Biomass-Printed Hybrid Solar Evaporator Derived from Bio-polluted Invasive Species, a Potential Step toward Carbon Neutrality.

Biomass-based photothermal conversion is of great importance for solar energy utilization toward carbon neutrality. Herein, a hybrid solar evaporator is innovatively designed via UV-induced printing of pyrolyzed Kudzu biochar on hydrophilic cotton fabric (KB@CF) to integrate all parameters in a single evaporator, such as solar evaporation, salt collection, waste heat recovery for thermoelectricity, sieving oil emulsions, and water disinfection from microorganisms. The UV-induced printed fabric demonstrates stronger material adhesion as compared to the conventional dip-dry technique. The hybrid solar evaporator gives an enhanced evaporation rate (2.32 kg/m2 h), and the complementary waste heat recovery system generates maximum open-circuit voltage (Vout ∼ 143.9 mV) and solar to vapor conversion efficiency (92%), excluding heat losses under one sun illumination. More importantly, 99.98% of photothermal-induced bacterial killing efficiency was achieved within 20 min under 1 kW m-2 using the hyperthermia effect of Kudzu biochar. Furthermore, numerical heat-transfer simulations were performed successfully to analyze the enhanced interfacial heat accumulation (75.3 °C) and heat flux distribution of the thermoelectric generators under one sun. We firmly believe that the safe use of bio-polluted invasive species in hybrid solar-driven evaporation systems eases the environmental pressure toward carbon neutrality.

Shensong Yangxin Capsule Reduces the Susceptibility of Arrhythmia in db/db Mice via Inhibiting the Inflammatory Response Induced by Endothelium Dysfunction.

Purpose: The aim of our study was to investigate the mechanism by which the Chinese compound Shensong Yangxin Capsule (SSYX) reduces susceptibility to arrhythmia in db/db mice. Methods: The db/db mice without drug treatment served as the model group. Other-treated db/db mice were administered SSYX for 8 weeks. Electrocardiogram (ECG), electrical mapping, pathological changes, immunofluorescence staining, real-time quantitative PCR, and Western blot analyses were then conducted. Results: SSYX decreased arrhythmia susceptibility and shortened the abnormal ECG parameters of db/db mice. Meanwhile, SSYX restored irregular conduction direction and shortened the conduction time of the isolated heart. HE and Masson staining showed that SSYX alleviated inflammatory infiltration and collagen fiber deposition. Western blot showed that SSYX decreased the protein expression of ICAM-1, VCAM-1, and MCP-1 and increased the protein expression of occludin, ZO-1, eNOS, and Cx43. SSYX also increased the content of NO, decreased ET-1, TNF-α, IL-1ß, IL-6, MCP-1, and CCR-2 mRNA expression, and increased Kv 4.2, Kv 4.3, Cav 1.2, and Nav 1.5 mRNA expression. Furthermore, SSYX decreased the fluorescence intensity of F4/80 and iNOS, increased the fluorescence intensity of CD31 and eNOS, and improved the Cx43 and α-actinin connection structure in cardiac tissues. The above therapeutic effects of SSYX were inhibited by L-NAME. Conclusion: SSYX reduced the susceptibility of db/db mice to arrhythmia by inhibiting the inflammatory response and macrophage polarization, and this effect of SSYX occurred through protection of endothelial cell function.

Bazi Bushen mitigates epigenetic aging and extends healthspan in naturally aging mice.

Bazi Bushen (BZBS), a traditional Chinese medicine, has been proven effective in the treatment of age-related disease in mouse models. However, whether its therapeutic effects are due to antiaging mechanism has not yet been explored. In the present study, we investigated the antiaging effects of BZBS in naturally aging mice by using behavioral tests, liver DNA methylome sequencing, methylation age estimation, and frailty index assessment. The methylome analysis revealed a decrease of mCpG levels in the aged mouse liver. BZBS treatment tended to restore age-associated methylation decline and prune the methylation pattern toward that of young mice. More importantly, BZBS significantly rejuvenated methylation age of the aged mice, which was computed by an upgraded DNA methylation clock. These results were consistent with enhanced memory and muscular endurance, as well as decreased frailty score and liver pathological changes. KEGG analysis together with aging-related database screening identified methylation-targeted pathways upon BZBS treatment, including oxidative stress, DNA repair, MAPK signaling, and inflammation. Upregulation of key effectors and their downstream effects on elevating Sod2 expression and diminishing DNA damage were further investigated. Finally, in vitro experiments with senescent HUVECs proved a direct effect of BZBS extracts on the regulation of methylation enzymes during cellular aging. In summary, our work has revealed for the first time the antiaging effects of BZBS by slowing the methylation aging. These results suggest that BZBS might have great potential to extend healthspan and also explored the mechanism of BZBS action in the treatment of age-related diseases.

