BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory ...BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.展开更多
AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD)alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited a...AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD)alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded.Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform.The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64%of epileptic infants showed an obvious improvement,with a 50%decrease in seizure frequency.GM structure in epileptic infants(P1 group)differed dramatically from that in healthy infants(Health group).Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group).Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups.Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group.KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.展开更多
BACKGROUND： Anti-epilepsy and anti-psychosis drugs have traditionally been used in the clinic to treat epilepsy complicated by mental disorders. However, there is still no effective therapy for refractory epilepsy pa...BACKGROUND： Anti-epilepsy and anti-psychosis drugs have traditionally been used in the clinic to treat epilepsy complicated by mental disorders. However, there is still no effective therapy for refractory epilepsy patients suffering from persistent mental disorders. OBJECTIVE： To explore the therapeutic effects of stereotactic multi-element localization and multi-target radiofrequency ablation on patients with refractory primary epilepsy and mental disorders. DESIGN： A retrospective case analysis. SETTING： Department of Neurosurgery, the 454 Hospital of Chinese PLA. PARTICIPANTS： Between June and November 2004, 13 patients with refractory primary epilepsy complicated by persistent mental disorders were admitted to the Department of Neurosurgery, the 454 Hospital of Chinese PLA. The patient group consisted of nine males and four females, with an average age of 25 years （range 18-39 years）, and a course of disease ranging 3-11 years. Diagnosis of mental disorders was in accordance with Chinese Classification of Mental Disorders. Written informed consent was obtained from all patients and their families, and the treatment protocol was approved by the Ethics Committee of the Hospital. METHODS： Under venous inhalation anesthesia, the disease targets, including bilateral corpus callosum, bilateral amygdala, and bilateral medial septal area, as well as unilateral Forel-H area, were coagulated by RFG-3CF radiofrequency thermocoagnlation at 75-80 ℃ for 60-70 seconds. During thermocoagulation, the targets were identified using deep-brain microelectrodes and localized according to electrophysiology and electric resistance values. MAIN OUTCOME MEASURES： One year post-surgery, epileptic seizures were assessed on the basis of the Tan classification, and psychogenic （non-epileptic） seizures were evaluated using a 5-grade system. RESULTS： All enrolled 13 epileptic patients were included in the final analysis. The results of follow-up evaluations demonstrated that epilepsy was well-controlled. In total, nine patients did not experience relapse, and the frequency of seizures was reduced by 75% in two patients, and 50%-74% in another two patients. Psychogenic seizures were ameliorated in 11 cases （class 1, recovery） and improved significantly in two cases （class 2, significant improvement）. CONCLUSION： Radiofrequency ablation of bilateral corpus callosum, bilateral amygdala, bilateral medial septal area, and unilateral Forel-H area exhibits certain efficacy in treating epileptic patients suffering from persistent mental disorders.展开更多
High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillim...High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillimeter or micrometer level.This entails connecting hundreds or thousands of electrode wires on a limited surface.This study reported a class of flexible,ultrathin,highdensity electrocorticogram(ECoG)electrode arrays.The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement.The flexible,ultrathin,high-density ECoG electrode array was conformably attached to the cortex for reliable,high spatial resolution electrophysiologic recordings.The minimum spacing between electrodes was 15μm,comparable to the diameter of a single neuron.Eight hundred electrodes were prepared with an electrode density of 4444 mm^(-2).In focal epilepsy surgery,the flexible,high-density,laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves inrabbits,improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level.The flexible,high-density,laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.展开更多
The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obt...The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.展开更多
