Phase-pure 2D tin halide perovskite thin flakes for stable lasing.

Ruddlesden-Popper tin halide perovskites are a class of two-dimensional (2D) semiconductors with exceptional optoelectronic properties, high carrier mobility, and low toxicity. However, the synthesis of phase-pure 2D tin perovskites is still challenging, and the fundamental understanding of their optoelectronic properties is deficient compared to their lead counterparts. Here, we report the synthesis of a series of 2D tin perovskite bulk crystals with high phase purity via a mixed-solvent strategy. By engineering the quantum-well thickness (related to n value) and organic ligands, the optoelectronic properties, including photoluminescence emission, exciton-phonon coupling strength, and exciton binding energy, exhibit a wide tunability. In addition, these 2D tin perovskites exhibited excellent lasing performance. Both high-n value tin perovskite (n > 1) and n = 1 tin perovskite thin flakes were successfully optically pumped to lase. Furthermore, the lasing from 2D tin perovskites could be maintained up to room temperature. Our findings highlight the tremendous potential of 2D tin perovskites as promising candidates for high-performance lasers.

Microbial metabolites in chronic heart failure and its common comorbidities.

This study aimed to identify microbial signatures that contribute to the shared etiologies between chronic heart failure (CHF), type 2 diabetes, and chronic kidney disease. The serum levels of 151 microbial metabolites were measured in 260 individuals from the Risk Evaluation and Management of heart failure cohort, and it was found that those metabolites varied by an order of 105 fold. Out of 96 metabolites associated with the three cardiometabolic diseases, most were validated in two geographically independent cohorts. In all three cohorts, 16 metabolites including imidazole propionate (ImP) consistently showed significant differences. Notably, baseline ImP levels were three times higher in the Chinese compared with the Swedish cohorts and increased by 1.1-1.6 fold with each additional CHF comorbidity in the Chinese population. Cellular experiments further supported a causal link between ImP and distinct CHF relevant phenotypes. Additionally, key microbial metabolite-based risk scores were superior in CHF prognosis than the traditional Framingham or Get with the Guidelines-Heart Failure risk scores. Interactive visualization of these specific metabolite-disease links is available on our omics data server (https://omicsdata.org/Apps/REM-HF/).

Polymeric coating lubricates nanocontainers to escape macrophage uptake for bioreceptor recognition.

Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through in vitro and in vivo studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.

Relationship between different air pollutants and total and cause-specific emergency ambulance dispatches in Shanghai, China.

OBJECTIVE: Air pollutants play a crucial role in human health and disease. Emergency ambulance dispatch data have excellent potential for public and environmental health research. This study aimed at investigating the impact of short-term exposure to air pollutants on the emergency ambulance dispatches. METHODS: We used data on emergency ambulance dispatches in Shanghai Municipality, China, from April 1, 2016 to December 31, 2017. The association of the daily emergency ambulance dispatches with air pollutants including PM2.5 (particles ≤ 2.5 µm in aerodynamic diameter), PM10, O3, NO2 and SO2 was analyzed with the use of time-series analyses. RESULTS: A total of 310,825 emergency ambulance dispatches for acute illness occurred in Shanghai during the study period. An increase in PM2.5 by 10 µg/m3 at lag1 and lag2 was shown to increase the risk of emergency ambulance dispatches (RR for lag1 = 1.05, 95% CI 1.00-1.11, RR for lag2 = 1.07, 95% CI 1.01-1.12). PM10, NO2, and SO2 also showed significant associations with emergency ambulance dispatches in single-pollutant models. Cause-specific analyses showed an elevation in PM2.5 by 10 µg/m3 was associated with an increased risk of emergency ambulance dispatches related to respiratory diseases on the current day (lag0, RR 1.17, 95% CI 1.01-1.33), while the impact on emergency ambulance dispatches related to other diseases presented 1-3 days later. The other pollutants have the similar trend. CONCLUSIONS: Our findings show a strong relationship between ambient air pollutants and emergency ambulance dispatches. Our study contributes to the growing body of evidence describing the adverse health effects of ambient air pollution and will benefit ambulance services for early warning and effective ambulatory planning.

Retraction: Development of functional hydrogels for heart failure.

