In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters . The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4 Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of exacerbation and remission associated with skin barrier dysfunction. A typical feature of this chronic dermatosis is the characteristic morphology and localization of skin lesions, persistent and recurrent pruritus, as well as skin lichenification ,2,3. In The incidence of AD is caused by genetic factors , environmental factors  and immune dysregulation ,6,7. OneRecent studies in humans and animal models demonstrate that the keratinocytes of atopic skin lesions synthesize and release thymic stromal lymphopoietin (TSLP), the expression of which is strongly correlated with the severity of disease activity. TSLP acts as a potent stimulator of the cytokines of the Th2 profile and induces the proliferation, differentiation and activation of mast cells. TSLP may work as a major mediator to initiate and maintain an inflammatory response in the skin of patients with AD. Studies also indicate the role of TSLP in the pathogenesis of perceived pruritus in atopic dermatitis ,9.The treatment of atopic dermatitis has two main aspects: relieving symptoms and eliminating the identified specific allergens from the patient’s environment, which cause exacerbations of skin lesions. The basic element of pharmacotherapy in AD is proper skin care with emollients. Symptomatic treatment includes: glucocorticosteroids , antihistamines, calcineurin inhibitors , phototherapy and photochemotherapy. In severe or refractory cases, immunosuppressive drugs are used (cyclosporine and methotrexate). There are also attempts to use biological treatment with monoclonal antibodies  ,11,12. CA new method of treatment of atopic dermatitis is hyperbaric oxygen therapy (HBOT). Although the results of the numerous studies enable its wide use in medicine, there are few reports on its use in children with AD ,11,12. TThe aim of this study was to evaluate the treatment effectiveness of severe cases of AD in children with the method of hyperbaric oxygen therapy (HBOT).The study was designed as a prospective study. It was approved by the Bioethics Committee at the Military Medical Chamber No. 159/18.A total of 15 children with severe atopic dermatitis  were enrolled in the study. AD was confirmed by the positive results of a skin prick test in all participants.Each time, before child qualification for treatment in a hyperbaric chamber, thorough medical history and physical examinations were performed. The inclusion and exclusion criteria for the study are presented in Before the oxygen hyperbaric therapy initiation, the patients, apart from complex topical therapy, were periodically administered orally with prednisone (3 patients) and cyclosporine (2 patients). However, during HBO treatment, patients used only topical treatment (skin care with emollients). Possible systemic glucocorticotherapy and/or cyclosporine treatment was discontinued at least 6 months before HBOT initiation. These assumptions eliminated the effect of the pharmacological suppression of the immune system. Ad hoc antihistamine intake (1st and 2nd generation) was also allowed in order to reduce the itching sensation.All patients completed a 30-day treatment cycle in a hyperbaric chamber.The clinical disease activity was analyzed by the SCORAD questionnaire and its modification, objective SCORAD (oSCORAD).The SCORAD method was used to assess objective symptoms (the extent and severity of skin lesions) and subjective symptoms (severity of pruritus and sleep disorders). The extent of the affected area was estimated using the rule of nines. Six symptoms were assessed to determine the severity of skin lesions—skin dryness, redness, swelling, oozing/crusting, scratch marks and lichenification—on a 4-point scale, from 0 to 3. Each grade was assigned an appropriate number of points: 0 points for no lesions and 3 points for the most severe cases, respectively. Skin dryness was assessed in the area not affected by the disease, and the remaining symptoms were assessed in the most representative areas. The severity of pruritus and sleep disorders was each scored by the patient on a visual analog scale (ranging from 0 to 10) as the mean value of the previous 3 days and 3 nights. In the case of children under the age of 7, this was performed by the child’s guardian. On the basis of the obtained results, AD was classified into mild (<25 points), moderate (25–50 points) or severe (>50 points). The maximum score on the SCORAD scale is 103 points.In order to eliminate subjective symptoms, i.e., pruritus and sleep disorders, clinical AD activity was assessed simultaneously with the objective SCOARD (oSCORAD) questionnaire. The severity of the disease on the oSCORAD scale was rated as mild (<15 points), moderate (15-40 points) or severe (>40 points). The maximum score on the oSCORAD scale is 83 points.SCORAD and oSCORAD (Assessment of the Severity/Activity of the Disease) Were Assessed up to 24 h before Blood Collection for Laboratory Tests, Always up to 24 h before the Initiation of HBO Therapy and no Later than 48 h after the End of a 30-day Cycle of Hyperbaric Oxygen Therapy. Blood Collection for Laboratory Tests Was Performed up to 24 h before the Initiation of HBO Therapy and up to 48 h after the End of a 30-Day Cycle of the Therapy. +CD25highCD127−FOXP3+ Treg and NKT peripheral blood lymphocytes, was determined. The analyses were performed before and 30 days after hyperbaric oxygen treatmentIn all treated patients, the serum concentration of total IgE antibodies and cytokines IL-4, IL-6 and IL-10, as well as the percentage of CD4g, 20 min), and the serum was collected. Immediately after the collection, total IgE concentration was determined. For cytokine examination, the serum was portioned and stored at −80 °C until the analysis. For immune cell analysis, vein blood was collected on EDTA. Immediately after isolation, nTREg and NKT lymphocyte analysis was performed.For serum analysis, the collected blood samples were allowed to clot. After 20 min (room temperature), the blood was centrifuged . Finally, the supernatant was collected from each sample, and 300 μL of washing buffer was added.Cytokine concentrations were determined by a cytometric bead array  on the FACSCalibur flow cytometer, according to the manufacturer’s procedure. In brief, the following were added to the cytometric tubes: 50 μL of capture beads, 50 μL of the detection reagent, 50 μL of the test serum (test sample), 50 μL of the known concentration of cytokines (standard curve: 20–5000 pg/mL) or 50 μL of blank (blind sample). The samples were then incubated for 3 h, washed and centrifuged . The results were converted into the value obtained from the standard curve and presented as the mean concentration of the tested cytokine (pg/mL) ± SD.The percentage of nTreg  and NKT lymphocytes in the blood (IMK assay) from BD Bioscience (Warsaw Poland) were analyzed as previously described . AnalyseThe course of the HBOT included three 20 min cycles, during which oxygen was administered under hyperbaric conditions, and 5 min air breaks between the cycles. The aim of the breaks was to increase the safety of the procedure and to reduce the possible side effects related to oxygen therapy. The total time of breathing with hyperbaric oxygen was 60 min for each session. During the session, the patients underwent two 10 min periods of compression to the desired ATA pressure in the patient’s environment and decompression, during which the participants were breathing air. These periods were performed at the beginning and at the end of the procedure, respectively . The pro2O, which corresponds to the value of 2.5 ATA (~250 kPa), with an individually tolerated velocity no faster than 1.5 m H2O/min. This protocol provides for a safety stop during decompression.The treatment protocol performed in a hyperbaric chamber included compressing the patient in the air atmosphere to the maximum operating depth (MOD) value of 15 m HDepending on the age and the cooperation degree with the staff, the patients were subjected to the therapy alone or with the assistance of a legal guardian as a medical attendant. The attendant did not breathe the hyperbaric oxygen for therapeutic purposes but performed oxygen denitrogenation with the use of a mask-type respiratory system 10 min before the start of decompression . The aim of pre-decompression denitrogenation was to minimize the risk of decompression sickness. Children subjected to HBOT procedures were treated mainly with the use of “S”-size “mask” respiratory systems. In the case of patients under 7 years of age, or those who did not tolerate the mask, a hood-type oxygen helmet was used with a continuous flow of oxygen of 15 L/min.t-test was used to compare normally distributed variables and the Mann–Whitney U test to compare variables of which the distribution was significantly different from the Gaussian distribution. Every time, the probability value of p < 0.05 was considered statistically significant. StatSoft, Inc.  and Statistica 12 were used for analysis.Before the analysis, the data were initially verified with the use of a normal probability plot and finally with the Kolmogorov–Smirnov and Lilliefors normality test. The Student’s Fifteen patients aged 3–16 years (7 girls and 8 boys) qualified for HBOT. The characteristics of the study group are presented in The following coexisting atopic diseases were observed in children undergoing HBOT: allergic rhinitis (3 patients), inhalation and/or food allergy (12 patients). Two out of fifteen patients had a positive family history of allergy. Due to severe itching, 11 children used antihistamines during hyperbaric sessions. All children completed a 30-day HBOT course.A statistically significant clinical improvement in the skin condition was observed in all children subjected to the therapy, which was assessed using SCORAD and oSCORAD questionnaires . ClinicaThe beneficial local effect of HBOT was observed in reducing the extent of skin lesions .There was also a reduction in skin dryness, erythema severity, the presence of edema, exudates, scratch marks and skin lichenification. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after HBOT .In conclusion, after the 30-day cycle of HBO treatment, a beneficial clinical improvement in the skin condition was observed. There was also a reduction in the intensity of pruritus and an improvement in sleep quality in all patients after HBOT.+CD25highCD127−FOXP3+ and NKT peripheral blood lymphocytes before and after the 30-day cycle of HBOT . No statistical significance was proved in the percentage changes of the Treg CD4 of HBOT .+CD25highCD127−FOXP3+ lymphocytes in the peripheral blood of patients with severe AD before and after the 30-day cycle of HBO therapy.In conclusion, there was no significant influence of HBOT on the concentrations of IL-4, IL-6 and IL-10 cytokines in the blood serum in the examined children before and after the therapy. There was no evidence of a change in the profile of cytokine production after the treatment in a hyperbaric chamber. There were no changes in the percentages of the NKT and TregCD4Atopic dermatitis is one of the most common inflammatory skin diseases in children. The course of AD is chronic and recurrent. The predominant symptom of the disease is intense pruritus, which occurs not only during the day but also at night . The conIn our study, it was shown that during hyperbaric oxygen therapy, all children with severe atopic dermatitis experienced a significant clinical improvement in their skin condition. After the 30-day treatment cycle in a hyperbaric chamber, there was a reduction in the extent and intensity of skin lesions, as well as a reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification. Moreover, patients reported a noticeable reduction in the intensity of pruritus and an improvement in sleep quality. The beneficial clinical effect of HBOT was achieved only with the use of systematic topical treatment emollients. In the course of hyperbaric therapy, no topical corticosteroids or other standard treatment methods were used. Similar results were obtained by Olszański et al. in their study concerning the treatment of AD in adults. All 10 patients after treatment with hyperbaric oxygenation experienced a significant local improvement in the field of skin lesions (in the opinion of a dermatologist who previously referred these patients to participate in hyperbaric exposures), while the patients themselves declared a noticeable reduction in perceived itching .In our study, we tried to answer the question regarding the impact of HBOT on the immune system of children suffering from severe atopic dermatitis. The immunomodulatory effect of HBOT is nonselective and affects the function of both T and B lymphocytes. In the experiments performed on animals, it was proved that during exposure to hyperbaric oxygenation (HBO), various types of immune responses are inhibited ,27. The The results of studies conducted around the world also show a significantly lower percentage of natural regulatory T cells (nTreg), defined as CD4+/CD25high/CD127low/FoxP3+, in the blood serum of children with AD than in the healthy population ,35,36,37+CD25highCD127−FOXP3+ (in the case of an increased concentration of IDO) or Th17 (in the case of the predominance of HIF-1α expression) [+CD25highCD127−FOXP3+Treg in diseased tissues. In biopsy samples of skin lesions collected from areas with high disease intensity, the number of these cells was significantly higher after HBOT treatment [Many publications emphasize the anti-inflammatory effect of HBOT in the treatment of diseases with an intense inflammatory reaction, e.g., psoriasis, difficult-to-heal wounds (such as a diabetic foot), ulcerations or skin burns ,39,40. Tression) ,49. The ression) . It was reatment .+CD25highCD127−FOXP3+ Treg and NKT cells in the peripheral blood, the concentration of IL-10 in blood serum was also assessed (cytokines secreted by induced Treg cells). Moreover, in the study, we investigated the changes in the Th2 cytokine profile–IL-4  and IL-6 (increased production in inflammatory reactions) in order to assess the influence of HBOT on the severity of inflammation in patients with AD.Taking into account the limitation associated with obtaining skin biopsies in children with AD, in our study, in addition to the percentage of CD4+CD25highCD127−FOXP3+ Treg lymphocytes and NKT cells, as well as relatively constant concentrations of IL-10 produced by induced Treg before and after HBOT, was demonstrated.In the study, however, it was not possible to confirm the above-mentioned hypothesis about the beneficial effect of HBOT on the Th2 cells in relation to the Th1 cells and the cytokines produced by them. In children undergoing the therapy, mean concentrations of Th2 cytokines (IL-4 and IL-6) before and after the 30-day cycle of HBOT were similar. A relatively constant percentage of CD4The lack of statistically significant differences in the concentration of cytokines before and after HBOT may result from the too-short duration of the therapy for changes in the serum concentrations of the analyzed immunological parameters. Perhaps the immune profile should be reassessed a few months after the end of the therapy or the number of HBOT sessions should be increased (>30). Greater differences could then be observed.B cells, as antigen-presenting cells and T-cell activators in allergic inflammation, play a major role in the secretion of specific antibodies. B cells are a source of IgE antibodies that initiate an allergic reaction by the attachment of an allergen, which then leads to the degranulation of mast cells and the release of inflammatory mediators ,52,53.In our study, a statistically significant decrease in the serum concentration of total IgE after the 30-day treatment cycle was shown, which proves the influence of HBOT on the synthesis of these specific immune proteins (IgE) by B cells. This confirms the conclusions resulting from the previously mentioned studies on the influence of HBOT on the reduction of the inflammatory reaction in the course of AD. In addition, the reduction in total IgE levels may be related to the reduction in pruritus observed in patients after HBOT therapy. For many years, the source of itching in AD has been seen in the mast cells-histamine axis, but recent studies show that IgE-R + basophil–neuronal interactions play a key role here ,9.The study showed a clear beneficial local effect of HBOT on the clinical skin condition and the alleviation of the course of AD. Therefore, we confirmed the conclusions drawn from the research studies cited in the article regarding the influence of tissue hyperoxygenation on the functioning of the immune system cells directly in the diseased skin. In the study, we did not assess immune cell activity and cytokine concentrations  directly in the skin biopsies. Therefore, due to the different methodology in the experiments mentioned in this article, it is impossible to unequivocally compare the results obtained by other researchers with our results.It is worth mentioning that HBOT is a highly safe method. Researches showed that the risk of symptoms of oxygen toxicity in the treated patients is low ,55.The use of hyperbaric therapy in children with a severe course of atopic dermatitis has a positive impact on the treatment results of this disease. It reduces the severity of skin lesions, as well as its dryness, the presence of redness, swelling, oozing/crusting, scratch marks and lichenification. HBOT has a positive effect on the reduction of pruritus intensity and improves sleep quality in patients with severe AD. This has a significant impact on improving the quality of life of these patients.Hyperbaric oxygen therapy may be a therapeutic option for some patients with atopic dermatitis, especially in severe cases that are resistant to the standard methods of treatment.The study did not show a clear effect of hyperbaric oxygen therapy on the functioning of the immune system. Immunological parameters presented in this study are not sufficient to discuss all of the molecular mechanisms underlying the immunomodulatory effects of HBOT.However, due to the promising results of the local effects of the therapy in the skin condition of patients with AD, it is necessary to conduct further studies in this area on a larger group of patients and randomized patients.The study was approved by the Bioethics Committee at the Military Medical Chamber No. 159/18.