Previous studies have focused on medial temporal lobe epilepsy secondary to central nervous system infections. Several large-sample analyses of multi-lobe injuries or complications of medial temporal lobe epilepsy hav...Previous studies have focused on medial temporal lobe epilepsy secondary to central nervous system infections. Several large-sample analyses of multi-lobe injuries or complications of medial temporal lobe epilepsy have been reported. The present study selected 29 patients （10 males and 19 females with a mean age of 18 years） with refractory epilepsy secondary to central nervous system infections （meningitis in 8, encephalitis in 21） from Beijing Functional Neurosurgical Institute from May 2006 to August 2008. All patients underwent computer tomography or magnetic resonance imaging, as well as electroencephalogram examinations; cortical electrodes were embedded in 11 patients. In addition, 13 （45%） patients underwent anterior temporal Iobectomy, and 16 （56%） underwent extratemporal corcticectomy. Results showed that 18 （62%） patients obtained favorable outcomes following surgical treatment, including 80% with temporal lobe epilepsy and 50% with extratemporal epilepsy. Central nervous system infection was not a contraindication for epilepsy treatment, and identification of epileptic foci proved to be crucial. In addition, a young age at infection, as well as prolonged latent period from time of infection to initial afebrile seizure, were 2 predictive factors for all patients. Cortical electrodes significantly increased the detection rate of epileptic foci, but did not improve prognosis of foci excision.展开更多
To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of l...To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.展开更多
A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The loci of 60% of the patients could be positioned using a combined positron emission tomogr...A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The loci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser＇s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser＇s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser＇s classification score was significantly higher in the single-focus group as compared with the multiple-foci group.展开更多
Electrical Source Imaging (ESI) is a non-invasive technique of reconstructing brain activities using EEG data. This technique has been applied to evaluate epilepsy patients being evaluated for epilepsy surgery, showin...Electrical Source Imaging (ESI) is a non-invasive technique of reconstructing brain activities using EEG data. This technique has been applied to evaluate epilepsy patients being evaluated for epilepsy surgery, showing encouraging results for mapping interictal epileptiform discharges (IED). However, ESI is underused in planning epilepsy surgery. This is basically due to the wide availability of methods for solving the electromagnetism inverse problem (e-IP) associated to few studies using EEG setups similar to those most commonly used in clinical setting. In this study, we applied six different methods of solving the e-IP based on IEDs of 20 focal epilepsy patients that presented abnormalities in their MRI. We compared the ESI maps obtained by each method with the location of the abnormality, calculating the Euclidian distances from the center of the lesion to the closest border of the method solution (CL-BM) and also to the solution’s maxima (CL-MM). We also applied a score system in order to allow us to evaluate the sensitivity of each method for temporal and extra temporal patients. In our patients, the Bayesian Model Averaging method had a sensitivity of 86% and the shortest CL-MM. This method also had more restricted solutions that were more representative of epileptogenic activities than those obtained by the other methods.展开更多
The service life of refractory brick in the slag tapping hole of gasifiers is a significant concern for long-term and stable operation.This study examined the damage mechanism of high chromia refractory of four commer...The service life of refractory brick in the slag tapping hole of gasifiers is a significant concern for long-term and stable operation.This study examined the damage mechanism of high chromia refractory of four commercial coal-water slurry gasifiers with their corresponding gasification coal samples and the corroded refractory bricks in the slag tapping hole of the gasifier.The slag characteristic,including crystallization and viscosity-temperature of four gasification coal samples were analyzed.The results revealed that the low viscosity slag could lead to more severe damage to refractory bricks.Given the risk of slag crystallization,it is recommended to establish a safe slag tapping temperature range should be set as tICT(initial crystallization temperature)−t_(2.5) when tICT is higher than t_(25).Upon examining interior morphology of these corroded refractory bricks,some cracks were observed within them.The chemical composition of molten slag was analyzed using SEM-EDS.However,XRD results found no spinel containing zirconium in these cracks.This suggests that the emergence of these cracks are mainly attributed to the molten slag penetration and the subsequent reaction with the refractory material.The difference in thermal expansion between the newly formed substances and refractory material is critical in forming these cracks.Furthermore,SEM-EDS analysis was also conducted on the slag-aggregate and the slag-matrix interface.The results reveal that the reduction in Cr_(2)O_(3) content is the earliest characteristic of damage in high chromia refractories.A proposed damage mechanism of refractory brick suggests that the matrix and aggregate of high chromia refractory are initially compromised because of the reduced Cr_(2)O_(3) content.Subsequently,the molten slag penetrates the interior of the refractory brick,forming new substances,leading to damage caused by the difference in thermal expansion between the new substances and the refractory brick.Understanding and preventing the reduction of Cr_(2)O_(3) content is vital to prolonging the service life of refractory brick in the slag tapping hole of the gasifier based on this damage mechanism.展开更多
