Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Effects of heat treatment temperature on oxidation behavior of glass-like carbon derived from acetone-furfural resin

Glass-like carbons （GCs） were prepared by carbonization of acetone-furfural resin in nitrogen atmosphere at 850℃, followed by heat treatment over a range of 1 200-2 500℃in inert atmosphere. The effect of heat treatment temperature （HTT） on the oxidation behavior was investigated by dynamic and isothermal thermogravimetric analyses. The structure of GC was examined by X-ray diffractometry （XRD） and the morphologies of GC before and after oxidation were examined by scanning electron microscopy （SEM）. It is shown that the GC samples present peculiar oxidation behavior. The anti-oxidation behavior increases with increasing the HTT to 1 600 ℃, whereas decreases gradually thereafter. GC sample heat treated at 1 600℃ obtains relatively optimal anti-oxidation properties under this condition. During the oxidation, this material produces grid network matrix surface and numerous nodular residues on the surface, resulting in excellent resistance to the attack of oxygen atoms.

Effect of Heat Treatment on the Mechanical Properties of FeCoZrWB Bulk Metallic Glass

A Fe61Co10Zr5W4B20 bulk metallic glass （BMG） with a diameter of 2 mm was prepared by using copper mould suction casting. The X-ray diffraction （XRD）, differential scanning calorimetry （DSC）, micro-hardness and compression tests were adopted to investigate the structure, thermal stability, especially, the effect of heat treatment on the micro-hardness and compression strength of this BMG. The BMG exhibits micro-hardness of about 1 207 Hv and compression fracture strength of about 1 707.6 MPa. After being annealed below the onset of crystallization temperature, the micro-hardness almost keeps constant. But after being annealed above the peak of crystallization temperature, the micro-hardness increases firstly and then declines gradually with the elongation of annealing time. However, annealed for the same period of time, the micro-hardness will increase with the rise of annealing temperature, while the compression fracture strength will apparently decrease.

Effect of Thermal Treatment and Acid Leaching Process on Pore Characteristics of Nanometer Porous Glass

Porous glass was prepared by thermally treating sodium borosilicate glass for different time, the effect of thermal treatment on pore size distribution was discussed and the pore size of the prepared porous glass was measured by scanning electron microscopy （SEM） and differential thermal analysis （DTA）. The results show that the optimum porous glass with an average diameter of 80 nm can be prepared by thermal treatment at 600℃ for 12 h and then acid treatment for 12 h in 2 mol·L^-1 hydrochloric acid solution.

Influence of flux treatment on the glass forming ability of Pd-Si binary alloys

Pd81Si19 amorphous alloys were prepared by combination methods of melt spinning and B2O3 flux treatment. A compari- son between the ribbons prepared from the fluxed ingots and the non-fluxed ones has been carried out. The result reveals that after fluxing treatment the glass transition temperature of the as-prepared glassy ribbons is reduced while the initial crystallization tem- perature is enhanced. It results in that the supercooled liquid region (defined as the difference between the initial crystallization tem- perature and the glass transition temperature) of the glassy alloy treated with fluxing technology has been increased from 31 to 42 K. This shows that fluxing technique can enhance the glass forming ability (GFA) of the binary alloy and improve the thermal stability of supercooled liquid of the glassy alloy.

The effects of heat treatment on microfluidic devices fabricated in silica glass by femtosecond lasers

We fabricated complex microfluidic devices in silica glass by water-assisted femtosecond laser ablation and sub- sequent heat treatment. The experimental results show that after heat treatment, the diameter of the microehannels is significantly reduced and the internal surface roughness is improved. The diameters of the fabricated microehannels can be modulated by changing the annealing temperature and the annealing time. During annealing, the temperature affects the diameter and shape of the protrusions in microfluidic devices very strongly, and these changes are mainly caused by uniform expansion and the action of surface tension.