The microscopic physical morphology and chemical components of the insulation specimens before and after modification were analyzed by atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), and an OIP bushing model based on the modified aramid insulation paper was constructed and its electric field distribution was analyzed. The simulation results show that the use of SiO2-modified aramid insulation paper can improve the electric field distribution of OIP bushings and increase the operating life of power transformers.The long-term safe and stable operation of oil-impregnated paper (OIP) bushings is of great significance to the operation of power systems. With the growth of OIP bushing, its internal insulation will gradually decay. Aramid insulation paper has excellent thermal aging characteristics and its insulation performance can be improved by using nano-modification technology. In this paper, the nano-SiO As an important part of power transformers, oil-impregnated paper (OIP) bushings assume the important roles of leading out the high and low voltage leads of power transformers, fixing the internal lead structure, and achieving insulation between the leads and the transformer tank . CurrentIn long-term operation of transformer bushings, due to the combined effect of high temperature and strong electric fields, oil-impregnated paper insulation will be aged with the operation of electrical equipment, thus causing a decline in electrical and mechanical properties. In actual operation, aging transformer oil can be filtered or even changed to remove aging products to restore insulation performance, but insulation paper in the bushing cannot be replaced, so the aging state of the insulation paper determines the aging life of the transformer.The main components of aramid paper are two polymers, aramid short-cut fiber and aramid pulp . It has 2, nano-Al2O3, nano-TiO2, nano-MgO, and nano-ZnO particles, and the performance of these nanoparticles can be different. The nano-SiO2 particles can reduce the dielectric constant of insulating paper, and at a content of 5%, the dielectric constant is 34% lower than that before modification [2O3 compared with the previous one [2 increases the frequency breakdown voltage of insulating paper [2O3, nano-TiO2 and nano-SiO2, whose dielectric constants are 9.8, 110 and 4.5, respectively. Meanwhile, scholars proposed a method to prepare low dielectric constant insulating paper using nano-SiO2 materials, which also provided ideas for this paper [In the field of using nanoparticles to improve the electrical properties of traditional insulating paper, scholars have tried to modify insulating paper by adding nano-SiOfication ; the theious one ,14; the ng paper ; nano-Mgng paper ; nano-Znng paper . Some scng paper . The litng paper ,24 shows2 particles were used as the modified additive of aramid insulating paper, and the nano-modified aramid insulating paper was prepared based on nano-modification technology, then the modified aramid insulating paper was tested by atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) to further analyze the effect of nano-SiO2 particles on the physical and chemical properties of the aramid insulating paper. Based on the results, an OIP bushing model was developed in Comsol to analyze the effect of modified aramid insulating paper on the actual electric field distribution of power transformers.Therefore, in this paper, nano-SiO2 particles as the modified additives of aramid insulating paper through four steps: ultrasonic stirring, fiber dissociation, paper sample copying and superheated calendering.In this paper, nano-modification technology was used to modify aramid insulating paper. The nano-modified aramid paper samples were prepared using nano-SiO2 particles, among which aramid staple fiber and aramid pulp, as important components of aramid insulating paper, play a decisive role in the material properties of aromatic insulating paper. The selected aramid short-cut fiber is 12 mm in length, about 10 μm in diameter and light yellow in color; the selected aramid pulp is 2 mm in length and light yellow in color; the selected SiO2 nanoparticles are about 12 nm in diameter, with a specific surface area of about 200 m2/g and are a white solid powder. The aramid short-cut fiber and aramid pulp selected for this paper were purchased from Yantai Teplon Advanced Manufacturing Technology Co. The nano-SiO2 powder was purchased from Guangzhou Wanjing Co. Raw materials used in the whole modified aramid sample preparation process include aramid staple fiber, aramid pulp and nano-SiOThe whole modified aramid insulating paper sample preparation process is shown in 2 nanoparticles with a diameter of about 12 nm are added to deionized water together with a 12% dispersant solution, and the mixed solution is dispersed ultrasonically with the aid of an ultrasonic cleaner;The SiO2 particles dispersion solution after being dispersed evenly, and stir it fully for 8 min. Subsequently add an appropriate amount of aramid pulp with a length of 2 mm, and stir it fully for 8 min to obtain a mixed original pulp containing nano-SiO2 particles;Take a fiber dissociator, add an appropriate amount of aramid short-cut fibers with a length of 12 mm to it, add the previously prepared nano-SiO2 particles to obtain dry paper containing the mixture of nano-SiO2 particles;Use a paper sample copying machine to copy and form the mixed original pulp containing the nano-SiO2 particles is superheated and calendered to obtain an improved aramid insulating paper containing nano-SiO2 particles.The obtained dry paper containing the mixture of nano-SiOThe specific process is as follows:2 nanoparticles to investigate the effect of SiO2 nanoparticles on the microscopic morphology of aramid insulating paper. Thermo SCIENTIFIC ESCALAB 250Xi X-ray photoelectron spectroscopy (XPS) was used to analyze the surface chemistry of the modified aramid insulating paper samples to obtain the composition elements of the modified aramid insulating paper samples.In this paper, a Dimension FastScan atomic force microscope (AFM)  and Quanta FEG 250 scanning electron microscope (SEM) were used to test the external physical morphology of modified aramid insulating paper samples containing SiO2 nanoparticles added during the preparation of the modified aramid insulating paper samples, the optimal modification ratio was investigated, and three groups of modified aramid insulating paper samples with different contents of SiO2 nanoparticles were produced. The modified aramid insulating paper samples with 0.5 wt%, 1 wt% and 3 wt% of nano-SiO2 particles were labeled as F1, F2 and F3, respectively, and the original aramid insulating paper samples without nano-SiO2 particles were labeled as F0.By controlling the amount of SiOThe AFM test results of the modified aramid insulating paper samples are shown in 2 particle filler, grooves on the surface of the modified aramid insulating paper samples increased significantly and surface roughness also increased, but when nano-SiO2 particle filler increased to a certain extent, grooves on the surface of the modified aramid insulating paper samples decreased again and surface roughness also decreased.From The results of the surface roughness Rq of the modified aramid paper samples are shown in 2 particle filler, the surface of the aramid insulating paper sample is gradually becoming etched by nano-SiO2 particles. The reason is that with an increase of nano-SiO2 particle modifier, the degree of etching of nano-SiO2 particle modifier on the surface of aramid insulating paper sample gradually increases, the surface of the aramid insulating paper sample is gradually changed, the surface of the substrate on the surface of the sample is gradually peeled off resulting in gradual exposure of the nano-SiO2 particle modifier, and the quantity shows an increasing trend.SEM tests were conducted on aramid insulating paper samples treated with the nano-modification technology, and test results are shown in 2 particle modifiers increased, the surface of the aramid paper sample was not further peeled off by the intermolecular force of the aggregation of SiO2 particle modifiers, which led to the reduction of surface roughness. The test results are shown in At the same time, as the number of SiO−6 Pa, setting the power to 500 W, using C1s as the energy counterpart for the whole XPS test process, and using MgKa rays as the energy source for the XPS test. The results of the whole XPS analysis are shown in XPS tests were performed on aramid insulation paper samples treated with nano-modification technology, and the results are shown in 2 nanoparticle filler, the characteristic peaks of C1s, N1s and O1s spectra changed, the chemical state of the surface of the aramid insulating paper samples treated by the nano-modification technology changed accordingly, and the contents of C, N and O all increased respectively. The content of the groups on the surface of the aramid fibers changed significantly, with the content of group –C–OH increasing and the content of the group –C=O showing an increasing and then decreasing trend, both of which were beneficial to improving the electrical properties of the aramid insulation paper samples, verifying the effectiveness of this modification method.It can be seen from test results that with a gradual increase of SiOIn order to understand the specific aramid modification results, a dielectric constant test was performed on this modified sample, and the test platform is shown in Oil-filled paper condenser type bushings are one of the common types of high-voltage bushings. Although the bushing structure under different voltage levels is slightly different, the structure of the internal capacitor packet is basically the same .This paper takes a 72.5 kV OIP bushing as the research object and uses COMSOL multiphysics 5.2a simulation software to simulate the electric field distribution before and after replacement of the capacitor packet. An oil-filled paper condenser type bushing is mainly composed of a connecting terminal, conservator, fastening spring, central guide rod, upper porcelain bushing, grounding flange, flange cylinder, lower