P T symmetry in a superconducting hybrid quantum system with longitudinal coupling.

We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.

Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis.

Purpose: The senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates the deterioration of the intestinal function in the central aging animal model. Methods: In our study, the SAMP8 mice were randomly divided into the model group, the BZ-low group (0.5 g/kg/d BZBS), the BZ-high group (1 g/kg/d BZBS) and the RAPA group (2 mg/kg/d rapamycin). Age-matched SAMR1 mice were used as the control group. Next, cognitive function was detected through Nissl staining and two-photon microscopy. The gut microbiota composition of fecal samples was analyzed by 16S rRNA gene sequencing. The Ileum tissue morphology was observed by hematoxylin and eosin staining, and the intestinal barrier function was observed by immunofluorescence. The expression of senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, and IL-10 was measured by real-time quantitative PCR. Macrophage infiltration and the proliferation and differentiation of intestinal cells were assessed by immunohistochemistry. We also detected the inflammasome and pyroptosis levels in ileum tissue by western blotting. Results: BZBS improved the cognitive function and neuronal density of SAMP8 mice. BZBS also restored the intestinal villus structure and barrier function, which were damaged in SAMP8 mice. BZBS reduced the expression of SASP factors and the infiltration of macrophages in the ileum tissues, indicating a lower level of inflammation. BZBS enhanced the proliferation and differentiation of intestinal cells, which are essential for maintaining intestinal homeostasis. BZBS modulated the gut microbiota composition, by which BZBS inhibited the activation of inflammasomes and pyroptosis in the intestine. Conclusion: BZBS could restore the dysbiosis of the gut microbiota and prevent the deterioration of intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested that BZBS attenuated the cognitive aging of SAMP8 mice, at least partially, by targeting the microbiota-gut-brain axis.

Interfacial Photothermal Heat Accumulation for Simultaneous Salt Rejection and Freshwater Generation; an Efficient Solar Energy Harvester.

Water scarcity has emerged as an intense global threat to humanity and needs prompt attention from the scientific community. Solar-driven interfacial evaporation and seawater desalination are promising strategies to resolve the primitive water shortage issue using renewable resources. However, the fragile solar thermal devices, complex fabricating techniques, and high cost greatly hinder extensive solar energy utilization in remote locations. Herein, we report the facile fabrication of a cost-effective solar-driven interfacial evaporator and seawater desalination system composed of carbon cloth (CC)-wrapped polyurethane foam (CC@PU). The developed solar evaporator had outstanding photo-thermal conversion efficiency (90%) with a high evaporation rate (1.71 kg m-2 h-1). The interfacial layer of black CC induced multiple incident rays on the surface allowing the excellent solar absorption (92%) and intensifying heat localization (67.37 °C) under 1 kW m-2 with spatially defined hydrophilicity to facilitate the easy vapor escape and validate the efficacious evaporation structure using extensive solar energy exploitation for practical application. More importantly, the long-term evaporation experiments with minimum discrepancy under seawater conditions endowed excellent mass change (15.24 kg m-2 in consecutive 8 h under 1 kW m-2 solar irradiations) and promoted its operational sustainability for multi-media rejection and self-dissolving potential (3.5 g NaCl rejected from CC@PU surface in 210 min). Hence, the low-cost and facile fabrication of CC@PU-based interfacial evaporation structure showcases the potential for enhanced solar-driven interfacial heat accumulation for freshwater production with simultaneous salt rejection.

