Integrative Proteomic Analysis Reveals the Cytoskeleton Regulation and Mitophagy Difference Between Ischemic Cardiomyopathy and Dilated Cardiomyopathy.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two primary etiologies of end-stage heart failure. However, there remains a dearth of comprehensive understanding the global perspective and the dynamics of the proteome and phosphoproteome in ICM and DCM, which hinders the profound comprehension of pivotal biological characteristics as well as differences in signal transduction activation mechanisms between these two major types of heart failure. We conducted high-throughput quantification proteomics and phosphoproteomics analysis of clinical heart tissues with ICM or DCM, which provided us the system-wide molecular insights into pathogenesis of clinical heart failure in both ICM and DCM. Both protein and phosphorylation expression levels exhibit distinct separation between heart failure and normal control heart tissues, highlighting the prominent characteristics of ICM and DCM. By integrating with omics results, Western blots, phosphosite-specific mutation, chemical intervention, and immunofluorescence validation, we found a significant activation of the PRKACA-GSK3ß signaling pathway in ICM. This signaling pathway influenced remolding of the microtubule network and regulated the critical actin filaments in cardiac construction. Additionally, DCM exhibited significantly elevated mitochondria energy supply injury compared to ICM, which induced the ROCK1-vimentin signaling pathway activation and promoted mitophagy. Our study not only delineated the major distinguishing features between ICM and DCM but also revealed the crucial discrepancy in the mechanisms between ICM and DCM. This study facilitates a more profound comprehension of pathophysiologic heterogeneity between ICM and DCM and provides a novel perspective to assist in the discovery of potential therapeutic targets for different types of heart failure.

Circulating mitochondria promoted endothelial cGAS-derived neuroinflammation in subfornical organ to aggravate sympathetic overdrive in heart failure mice.

BACKGROUND: Sympathoexcitation contributes to myocardial remodeling in heart failure (HF). Increased circulating pro-inflammatory mediators directly act on the Subfornical organ (SFO), the cardiovascular autonomic center, to increase sympathetic outflow. Circulating mitochondria (C-Mito) are the novel discovered mediators for inter-organ communication. Cyclic GMP-AMP synthase (cGAS) is the pro-inflammatory sensor of damaged mitochondria. OBJECTIVES: This study aimed to assess the sympathoexcitation effect of C-Mito in HF mice via promoting endothelial cGAS-derived neuroinflammation in the SFO. METHODS: C-Mito were isolated from HF mice established by isoprenaline (0.0125 mg/kg) infusion via osmotic mini-pumps for 2 weeks. Structural and functional analyses of C-Mito were conducted. Pre-stained C-Mito were intravenously injected every day for 2 weeks. Specific cGAS knockdown (cGAS KD) in the SFO endothelial cells (ECs) was achieved via the administration of AAV9-TIE-shRNA (cGAS) into the SFO. The activation of cGAS in the SFO ECs was assessed. The expression of the mitochondrial redox regulator Dihydroorotate dehydrogenase (DHODH) and its interaction with cGAS were also explored. Neuroinflammation and neuronal activation in the SFO were evaluated. Sympathetic activity, myocardial remodeling, and cardiac systolic dysfunction were measured. RESULTS: C-Mito were successfully isolated, which showed typical structural characteristics of mitochondria with double-membrane and inner crista. Further analysis showed impaired respiratory complexes activities of C-Mito from HF mice (C-MitoHF) accompanied by oxidative damage. C-Mito entered ECs, instead of glial cells and neurons in the SFO of HF mice. C-MitoHF increased the level of ROS and cytosolic free double-strand DNA (dsDNA), and activated cGAS in cultured brain endothelial cells. Furthermore, C-MitoHF highly expressed DHODH, which interacted with cGAS to facilitate endothelial cGAS activation. C-MitoHF aggravated endothelial inflammation, microglial/astroglial activation, and neuronal sensitization in the SFO of HF mice, which could be ameliorated by cGAS KD in the ECs of the SFO. Further analysis showed C-MitoHF failed to exacerbate sympathoexcitation and myocardial sympathetic hyperinnervation in cGAS KD HF mice. C-MitoHF promoted myocardial fibrosis and hypertrophy, and cardiac systolic dysfunction in HF mice, which could be ameliorated by cGAS KD. CONCLUSION: Collectively, we demonstrated that damaged C-MitoHF highly expressed DHODH, which promoted endothelial cGAS activation in the SFO, hence aggravating the sympathoexcitation and myocardial injury in HF mice, suggesting that C-Mito might be the novel therapeutic target for sympathoexcitation in HF.