porcelain bushing and capacitor packet. The bushing is filled with insulating oil, which together with the capacitor packet composed of insulating paper and aluminum foil forms the oil-impregnated paper insulation system. The length of the bushing is 2245 mm, the length of the upper porcelain bushing is 850 mm, the length of the lower porcelain bushing is 210 mm, the lead-in length of the cable is 1865 mm, the inner diameter of the conductive rod is 35 mm, and the maximum radius of the capacitor packet is 43.6 mm. The structure of this 72.5 kV OIP bushing is shown in In actual operation, the central guide rod of the bushing carries current and is fixed to the top of the transformer through a grounding flange. The capacitor packet uniformizes the electric field distribution between the central guide rod and the ground potential through an internal insulation system composed of insulating oil, insulating paper and aluminum foil. The thin capacitor packet bears the transformer phase voltage, the electric field strength is large, the operating environment is harsh, and manufacturing process requirements are high. Due to the existence of air bubbles in the capacitor packet, poor impregnation, and air gaps between oil and paper and other process problems, bushing failures and even transformer explosion accidents occur from time to time ,26,27.The oil-impregnated paper insulation system composed of insulating oil, insulating paper and aluminum foil is the main insulation for the transformer bushing. By alternately winding 0.08 mm–0.12 mm-thick insulating paper and 0.01 mm-thick aluminum foil on the central guide rod to form a plurality of capacitors with the same capacitance value, uniform voltage and electric fields are achieved . GeneralD is the electric flux, S is the area of the electrode plate, ε0 is the dielectric constant in vacuum, εr is the relative permittivity of the material, rE is the radial electric field strength here, r is the radius of the electrode, l is the length of the electrode, and c1 is a constant.If the error caused by the edge effect of the capacitor plate is ignored, it can be considered the electric flux passing through each level of the plate does not change:dU, and the axial field strength is lE, there are:Structure of the bushing capacitor packet is shown in Assuming the axial field strength as a constant, it can be obtained from Equation (1) that:c2 and c3 are constants. Integrate formula (4) to obtain:In the formula, c4 is a constant. Substituting formula (3) and boundary conditions r = r0, l = l0n; r = r, nl = l into formula (5), it can be solved as follows:In the formula, lE is a constant, the product of rE and rl is inversely proportional. The radial field strength of the capacitor packet presents a U-shaped distribution, the electric field strength is higher near the end screen and the center guide rod, and the electric field strength in the middle part is lower. Through the equal-capacitance design method, the length of each plate in the packet is solved by using the fact that the capacitance of each plate is equal. Suppose the interlayer capacitance is kC, then:From formula (7), it can be seen when It can be seen from formulas (7) and (8) that replacing the insulating material of the capacitor packet causes a change in the dielectric constant, resulting in a change in the electric field strength.The finite element method is a numerical calculation method based on the difference method and the variational principle. It was used in the structural mechanics in early days and was then gradually applied in the fields of electromagnetic field and fluid mechanics .The electric field of the high-voltage bushing is generated by the industrial-frequency alternating current passing through the center guide rod. The frequency is 50 Hz, which can be reduced to a two-dimensional axisymmetric electrostatic field problem. The Laplace equation of the potential is:The boundary conditions are the first and second types of boundary conditions, which are:Solving the electric field of the transformer bushing in the COMSOL finite element software can be divided into six steps, including selecting the electric field module according to the physical field of the problem to be solved; building the model according to the structure; setting the material parameters of each part; setting the load and boundary conditions; performing meshing according to the characteristics of the electric field and selecting a solver to solve the model .Due to highly axisymmetric characteristics of the transformer bushing, the three-dimensional model can be simplified into a two-dimensional axisymmetric model for calculation, and this has little effect on calculation accuracy. According to the structure of the transformer bushing, a two-dimensional symmetrical model is established in COMSOL, as shown in We add material properties to the solution domain according to bushing structure. In the simulation calculation, the relative permittivity of each material is set as shown in According to actual working conditions of the transformer bushing, a working voltage of 41.9 kV is applied to one end of the center guide rod, and a working current of 630 A is applied to the other end. The pole plate in the capacitor packet is set to a floating potential, and the end screen is connected to the flange by a grounding lead, which is set to the ground potential in the model, and the flange is also set to the ground potential. An air area at the length of 1.5 m and a fuel tank area at the length of 0.5 m are set outside the bushing to simulate actual working conditions.Since the thickness of the aluminum foil is only 0.01 mm, the mesh size will be extremely small, the number of meshes will be greatly increased, the quality of the mesh will be low, and the calculation accuracy will be affected when the finite element method is used for meshing. Setting it as a single-layer material in the simulation can avoid meshing problems.The simulation yields a cloud diagram of electric field distribution of the transformer bushing as shown in The radial electric field distribution of 72.5 kV bushing can be calculated using Equation (7). As shown in To investigate the effect of the relative permittivity of the capacitor packet on the electric field intensity of the OIP bushing, a parametric scan is performed using COMSOL simulation software. A variety of electric field distributions were obtained by setting different dielectric constants. By comparing each electric field distribution, the dielectric constant for optimal electric field intensity distribution can be found. Set the dielectric constant variation interval as  and the variation step as 0.2. The simulation solves the electric field intensity at each value, and takes the electric field intensity of the same position of the capacitor packet for comparison, as shown in The maximum and variance of the electric field intensity in the capacitor packet under each electric field distribution are calculated, as shown in As shown in 2 particle modifier on its surface gradually and the surface roughness of the sample, making the surface gouge situation increase significantly. However, with the increase of nano-SiO2 particle modifier content, it is influenced by the aggregation of nano-particles into clusters, which leads to the reduction of its surface roughness instead.The surface of aramid insulation paper sample can be effectively stripped by nano-modification technology, which increases the degree of etching of a nano-SiO2 particles with those of aramid insulating paper without nano-SiO2 particles, it can be seen that with the gradual increase of nano-SiO2 particles filler, the chemical state of its surface changed accordingly, the content of groups on the surface of aramid fiber changed significantly, the content of group-C-OH increased, and the content of group-C=O showed a trend of first increasing and then decreasing.After comparing the samples of aramid insulation paper modified with nano-SiOElectric intensity has the smallest variance and the electric field distribution is the most uniform. However, the manufacturing process of the material does not guarantee that the dielectric constant is accurately controlled at 2.8. Controlling the relative dielectric constant between 2.4 and 3.4 can achieve a more uniform electric field and a smaller maximum intensity. In this paper, the modified aramid paper insulation dielectric constant is basically close to the range of 2.4–3.4, which can achieve a more uniform electric field and a smaller maximum electric intensity.In this paper, nano-modification technology was used to modify aramid insulation paper, and the physical and chemical properties of the aramid insulation paper before and after modification were tested and analyzed. Based on the technical parameters of the modified aramid insulation paper, a model of OIP bushing was constructed, and its effect on the electric field distribution was studied. The main conclusions of this paper are as follows:


