Search

Abstract Background Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. Methods A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. Results Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10–0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12–0.95]; P = 0.029). Conclusions In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Abstract Background Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. Method and Results From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). Conclusion Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

This study reports on the synthesis, design and evaluation of a novel, interesting type of gradient-side-chain polyphenyl ether anion exchange membranes (AEMs) as the electrolytes for alkali fuel cells. Such membranes were fabricated by co-grafting of quaternized side chains with different lengths onto the polymer backbone. Based on our transmission electron microscopy and small angle X-ray scattering results, the gradient side chain structured AEM can enhance microphase and produce significantly larger ion clusters than that with purely long side chains; this is probably because the gradient side chain structure can possibly reduce the steric hindrance and facilitate cation aggregation during microphase separation. The gradient side chain AEM exhibited enhanced conductivity of hydroxide ions (107.7 mS cm−1 at 80 °C) compared to the uniform-side-chain membrane. It also demonstrated superior alkaline stability, retaining ca. 80% of conductivity and ion exchange capacity after a harsh alkali treatment at 80 °C in 1 M NaOH for 552 hours. Our study preliminarily demonstrates that gradient side chain structure is advantageous over conventional uniform side chains in promoting microphase separation of AEM, and deserves further investigations to optimize the gradient structure for better membrane performance.

Abstract Background Myocardial ischemia-reperfusion (I/R) injury is accompanied by an imbalance in the cardiac autonomic nervous system, characterized by over-activated sympathetic tone and reduced vagal nerve activity. In our preceding study, we pioneered the development of the magnetic vagus nerve stimulation (mVNS) system. This system showcased precise vagus nerve stimulation, demonstrating remarkable effectiveness and safety in treating myocardial infarction. However, it remains uncertain whether mVNS can mitigate myocardial I/R injury and its specific underlying mechanisms. In this study, we utilized a rat model of myocardial I/R injury to delve into the therapeutic potential of mVNS against this type of injury. Results Our findings revealed that mVNS treatment led to a reduction in myocardial infarct size, a decrease in ventricular fibrillation (VF) incidence and a curbing of inflammatory cytokine release. Mechanistically, mVNS demonstrated beneficial effects on myocardial I/R injury by inhibiting NLRP3-mediated pyroptosis through the M2AChR/OGDHL/ROS axis. Conclusions Collectively, these outcomes highlight the promising potential of mVNS as a treatment strategy for myocardial I/R injury.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Background: The relationship between the multivariable apnea prediction (MAP) index and lipid levels was examined using a cross-sectional and retrospective study of National Health and Nutrition Examination Surveys (2015–2018). A total of 3195 participants with MAP scores were included in the analysis. Methods: The MAP index, an algorithm leveraging sleep apnea symptom frequency, body mass index (BMI), age, and sex, estimates the risk of obstructive sleep apnea (OSA). We investigated the associations between the MAP index and lipid profiles—specifically, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) —using weighted linear regression and restricted cubic splines (RCS) analysis. Additionally, mediation analysis was conducted to explore the potential mediating role of physical activity on the link between OSA risk, hyperlipidemia, and cardiovascular mortality. Results: A non-linear relationship was observed between OSA severity and lipid profiles, including elevated levels of TC, increased LDL-C, higher TG, and decreased HDL-C (All p for non-linearity

Abstract Background Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. Methods Records of 1488 patients with stage I‐–III GC and 3327 patients with stage I–III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. Results Patients with stage I–III GC had a significantly higher incidence of LVI/PNI than patients with stage I–III CRC (50.54% vs. 21.91%, p

Ginseng peptide (GP) (100, 200, 400 mg/kg bw) lowered blood glucose levels, explored the relationship between GP and gut microbiota-based hypoglycemic effects. GP significantly reduced fasting blood glucose levels (25.38–13.37 mM), improved insulin resistance (IR) (9.78–5.02), considerably increased liver glycogen content (64.71–97.95 mg/g), glycolytic and gluconeogenesis enzyme activities in T2DM mice, significantly reduced free fatty acids (1.65–0.93 mM), triglycerides (1.55–0.66 mM), total cholesterol (14.75–5.43 mM), and low-density lipoprotein (4.12–2.36 mM) in the serum, significantly increased high-density lipoprotein levels (6.20–17.44 mM) to improve lipid metabolism disorders. According to colonic 16S rDNA sequencing results, GP-H regulated gut microbiota disorders and short chain fatty acid metabolism. Western blot analysis showed that GP could regulate glycogen synthesis, gluconeogenesis, and glucose transport by activating IRS-1/PI3K/Akt and AMPK signaling pathways and improve IR by inhibiting the mitochondrial apoptosis signaling pathway.

Abstract Background Pre-eclampsia (PE) is one of the leading causes of maternal and fetal morbidity/mortality during pregnancy, and alpha-2-macroglobulin (A2M) is associated with inflammatory signaling; however, the pathophysiological mechanism by which A2M is involved in PE development is not yet understood. Methods Human placenta samples, serum, and corresponding clinical data of the participants were collected to study the pathophysiologic mechanism underlying PE. Pregnant Sprague–Dawley rats were intravenously injected with an adenovirus vector carrying A2M via the tail vein on gestational day (GD) 8.5. Human umbilical artery smooth muscle cells (HUASMCs), human umbilical vein endothelial cells (HUVECs), and HTR-8/SVneo cells were transfected with A2M-expressing adenovirus vectors. Results In this study, we demonstrated that A2M levels were significantly increased in PE patient serum, uterine spiral arteries, and feto-placental vasculature. The A2M-overexpression rat model closely mimicked the characteristics of PE (i.e., hypertension in mid-to-late gestation, histological and ultrastructural signs of renal damage, proteinuria, and fetal growth restriction). Compared to the normal group, A2M overexpression significantly enhanced uterine artery vascular resistance and impaired uterine spiral artery remodeling in both pregnant women with early-onset PE and in pregnant rats. We found that A2M overexpression was positively associated with HUASMC proliferation and negatively correlated with cell apoptosis. In addition, the results demonstrated that transforming growth factor beta 1 (TGFβ1) signaling regulated the effects of A2M on vascular muscle cell proliferation described above. Meanwhile, A2M overexpression regressed rat placental vascularization and reduced the expression of angiogenesis-related genes. In addition, A2M overexpression reduced HUVEC migration, filopodia number/length, and tube formation. Furthermore, HIF-1α expression was positively related to A2M, and the secretion of sFLT-1 and PIGF of placental origin was closely related to PE during pregnancy or A2M overexpression in rats. Conclusions Our data showed that gestational A2M overexpression can be considered a contributing factor leading to PE, causing detective uterine spiral artery remodeling and aberrant placental vascularization.

