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The regulation of membrane potential and the contractility of vascular smooth muscle cells (VSMCs) by voltage‐dependent K+ (Kv) potassium channels are well‐established. In this study, native VSMCs from rabbit coronary arteries were used to investigate the inhibitory effect of sertindole, an atypical antipsychotic agent, on Kv channels. Sertindole induced dose‐dependent inhibition of Kv channels, with an IC50 of 3.13 ± 0.72 μM. Although sertindole did not cause a change in the steady‐state activation curve, it did lead to a negative shift in the steady‐state inactivation curve. The application of 1‐ or 2‐Hz train pulses failed to alter the sertindole‐induced inhibition of Kv channels, suggesting use‐independent effects of the drug. The inhibitory response to sertindole was significantly diminished by pretreatment with a Kv1.5 inhibitor but not by Kv2.1 and Kv7 subtype inhibitors. These findings demonstrate the sertindole dose‐dependent and use‐independent inhibition of vascular Kv channels (mainly the Kv1.5 subtype) through a mechanism that involves altering steady‐state inactivation curves. Therefore, the use of sertindole as an antipsychotic drug may have adverse effects on the cardiovascular system. Native VSMCs from rabbit coronary arteries were used to investigate the inhibitory effect of sertindole, an atypical antipsychotic agent, on Kv channels. Our findings demonstrate the sertindole dose‐dependent and use‐independent inhibition of vascular Kv channels (mainly the Kv1.5 subtype) through a mechanism that involves altering steady‐state inactivation curves. [ABSTRACT FROM AUTHOR]

Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage‐dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells. Paliperidone reduced Kv channel activity in a concentration‐dependent manner with a half‐maximal inhibitory concentration (IC50) of 16.58 ± 3.03 μM and a Hill coefficient of 0.60 ± 0.04. It did not significantly shift the steady‐state activation or inactivation curves, suggesting that the drug did not affect the gating properties of Kv channels. In the presence of paliperidone, the application of 20 repetitive depolarizing pulses at 1 and 2 Hz gradually increased the inhibition of the Kv current. Further, the recovery time constant after Kv channel inactivation was increased by paliperidone, indicating that it inhibited the Kv channel in a use (state)‐dependent manner. Its inhibitory effects were reduced by pretreatment with a Kv1.5 subtype inhibitor. However, pretreatment with a Kv2.1 or Kv7 inhibitor did not reduce its inhibitory effect. We conclude that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration‐ and use (state)‐dependent manner without changing channel gating. Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage‐dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells. Our results indicate that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration‐ and use (state)‐dependent manner without changing channel gating. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with severe cognitive impairment. Several studies have reported that brain functional network connectivity (FNC) has great potential for identifying ASD from healthy control (HC) and revealing the relationships between the brain and behaviors of ASD. However, few studies have explored dynamic large‐scale FNC as a feature to identify individuals with ASD. This study used a time‐sliding window method to study the dynamic FNC (dFNC) on the resting‐state fMRI. To avoid arbitrarily determining the window length, we set a window length range of 10–75 TRs (TR = 2 s). We constructed linear support vector machine classifiers for all window length conditions. Using a nested 10‐fold cross‐validation framework, we obtained a grand average accuracy of 94.88% across window length conditions, which is higher than those reported in previous studies. In addition, we determined the optimal window length using the highest classification accuracy of 97.77%. Based on the optimal window length, we found that the dFNCs were located mainly in dorsal and ventral attention networks (DAN and VAN) and exhibited the highest weight in classification. Specifically, we found that the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly negatively correlated with social scores of ASD. Finally, using the dFNCs with high classification weights as features, we construct a model to predict the clinical score of ASD. Overall, our findings demonstrated that the dFNC could be a potential biomarker to identify ASD and provide new perspectives to detect cognitive changes in ASD. Lay Summary: In this study, we proposed a new ASD/HC classification framework based on the dynamic FNC (dFNC), obtaining an accuracy of 97.77%. Based on the classification weights, we found that the dFNC patterns of the attention networks (DAN and VAN) played a key role in ASD. In addition, the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly correlated with the clinical symptoms of ASD. [ABSTRACT FROM AUTHOR]