The proliferative activity was estimated for the case of human dermal fibroblast culture grown onto the surfaces of these types of substrates. Spherical non-agglomerated nanoparticles (NPs) of 20–40 nm in diameter were prepared by laser target evaporation (LTE) electrophysical technique. The concentration of the NPs in gel was fixed at 0.0, 0.3, 0.6, or 1.2 wt.%. Mechanical, electrical, and magnetic properties of composite gels were characterized by the dependence of Young’s modulus, electrical potential, magnetization measurements on the content of embedded NPs. The fibroblast monolayer density grown onto the surface of composite substrates was considered as an indicator of the material biocompatibility after 96 h of incubation. Regardless of the superparamagnetic or diamagnetic nature of nanoparticles, the increase in their concentration in the PAAm composite provided a parallel increase in the cell culture proliferation when grown onto the surface of composite substrates. The effects of cell interaction with the nanostructured surface of composites are discussed in order to explain the results.Two series of composite polyacrylamide (PAAm) gels with embedded superparamagnetic Fe Amongof cells ,7 by theof cells ,9,10.2O3) magnetic nanoparticles (MNPs) fabricated by the electrophysical technique of the laser target evaporation (LTE) [In our earlier studies, we tested the biocompatibility of ferrogel based on the polyacrylamide (PAAm) polymer network with embedded maghemite (γ-Feon (LTE) . Such paon (LTE) ,13. In pon (LTE) . Meanwhile, the nature of the positive impact of MNPs on the biocompatibility of ferrogels is still not clear. Many direct and/or indirect factors can contribute to this phenomenon. In particular, the addition of magnetic nanoparticles to the network of PAAm gel significantly changes the electrical and mechanical properties of FG that strongly control the cell adhesion and proliferation on the ferrogel substrate ,14,15. TThe aim of the present study was to check whether the magnetic MNPs per se affect the ferrogel biocompatibility. In particular, we intended to compare the biocompatibility of series of composite gels with embedded superparamagnetic and diamagnetic nanoparticles, which were almost the same in terms of their characteristic dimensions, morphology, and the properties of their suspensions in water. We analyzed the mechanical properties of these series of composite gels, their electrical potential, and the proliferative activity of human dermal fibroblasts on the surface of these two series of gel-based substrates.Here, we show that regardless of the superparamagnetic or diamagnetic nature of nanoparticles, the increase in NPs concentration in the nanostructured PAAm gel was accompanied by a similar increase in the cell proliferation on the surface of the gel-based substrates.2O3) and alumina (Al2O3) diamagnetic nanoparticles, denoted as MNPs (maghemite) and ANPs , were accordingly synthesized by means of laser target evaporation (LTE) method. The main details of the fabrication technology and the apparatus of LTE were described in detail in our previous reports [Maghemite superparamagnetic  and a scintillation detector. The diffractograms were processed by Rietveld full-profile refinement using built-in Bruker software TOPAS-3. The specific surface area (Ssp) of nanoparticles was measured using Micromeritics TriStar3000 analyzer .As-synthesized air-dry MNPs and ANPs were studied using transmission electron microscopy  operated at 200 kV. For TEM studies MNPs and ANPs were spread onto a Cu grid. Characterization of phase composition of MNPs and ANPs was done using X-ray diffraction technique  with a graphite monochromator . All magnetic measurements were made at room temperature. Apart from the measurements of the magnetic hysteresis loops M(H) for MNPs and ANPs, M(H) loops were also measured for all kinds of gels . For magnetic measurements of MNPs and ANPs, samples of about 5 mg for MNPs and 10 mg for AMPs were used. For gel-based composites, samples of about 60 mg were employed. The mean hydrodynamic diameter of particles/aggregates in suspensions was measured by the dynamic light scattering (DLS) using Brookhaven ZetaPlus analyzer . The same instrument was used for the measurement of the zeta-potential in suspensions by the electrophoretic light scattering (ELS).In addition, scanning electron microscopy (SEM) of dried MNPs and ANPs filled gel composites were performed with 20 kV accelerating voltage . In order to avoid the surface charging of the polymer composite, a carbon film using a sputtering technique was deposited onto the composite surfaces with a thickness of about 20 nm.Synthesis of composite gels with embedded MNPs and ANPs was performed by free-radical polymerization of acrylamide monomers  dissolved in water suspensions of MNPs and ANPs. The suspensions were prepared by the dispersion of nanoparticles in 5 mM water solution of sodium citrate, which was an electrostatic stabilizer of the suspension. Dispersions were de-aggregated by ultrasound treatment with permanent cooling for 30 min using Cole-Parmer CPX-750  processor operated at 250 W. Remained large aggregates were precipitated by centrifuging for 5 min at 8000 rpm using Hermle Z383 centrifuge . De-aggregation in suspensions was controlled using DLS. The concentration of nanoparticles in these stock suspensions was determined using the weight of a dry residue after drying at 90 °C to the constant weight (with the correction for the dissolved sodium citrate). The content of MNPs in the stock suspension was as high as 4.8% by weight, and the content of ANPs was as high as 4.0%.Stock suspensions were diluted by 5 mM water solution of sodium citrate to provide variation of nanoparticle content in the resulted composite gels. Monomer AAm was dissolved in MNPs and ANPs suspensions in 1.6 M concentration. Cross-linking agent N,N’-methylene bisacrylamide  was added in 1:100 molar ratio to AAm. An initiator, ammonium persulfate (APS), was used at a 3 mM concentration. Polymerization was performed at room temperature employing N,N,N’,N’-tetra-ethylene-methylenediamine  in 5 mM concentration as a catalyst.For the implication of substrates for cell cultivation, the composite gels were synthesized in the shape of thin sheets. Therefore, polymerization was done between two polished glass plates, separated by 0.8 mm spacers and using the mold sealing by a silicon resin. The reaction mixture was poured between the plates using a syringe. It took approximately 5 min for the gelation of the reaction mixture in the mold. The mold was kept for an extra 60 min to complete the polymerization, and then it was disassembled. The resulted sheets of composite gels with embedded MNPs and ANPs were extensively washed in distilled water with daily water renewal in order to remove salts and unreacted monomer until the equilibrium water uptake was achieved. The final contents of nanoparticles in the composite gels swollen to equilibrium were as high as 0.33%, 0.63%, and 1.19% in the gel series with embedded MNPs, and 0.34%, 0.61%, and 1.23% in the gel series with embedded ANPs.Afterward, the gel sheets were equilibrated for 2 days in Hanks Balanced Salt Solution (HBSS) pH = 6.8–7.2  with gentamicin (100 mg/L) with a daily renewal of the solution. Then for 2 days, they were kept in 199 solution pH = 7.0–7.4, osmolality 300 ± 20 mmol/kg, and a buffering capacity of ≤ 1.5 mL  with gentamicin (100 mg/L) with daily renewal. Then the substrates in the shape of disks (13 mm in diameter) were cut from the gel sheets to fit the wells of the standard 24-well polystyrene plate for cell culturing. Prior to their use in the cell culture, the gel-based substrates were sterilized in an autoclave at 121 °C for 20 min.The elastic properties of gels and FGs were determined using a laboratory setup for mechanical tests ,15. CyliThe electrical potential of gels was determined using the standard technique, which is routinely applied to living cells. Specifically, two identical silver-chloride electrodes in glass micropipettes TW150F-6  with a tip diameter of ~1 μm filled with a 3 M KCl solution were used. One electrode was placed in the solution surrounding the gel, and the other one was introduced into the studied sample. The potential difference was measured with an INA 129 instrumentation amplifier .2. Cells were passaged when they covered 80% of the flask surface area. Then sub-culturing cells were treated with 0.25% trypsin-EDTA solution . Cell number was estimated by cell counter TC-20 device . The cell viability was measured by staining with trypan blue. Fibroblasts were stored in liquid nitrogen.The lines of human dermal fibroblasts were obtained from donor skin, as described previously ,13,14. B2 (viability ≥ 95%) for all types of substrates. Plates were incubated at 37 °C, in the 5% CO2 atmosphere for 96 h. All cell experiments were performed without the application of the external magnetic field. However, we did not shield possible laboratory magnetic fields, which usually do not exceed one Oersted strength. After incubation, cells in the monolayer were fixed with 2.5% glutaric aldehyde. Fibroblasts on the substrate surfaces were visualized by staining cell nuclei with 4’,6-diamidino-2-phenylindole  and cytoplasm with 0.3% pyrazolone yellow solution. Cells were counted using a fluorescent Axio Lab A1 FL  microscope. The analysis for nine fields of view for each sample at “×100” magnification was done. The number of cells in images was estimated using the ImageJ software .Thawed cells were passaged 2 times before they were used in experiments. Fibroblasts (fifth passage) were detached from the flask surface by trypsin. After detachment of cells, trypsin was neutralized by fetal bovine serum. Gel discs with MNPs, ANPs, and blank gel discs were placed into the wells of 24-well tissue-treated culture plates . Some wells were left empty to be used as controls of cell growth on tissue-treated culture plastic. Fibroblasts were re-suspended in a growth medium. The suspension was dispensed in wells with a seeding density of 3000 viable cells/cmThe experiment was performed in 6 replicates. We used the non-parametric Mann–Whitney U-test in order to compare the statistical significance of the difference between two independent groups with a level of significance set at 0.05. Statistical data processing was performed employing the application software package “STATISTICA 6.0” .Both MNPs and ANPs embedded into gel-based substrates were synthesized by the LTE method, which provided their basic similarity despite different chemical compositions. In both cases, the shape of nanoparticles was very close to being spherical, which was the result of their condensation from the vapor phase. The histograms were plotted as a result of the graphical analysis of 2572 images in the case of MNPs and 2206 images in the case of ANPs. In both cases, the diameter of nanoparticles fell within the 5–50 nm interval with a probability maximum of 14 nm. The histograms were nicely fitted by a lognormal distribution function:Parameters of the distributions are given in 2O3 with a cubic lattice . The average size of the coherent diffraction domains in ANPs was 17 nm.The crystal structure of MNPs corresponded to single-phase maghemite with an inverse spinel cubic lattice , space group Fd3m). The average size of the