Intelligent refractory materials represent a new generation of high-temperature functional materials that significantly enhance the service performance of traditional refractories in extreme environments through integ...Intelligent refractory materials represent a new generation of high-temperature functional materials that significantly enhance the service performance of traditional refractories in extreme environments through integrated sensing,response,and adaptive mechanisms.A comprehensive overview of intelligent refractory materials was provided,focusing on their classification,preparation techniques,and industrial applications.Firstly,the categories and design principles of intelligent refractory materials are introduced,including self-healing,self-regulating,and self-diagnosing types,which enhance durability and performance under extreme conditions.Subsequently,advanced preparation technologies are discussed,such as 3D printing for complex geometries,nanocomposite engineering for improved mechanical and thermal properties,gradient design for optimized thermal stress resistance and information technology including machine learning,health monitoring,digital twin.Finally,the industrial applications of these materials are highlighted,particularly in steel metallurgy,building materials industry,and energy.It aims to bridge the gap between research advancements and practical implementation,offering insights into future trends in intelligent refractory material development.展开更多
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ...Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.展开更多
Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which ...Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which relies on lixiviants prepared using volatilized sulfur obtained from roasting,has not been fully elucidated.This study employs the response surface methodology to optimize processing parameters,resulting in an increased gold extraction rate of 96.18%.Analytical factorization and the Tafel curve indicate that CuSO_(4) and NH_(3)·H_(2)O significantly influence the self-leaching process.Furthermore,X-ray photoelectron spectroscopy(XPS)analysis reveals that S^(2−),S_(2)^(2−),polysulfides(S_(n)^(2−)),and thiosulfate(S_(2)O_(3)^(2−))are involved in the gold leaching reaction,with S^(2−),S_(2)^(2−),and S_(n)^(2−) serving as primary ligands for gold complexation.The role of S_(2)O_(3)^(2−) in the early stages of the gold-leaching reaction is also noteworthy.The copper–ammonia complex catalyzes the self-leaching gold reaction;however,an improper addition ratio can lead to copper-sulfur compound precipitates,reducing the extraction rate.展开更多
Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from cli...Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.展开更多
Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various ne...Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.展开更多
Refractory metals,including tungsten(W),tantalum(Ta),molybdenum(Mo),and niobium(Nb),play a vital role in industries,such as nuclear energy and aerospace,owing to their exceptional melting temperatures,thermal durabili...Refractory metals,including tungsten(W),tantalum(Ta),molybdenum(Mo),and niobium(Nb),play a vital role in industries,such as nuclear energy and aerospace,owing to their exceptional melting temperatures,thermal durability,and corrosion resistance.These metals have body-centered cubic crystal structure,characterized by limited slip systems and impeded dislocation motion,resulting in significant low-temperature brittleness,which poses challenges for the conventional processing.Additive manufacturing technique provides an innovative approach,enabling the production of intricate parts without molds,which significantly improves the efficiency of material usage.This review provides a comprehensive overview of the advancements in additive manufacturing techniques for the production of refractory metals,such as W,Ta,Mo,and Nb,particularly the laser powder bed fusion.In this review,the influence mechanisms of key process parameters(laser power,scan strategy,and powder characteristics)on the evolution of material microstructure,the formation of metallurgical defects,and mechanical properties were discussed.Generally,optimizing powder characteristics,such as sphericity,implementing substrate preheating,and formulating alloying strategies can significantly improve the densification and crack resistance of manufactured parts.Meanwhile,strictly controlling the oxygen impurity content and optimizing the energy density input are also the key factors to achieve the simultaneous improvement in strength and ductility of refractory metals.Although additive manufacturing technique provides an innovative solution for processing refractory metals,critical issues,such as residual stress control,microstructure and performance anisotropy,and process stability,still need to be addressed.This review not only provides a theoretical basis for the additive manufacturing of high-performance refractory metals,but also proposes forward-looking directions for their industrial application.展开更多
Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The ...Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.展开更多
