KN-93, A CaMKII inhibitor, suppresses ventricular arrhythmia induced by LQT2 without decreasing TDR.

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 µmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 µmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.

The Circular RNA circSKA3 Facilitates the Malignant Biological Behaviors of Medulloblastoma via miR-520 h/CDK6 Pathway.

Circular RNAs (circRNAs) are reported to participate in the development of diverse human malignancies. This work investigated the mechanism of circSKA3 in modulating medulloblastoma progression. A total of 15 cases of medulloblastoma were collected in this work. Daoy cells were used to construct cell models. The expression level of circSKA3, microRNA-520 h (miR-520 h), and cyclin-dependent kinase 6 (CDK6) mRNA in tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was employed to detect CDK6 protein expression. CCK-8 experiment, Transwell assay, and flow cytometry were applied to detect the regulatory effects of circSKA3 on cell proliferation, migration, invasion, and cell cycle. Dual-luciferase reporter gene experiment was executed to determine the relationship between circSKA3 and miR-520 h, and between miR-520 h and CDK6. circSKA3 was remarkably up-modulated in medulloblastoma tissues. CircSKA3 depletion markedly suppressed Daoy cell viability, migration, invasion, and cell cycle progression. CircSKA3 overexpression induced the opposite effects. circSKA3 could decoyed miR-520 h, which targeted the 3' UTR of CDK6. circSKA3 expression in medulloblastoma tissues was negatively correlated with miR-520 h expression and positively correlated with CDK6 expression. "Rescue" experiments revealed that miR-520 h down-modulation or CDK6 overexpression remarkably counteracted the inhibitory effect of circSKA3 knockdown on Daoy cells. circSKA3 facilitates medulloblastoma progression through miR-520 h/CDK6.

Spreading predictability in complex networks.

Many state-of-the-art researches focus on predicting infection scale or threshold in infectious diseases or rumor and give the vaccination strategies correspondingly. In these works, most of them assume that the infection probability and initially infected individuals are known at the very beginning. Generally, infectious diseases or rumor has been spreading for some time when it is noticed. How to predict which individuals will be infected in the future only by knowing the current snapshot becomes a key issue in infectious diseases or rumor control. In this report, a prediction model based on snapshot is presented to predict the potentially infected individuals in the future, not just the macro scale of infection. Experimental results on synthetic and real networks demonstrate that the infected individuals predicted by the model have good consistency with the actual infected ones based on simulations.

Brief report: How do they manage social interaction? The influence of concealing academic achievement information on self-monitoring by adolescents with low achievement.

During social interactions people self-monitor their behavior at least partially to conceal socially devalued characteristics. This study examined the influences of concealing academic achievement on self-monitoring in an academically-relevant social interaction. An interview paradigm called for school-aged adolescent participants (total N=86) who either did or did not have low (academic) achievement to play the role of someone who did or did not have low achievement while answering academically-relevant questions. The data suggest that adolescents with low achievement (low achievers) were more likely to tailor their behaviors according to the situational cues than did those without low achievement (non-low achievers). On the other hand, low achievers who played the role of good students (these adolescents could conceal their low academic achievement characteristics) were most likely to regulate their behaviors according to their inner cues (e.g., real feelings).

Clinical Characteristics and Blood Test Results in COVID-19 Patients.

OBJECTIVE: An outbreak of pneumonia named COVID-19 caused by a novel coronavirus in Wuhan is rapidly spreading worldwide. The objective of the present study was to clarify further the clinical characteristics and blood parameters in COVID-19 patients. MATERIALS AND METHODS: Twenty-three suspected patients and 64 patients with laboratory-confirmed SARS-Cov-2 infection were admitted to a designated hospital. Epidemiological, clinical, laboratory, and treatment data were collected and analyzed. RESULTS: Of the 64 patients studied, 47 (73.4%) had been exposed to a confirmed source of COVID-19 transmission. On admission, the most common symptoms were fever (75%) and cough (76.6%). Twenty-eight (43.8%) COVID-19 patients showed leukopenia, 10 (15.6%) showed lymphopenia, 47 (73.4%) and 41 (64.1%) had elevated high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), respectively, and 30 (46.9%) had increased fibrinogen concentration. After the treatment, the counts of white blood cells and platelets, and the level of prealbumin increased significantly, while aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hsCRP decreased. COVID-19 patients with the hospital stay longer than 12 days had higher body mass index (BMI) and increased levels of AST, LDH, fibrinogen, hsCRP, and ESR. CONCLUSIONS: Results of blood tests have potential clinical value in COVID-19 patients.

[Effect of ERK/AP-1 signaling pathway on proliferation of hepatoma cells induced by PAR-2 agonists].

