Low-frequency stimulation in the zona incerta attenuates seizure via driving GABAergic neuronal activity.

BACKGROUND: Managing refractory epilepsy presents a significant a substantial clinical challenge. Deep brain stimulation (DBS) has emerged as a promising avenue for addressing refractory epilepsy. However, the optimal stimulation targets and effective parameters of DBS to reduce seizures remian unidentified. OBJECTIVES: This study endeavors to scrutinize the therapeutic potential of DBS within the zona incerta (ZI) across diverse seizure models and elucidate the associated underlying mechanisms. METHODS: We evaluated the therapeutic potential of DBS with different frequencies in the ZI on kainic acid (KA)-induced TLE model or M1-cortical seizures model, pilocarpine-induced M1-cortical seizure models, and KA-induced epilepsy model. Further, employing calcium fiber photometry combined with cell-specific ablation, we sought to clarified the causal role of ZI GABAergic neurons in mediating the therapeutic effects of DBS. RESULTS: Our findings reveal that DBS in the ZI alleviated the severity of seizure activities in the KA-induced TLE model. Meanwhile, DBS attenuated seizure activities in KA- or pilocarpine-induced M1-cortical seizure model. In addition, DBS exerts a mitigating influence on KA induced epilepsy model. DBS in the ZI showed anti-seizure effects at low frequency spectrum, with 5 Hz exhibiting optimal efficacy. The low-frequency DBS significantly increased the calcium activities of ZI GABAergic neurons. Furthermore, selective ablation of ZI GABAergic neurons with taCasp3 blocked the anti-seizure effect of low-frequency DBS, indicating the anti-seizure effect of DBS is mediated by the activation of ZI GABAergic neurons. CONCLUSION: Our results demonstrate that low-frequency DBS in the ZI attenuates seizure via driving GABAergic neuronal activity. This suggests that the ZI represents a potential DBS target for treating both hippocampal and cortical seizure through the activation of GABAergic neurons, thereby holding therapeutic significance for seizure treatment.

Recognition memory deficits detected through eye-tracking in well-controlled children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Children with self-limited epilepsy characterized by centrotemporal spikes (SeLECTS) exhibit cognitive deficits in memory during the active phase, but there is currently a lack of studies and techniques to assess their memory development after well-controlled seizures. In this study, we employed eye-tracking techniques to investigate visual memory and its association with clinical factors and global intellectual ability, aiming to identify potential risk factors by examining encoding and recognition processes. METHODS: A total of 26 recruited patients diagnosed with SeLECTS who had been seizure-free for at least 2 years, along with 24 control subjects, underwent Wechsler cognitive assessment and an eye-movement-based memory task while video-electroencephalographic (EEG) data were recorded. Fixation and pupil data related to eye movements were utilized to detect distinct memory processes and subsequently to compare the cognitive performance of patients exhibiting different regression patterns on EEG. RESULTS: The findings revealed persistent impairments in visual memory among children with SeLECTS after being well controlled, primarily observed in the recognition stage rather than the encoding phase. Furthermore, the age at onset, frequency of seizures, and interictal epileptiform discharges exhibited significant correlations with eye movement data. SIGNIFICANCE: Children with SeLECTS exhibit persistent recognition memory impairment after being well controlled for the disease. Controlling the frequency of seizures and reducing prolonged epileptiform activity may improve memory cognitive development. The application of the eye-tracking technique may provide novel insights into exploring memory cognition as well as underlying mechanisms associated with pediatric epilepsy.

A fast and non-invasive artificial intelligence olfactory-like system that aids diagnosis of Parkinson's disease.

BACKGROUND AND PURPOSE: Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory-like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD. METHODS: The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity. RESULTS: A 20-s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5-12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn-Yahr stage. CONCLUSIONS: This study provides a fast, low-cost and non-invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.

Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures.

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Superheated steam processing: An emerging technology to improve food quality and safety.

