A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Feasibility and prognostic value of tissue motion annular displacement in patients with heart transplantation.

BACKGROUND: Tissue motion of mitral annular displacement (TMAD) assessment has proved to be an effective method for several cardiovascular diseases including hypertrophic cardiomyopathy, heart failure, non-ST-elevation myocardial infarction, etc. However, there are no studies exploring the feasibility of TMAD in heart transplantation (HT) recipients, and the predictive value of this parameter for adverse outcomes in these patients remains unknown. Consequently, this study aimed to evaluate the feasibility of TMAD in the evaluation of left ventricular (LV) systolic function in clinically well adult HT patients, and further investigate the prognostic value of TMAD. METHODS: Echocardiography was performed in 155 adult HT patients and 49 healthy subjects. All the subjects were examined by conventional transthoracic two-dimensional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE) with evaluation of the LV end-diastolic diameter, LV end-diastolic volume index, LV end-systolic volume index, interventricular septal thickness, left atrial diameter, mitral annular plane systolic excursion (MAPSE), LV ejection fraction (LVEF), TMAD and LV global longitudinal strain (LVGLS). The end point was defined as all-causes mortality or posttransplant related hospitalization during follow up. Cox proportional hazards regression was performed to evaluate the prognostic value of the parameters for predicting poor outcomes in HT patients. RESULTS: A significant positive correlation was found between the measurements of TMAD and LVGLS (r = .714, p < .001). TMAD obtained by 2D-STE had good reproducibility. The LVGLS and TMAD were significantly lower in HT group than in control group (both p < .001). In HT patients, compared with event free group, adverse outcome group displayed reduced TMAD and LVGLS, and elevated age (p < .001, < .001, = .017, respectively). Patients with higher TMAD (> 9.1 mm) had comparatively better survival when stratified by cutoff value (log-rank p < .001). LVGLS and TMAD were independently associated with adverse outcomes in multivariable analysis (both p < .001). CONCLUSION: Assessment of TMAD is effective for evaluating LV longitudinal systolic function and predicting adverse outcomes in clinically well adult HT patients.

Feasibility Value of Right Ventricular Longitudinal Shortening Fraction and the Prognostic Implications in Patients With Heart Transplantation.

BACKGROUND: Right ventricular longitudinal shortening fraction (RVLSF) is a 2-dimensional speckle tracking echocardiography parameter based on tricuspid annular displacement analysis that could be used to assess right ventricular (RV) systolic function. The value of RVLSF in the assessment of RV systolic function in recipients of heart transplantation (HT) and whether RVLSF can replace strain parameters remains unknown. METHODS AND RESULTS: A total of 153 adult patients who underwent HT were consecutively enrolled in this prospective longitudinal study. All subjects were examined by conventional transthoracic 2-dimensional echocardiography and 2-dimensional speckle tracking echocardiography to evaluate the RV end-diastolic basal diameter, RV end-diastolic area, fractional area change, peak systolic velocity of tricuspid annulus, tricuspid annular plane systolic excursion, RV free wall strain, and RVLSF. Cox proportional hazards regression was used to test if the parameters of interest had independent prognostic value for adverse outcome prediction in patients who underwent HT. A significant positive correlation was found between the measurements of RVLSF and RV free wall strain (r=0.927, P<0.001). Compared with the event-free group, the adverse outcome group displayed reduced RVLSF and RV free wall strain and higher age (P<0.001, <0.001, =0.016, respectively) in patients who underwent HT. RVLSF and RV free wall strain were independently associated with poor prognosis in multivariable analysis (both P<0.001). CONCLUSIONS: RVLSF assessment provides an effective evaluation of RV longitudinal systolic function in the transplanted hearts and has prognostic value for adverse outcomes in patients undergoing HT.

Echocardiographic assessment of pediatric heart transplantation: A single-center experience in China.