OBJECTIVE: To investigate the expression of protease activated receptor-2 (PAR-2) in human HepG2 hepatoma cells and elucidate the effects of trypsin and PAR-2 agonist peptide SLIGKV-NH(2) upon the proliferation of hepatoma cells and its intracellular signaling mechanism. METHODS: PAR-2 protein and mRNA expression were detected by immunofluorescence and RT-PCR. The cells were treated with SLIGKV-NH(2), trypsin, reverse PAR-2 agonist peptide VKGILS-NH(2) or PD98059. The changes of cell cycle distribution were evaluated by flow cytometry. The proliferative potential of HepG2 cells was estimated by MTT. The changes of PAR-2, c-fos and PCNA mRNA expression were detected by RT-PCR. The changes of c-fos and PCNA protein expression were detected by Western blotting. RESULTS: PAR-2 protein and mRNA were expressed in HepG2 cells. PAR-2 mRNA expression (PAR-2/beta-actin) were 0.70 +/- 0.04 and 0.99 +/- 0.05 respectively in cells treated with trypsin and SLIGKV-NH(2). They were both significantly higher than that in the control group (0.35 +/- 0.05, F = 135.534, P < 0.01). Percent G(0)/G(1) phase of HepG2 cells treated with trypsin or SLIGKV-NH(2) were significantly lower than those in the control group [(56.11 +/- 0.85)%, (57.85 +/- 0.46)% vs (79.12 +/- 0.67)%, both P < 0.01] Percent S phase, G(2)/M phase and proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH(2) were significantly elevated (P < 0.01). The proliferation-enhancing effects and the up-regulation of mRNA and protein of c-fos and PCNA induced by trypsin or SLIGKV-NH(2) were significantly blocked by pretreatment with PD98059 (P < 0.01). There was no statistical significance in proliferation of HepG2 cells between the reverse PAR-2 agonist peptide VKGILS-NH(2) and control group (P > 0.05). CONCLUSION: PAR-2 is expressed in HepG2 hepatoma cells. PAR-2 activation induced by trypsin or SLIGKV-NH(2) promotes the proliferation of HepG2 cells partially via the ERK/AP-1 pathway.

Adolescents' cognition of projectile motion: a pilot study.

Previous work on the development of intuitive knowledge about projectile motion has shown a dissociation between action knowledge expressed on an action task and conceptual knowledge expressed on a judgment task for young children. The research investigated the generality of dissociation for adolescents. On the action task, participants were asked to swing Ball A of a bifilar pendulum to some height then release it to collide with Ball B, which was projected to hit a target. On the judgment task, participants indicated orally the desired swing angle at which Ball A should be released so that Ball B would strike a target. Unlike previous findings with adults, the adolescents showed conceptual difficulties on the judgment task and well-developed action knowledge on the action task, which suggests dissociation between the two knowledge systems is also present among adolescents. The result further supports the hypothesis that the two knowledge systems follow different developmental trajectories and at different speeds.

[Effect of matrine and oxymatrine on proliferation and expression of Stat3 and Stat5 in SMMC-7721 cell line].

OBJECTIVE: To study the effect of matrine and oxymatrine on proliferation and the expression of Stat3, Stat5 mRNA in SMMC-7721 cell line. METHOD: Treated with matrine and oxymatrine, the inhibitory effect on SMMC-7721 cell proliferation was detected by MTT, double fluorescence labeling was applied to measure the apotosis ratios of SMMC-7721cells, the expression of Stat3 and Stat5 mRNA in SMMC-7721 cell line were assessed with RT-PCR. RESULT: Matrine and oxymatrine could inhibit the proliferation and induce the apoptosis of SMMC-7721 cells and it was time and dose dependent, the expression of Stat3 and Stat5 mRNA in SMMC-7721 cell with matrine and oxymatrine were significantly lower than those in control group (P<0.05 or P<0.01). Compared with the same dose of matrine and oxymatrine, matrine showed stronger effect on cell proliferation, apoptosis, and Stat3 and Stat5 mRNA (P<0.05 or P<0.01). CONCLUSION: Matrine and oxymatrine inhibited the proliferation and induced the of SMMC-7721 cells significantly, the mechanism of which might be related to the down-regulation of stat3 and stat5 mRNA and inhibition of the signaling transduction pathway.

Identifying critical edges in complex networks.

The critical edges in complex networks are extraordinary edges which play more significant role than other edges on the structure and function of networks. The research on identifying critical edges in complex networks has attracted much attention because of its theoretical significance as well as wide range of applications. Considering the topological structure of networks and the ability to disseminate information, an edge ranking algorithm BCCMOD based on cliques and paths in networks is proposed in this report. The effectiveness of the proposed method is evaluated by SIR model, susceptibility index S and the size of giant component σ and compared with well-known existing metrics such as Jaccard coefficient, Bridgeness index, Betweenness centrality and Reachability index in nine real networks. Experimental results show that the proposed method outperforms these well-known methods in identifying critical edges both in network connectivity and spreading dynamic.

Verapamil suppresses cardiac alternans and ventricular arrhythmias in acute myocardial ischemia via ryanodine receptor inhibition.

T-wave alternans (TWA) is a potent arrhythmia substrate under the conditions of acute myocardial ischemia. Abnormal intracellular calcium cycling contributes to the genesis of cardiac alternans. Ryanodine receptor (RyR) is a pivotal Ca2+ cycling protein central to Ca2+ signaling in the heart. Here, we investigated the potential role of RyR in cardiac alternans and ventricular arrhythmias in acute myocardial ischemia. Transmembrane action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedge preparations. Calcium alternans were induced by incremental frequency of field stimulation in rat ventricular myocytes. TWA, mechanical alternans and ventricular arrhythmias were reproducibly induced by rapid pacing in the acute ischemic wedge preparations. Compared with control group, calcium alternans ratio and spontaneous calcium release were increased in acute ischemic myocytes. Verapamil, a phenylalkylamine calcium channel blocker, can successfully abolish spontaneous calcium release, TWA, and ventricular arrhythmias. The inhibition effect of verapamil could be diminished by low concentration of ryanodine (10 nmol/L). However, nifedipine, a dihydropyridine calcium channel blocker, could not block TWA or arrhythmias. Moreover, verapamil, but not nifedipine, significantly decreased ROS production in ischemic myocytes. Collectively, our results indicate that verapamil can significantly inhibit the development of cardiac alternans and ventricular arrhythmias in acute myocardial ischemia, and the mechanism was related to the inhibition of RyR and the protective function to oxidative stress.