Abstract Background Mesenchymal stromal cells (MSCs) activated with IFN-γ elicit stronger physical effects. Exosomes (Exos) secreted from MSCs show protective effects against myocardial injury. This study aimed to determine whether Exos derived from IFN-γ-treated MSCs exhibit more potent cardioprotective function and the underlying mechanisms. Methods H9c2 cells or human umbilical vein endothelial cells (HUVECs) were treated with Exos isolated from MSCs (Ctrl-Exo) or IFN-γ-primed MSCs (IFN-γ-Exo) under oxygen and glucose deprivation (OGD) conditions in vitro and in vivo in an infarcted rat heart. RNA sequencing was used to identify differentially expressed functional transcription factors (TFs). Quantitative reverse transcription-PCR (qPCR) was used to confirm the upregulated TFs and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay was used to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was determined by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD conditions. Result IFN-γ-Exo accelerated migration and tube-like structure formation and prevented OGD-induced apoptosis in H9c2. Similarly, IFN-γ-Exo treatment caused a decrease in fibrosis, reduced cardiomyocyte apoptosis, and improved cardiac function compared to Ctrl-Exo treatment. MiR-21 was significantly upregulated in IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 could inhibit BTG anti-proliferation factor 2 (BTG2) expressions. BTG2 promoted H9c2 cell apoptosis and reversed the protective effects of miR-21 under OGD conditions. Conclusion IFN-γ-Exo showed enhanced therapeutic efficacy against acute MI, possibly by promoting angiogenesis and reducing apoptosis by upregulating miR-21, which directly targeted BTG2.

Objective: Post-treatment contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes in patients with acute myocardial infarction (AMI). A lower free triiodothyronine (FT3) level predicts a poor prognosis of AMI patients. This study evaluated the effect of plasma FT3 level in predicting CI-AKI and short-term survival among AMI patients. Methods: Coronary arteriography or percutaneous coronary intervention was performed in patients with AMI. A 1:3 propensity score (PS) was used to match patients in the CI-AKI group and the non-CI-AKI group. Results: Of 1480 patients enrolled in the study, 224 (15.1%) patients developed CI-AKI. The FT3 level was lower in CI-AKI patients than in non-CI-AKI patients (3.72 ± 0.88 pmol/L vs 4.01 ± 0.80 pmol/L, P < 0.001). Compared with those at the lowest quartile of FT3, the patients at quartiles 2–4 had a higher risk of CI-AKI respectively (P for trend = 0.005). The risk of CI-AKI increased by 17.7% as FT3 level decreased by one unit after PS-matching analysis (odds ratio: 0.823; 95% CI: 0.685–0.988, P = 0.036). After a median of 31 days of follow-up (interquartile range: 30–35 days), 78 patients died, including 72 cardiogenic deaths and 6 non-cardiogenic deaths, with more deaths in the CI-AKI group than in the non-CI-AKI group (53 vs 25, P < 0.001). Kaplan–Meier survival analysis showed that patients at a lower FT3 quartile achieved a worse survival before and after matching. Conclusion: Lower FT3 may increase the risk of CI-AKI and 1-month mortality in AMI patients.

Abstract Background Patients with ulcerative colitis are at an increased risk of developing colorectal cancer with a prolonged disease course. Many studies have shown that alterations in the immune microenvironment play a key role in ulcerative colitis-associated colorectal cancer. Additionally, competing endogenous RNAs have important functions in immunoregulation, affecting inflammation and tumorigenesis. However, the complexity and behavioral characteristics of the competing endogenous RNA immunoregulatory network in ulcerative colitis-associated colorectal cancer remain unclear. We constructed a competing endogenous RNA immunoregulatory network to discover and validate a novel competing endogenous RNA immunoregulatory axis to provide insight into ulcerative colitis-associated colorectal cancer progression. Methods The competing endogenous RNA immunoregulatory network was constructed using differential expression analysis, weighted gene co-expression network analysis, and immune-related genes. Cmap was used to identify small-molecule drugs with therapeutic potential in ulcerative colitis-associated colorectal cancer. The ulcerative colitis-associated colorectal cancer-related pathways were identified by gene set variation and enrichment analysis. CIBERSORT, single-sample Gene Set Enrichment Analysis, and xCell were used to evaluate the infiltration of immune cells and screen hub immunocytes. The competing endogenous RNA immunoregulatory axis was identified by correlation analysis. Results We identified 130 hub immune genes and constructed a competing endogenous RNA immunoregulatory network consisting of 56 long non-coding RNAs, four microRNAs, and six targeted hub immune genes. Four small-molecule drugs exerted potential therapeutic effects by reversing the expression of hub immune genes. Pathway analysis showed that the NF-κB pathway was significantly enriched. Neutrophils were identified as hub immunocytes, and IL6ST was significantly positively correlated with the neutrophil count. In addition, NEAT1 may serve as a competing endogenous RNA to sponge miR-1-3p and promote IL6ST expression. Conclusions The competing endogenous RNA immunoregulatory axis may regulate neutrophil infiltration, affecting the occurrence of ulcerative colitis-associated colorectal cancer.

Aspartokinase (AK) is synergistically suppressed by Thr and Lys in the Corynebacterium metabolic pathway. Site-directed mutations can significantly improve AK inhibition. Our previous studies confirmed that sites 379 and 380 were important sites affecting enzyme activity, so we further screen the double mutants with excellent enzymatic properties from sites 379 and 380, and discuss the difference of enzyme activity between the double mutants and single mutants. Here, a double mutant, T379L/A380 M, with improved enzyme activity (2.74-fold) was obtained. Enzymatic property experiments showed that the optimum temperature of T379L/A380 M increased from 26 °C (recombinant Escherichia coli; WT-AK) to 45 °C and that the optimal pH decreased from 8.0 (WT-AK) to 7.5. Further, the half-life decreased from 4.5 to 3.32 h. These enzymatic properties were better than other mutant strains. Inhibition was diminished with low concentrations of Lys, and Lys + Thr presented an activating role. Subsequently, the reasons for the improved AK enzyme activity were illustrated with microscale thermophoresis (MST) experiments and molecular dynamic (MD) simulation by measuring ligand affinity and AK conformational changes. MST showed that the affinity between T379L/A380 M and Lys decreased, but the affinity between T379L/A380 M and Asp increased, promoting T379L/A380 M enzyme activity. MD experiments showed that T379L/A380 M enhanced the Asp-ATP affinity and catalyzed the transfer of residues S192 and D193 to Asp, promoting T379L/A380 M enzyme activity. However, the mutation did not cause fluctuations in the substrate Asp and ATP pockets. This might be why the enzyme activity was inferior to that of the single mutants (T379L and A380 M).