Retraction for 'Development of functional hydrogels for heart failure' by Yanxin Han et al., J. Mater. Chem. B, 2019, 7, 1563-1580, DOI: .

Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure.

ABSTRACT: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.

Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional Changes in Ischemia-Induced Heart Failure via the BMI1-p15-Rb Signalling Pathway.

BACKGROUND: Cardiac fibrosis is an important cause of heart failure (HF) after myocardial infarction (MI). Cyclin-dependent kinase inhibitor 2b (CDKN2b) regulates the cell cycle by encoding the p15 protein and participates in the development of various tumours. However, the role of CDKN2b/p15 in cardiac fibrosis and HF after MI remains unclear. METHODS: Lentivirus was used to induce the silence and overexpression of CDKN2b. Cardiac function was detected with the use of echocardiography. Immunohistochemistry, immunofluorescence, Western blotting, Cell Counting Kit 8, and wound healing assay were used to illustrate the potential mechanism associated with CDKN2b. RESULTS: The p15 protein expression was significantly down-regulated in both human and mouse failing hearts. Cardiac down-regulation of CDKN2b promoted myocardial fibrosis and worsened cardiac function in MI mice, while systemic CDKN2b silencing induced diastolic dysfunction in vivo. In addition, cardiac overexpression of CDKN2b ameliorated cardiac fibrosis and improved cardiac function in MI mice. Mechanistically, silencing CDKN2b gene enhanced the phosphorylation of retinoblastoma (Rb) protein and reinforced the migration and proliferation capabilities of cardiac fibroblasts. B Lymphoma Mo-MLV insertion region 1 homolog (BMI1) was up-regulated in failing heart and inversely regulated the expression of CDKN2b/p15 and the phosphorylation of Rb protein. The BMI1-p15-Rb signalling pathway is a potential mechanism of ischemia-induced cardiac fibrosis and HF. CONCLUSIONS: Cardiac fibrosis and heart function could be worsened by the down-regulation and relieved by the up-regulation of CDKN2b/p15 in ischemia-induced HF via regulating the proliferation and migration capabilities of cardiac fibroblasts. These effects could be partially explained by the regulation of the BMI1-p15-Rb signalling pathway.

Effects of Cardiomyocyte-Specific Deletion of STAT3-A Murine Model of Heart Failure With Preserved Ejection Fraction.

Aims: There is a high incidence of heart failure with preserved ejection fraction (HFpEF), but the options of treatment are limited. A new animal model of HFpEF is urgently needed for in-depth research on HFpEF. Signal transducer and activator of transcription 3 (STAT3) may affect the passive stiffness of myocardium, which determines cardiac diastolic function. We hypothesized that cardiomyocyte-specific deletion of STAT3 increases cardiac passive stiffness, which results the murine features of HFpEF. Methods and Results: Cardiomyocyte-specific deletion of STAT3 (STAT3cKO) mice was generated by the Cre/FLOXp method. The STAT3cKO mice showed heavier cardiac fibrosis and cardiac hypertrophy comparing with wild-type (WT) mice. Furthermore, STAT3cKO mice showed increased serum brain natriuretic peptide (BNP) level, and growth stimulation expressed gene 2 (ST2) level. Other indicators reflecting cardiac passive stiffness and diastolic function, including end diastolic pressure volume relation, MV A value, MV E value, E/A and E/E' had different fold changes. All these changes were accompanied by decreasing levels of protein kinase G (PKG). Bioinformatic analysis of STAT3cKO mice hearts suggested cGMP-PKG signaling pathway might participate in the pathogenesis of HFpEF by means of adjusting different biological functions. Conclusions: Cardiomyocyte-specific deletion of STAT3 results in a murine HFpEF model which imitates the clinical characteristics partly by affecting cardiac PKG levels. Better understanding of the factors influencing HFpEF may finally provided innovative therapies.

Reference-frame-independent measurement-device-independent quantum key distribution with mismatched-basis statistics.