BACKGROUND: Pediatric heart transplant (HT) has become the standard of care for end-stage heart failure in children worldwide. Serial echocardiographic evaluations of graft anatomy and function during follow-up are crucial for post-HT management. However, evolution of cardiac structure and function after pediatric HT has not been well described, especially during first year post-HT. This study aimed to characterize the evolution of cardiac structure and function after pediatric HT and investigate the correlation between biventricular function with adverse clinical outcomes. METHODS: A single-center retrospective study of echocardiographic data obtained among 99 pediatric HT patients was conducted. Comprehensive echocardiographic examination was performed in all patients at 1-, 3-, 6-, 9- and 12-months post-HT. We obtained structural, functional and hemodynamic parameters from both left- and right-side heart, such as left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), right ventricular fractional area change (RVFAC), etc. The cardiac evolution of pediatric HT patients during first post-HT year was described and compared between different time points. We also explored the correlation between cardiac function and major adverse transplant events (MATEs). RESULTS: 1) Evolution of left heart parameters: left atrial length, mitral E velocity, E/A ratio, LVSV and LVEF significantly increased while mitral A velocity significantly decreased over the first year after HT (P < .05). Compared with 1 month after HT, interventricular septum (IVS) and left ventricular posterior wall (LVPW) decreased at 3 months but increased afterwards. (2) Evolution of right heart parameters: right ventricular base diameter and mid-diameter; right ventricular length diameter, tricuspid E velocity, E/A ratio, tricuspid annular velocity e' at free wall, and RVFAC increased, while tricuspid A velocity decreased over the first year after HT (P < .05). (3) Univariate logistic regression model suggests that biventricular function parameters at 1-year post-HT (LVEF, RVFAC, tricuspid annular plane systolic excursion and tricuspid lateral annular systolic velocity) were associated with MATEs. CONCLUSION: Gradual improvement of LV and RV function was seen in pediatric HT patients within the first year. Biventricular function parameters associated with MATEs. The results of this study pave way for designing larger and longer follow-up of this population, potentially aiming at using multiparameter echocardiographic prediction of adverse events.

Early left ventricular systolic function is a more sensitive predictor of adverse events after heart transplant.

BACKGROUND: First-phase ejection fraction (EF1) is a novel measure of early changes in left ventricular systolic function. This study was to investigate the prognostic value of EF1 in heart transplant recipients. METHODS: Heart transplant recipients were prospectively recruited at the Union Hospital, Wuhan, China between January 2015 and December 2019. All patients underwent clinical examination, biochemistry measures [brain natriuretic peptide (BNP) and creatinine] and transthoracic echocardiography. The primary endpoint was a combined event of all-cause mortality and graft rejection. RESULTS: In 277 patients (aged 48.6 ± 12.5 years) followed for a median of 38.7 [26.8-45.0] months, there were 35 (12.6%) patients had adverse events including 20 deaths and 15 rejections. EF1 was negatively associated with BNP (ß = -0.220, p < 0.001) and was significantly lower in patients with events compared to those without. EF1 had the largest area under the curve in ROC analysis compared to other measures. An optimal cut-off value of 25.8% for EF1 had a sensitivity of 96.3% and a specificity of 97.1% for prediction of events. EF1 was the most powerful predictor of events with hazard ratio per 1% change in EF1: 0.628 (95%CI: 0.555-0.710, p < 0.001) after adjustment for left ventricular ejection fraction and global longitudinal strain. CONCLUSIONS: Early left ventricular systolic function as measured by EF1 is a powerful predictor of adverse outcomes after heart transplant. EF1 may be useful in risk stratification and management of heart transplant recipients.

Biventricular longitudinal strain as a predictor of functional improvement after D-shant device implantation in patients with heart failure.