Summary: To improve the treatment of pigmentation disorders, looking for natural and safe inhibitors of melanin synthesis has become an area of research interest. The quinoa husk peptides reportedly elicit various biological activities (e.g., anti-cancer, antioxidant, anti-hypertensive, and so forth), but its effects on melanin inhibition remain unknown. In the current study, we purified quinoa husk peptides with 30 and 80% ethanol using a macroporous adsorption resin (DA201-C). Component screening revealed that the 80%-ethanol fraction (i.e., QHP fraction) contained numerous short peptides (84.41%) and hydrophobic amino acids (45.60%), while eliciting a superior tyrosinase [TYR]-inhibition rate, 2,2-diphenyl-1-picryhydrazil-scavenging rate, reducing activity, and chelating capacity compared to the 30% fraction and was thus applied in subsequent analyses. Differentially expressed genes in the QHP fraction were primarily enriched in the Akt-signaling pathways based on transcriptomics. Thus, we assessed the expression of related proteins and genes in A375 cells and rat skin cells following treatment with QHP.

Abstract Background The clinical characteristics of synchronous colorectal cancer (SCRC) reported in previous studies differ significantly. Furthermore, little is known about the characteristics of early-onset synchronous colorectal cancer (EO-SCRC). The aim of this retrospective study was to identify the clinicopathological characteristics of SCRC and EO-SCRC and define their relevant prognostic factors. Methods Patients who underwent surgery for SCRC and primary unifocal colorectal cancer (PCRC) between January 2007 and December 2020 were included in this study. The clinical, histological, and molecular characteristics of the patient’s tumours were analysed. The primary endpoint was overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess the association between clinicopathological factors and patient survival. Results A total of 1554 patients were included in the analysis. Of these, 1132 (72.84%) had PCRC and 422 (27.16%) had SCRC. SCRC occurred more frequently in the elderly (P

Abstract Background Accelerated idioventricular rhythm (AIVR) is often transient, considered benign and requires no treatment. This observational study aims to investigate the clinical manifestations, treatment, and prognosis of frequent AIVR. Methods Twenty-seven patients (20 male; mean age 32.2 ± 17.0 years) diagnosed with frequent AIVR were enrolled in our study. Inclusion criteria were as follows: (1) at least three recordings of AIVR on 24-h Holter monitoring with an interval of over one month between each recording; and (2) resting ectopic ventricular rate between 50 to 110 bpm on ECG. Electrophysiological study (EPS) and catheter ablation were performed in patients with distinct indications. Results All 27 patients experienced palpitation or chest discomfort, and two had syncope or presyncope on exertion. Impaired left ventricular ejection fraction (LVEF) was identified in 5 patients, and LVEF was negatively correlated with AIVR burden (P

BackgroundThree-dimensional activation mapping during sinus rhythm can demonstrate the earliest atrial activation (EAA) site, which could be the sinoatrial node (SAN). We aimed to compare the electroanatomical characteristics of superior vena cava (SVC), myocardial sleeve, and SAN between patients with atrial fibrillation (AF) and non-AF.Materials and methodsIn this study, 136 patients with AF were assigned to the study group, and 20 patients with premature ventricular contractions (PVCs) who had no history of AF were assigned to the control group. The right atrium (RA) and SVC anatomical activation models were constructed, and the EAA of SAN was delineated using the CARTO3 mapping system. The length of the SVC myocardial sleeve (LSVC) was measured.ResultsOf the 136 patients, 93 patients had paroxysmal AF (PAF), and 43 patients had persistent AF (PsAF). The LSVC was not significantly different among AF and non-AF, PAF, and PsAF. The LSVC in men was longer than in women (42.1 ± 9.4 mm vs. 35.4 ± 8.1 mm, p < 0.001). The LSVC was longer in patients with EAA of SAN above the RA-SVC junction than in those with below the RA-SVC junction (p < 0.001). The EAA of SAN was below the RA-SVC junction in 64/136 (47.1%) and was above the junction in 72/136 (52.9%) patients with AF. The spatial distribution of the EAA of SAN between PAF and PsAF was not different. There was a trend of statistical difference in the distribution of the EAA of SAN between PsAF and non-AF.ConclusionThe EAA of SAN was located in the SVC in most of the patients, especially in patients with PsAF.

Objective To analyse the prevalence and heart rate variability (HRV) characteristics of premature ventricular contraction (PVC) detected by 24-hour Holter among Chinese outpatients with palpitations.Design A cross-sectional study.Setting This study was conducted in a tertiary hospital.Participants A total of 4754 outpatients who received 24-hour Holter for palpitations.Main outcome measures Prevalence, HRV time-domain and frequency-domain analyses of 24-hour Holter, and echocardiographic parameters were assessed. Propensity score matching (PSM) was applied to balance baseline variables (age, gender) to decrease the bias between comparison groups.Results The prevalence of PVC was 67.7% (3220/4754), and was higher in men than women (69.9% vs 66.0%, p=0.004); the prevalence of frequent PVCs (PVC burden≥5%) was 7.7% (368/4754). Older patients had the highest frequency of PVC among all patients. However, among 3220 patients with PVC, younger patients’ PVC burden was much higher. Matched 1:1 by age and gender, the HRV time-domain parameters in patients with PVC were all lower than those in patients without PVC (all p

Background: Long non-coding RNA (lncRNA) PMS2L2 can inhibit inflammation induced by LPS, while LPS plays an important role in sepsis, indicating the possible involvement of PMS2L2 in sepsis. Methods: Expressions of miR-21 and PMS2L2 in patients with acute kidney injury (AKI), sepsis patients without AKI induced and healthy controls was determined by performing RT-qPCR. Overexpression assay was performed to explore the crosstalk between miR-21 and PMS2L2. Methylation-specific PCR (MSP) was performed to explore the role of PMS2L2 in regulating the methylation of miR-21 gene. The role of miR-21 and PMS2L2 in the apoptosis of CIHP-1 cells induced by LPS was assessed by cell apoptosis assay. Results: PMS2L2 was downregulated in AKI patients induced by sepsis compared to sepsis patients without AKI and healthy controls. MiR-21 was also downregulated in AKI induced by sepsis and positively correlated with PMS2L2. In addition, in cells of human podocyte cell line (CIHP-1), overexpression of PMS2L2 promoted the expression of miR-21, while miR-21 did not affect the expression of PMS2L2. MSP analysis showed that overexpression of PMS2L2 decreased methylation of miR-21. LPS treatment downregulated PMS2L2 and miR-21 in a time-dependent manner. PMS2L2 and miR-21 decreased the apoptosis of CIHP-1 cells induced by LPS, and co-overexpression of PMS2L2 and miR-21 showed stronger inhibitory effect. Conclusions: PMS2L2 is downregulated in AKI induced by sepsis and inhibits LPS-induced apoptosis of podocytes.