coherent diffraction domains was 12 nm estimated using the Scherrer approach . The crysp) of nanoparticles, determined using low-temperature adsorption of nitrogen (BET method), was 93 m2/g for MNPs and 78 m2/g for ANPs. These values could be used for the evaluation of the average diameter of particles according to the following Equation (2) [The specific surface area (Stion (2) , which r3 in the case of MNPs, and it was 3.6 g/cm3 in the case of ANPs. Given these values and the values of the specific surface area, the average diameter of MNPs was evaluated to be 14.0 nm, and the diameter of ANPs was 21.4 nm.The crystallographic density of particles was 4.6 g/cm4 K) at the laser spot on the surface of the target during its evaporation. Nitrogen oxides then provide traces of metal nitrides on the surface of condensed nanoparticles. In water suspensions, nitrides dissociate, and the surface gets a net positive electrical charge due to the metal ions while nitride ions migrate to the water medium as counterions of the double electrical layer. It provides the colloidal stability of the suspension, which can be characterized by the value of the zeta-potential of the suspension. The values of zeta-potential for the self-stabilized suspensions of MNPs and ANPs are given in The specific feature of metal oxide nanoparticles synthesized by the method of gas-phase physical dispersion is their self-stabilization in water suspensions . It meanMeanwhile, self-stabilization of suspension of LTE nanoparticles is a limiting factor, and it can not provide the colloidal stability of these suspensions in the solutions with high ionic strength, which is typical in biological systems. Therefore, suspensions for biomedical applications were additionally stabilized by sodium citrate. Citrate ions adsorb on the surface and reverse their electrical charge from positive to negative; sodium cations become the counterions of the double electrical layer. The colloidal stability of the citrate-stabilized suspensions increases. hd) of a nanoparticle in a suspension, is given in i. There was a certain difference between the values of dhd and di. This difference partly stems from the solvation layers on the surface of nanoparticles in water medium. In addition, some small aggregates of nanoparticles still could remain in the suspension after centrifuging. The values of the fifth moment of distribution are highly sensitive even to the presence of a small number of aggregates. However, their total fraction is not dominant.The average hydrodynamic diameter of the ensemble of nanoparticles is related to the fifth moment of PSD, which is given in Thus, the analysis of the properties of MNPs and ANPs shows that these two batches of LTE nanoparticles are very similar concerning their shape, dimensions, surface properties in water suspension, and colloidal stability. The only difference between them is in their magnetic properties.2O3 magnetic nanoparticles are a well-known and well-studied biocompatible magnetic nanomaterial with high saturation magnetization. As expected for superparamagnetic nanoparticles of the size under consideration, the saturation magnetization (Ms) was significantly reduced in comparison with the bulk case [s previously obtained for MNPs of this size.ulk case . The S-s2O3 magnetic nanoparticles, and the magnetic field dependence of the magnetization of Al2O3 nanoparticles was not visible. However, it became noticeable at a low magnetization scale , as expected for this kind of material. Again, the difference was huge for the scale appropriate for M(H) hysteresis loop of γ-Fele Inset .We have focused on the properties of the suspensions of nanoparticles because these features strongly determine the arrangement of the embedded NPs in the composite gels. Currently, there is no reliable experimental method for the direct observation of the arrangement of the embedded nanoparticles in swollen composite gels. Any microscopic technique presumes certain dehydration of the gel, which inevitably would disturb its intact structure. In this respect, we have to rely somehow on the indirect features of the synthetic procedure and the macroscopic properties of the fabricated composite gels.As shown above, the precursor suspensions of MNPs and ANPs were almost de-aggregated and contained mostly individual nanoparticles with a fraction of small aggregates. These suspensions were transparent, which meant that there were no moieties larger than the wavelength of the visual light—approximately 600 nm. Moreover, there was no visual opalescence in the suspensions, and consequently, the limit might be lowered down to a quarter of a wavelength, which was approximately 150 nm. This estimation of the upper limit in the characteristic dimension of moieties present in the suspensions correlated well with the PSD given in During the synthesis, the visual appearance of the precursor suspensions did not change. They remain transparent at the stage of the mixing with reactants and at the stage of gelation as well. Visually, the gels look the same as the precursor suspensions. It made us assume that the distribution of the nanoparticles that were established in the precursor suspensions preserved, in general, in the resulted composite gels. g the mass of a gel sample and mdr is the mass of the dry residue after the gel sample is dried to the constant weight.The mesh size of the PAAm network in composite gels was estimated based on the value of the swelling ratio of gel. The swelling ratio (α) is given by Equation (3):dr includes both the mass of the dry polymeric network and the mass of the embedded solid nanoparticles. To obtain the swelling ratio of the polymeric network (αp), the correction should be done according to Equation (4):However, in composite gels the value of mThe swelling ratio of composite PAAm gels determined using Equations (3) and (4) was found to be 12.6 ± 0.4 both for gel series with MNPs and ANPs independently of the content of nanoparticles. C is the number of monomer units among cross-links of the network; V1 and V2 are the molar volumes of water and of PAAm, respectively; χ is Flory–Huggins parameter for a binary interaction between water and PAAm; α0 is the swelling degree of PAAm gel as provided by the composition of the reaction mixture in the synthesis. We used V1 = 18 cm3/mol (water), V2 = 56.2 cm3/mol (PAAm) and χ = 0.12. The last two values were calculated by means of quantum mechanics molecular modeling software package CAChe7.5. As it was given above, the equilibrium swelling ratio was 12.6; the swelling ratio of as-synthesized gel was 10. Given these values, the average number of monomer units among cross-links of the network according to Equation (5) was found to be NC = 64.The swelling ratio of a hydrogel network is, in other words, the water uptake of the network, i.e., the amount of water that the network can hold within it. Its value, in principle, depends on the mesh size of the network and the energy of interaction between water and polymeric sub-chains. This dependence is given by the Flory–Rehner equation ,22. Usina is the bond length, θ is the bond angle, and φ is the angle of hindered rotation. In a PAAm polymeric chain, the bond length a = 0.154 nm for the ordinary C–C bond, the bond angle θ = 109.5°, the angle of hindered rotation φ = 120°, and N = 2NC. It is two-fold larger than NC as it includes the bonds in monomer units and bonds between them. Given these values, the average distance among the cross-links according to Equation (6) was found to be 4.3 nm. This value was the effective mesh size of the PAAm network in the composite gels. It was evident that the mesh size of the network is much smaller than the characteristic dimensions of MNPs and ANPs  :(6)〈R2〉=ANPs see . Thus, wThe substantial difference between these two series of gel-based composites was in their magnetic properties. The main methodological advantage of the present study is the employment of the same synthesis technique for the fabrication of two different types of nanoparticles, which we denote as ferromagnetic (iron oxide) and non-ferromagnetic . Here we keep in mind the most general division of magnetics is in ferro-, antiferro-, para-, and dia-magnetics . The bulDespite small concentrations of MNPs the magnetic properties of ferrogels were very different for the range of selected concentrations a; the hiMeanwhile, for the same concentrations of the ANPs in gel-based composites b, we couAt higher content of nanoparticles in composite gels, their concentration connection with Young’s modulus was different. While in the case of MNPs the rigidity of composite gels increased further with the concentration increase, the gels filled with ANPs showed a tendency to decrease Young’s modulus. The increase om the ANPs concentration from 0.3% to 1.2% was accompanied by the subsequent decay of rigidity of composite gels so that at ANPs concentration of 1.2%, the modulus was significantly smaller than that one at 0.3%. At the same range of MNPs concentrations, the rigidity of ferrogels was gradually increasing. Noteworthy, at nanoparticle concentrations of 0.6% or 1.2%, the Young’s modulus of composite gels with embedded MNPs was significantly larger in comparison with the composite gels with embedded ANPs. n = 54). To assess the viability evaluation of the used fibroblasts, cells were also seeded onto the standard substrate—tissue-culturing polystyrene (TCPS). At the end of incubation, the number of cells was 21,000 ± 1000 per cm2, which corresponded to good cell viability.According to the obtained data, the addition of both MNPs and ANPs to the PAAm gel network led to a significant and almost the same increase in the proliferation activity of fibroblasts. Importantly, at the initial NPs concentration of 0.3%, both of the gel-based composites with MNPs and ANPs had similar Young’s modules and electrical potentials see . In gene2O3 NPs, and from 0.6% to 1.2% for gels with Fe2O3t NPs, was significant and approximately the same. The contribution of specific NPs to cell proliferation rate must be compared in the gel-based substrates with approximately the same mechanical and electrical properties. According to the