Heat processing is one of the most efficient strategies used in food industry to improve quality and prolong shelf life. However, conventional processing methods such as microwave heating, burning charcoal treatment, boiling, and frying are energy-inefficient and often lead to inferior product quality. Superheated steam (SHS) is an innovative technology that offers many potential benefits to industry and is increasingly used in food industry. Compared to conventional processing methods, SHS holds higher heat transfer coefficients, which can reduce microorganisms on surface of foodstuffs efficiently. Additionally, SHS generates a low oxygen environment, which prevents lipid oxidation and harmful compounds generation. Furthermore, SHS can facilitate development of desired product quality, such as protein denaturation with functional characteristics, proper starch gelatinization, and can also reduce nutrient loss, and improve the physicochemical properties of foodstuffs. The current work provides a comprehensive review of the impact of SHS on the nutritional, physicochemical, and safety properties of various foodstuffs including meat, fruits, and vegetables, cereals, etc. Additionally, it also provides food manufacturers and researchers with basic knowledge and practical techniques for SHS processing of foodstuffs, which may improve the current scope of SHS and transfer current food systems to a healthy and sustainable one.

Driving status and attitudes of patients with epilepsy holding a driving license in eastern China.

PURPOSE: Patients with epilepsy (PWE) remain completely and permanently banned from driving under the latest changes to China's laws. The twoaims of this study were, firstly, to evaluate the driving status of PWE with a driving license and the determinants of them continuing to drive; secondly, to investigate awareness and perceptions of epilepsy driving restrictions among PWE and the general population. METHODS: Patients with epilepsy with a driver's license who attended the Fourth Affiliated Hospital and the Second Affiliated Hospital of Zhejiang University for treatment of their condition were invited to participate in a questionnaire survey between June 2021 and June 2022. During the same period, age-matched people with driver's licenses without epilepsy living in the cities of Hangzhou and Yiwu, Zhejiang province were invited to participate in the questionnaire study. RESULTS: A total of 291 PWE with a driver's license and 289 age-matcheddrivers among the general public participated in the survey. Of the sample, 41.6% of PWE and 26.0% of general drivers stated that they were aware of legal driving restrictions for PWE in China. In the past year, 54% of PWE had driven and 42.5% drove a vehicle daily. Logistic regression revealed that male sex (95% confidence interval [CI]: 1.36-3.61, P = 0.001), age (95% CI: 1.12-3.27, P ≤ 0.036), and the number of antiseizure medications taken (95% CI: 0.24-0.25, P ≤ 0.001) were independently associated with illegally driving with epilepsy. In terms of legalissues, 71.1% of PWE did not support a lifetime ban on driving and 50.2% disagreedwith physician reporting of PWE to the traffic authorities. CONCLUSION: Illegal driving is highly prevalent among PWE who hold a driving license, and male gender, age, and number of ASMs had an independent association with illegal driving in patients with epilepsy. There are highly varying opinions on the current driving laws with respect to PWE. Detailed national standards for medical fitness for driving that are easy to implement and enforce are urgently required for China.

An Intelligent Epileptic Prediction System Based on Synchrosqueezed Wavelet Transform and Multi-Level Feature CNN for Smart Healthcare IoT.

Epilepsy is a common neurological disease worldwide, characterized by recurrent seizures. There is currently no cure for epilepsy. However, seizures can be controlled by drugs and surgeries in about 70% of epileptic patients. A timely and accurate prediction of seizures can prevent injuries during seizures and improve the patients' quality of life. In this paper, we proposed an intelligent epileptic prediction system based on Synchrosqueezed Wavelet Transform (SWT) and Multi-Level Feature Convolutional Neural Network (MLF-CNN) for smart healthcare IoT network. In this system, we used SWT to map EEG signals to the frequency domain, which was able to measure the energy changes in EEG signals caused by seizures within a well-defined Time-Frequency (TF) plane. MLF-CNN was then applied to extract multi-level features from the processed EEG signals and classify the different seizure segments. The performance of our proposed system was evaluated with the publicly available CHB-MIT dataset and our private ZJU4H dataset. The system achieved an accuracy of 96.99% and 94.25%, a sensitivity of 96.48% and 97.76%, a specificity of 97.46% and 94.07% and a false prediction rate (FPR/h) of 0.031 and 0.049 FPR/h on the CHB-MIT dataset and the ZJU4H dataset, respectively.

Genome-wide analysis of chloride channel-encoding gene family members and identification of CLC genes that respond to Cl-/salt stress in upland cotton.