Background: The creation of an atrial shunt is a novel approach for the management of heart failure (HF), and there is a need for advanced methods for detection of cardiac function response to an interatrial shunt device. Ventricular longitudinal strain is a more sensitive marker of cardiac function than conventional echocardiographic parameters, but data on the value of longitudinal strain as a predictor of improvement in cardiac function after implantation of an interatrial shunt device are scarce. We aimed to investigate the exploratory efficacy of the D-Shant device for interatrial shunting in treating heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), and to explore the predictive value of biventricular longitudinal strain for functional improvement in such patients. Methods: A total of 34 patients were enrolled (25 with HFrEF and 9 with HFpEF). All patients underwent conventional echocardiography and two-dimensional speckle tracking echocardiogram (2D-STE) at baseline and 6 months after implantation of a D-Shant device (WeiKe Medical Inc., WuHan, CN). Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were evaluated by 2D-STE. Results: The D-Shant device was successfully implanted in all cases without periprocedural mortality. At 6-month follow-up, an improvement in New York Heart Association (NYHA) functional class was observed in 20 of 28 patients with HF. Compared with baseline, patients with HFrEF showed significant reduced left atrial volume index (LAVI) and increased right atrial (RA) dimensions, as well as improved LVGLS and RVFWLS, at 6-month follow-up. Despite reduction in LAVI and increase in RA dimensions, improvements in biventricular longitudinal strain did not occur in HFpEF patients. Multivariate logistic regression demonstrated that LVGLS [odds ratio (OR): 5.930; 95% CI: 1.463-24.038; P = 0.013] and RVFWLS (OR: 4.852; 95% CI: 1.372-17.159; P = 0.014) were predictive of improvement in NYHA functional class after D-Shant device implantation. Conclusion: Improvements in clinical and functional status are observed in patients with HF 6 months after implantation of a D-Shant device. Preoperative biventricular longitudinal strain is predictive of improvement in NYHA functional class and may be helpful to identify patients who will experience better outcomes following implantation of an interatrial shunt device.

Granzyme B-responsive fluorescent probe for non-invasive early diagnosis of transplant rejection.

Allograft rejection has always been a major obstacle in organ transplantation. The current clinical diagnostic gold standard for allograft rejection is an invasive biopsy. However, biopsy has some limitations, such as sampling errors, risk of serious complications, and high cost. In this study, we have rationally developed an activatable fluorescent probe CYGB for imaging of granzyme B, which is a biomarker released by CD8+T cells attacking the graft. Moreover, the ability of CYGB to detect rejection early in mouse heart and skin transplantation models was evaluated. The probe CYGB consists of a caged hemicyanine-based fluorophore and a GzmB-specifically cleaved peptide substrate linked via a self-immolating spacer, p-aminobenzyl alcohol. Endogenous GzmB in CD8+ T cells specifically activated the near-infrared fluorescence (NIRF) signal of CYGB. In vivo imaging in mice skin and heart graft models, showed that CYGB preferentially accumulates in grafts, enabling early diagnosis of rejection. Moreover, CYGB enables non-invasive assessment of the level of immunosuppression in allogeneic mice treated with FK506. This study provides an alternative method for monitoring the status of allografts without biopsy.

Targeted microRNA delivery by lipid nanoparticles and gas vesicle-assisted ultrasound cavitation to treat heart transplant rejection.

Despite exquisite immune response modulation, the extensive application of microRNA therapy in treating heart transplant rejection is still impeded by poor stability and low target efficiency. Here we have developed a low-intensity pulsed ultrasound (LIPUS) cavitation-assisted genetic therapy after executing the heart transplantation (LIGHT) strategy, facilitating microRNA delivery to target tissues through the LIPUS cavitation of gas vesicles (GVs), a class of air-filled protein nanostructures. We prepared antagomir-155 encapsulated liposome nanoparticles to enhance the stability. Then the murine heterotopic transplantation model was established, and antagomir-155 was delivered to murine allografted hearts via the cavitation of GVs agitated by LIPUS, which reinforced the target efficiency while guaranteeing safety owing to the specific acoustic property of GVs. This LIGHT strategy significantly depleted miR-155, upregulating the suppressors of cytokine signaling 1 (SOCS1), leading to reparative polarization of macrophages, decrease of T lymphocytes and reduction of inflammatory factors. Thereby, rejection was attenuated and the allografted heart survival was markedly prolonged. The LIGHT strategy achieves targeted delivery of microRNA with minimal invasiveness and great efficiency, paving the way towards novel ultrasound cavitation-assisted strategies of targeted genetic therapy for heart transplantation rejection.

Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy.

BACKGROUND: Cancer stem cells (CSCs) are crucial for the growth, metastasis, drug resistance, recurrence, and spread of tumors. Napabucasin (NAP) could effectively inhibit CSC, but its mechanism has not been fully explained. Additionally, NAP also has the drawbacks of poor water solubility and low utilization. Therefore, this study not only elaborated the new mechanism of NAP inhibiting CSCs, but also built NAP-loaded nanoprobes using apoptotic tumor-derived microparticles (TMPs) as carriers to combine diagnose and treat of colon cancer and lessen the adverse effects of NAP. RESULTS: The study discovered a new mechanism for NAP inhibiting tumors. NAP, in addition to inhibiting STAT3, may also inhibit STAT1, thereby inhibiting the expression of CD44, and the stemness of colon cancer. N3-TMPs@NAP was successfully synthesized, and it possessed a lipid bilayer with a particle size of 220.13 ± 4.52 nm, as well as strong tumor binding ability and anti-tumor effect in vitro. In static PET/CT imaging studies, the tumor was clearly visible and showed higher uptake after N3-TMPs@NAP injection than after oral administration. The average tumor volume and weight of the N3-TMPs@NAP group on day 14 of the treatment studies were computed to be 270.55 ± 107.59 mm3 and 0.30 ± 0.12 g, respectively. These values were significantly lower than those of the other groups. Additionally, N3-TMPs@NAP might prevent colon cancer from spreading to the liver. Furthermore, due to TMPs' stimulation of innate immunity, N3-TMPs@NAP might stimulate anti-tumor. CONCLUSIONS: As a combined diagnostic and therapeutic nanoprobe, N3-TMPs@NAP could successfully conduct PET/CT imaging, suppress CSCs, and synergistically stimulate anticancer immune responses. Additionally, this nanoprobe might someday be employed in clinical situations because TMPs for it can be produced from human tissue and NAP has FDA approval.

Engineering goat milk-derived extracellular vesicles for multiple bioimaging-guided and photothermal-enhanced therapy of colon cancer.

Multimodal image-guided photothermal therapy (PTT) has great application potential in cancer treatment due to its advantages of low side effects and good efficacy. There is an urgent need for PTT nanocarriers with high loading efficiency and modified surfaces. Goat milk-derived extracellular vesicles (GMVs) an ideal PTT nanoplatforms due to their anti-inflammatory ability, tumor retention ability, high yield, and high biosafety. This study used GMVs to design a theranostic nanoprobe for positron emission tomography/computer tomography/near-infrared fluorescence (PET/CT/NIRF) imaging and image-guided PTT for colon cancer. The key genes, important biological processes, and important signaling pathways of indocyanine green (ICG)-mediated PTT and N3-GMV@ICG-mediated PTT were analyzed. The nanoprobe triggered anti-tumor immune and inflammation responses to enhance PTT. In addition, the nanoprobe could attenuate PTT-induced inflammation benefiting from the anti-inflammatory efficacy of GMVs. Therefore, our findings conceptually advanced the diagnosis and treatment of colon cancer. We believed that the nanoprobe had broad clinical transformation prospects, and GMVs might be ideal nanocarriers for constructing integrated diagnostic and PTT probes.

Orally Administrable Aggregation-Induced Emission-Based Bionic Probe for Imaging and Ameliorating Dextran Sulfate Sodium-Induced Inflammatory Bowel Diseases.