Glass-forming ability, microhardness, corrosion resistance, and dealloying treatment of Mg60.xCu40Ndx alloy ribbons

The influence of Nd addition on the glass-forming ability (GFA), microhardness, and corrosion resistance of Mg60−xCu40Ndx(x = 5, 10, 15, 20, and 25, at%) alloys were investigated by differential scanning calorimetry, Vickers-type hardness tests, and electrochemical methods. The results suggest that the GFA and microhardness of the amorphous alloys increase until the Nd content reaches 20at%. The corrosion potential and corrosion current density obtained from the Tafel curves indicate that the Mg35Cu40Nd25ternary alloy exhibits the best corrosion resistance among the investigated alloys. Notably, nanoporous copper (NPC) was synthesized through a single-step dealloying of Mg60−xCu40Ndx(x = 5, 10, 15, 20, and 25) ternary alloys in 0.04 mol·L−1H2SO4solution under free corrosion conditions. The influence of dealloying process parameters, such as dealloying time and temperature, on the microstructure of the ribbons was also studied using the surface diffusivity theory. The formation mechanism of dealloyed samples with a multilayered structure was also discussed. © 2017, University of Science and Technology Beijing and Springer-Verlag Berlin Heidelberg.

Effect of Heat Treatment Method on Microstructure of Tailings Glass Ceramics

A Cao-Mgo-Al2O3-SiO2 quaternary system was established with the main crystal phase design based on Diopside, and the effect of once-through sintering heat treatment on microstructure of iron railings glass ceramics was studied by using DTA, SEM along with measurement of microhardness and volume density. The experimental results show that, when the total amount of FeO and Fe2O3 exceeds 10wt%, a large number of fine nuclei are produced in the annealing process, and the phenomenon of nucleus resorption happens during the process of nucleation heat treatment, which is unfavorable for preparing iron tailings glass ceramics through once-through sintering method. When the annealing temperature from 1250 ℃ to 830 ℃, setting crystallization time for 4h, without heat treatment, crystals are well grown with arrangement and interlocking in glass phase. At 830 ℃ the crystals are well developed, well distributed and of good size; with crystallization time of 4 h the crystals with radial shape have high content and regular arrangement.

THE INFLUENCE OF HEAT TREATMENT ON OPTICAL PROPERTY OF ION EXCHANGE PHOTOCHROMIC GLASS

In this paper, the influence of heat treatment on transmittance and the photochromic of ion exchange photochromic glass was studied, the microstructure of glass as well as the forming of AgX crystals were discussed. It is believed that heat treatment temperature affects precipitating of AgX crystal, and the AgX crystal is a dominant factor affecting surface photochromic properties of ion exchange photochromic glass.

The Dynamics of Acid Treatment in the Preparation of Porous Glass

The phase-separation glasses with composition of Na 2O(9.0)B 2O 3(25.0)-SiO 2(66.0)(in mole ratio)were leached with hydrochloric acid,and porous glasses were prepared.The dynamics of the acid treatment was investigated.The effects of treatment time,temperature and acid concentration on the acid treatment process were studied using HCl as treatment solution.The dynamics equation and apparent activation energy obtained in acid treatment process were dw/dt=a/2t and E=57.74 kJ·mol -1,respectively.The constants of the reaction rate at different temperatures were calculated.On the basis of experimental data the mechanism of acid treatment process and the source of swollen stress,which was the main stress during treatment process,were discussed.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Structural Changes by Thermal Treatment up to Glass Obtention of P₂O₅-Na₂O-CaO-SiO₂Compounds with Bioglass Composition Types

P2O5-Na2O-CaO-SiO2 compounds are the base of certain glass types. Glasses are solids obtained by fast cooling of melted mix of certain compounds. Different compositions give origin to many products with a variety of applications such as: bottles, coatings, windows, tools for chemical industry, laboratory equipment, optics, as bioceramics, etc. The aim of this work was to analyze structural changes of different composition in the P2O5-Na2O-CaO-SiO2 systems thermally treated up to 1250?C, that is to say, before glass formation, by X ray diffraction. Intermediate and final developed phases up to 1100?C thermal treatment in samples were generated as a function of Na2O/CaO (1 and 1.62) and P2O5/Na2O ratios (0, 0.2 and 0.245). High-and low-combeites, calcium and sodium-calcium silicate were found at the highest studied temperature.