Abstract Ischemic cardiomyopathy seriously endangers human health leading to a poor prognosis. Acute myocardial infarction (AMI) is the primary etiology, and the pathophysiological process concludes with the death of cardiomyocytes caused by acute and persistent ischemia and hypoxia in the coronary arteries. We identified a circRNA (circSNRK) which was downregulated in rats with myocardial infarction (MI), however, the role it plays in the MI environment is still unclear. This study contained experiments to investigate the role of circSNRK in the regulation of cardiac survival and explore the mechanisms underlying circSNRK functions. Quantitative real-time PCR (qRT-PCR) was performed to determine the circSNRK expression patterns in hearts. Gain-of-function assays were also conducted in vitro and in vivo to determine the role of circSNRK in cardiac repair. qRT-PCR, western blot, and luciferase reporter assays were used to study circRNA interactions with micro RNAs (miRNAs). Overexpression of circSNRK in cardiomyocytes reduced apoptosis and increased proliferation. Adeno associated virus 9 (AAV9) mediated myocardium overexpression of circSNRK in post MI hearts reduced cardiomyocyte apoptosis, promoted cardiomyocyte proliferation, enhanced angiogenesis, and improved cardiac functions. Overall, upregulation of circSNRK promotes cardiac survival and functional recovery after MI. Mechanistically, circSNRK regulates cardiomyocyte apoptosis and proliferation by acting as a miR-103-3p sponge and inducing increased expression of SNRK which can bind GSK3β to regulate its phosphorylated activity. And thus circSNRK may be a promising therapeutic target for improving clinical prognosis after MI.

BackgroundNon-valvular atrial fibrillation (NVAF) in patients at low risk of thromboembolism (TE) does not mean “no risk.” We sought to assess the risk factors associated with TE in clinically low-risk AF patients with a non-gender CHA2DS2-VASc score (CHA2DS2-VA score) of 0 or 1.MethodsIn this single-center cross-sectional study, NVAF patients with a CHA2D-VA score of 0 or 1 who underwent index high-density bipolar voltage mapping of the left atrium (LA) and AF ablation were consecutively enrolled from 2017 to 2020. The population was divided into patients with and without TE history before voltage mapping. AF patients with CHA2DS2-VA score of 0 to 1 before TE (TE group) were analyzed and compared with clinically low-risk AF patients without TE history (non-TE group). The association among LA low voltage area (LVA), other clinical factors and TE history was analyzed with logistic regression.ResultsIn the TE group, LVA was more prevalent [15/25 (60%) vs. 105/359 (29.2%), p = 0.003] and more preferentially located at the anterior wall [8/15 (53%) vs. 24/105 (23%), p = 0.025]. Among patients with LVA, the activation time from the sinus node to the left atrial appendage was significantly longer in the TE group (77.09 ± 21.09 vs. 57.59 ± 15.19 ms, p < 0.001). Multivariate analysis demonstrated that LVA at the anterior wall of the LA [OR: 4.17 (95% CI: 1.51 to 11.51); p = 0.006] and being female [OR: 3.40 (95% CI: 1.36 to 8.51); p = 0.009] were associated with TE history.ConclusionsLVA at the anterior wall of the LA is associated with TE history in NVAF patients with a low CHA2DS2-VA score.

Abstract Background Exosome transplantation is a promising cell-free therapeutic approach for the treatment of ischemic heart disease. The purpose of this study was to explore whether exosomes derived from Macrophage migration inhibitory factor (MIF) engineered umbilical cord MSCs (ucMSCs) exhibit superior cardioprotective effects in a rat model of AMI and reveal the mechanisms underlying it. Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF downregulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration, and angiogenesis of HUVECs and inhibited H9C2 cardiomyocyte apoptosis under H/SD in vitro. MIF-Exo also significantly inhibited cardiomyocyte apoptosis, reduced fibrotic area, and improved cardiac function as measured by echocardiography in infarcted rats in vivo. Exosomal miRNAs sequencing and qRT-PCR confirmed miRNA-133a-3p significantly increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. These effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics that increased the phosphorylation of AKT protein in these cells. Conclusion MIF-Exo can provide cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, reducing fibrosis, and preserving heart function in vitro and in vivo. The mechanism in the biological activities of MIF-Exo involves miR-133a-3p and the downstream AKT signaling pathway.

Background: Ginsenosides, which have strong biological activities, can be divided into polar or less-polar ginsenosides. Methods: This study evaluated the phytochemical diversity of the saponins in Panax ginseng (PG) root, American ginseng (AG) root, and Panax notoginseng (NG) root; the stem-leaves from Panax ginseng (SPG) root, American ginseng (SAG) root, and Panax notoginseng (SNG) root as well as the saponins obtained following heating and acidification [transformed Panax ginseng (TPG), transformed American ginseng (TAG), transformed Panax notoginseng (TNG), transformed stem-leaves from Panax ginseng (TSPG), transformed stem-leaves from American ginseng (TSAG), and transformed stem-leaves from Panax notoginseng (TSNG)]. The diversity was determined through the simultaneous quantification of the 16 major ginsenosides. Results: The content of ginsenosides in NG was found to be higher than those in AG and PG, and the content in SPG was greater than those in SNG and SAG. After transformation, the contents of polar ginsenosides in the raw saponins decreased, and contents of less-polar compounds increased. TNG had the highest levels of ginsenosides, which is consistent with the transformation of ginseng root. The contents of saponins in the stem-leaves were higher than those in the roots. The transformation rate of SNG was higher than those of the other samples, and the loss ratios of total ginsenosides from NG (6%) and SNG (4%) were the lowest among the tested materials. In addition to the conversion temperature, time, and pH, the crude protein content also affects the conversion to rare saponins. The proteins in Panax notoginseng allowed the highest conversion rate. Conclusion: Thus, the industrial preparation of less-polar ginsenosides from SNG is more efficient and cheaper.