Retrieving High-Dimensional Quantum Steering from a Noisy Environment with N Measurement Settings.

One of the most often implied benefits of high-dimensional (HD) quantum systems is to lead to stronger forms of correlations, featuring increased robustness to noise. Here, we experimentally demonstrate the n-setting linear HD quantum steering criterion. We verify the large violation of the steering inequalities without full-state tomography. The lower bound of the violation is 2.24±0.01 in 11 dimensions, exceeding the bound (V<2) of two-setting criteria. Hence, a higher strength of steering has been revealed. Moreover, we demonstrate the method for enhancing the noise robustness without increasing dimension, alternatively, by increasing measurement settings. Using the entanglement in 11 dimensions, we experimentally retrieve steering nonlocality with 63.4±1.4% isotropic noise fraction, surpassing the 50% limitation of two-setting criteria. Our Letter offers the potential for practical one-sided device-independent quantum information processing that tolerates the noisy environment, lossy detection, and transcends the present transmission distance limitation.

Prevalence and risk factors for congenital heart defects among children in the Multi-Ethnic Yunnan Region of China.

Background: To determine the congenital heart defect (CHD) prevalence and identify the associated risk factors in children within the multi-ethnic Yunnan Region of China. Methods: This is a prospective matched case-control screening study. Screening for CHD in children residing within 28 county districts of Yunnan Province during the period of January 2001 to December 2016 was conducted. A total of 2,421 and CHD cohort and 24,210 control cohort were derived from a total population of 400,855 children (under 18 years of age). Results: A total of 2,421 children were diagnosed with CHD, yielding a CHD prevalence of 6.04 cases per 1,000 children. The prevalence of CHD by sex was 6.54 per 1,000 females versus 5.59 per 1,000 males. The ethnic groups displaying the highest CHD prevalence were the Lisu (15.51 per 1,000), Achang (13.18 per 1,000), Jingpo (12.32 per 1,000), Naxi (9.68 per 1,000), and Tibetan (8.57 per 1,000), respectively. The most common CHD was atrial septal defect, amounting to 1.94 instances per 1,000 children. We identified a number of child-associated parameters that significantly correlated with greater CHD risk, such as lower mass at birth, shorter duration of gestation, and younger age at the time of screening. We also identified a number of maternal and familial risk factors. Conclusions: This ultrasonic color Doppler imaging study revealed a relatively commonplace prevalence of CHD. Moreover, the prevalence of CHD in Yunnan Region significantly varied with sex and ethnic status. Certain child-associated, maternal, and familial risk factors may contribute to CHD risk.

Endothelial cyclin I reduces vulnerability to angiotensin II-induced vascular remodeling and abdominal aortic aneurysm risk.

BACKGROUND: Retinoblastoma protein (Rb) supports vasoprotective E2F Transcription Factor 1 (E2f1)/Dihydrofolate Reductase (Dhfr) pathway activity in endothelial cells. Cyclin I (Ccni) promotes Cyclin-Dependent Kinase-5 (Cdk5)-mediated Rb phosphorylation. Therefore, we hypothesized that endothelial Ccni may regulate cardiovascular homeostasis, vessel remodeling, and abdominal aortic aneurysm (AAA) formation. METHODS: Aortic CCNI mRNA expression was analyzed in the Gene Expression Omnibus (GEO) GSE57691 cohort consisting of AAA patients (n = 39) and healthy controls (n = 10). We employed wild-type (WT) mice and endothelial Ccni knockout (Ccnifl/flTie2-Cre) mice to conduct in vivo and ex vivo experimentation using an Angiotensin (Ang) II hypertension model and a CaCl2 AAA model. Mice were assessed for Rb/E2f1/Dhfr signaling, biopterin (i.e., biopterin [B], dihydrobiopterin [BH2], and tetrahydrobiopterin [BH4]) production, cardiovascular homeostasis, vessel remodeling, and AAA formation. RESULTS: Aortic CCNI mRNA expression was downregulated in AAA patients. Both Ang II- and CaCl2-induced WT mice showed aortic Ccni upregulation coupled with vasculoprotective upregulation of Rb/E2f1/Dhfr signaling and biopterins. Endothelial Ccni knockout downregulated medial Rb/E2f1/Dhfr signaling and biopterins in Ang II-induced hypertensive mice, which exacerbated eNos uncoupling and H2O2 production. Endothelial Ccni knockout impaired in vivo hemodynamic responses and endothelium-dependent vasodilatation in ex vivo mesenteric arteries in response to Ang II. Endothelial Ccni knockout exacerbated mesenteric artery remodeling and AAA risk in response to Ang II and CaCl2. CONCLUSIONS: Endothelial Ccni acts as a critical negative regulator of eNos uncoupling-mediated ROS generation and thereby reduces vulnerability to hypertension-induced vascular remodeling and AAA development in mice.

