Accurate prediction of solvent flux in sub-1-nm slit-pore nanosheet membranes.

Nanosheet-based membranes have shown enormous potential for energy-efficient molecular transport and separation applications, but designing these membranes for specific separations remains a great challenge due to the lack of good understanding of fluid transport mechanisms in complex nanochannels. We synthesized reduced MXene/graphene hetero-channel membranes with sub-1-nm pores for experimental measurements and theoretical modeling of their structures and fluid transport rates. Our experiments showed that upon complete rejection of salt and organic dyes, these membranes with subnanometer channels exhibit remarkably high solvent fluxes, and their solvent transport behavior is very different from their homo-structured counterparts. We proposed a subcontinuum flow model that enables accurate prediction of solvent flux in sub-1-nm slit-pore membranes by building a direct relationship between the solvent molecule-channel wall interaction and flux from the confined physical properties of a liquid and the structural parameters of the membranes. This work provides a basis for the rational design of nanosheet-based membranes for advanced separation and emerging nanofluidics.

TAT-Modified Martentoxin Displays Intravenous Antiseizure Activities.

Epilepsy is a chronic disease of brain dysfunction, which arises from imbalance between excitatory and inhibitory activities in neural circuits. Previously, we reported that peptide Martentoxin (MarTX), from scorpion Buthus martensii Karsch, displayed antiseizure activities by specifically inhibiting BK(α + ß4) channel currents. Injection of MarTX into the hippocampal region of mice significantly alleviated convulsive seizures. However, intravenous injection of MarTX had no antiepileptic efficacy due to the blood-brain barrier (BBB). To address this, here, we designed cell-penetrating peptide TAT-modified MarTX, in which the linker containing three glycines was put between TAT and the N-terminus of MarTX (forming MTX-N-TAT) or between TAT and the C-terminus of MarTX (forming MTX-C-TAT), respectively. We prepared them in a large amount through Escherichia coli overexpression system and then probed their antiseizure activities. Our results indicated that intravenous injection of MTX-C-TAT showed significant therapeutic efficacy of antiseizure. It increased seizure latency, reduced the total seizure duration and the number of seizures at stages 3, 4, and 5, inhibited hippocampal neuronal hyperexcitability, and exhibited neuroprotective effects on hippocampal neurons. These studies implied that MTX-C-TAT displayed intravenous antiseizure activities properly through crossing BBB and would be a potential antiepileptic drug in the future.

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice.

Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities.

Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch.

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The ß or ß-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.

Atomic force microscopy probing interactions and microstructures of ionic liquids at solid surfaces.

Ionic liquids (ILs) are room temperature molten salts that possess preeminent physicochemical properties and have shown great potential in many applications. However, the use of ILs in surface-dependent processes, e.g. energy storage, is hindered by the lack of a systematic understanding of the IL interfacial microstructure. ILs on the solid surface display rich ordering, arising from coulombic, van der Waals, solvophobic interactions, etc., all giving near-surface ILs distinct microstructures. Therefore, it is highly important to clarify the interactions of ILs with solid surfaces at the nanoscale to understand the microstructure and mechanism, providing quantitative structure-property relationships. Atomic force microscopy (AFM) opens a surface-sensitive way to probe the interaction force of ILs with solid surfaces in the layers from sub-nanometers to micrometers. Herein, this review showcases the recent progress of AFM in probing interactions and microstructures of ILs at solid interfaces, and the influence of IL characteristics, surface properties and external stimuli is thereafter discussed. Finally, a summary and perspectives are established, in which, the necessities of the quantification of IL-solid interactions at the molecular level, the development of in situ techniques closely coupled with AFM for probing IL-solid interfaces, and the combination of experiments and simulations are argued.

Aerobic Physical Exercise as a Non-medical Intervention for Brain Dysfunction: State of the Art and Beyond.