BackgroundLeft anterior fascicle (LAF) premature ventricular contractions (PVC) are rarely reported. We described the electrocardiographic and electrophysiological characteristics of PVCs originating from LAF and evaluated the results of catheter ablation.MethodsThe baseline AH and HV intervals were recorded during normal sinus rhythm (NSR), and the HV interval of LAF-PVC was measured during the procedure. During the index procedure, the conduction interval from the earliest Purkinje potential (PP) site to the His was labeled as time A, the conduction interval from the earliest site to the onset of the QRS as time B, then the HV interval during NSR (HVNSR) is A + B, and the HV interval during PVC (HVPVC) is B-A; a predicted PP time was calculated using HVNSR and HVPVC. The calculated formula is as follows: Predicted target PP = (HVNSR + HVPVC)/2. During the repeat procedure, the mapping strategy only focuses on the earliest retrograde PP due to the injury or block of LAF sustained at the index procedure.ResultsNotably, 24 patients with LAF-PVC were included. The ECG characteristics of PVC exhibited right bundle branch block (RBBB) morphology with right-axis deviation (RAD) in 18 patients and only RAD in 6 patients. The QRS durations of NSR and PVC were 78.8 ± 7.9 and 106.8 ± 12.3 ms, respectively. There was no significant difference between the predicted and mapped PP site (31.5 ± 8.1 vs. 30.6 ± 7.8 ms; P = 0.17). There was a significant difference between the mean axis deviation before and after ablation (46.3 ± 25.4° vs. 18.3 ± 44.1°; P = 0.001); however, only 10 patients had a complete LAF block. Eight patients had a recurrence, the QRS morphology of LAF-PVC became narrower (95.9 ± 17.2 vs. 105.3 ± 16.9 ms, P = 0.003), and 4 patients’s PVC QRS morphology was similar to NSR. During the repeat procedure, the earliest retrograde PP interval was longer than the index procedure in four patients (12.0 ± 1.9 vs. 37.8 ± 1.1 ms; P < 0.001).ConclusionThe target PP site for ablation of the LAF region can be calculated using the HV interval during NSR and PVC at the index procedure. The mapping strategy at repeat procedures focused on the earliest retrograde PP interval.

BackgroundLymph node metastasis (LNM) is a critical factor in determining the prognosis of gastric cancer (GC), but its underlying mechanism remains unclear. The tumor mutational burden (TMB) has recently been recognized as a biomarker for predicting prognosis and response to immune checkpoint inhibitors, while mucin 16, cell surface associated (MUC16) is frequently mutated in GC. This study explored whether MUC16 mutation status is associated with TMB, LNM, and prognosis in patients with GC.MethodsSomatic mutation data were downloaded from three GC cohorts. TMB values were calculated and associations between the TMB and clinical characteristics were analyzed. The mutational landscapes of these three GC cohorts were individually explored and visualized using waterfall diagrams. Univariate logistic regression and Kaplan-Meier survival analysis were performed to screen for mutated genes associated with LNM and overall survival (OS). Associations between MUC16 mutations and TMB, microsatellite instability (MSI), LNM, and tumor microenvironment signatures were explored.ResultsTMB was associated with LNM and OS in patients with GC. Analyzing the three GC cohorts (The Cancer Genome Atlas-Stomach Adenocarcinoma, International Cancer Genome Consortium [ICGC]-China, and ICGC-Japan) revealed that MUC16 was one of the most frequently mutated genes in patients with GC. MUC16 mutations were associated with better prognosis, including lower LNM rates and improved OS rates. In addition, MUC16 mutation status was associated with TMB and MSI statuses. Fifteen upregulated and 222 downregulated genes were identified in patients with MUC16 mutations, compared to in those in patients with wild-type MUC16. An altered tumor microenvironment signature was also identified in GC samples with MUC16 mutations; it was characterized by significantly decreased infiltration regarding stromal cells, CD4+ T cells, and macrophages.ConclusionMUC16 mutation status was associated with TMB, microsatellite status, LNM, and survival in patients with GC. These findings may provide new insights into the mechanism of LNM and could act as a signpost for prognostic predictions and immunotherapy guidance for patients with GC.

Aim to investigate the effect of miR-206 on the growth and metastasis of breast cancer stem cells and clarify the precise mechanism of miR-206 on EVI-1-mediated CALR expression in driving malignant phenotype. Our results showed that miR-206 mimics suppressed CALR expression, inhibited the proliferation and metastasis ability of breast cancer stem cells and finally induced cellular apoptosis. Over-expression of CALR could effectively attenuate the cytotoxic effect of miR-206. Further studies demonstrated that EVI-1 could be served as a key regulator of miR206-mediated CALR expression. Elevation of EVI-1 can reverse the function of miR-206 on induction of CALR.

This paper focuses on semi-partitioned cyclic executives for mixed-criticality multiprocessor systems in the case of which a job can be split and execute on different processors, this strategy incorporates most of the advantages of the fully partitioned scheduling while further maximising the total processor utilization. We propose algorithms in order to improve the schedulability of such a system. The length of each frame can be reduced to an optimal (minimum) value, which is a necessary schedulability condition for any schedule under this system model (i.e. every processor's capacity is fully utilized within each frame so that the frame cannot be further shortened), whilst all timing requirements of the system are satisfied. By conducting extensive experiments on a very large number of randomly generated job sets, it is demonstrated that our proposed algorithms significantly reduce the required length of each frame; it is possible for almost 100% of the job sets in the experiments to obtain their optimal values with the exception of a very limited number of specific situations. We also prove that when the complete times of some specific jobs are fixed given values, the strategy to shorten the frame presented in this paper is optimal.

Abstract Different food processing methods will influence the structure and activity of compounds. In this work, molecular structure and different content crude saponins that were extracted from quinoa, treated with water soaking, water boiling, and water steaming were analyzed by HPLC. Flow cytometry was employed to investigate the effects of the main saponins on the GES‐1 cell line. HPLC/MS analysis revealed that water soaking induced an extensive conversion of polar saponin Qc (424.41 ± 21.11 mg/g) to the less polar compound Qf (247.04 ± 15.71 mg/g). After treatment with 100 μg of Qf instead of Qc for 24 hr, the percentage of dead cells increased from 20.1 ± 2.2% to 86.2 ± 4.8%. One major reason of this result is that less polar saponins could damage membrane integrity more easier than polar saponins. The results indicate that saponin toxicity is enhanced after degradation, so it is necessary to avoid degradation before use.

