A small-molecule activation mechanism that directly opens the KCNQ2 channel.

Pharmacological activation of voltage-gated ion channels by ligands serves as the basis for therapy and mainly involves a classic gating mechanism that augments the native voltage-dependent open probability. Through structure-based virtual screening, we identified a new scaffold compound, Ebio1, serving as a potent and subtype-selective activator for the voltage-gated potassium channel KCNQ2 and featuring a new activation mechanism. Single-channel patch-clamp, cryogenic-electron microscopy and molecular dynamic simulations, along with chemical derivatives, reveal that Ebio1 engages the KCNQ2 activation by generating an extended channel gate with a larger conductance at the saturating voltage (+50 mV). This mechanism is different from the previously observed activation mechanism of ligands on voltage-gated ion channels. Ebio1 caused S6 helices from residues S303 and F305 to perform a twist-to-open movement, which was sufficient to open the KCNQ2 gate. Overall, our findings provide mechanistic insights into the activation of KCNQ2 channel by Ebio1 and lend support for KCNQ-related drug development.

Construction of Dual-Shell Mo2C/C Microsphere towards Efficient Electromagnetic Wave Absorption.

Carbon-based carbides have attracted tremendous attention for electromagnetic energy attenuation due to their adjustable dielectric properties, oxidation resistance, and good chemical stability. Herein, we reasonably regulate the growth of dopamine hydrochloride on the surface of the Mo-glycerate (Mo-GL) microsphere and then transform the resultant Mo-polydopamine (Mo-PD) microsphere into a dual-shell Mo2C/C (DS-Mo2C/C) microsphere in a high-temperature pyrolysis process under an inert atmosphere. It is found that the pyrolysis temperature plays an important role in the graphitization degree of the carbon matrix and internal architecture. The fabrication of a dual-shell structure can be propitious to the optimization of impedance matching, and the introduction of Mo2C nanoparticles also prompts the accumulation of polarization loss. When the pyrolysis temperature reaches 800 °C, the optimized composite of DS-Mo2C/C-800 exhibits good EM absorption performance in the frequency range of 2.0-18.0 GHz. DS-Mo2C/C-800's qualified bandwidth can reach 4.4 GHz at a matching thickness of 1.5 mm, and the integrated qualified bandwidth (QBW) even exceeds 14.5 GHz with a thickness range of 1.5-5.0 mm. The positive effects of the dual-shell structure and Mo2C nanoparticles on EM energy attenuation may render the DS-Mo2C/C microsphere as a promising candidate for lightweight and broad bandwidth EM absorption materials in the future.

Association of metabolic syndrome with carotid atherosclerosis in low-income Chinese individuals: A population-based study.

Background: This study aimed to explore the association of the presence and number of components of metabolic syndrome (MetS) with carotid atherosclerosis by measuring the presence of carotid plaque and total plaque area (TPA) in a population from a low-income area with high incidence of stroke of northern China. Methods: A cross-sectional study was conducted in a rural area of Tianjin, China from April 2014 to January 2015. The presence of plaque and TPA measurement was determined by carotid ultrasound. The presence and number of components of MetS was ascertained using the modified International Diabetes Federation criteria for the Asian population. Results: Among a total of 3,583 individuals aged ≥ 45 years, the overall prevalence of MetS was 54.5%. MetS and its components were related to the presence of carotid plaque as well as TPA. Multivariate analysis showed MetS was associated with a 20% higher risk of carotid plaque presence (95% confidence interval: 1.01, 1.42; P = 0.036) and an 18% increase in TPA (95% confidence interval: 0.08, 0.27; P < 0.001). The number of MetS components showed an increasing trend with the risk of carotid plaque presence and increased TPA. Among single components of MetS, high BP accounted for the largest proportion and was an independent risk factor of carotid plaque and increased TPA. Conclusions: Among individuals aged 45 years or more, we confirmed MetS and its components were associated with carotid atherosclerosis in a low-income population of northern China. The presence of MetS and a higher number of MetS components exacerbated the risk of carotid atherosclerosis; among the five MetS components, high blood pressure was associated with the greatest risk. Targeted atherosclerosis prevention and intervention should include identification and treatment of MetS, especially high blood pressure.

Relationship Between Metabolic Syndrome and Cognitive Function: A Population-Based Study of Middle-Aged and Elderly Adults in Rural China.

INTRODUCTION: To explore the relationship between metabolic syndrome (MetS) and cognitive impairment in a low-income and low-education population. METHODS: All residents aged ≥45 years in a low-income population in Tianjin, China, were eligible to participate in this study. The Mini-Mental State Examination (MMSE) scale was used to conduct a preliminary screening and assessment of the participants' cognitive statuses. The MMSE components are orientation, registration, attention and calculation, recall, and language. RESULTS: In this population, the prevalences of MetS and cognitive impairment were 54.1% and 44.5%, respectively. In the overall population, the registration score was 0.105 points lower in the elevated triglycerides (TG) group than in the normal TG group (ß, -0.105; 95% confidence interval [CI]: -0.201, -0.010; P=0.030). In men, high TG was associated with registration scores that were 0.152 points lower than those in the normal TG group (95% CI: -0.281, -0.022; P=0.022), while larger WC and lower HDL-C had positive effects on cognitive scores (all P<0.05). However, in women, there were no significant differences between cognitive scores and MetS or its components. CONCLUSION: In this population, first, TG had a great impact on cognition, even greater than the impact of MetS on cognition. Second, the impact of MetS components on cognition was more obvious in men, and not all of the effects were negative. Therefore, the effect of MetS on cognition may need to be analyzed separately for different populations, and it may be that the effect of a single component is greater than the overall effect. When formulating prevention strategies for cognitive impairments, population differences must also be taken into consideration.

Correlation of thyroid dysfunction and cognitive impairments induced by subcortical ischemic vascular disease.

BACKGROUND: To date, the relationship between thyroid dysfunction and subcortical ischemic vascular disease (SIVD)-induced cognitive impairments still remains elusive. METHODS: Cognitive performances were examined in 215 participants, including 54 healthy participants, 52 SIVD patients with no dementia (SIVDND), 55 patients with mild cognitive impairment (SVMCI), and 54 patients with vascular dementia (VD). Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4) and free thyroxine (FT4), thyroglobulin antibody (TGA), and antithyroid peroxidase antibody (TPO-Abs) were quantified by radioimmunoassay or ELISA. RESULTS: A close correlation between thyroid status and cognitive dysfunction in SIVD was observed. Serum TT3 and FT3 levels decreased, whereas serum TSH level increased, with the decline in cognitive functions. Furthermore, TT3 levels showed a positive correlation, whereas TSH level showed a negative correlation, with the Mini-Mental State Examination (MMSE) scores. Our results suggested that thyroid function was associated with cognitive impairments induced by SIVD. Also, thyroid function and thyroid hormone level could be a risk factor in the development of SIVD. Serum TT3 and TSH levels might also be used as biomarkers for cognitive dysfunction. CONCLUSIONS: These findings might contribute to a more accurate clinical diagnosis and differentiation among normal controls, SIVDND, SVMCI, and VD patients, in order to develop appropriate intervention approaches for SIVD therapeutic treatment.