Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii.

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed. Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

Effect of supervised exercise training on cardiovascular function in patients with intermittent claudication: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO2peak), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD = - 7.40, 95% CI - 10.69 ~ - 4.11, p < 0.001, I2 = 15.2%), DBP (WMD = - 1.92, 95% CI - 3.82 ~ - 0.02, p = 0.048, I2 = 0.0%), HR (WMD = - 3.38, 95% CI - 6.30 ~ - 0.46, p = 0.023, I2 = 0.0%), RPP (WMD = - 1072.82, 95% CI - 1977.05 ~ - 168.59, p = 0.020, I2 = 42.7%), and VO2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I2 = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I2 = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I2 = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC.

Multifield-Modulated Spintronic Terahertz Emitter Based on a Vanadium Dioxide Phase Transition.

The efficient generation and active modulation of terahertz (THz) waves are strongly required for the development of various THz applications such as THz imaging/spectroscopy and THz communication. In addition, due to the increasing degree of integration for the THz optoelectronic devices, miniaturizing the complex THz system into a compact unit is also important and necessary. Today, integrating the THz source with the modulator to develop a powerful, easy-to-adjust, and scalable or on-chip THz emitter is still a challenge. As a new type of THz emitter, a spintronic THz emitter has attracted a great deal of attention due to its advantages of high efficiency, ultrawide band, low cost, and easy integration. In this study, we have proposed a multifield-modulated spintronic THz emitter based on the VO2/Ni/Pt multilayer film structure with a wide band region of 0-3 THz. Because of the pronounced phase transition of the integrated VO2 layer, the fabricated THz emitter can be efficiently modulated via thermal or electric stimuli with a modulation depth of about one order of magnitude; the modulation depths under thermal stimulation and electrical stimulation were 91.8% and 97.3%, respectively. It is believed that this multifield modulated spintronic THz emitter will provide various possibilities for the integration of next-generation on-chip THz sources and THz modulators.

Enhanced ferromagnetic properties achieved by F-doping in BaFe1-xMnxO3-δ.

Tailoring the crystal structure, spin, and charge state of perovskite oxides through fluorine ion doping is an attractive and effective strategy, which could significantly modify the physical and chemical properties of base oxides. Here, BaFe1-xMnxO3-δ (x = 0, 0.1, 0.2, 0.3) and BaFe1-xMnxO2.9-δF0.1 (x = 0.1, 0.2, 0.3), belonging to 6H-type BaFeO3-δ, are prepared and investigated to evaluate the impact of F- doping. The distortion of crystal structure and the reduced average valence of Mn and Fe confirm the preference for F- substitution in the hexagonal layer, which are found as the key factors for the improved magnetic properties, including ferromagnetic ordering temperature, coercive force, and remanent magnetization. Moreover, the valence reduction of B-site ions and the increased resistance distinctly indicate the expense of electron hole via fluorine doping. This work describes the adjustment of crystal structure, electronic configuration, and ferromagnetic performance by simple F- doping, which provides a prospect for practical magnetic materials.

miR-22-3p in the rostral ventrolateral medulla promotes hypertension through inhibiting ß-arrestin-1.

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that ß-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in ß-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the ß-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of ß-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by ß-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced ß-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting ß-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of ß-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of ß-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the ß-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of ß-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting ß-arrestin-1 in the RVLM.

Preparation of High-Ductility Cement-Calcined Coal-Gangue-Powder-Composite-Based Rapid Repair Material.

Coal gangue is a kind of solid waste. A high-ductility cement-calcined coal-gangue-powder-composite-based rapid repair material (HD-RRM) was prepared by partially replacing cement with calcined coal gangue powder (CCGP) for achieving high ductility and rapid hardening and conforming to the strength requirements of pavement layers. First, the physical and chemical properties and the reactivity of the CCGP were investigated. Second, HD-RRM material was prepared, and its tensile performance characteristic parameters were investigated. Lastly, the hydration products and microstructure of HD-RRM were characterized through tests (e.g., non-evaporable water content, scanning electron microscopy (SEM), X-ray diffraction (XRD), and comprehensive thermogravimetric analysis and differential scanning calorimetry (TG-DSC)). As indicated by the experimental results, the CCGP with a particle size of 1250 mesh exhibited the maximum potential reactivity. The optimal mixing ratio for HD-RRM in the experiments comprised a water-cement ratio of 0.27, a sand-cement ratio of 0.3, a fiber volume fraction of 2%, a cement content of 70%, a CCGP content of 20%, a fly ash (FA) content of 10%, and a superplasticizer content of 0.1%. Using the abovementioned mix design, the prepared HD-RRM was endowed with a 6 h ultimate elongation of 2.75%, an ultimate tensile strength of 7.58 MPa, a compressive strength of 45.4 MPa, and an average crack width of 125.53 µm, which meets the requirements of repair materials and provides a design method for CCGP resource utilization and asphalt concrete road and bridge deck repair.