Brain disorders, including stroke, Alzheimer's disease, depression, and chronic pain, are difficult to effectively treat. These major brain disorders have high incidence and mortality rates in the general population, and seriously affect not only the patient's quality of life, but also increases the burden of social medical care. Aerobic physical exercise is considered an effective adjuvant therapy for preventing and treating major brain disorders. Although the underlying regulatory mechanisms are still unknown, systemic processes may be involved. Here, this review aimed to reveal that aerobic physical exercise improved depression and several brain functions, including cognitive functions, and provided chronic pain relief. We concluded that aerobic physical exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms and enhanced synaptic plasticity and inhibition of hippocampal atrophy and neuronal apoptosis. In addition, we also discussed the cross-system mechanisms of aerobic exercise in regulating imbalances in brain function, such as the "bone-brain axis." Furthermore, our findings provide a scientific basis for the clinical application of aerobic physical exercise in the fight against brain disorders.

Glycosylation of ß1 subunit plays a pivotal role in the toxin sensitivity and activation of BK channels.

BACKGROUND: The accessory ß1 subunits, regulating the pharmacological and biophysical properties of BK channels, always undergo post-translational modifications, especially glycosylation. To date, it remains elusive whether the glycosylation contributes to the regulation of BK channels by ß1 subunits. METHODS: Herein, we combined the electrophysiological approach with molecular mutations and biochemical manipulation to investigate the function roles of N-glycosylation in ß1 subunits. RESULTS: The results show that deglycosylation of ß1 subunits through double-site mutations (ß1 N80A/N142A or ß1 N80Q/N142Q) could significantly increase the inhibitory potency of iberiotoxin, a specific BK channel blocker. The deglycosylated channels also have a different sensitivity to martentoxin, another BK channel modulator with some remarkable effects as reported before. On the contrary to enhancing effects of martentoxin on glycosylated BK channels under the presence of cytoplasmic Ca2+, deglycosylated channels were not affected by the toxin. However, the deglycosylated channels were surprisingly inhibited by martentoxin under the absence of cytoplasmic Ca2+, while the glycosylated channels were not inhibited under this same condition. In addition, wild type BK (α+ß1) channels treated with PNGase F also showed the same trend of pharmacological results to the mutants. Similar to this modulation of glycosylation on BK channel pharmacology, the deglycosylated forms of the channels were activated at a faster speed than the glycosylated ones. However, the V1/2 and slope were not changed by the glycosylation. CONCLUSION: The present study reveals that glycosylation is an indispensable determinant of the modulation of ß1-subunit on BK channel pharmacology and its activation. The loss of glycosylation of ß1 subunits could lead to the dysfunction of BK channel, resulting in a pathological state.

[Characteristics of crustaceans community structure and its relationship with environmental factors in Dachenyang Spawning Ground Reserve, China.] / å¤§é™ˆæ´‹äº§åµåœºä¿æŠ¤åŒºç”²å£³ç±»ç¾¤è½ç»“æž„ç‰¹å¾åŠå ¶ä¸ŽçŽ¯å¢ƒå› å­çš„å ³ç³».

To elucidate the characteristics of fishery resources structure in the Dachenyang Spaw-ning Ground Reserve, the index of relative importance (IRI), biodiversity index and canonical correspondence analysis (CCA) were used to explore the relationship between crustaceans community and marine environment based on the bottom trawl survey data collected from April and November in 2018. A total of 38 crustaceans species were recorded, belonged to 25 genera in 14 families. The dominant species were Oratosquilla oratoria, Portunus trituberculatus, Charybdis bimaculata, and Parapenaeopsis hardwickii. The resource density of crustaceans was generally high in depths below 50 m in spring and in depths above 50 m in autumn. The density in the southern area was higher than nouthern area. The Margalef species richness index (D), Shannon diversity index (H) and Pielou evenness index (J) of crustaceans in spring was higher than that in autumn. The H of crustaceans in depths above 50 m was the highest. Based on cluster analysis and non-matrix multidimentional scaling analysis, the crustaceans could be classified into three groups in spring and four groups in autumn. The differences in crustacean community structure in spring were more significant than in autumn. The results of canonical correspondence analysis (CCA) showed that water depth, bottom temperature, salinity and dissolved oxygen were the main environmental factors affecting species composition and spatial structure of crustaceans in the surveyed area.