Protocatechuic acid protects mice from influenza A virus infection.

Influenza A virus (IAV) H1N1 infection remains great challenge to public health and causes great burden over the world. Although there are anti-viral agents available, searching for effective agents to treat H1N1 infection is still in urgent because of the emergence of resistant strain. Protocatechuic acid (PCA) is a biological agent with multiple functions. In present study, we explored the effects of PCA on H1N1 infection. Mice infected with mouse adapted influenza strain A/Font Monmouth were administrated with PCA. The body weight change, mortality, lung index, viral titer, immune cell infiltration, and cytokine production in the lung were monitored. The activation of toll-like receptor 4 (TLR4) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway was investigated. PCA treatment prevented H1N1 infection-induced mice body weight loss and death. PCA reduced the lung index, viral titer, infiltration of immune cells, and cytokine level in the lung, as well as suppressed H1N1-induced TLR4/NF-κB activation. PCA protects mice against H1N1 infection and could be a potential therapeutic agent to treat influenza.

Differences in Axial Length and IOL Power Based on Alternative A-Scan or Fellow-Eye Biometry in Macula-Off Rhegmatogenous Retinal Detachment Eyes.

INTRODUCTION: This study was performed to observe the potential refractive prediction error based on alternative A-scan ultrasound and fellow-eye biometry for phacovitrectomy in macula-off rhegmatogenous retinal detachment (RRD) eyes. METHODS: Phakic macula-off RRD eyes without axial length (AL) measurements obtained using IOLMaster were included. Vitrectomy without lens extraction was performed for RRD repair. Preoperative AL was measured using alternative A-scan ultrasound (AL-US). Postoperative AL was obtained in eyes with silicone oil tamponade (AL-SO) and preoperative fellow-eye biometry (AL-FE) using IOLMaster. Other eyes that faced the same preoperative situation but underwent phacovitrectomy based on fellow-eye biometry were recruited as controls. RESULTS: AL-US, AL-FE, and AL-SO were 25.39 ± 2.14 mm, 25.85 ± 2.16 mm and 26.08 ± 2.53 mm, respectively. The Bland-Altman agreement among AL-US, AL-FE and AL-SO was good (95.5%, 21/22 of cases were in the LoA). The mean IOL power calculated using AL-US (Power-US), AL-FE (Power-FE) and AL-SO (Power-SO) was 16.81 ± 7.19 D, 14.74 ± 6.95 D and 13.54 ± 8.32 D, respectively. The difference between AL-US and AL-SO was significant (P < 0.05), while that between AL-FE and AL-SO was not (P > 0.05). The difference between Power-US and Power-SO was significant (P < 0.05), while that between Power-FE and Power-SO was not (P > 0.05). Nine eyes underwent phacovitrectomy based on fellow-eye biometry and had a final postoperative myopic shift of 0.64 ± 0.78 D. CONCLUSIONS: Alternative A-scan ultrasound led to a significant difference in AL and a prediction error in IOL power, while fellow-eye biometry provided similar results to silicone oil-filled eyes after RRD repair.

RYR2 mutation in non-small cell lung cancer prolongs survival via down-regulation of DKK1 and up-regulation of GS1-115G20.1: A weighted gene Co-expression network analysis and risk prognostic models.

RYR2 mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan-Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1-115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1-115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down-regulating DKK1 and up-regulating GS1-115G20.1.

The Transcription Factor SUB1 Is a Master Regulator of the Macrophage TLR Response in Atherosclerosis.