Fenton-like technology based on peroxymonosulfate activation has shown great potential in refractory organics degradation.In this work,single Fe atom catalysts were synthesized through facile ball milling and exhibite...Fenton-like technology based on peroxymonosulfate activation has shown great potential in refractory organics degradation.In this work,single Fe atom catalysts were synthesized through facile ball milling and exhibited very high performance in peroxymonosulfate activation.The Fe single-atom filled an N vacancy on the triazine ring edge of C_(3)N_(4),as confirmed through X-ray absorption fine structure,density functional calculation and elec-tron paramagnetic resonance.The SAFe_(0.4)–C_(3)N_(4)/PMS system could completely remove phenol(20 mg/L)within 10 min and its first-order kinetic constant was 12.3 times that of the Fe_(3)O_(4)/PMS system.Under different ini-tial pH levels and in various anionic environments,SAFe_(0.4)–C_(3)N_(4) still demonstrated excellent catalytic activity,achieving a removal rate of over 90%for phenol within 12 min.In addition,SAFe_(0.4)–C_(3)N_(4) exhibited outstanding selectivity in reaction systems with different pollutants,showing excellent degradation effects on electron-rich pollutants only.Hydroxyl radicals(•OH),singlet oxygen(1O_(2))and high-valent iron oxide(Fe(Ⅳ)=O)were de-tected in the SAFe_(0.4)–C_(3)N_(4)/PMS system through free radical capture experiments.Further experiments on the quenching of active species and a methyl phenyl sulfoxide probe confirmed that 1O_(2) and Fe(Ⅳ)=O played dom-inant roles.Additionally,the change in the current response after adding PMS and phenol in succession proved that a direct electron transfer path between organic matter and the catalyst surface was unlikely to exist in the SAFe_(0.4)–C_(3)N_(4)/PMS/Phenol degradation system.This study provides a new demonstration of the catalytic mech-anism of single-atom catalysts.展开更多
Exploiting effective approaches to achieve superior ductility has consistently been a topic of widespread interest in refractory multi-principal-element alloys(RMPEAs).Herein,we developed a one-step forming method,ele...Exploiting effective approaches to achieve superior ductility has consistently been a topic of widespread interest in refractory multi-principal-element alloys(RMPEAs).Herein,we developed a one-step forming method,electron-beam directional-solidification(EB-DS),to fabricate an equiatomic Hf-Nb-Ta-Zr RMPEA,and compared its microstructures as well as mechanical properties with those of the as-cast alloy fabricated by levitation induction melting.EB-DS method can transform the equiaxed grain microstructures in the as-cast alloy to columnar grain microstructures as well as eliminate the slight segregation.The room-temperature tensile test demonstrates that the ductility is substantially improved from 3.9%for the as-cast alloy to 23%for EB-DS alloy,accompanied by the slight enhancement in yield strength from 946 to 991 MPa.The microstructural investigations indicate that EB-DS alloys with columnar grains present a significantly optimized coordinated plastic deformation between the grain boundary region and the grain interior region,leading to the suppression of cracking along grain boundaries.展开更多
The deformation characteristics and activation mechanisms of kink bands in refractory multi-principal element alloys with local chemical fluctuations(LCFs)were systematically studied.These alloys were fabricated using...The deformation characteristics and activation mechanisms of kink bands in refractory multi-principal element alloys with local chemical fluctuations(LCFs)were systematically studied.These alloys were fabricated using laser-directed energy deposition technology and characterized by room-temperature compression testing,electron backscatter diffraction(EBSD),transmission electron microscopy(TEM),and high-angle annular dark-field(HAADF)imaging.The results reveal that kinking is a gradual rotational diffusion process,during which the misorientation difference between the kink and the matrix varies.A low Schmid factor is a prerequisite for kink excitation.The slip system closest to the loading axis is passively activated by the applied external force,leading to the accumulation of geometrically necessary dislocations(GNDs)required for lattice rotation.The widespread LCFs within the matrix reduce the migration rate of edge dislocations,promoting GND accumulation and enhancing the propensity for kink band formation.During deformation,the occurrence of kinking enables continuous lattice rotation to accommodate the exceptionally high strain in the vicinity,when the stress concentration in the primary kink cannot be fully released,double kinks are activated to reduce strain energy.展开更多
基金the Doctoral Foundation of the Third Xiangya Hospital of Central South University,No. 2005-08
文摘BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.
基金Supported by the Innovation Fund of Science and Technology Commission of Shenzhen Municipality,China,No.JCYJ-2015-0403100317071
文摘AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD)alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded.Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform.The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64%of epileptic infants showed an obvious improvement,with a 50%decrease in seizure frequency.GM structure in epileptic infants(P1 group)differed dramatically from that in healthy infants(Health group).Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group).Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups.Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group.KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.