Molecular Mechanisms of Epileptic Encephalopathy Caused by KCNMA1 Loss-of-Function Mutations.

The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K+ (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the ß4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy.

Glycosylation of ß1 subunit plays a pivotal role in the toxin sensitivity and activation of BK channels

The accessory ß1 subunits, regulating the pharmacological and biophysical properties of BK channels, always undergo post-translational modifications, especially glycosylation. To date, it remains elusive whether the glycosylation contributes to the regulation of BK channels by ß1 subunits. Methods: Herein, we combined the electrophysiological approach with molecular mutations and biochemical manipulation to investigate the function roles of N-glycosylation in ß1 subunits. Results: The results show that deglycosylation of ß1 subunits through double-site mutations (ß1 N80A/N142A or ß1 N80Q/N142Q) could significantly increase the inhibitory potency of iberiotoxin, a specific BK channel blocker. The deglycosylated channels also have a different sensitivity to martentoxin, another BK channel modulator with some remarkable effects as reported before. On the contrary to enhancing effects of martentoxin on glycosylated BK channels under the presence of cytoplasmic Ca2+, deglycosylated channels were not affected by the toxin. However, the deglycosylated channels were surprisingly inhibited by martentoxin under the absence of cytoplasmic Ca2+, while the glycosylated channels were not inhibited under this same condition. In addition, wild type BK (α+ß1) channels treated with PNGase F also showed the same trend of pharmacological results to the mutants. Similar to this modulation of glycosylation on BK channel pharmacology, the deglycosylated forms of the channels were activated at a faster speed than the glycosylated ones. However, the V1/2 and slope were not changed by the glycosylation. Conclusion: The present study reveals that glycosylation is an indispensable determinant of the modulation of ß1-subunit on BK channel pharmacology and its activation. The loss of glycosylation of ß1 subunits could lead to the dysfunction of BK channel, resulting in a pathological state.(AU)

Comparison of efficacy between sequential ventilation and conventional invasive mechanical ventilation in the treatment of pulmonary hypertension complicated with respiratory failure.

OBJECTIVE: Pulmonary hypertension (PAH) is a serious progressive and fatal pulmonary disease characterized by elevated pulmonary artery pressure. Mechanical sequential ventilation has been gradually applied in the treatment of patients with PAH complicated with RF, which can effectively reduce the incidence of VAP and better promote the recovery of respiratory function. This study is aimed to determine the efficacy of sequential ventilation and conventional invasive mechanical ventilation in the treatment of pulmonary hypertension (PAH) complicated with respiratory failure (RF). METHODS: A total of 198 patients with both PAH and RF admitted to our hospital were enrolled. Among them, 102 patients were treated with sequential ventilation as a study group (stu group), and 96 patients were treated with conventional invasive mechanical ventilation as a control group (con group). Then the two groups were compared in efficacy and related indexes before and after treatment. RESULTS: The stu group experienced significantly shorter invasive ventilation time, total mechanical ventilation time, and hospitalization time than the con group (all P<0.05), and showed a significantly lower complication rate than the con group (P<0.05). The reintubation rate, weaning failure rate, and ventilator-associated pneumonia (VAP) rate of the stu group were all significantly lower than those of the con group (all P<0.05), and the stu group showed significantly higher pondus hydrogenii (pH) and arterial partial pressure of oxygen (PaO2) and significantly lower arterial carbondioxide partial pressure (PaCO2) than the con group after treatment (all P<0.05). Additionally, after treatment, the level of brain natriuretic peptide (BNP) and pulmonary artery pressure in both groups declined significantly (P<0.05), and the decline of them in the stu group was more significant than that in the con group (P<0.05). Moreover, after treatment, endothelin (ET) and angiotensin II (Ang II) in both groups declined significantly, and the decline of them in the stu group was also more significant than that in the con group (P<0.05). CONCLUSION: Compared with conventional invasive mechanical ventilation, sequential ventilation can effectively minimize the treatment time of patients with PAH complicated with RF, reduce the incidences of adverse events and complications in them, and significantly improve the blood gas analysis indexes and BNP in them, so it is worthy of clinical promotion.