Toll-like receptor 2 and 4 (TLR2, TLR4) signaling is implicated in atherosclerotic plaque formation. The two-stage master regulator Virtual Inference of Protein-activity by Enriched Regulon (VIPER) analysis of macrophage TLR2 and TLR4 signature genes integrated with coexpression network genes derived from 371 patient-derived carotid specimens identifies activated RNA polymerase II transcriptional coactivator p15 (SUB1/Sub1, PC4) as a master regulon in the atherogenic TLR response. It is found that TLR2 and TLR4 signaling is proinflammatory and proatherosclerotic in chow-fed apolipoprotein E-deficient (ApoE-/- ) mice. Through transgenic myeloid-specific Sub1 knockout in ApoE-/- mice, it is discovered that these proatherosclerotic effects of TLR2 and TLR4 signaling are mediated by Sub1. Sub1 knockout in macrophages enhances anti-inflammatory M2 macrophage polarization and cholesterol efflux. Irradiated low density lipoprotein receptor-deficient (Ldlr-/- ) mice transplanted with Sub1-/- murine bone marrow display reduced atherosclerosis. Promoter analysis reveals Sub1-dependent activation of interferon regulatory factor 1 (Irf1) transcription in a casein kinase 2 (Ck2)-dependent manner, and Sub1-knockout macrophages display decreased Irf1 expression. Artificial Irf1 overexpression in Sub1-knockout macrophages enhances proinflammatory M1 skewing and lowers cholesterol clearance. In conclusion, the TLR master regulon Sub1, and its downstream effect on the transcription factor Irf1, promotes a proinflammatory M1 macrophage phenotype and enhances atherosclerotic burden in vivo.

Diffusion Biased by a Soft Neck Linker Regulates Kinesin Stepping.

Conventional kinesin is a high-performance motor that moves primarily toward the plus end of microtubules and occasionally toward the opposite direction. The physical mechanism of this directional stepping remains unclear. Here we develop a kinetic two-cycle model incorporating kinesin forward and backward stepping, in which the neck linker zippering and ATP catalysis process are conserved in backward steps. This model is quantitatively validated by a variety of experimental data, including load dependence of velocity, stepping ratio, and dwell time. The physical mechanism of kinesin stepping regulated by a biased diffusion process is identified by analyzing the load dependence and relevant thermodynamic properties of the model. Furthermore, the model suggests the kinesin directionality is optimized resulting from fulfilling a thermodynamic constraint. Our modeling provides a chemomechanical coupling mechanism that connects the flexibility of the neck linker zippering effect for direction rectification and the measured performance into a consistent frame.

Tunable Chiral Bound States with Giant Atoms.

We propose tunable chiral bound states in a system composed of superconducting giant atoms and a Josephson photonic-crystal waveguide (PCW), with no analog in other quantum setups. The chiral bound states arise due to interference in the nonlocal coupling of a giant atom to multiple points of the waveguide. The chirality can be tuned by changing either the atom-waveguide coupling or the external bias of the PCW. Furthermore, the chiral bound states can induce directional dipole-dipole interactions between multiple giant atoms coupling to the same waveguide. Our proposal is ready to be implemented in experiments with superconducting circuits, where it can be used as a tunable toolbox to realize topological phase transitions and quantum simulations.

Curcumin promotes functional recovery and inhibits neuronal apoptosis after spinal cord injury through the modulation of autophagy.

Objective: The study was aimed to investigate whether the neuroprotective role of curcumin is associated with regulation of autophagy.Methods: Rat spinal cord injury (SCI) models were established according to Allen's weight-drop trauma method. Curcumin was administered 30 min after the contusion and continued weekly. At 3, 7, 14, 21, and 28 days after SCI, functional recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring and the oblique plate test, following which, spinal cord tissues were obtained. Histological changes and apoptosis were then measured with H&E staining and TUNEL assay. Glia activation, inflammatory infiltration, inflammatory factor release, and myelination were observed through immunohistochemical (IHC) staining and ELISA. Autophagy and Akt activation were detected by western blotting. After autophagy was inhibited by injection of chloroquine, TUNEL, inflammatory factor release, myelin basic protein (MBP) IHC staining and functional recovery evaluation were performed again.Results: Curcumin treatment promoted functional recovery after SCI and reduced neuron apoptosis, improved spinal cord integrity, recovery, and re-myelination, and suppressed the inflammatory response. Autophagy was enhanced and Akt/mTOR pathway was inhibited by curcumin. Autophagy inhibition partially eliminated the protective effect of curcumin on SCI.Conclusion: Curcumin may exert its therapeutic effect on SCI through the enhancement of autophagy, in which, inhibition of the Akt/mTOR signaling pathway may be also involved.