The source flaw associated with the basis vector in the reference-frame-independent measurement-device-independent quantum key distribution (RFI-MDI-QKD) has not been systematically studied. As a result, it is often assumed that bit error is equal to phase error, which is not theoretically rigorous. Here, we propose a postprocessing method to estimate the phase error rate from the discarded mismatched-basis statistics, where the qubit source does not need to be characterized in detail. The source flaw in the basis vector of the RFI-MDI-QKD protocol can thus be corrected using this method. The numerical simulation results clearly demonstrate that the RFI-MDI-QKD protocol with uncharacterized sources is also insensitive to the misalignment of the reference frame.

Ibutilide Reduces Ventricular Defibrillation Threshold and Organizes Ventricular Fibrillation Activation in Canine Heart Failure Model.

PURPOSE: To compare the effects of class III antiarrhythmic agents (amiodarone vs. ibutilide) on ventricular fibrillation (VF) and hemodynamic status in a canine heart failure (HF) model. METHODS: A total of 12 beagles were used to establish the HF model by rapid pacing for 4 consecutive weeks. These canines were randomly divided into two groups based on the administration of ibutilide and amiodarone. A 12 × 12 unipolar electrode plaque was used for ventricular epicardial mapping, and a 6-electrode plunge needle was inserted for ventricular transmural mapping. The restitution curve was estimated from activation recovery intervals (ARIs) by pacing from the plaque electrodes before and after drug administration. The defibrillation threshold (DFT) and VF activation patterns, including the activation rate, cycle length (VF-CL) and the transmural dispersion of the activation rate, were evaluated and the hemodynamic parameters were mearsured and compared before and after drug administration. RESULTS: Compared to HF baseline, ibutilide administration has markedly decreased the DFT by 28% (18 ± 2 J vs. 13 ± 2.7 J, P < 0.01) without affecting the canine's hemodynamics (mean arterial pressure 91 ± 15 mmHg vs. 92 ± 17 mmHg, P > 0.05). Furthermore, VF activation pattern became more organized, and spontaneous termination was observed only after ibutilide administration. Conversely, amiodarone has significantly compromised the hemodynamic status (mean arterial pressure 92 ± 6.1 mmHg vs. 52 ± 11.6 mmHg, P < 0.05), but did not alter the DFT (17 ± 2.3 J vs. 16 ± 2.0 J, P > 0.05). Compared to pre-medication, both ibutilide and amiodarone have significantly prolonged the VERP (178 ± 9.6 ms vs. 208 ± 8.9 ms, P < 0.05; 185 ± 10.5 ms vs. 202 ± 7.5 ms, P < 0.05, respectively) and reduced the dispersion of refractoriness, the maximal slope of restitution curve, and the epicardial dispersion during pacing. Additionally, both drugs have significantly increased the VF-CL and reduced the transmural dispersion of the VF activation rate. CONCLUSIONS: Ibutilide had potential antifibrillatory properties, which was shown by decreasing the DFT and organizing the VF activation in HF, and with no apparent impact on the hemodynamic status. In contrast, intravenous amiodarone administration demonstrated prominent negative effects on the hemodynamic status possibly by affecting the myocardial contractility before and after defibrillation but did not alter the DFT.

Effect of HIF-1α/miR-10b-5p/PTEN on Hypoxia-Induced Cardiomyocyte Apoptosis.

Background Few reports have addressed the mechanism by which microRNA miR-10b-5p regulates post-myocardial infarction (post-MI) cardiomyocyte apoptosis under hypoxic conditions. Methods and Results C57BL/6 mice underwent surgical ligation of the left anterior descending artery to create an MI or ischemia/reperfusion animal model. The expression of miR-10b-5p, PTEN (phosphatase and tensin homolog), and HIF-1α (hypoxia-inducible factor 1α) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR-10b-5p, overexpression lentiviruses were made in the areas surrounding the MI sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR-10b-5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and PTEN expression. Meanwhile, PTEN as a target of miR-10b-5p was verified via luciferase reporter gene assays. Cotransfection of miR-10b-5 and PTEN verified the relationship between miR-10b-5 and PTEN. Under hypoxic stress, the expression of HIF-1α and miR-10b-5p was examined. The results showed that miR-10b-5p expression was markedly reduced in the infarct border zone. Overexpression of miR-10b-5p in the murine model of MI significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR-10b-5p in vitro antagonized hypoxia-induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis-related gene PTEN, but overexpression of PTEN weakened these effects. We also found that hypoxia-induced accumulation of HIF-1α resulted in decreased expression of miR-10b-5p. Interfering with the activation of the HIF-1α signaling pathway promoted Pri-miR-10b and miR-10b-5p expression and inhibited PTEN expression. Conclusions MicroRNA miR-10b-5p antagonizes hypoxia-induced cardiomyocyte apoptosis, indicating that miR-10b-5p may serve as a potential future clinical target for the treatment of MI.

siPRDX2-elevated DNM3 inhibits the proliferation and metastasis of colon cancer cells via AKT signaling pathway.