Clinical characteristics associated with long-term viral shedding in patients with coronavirus disease 2019.

BACKGROUND: To delineate the clinical characteristics associated with long-term viral shedding (>21 days) in patients with coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, factors associated with long-term (>21 days) severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a conhort of 609 patients from two hospitals in Wuhan. RESULTS: The median duration of SARS-CoV-2 viral shedding was 19 days (interquartile range, 10-28 days) among all patients. There were 42% of patients having prolonged viral shedding time (>21 days), in which the longest viral shedding time was 58 days. When comparing patients with early (≤21 days) and late viral RNA clearance (>21 days), prolonged viral shedding was associated with age <65 (P=0.015), female sex (P=0.028), cough (P=0.025), fatigue (P=0.035), sore throat (P=0.013), aspartate aminotransferase (P=0.038), procalcitonin (P=0.010), albumin (P=0.003), D-dimer (P=0.011), lung involvement (P=0.014), reticular shadow (P<0.001) and lung consolidation (P=0.004). Age range (<65 years) (odds ratio [OR], 1.46 [95% CI, 1.05-2.03]) and female sex (odds ratio [OR], 1.40 [95% CI, 1.00-1.94]) were independent risk factors. CONCLUSIONS: Long-term viral shedding (>21 days) is not a rare phenomenon among COVID-19 infectious patients. Age range (<65) and female sex are independent risk factors for long-term viral shedding. Early antiviral treatment should be considered for COVID-19 patients with such risk factors. Further study should be conducted to know the infectivity of patients with long-term viral shedding in order to develop reasonable control measures.

[Spatial niche of major fish species in spring in the coastal waters of central and southern Zhejiang Province, China]. / 浙江中南部近岸海域春季主要鱼类空间生态位.

The relative importance index (IRI), mean crowding, niche breadth, and niche overlap (Qik) of major fish species were calculated based on two fishery resource surveys from April to May 2016 (spring) in the coastal waters of central and southern Zhejiang Province. The results showed that there were 24 major fish species (IRI:100), the niche breadth values of which differed greatly and were positively correlated with IRI. The niche overlaps of fishes were extremely low in spring. The total amount of species pairs with niche overlap 0.6 (Qik :0.6) were six in April and five in May, which represented 3.9% and 4.8% of the total pairs, respectively. Results from the redundancy analysis showed that the distribution of major fish species were mainly affected by temperature, salinity, water depth, and dissolved oxygen, which caused ecological differentiation of fish species.

Corrigendum: Kv1.3 Channel as a Key Therapeutic Target for Neuroinflammatory Diseases: State of the Art and Beyond.

[This corrects the article DOI: 10.3389/fnins.2019.01393.].

Occurrence and Characterization of Fungi and Mycotoxins in Contaminated Medicinal Herbs.

Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In total, 70.8% of herbs were slightly contaminated with aflatoxins (<5 µg kg-1). Codonopsis radix samples contained ochratoxin A (OTA) (360-515 µg kg-1), and Scutellariae radix samples contained OTA (49-231 µg kg-1) and citrinin (15-53 µg kg-1). Forty samples (83.3%) contained fungal contamination. Sixty-nine strains were characterized via morphological and molecular identification. The predominant mycoflora comprised four genera, Aspergillus spp. (26.1%), Penicillium spp. (24.6%), Rhizopus spp. (14.5%), and Trichoderma spp. (11.6%). Aflatoxins, OTA, and citrinin were detected in 37 cultures by high-performance liquid chromatography-tandem mass spectrometry. Approximately 21.6% of Aspergillus and Penicillium isolates produced mycotoxins. One Penicillium polonicum strain isolated from Scutellariae radix synthesized citrinin. Multiplex PCR analysis showed that three Aspergillus flavus strains harbored aflatoxin biosynthesis genes. One Aspergillus flavus strain isolated from Amomi fructus produced AFB1 and AFB2. To the best of our knowledge, the citrinin production by Aspergillus chevalieri and Penicillium sacculum was first reported in this study, which poses a potential risk of mycotoxin contamination in medicinal herbs.