Single-pixel imaging with high spectral and spatial resolution.

It has long been a challenge to obtain high spectral and spatial resolution simultaneously for the field of measurement and detection. Here we present a measurement system based on single-pixel imaging with compressive sensing that can realize excellent spectral and spatial resolution at the same time, as well as data compression. Our method can achieve high spectral and spatial resolution, which is different from the mutually restrictive relationship between the two in traditional imaging. In our experiments, 301 spectral channels are obtained in the band of 420-780 nm with a spectral resolution of 1.2 nm and a spatial resolution of 1.11 mrad. A sampling rate of 12.5% for a 64×64p i x e l image is obtained by using compressive sensing, which also reduces the measurement time; thus, high spectral and spatial resolution are realized simultaneously, even at a low sampling rate.

Image-free real-time target tracking by single-pixel detection.

Image-based target tracking methods rely on continuous image acquisition and post-processing, which will result in low tracking efficiency. To realize real-time tracking of fast moving objects, we propose an image-free target tracking scheme based on the discrete cosine transform and single-pixel detection. Our method avoids calculating all the phase values, so the number of samples can be greatly reduced. Furthermore, complementary modulation is applied to reduce the measurement noise, and background subtraction is applied to enhance the contrast. The results of simulations and experiments demonstrate that the proposed scheme can accomplish the tracking task in a complex background with a sampling ratio of less than 0.59% of the Nyquist-Shannon criterion, thereby significantly reducing the measurement time. The tracking speed can reach 208 fps at a spatial resolution of 128 × 128 pixels with a tracking error of no more than one pixel. This technique provides a new idea for real-time tracking of fast-moving targets.

Giant cardiac myxoma presenting with exertional angina: Coronary steal due to neovascularization?

Myxoma is the most common benign tumor of the heart. Most patients present with no symptoms, only a few patients present with exertional dyspnea and stroke. We introduce this rare case presenting with exertional angina, which was caused by coronary steal due to neovascularization, proved by coronary angiography and cardiac stress testing.

Unusual cardiac tamponade: Giant primary cardiac myxoid liposarcoma.

Primary cardiac myxoid liposarcoma is an extremely rare disease. We reported a 61-year-old man with a 1-month history of aggressive dyspnea and anorexia due to a giant primary cardiac myxoid liposarcoma. Radical resection, whenever feasible, is considered to be an appropriate surgical strategy for this disease. Heart transplantation may be an alternative therapy for such isolated and unresectable tumor.

Enlargement of left ventricular outflow tract using an autologous pericardial patch for anterior mitral valve leaflet and septal myectomy through trans-mitral approach for the treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVE: Modified Morrow procedure is the gold standard of surgical intervention for hypertrophic obstructive cardiomyopathy (HOCM). However, there are certain cases without complete relief of obstruction through trans-aortic approach, we, therefore, described an unusual technique. We aimed to retrospectively analyze this series of patients to reveal its safety and efficiency. METHODS: We retrospectively analyzed a total of 247 consecutive HOCM patients in our center from January 2016 to December 2019. Sixteen of them who underwent enlargement of left ventricular outflow tract (LVOT) using an autologous pericardial patch for anterior mitral valve leaflet and septal myectomy through trans-mitral approach were recruited in this study. Baseline characteristics, perioperative data, and the outcomes were studied. RESULTS: Of the 16 patients, there was no operative mortality. No permanent pacemaker implantation and ventricular septal defects formation were observed. The peak pressure gradient of LVOT decreased from 97.56 ± 23.81 mmHg to 7.56 ± 2.13 mmHg (p < .01) after operation and 10.19 ± 2.93 mmHg (p < .01) 3 months later. The average septal thickness decreased from 18.38 ± 3.56 mm to 10.00 ± 2.74 mm (p < .01). During a mean follow-up of 34.25 ± 12.85 months (range, 15-57), no patient required cardiac reoperation. At the last follow up, the mean peak pressure gradient of LVOT was 10.12 ± 2.03 mmHg and no patient had more than moderate mitral regurgitation. CONCLUSION: Enlargement of LVOT using an autologous pericardial patch for anterior mitral valve leaflet and septal myectomy through trans-mitral approach is feasible and reliable for the treatment of certain types of HOCM cases.