Voltage-dependent K+ (Kv) channels play the role of returning the membrane potential to the resting state, thereby maintaining the vascular tone. Here, we used native smooth-muscle cells from rabbit coronary arteries to investigate the inhibitory effect of lorcainide, a class Ic antiarrhythmic agent, on Kv channels. Lorcainide inhibited Kv channels in a concentration-dependent manner with an IC 50 of 4.46 ± 0.15 μM and a Hill coefficient of 0.95 ± 0.01. Although application of lorcainide did not change the activation curve, it shifted the inactivation curve toward a more negative potential, implying that lorcainide inhibits Kv channels by changing the channels' voltage sensors. The recovery time constant from channel inactivation increased in the presence of lorcainide. Furthermore, application of train steps (of 1 or 2 Hz) in the presence of lorcainide progressively augmented the inhibition of Kv currents, implying that lorcainide-induced inhibition of Kv channels is use (state)-dependent. Pretreatment with Kv1.5 or Kv2.1/2.2 inhibitors effectively reduced the amplitude of the Kv current but did not affect the inhibitory effect of lorcainide. Based on these results, we conclude that lorcainide inhibits vascular Kv channels in a concentration and use (state)-dependent manner by changing their inactivation gating properties. Considering the clinical efficacy of lorcainide, and the pathophysiological significance of vascular Kv channels, our findings should be considered when prescribing lorcainide to patients with arrhythmia and vascular disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The regulation of membrane potential and the contractility of vascular smooth muscle cells (VSMCs) by voltage-dependent K + (Kv) potassium channels are well-established. In this study, native VSMCs from rabbit coronary arteries were used to investigate the inhibitory effect of sertindole, an atypical antipsychotic agent, on Kv channels. Sertindole induced dose-dependent inhibition of Kv channels, with an IC 50 of 3.13 ± 0.72 μM. Although sertindole did not cause a change in the steady-state activation curve, it did lead to a negative shift in the steady-state inactivation curve. The application of 1- or 2-Hz train pulses failed to alter the sertindole-induced inhibition of Kv channels, suggesting use-independent effects of the drug. The inhibitory response to sertindole was significantly diminished by pretreatment with a Kv1.5 inhibitor but not by Kv2.1 and Kv7 subtype inhibitors. These findings demonstrate the sertindole dose-dependent and use-independent inhibition of vascular Kv channels (mainly the Kv1.5 subtype) through a mechanism that involves altering steady-state inactivation curves. Therefore, the use of sertindole as an antipsychotic drug may have adverse effects on the cardiovascular system., (© 2023 John Wiley & Sons Ltd.)

Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage-dependent K + (Kv) channels of rabbit coronary arterial smooth muscle cells. Paliperidone reduced Kv channel activity in a concentration-dependent manner with a half-maximal inhibitory concentration (IC 50 ) of 16.58 ± 3.03 μM and a Hill coefficient of 0.60 ± 0.04. It did not significantly shift the steady-state activation or inactivation curves, suggesting that the drug did not affect the gating properties of Kv channels. In the presence of paliperidone, the application of 20 repetitive depolarizing pulses at 1 and 2 Hz gradually increased the inhibition of the Kv current. Further, the recovery time constant after Kv channel inactivation was increased by paliperidone, indicating that it inhibited the Kv channel in a use (state)-dependent manner. Its inhibitory effects were reduced by pretreatment with a Kv1.5 subtype inhibitor. However, pretreatment with a Kv2.1 or Kv7 inhibitor did not reduce its inhibitory effect. We conclude that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration- and use (state)-dependent manner without changing channel gating., (© 2023 John Wiley & Sons Ltd.)