Effect of angiotensin II on irradiation exacerbated decompression sickness.

In some complicated situations, decompression sickness (DCS) combined with other injuries, such as irradiation, will seriously endanger life safety. However, it is still unclear whether irradiation will increase the incidence of DCS. This study was designed to investigate the damage effects of irradiation on decompression injury and the underlying mechanism. Sprague-Dawley rats were exposed to irradiation followed by hyperbaric decompressing and the mortality and decompression symptoms were observed. Lung tissue and bronchoalveolar lavage fluid were collected to detect the lung lesion, inflammation response, activity of the angiotensin system, oxidative stress, and relative signal pathway by multiple methods, including Q-PCR, western blot, and ELISA. As a result, pre-exposure to radiation significantly exacerbated disease outcomes and lung lesions of DCS. Mechanically, the up-regulation of angiotensin-converting enzyme expression and angiotensin II levels was responsible for the exacerbated DCS and lung lesions caused by predisposing irradiation exposure. Oxidative stress and PI3K/AKT signal pathway activation in pulmonary tissue were enhanced after irradiation plus decompression treatment. In conclusion, our results suggested that irradiation could exacerbate lung injury and the outcomes of DCS by activating the angiotensin system, which included eliciting oxidative stress and activation of the PI3K/AKT signal pathway.

The Effects of MicroRNAs in the Development of Heart Failure.

PURPOSE OF REVIEW: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment. RECENT FINDINGS: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure.

A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.

Identifying the critical state of complex biological systems by the directed-network rank score method.

MOTIVATION: Catastrophic transitions are ubiquitous in the dynamic progression of complex biological systems; that is, a critical transition at which complex systems suddenly shift from one stable state to another occurs. Identifying such a critical point or tipping point is essential for revealing the underlying mechanism of complex biological systems. However, it is difficult to identify the tipping point since few significant differences in the critical state are detected in terms of traditional static measurements. RESULTS: In this study, by exploring the dynamic changes in gene cooperative effects between the before-transition and critical states, we presented a model-free approach, the directed-network rank score (DNRS), to detect the early-warning signal of critical transition in complex biological systems. The proposed method is applicable to both bulk and single-cell RNA-sequencing (scRNA-seq) data. This computational method was validated by the successful identification of the critical or pre-transition state for both simulated and six real datasets, including three scRNA-seq datasets of embryonic development and three tumor datasets. In addition, the functional and pathway enrichment analyses suggested that the corresponding DNRS signaling biomarkers were involved in key biological processes. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/zhongjiayuan/DNRS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The interleukin-enhanced binding factor 3-mediated inhibition of nitric oxide production via phosphoinositide 3-kinase/protein kinase B pathway contributes to central cardiovascular regulation in the rostral ventrolateral medulla in hypertension.

Hypertension is characterized by sympathetic hyperactivity, which is related to the overexcitation of the presympathetic neurons in the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) has been reported to be a vital neuromodulator involved in central cardiovascular regulation. However, the mechanism of interleukin-enhanced binding factor 3 (ILF3) participating in blood pressure (BP) regulation is still unclear. Therefore, this study aims to clarify the role of ILF3 within the rostral ventrolateral medulla (RVLM) in regulating NO in hypertension. It was found that the expression level of ILF3 was significantly increased in the RVLM of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats through microarray gene expression analysis, Western blot, and immunofluorescence. Overexpression of ILF3 by injecting constructed adenovirus into the RVLM increased the BP and renal sympathetic nerve activity (RSNA) of the WKY rats, significantly decreasing NO production and neuronal nitric oxide synthase (nNOS) expression. Knockdown of ILF3 in the RVLM of SHR significantly reduced BP but increased NO production and the neuronal nitric oxide synthase (nNOS) expression. Furthermore, it was found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was activated via Western blotting in the RVLM after overexpression of ILF3, whereas it was attenuated after knockdown of ILF3 in SHR. In addition, inhibition of PI3K by intracisternal infusion of the PI-103 attenuated the increase in Akt phosphorylation and decrease in nNOS expression and NO production caused by overexpressing ILF3, which ultimately blunted high BP induced by overexpressing ILF3. Taken together, this current study suggests that ILF3 participates in high BP via reducing NO production in the RVLM through PI3K/Akt pathway.