A New Method for Analyzing Aero-Optical Effects with Transient Simulation.

Aero-optical effects reduce the accuracy of optical sensors on high-speed aircraft. Current research usually focuses on light refraction caused by large-scale density structures in turbulence. A method for analyzing photon energy scattering caused by micro-scale structures is proposed in this paper, which can explain the macro image distortion caused by moving molecules in inhomogeneous airflow. Quantitative analysis of the propagation equation indicates that micro-scale structures may contribute more to the wavefront distortion than the widely considered large-scale structures. To analyze the micro mechanism of aero-optical effects, a transient simulator is designed based on the scaling model of transient distorted wavefronts and the artificial vortex structure. The simulation results demonstrate that correct aero-optical phenomena can be obtained from the micro mechanism of photon energy scattering. Examples of using the transient simulator to optimize the parameters of the star sensor on a hypersonic vehicle are provided. The proposed analysis method for micro-scale structures provides a new idea for studying the aero-optical effects.

Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury.

Coronavirus disease-2019 (COVID-19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. The pathological investigation of COVID-19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.

Mitral valve annuloplasty versus no intervention for mild-to-moderate secondary mitral regurgitation in severe aortic regurgitation: a propensity-score matched analysis.

BACKGROUND: The management strategy for secondary mitral regurgitation (MR) during aortic valve surgery for aortic regurgitations (ARs) remains controversial. This study aimed to compare the outcomes between mitral valve annuloplasty (MVP) and no intervention for managing 2+ or 3+ MR among severe patients with AR. METHODS: Eighty-seven eligible patients with complete echocardiographic follow-up were included, with 51 patients in the MVP group and 36 in the No-MVP group. The MVP group had a larger left atrial (LA) diameter (44.2 ± 6.6 vs 49.4 ± 7.6 mm; P = .001) and a higher proportion of 3+ MR (33.3% vs 76.5%; P < .001) than the No-MVP group. After 1:1 propensity-score matching, the patients treated with and without MVP were balanced on 14 preoperative characteristics. RESULTS: There was one in-hospital death in each group. In the propensity-score matched cohort, there was no statistically significant difference between the two groups in the cumulative incidence of residual 2+ MR during a follow-up of 26.4 ± 14.8 months (P = .64). The No-MVP group was associated with a more significant change in the left ventricular end-diastolic dimension (18.1 ± 7.9 vs 13.7 ± 8.7 mm; P = .02), while the changes in the LA diameter, left ventricular end-systolic dimension, and left ventricular ejection fraction were similar between the two groups. CONCLUSIONS: The severity of MR and the LA size may impact surgeons' decisions. MVP does not seem to add extra benefits to the outcomes, and it may be associated with worse left ventricular remodeling.

Improvement of long-term stability of hollow-core photonic-crystal fiber optic gyro based on single-polarization resonator.

To improve long-term stability, we present a single-polarization resonator optic gyro based on a hollow-core photonic-crystal fiber (HCPCF), utilizing a micro-optical polarizing coupler formed by pairs of collimators and a series of polarization-dependent devices. We build the mathematical model of the polarization noise of the proposed gyro and experimentally validate the elimination of the undesired polarization eigenstate, which is the basis of the system's improved long-term stability. We use multi-modulation to suppress the backscattering noise and the closed-loop detection method to eliminate the effect of fluctuating output power on the gyro bias. A long-term bias stability of 20°/h is successfully demonstrated.

