producing reactive oxygen species. However, the contribution of VPO1 to the development of vascular remodeling (VR) remains to be fully characterized. We explored the role of VPO1 in VR in spontaneously hypertensive rats (SHRs) and the underlying mechanism of losartan in inhibiting VR. Compared to Wistar-Kyoto (WKY) rats, the SHR showed remodeling of their vascular walls. The level of VPO1 and the hydrogen peroxide (H

Objective Status epilepticus (SE) is a common, life-threatening neurological emergency that confers a high degree of morbidity and mortality. Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of SE. MicroRNA-146a (miR-146a) has been reported to be an important posttranscriptional inflammation-associated microRNA. The aim of this study was to investigate the effect of miR-146a in SE and the mechanism by which it operates. Methods To study the effect of miR-146a in SE, we chose intracerebroventricular injection for rat at 21–28 days old, and made a lithium-pilocarpine-induced SE rat model. We assessed latency time and Lado grade by behavior observation. We performed qPCR, ELISA and western blot tests on rat hippocampus to measure the expression levels of miR-146a, IL-1β, TNF-α, TLR4 and NF-κB. Results In the miR-146a antagomir injection group, the latency to generalized convulsions was shorter, the duration and degree of seizures were more severe, the expression level of miR-146a was clearly decreased, and IL-1β, TNF-α, TLR4 and NF-κB were all significantly up-regulated. The opposite was true for rats treated with miR-146a agomir. Conclusion Our findings elucidate the role of inflammation in the pathogenesis of SE in immature rats, and show that regulating the expression level of miR-146a may provide a novel insights into the pathogenesis of SE.