Chloride channels (CLCs) are kinds of anion transport protein family members that are mainly distributed in cell endomembrane systems of prokaryotic and eukaryotic organisms and mediate anion (Cl-, as a representative) transport and homeostasis. Some CLC genes have been reported to be involved in Cl-/salt tolerance of plants exposed to NaCl stress. Through BLAST in cotton database, a total of 22 CLCs were identified in genomes A and D in upland cotton (Gossypium hirsutum L.), and except for GhCLC6 and GhCLC17, they formed highly similar homologous genes pairs. According to the prediction in PlantCARE database, many cis-acting elements related to abiotic stress responses, including ABREs, AREs, GT-1s, G-boxes, MYBs, MYCs, etc., were found in the promoters of GhCLCs. qRT-PCR revealed that most GhCLC gene expression was upregulated in the roots and leaves of cotton seedlings under salt stress, and those of homologous GhCLC4/15, GhCLC5/16, and GhCLC7/18 displayed more obvious expression. Furthermore, according to leaf virus-induced gene silencing (VIGS) assay and compared with the salt-stressed GhCLC4/15- and GhCLC7/18-silenced cotton plants, the salt-stressed GhCLC5/16-silenced plants displayed relatively better growth with significant increases in both Cl- content and Cl-/NO3- ratio in the roots and drop of the same parameters in the leaves. These results indicate that homologous GhCLC5/16, with the highest NaCl-induced upregulation of expression and the maximum number of MYC cis-acting elements, might be the key members contributing to cotton Cl-/salt tolerance by regulating the transport, interaction and homeostasis of Cl- and NO3-.

Neurologists' attitudes toward driving among persons with epilepsy in China: A pilot electronic survey.

PURPOSE AND METHODS: Persons with epilepsy (PWE) remain completely and permanently prohibited from driving in China currently. Previous studies have shown that a considerable proportion of PWE with uncontrolled seizures in China continue to drive motor vehicles. Discrepancy between Chinese policy and driving practices for PWE is potentially concerning. We conducted a preliminary online electronic questionnaire (e-questionnaire) survey among neurologists in China aiming to explore neurologists' attitudes toward the issue of driving among PWE. RESULTS: A total of 358 neurologists completed the e-questionnaire with a response rate of 75.8%. 50.3% of neurologists stated that they knew the driving restriction law in China. With respect to reporting of cases to relevant driving authorities, 82.4% of neurologists never directly report PWE, and 90.8% consider that it is PWE's responsibility to report themselves. 87.4% of physicians surveyed indicated that the lack of clearly-articulated guidelines is a major impediment to their routine discussions of driving fitness for PWE. Subgroup analysis indicated that 76.2% of epileptologists were of the opinion that persons with well-controlled epilepsy should be allowed to drive versus 56.2% of general neurologists (P < 0.05). CONCLUSION: Currently, neurologists in China have a low awareness of the legal driving restriction for PWE and have highly varying practices with respect to counseling PWE about driving. According to our preliminary results, a clearly-articulated published national document for medical fitness for driving in China is necessary in order to standardize physicians' practices.

The Recretohalophyte Tamarix TrSOS1 Gene Confers Enhanced Salt Tolerance to Transgenic Hairy Root Composite Cotton Seedlings Exhibiting Virus-Induced Gene Silencing of GhSOS1.

The salt overly sensitive 1 (SOS1) gene encodes the plasma membrane Na+/H+ antiporter, SOS1, that is mainly responsible for extruding Na+ from the cytoplasm and reducing the Na+ content in plants under salt stress and is considered a vital determinant in conferring salt tolerance to the plant. However, studies on the salt tolerance function of the TrSOS1 gene of recretohalophytes, such as Tamarix, are limited. In this work, the effects of salt stress on cotton seedlings transformed with tobacco-rattle-virus-based virus-induced gene silencing (VIGS) of the endogenous GhSOS1 gene, or Agrobacterium rhizogenes strain K599-mediated TrSOS1-transgenic hairy root composite cotton plants exhibiting VIGS of GhSOS1 were first investigated. Then, with Arabidopsis thaliana AtSOS1 as a reference, differences in the complementation effect of TrSOS1 or GhSOS1 in a yeast mutant were compared under salt treatment. Results showed that compared to empty-vector-transformed plants, GhSOS1-VIGS-transformed cotton plants were more sensitive to salt stress and had reduced growth, insufficient root vigor, and increased Na+ content and Na+/K+ ratio in roots, stems, and leaves. Overexpression of TrSOS1 enhanced the salt tolerance of hairy root composite cotton seedlings exhibiting GhSOS1-VIGS by maintaining higher root vigor and leaf relative water content (RWC), and lower Na+ content and Na+/K+ ratio in roots, stems, and leaves. Transformations of TrSOS1, GhSOS1, or AtSOS1 into yeast NHA1 (Na+/H+ antiporter 1) mutant reduced cellular Na+ content and Na+/K+ ratio, increased K+ level under salt stress, and had good growth complementation in saline conditions. In particular, the ability of TrSOS1 or GhSOS1 to complement the yeast mutant was better than that of AtSOS1. This may indicate that TrSOS1 is an effective substitute and confers enhanced salt tolerance to transgenic hairy root composite cotton seedlings, and even the SOS1 gene from salt-tolerant Tamarix or cotton may have higher efficiency than salt-sensitive Arabidopsis in regulating Na+ efflux, maintaining Na+ and K+ homeostasis, and therefore contributing to stronger salt tolerance.

Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: A systematic review of reported cases.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently recognized autoimmune disorder which is responsive to immunotherapy. However, the outcomes of different immunotherapies have not been defined and there have been few studies that carried out a comparison among them. To provide an overview of the clinical characteristics, treatments, and outcomes of anti-NMDAR encephalitis, we systematically reviewed the literature in the PubMed, Medline, Embase, Cochrane Library, BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang databases. Eighty-three studies with a total of 432 patients were included. The median age was 22years. Two hundred ninety-three (68%) patients were female, 87 (21%) of 412 patients had a tumor, including 68 (78%) patients with ovarian teratoma. Pediatric patients had a higher ratio of seizures to psychiatric symptoms as the initial manifestation (p=0.0012), a lower proportion with a tumor (p<0.0001) and CSF pleocytosis (p=0.0163), and a better outcome (p=0.0064) than adults. Patients who died had a higher proportion of CSF pleocytosis than the patients who survived (p=0.0021). There were no significant differences among three first-line immunotherapy used alone (p=0.9172) or among combinations of every two of them (p=0.3059). With regard to the use of corticosteroid and IVIG, there were no significant differences between the outcomes of early combined treatment and sequential treatment (p=0.7277), or between using corticosteroid first and IVIG first (p=0.5422). Our findings suggest that the clinical characteristics and outcomes for pediatric patients were different from adult patients, and no significant differences were found among different immunotherapies.

Hormonal Changes in Women with Epilepsy.

Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.

Pregnancy-related knowledge in women with epilepsy in childbearing age: A pilot questionnaire survey from China.

PURPOSE: We aim to understand the knowledge of and attitudes toward pregnancy issues among women with epilepsy (WWE) and their caregivers and analyze the answers from the questionnaire to expose topics that require educational activities; thus, WWE experiences pregnancy better. METHODS: WWE at their childbearing age and/or their caregivers who entered the Fourth Affiliated Hospital of Zhejiang University for treatment of their condition were invited to fill out a questionnaire between March 1 and November 31, 2022. RESULTS: A combined total of 205 WWE and 142 caregivers completed the questionnaires. Among the surveyed WWE, a majority (63.74%) reported experiencing at least one miscarriage or induced abortion. However, a significant proportion (84.62%) of these WWE were still able to successfully give birth to at least one child. Furthermore, the offspring of these WWE showed no significant differences compared to the offspring of women without epilepsy, as reported by 93.51% of the participants. The participants' knowledge regarding the impact of epilepsy on pregnancy was found to be comparable, with average scores of 7.74 and 7.84, respectively. The participants exhibited a limited comprehension of antiseizure medications (ASMs)-related knowledge, specifically pertaining to ASMs adjustment during pregnancy (17.56% vs. 16.90%) and offspring outcomes (30.24% vs. 26.06%). Statistical analysis revealed significant correlations between the overall score and education level (p < .001), as well as epilepsy duration (p = .008). Regarding the source of knowledge, participants acknowledged primarily relying on neurologists, who remained their preferred choice for consultation. CONCLUSION: In our study, the understanding of pregnancy-related knowledge did not differ from WWE and their caregivers, both are far from satisfactory in certain areas. It is urgent for WWE and their caregivers to improve their pregnancy-related knowledge of epilepsy. As their primary access is from knowledgeable health care professionals like neurologists, well-trained neurologists in epilepsy management during pregnancy are in need.

Analysis of Amplitude Modulation of EEG Based on Holo-Hilbert Spectrum Analysis During General Anesthesia.