Correlation of GLUT1 and GLUT4 with prognosis of patients with hypothyroidism and cardiac insufficiency.

OBJECTIVE: Hypothyroidism is a disease with symptoms of collective metabolic dysfunction and systemic dysfunction due to the lack of serum thyroid hormones caused by various reasons. GLUT4 is over-expressed in monocytes of patients with hyperthyroidism, there are also studies suggesting that there is a certain regulatory relationship of GLUT1 and GLUT4 with thyroid function. This study is aimed to explore the correlation of glucose transporter 1 (GLUT1) and GLUT4 with prognosis of patients with hypothyroidism and cardiac insufficiency. METHODS: From July 2016 to October 2019, totally 116 patients with cardiac insufficiency complicated with subclinical hypothyroidism treated in our hospital were enrolled in the research group (RG), and 110 patients with cardiac insufficiency but normal thyroid function were enrolled in the control group (CG). Serum GLUT1, GLUT4, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were detected, and the correlation between them was analyzed. Then the predictive value and risk factors of GLUT1 and GLUT4 for poor prognosis of hypothyroidism complicated with cardiac insufficiency were analyzed. RESULTS: The expression levels of GLUT1, GLUT4, FT3 and FT4 in serum of patients in RG was notably lower than that in CG, and TSH expression was remarkably higher than those in CG (P<0.05). In RG, GLUT1 and GLUT4 expression levels were positively correlated with FT3 and FT4 expression (P<0.05), but negatively correlated with TSH expression (P<0.05). ROC of GLUT1 and GLUT4 in RG in predicting poor prognosis of patients was over 0.8. Low expression of GLUT1 and GLUT4 and diabetes were independent risk factors for poor prognosis in patients with hypothyroidism complicated with cardiac insufficiency. CONCLUSION: GLUT1 and GLUT4 expression levels were significantly decreased in serum of patients with hypothyroidism complicated with cardiac insufficiency. Both of them have high predictive value for poor prognosis of patients, and are independent risk factors for poor prognosis of patients.

SCN9A Epileptic Encephalopathy Mutations Display a Gain-of-function Phenotype and Distinct Sensitivity to Oxcarbazepine.

Genetic mutants of voltage-gated sodium channels (VGSCs) are considered to be responsible for the increasing number of epilepsy syndromes. Previous research has indicated that mutations of one of the VGSC genes, SCN9A (Nav1.7), result in febrile seizures and Dravet syndrome in humans. Despite these recent efforts, the electrophysiological basis of SCN9A mutations remains unclear. Here, we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A (W1150R). Electrophysiological characterization of different SCN9A mutants in HEK293T cells, the previously-reported N641Y and K655R variants, as well as the newly-found W1150R variant, revealed that the current density of the W1150R and N641Y variants was significantly larger than that of the wild-type (WT) channel. The time constants of recovery from fast inactivation of the N641Y and K655R variants were markedly lower than in the WT channel. The W1150R variant caused a negative shift of the G-V curve in the voltage dependence of steady-state activation. All mutants displayed persistent currents larger than the WT channel. In addition, we found that oxcarbazepine (OXC), one of the antiepileptic drugs targeting VGSCs, caused a significant shift to more negative potential for the activation and inactivation in WT and mutant channels. OXC-induced inhibition of currents was weaker in the W1150R variant than in the WT. Furthermore, with administering OXC the time constant of the N641Y variant was longer than those of the other two SCN9A mutants. In all, our results indicated that the point mutation W1150R resulted in a novel gain-of-function variant. These findings indicated that SCN9A mutants contribute to an increase in seizure, and show distinct sensitivity to OXC.