Noise reduction in computational ghost imaging by interpolated monitoring.

An interpolation computational ghost imaging (ICGI) method is proposed and demonstrated that is able to reduce the noise interference from a fluctuating source and background. The noise is estimated through periodic illuminations by a specific assay pattern during sampling, which is then used to correct the bucket detector signal. To validate this method simulations and experiments were conducted. Light source intensity and background lighting were randomly varied to modulate the noise. The results show that good quality images can be obtained, while with conventional computational ghost imaging (CGI) the reconstructed object is barely recognizable. The ICGI method offers a general approach applicable to all CGI techniques, which can attenuate the interference from source fluctuations, background light noise, dynamic scattering, and so on.

Analysis of polarization noise in transmissive single-beam-splitter resonator optic gyro based on hollow-core photonic-crystal fiber.

We realize a transmissive single-beam-splitter resonator optic gyro based on a hollow-core photonic-crystal fiber (HCPCF), utilizing a micro-optical coupler formed by pairs of lenses and one filter, which is a new type of resonator fiber optic gyro based on the HCPCF (HC-RFOG). We build a mathematical model of the polarization noise based on the transfer function of this novel transmissive single-beam-splitter resonator. We construct a HC-RFOG and simulate and validate the effects of polarization noise on the gyro system. In addition, we apply an effective method to suppress the polarization noise and prove its efficacy through experiments. The bias stability of the gyro system is successfully improved from 25 °/h to 2 °/h, which indicates a remarkable advance of performance of HC-RFOG.

Transmissive single-beam-splitter resonator optic gyro based on a hollow-core photonic-crystal fiber.

We propose a transmissive single-beam-splitter resonator optic gyro based on a hollow-core photonic-crystal fiber (HCPCF), which is a new regime of resonator fiber optical gyro based on an HCPCF, a hollow-core resonator fiber optical gyro (HC-RFOG), for the first time, to the best of our knowledge. We evaluate the transfer function of this novel transmissive single-beam-splitter resonator, and the resonance characteristics are simulated to optimize the element parameters. We utilize a micro-optical coupler formed by pairs of lenses and one filter to realize this novel resonator. Our approach yields a fineness of 12 and a transmittance of about 5%. Based on this novel resonator, we construct a HC-RFOG, and we simulate and analyze the effects of polarization noise on the gyro system. In addition, an effective method to suppress polarization noise is employed, and the efficacy of this method is confirmed by experiments. A bias stability of 1.3°/h is successfully demonstrated, which is the best result reported to date, to the best of our knowledge, for RFOGs based on an HCPCF resonator.

Clinical Characteristics and Surgical Treatment of Infective Endocarditis With Bicuspid Aortic Valve.

This study aimed to evaluate the clinical characteristics and surgical treatment of bicuspid aortic valve (BAV) infective endocarditis (IE) compared with tricuspid aortic valve (TAV) IE in China.The relevant pre-, intra- and post-operative materials of all IE patients undergoing cardiac surgery in our center between January 2003 and December 2012 were investigated and analyzed retrospectively.From January 2003 to December 2012, 345 consecutive IE patients received surgery in our center. A total of 171 native aortic valve IE patients were enrolled in this study, accounting for 49.6% of the total population. Among these 171 IE patients, 29.8% (n = 51) were BAV, and the remaining (n = 120) were TAV. There was a strong male predominance (92.2% versus 70.8%, P = 0.002) and a higher frequency of aortic perivalvular abscess (45.1% versus 18.3%, P < 0.001) in the BAV IE group compared with the TAV IE group. In multivariate analysis, BAV was the only independent predictor associated with an increased risk of aortic perivalvular abscess (OR = 4.365, 95% CI 1.30-14.65, P = 0.017). Six patients died postoperatively and no significant difference was found about in-hospital mortality between the BAV IE group and TAV IE group (2.0% versus 4.2%, P = 0.793).BAV is common in patients with confirmed aortic valve IE. BAV IE patients have a significantly increased risk of perivalvular abscess. Prompt diagnosis and timely surgery for BAV IE patients might be needed to prevent the formation and extension of perivalvular abscess.