Purpose: We have previously reported that PRDX2 plays an oncogenic role in colon cancer. In this study, the mRNA expression profile of PRDX2 in HCT116 cells was investigated. Furthermore, we selected Dynamin 3 (DNM3), which is up-regulated by siPRDX2, to investigate its expression pattern and functions in colon cancer. Patients and methods: PRDX2 siRNA was transfected into HCT116 cells and the mRNA profile was tested by RNA-Sequencing. The expression of interest proteins was determined by Western blot. DNM3 expression in colon cancer tissues and para-carcinoma tissues was evaluated by Western blot and immunohistochemistry assays. Full-length cDNA of DNM3 was cloned into pcDNA3.1 and introduced into HCT116 and HT29 cells. Cell proliferation was tested by CCK-8 and colony formation assays. Cell invasion and migration were tested by transwell assays. Gelatin zymography was utilized for detection of MMP9 activity. Cell apoptosis was investigated with Annexin V/PI staining and flow cytometry and visualized with Hoechst/PI staining assay. All statistical analysis was performed with SPSS 17.0 software. Results: PRDX2 knockdown led to 210 up-regulated genes and 16 down-regulated genes in HCT116 cells. We also found that DNM3 expression was up-regulated following PRDX2 silencing in HCT116 and HT29 cells. In colon cancer patients, DNM3 was down-regulated and showed a significant association with pathologic grading. DNM3 overexpression inhibited cell proliferation and induced apoptosis in HCT116 and HT29 cells. Cell migration and invasion were also down-regulated in DNM3 overexpressing colon cancer cells, which might be due to the inhibition of MMP9 proteolytic activities. After thorough investigation of the potential mechanism involved, we hypothesized that DNM3 overexpression induced activation of the mitochondrial apoptosis pathway and inhibition of the AKT pathway. Conclusion: These data suggest that DNM3 is down-regulated in colon cancer, serving as a tumor suppressor. Our study provides new sights into the prognostic value and therapeutic application of DNM3 in colon cancer.

MicroRNA-19b-1 reverses ischaemia-induced heart failure by inhibiting cardiomyocyte apoptosis and targeting Bcl2 l11/BIM.

Ischaemia induces cardiac apoptosis and leads to a loss of cardiac function and heart failure after myocardial infarction. MicroRNA-19b-1 (miR-19b-1), a key member of the miR-17/92 cluster, plays crucial roles in inhibiting apoptosis. However, the role of miR-19b-1 in ischaemia-induced heart failure remains unknown. In this study, ischaemia resulted in cardiac apoptosis and the suppression of miR-19b-1 expression, whereas miR-19b-1 overexpression inhibited ischaemia-induced cardiac apoptosis in vivo and in vitro. Moreover, miR-19b-1 not only attenuated the infarct size but also ameliorated heart failure after myocardial infarction, including the changes in the left ventricular ejection fraction and volume load. Mechanically, miR-19-1 targeted and downregulated the mRNA and protein expression of Bcl2l11/BIM, a pro-apoptotic gene of the Bcl-2 family. Together, these results revealed an essential role of miR-19b-1 in ischaemia-induced heart failure.

Development of functional hydrogels for heart failure.

Although some advanced treatments of heart failure (HF) have experienced great development in recent decades, morbidity and mortality associated with HF have not improved significantly. Hydrogels have some unique advantages for the delivery and controlled release of bioactive molecules, drugs, and cells, which can directly affect the heart locally. Many studies have shown that hydrogels represent a new approach for the treatment of HF. In this review, we present a current perspective of hydrogel-based approaches for cardiac tissue engineering and myocardial regeneration in ischemia-induced HF, with an emphasis on functional studies, translation, and clinical advancements.