results presented above see , the gel2O3 or Al2O3 nanoparticles in different concentrations. Despite the difference in the chemical composition of the nanoparticles , these two series of substrates were similar in many senses. Both were based on PAAm gel with the same concentration of monomer (1.6 M) and the same concentration of cross-linker (1:100 molar ratio to monomer). The nanoparticles were synthesized by the same method (LTE) using the same laboratory installation; both types of nanoparticles were spherical, non-agglomerated, and had close characteristic dimensions (10–40 nm) and parameters of PSD. In both series of gel-based substrates, the inner distribution of NPs in the PAAm matrix was approximately the same. In the present study, the biological activity of cells was investigated for two types of gel-based composites: PAAm hydrogels filled with γ-FeAs discussed in previous work ,13, as tThe magnetic characterization revealed that two series of gel-based composite substrates were very different in terms of their magnetic properties. While gels with MNPs showed ferromagnetic behavior with magnetization proportional to the content of iron oxide, gels with ANPs are diamagnetic, it is clear that any difference in the cell cultivation results of gel substrates with embedded ANPs could not be assigned to the difference of magnetic properties of gel composites with different concentration of ANPs.The possible influence of magnetic interactions between iron oxide nanoparticles could be taken into account for the gel-based composites with embedded MNPs. However, as in the present study, all cell proliferation experiments were performed without the application of the external magnetic field. Although it is unlikely that they might provide a substantial contribution, this point requires further investigation as many other cases involving small magnetic fields . From thThe electrical potential and the mechanical properties of composite gels were almost the same at the lowest content of NPs (0.3%), no matter whether NPs were magnetic (maghemite) or diamagnetic . Meanwhile, different trends in Young’s modulus and in the electrical potential were found as the content of NPs increased see . In the However, despite the marked difference in the magnetic properties, the electrical potential, and the elasticity between magnetic and diamagnetic gel-based substrates, the proliferation of human fibroblasts on these two platforms revealed qualitatively the same result. In both series of gel-based substrates, the increase in NPs content resulted in the enhancement of the proliferation activity of fibroblasts. In meant that the magnetic properties of maghemite NPs did not play a significant role in the determination of the biological activity of fibroblasts on the PAAm gel-based substrates with embedded NPs. In other words, a key factor other than the magnetic properties of the gel-based substrates governs the biocompatibility of nanostructured composites.Fibroblasts are a type of mechanically sensitive cells, which are able to accept and transform mechanical signals for their vital activity ,27,28. TIn vitro experiments have shown that the surface geometry pattern played a significant role in the realization of the mechanical transduction phenomenon in cells together with chemical composition, wettability, surface charge, elasticity, and other factors ,34,35. T2O3 were characterized by higher “electronic density”, i.e., they interacted more actively with the electronic beam, they look much brighter . Thus, the surface of the gel substrate might be covered with small dimples separated by ca. 0.15 μm.It is also feasible that NPs, which disentangle from the gel network, do not move to the bulk of the liquid phase but provide the adsorption layer at the surface. There are certain grounds for such supposition. It was shown in previous work  that theThe mechanism of the bonding of the mechanically sensitive receptors of cells to the heterogeneous surface patterns of nanocomposites is not elucidated yet. Supposedly it may be provided by a certain packing of integrins, which match the characteristic dimensions of nanostructures, like the diameter of nanotubes ,45. A mo2O3 bi-phasic nanowires (NWs) [Besides, we may suppose that the adhesion of cells to the scaffold can be mediated by proteins, which are the components of the medium for the cell culturing and better adsorb at the rough surface. It was reported that even a small amount of vitronectin and fibronectin at the surface of ferrogel substantially promoted the adhesion of cells due to the presence of a specific amino acid sequence (Arg-Gly-Asp) in their chemical structure, which is favorable for the interaction with membrane receptors of fibroblasts ,49. Simies (NWs) . Thus, it is reasonable to interpret the results obtained in the present study from the viewpoint of the structuring of the surface of the gel-based composites by the exudation or/and adsorption of nanoparticles. The mechanisms of the surface structuring are likely the same for the composite PAAm gels filled with alumina or magnetite, and therefore the effect of gel-based composites on the adhesion and proliferation of human fibroblasts might be the same as well, i.e., gel-based composites provide a heterogeneous surface geometry pattern, which is favorable for the adhesion of cells.In general, the obtained results showed that in the elaborated experimental conditions, the proliferation activity of human fibroblasts on the surface of gel-based composites did not depend on the magnetic properties of the embedded nanoparticles. It is worth mentioning that this finding was not influenced by the fact that the gel-based composites of the magnetic and diamagnetic origin significantly differed in their Young’s modulus and electrical potential. It may be taken as additional support for the hypothesis that the surface geometry pattern has a key role in the biocompatibility of gel-based composites.In the meantime, there is quite a lot of studies that address ferrogels as prospective magnetically controlled composites for applications in tissue engineering, regenerative medicine, field-assisted drug delivery, and magnetic biosensing. Various polymers: synthetic, biological, and their blends are used as matrices for these composites. Iron oxide magnetic particles embedded in composite ferrogels also vary in dimensions, chemical compositions, synthetic routes, and other parameters. In general, results obtained in these studies confirm good biocompatibility of ferrogels, and the achieved level of magnetic properties of these materials makes them especially attractive for magnetic field-assisted drug delivery and magnetic biosensing ,51. The 2O3 from the same batch, PAAm gel with the same networking, the same procedures, and experimental techniques. According to these studies, the increase in MNPs content in ferrogel always led to the reliable enlargement of the density of cells monolayer at the surface of magnetic composites. Similar results were obtained in the present research, which compared the biocompatibility of gel composites with embedded magnetic iron oxide nanoparticles and embedded non-magnetic alumina nanoparticles, which were very close in terms of their shape and dimensions.The present study is a special step allowing a comparative evaluation of the contributions of MNPs and ANPs. This comparison finally became possible because of our research works related to the biological activity of cells at hydrogels and ferrogels in similar experimental conditions ,11,12,132O3 or diamagnetic Al2O3 nanoparticles. Composite polyacrylamide gels with Fe2O3 or Al2O3 embedded nanoparticles were synthesized, aiming to study the magnetic contribution to the ferrogel biocompatibility. The proliferative activity of human dermal fibroblast cell cultures on the surface of these gel-based composites was estimated. The concentration of the fillers in the gel was fixed at 0.0, 0.3, 0.6, or 1.2 wt.%. Mechanical, electrical, and magnetic properties of the composites were characterized by the dependence of Young’s modulus, electrical potential, magnetization measurements on the content of embedded nanoparticles. The fibroblast monolayer density on the surface of composite substrates after 96 h of incubation without application of external magnetic field was evaluated for estimation of the composites biocompatibility. It was found that regardless of the nature of the nanoparticles, the increase in their concentration in the composite provided a parallel increase in the cell proliferation on the surface of composite substrates.Two series of non-agglomerated spherical nanoparticles of 20–40 nm in diameter were fabricated by laser target evaporation technique: superparamagnetic FeThe main conclusion of the present study is the statement that the biological activity of cells on the surface of composite gels does not depend on the magnetic properties of nanoparticles, at least in the elaborated experimental conditions. In other words, the obtained results exclude a significant contribution of the magnetic field provided by magnetic nanoparticles inside ferrogel and near its surface on the biocompatibility of magnetic gel composites in the conditions under consideration.2O3 and Al2O3 systems fabricated by the same technique and characterized in the same conditions.In general, the present study has more methodological than applied value. It is addressed toward the search of a key determinant of FG biocompatibility. In a series of preliminary experiments performed under the same experimental conditions, we tried to exclude systematically the indirect contribution of various factors that can determine cell biological activity at the surface of ferrogels, in particular, the mechanical properties and electrical potential of composites. In this study, we excluded the direct contribution of the FG magnetic effects in very low magnetic fields of the order of terrestrial magnetic field values. Finally, we assumed that the FG biocompatibility is most likely associated with the effect of the particles on the composite surface. At the same time, the results obtained can be useful in the design of gel-based composites for cell technologies. In this context, the application of ferrogels with the use of an external magnetic field is of the greatest interest. From our point of view, research in this direction will make it possible to optimize the principles of controlling biological processes in cell cultures grown onto FG. Special attention should be paid to one very important aspect of this study: iron oxide magnetic nanoparticles from the same batch were used in previous experiments, ensuring a very good basis for comparison of the results obtained for Fe