文摘BACKGROUND： Anti-epilepsy and anti-psychosis drugs have traditionally been used in the clinic to treat epilepsy complicated by mental disorders. However, there is still no effective therapy for refractory epilepsy patients suffering from persistent mental disorders. OBJECTIVE： To explore the therapeutic effects of stereotactic multi-element localization and multi-target radiofrequency ablation on patients with refractory primary epilepsy and mental disorders. DESIGN： A retrospective case analysis. SETTING： Department of Neurosurgery, the 454 Hospital of Chinese PLA. PARTICIPANTS： Between June and November 2004, 13 patients with refractory primary epilepsy complicated by persistent mental disorders were admitted to the Department of Neurosurgery, the 454 Hospital of Chinese PLA. The patient group consisted of nine males and four females, with an average age of 25 years （range 18-39 years）, and a course of disease ranging 3-11 years. Diagnosis of mental disorders was in accordance with Chinese Classification of Mental Disorders. Written informed consent was obtained from all patients and their families, and the treatment protocol was approved by the Ethics Committee of the Hospital. METHODS： Under venous inhalation anesthesia, the disease targets, including bilateral corpus callosum, bilateral amygdala, and bilateral medial septal area, as well as unilateral Forel-H area, were coagulated by RFG-3CF radiofrequency thermocoagnlation at 75-80 ℃ for 60-70 seconds. During thermocoagulation, the targets were identified using deep-brain microelectrodes and localized according to electrophysiology and electric resistance values. MAIN OUTCOME MEASURES： One year post-surgery, epileptic seizures were assessed on the basis of the Tan classification, and psychogenic （non-epileptic） seizures were evaluated using a 5-grade system. RESULTS： All enrolled 13 epileptic patients were included in the final analysis. The results of follow-up evaluations demonstrated that epilepsy was well-controlled. In total, nine patients did not experience relapse, and the frequency of seizures was reduced by 75% in two patients, and 50%-74% in another two patients. Psychogenic seizures were ameliorated in 11 cases （class 1, recovery） and improved significantly in two cases （class 2, significant improvement）. CONCLUSION： Radiofrequency ablation of bilateral corpus callosum, bilateral amygdala, bilateral medial septal area, and unilateral Forel-H area exhibits certain efficacy in treating epileptic patients suffering from persistent mental disorders.
基金support of the National Natural Science Foundation of China(Nos.U20A6001,12002190,11972207,and 11921002)the Fundamental Research Funds for the Central Universities,China(No.SWUKQ22029)the Chongqing Natural Science Foundation of China(No.CSTB2022NSCQ-MSX1635).
文摘High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillimeter or micrometer level.This entails connecting hundreds or thousands of electrode wires on a limited surface.This study reported a class of flexible,ultrathin,highdensity electrocorticogram(ECoG)electrode arrays.The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement.The flexible,ultrathin,high-density ECoG electrode array was conformably attached to the cortex for reliable,high spatial resolution electrophysiologic recordings.The minimum spacing between electrodes was 15μm,comparable to the diameter of a single neuron.Eight hundred electrodes were prepared with an electrode density of 4444 mm^(-2).In focal epilepsy surgery,the flexible,high-density,laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves inrabbits,improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level.The flexible,high-density,laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.
基金the "211 Project" Foundation of Jilin University,No.450101120008
文摘The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.
基金Supported by the Scientific Research Foundation of the Returned Overseas Chinese Scholars
文摘Previous studies have focused on medial temporal lobe epilepsy secondary to central nervous system infections. Several large-sample analyses of multi-lobe injuries or complications of medial temporal lobe epilepsy have been reported. The present study selected 29 patients （10 males and 19 females with a mean age of 18 years） with refractory epilepsy secondary to central nervous system infections （meningitis in 8, encephalitis in 21） from Beijing Functional Neurosurgical Institute from May 2006 to August 2008. All patients underwent computer tomography or magnetic resonance imaging, as well as electroencephalogram examinations; cortical electrodes were embedded in 11 patients. In addition, 13 （45%） patients underwent anterior temporal Iobectomy, and 16 （56%） underwent extratemporal corcticectomy. Results showed that 18 （62%） patients obtained favorable outcomes following surgical treatment, including 80% with temporal lobe epilepsy and 50% with extratemporal epilepsy. Central nervous system infection was not a contraindication for epilepsy treatment, and identification of epileptic foci proved to be crucial. In addition, a young age at infection, as well as prolonged latent period from time of infection to initial afebrile seizure, were 2 predictive factors for all patients. Cortical electrodes significantly increased the detection rate of epileptic foci, but did not improve prognosis of foci excision.