As macrophage infiltration is significantly related to the progression of inflammatory bowel disease (IBD), monitoring the macrophages is a valuable strategy for IBD diagnosis. However, owing to the harsh physiological environment of the gastrointestinal tract and enzymatic degradation, the development of orally administrable imaging probes for tracking macrophages remains a considerable challenge. Accordingly, herein, an orally administrable aggregation-induced emission biomimetic probe (HBTTPIP/ß-glucan particles [GPs]) is developed for tracing macrophages; HBTTPIP/GPs can diagnose and alleviate dextran sulfate sodium (DSS)-induced colonic inflammation and self-report the treatment efficiency. The fluorophore HBTTPIP can effectively aggregate in GPs, restricting intramolecular rotation and activating the fluorescence of HBTTPIP. After being orally administrated, HBTTPIP/GPs are phagocytosed by intestinal macrophages, which then migrate to colonic lesions, enabling non-invasive monitoring of the severity of IBD via in vivo fluorescence imaging. Notably, oral HBTTPIP/GPs ameliorate DSS-induced IBD by inhibiting the expressions of pro-inflammatory factors and improving colonic mucosal barrier function. Furthermore, these HBTTPIP/GPs realize self-feedback of the therapeutic effects of GPs on DSS-induced colitis. The oral biomimetic probe HBTTPIP/GPs reported herein provide a novel theranostic platform for IBD, integrating non-invasive diagnosis of IBD in situ and the corresponding treatment.

Incremental value of preoperative right ventricular function in predicting moderate to severe acute kidney injury after heart transplantation.

Background: Acute kidney injury (AKI) commonly occurs after heart transplantation (HTx), but its association with preoperative right ventricular (RV) function remains unknown. Consequently, we aimed to determine the predictive value of preoperative RV function for moderate to severe AKI after HTx. Materials and methods: From 1 January 2016 to 31 December 2019, all the consecutive HTx recipients in our center were enrolled and analyzed for the occurrence of postoperative AKI staged by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Conventional RV function parameters, including RV fractional area change (RVFAC) and tricuspid annular plane systolic excursion (TAPSE), were obtained. The primary endpoint was moderate to severe AKI (the KDIGO stage 2 or 3). The secondary endpoints included the impact of AKI on intensive care unit (ICU) mortality, in-hospital mortality, and 1-year mortality. Results: A total of 273 HTx recipients were included in the study. Postoperative AKI occurred in 209 (77%) patients, including 122 (45%) patients in stage 1 AKI, 49 (18%) patients in stage 2 AKI, and 38 (14%) patients in stage 3 AKI. Patients with higher AKI stage had lower baseline estimated glomerular filtration rate (eGFR), more frequent diabetes, higher right atrial pressure (RAP), longer cardiopulmonary bypass (CPB) duration, more perioperative red blood cell (RBC) transfusions, and worse preoperative RV function. A multivariate logistic regression model incorporating previous diabetes mellitus [odds ratio (OR): 2.21; 95% CI: 1.06-4.61; P = 0.035], baseline eGFR (OR: 0.99; 95% CI: 0.97-0.10; P = 0.037), RAP (OR: 1.05; 95% CI: 1.00-1.10; P = 0.041), perioperative RBC (OR: 1.18; 95% CI: 1.08-1.28; P < 0.001), and TAPSE (OR: 0.84; 95% CI: 0.79-0.91; P < 0.001) was established to diagnose moderate to severe AKI more accurately [the area under the curve (AUC) = 79.8%; Akaike information criterion: 274]. Conclusion: Preoperative RV function parameters provide additional predicting value over clinical and hemodynamic parameters, which are imperative for risk stratification in patients with HTx at higher risk of AKI.

Evaluation of Right Ventricular Myocardial Mechanics by 2- and 3-Dimensional Speckle-Tracking Echocardiography in Patients With an Ischemic or Non-ischemic Etiology of End-Stage Heart Failure.