DPP3: From biomarker to therapeutic target of cardiovascular diseases.

Cardiovascular disease is the leading cause of death globally among non-communicable diseases, which imposes a serious socioeconomic burden on patients and the healthcare system. Therefore, finding new strategies for preventing and treating cardiovascular diseases is of great significance in reducing the number of deaths and disabilities worldwide. Dipeptidyl peptidase 3 (DPP3) is the first zinc-dependent peptidase found among DPPs, mainly distributes within the cytoplasm. With the unique HEXXGH catalytic sequence, it is associated with the degradation of oligopeptides with 4 to 10 amino acids residues. Accumulating evidences have demonstrated that DPP3 plays a significant role in almost all cellular activities and pathophysiological mechanisms. Regarding the role of DPP3 in cardiovascular diseases, it is currently mainly used as a biomarker for poor prognosis in patients with cardiovascular diseases, suggesting that the level of DPP3 concentration in plasma is closely linked to the mortality of diseases such as cardiogenic shock and heart failure. Interestingly, it has been reported recently that DPP3 regulates blood pressure by interacting with the renin-angiotensin system. In addition, DPP3 also participates in the processes of pain signaling, inflammation, and oxidative stress. But the exact mechanism by which DPP3 affects cardiovascular function is not clear. Hence, this review summarizes the recent advances in the structure and catalytic activity of DPP3 and its extensive biological functions, especially its role as a therapeutic target in cardiovascular diseases. It will provide a theoretical basis for exploring the potential value of DPP3 as a therapeutic target for cardiovascular diseases.

Contribution of cyclooxygenase-2 overexpression to enhancement in tonically active glutamatergic inputs to the rostral ventrolateral medulla in hypertension.

OBJECTIVE: Cyclooxygenase (COX) is critical in regulating cardiovascular function, but its role involved in the central control of blood pressure (BP) is uncovered. The tonic glutamatergic inputs to the rostral ventrolateral medulla (RVLM) are enhanced in hypertension. Here, the present study was designed to investigate the effect and mechanism of central COX on tonic glutamatergic inputs to the RVLM and BP regulation. METHODS: Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) received RVLM microinjection of adeno-associated viral vectors to promote or inhibit the COX2 expression were subjected to subsequent experiments. Glutamate level and glutaminase expression were detected by ELISA and western blot, respectively. The function of tonic glutamatergic inputs was assessed by BP response to microinjection of the glutamate receptor antagonist into the RVLM. PC12 cells were used to detect the underlying signal pathway. RESULTS: The RVLM COX2 expression and prostaglandin E2 level were significant higher in SHRs than in WKY rats. Overexpression of COX2 in the RVLM produced an increase in basal BP, RVLM glutamate level, and glutaminase expression in WKY rats, while they were significantly reduced by interfering with COX2 expression in SHRs. Microinjections of the glutamate receptor antagonist into the RVLM produced a significant BP decrease in WKY rats with COX2 overexpression pretreatment. Furthermore, the increased levels of BP, glutamate content, and glutaminase activity in the RVLM evoked by central infusion of angiotensin II were attenuated in COX2 knockout mice. It was also found that prostaglandin E2 increased supernatant glutamate level and phosphorylation of signal transducer and activator of transcription 3 in PC12 cells. CONCLUSION: Our findings suggest that upregulated COX2 expression enhances the tonically active glutamatergic inputs to the RVLM, which is associated with cardiovascular regulation in hypertension.

Short grain 5 controls grain length in rice by regulating cell expansion.