文摘To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.
基金supported by the Natural ScienceFoundation of Inner Mongolia, No. 20080404Zd29
文摘A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The loci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser＇s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser＇s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser＇s classification score was significantly higher in the single-focus group as compared with the multiple-foci group.
文摘Electrical Source Imaging (ESI) is a non-invasive technique of reconstructing brain activities using EEG data. This technique has been applied to evaluate epilepsy patients being evaluated for epilepsy surgery, showing encouraging results for mapping interictal epileptiform discharges (IED). However, ESI is underused in planning epilepsy surgery. This is basically due to the wide availability of methods for solving the electromagnetism inverse problem (e-IP) associated to few studies using EEG setups similar to those most commonly used in clinical setting. In this study, we applied six different methods of solving the e-IP based on IEDs of 20 focal epilepsy patients that presented abnormalities in their MRI. We compared the ESI maps obtained by each method with the location of the abnormality, calculating the Euclidian distances from the center of the lesion to the closest border of the method solution (CL-BM) and also to the solution’s maxima (CL-MM). We also applied a score system in order to allow us to evaluate the sensitivity of each method for temporal and extra temporal patients. In our patients, the Bayesian Model Averaging method had a sensitivity of 86% and the shortest CL-MM. This method also had more restricted solutions that were more representative of epileptogenic activities than those obtained by the other methods.
基金Supported by Carbon Neutrality and Energy System Transformation (CNEST) ProgramScience and Technology Innovation Project of CHN Energy (GJNY-24-26)。
文摘The service life of refractory brick in the slag tapping hole of gasifiers is a significant concern for long-term and stable operation.This study examined the damage mechanism of high chromia refractory of four commercial coal-water slurry gasifiers with their corresponding gasification coal samples and the corroded refractory bricks in the slag tapping hole of the gasifier.The slag characteristic,including crystallization and viscosity-temperature of four gasification coal samples were analyzed.The results revealed that the low viscosity slag could lead to more severe damage to refractory bricks.Given the risk of slag crystallization,it is recommended to establish a safe slag tapping temperature range should be set as tICT(initial crystallization temperature)−t_(2.5) when tICT is higher than t_(25).Upon examining interior morphology of these corroded refractory bricks,some cracks were observed within them.The chemical composition of molten slag was analyzed using SEM-EDS.However,XRD results found no spinel containing zirconium in these cracks.This suggests that the emergence of these cracks are mainly attributed to the molten slag penetration and the subsequent reaction with the refractory material.The difference in thermal expansion between the newly formed substances and refractory material is critical in forming these cracks.Furthermore,SEM-EDS analysis was also conducted on the slag-aggregate and the slag-matrix interface.The results reveal that the reduction in Cr_(2)O_(3) content is the earliest characteristic of damage in high chromia refractories.A proposed damage mechanism of refractory brick suggests that the matrix and aggregate of high chromia refractory are initially compromised because of the reduced Cr_(2)O_(3) content.Subsequently,the molten slag penetrates the interior of the refractory brick,forming new substances,leading to damage caused by the difference in thermal expansion between the new substances and the refractory brick.Understanding and preventing the reduction of Cr_(2)O_(3) content is vital to prolonging the service life of refractory brick in the slag tapping hole of the gasifier based on this damage mechanism.
基金supported by the Natural Science Foundation of Shaanxi Province(No.2023-JC-QN-0615)the National Natural Science Foundation of China(Nos.52272027 and 52372034).