Background: The aims of our study were (1) to assess the right ventricular (RV) myocardial mechanics by two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) in patients with an ischemic or non-ischemic etiology of end-stage heart failure (HF) and (2) to explore which RV index evaluated by 2D- and 3D-STE was the most powerful indicator for identifying the ischemic and non-ischemic etiologies of end-stage HF. Methods: A total of 96 patients with left ventricular ejection fraction (LVEF) < 30% were enrolled in our study: 42 patients (mean age, 52 ± 10 years; 9.5% female) with ischemic cardiomyopathy and 54 patients (mean age, 46 ± 14 years; 16.7% female) with non-ischemic cardiomyopathy. A total of 45 healthy subjects (mean age, 46 ± 13 years; 24.4% female) served as controls. The longitudinal strain of the RV free wall (RVFWLS) was determined by both 2D- and 3D-STE. Results: Compared to controls, patients with an ischemic or non-ischemic etiology of end-stage HF had lower 2D-RVFWLS, 3D-RVFWLS and RV ejection fraction (RVEF) values (P < 0.05). Patients with non-ischemic cardiomyopathies (NICMs) had significantly lower 3D-RVFWLS and RVEF values than in those with ischemic cardiomyopathies (ICMs), whereas 2D-RVFWLS and conventional RV function parameters did not differ between the two subgroups. RVEF was highly related to 3D-RVFWLS (r = 0.72, P < 0.001), modestly related to 2D-RVFWLS (r = 0.51, P < 0.001), and weakly related to conventional RV function indices (r = -0.26 to 0.46, P < 0.05). Receiver operating characteristic curve analysis revealed that the optimal 3D-RVFWLS cut-off value to distinguish NICM from ICM patients was -14.78% (area under the curve: 0.73, P < 0.001), while 2D-RVFWLS and conventional RV echocardiographic parameters did not. Conclusion: Our study demonstrated the superiority of 3D-RVFWLS over 2D-RVFWLS and conventional RV function indices in identifying the ischemic and non-ischemic etiologies of end-stage HF. These findings support the idea that 3D-RVFWLS may be a promising non-invasive imaging marker for distinguishing NICM from ICM.

Left Heart Chamber Volumetric Assessment by Automated Three-Dimensional Echocardiography in Heart Transplant Recipients.

Background: Recently, a new automated software (Heart Model) was developed to obtain three-dimensional (3D) left heart chamber volumes. The aim of this study was to verify the feasibility and accuracy of the automated 3D echocardiographic algorithm in heart transplant (HTx) patients. Conventional manual 3D transthoracic echocardiographic (TTE) tracings and cardiac magnetic resonance (CMR) images were used as a reference for comparison. Methods: This study enrolled 103 healthy HTx patients prospectively. In protocol 1, left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), left atrial max volume (LAVmax), LA minimum volume (LAVmin) and LV ejection fraction (LVEF) were obtained using the automated 3D echocardiography (3DE) and compared with corresponding values obtained through the manual 3DE. In protocol 2, 28 patients' automated 3DE measurements were compared with CMR reference values. The impacts of contour edit and surgical technique were also tested. Results: Heart Model was feasible in 97.1% of the data sets. In protocol 1, there was strong correlation between 3DE and manual 3DE for all the parameters (r = 0.77 to 0.96, p<0.01). Compared to values obtained through manual measurements, LV volumes and LVEF were overestimated by the automated algorithm and LA volumes were underestimated. All the biases were small except for that of LAVmin. After contour adjustment, the biases reduced and all the limits of agreement were clinically acceptable. In protocol 2, the correlations for LV and LA volumes were strong between automated 3DE with contour edit and CMR (r = 0.74 to 0.93, p<0.01) but correlation for LVEF remained moderate (r = 0.65, p < 0.01). Automated 3DE overestimated LV volumes but underestimated LVEF and LA volumes compared with CMR. The limits of agreement were clinically acceptable only for LVEDV and LAVmax. Conclusion: Simultaneous quantification of left heart volumes and LVEF with the automated Heart Model program is rapid, feasible and to a great degree it is accurate in HTx recipients. Nevertheless, only LVEDV and LAVmax measured by automated 3DE with contour edit seem applicable for clinical practice when compared with CMR. Automated 3DE for HTx recipients is a worthy attempt, though further verification and optimization are needed.