Background: New-onset atrial fibrillation (AF) after ablation of typical atrial flutter (AFL) is not rare. This study aimed to investigate the predictive value of electrocardiographic parameters on new-onset AF post-typical AFL ablation.Methods: A total of 158 consecutive patients (79.1% males, mean age 57.8 ± 14.3 years) with typical AFL were enrolled between January 2012 and August 2017 in this single-center study. Patients with a history of AF before ablation were excluded. ECGs during sinus rhythm (SR) and AFL were collected. The duration of the negative component of flutter wave in lead II (DFNII), proportion of the DFNII of the total circle length of AFL (DFNII%), amplitude of the negative component of flutter wave in lead II (AFNII), duration (DPNV1), and amplitude (APNV1) of negative component of the P wave in lead V1, and P wave duration in lead II (DPII) during sinus rhythm were measured.Results: During a median follow-up of 26.9 ± 11.8 months, 22 cases (13.9%) developed new-onset AF. DFNII was significantly longer in patients with new-onset AF compared to patients without AF (114.7 ± 29.6 ms vs. 82.7 ± 12.8 ms, p < 0.0001). AFNII was significantly lower (0.118 ± 0.034 mV vs. 0.168 ± 0.051 mV, p < 0.0001), DPII (144.21 ± 23.77 ms vs. 111.46 ± 14.19 ms, p < 0.0001), and DPNV1 was significantly longer (81.07 ± 16.87 ms vs. 59.86 ± 14.42 ms, p < 0.0001) in patients with new-onset AF. In the multivariate analysis, DFNII [odds ratio (OR), 1.428; 95% CI, 1.039–1.962; p = 0.028] and DPII (OR, 1.429; 95% CI, 1.046–1.953; p = 0.025) were found to be independently associated with new-onset AF after typical AFL ablation.Conclusion: Parameters representing left atrial activation time under both the SR and AFL were independently associated with new-onset AF post-typical AFL ablation and may be useful in risk prediction, which needs to be confirmed by further prospective studies.

Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality in pregnant women. This study aimed to investigate the potential impact and regulatory mechanisms of bone morphogenetic protein receptor 2 (BMPR2) on the progression of PE. We obtained placental tissues from pregnant women with PE and normal pregnant women, and the results showed that BMPR2 was expressed at low levels in the tissue from PE women. Genetic knockdown of BMPR2 increased the proliferation and invasion of cultured trophoblast cells, whereas its overexpression reduced these characteristics. Bioinformatics analysis and luciferase reporter gene assays confirmed that BMPR2 is a direct target of miR-21. Overexpression of a miR-21 inhibitor promoted the growth and invasiveness of trophoblast cells, whereas the opposite results were observed for the miR-21 mimic. Furthermore, miR-21 was sponged by the lncRNA MEG3, and shRNA inhibition of MEG3 reduced trophoblast cell growth and invasiveness. miR-21 was upregulated in the tissues from PE women, whereas MEG3 was downregulated, and the two were negatively correlated. Collectively, this study demonstrates that the lncRNA MEG3 acts as a sponge for miR-21, which regulates BMPR2 expression and promotes trophoblast cell proliferation and invasiveness, thereby preventing the development of PE. These findings provide novel insight into a targeted therapy that could be used to treat or prevent the development of PE.

Purpose: Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stage (stages I and II) colorectal cancer (CRC).Methods: m6A-related lncRNA data were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen for prognostic m6A-related lncRNAs. Immune characteristics were analyzed in different subgroups created via unsupervised clustering analysis. Next, patients were randomly divided into training and test cohorts. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was performed to establish a prognostic model. The predictive value of the signature was evaluated in the training and test cohorts. Drug sensitivity was also examined.Results: A total of 1,478 m6A-related lncRNAs were identified. Two subgroups were created based on the expression of seven prognostic m6A-related lncRNAs. Prognosis was worse for cluster 1 than for cluster 2, and cluster 1 was characterized by increased numbers of M2 macrophages, decreased numbers of memory B cells, and higher expression of checkpoint genes when compared with cluster 2. Five m6A-related lncRNAs were selected to establish a risk prediction signature via LASSO regression. The 3 years overall survival (OS) was higher in the low-risk group than in the high-risk group. The area under the curve at 1, 2, and 3 years was 0.929, 0.954, and 0.841 in the training cohort and 0.664, 0.760, and 0.754 in the test cohort, respectively. Multivariate Cox regression analysis suggests that the risk score was an independent predictor of OS in both the training and test cohorts. A prognostic nomogram based on the five m6A-related lncRNAs and their clinical features was built and verified. The high-risk group was more sensitive to chemotherapeutic drugs (camptothecin and cisplatin) than the low-risk group.Conclusion: We identified two molecular subgroups of early-stage CRC with unique immune features based on seven prognostic m6A-related lncRNAs. Subsequent analyses demonstrated the usefulness of a five m6A-related lncRNA signature as a potential indicator of prognosis in patients with early-stage CRC.

Background: Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HCM), but identification of patients at a high risk of SCD is challenging. The study aimed to validate the three SCD risk stratifications recommended by the 2011 ACCF/AHA guideline, the 2014 ESC guideline, and the 2020 AHA/ACC guideline in Chinese HCM patients.Methods: The study population consisted of a consecutive cohort of 511 patients with HCM without a history of SCD event. The endpoint was a composite of SCD or an equivalent event (appropriate implantable cardioverter defibrillator therapy or successful resuscitation after cardiac arrest).Results: During a follow-up of 4.7 ± 1.7 years, 15 patients (2.9%) reached the SCD endpoint and 12 (2.3%) were protected by implantable cardioverter defibrillator for primary prevention. A total of 13 (2.8%) patients experiencing SCD events were misclassified as low-risk patients by the 2011 ACCF/AHA guideline, 12 (2.3%) by the 2014 ESC model, and 7 (1.6%) by the 2020 AHA/ACC guideline. The SCD risk stratification in the 2020 AHA/ACC guideline showed greater area under the curve (0.71; 95% CI 0.56–0.87, p < 0.001) than the one in the 2011 ACCF/AHA guideline (0.52; 95% CI 0.37–0.67, p = 0.76) and 2014 ESC guideline (0.68; 95% CI 0.54–0.81, p = 0.02).Conclusion: The SCD risk stratification recommended by the 2020 AHA/ACC guideline showed a better discrimination than previous stratifications in Chinese patients with HCM. A larger multicenter, independent, and prospective study with long-term follow-up would be warranted to validate our result.