文摘Intelligent refractory materials represent a new generation of high-temperature functional materials that significantly enhance the service performance of traditional refractories in extreme environments through integrated sensing,response,and adaptive mechanisms.A comprehensive overview of intelligent refractory materials was provided,focusing on their classification,preparation techniques,and industrial applications.Firstly,the categories and design principles of intelligent refractory materials are introduced,including self-healing,self-regulating,and self-diagnosing types,which enhance durability and performance under extreme conditions.Subsequently,advanced preparation technologies are discussed,such as 3D printing for complex geometries,nanocomposite engineering for improved mechanical and thermal properties,gradient design for optimized thermal stress resistance and information technology including machine learning,health monitoring,digital twin.Finally,the industrial applications of these materials are highlighted,particularly in steel metallurgy,building materials industry,and energy.It aims to bridge the gap between research advancements and practical implementation,offering insights into future trends in intelligent refractory material development.
基金supported by the National Key Research and Development Program of China,No. 2023YFF0714200 (to CW)the National Natural Science Foundation of China,Nos. 82472038 and 82202224 (both to CW)+3 种基金the Shanghai Rising-Star Program,No. 23QA1407700 (to CW)the Construction Project of Shanghai Key Laboratory of Molecular Imaging,No. 18DZ2260400 (to CW)the National Science Foundation for Distinguished Young Scholars,No. 82025019 (to CL)the Greater Bay Area Institute of Precision Medicine (Guangzhou)(to CW)。
文摘Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
基金supported by the National Natural Science Foundation of China(No.51974016).
文摘Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which relies on lixiviants prepared using volatilized sulfur obtained from roasting,has not been fully elucidated.This study employs the response surface methodology to optimize processing parameters,resulting in an increased gold extraction rate of 96.18%.Analytical factorization and the Tafel curve indicate that CuSO_(4) and NH_(3)·H_(2)O significantly influence the self-leaching process.Furthermore,X-ray photoelectron spectroscopy(XPS)analysis reveals that S^(2−),S_(2)^(2−),polysulfides(S_(n)^(2−)),and thiosulfate(S_(2)O_(3)^(2−))are involved in the gold leaching reaction,with S^(2−),S_(2)^(2−),and S_(n)^(2−) serving as primary ligands for gold complexation.The role of S_(2)O_(3)^(2−) in the early stages of the gold-leaching reaction is also noteworthy.The copper–ammonia complex catalyzes the self-leaching gold reaction;however,an improper addition ratio can lead to copper-sulfur compound precipitates,reducing the extraction rate.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111123(to JQ)。
文摘Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
基金supported by the National Natural Science Foundation of China,Nos.82471471(to WJ),82471485(to FY)Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation,No.tzjhjw(to WJ)+1 种基金Shaanxi Key Research and Development Plan Project,No.2023-YBSF-353(to XW)the Joint Fund Project of Innovation Research Institute of Xijing Hospital,No.LHJJ24JH13(to ZS)。
文摘Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.
基金National MCF Energy R&D Program(2024YFE03260300)。
文摘Refractory metals,including tungsten(W),tantalum(Ta),molybdenum(Mo),and niobium(Nb),play a vital role in industries,such as nuclear energy and aerospace,owing to their exceptional melting temperatures,thermal durability,and corrosion resistance.These metals have body-centered cubic crystal structure,characterized by limited slip systems and impeded dislocation motion,resulting in significant low-temperature brittleness,which poses challenges for the conventional processing.Additive manufacturing technique provides an innovative approach,enabling the production of intricate parts without molds,which significantly improves the efficiency of material usage.This review provides a comprehensive overview of the advancements in additive manufacturing techniques for the production of refractory metals,such as W,Ta,Mo,and Nb,particularly the laser powder bed fusion.In this review,the influence mechanisms of key process parameters(laser power,scan strategy,and powder characteristics)on the evolution of material microstructure,the formation of metallurgical defects,and mechanical properties were discussed.Generally,optimizing powder characteristics,such as sphericity,implementing substrate preheating,and formulating alloying strategies can significantly improve the densification and crack resistance of manufactured parts.Meanwhile,strictly controlling the oxygen impurity content and optimizing the energy density input are also the key factors to achieve the simultaneous improvement in strength and ductility of refractory metals.Although additive manufacturing technique provides an innovative solution for processing refractory metals,critical issues,such as residual stress control,microstructure and performance anisotropy,and process stability,still need to be addressed.This review not only provides a theoretical basis for the additive manufacturing of high-performance refractory metals,but also proposes forward-looking directions for their industrial application.