OBJECTIVE: The study aims to investigate the relationship between amplitude modulation (AM) of EEG and anesthesia depth during general anesthesia. METHODS: In this study, Holo-Hilbert spectrum analysis (HHSA) was used to decompose the multichannel EEG signals of 15 patients to obtain the spatial distribution of AM in the brain. Subsequently, HHSA was applied to the prefrontal EEG (Fp1) obtained during general anesthesia surgery in 15 and 34 patients, and the α-θ and α-δ regions of feature (ROFs) were defined in Holo-Hilbert spectrum (HHS) and three features were derived to quantify AM in ROFs. RESULTS: During anesthetized phase, an anteriorization of the spatial distribution of AMs of α-carrier in brain was observed, as well as AMs of α-θ and α-δ in the EEG of Fp1. The total power ([Formula: see text]), mean carrier frequency ([Formula: see text]) and mean amplitude frequency ([Formula: see text]) of AMs changed during different anesthesia states. CONCLUSION: HHSA can effectively analyze the cross-frequency coupling of EEG during anesthesia and the AM features may be applied to anesthesia monitoring. SIGNIFICANCE: The study provides a new perspective for the characterization of brain states during general anesthesia, which is of great significance for exploring new features of anesthesia monitoring.

Septal stimulation attenuates hippocampal seizure with subregion specificity.

OBJECTIVE: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. METHODS: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model. RESULTS: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons. SIGNIFICANCE: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. PLAIN LANGUAGE SUMMARY: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.

Identification of four biotypes in temporal lobe epilepsy via machine learning on brain images.

Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication - a necessary step for precise medicine.

Study of the Structural Changes and Internal Activator Transport Behavior after Activation of Aluminum-Based Flameless Ration Heaters: Experimental and Molecular Dynamics Simulations.

Aluminum-based flameless ration heaters (AFRHs) are heating elements in food packaging. Water is used to activate AFRHs. The material properties of each region of AFRHs were determined by X-ray diffraction, scanning electron microscopy, and hydrogen and heat generation. The results show that the internal cross-section shows stratification with hydrogen and heat production capacities of 105.2 ± 9.7 mL/g and 1435.0 ± 30.3 J/g for the outer layer, 27.1 ± 4.4 mL/g and 80.4 ± 3.1 J/g for the inner layer, and 1.1 ± 0.01 mL/g and 1.2 ± 0.05 J/g for the middle layer, respectively. According to the correspondence between aluminum and hydrogen in the aluminum-water reaction relationship, the reaction efficiency of the outer layer and the inner layer is as low as 64 and 80%, which is an indication of low reaction efficiency. To analyze the reasons for low reaction efficiency, a pore channel model of 3.5 nm tricalcium aluminate (C3A) was developed using molecular dynamics (MD) to reveal the adsorption behavior of the activator in the pore channel. The results show that the activator is subject to solid surface adsorption in the pore channel with a low diffusion coefficient. Oxygen atoms on the surface adsorb hydrogen atoms to form hydrogen bonds and sodium ions to form ionic bonds with calcium ions. This increases the retention time of the activator on the surface. The MD results explain the low reaction efficiency of AFRHs at the microscopic scale. Moreover, it provides ideas and a basis for the optimization of AFRHs.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy.

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal sclerosis. There is no effective treatment for cognitive impairment. Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in temporal lobe epilepsy. However, their role in the cognitive impairment of temporal lobe epilepsy remains unclear. In this study, we found that patients with temporal lobe epilepsy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory, but had no impairment in nonverbal memory. The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tracts measured by diffusion tensor imaging. In a mouse model of chronic temporal lobe epilepsy induced by kainic acid, the number of medial septum cholinergic neurons was reduced and acetylcholine release was reduced in the hippocampus. Furthermore, selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice, and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid- and kindling-induced epilepsy models. These results suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Ligand activation mechanisms of human KCNQ2 channel.

The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP2), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP2, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2.

Excitatory somatostatin interneurons in the dentate gyrus drive a widespread seizure network in cortical dysplasia.

Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous studies have primarily focused on the disruption of dysplastic lesions, rather than remote regions such as the hippocampus. Here, we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia. We further investigated the cellular substrates leading to the epileptic hippocampus, using multiscale tools including calcium imaging, optogenetics, immunohistochemistry and electrophysiology. For the first time, we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures. Somatostatin-positive were recruited during cortical dysplasia-related seizures. Interestingly, optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization. By contrast, parvalbumin-positive interneurons retained an inhibitory role as in controls. Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus. Taken together, our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.