Erratum: Myocardium-targeted transplantation of PHD2 shRNA-modified bone mesenchymal stem cells through ultrasound-targeted microbubble destruction protects the heart from acute myocardial infarction: Erratum.

[This corrects the article DOI: 10.7150/thno.43233.].

Feasibility, Reproducibility, and Prognostic Value of Fully Automated Measurement of Right Ventricular Longitudinal Strain.

BACKGROUND: Right ventricular free wall longitudinal strain (RVFWLS) carries important diagnostic and prognostic significance in a variety of clinical settings, but its measurement is time consuming and operator dependent, limiting its value in routine clinical practice. Automated RVFWLS measurements can overcome these limitations. The purpose of this study was to determine the feasibility, reproducibility, and prognostic implications of automated RVFWLS compared with manual assessment of RVFWLS. METHODS: A total of 206 patients with a wide range of right ventricular (RV) function were retrospectively selected for this study. Fully automated (Auto-Strain), semiautomated (automated with editing), and manual (standard manual assessment) RVFWLS were measured using two-dimensional speckle-tracking echocardiography in the same RV-focused apical four-chamber view. RV ejection fraction (RVEF) was measured using three-dimensional echocardiography. Abnormal RV systolic function was defined as RVEF < 45%. Agreement for RVFWLS measurements among the three different methods was based on a combination of Pearson correlation, Bland-Altman analyses, and coefficients of variation (CVs). RESULTS: Automated RVFWLS measurements were feasible in 204 subjects (99%). Automated (8 ± 1 sec/patient) and semiautomated (50 ± 10 sec/patient) assessments had shorter analysis times compared with manual measurement (103 ± 25 sec/patient, P < .001 for both). Semiautomated RVFWLS had a stronger correlation with manual RVFWLS than automated RVFWLS (r = 0.850 vs r = 0.708, P < .001). Semiautomated RVFWLS had smaller biases, narrower limits of agreement (LOA), and lower CVs against manual assessment in comparison with the fully automated method in the whole study population (bias of 0.62 and 1.15, LOA of 6.54 and 10.50, and CVs of 9.3% and 16.9%, respectively), in the subgroup with RVEF < 45% (bias of 0.81 and 1.43, LOA of 6.32 and 10.42, and CVs of 10.2% and 18.6%, respectively), and in those with RVEF ≥ 45% (bias of 0.34 and 0.73, LOA of 6.86 and 10.63, and CVs of 8.0% and 14.5%, respectively). Seventy-six patients experienced adverse cardiovascular events during a median follow-up period of 26 months. Fully automated, semiautomated, and manual RVFWLS were associated with poor outcomes. The prognostic implications of fully automated RVFWLS were inferior to those of semiautomated and manual RVFWLS. Three RVFWLS measurements were highly reproducible. CONCLUSIONS: Both fully automated and semiautomated RVFWLS provide rapid and reproducible assessments of RV function and carry important prognostic implication. Moreover, the semiautomated approach performs better than the fully automated method. Therefore, semiautomated RVFWLS can provide a better balance between feasibility and clinical significance and displays potential for clinical application.

Biogenic Gas Vesicles for Ultrasound Imaging and Targeted Therapeutics.

Ultrasound is not only the most widely used medical imaging mode for diagnostics owing to its real-time, non-radiation, portable and low-cost merits, but also a promising targeted drug/gene delivery technique by producing a series of powerful bioeffects. The development of micron-sized or nanometer-sized ultrasound agents or delivery carriers further makes ultrasound a distinctive modality in accurate diagnosis and effective treatment. In this review, we introduce one kind of unique biogenic gas-filled protein nanostructures called gas vesicles, which present some unique characteristics beyond the conventional microbubbles. Gas vesicles can not only serve as ultrasound contrast agent with innovative imaging methods such as cross-amplitude modulation harmonic imaging, but also can further be adjusted and optimized via genetic engineered techniques. Moreover, they could not only serve as acoustic gene reporters, acoustic biosensors to monitor the cell metabolism, but also serve as cavitation nuclei and drug carrier for therapeutic purpose. We focus on the latest development and applications in the area of ultrasound imaging and targeted therapeutics, and also give a brief introduction to the corresponding mechanisms. In summary, these biogenic gas vesicles show some advantages over conventional MBs that deserve making more efforts to promote their development.