Measuring the complex spectrum of orbital angular momentum and radial index with a single-pixel detector.

Typical methods to decode a complex orbital-angular-momentum (OAM) spectrum suffer from issues such as a narrow OAM range, unstable interferometer, and long measuring time. In this Letter, we use a single-beam interferometer to measure the complex OAM spectrum with a single-pixel detector. The complex OAM spectrum ranging from -10 to 10 can be measured in 11 ms with the fidelity approach of 97.0%, experimentally. Our approach allows one to characterize an unknown coherent field with any complex basis, e.g., the Laguerre-Gaussian (LG) basis is used for radial index spectrum measurement. Furthermore, single-pixel complex amplitude imaging based on the LG spectrum acquisition is presented, and the advantages in resolution and flexibility are demonstrated.

miR-532-3p-CSF2RA Axis as a Key Regulator of Vulnerable Atherosclerotic Plaque Formation.

BACKGROUND: The most dangerous atherosclerotic plaques, referred to as "vulnerable," are most likely to trigger acute atherothrombotic events such as myocardial infarction (heart attack) and stroke. Our goal was to uncover the molecular drivers of vulnerable plaque formation. METHODS: To elucidate the functional gene modules that drive vulnerable plaque formation, we performed a weighted gene coexpression network analysis integrated with a protein-protein interaction network analysis in human atherosclerotic carotid samples, which identified the candidate gene granulocyte-macrophage colony-stimulating factor 2 (GM-CSF) receptor alpha subunit (CSF2RA). Follow-up in vitro experiments were performed to elucidate the regulatory relationship between CSF2RA and the microRNA miR-532-3p as well as modifiers of macrophagic miR-532-3p-CSF2RA axis expression. Microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) studies elucidated the effect of statins on carotid miR-532-3p-CSF2RA axis expression in patients with carotid atherosclerotic disease. Apoe-/-, Ldlr-/-, and Csf2ra mutant Apoe-/- mouse models of atherosclerosis were employed to assess the effects of agomiR-532-3p therapy in vivo. RESULTS: The integrated weighted gene coexpression network analysis/protein-protein interaction network analysis revealed that the macrophagic GM-CSF receptor CSF2RA is significantly upregulated in macrophage-rich vulnerable plaques. Follow-up analysis identified the miR-532-3p-CSF2RA axis, as miR-532-3p downregulates CSF2RA via binding to CSF2RA's 3'UTR. Macrophagic miR-532-3p-CSF2RA dysregulation was enhanced via modified low-density lipoprotein or tumor necrosis factor α exposure in vitro. Moreover, this miR-532-3p-CSF2RA dysregulation was observed in human vulnerable plaques and Apoe-/- mouse plaques, effects rescued by statin therapy. In vivo, agomiR-532-3p therapy suppressed murine plaque formation and promoted plaque stabilization in a Csf2ra-dependent manner. CONCLUSION: Macrophagic miR-532-3p-CSF2RA axis dysregulation is a key driver in vulnerable plaque formation.

Upregulation of miR­423 improves autologous vein graft restenosis via targeting ADAMTS­7.

Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR­423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs­7 (ADAMTS­7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR­423 target, ADAMTS­7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR­423 in plasma of patients with CHD prior to and following CABG confirms that miR­423 may be a suitable target for preventing VGF. Furthermore, a dual­luciferase reporter gene assay indicated that miR­423 directly interacted with ADAMTS­7 and suppressed its expression. Ectopic expression of miR­423 suppressed ADAMTS­7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS­7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR­423 also enhanced re­endothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR­423/ADAMTS­7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.