Grain shape is a crucial determinant of grain weight and quality and plays a vital role in rice breeding. Although many grain shape-related genes have been reported, the regulatory relationship between them has not been well characterized in rice. In this study, we report the isolation of a short-grain-length mutant called sg5 from the heavy-panicle-type hybrid rice elite restorer line 'ShuhuiR498' (R498) after ethyl methanesulfonate (EMS) treatment. MutMap cloning revealed that SG5 encodes a Myb-like transcription factor. A missense mutation in the first exon of SG5 was found to cause an amino acid change from leucine to proline at position 197 in the mutant SG5 protein. Gene knockout and genetic complementation experiments confirmed that the point mutation in SG5 was responsible for the sg5 mutant phenotype. SG5 is mainly expressed in young panicles and hulls. In addition, the SG5 protein is found in the nucleus and does not affect subcellular localization. Histochemical observation and gene expression analysis indicated that SG5 regulates spikelet hull development by mediating cell expansion. Moreover, the expression levels of BG1, GS2, and DEP1 were reduced in sg5 plants, and dual-luciferase (LUC) assays showed that SG5 can bind to the BG1 gene promoter. The effect of pyramiding sg5 and GS3 suggests that sg5 and GS3 regulate grain length independently. The results of our study show that the missense mutation in sg5 is essential for the molecular function of SG5 and SG5 is involved in regulating cell expansion and expression of grain-shape-related genes to regulate grain length. This work provides new data to help study and understand the molecular function of SG5.

SIRT1 exerts anti-hypertensive effect via FOXO1 activation in the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is a pivotal region in the central regulation of blood pressure (BP). It has been documented that silent information regulator 2 homolog 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent multifunctional transcription regulatory factor, has many cardiovascular protective effects. However, the role and significance of SIRT1 in the central regulation of cardiovascular activity, especially in RVLM, remains unknown. Therefore, the aim of this study was to explore the role and underlying mechanism of SIRT1 in the central regulation of cardiovascular activity in hypertension. Spontaneously hypertensive rats (SHRs) were given resveratrol (RSV) via intracerebroventricular (ICV) infusion or injected with SIRT1-overexpressing lentiviral vectors into the RVLM. In vitro experiments, angiotensin II (Ang II)-induced rat pheochromocytoma cell line (PC12 cells) were transfected with forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) before treatment with RSV. Our results showed that SIRT1 activation with RSV or overexpression in the RVLM significantly decreased BP and sympathetic outflow of SHRs. Furthermore, SIRT1 overexpression in the RVLM significantly decreased reactive oxygen species (ROS) production and facilitated the forkhead box protein O1 (FOXO1) activation, accompanied by upregulation of the ROS-detoxifying enzyme superoxide dismutases 1 (SOD1) in the RVLM of SHRs. In PC12 cells, it was found that Ang II could induce oxidative stress and downregulate the SIRT1-FOXO1-SOD1 signaling pathway, which indicated that the suppressed expression of SIRT1 in the RVLM of SHRs might relate to the elevated central Ang II level. Furthermore, the enhanced oxidative stress and decreased SIRT1-FOXO1-SOD1 axis induced by Ang II were restored by treatment with RSV. However, these favorable effects mediated by SIRT1 activation were blocked by FOXO1 knockdown. Based on these findings, we concluded that SIRT1 activation or overexpression in the RVLM exerts anti-hypertensive effect through reducing oxidative stress via SIRT1-FOXO1-SOD1 signaling pathway, which providing a new target for the prevention and intervention of hypertension.

The Peripheral Circulating Exosomal microRNAs Related to Central Inflammation in Chronic Heart Failure.

Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood-brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.

Arbitrary active control of the Pancharatnam-Berry phase in a terahertz metasurface.

Active phase-control metasurfaces show outstanding capability in the active manipulation of light propagation, while the previous active phase control methods have many constraints in the cost of simulation or the phase modulation range. In this paper, we design and demonstrate a phase controlled metastructure based on two circular split ring resonators (CSRRs) composed of silicon and Au with different widths, which can continuously achieve an arbitrary Pancharatnam-Berry (PB) phase between -π and π before or after active control. The PB phase of such a metasurface before active control is determined by the rotation angle of the Au-composed CSRR, while the PB phase after active control is determined by the rotation angle of the silicon-composed CSRR. And active control of the PB phase is realized by varying conductivity of silicon under an external optical pump. Based on this metastructure, active control of light deflection, metalens with arbitrary reconfigurable focal points and achromatic metalens under selective frequencies are designed and simulated. Moreover, the experimental results demonstrate that focal spots of metalens can be actively controlled by the optical pump, in accord with the simulated ones. Our metastructure implements a plethora of metasurfaces' active phase modulation and provides applications in active light manipulation.