基金supported by the National Natural Science Foundation of China,No.32130060(to XG).
文摘Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.
基金supported by the National Natural Science Foundation of China(Nos.22406081,22276086,22306086)the Natural Science Foundation of Jiangxi Province(No.20232BAB213029),all of which are greatly acknowledged by the authors.
文摘Fenton-like technology based on peroxymonosulfate activation has shown great potential in refractory organics degradation.In this work,single Fe atom catalysts were synthesized through facile ball milling and exhibited very high performance in peroxymonosulfate activation.The Fe single-atom filled an N vacancy on the triazine ring edge of C_(3)N_(4),as confirmed through X-ray absorption fine structure,density functional calculation and elec-tron paramagnetic resonance.The SAFe_(0.4)–C_(3)N_(4)/PMS system could completely remove phenol(20 mg/L)within 10 min and its first-order kinetic constant was 12.3 times that of the Fe_(3)O_(4)/PMS system.Under different ini-tial pH levels and in various anionic environments,SAFe_(0.4)–C_(3)N_(4) still demonstrated excellent catalytic activity,achieving a removal rate of over 90%for phenol within 12 min.In addition,SAFe_(0.4)–C_(3)N_(4) exhibited outstanding selectivity in reaction systems with different pollutants,showing excellent degradation effects on electron-rich pollutants only.Hydroxyl radicals(•OH),singlet oxygen(1O_(2))and high-valent iron oxide(Fe(Ⅳ)=O)were de-tected in the SAFe_(0.4)–C_(3)N_(4)/PMS system through free radical capture experiments.Further experiments on the quenching of active species and a methyl phenyl sulfoxide probe confirmed that 1O_(2) and Fe(Ⅳ)=O played dom-inant roles.Additionally,the change in the current response after adding PMS and phenol in succession proved that a direct electron transfer path between organic matter and the catalyst surface was unlikely to exist in the SAFe_(0.4)–C_(3)N_(4)/PMS/Phenol degradation system.This study provides a new demonstration of the catalytic mech-anism of single-atom catalysts.
基金supported by the National Key R&D Program of China(Grant No.2023YFB3508700)the National Natural Science Foundation of China(NSFC,Grant Nos.52227801 and 52271162)the Fundamental Research Funds for the Central Universities.
文摘Exploiting effective approaches to achieve superior ductility has consistently been a topic of widespread interest in refractory multi-principal-element alloys(RMPEAs).Herein,we developed a one-step forming method,electron-beam directional-solidification(EB-DS),to fabricate an equiatomic Hf-Nb-Ta-Zr RMPEA,and compared its microstructures as well as mechanical properties with those of the as-cast alloy fabricated by levitation induction melting.EB-DS method can transform the equiaxed grain microstructures in the as-cast alloy to columnar grain microstructures as well as eliminate the slight segregation.The room-temperature tensile test demonstrates that the ductility is substantially improved from 3.9%for the as-cast alloy to 23%for EB-DS alloy,accompanied by the slight enhancement in yield strength from 946 to 991 MPa.The microstructural investigations indicate that EB-DS alloys with columnar grains present a significantly optimized coordinated plastic deformation between the grain boundary region and the grain interior region,leading to the suppression of cracking along grain boundaries.
文摘The deformation characteristics and activation mechanisms of kink bands in refractory multi-principal element alloys with local chemical fluctuations(LCFs)were systematically studied.These alloys were fabricated using laser-directed energy deposition technology and characterized by room-temperature compression testing,electron backscatter diffraction(EBSD),transmission electron microscopy(TEM),and high-angle annular dark-field(HAADF)imaging.The results reveal that kinking is a gradual rotational diffusion process,during which the misorientation difference between the kink and the matrix varies.A low Schmid factor is a prerequisite for kink excitation.The slip system closest to the loading axis is passively activated by the applied external force,leading to the accumulation of geometrically necessary dislocations(GNDs)required for lattice rotation.The widespread LCFs within the matrix reduce the migration rate of edge dislocations,promoting GND accumulation and enhancing the propensity for kink band formation.During deformation,the occurrence of kinking enables continuous lattice rotation to accommodate the exceptionally high strain in the vicinity,when the stress concentration in the primary kink cannot be fully released,double kinks are activated to reduce strain energy.