Effect of surface treatment on rheological behaviors of glass bead/hydroxyl terminated polybutadiene suspensions

Surface treatment of glass bead(GB) was carried out by using γ-glycidoxypropyltrimethoxy silane(GPTES) and γ-methacryloxypropyltrimethoxy silane(MPTMS) as coupling agents,respectively.The steady viscosity and yield stress of the GB/hydroxyl terminated polybutadiene(HTPB) suspensions were determined by Brookfield R/S rheometer.The effect of surface treatment on the viscosity and yield stress of GB/HTPB suspension was investigated.The results indicate that the viscosity of the pristine GB/HTPB suspension increases with increasing GB,and the relationship between its viscosity and volume fraction of GB depends on the shear rate.The modification of GB by MPTMS changes the viscosity of the MPTMS@GB/HTPB suspension,and its viscosity is the minimum at the MPTMS dosage of 0.3 g per 1 g GB.Additionally,the modification of GB by MPTMS increases the yield stress of the GB/HTPB suspension,and its yield stress is the maximum at the MPTMS dosage of 0.1 g per 1 g GB.The GPTES modified GB/HTPB suspension behaves lower viscosity and weaker shear thinning than the MPTMS modified GB/HTPB suspension within the range of experimental shear rate.

Preparation of AgCl Nano-Crystal Embedded Tellurite Nonlinear Optical Glasses under Electric Field Accompanied Heat Treatment

The quantum effect of nano-crystals is an important factor to improve nonlinear optical performance of nanocrystal embedded glasses, while controlling the size distribution and content of nano-crystals in the glass accurately is a key to obtain good quality. The auxiliary direct current electric field, accompanied with heat treatment, was applied on AgCI containing niobic tellurite glass sheet. The nucleation and crystallization of the glass were well controlled under auxiliary electric field. It was found that the average size of AgCI nano-crystal particles in the glass is smaller than that under single heat treatment, and the content of nano- crystals is higher. Therefore the third-order nonlinear optical performance of the glass was increased a lot. The local-area distributed AgCl nano-crystal particles can also be embedded into a glass sheet by using locally applied electric field.

Effect of Nucleating Agents and Heat Treatments on the Crystallization of Magnesium Aluminosilicate Transparent Glass-ceramics

The crystallization behavior and transparent property of MgO-A1203-SiO2 （MAS） glasses with TiO2 and TiO2＋ZrO2 as nucleating agents were discussed by differential thermal analysis, X-ray diffraction, field emission-environment scanning electron microscope, energy dispersive spectrum and UV-VIS-NIR scanning spectrophotometer. It was found that the glass crystallized at 950 ℃ with ZrO2 less than 3% could obtain transparent glass ceramic, which presented purple to colorless. With the nucleating agent additives （5% TIO2＋3% ZrO2）, the colorless transparent glass-ceramics with spinel as the main crystal phase could be prepared, and the transmittance reached about 80%. As the crystallized temperature increase to 1 000 ℃, besides spinel（MgA1204）, sapphirine （Mg3.5A19Si1.5O20） and ZrTiO4 precipitated from matrix glass, and the transmitance of glass-ceramic decreased.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Effect of Water Washing Pre-treatment on the Properties of Glass-ceramics from Incinerator Fly Ash Using Electronic Arc Furnace

Production of glass-ceramics by sintering the molten slag obtained from electric arc furnace treatment of fly ash was investigated. The effect of washing pretreatment prior to melting the fly ash on the microstructure and properties of the glass-ceramics was examined. The results show that washing pretreatment of fly ash can decrease alkali metal chloride and increase network former in fly ash, which results in the increase of peak crystallization temperature of parent glass and strengthening of properties of bending strength and chemical stability of the glass-ceramics. The optimal heat treatment temperature for parent glass of washed fly ash is 1 173 K, at which the crystalline phase of glass-ceramics is composed of gelignite （Ca2A12SiO7） and akermanite （Ca2MgSi207）. Glass-ceramics produced at optimal heat treatment temperature are excellent in term of the physical and chemical properties and leaching characteristics, indicating attractive potential as substitute of nature materials.