Atomistic Insights into the Layered Microstructure and Time-Dependent Stability of [BMIM][PF6] Confined within the Meso-Slit of Carbon.

Clarifying the microstructures and time-dependent stability of ionic liquids (ILs) within the confinement of the meso-slit of carbon is the first step to understand the intrinsic synergy effect between ILs and a promising mesoporous carbon electrode. In this work, we adopted molecular dynamics to systematically investigate the behavior of [BMIM][PF6] in the 2.8 nm-wide meso-slit of carbon. The confined ILs formed a pronounced layered spatial distribution and can be divided into three distinct regions, namely, com-, sub-, and cen-layer, according to valley coordinates in the number density profiles. In the com-layer region, the imidazolium rings of ILs possess two dominant orientations, namely, "parallel" and "tilted standing". The rotation ability of all the ions is highly restrained. In the sub-layer and cen-layer regions, a part of the [BMIM] imidazolium ring has a preferred "tilted standing" orientation. The [BMIM] cations are still in a rotational restrain state and show a preferred rotation motion along the x-y plane. The hydrogen bond between [BMIM] cations and [PF6] anions play a crucial role in determining the confined multilayered spatial distribution and distinctive orientation properties of ILs.

Neuroprotective effects of lithium on a chronic MPTP mouse model of Parkinson's disease via regulation of α­synuclein methylation.

The pathological process of Parkinson's disease (PD) is closely associated with the death of nigral neurons, for which an effective treatment has yet to be found. Lithium, one of the most widely certified anticonvulsant and mood­stabilizing agents, exhibits evident neuroprotective effects in the treatment of epilepsy and bipolar disorder. In the present study, the neuroprotective mechanisms by which lithium acts on a chronic 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP) mouse model of PD were investigated by employing animal behavioral tests, immunohistochemistry, RT­PCR, and western blotting. The results revealed that, in open field tests, lithium treatment counteracted the reduction in movement distance as well as activity time induced by MPTP administration. The compound could also prolong the drop time of MPTP­treated mice in rotarod tests. Moreover, lithium treatment corrected the loss of nigral neurons, the increase of α­synuclein (SNCA) in substantia nigra as well as in the striatum of MPTP­treated mice, and decreased the methylation of SNCA intron 1 in DNA from the same regions. Furthermore, marked changes were observed in the expression of miRNAs including miR­148a, a potential inhibitor of DNMT1, in the MPTP­treated mice. These results suggested that the early application of lithium was important for alleviating the behavioral deficits experienced in the PD model, and that the neuroprotective action of lithium was achieved through a lithium­triggered miRNA regulation mechanism. Essentially, our findings indicated that lithium may be beneficial in the prevention and treatment of PD through the regulation of α­synuclein methylation.

Anticonvulsant Effects of Dingxian Pill in Pentylenetetrazol-Kindled Rats.

Dingxian pill has been used as an antiepilepsy agent in China from ancient to modern times, of which the concrete pharmacological characterization and the underlying molecular mechanism remain unclear. The present study was undertaken to investigate them by animal behavior, electroencephalogram (EEG), Morris water maze, immunohistochemistry, transcriptomics, and real-time PCR. In our results, the treatment of Dingxian pill dose-dependently inhibited PTZ-induced seizure-like behavior and reduced the seizure grades, LFP power spectral density, and brain wave of the epileptiform EEG component induced by PTZ. In Morris water maze tests, the learning and memory ability of kindled epileptic rats could be attenuated more efficiently by Dingxian pill. For the immediate early gene c-fos, the expression was reduced after Dingxian pill treatment, and the difference was significant between the treatment and the model group. Through the transcriptome analysis of the gene expression in hippocampus, Egr3, Nrg, Arc, and Ptgs2, closely related to epilepsy, had been proved to be downregulated by application of Dingxian pill. All of the results not only highlight the antiepileptic effects of Dingxian pill and its molecular mechanism, but also provide a modern validity theory for the clinical application of traditional Chinese medicine (TCM).