BMI1 promotes cardiac fibrosis in ischemia-induced heart failure via the PTEN-PI3K/Akt-mTOR signaling pathway.

Cardiac fibrosis has been known to play an important role in the etiology of heart failure after myocardial infarction (MI). B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a transcriptional repressor, is important for fibrogenesis in the kidneys. However, the effect of BMI1 on ischemia-induced cardiac fibrosis remains unclear. BMI1 was strongly expressed in the infarct region 1 wk post-MI in mice and was detected by Western blot and histological analyses. Lentivirus-mediated overexpression of BMI1 significantly promoted cardiac fibrosis, worsened cardiac function 4 wk after the intervention in vivo, and enhanced the proliferation and migration capabilities of fibroblasts in vitro , whereas downregulation of BMI1 decreased cardiac fibrosis and prevented cardiac dysfunction in mice 4 wk post-MI in vivo. Furthermore, upregulated BMI1 inhibited phosphatase and tensin homolog (PTEN) expression, enhanced phosphatidylinositol 3-kinase (PI3K) expression, and increased the phosphorylation level of Akt and mammalian target of rapamycin (mTOR) in mice 4 wk after lentiviral infection, which was in accordance with the changes seen in their infarcted myocardial tissues. At the same time, the effects of BMI1 on cardiac fibroblasts were reversed in vitro when these cells were exposed to NVP-BEZ235, a dual-kinase (PI3K/mTOR) inhibitor. In conclusion, BMI1 is associated with cardiac fibrosis and dysfunction after MI by regulating cardiac fibroblast proliferation and migration, and these effects could be partially explained by the regulation of the PTEN-PI3K/Akt-mTOR pathway. NEW & NOTEWORTHY Ischemia-induced B lymphoma Mo-MLV insertion region 1 homolog (BMI1) significantly promoted cardiac fibrosis and worsened cardiac function in vivo, whereas downregulation of BMI1 decreased cardiac fibrosis and prevented cardiac dysfunction in myocardial infarcted mice. BMI1 also enhanced proliferation and migration capabilities of fibroblasts in vitro; these effects were reversed by NVP-BEZ235. Effects of BMI1 on cardiac fibrosis could be partially explained by regulation of the phosphatase and tensin homolog-phosphatidylinositol 3-kinase/Akt-mammalian target of rapamycin pathway.

Impact of Pulmonary Vein Anatomy on Long-term Outcome of Cryoballoon Ablation for Atrial Fibrillation.

Variant pulmonary vein anatomy (PVA) has been reported to influence the recurrence of atrial fibrillation (AF) after radiofrequency ablation. However, the effects of PVA on AF in patients undergoing cryoballoon ablation (CBA) remain unknown. The present study aimed to examine the impact of PVA on the long-term outcome of CBA for AF. A total of 78 patients (mean age 60.7±10.9 years, 64.1% males) with symptomatic and drug-refractory paroxysmal AF were enrolled in the study. Left atrium (LA) and PVA acquired at computed tomography angiography (CTA) were reconstructed with CARTO® 3 SYSTEM. Patients were routinely evaluated by 24-hour Holter monitoring following CBA. Cox regression was used to detect the predictors of AF recurrence after CBA. The results showed abnormal PVA in 30 patients (38.5%) and 18 patients (23.1%) had left common PV (LCPV). Electrical pulmonary vein isolation was achieved in all patients. After a mean follow-up of 689.5±103.8 days, it was found that patients with abnormal PVA had similar AF recurrence rate to those with normal PVA (26.7% vs. 25.0%, P=0.54), and there was no significant difference in AF recurrence rate between LCPV patients and non-LCPV patients (33.7% vs. 23.3%, P=0.29). Cox regression analysis showed that AF duration (72.9±9.0 vs. 42.3±43.2 months, HR 1.001; 95%CI 1.003-1.014; P<0.001) and cryo-applications of right-side PVs (3.0±1.6 vs. 4.7±1.7, HR 0.661; 95% CI 0.473-0.925; P=0.016) were independent predictors of freedom from AF, but PVA was not identified as a predictor of long-term success. In conclusion, the variant PVA cannot significantly influence the long-term outcome of AF patients undergoing CBA; longer AF duration and less cryo-applications of right-side PVs are associated with higher AF recurrent rate.

Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

NEW FINDINGS: What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P < 0.01). However, RDN increased the VFT by 13% (135 ± 10 versus 118 ± 7.5 ms, P < 0.05) and decreased the DFT by 27% (30 ± 6.3 versus 21.8 ± 4.7 J, P < 0.05) in the treated hearts compared with the failing hearts. Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1.48 ± 0.2 versus 1.26 ± 0.11, P < 0.05) and decreased the dispersion of ARI by 25% (0.08 ± 0.02 versus 0.06 ± 0.01, P < 0.01) in the treated group compared with the HF group. The findings of this study suggest that RDN can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action on VF in a canine model of pacing-induced HF.

Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines.

BACKGROUND: The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF) canine hearts. METHODS: Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. RESULTS: In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. CONCLUSIONS: A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.

Normal range and genetic analysis of coagulation factor XII in the general Chinese population.

BACKGROUND: It has been reported that the average activity of coagulation factor XII depends on the ethnicity of the population under study but little information is available on Chinese. We here provide an analysis of the range of activities and antigenic levels of factor XII in healthy Han Chinese and correlate the measurements with polymorphisms and mutations in the corresponding gene. METHODS: Plasma samples were obtained from 549 healthy Chinese adults (264 men, 285 women; age 16-79years) undergoing routine check-ups. The samples were subjected to an activated partial thromboplastin time-based factor XII activity assay as well as an enzyme-linked immunosorbent assay. Partial gene sequence analyses were performed in subjects with low factor XII activity and in normal controls. RESULTS: Ninety-five percent of the subjects had factor XII activities between 47% and 160.25%, with no evidence for an influence of sex or age. Among 15 subjects with activity levels ≤47%, we found one novel nonsense and two missense mutations that may lead to dysfunctional proteins. No mutations were found in a selection of subjects with activities above 47%. Interestingly, however, the particular sequence at a known C/T polymorphism at position 46 just upstream of the translational start codon was correlated with factor XII activity. Subjects homozygous for the T allele, which has an allelic frequency of 0.69, showed significantly lower factor XII activities compared to subjects homozygous for the C allele or those heterozygous for C/T. CONCLUSIONS: The survey determined the normal range of factor XII activities in healthy Chinese and identified mutations as well as a biased representation of a polymorphic nucleotide in subjects with abnormally low activities. The results provide an essential basis for the diagnosis of FXII deficiencies in Chinese.

Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus.

Heat stress cognate 70 (Hsc70) is a host protein associated with hepatitis B virus (HBV) replication. The goal of this study was to investigate whether Hsc70 could be an anti-HBV drug target. Our results showed that introducing Hsc70 increased HBV replication in HBV(+) human hepatocytes (HepG2.2.15 cells). The coiled-coil region on Hsc70 (nucleotides 1533 to 1608; amino acids 511 to 536) was the key sequence for HBV replication. Knockdown of Hsc70 expression by RNA interference (RNAi) largely inhibited HBV replication with no cytotoxicity to the host. Using an Hsc70 mRNA screening assay, the natural compound oxymatrine (OMTR) was found to be a selective inhibitor for Hsc70 expression. Then, OMTR was used to investigate the potential of Hsc70 as an anti-HBV drug target. OMTR inhibited Hsc70 mRNA expression by 80% and HBV DNA replication by over 60% without causing cytotoxicity. The anti-HBV effect of OMTR appeared to be mediated by destabilizing Hsc70 mRNA. The half-life (T(1/2)) of Hsc70 mRNA decreased by 50% in OMTR-treated hepatocytes. The Hsc70 mRNA 3'-untranslated-region (UTR) sequence was the element responsible for OMTR's destabilization activity. OMTR suppressed HBV de novo synthesis at the reverse transcription stage from pregenomic RNA (pgRNA) to DNA and was active against either wild-type HBV or strains resistant to lamivudine, adefovir, and entecavir. Therefore, host Hsc70 could be a novel drug target against HBV, and OMTR appears to inhibit HBV replication by destabilizing Hsc70 mRNA. As the target is not a viral protein, OMTR is active for either wild-type HBV or strains resistant to reverse transcriptase (RT) inhibitors.