Association Between 2D- and 3D-Speckle-Tracking Longitudinal Strain and Cardiovascular Magnetic Resonance Evidence of Diffuse Myocardial Fibrosis in Heart Transplant Recipients.

Objective: This study aimed to: (1) evaluate the association between myocardial fibrosis (MF) quantified by extracellular volume fraction (ECV) and myocardial strain measured by two-dimensional (2D)- and three-dimensional speckle-tracking echocardiography (3D-STE) and (2) further investigate which strain parameter measured by 2D- and 3D-STE is the more robust predictor of MF in heart transplant (HT) recipients. Methods: A total of 40 patients with HT and 20 healthy controls were prospectively enrolled. Left ventricular (LV)-global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured by 2D- and 3D-STE. LV diffuse MF was defined by cardiovascular magnetic resonance (CMR)-ECV. Results: The HT recipients had a significantly higher native T1 and ECV than healthy controls (1043.8 ± 34.0 vs. 999.7 ± 19.7 ms, p < 0.001; 26.6 ± 2.7 vs. 24.3 ± 1.8%, p = 0.02). The 3D- and 2D-STE-LVGLS and LVGCS were lower (p < 0.005) in the HT recipients than in healthy controls. ECV showed a moderate correlation with 2D-LVGLS (r = 0.53, p = 0.002) and 3D-LVGLS (r = 0.60, p < 0.001), but it was not correlated with 2D or 3D-LVGCS, or LVGRS. Furthermore, 3D-LVGLS and 2D-LVGLS had a similar correlation with CMR-ECV (r = 0.60 vs. 0.53, p = 0.670). A separate stepwise multivariate linear analysis showed that both the 2D-LVGLS (ß = 0.39, p = 0.019) and 3D-LVGLS (ß = 0.54, p < 0.001) were independently associated with CMR-ECV. Conclusion: CMR marker of diffuse MF was present in asymptomatic patients with HT and appeared to be associated with decreased myocardial strain by echocardiography. Both the 2D- and 3D-LVGLS were independently correlated with diffuse LVMF, which may provide an alternative non-invasive tool for monitoring the development of adverse fibrotic remodeling during the follow-up of HT recipients.

First aggregation-induced emission-active probe for species-specific detection of ß-galactosidase.

Sensitive detection of ß-galactosidase (ß-gal) is of great significance for early diagnosis of ovarian cancer. Fluorescent probes for detecting ß-gal have received great interest due to the non-invasiveness, excellent sensitivity, high temporal, and superior spatial resolution. However, most reported fluorescent sensors for ß-gal suffer from aggregation caused quenching effect when accumulated, and cannot discriminate ß-gal from other species, especially, Escherichia coliß-gal. Herein, we report the first aggregation-induced emission (AIE)-active fluorescent probe HBTTPAG, which achieves species-selective detection of ß-gal. Probe HBTTPAG can discriminate Aspergillus oryzae ß-gal from Escherichia coliß-gal, with high sensitivity (detection limit of 3.7 × 10-3 UmL-1), superior selectivity and low cytotoxicity. Furthermore, HBTTPAG is utilized to visualize endogenous ß-gal in lysosomes of SKOV-3 cells, as well as to detect ß-gal activity in ovarian cancer tissues. Notably, owing to the AIE-active, HBTTPAG realizes long-term (12 h) tracking ß-gal in ovarian cancer cells. This work provides a promising method for species-selective detection of ß-gal in preclinical.