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with severe cognitive impairment. Several studies have reported that brain functional network connectivity (FNC) has great potential for identifying ASD from healthy control (HC) and revealing the relationships between the brain and behaviors of ASD. However, few studies have explored dynamic large-scale FNC as a feature to identify individuals with ASD. This study used a time-sliding window method to study the dynamic FNC (dFNC) on the resting-state fMRI. To avoid arbitrarily determining the window length, we set a window length range of 10-75 TRs (TR = 2 s). We constructed linear support vector machine classifiers for all window length conditions. Using a nested 10-fold cross-validation framework, we obtained a grand average accuracy of 94.88% across window length conditions, which is higher than those reported in previous studies. In addition, we determined the optimal window length using the highest classification accuracy of 97.77%. Based on the optimal window length, we found that the dFNCs were located mainly in dorsal and ventral attention networks (DAN and VAN) and exhibited the highest weight in classification. Specifically, we found that the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly negatively correlated with social scores of ASD. Finally, using the dFNCs with high classification weights as features, we construct a model to predict the clinical score of ASD. Overall, our findings demonstrated that the dFNC could be a potential biomarker to identify ASD and provide new perspectives to detect cognitive changes in ASD., (© 2023 International Society for Autism Research and Wiley Periodicals LLC.)

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by a core deficit in social processes. However, it is still unclear whether the core clinical symptoms of the disorder can be reflected by the temporal variability of resting-state network functional connectivity (FC). In this article, we examined the large-scale network FC temporal variability at the local region, within-network, and between-network levels using the fuzzy entropy technique. Then, we correlated the network FC temporal variability to social-related scores. We found that the social behavior correlated with the FC temporal variability of the precuneus, parietal, occipital, temporal, and precentral. Our results also showed that social behavior was significantly negatively correlated with the temporal variability of FC within the default mode network, between the frontoparietal network and cingulo-opercular task control network, and the dorsal attention network. In contrast, social behavior correlated significantly positively with the temporal variability of FC within the subcortical network. Finally, using temporal variability as a feature, we construct a model to predict the social score of ASD. These findings suggest that the network FC temporal variability has a close relationship with social behavioral inflexibility in ASD and may serve as a potential biomarker for predicting ASD symptom severity., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Atherosclerosis is a common pathological change in cardiovascular disease. Vascular smooth muscle cell is the main source of plaque cell and extracellular matrix, and nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the function of vascular smooth muscle cell. In the process of atherosclerosis, Nrf2 signaling pathway has the following regulatory effects on vascular smooth muscle cell: regulating the phenotype of vascular smooth muscle cell to change to the direction conducive to the alleviation of disease progression; inhibiting the proliferation and migration of vascular smooth muscle cell; mitigating the level of blood lipid; alleviating vascular smooth muscle cell calcification, aging and apoptosis process. This article reviews the specific mechanisms of Nrf2 regulating atherosclerosis, such as phenotypic transformation, proliferation and migration, lipid metabolism, calcification, aging and apoptosis in atherosclerosis, in order to provide a basis for understanding the molecular mechanism of atherosclerosis development and finding therapeutic targets.

Fusarium head blight (FHB), a fungal disease caused by Fusarium species that produce food toxins, currently devastates wheat production worldwide, yet few resistance resources have been discovered in wheat germplasm. Here, we cloned the FHB resistance gene Fhb7 by assembling the genome of Thinopyrum elongatum , a species used in wheat distant hybridization breeding. Fhb7 encodes a glutathione S-transferase (GST) and confers broad resistance to Fusarium species by detoxifying trichothecenes through de-epoxidation. Fhb7 GST homologs are absent in plants, and our evidence supports that Th. elongatum has gained Fhb7 through horizontal gene transfer (HGT) from an endophytic Epichloë species. Fhb7 introgressions in wheat confers resistance to both FHB and crown rot in diverse wheat backgrounds without yield penalty, providing a solution for Fusarium resistance breeding., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)