Cellular Phenotypic Transformation in Heart Failure Caused by Coronary Heart Disease and Dilated Cardiomyopathy: Delineating at Single-Cell Level.

Heart failure (HF) is known as the final manifestation of cardiovascular diseases. Although cellular heterogeneity of the heart is well understood, the phenotypic transformation of cardiac cells in progress of HF remains obscure. This study aimed to analyze phenotypic transformation of cardiac cells in HF through human single-cell RNA transcriptome profile. Here, phenotypic transformation of cardiomyocytes (CMs), endothelial cells (ECs), and fibroblasts was identified by data analysis and animal experiments. Abnormal myosin subunits including the decrease in Myosin Heavy Chain 6, Myosin Light Chain 7 and the increase in Myosin Heavy Chain 7 were found in CMs. Two disease phenotypes of ECs named inflammatory ECs and muscularized ECs were identified. In addition, myofibroblast was increased in HF and highly associated with abnormal extracellular matrix. Our study proposed an integrated map of phenotypic transformation of cardiac cells and highlighted the intercellular communication in HF. This detailed definition of cellular transformation will facilitate cell-based mapping of novel interventional targets for the treatment of HF.

ß-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension.

Oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for blood pressure (BP) regulation, has been demonstrated to be responsible for the overactivity of the sympathetic nervous system in hypertension and heart failure. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is a key transcription factor that maintains redox homeostasis by governing a broad array of antioxidant genes in response to oxidative stress. ß-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors (GPCRs), and its overexpression in the RVLM could reduce BP and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHR). The goal of this study was to investigate whether Nrf2-mediated antioxidative stress is involved in the antihypertensive effect of ß-arrestin1 in the RVLM. It was found that the activation level of Nrf2 in the RVLM of SHR was significantly reduced, compared with normotensive Wistar-Kyoko (WKY) rats. Overexpression of ß-arrestin1 in the RVLM significantly decreased ROS production and facilitated the Nrf2 activation in the RVLM of SHR, accompanied by upregulating the expression of HO-1 and NQO-1. However, Nrf2 knockdown attenuated the antioxidant effect of ß-arrestin1 overexpression in the RVLM by downregulating HO-1 and NQO-1 expression levels. In conclusion, the current results suggested that the antihypertensive effect of ß-arrestin1 overexpression in the RVLM is mediated by decreased ROS production, which is associated with Nrf2 activation.

Constant Light Exerted Detrimental Cardiovascular Effects Through Sympathetic Hyperactivity in Normal and Heart Failure Rats.

It has been documented that constant light exposure exerts complicated cardiovascular effects. However, a mounting collection of conflicting results did not make it any easier for researchers and physicians to consider the role of light on cardiovascular function. This study was designed to investigate how constant light exposure (24 h light/day) influences the cardiac function in normal and heart-failure (HF) rats. In normal rats, two groups of SD rats were accustomed in 12 h light/12 h dark (LD) or 24 h light (constant light, CL) for 4 weeks. In HF rats which was induced by myocardial infarction (MI) was let recover in LD for 4 weeks. Interestingly, compared with rats in LD environment (ejection fraction, EF%: 93.64 ± 2.02 in LD, 14.62 ± 1.53 in HF-LD), constant light (2 weeks) weakened the cardiac function in normal and HF rats (EF%: 79.42 ± 2.91 in CL, 11.50 ± 1.08 in HF-CL). The levels of renal sympathetic nerve activity and c-fos expression in the rostral ventrolateral medulla (RVLM), a key region controlling sympathetic outflow, were significantly increased in normal and HF rats after constant light (RSNA, Max%: 8.64 ± 0.48 in LD, 20.02 ± 1.24 in CL, 20.10 ± 1.16 in HF-LD, 26.82 ± 1.69 in HF-CL). In conclusion, it is suggested that constant light exposure exerts detrimental cardiovascular effects, which may be associated with the RVLM-related sympathetic hyperactivity.