Background: Pulmonary vein isolation (PVI) is an effective strategy in the treatment of paroxysmal atrial fibrillation (PAF). Yet, there are limited data on additional ablation beyond PVI. In this study, we sought to assess the prevalence, predictors, and outcomes of additional ablation in PAF patients.Methods: A total of 537 consecutive patients with PAF were retrospectively evaluated for the index procedure. PVI was successfully conducted in all patients, after which electrophysiological study and drug provocation were performed, and additional ablations were delivered for concomitant arrhythmias, non-PV triggers, and low voltage zone (LVZ). The prevalence, predictors, and outcomes of additional ablation were analyzed.Results: Among 537 consecutive patients, 372 addition ablations were performed in 241 (44.88%) patients, including 252 (67.74%) concomitant arrhythmias in 198 (36.87%) patients, 56 (15.05%) non-PV triggers in 52 (9.68%) patients and 64 (17.20%) LVZ modification in 47 (8.75%) patients. Lower LVEF (OR = 0.937, p = 0.015), AF episode before procedure (OR = 2.990, p = 0.001), AF episode during procedure (OR = 1.998, p = 0.002) and AF episode induced after PVI (OR = 15.958, p < 0.001) were independent predictors of additional ablation. Single-procedure free from atrial arrhythmias at 58.36 ± 7.12 months post-ablation was 70.48%.Conclusions: Additional ablations were common in patients with PAF for index procedure. Lower LVEF and AF episodes before, during the procedure, and induced after PVI predicts additional ablation.

BackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues.ResultsA total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis.ConclusionThis study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment.

Listeria monocytogenes widely exists in the natural environment and does great harm, which can cause worldwide public safety problem. Infection with L. monocytogenes can cause rapid death of Kupffer cell (KCs) in liver tissue and liver damage. American ginseng saponins is a natural compound in plants, which has great potential in inhibiting L. monocytogenes infection. Therefore, American ginseng stem-leaf saponins (AGS) and American ginseng heat-transformed saponins (HTS) were used as raw materials to study their bacteriostatic experiments in vivo and in vitro. In this experiment, female Kunming mice were randomly divided into five groups: control group, negative group, AGS group, HTS group (10 mg/kg/day in an equal volume via gastric administration) and penicillin group, each group containing six mice. Profiles AGS and HTS components were evaluated by high-performance liquid chromatography (HPLC) analysis. The bacteriostatic effect of AGS and HTS on L. monocytogenes was evaluated by inhibition zone test, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The bacteriostatic effect of AGS and HTS pretreatment on mice infected with L. monocytogenes were studies by animal experimental. The results showed that the content of polar saponins in AGS was 0.81 ± 0.003 mg/mg, less polar saponins was 0.08 ± 0.02 mg/mg, the content of polar saponins in HTS was 0.10 ± 0.01 mg/mg, less polar saponins was 0.76 ± 0.02 mg/mg. The in vitro bacteriostatic diameter of HTS (16.6 ± 0.8 mm) is large than that of AGS (10.2 ± 1.2 mm). AGS and HTS pretreatment could reduce the colony numbers in the livers of mice infected with Listeria monocytogenes. The levels of alanine aminotransferase (ALT), IL-1β, IL-6, TNF-α and IFN-γ in the livers of mice in the pretreatment group were significantly lower than those in the negative group. There were obvious leukoplakia, calcification and other liver damage on the liver surface in the negative control group, and obvious inflammatory cell infiltration in HE sections. AGS and HTS pretreatment can reduce liver injury caused by L. monocytogenes and protect the liver. Compared with AGS, HTS has higher content of less polar saponins and better bacteriostatic effect in vitro. The count of bacterial in liver tissue of HTS group was significantly lower, the survival rate was significantly higher than that of AGS group. Less polar saponins had better bacteriostatic effect. Collectively, less polar saponins pretreatment has a protective effect on mice infected with L. monocytogenes, to which alleviated liver damage, improved anti-inflammatory ability and immunity of the body, protected liver may contribute.

Low-cost and ecofriendly electrolytes with suppressed water reactivity and raised ionic conductivity are desirable for aqueous rechargeable batteries because it is a dilemma to decrease the water reactivity and increase the ionic conductivity at the same time. In this paper, Li2SO4–Na2SO4–sodium dodecyl sulfate (LN-SDS)-based aqueous electrolytes are designed, where: (i) Na+ ions dissociated from SDS increase the charge carrier concentration, (ii) DS−/SO42− anions and Li+/Na+ cations are capable of trapping water molecules through hydrogen bonding and/or hydration, resulting in a lowered melting point, (iii) Li+ ions reduce the Krafft temperature of LN-SDS, (iv) Na+ and SO42− ions increase the low-temperature electrolyte ionic conductivity, and (v) SDS micelle clusters are orderly aggregated to form directional ion transport channels, enabling the formation of quasi-continuous ion flows without (r.t.) and with (≤0 °C) applying voltage. The screened LN-SDS is featured with suppressed water reactivity and high ionic conductivity at temperatures ranging from room temperature to −15 °C. Additionally, NaTi2(PO4)3‖LiMn2O4 batteries operating with LN-SDS manifest impressive electrochemical performance at both room temperature and −15 °C, especially the cycling stability and low-temperature performance.

Objective: To develop predictive models for contrast induced acute kidney injury (CI-AKI) among acute myocardial infarction (AMI) patients treated invasively.Methods: Patients with AMI who underwent angiography therapy were enrolled and randomly divided into training cohort (75%) and validation cohort (25%). Machine learning algorithms were used to construct predictive models for CI-AKI. The predictive models were tested in a validation cohort.Results: A total of 1,495 patients with AMI were included. Of all the patients, 226 (15.1%) cases developed CI-AKI. In the validation cohort, Random Forest (RF) model with top 15 variables reached an area under the curve (AUC) of 0.82 (95% CI: 0.76–0.87), while the best logistic model had an AUC of 0.69 (95% CI: 0.62–0.76). ACEF (age, creatinine, and ejection fraction) model reached an AUC of 0.62 (95% CI: 0.53–0.71). RF model with top 15 variables achieved a high recall rate of 71.9% and an accuracy of 73.5% in the validation group. Random Forest model significantly outperformed logistic regression in every comparison.Conclusions: Machine learning algorithms especially Random Forest algorithm improves the accuracy of risk stratifying patients with AMI and should be used to accurately identify the risk of CI-AKI in AMI patients.

The composition and biological activity of donor cells is largely determined by the exosomes they secrete. In this study, we isolated exosomes from young (Young-Exo) and aged (Age-Exo) mesenchymal stem cells (MSCs) and compared their regeneration activity. Young Exo MSCs were more efficient than Aged-Exo at promoting the formation of endothelial tube, reducing fibrosis, and inhibiting apoptosis of cardiomyocytes in vitro; and improving cardiac structure and function in vivo in the hearts of rats following myocardial infarction (MI). MicroRNA sequencing and polymerase chain reaction (PCR) analysis revealed that miR-221-3p was significantly down-regulated in Aged-Exo. The aged MSCs were rejuvenated and their reparative cardiac ability restored when miR-221-3p was overexpressed in Aged-Exo. The protective effect was lost when miR-221-3p expression was knocked down in Young-Exo. These effects of miR-221-3p were achieved through enhancing Akt kinase activity by inhibiting phosphatase and tensin homolog (PTEN). In conclusion, exosomal miR-221-3p secreted from Aged MSCs attenuated the function of angiogenesis and promoted survival of cardiomyocytes. Up-regulation of miR-221-3p in aged MSCs improved their ability of angiogenesis, migration and proliferation, and suppressed apoptosis via the PTEN/Akt pathway.