Contemporary In-Hospital and Long-Term Outcomes of Surgical Management for Fungal Endocarditis.

Fungal endocarditis (FE) is a rare and fatal disease. The contemporary in-hospital and long-term surgical outcomes of FE have not been adequately evaluated. This study describes our experience with the surgical management of FE.Eight FE patients who underwent surgery in our center from January 2004 to November 2016 were included in this study. Seven had fungal prosthetic valve endocarditis (PVE) and one fungal native valve endocarditis (NVE). The Bentall operation, Cabrol operation, and mitral valve replacement were performed in 4, 3, and 1 patient, respectively. The overall in-hospital mortality rate was 25% (2/8). The follow-up was completed in all surviving patients and the mean follow-up time was 55.5 ± 63.3 (range, 1-154) months. Two late deaths occurred at 2 months and 4 months after discharge. The other patients recovered well during the follow-up.FE is a devastating disease and surgical treatment has acceptable in-hospital and long-term mortality rates.

"Pacing Bigeminal".

A rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a single chamber pacemaker specific for animals that had a high frequency. However, the pacemaker used in this model is commercially unavailable. We developed a "pacing bigeminal" method using a commercially available dual-chamber (DDD) pacemaker to achieve high-frequency pacing. Twenty beagles were assigned to group A (n = 10) (pacing bigeminal method) and group B (n = 10) (traditional method). Echocardiographic measurements and electrocardiograms were obtained at baseline, at two weeks of pacing, and at 4 weeks of end pacing. LV anterior wall cardiac samples were obtained at 2 weeks of pacing and 4 weeks of end pacing for myocardial microscopic evaluation. Clinical manifestation and exposure time were also observed. After pacing for 10.5 ± 2.3 (714) days, the beagles in group B experienced heart failure, whereas in group A, only 7.9 ± 2.5 (5-12) days (P < 0.05) were needed to reach heart failure. Both methods could induce wide QRS duration, heart rate elevation, and myocardial microscopic changes (P > 0.05). In conclusion, this pacing bigeminal-induced heart failure method is feasible and can induce heart failure faster than the traditional method, which makes it a promising alternative method.

Type A Aortic Dissection Occurring After Previous Cardiac Surgery.

BACKGROUND: We retrospectively reviewed our experience of total arch replacement in patients undergoing repair of an ascending aortic dissection following previous cardiac surgery. METHODS: Data were collected for patients with acute type A aortic dissection following previous cardiac surgery between January 2005 and December 2014. Clinical and prognostic features were retrospectively analyzed. RESULTS: Twenty-eight eligible patients (nonelective: 10, elective: 18) were identified. There was a mean period of 44.5 months between the first operation and the subsequent surgery. The overall 30-day mortality rate was 21.4%; 30.0% for nonelective patients and 16.7% for elective patients. Postoperative morbidity rate was higher among nonelective patients versus elective group. During follow-up, two patients died: one from intracranial hemorrhage and the other from a noncardiac cause. One patient received endografting as a result of the true lumen being compressed by the false lumen following aortic repair. CONCLUSIONS: When hemodynamically stable, patients with acute ascending aortic dissection following previous cardiac surgery may have improved outcomes if the surgery can be performed on an elective basis.

Heart transplantation under mechanical circulatory support for fulminant myocarditis: a Case Report.

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 17-year-old boy with hemodynamic derangement and cardiac arrest due to fulminant myocarditis. After about 2 h of intensive cardiopulmonary resuscitation, with 13 days of extracorporeal membrane oxygenation support, the patient finally bridged to orthotopic heart transplantation. The patient recovered uneventfully and was discharged 37 days after transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls confirming the diagnosis and identifying the underlying cause of fulminant myocarditis.

Irisin ameliorates UUO-induced renal interstitial fibrosis through TGF-ß1/periostin/MMP-2 signaling pathway.

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-ß1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-ß1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-ß1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.