Background: Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF). Methods: A total of 16 consecutive adult patients with CAF who underwent catheter ablation were enrolled. Blood samples for measurement of TGF-β1 were collected from periphery veins and coronary sinus before pulmonary vein isolation. The measurement was performed with a commercially available ELISA kit. Cardiac indices were measured using echocardiography. The left atrial electroanatomic mapping was performed after pulmonary vein isolation. Results: Serum level of TGF-β1 in peripheral blood was higher than that in coronary sinus (p

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.

Perchlorate removal was tested in the cathode chamber of microbial electrochemical systems (MESs). Dual-chambers MESs were constructed and operated in batch mode with four kinds of cathode materials including Fe/C particles (Fe/C), zero valent iron particles (ZVI), blank carbon felt (CF), and active carbon (AC). Without external energy supply or perchlorate-reducing microbial pre-enrichment, perchlorate (ClO4-) removal could be achieved in the cathode chambers of MESs at different efficiencies. The highest ClO4- removal rates in these reactors were 18.96 (Fe/C, 100 Ω, 2 days), 15.84 (ZVI, 100 Ω, 2 days), 14.37 (CF, 100 Ω, 3 days), and 19.78 mg/L/day (AC, 100 Ω, 2 days). ClO4- degradation products were mainly Cl− and ClO3-, and the total chlorine in the products was lower than the theoretical input. The non-conservation of the total chlorine may be caused by the adsorption and co-precipitation related to the electrode materials. Coulombs and coulombic efficiency calculation showed that electron provided by MESs was partially responsible for ClO4- reduction, for the Fe/C cathode reactors, about a quarter of electron was provided by MESs.

Backgrounds and Objective. During the procession of radiofrequency catheter ablation (RFCA) in persistent atrial fibrillation (AF), transthoracic electrical cardioversion (ECV) is required to terminate AF. The purpose of this study was to determine the impact of additional ECV on cardiac function and recurrence of AF. Methods and Results. Persistent AF patients received extensive encircling pulmonary vein isolation (PVI) and additional line ablation. Patients were divided into two groups based on whether they need transthoracic electrical cardioversion to terminate AF: electrical cardioversion (ECV group) and nonelectrical cardioversion (NECV group). Among 111 subjects, 35 patients were returned to sinus rhythm after ablation by ECV (ECV group) and 76 patients had AF termination after the ablation processions (NECV group). During the 12-month follow-ups, the recurrence ratio of patients was comparable in ECV group (15/35) and NECV group (34/76) (44.14% versus 44.74%, P=0.853). Although left atrial diameters (LAD) decreased significantly in both groups, there were no significant differences in LAD and left ventricular cardiac function between ECV group and NECV group. Conclusions. This study revealed that ECV has no significant impact on the maintenance of SR and the recovery of cardiac function. Therefore, ECV could be applied safely to recover SR during the procedure of catheter ablation of persistent atrial fibrillation.

The industrial wireless network (IWN) is an important part of industrial CPS, which must address the key issue of reliable and real-time communication as well as the desired network lifetime. The nodes of IWN are usually fixed on the devices for better monitoring of the state information of the equipment and environment, while the relay node placement plays a significant role on network performance guarantee. This paper proposes an Integer Linear Program (ILP) placement strategy to meet the fault tolerance and survivability requirement. In addition, an edge coloring algorithm is proposed to solve the conflict of TDMA communication, which improves paralleled and real-time communication performance. Simulation results show that this placement strategy not only meets the requirements of robust communication and survivability, but also enhances real-time communication of IWN.

The gene zinc finger homeobox 3 (ZFHX3) encodes a transcription factor with cardiac expression and its genetic variants are associated with atrial fibrillation (AF). We aimed to explore the associations between single nucleotide polymorphisms (SNPs) of ZFHX3 and the risk of AF in a Chinese Han population.We genotyped eight SNPs, including seven potentially functional SNPs and one previously reported SNP by using the middle-throughput iPLEX Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models.We enrolled a total of 1,593 Chinese Han origin individuals in the study, including 597 AF patients and 996 non-AF controls. Logistic regression analyses revealed that potentially functional SNPs rs6499600 and rs16971436 were associated with a decreased risk of AF (adjusted OR = 0.73, 95% CI: 0.63-0.86, P = 1.07×10-4; adjusted OR = 0.74, 95% CI: 0.56-0.98, P = 0.039, respectively). In addition, rs2106261 showed a robust association with an increased risk of AF (adjusted OR = 1.71, 95% CI: 1.46-2.00, P = 1.85×10-11). After multiple comparisons, rs16971436 conferred a borderline significant association with the risk of AF. Stratification analysis indicated that the risks of AF were statistically different among subgroups of age for rs2106261, and the effect for rs16971436 was more evident in subgroups of patients with coronary artery disease.In summary, our study investigated the role of genetic variants of ZFHX3 in AF and two SNPs (rs2106261, rs6499600) showed significant associations while rs16971436 conferred a borderline significant association with AF risk in Chinese Han populations. However, further large and functional studies are warranted to confirm our findings.

Conventional oil sewage treatment methods can achieve satisfactory removal efficiency, but energy consumption problems during the process of oil sewage treatment are worth attention. The integration of a constructed wetland reactor and a microbial fuel cell reactor (CW-MFC) to treat oil-contaminated wastewater, compared with a microbial fuel cell reactor (MFC) alone and a constructed wetland reactor (CW) alone, was explored in this research. Performances of the three reactors including chemical oxygen demand (COD), oil removal, and output voltage generation were continuously monitored. The COD removals of three reactors were between 73% and 75%, and oil removals were over 95.7%. Compared with MFC, the CW-MFC with a MnO2 modified cathode produced higher power density and output voltage. Maximum power densities of CW-MFC and MFC were 3868 mW/m3 (102 mW/m2) and 3044 mW/m3 (80 mW/m2), respectively. The plants in CW-MFC play a positive role for reactor cathode potential. Both plants and cathode modification can improve reactor performance of electricity generation.

Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p

BACKGROUND: Induced pluripotent stem cells (iPSCs) are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. METHODOLOGY/PRINCIPAL FINDINGS: We transplanted 2 × 10(4), 2 × 10(5), or 2 × 10(6) cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.