Recently, a study led by the Academician Zhong Nanshan in China on the treatment of the patients with the COVID-19 by inhalation of a mixed gas composed of hydrogen and oxygen has attracted widespread international attention and hydrogen therapy has also been included in a new treatment plan for the COVID-19 in China. This study mainly describes the mechanism of occurrence of the COVID-19, summarizes the therapeutic effects and underlying mechanisms of hydrogen on the critical disease, and analyzes the feasibility and potential therapeutic targets of hydrogen for the treatment of the COVID-19.Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has no specific and effective treatment. The pathophysiological process of the COVID-19 is an excessive inflammatory response after an organism infects with a virus. Inflammatory storms play an important role in the development of the COVID-19. A large number of studies have confirmed that hydrogen has a therapeutic effect on many diseases  The WHO pointed out that the patients whose main symptoms are fever, cough, and fatigue, 80% of the patients have a good prognosis. Their radiological features are the interstitial changes in the lungs. However, about 14% of the patients have a critical illness and 5% of the patients have a severe infection combined with dyspnea and/or hypoxemia followed by the rapid progression to acute respiratory distress syndrome, septic shock, and multiple organ Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a novel virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of August 2021, the number of cases of infection and death has increased to 218 million and 4 million, respectivelyvia the S protein on the envelope surface  receptor on the surface of the tissue cells  surface –3. After surface , 5. AfteAutopsy of the deceased cases revealed that the lung tissues were congested, edematous, and enlarged in size with various degrees of consolidation . The conin vivo, and reducing cell damage caused by the products of inflammatory response can become the potential therapeutic targets of the COVID-19. Inflammatory storm and ROS are both the targets of hydrogen therapy.Simultaneously, Erlich et al. found that the excessive activation of the immune cells and persistent inflammation caused by the viral infection generate large amounts of reactive oxygen species (ROS) . Pro-infHydrogen, the lowest density gas known in the world, has the smallest molecular mass and some degree of reducibility. Biological research on hydrogen began in 1975 using 97.5% hydrogen and 2.5% oxygen mixture to treat the UV radiation-induced squamous cell carcinoma of mouse skin . In 20012. Initially, the hydrogen element used in the clinical trials was mainly in a non-gaseous form. Clinical studies have shown that drinking HRW is safe and well-tolerated and HRW containing 0.8 or 5 mM dissolved H2 improves the clinical symptoms in the patients with Parkinson's disease (2 (3.5 mg H2 in 500 ml water) could protect the vascular endothelium from ROS 2 + H2 supplying 6 ppm of H2 per day , injection of HRW, bathing with HRW, and eye drops containing dissolved H disease –22. HRW from ROS . Healthy012 mg/l . A hydrorthritis . Frequenrthritis . Oral hy per day .via nasal cannula by using the Hydrogen/Oxygen Generator . H2-O2 inhalation for 7.7 h on the basis of standard of care significantly improved the severity of the disease on day 2, including dyspnea scale, chest distress, chest pain, cough scale, and resting oxygen saturation, compared with the control group of the patients who received daily standard of care with oxygen therapy. This may be related to the reduction of inhalation resistance by hydrogen/oxygen mixture -/CD8+ T cells in the peripheral blood, significantly longer progression-free survival, and improved prognosis . In addi mixture . Neverth mixture . Moreove mixture .Neutrophils, as the first defense part of the innate immunity, are considered to play a protective role upon the bacterial or fungal infection. They kill the bacteria or fungi through phagocytosis and neutrophil extracellular traps (NETs) . Howevervia nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway and significantly reduced ovalbumin-induced airway hyperreactivity and inhibited inflammation and goblet cell proliferation , and •OH , and a negligible scavenging effect on other reactive oxygen species such as superoxide anion radical (O2•)  species  such as  and •OH . The elentiation . Similarntiation . Hydrogeal (O2•) , which mal (O2•) . Howeveral (O2•) . Therefoal (O2•) . Therefovia its anti-inflammatory effect, which may be a therapeutic target for its treatment of Kawasaki-like diseases caused by the COVID-19  Hydrogen can directly enter the lung tissue through respiratory activities. If inhaled in combination with oxygen, oxygen can be brought into the deeper bronchus space, reducing airway resistance, increasing oxygen dispersion, and improving the respiratory function of the patient; (2) Hydrogen has a selective antioxidant effect that neutralizes the hydroxyl radicals without affecting the functional reactive oxygen. When mixed with oxygen, the potential damage from the high concentrations of oxygen can be reduced; (3) After hydrogen enters the lung tissue, it exerts anti-inflammatory effects at the multiple stages of the inflammatory response, alleviating the airway damage caused by the excessive activation of the inflammatory cells and the massive release of inflammatory factors; (4) Hydrogen can be obtained by electrolyzing water and the raw materials of the reaction are cheap and the resources are extensive. The safety of inhaling hydrogen has been demonstrated in diving medicine  and the YL wrote the first draft of the manuscript. WZ and YW wrote the section of the manuscript. ZW and KX contributed to manuscript revision. All authors contributed to the article and approved the submitted version.This study was supported by a Grant from the Natural Science Foundation of Tianjin (17JCYBJC24800 to KX), the Science and Technology Support Key Program Affiliated to the Key Research and Development Plan of Tianjin Science and Technology Project (18YFZCSY00560 to KX), and the National Natural Science Foundation of China , Beijing, China.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The oblique-incidence ionosonde network in North China is a very unique system for regional ionospheric observation. It contains 5 transmitters and 20 receivers, and it has 99 ionospheric observation points between 22.40° N and 33.19° N geomagnetic latitudes. The data of the ionosonde network were used to investigate the statistical characteristics of the quasi-3-h large-scale traveling ionospheric disturbances (LSTIDs). From September 2009 to August 2011, 157 cases of the quiet-time LSTIDs were recorded; 110 cases traveled southward, 46 cases traveled southwestward and only 1 case traveled southeastward. The LSTIDs mainly appeared between 10:00 and 19:00 LT in the months from September to the following May. We compared the data of the Beijing, Mohe and Yakutsk digisondes and found that the LSTIDs are most likely to come from the northern auroral region. These LSTIDs may be induced by the atmospheric gravity waves (AGWs) and presented obvious seasonal and diurnal varying features, indicating that the thermospheric wind field has played an important role. Large-scale traveling ionospheric disturbances (LSTIDs) are generally considered as the manifestation of the atmospheric gravity waves (AGWs) in the ionosphere and are usually observed while the geomagnetic storms and auroral substorms occur ,2,3,4,5.A variety of equipment types, such as ionosondes ,15,16, iAs shown in ofF2) used in the following is obtained by this echo trace conversion method, and the long period observation verified the accuracy of this method with the comparison of the VI observation [ofF2 between the vertical and oblique observations never exceed 1 MHz and are generally less than 0.5 MHz.Different from the traditional VI ionosonde, the transmitter and receiver of an OI ionosonde are separated, and it can also measure the ionospheric parameters such as the virtual and peak heights, as well as the critical frequency, like a traditional VI ionosonde ,28. As servation ,31. ChenofF2 at all the observation points of the ionosonde network. In order to eliminate the day-to-day variations and so highlight the periodic disturbances in the F2 layer, we estimate the difference ofF2 (∆ofF2) compared with the monthly value,ofF2m represents the monthly mean of the ofF2 during the magnetically quiet days.In a network consisting of many OI ionosondes, the signal of one transmitter can be received by several receivers, and one receiver can receive the signal of several transmitters; thus, fewer radio systems can be used to obtain more ionospheric observation points. In North China, the OI ionosonde network composed of 5 transmitters and 20 receivers was constructed to observe the regional ionosphere with 99 observation points . The bluThe data of the OI ionosonde network from 1 September 2009 to 21 August 2011 are analyzed. Except for the maintenance time, the network has been working for 684 days. Excluding the impact of geomagnetic activities, there are 595 magnetically quiet days with the maximum Kp index ≤ 3. During these days, 157 cases of the LSTIDs from the north have been recorded. The observed LSTIDs mainly traveled to the south and southwest. We introduce two typical cases of them firstly.ofF2 depletion firstly appeared at 14:30 LT in the top right corner of ofF2 enhancement emerged in the top right corner of ofF2 enhancement occurred in the northeast in ofF2 enhancement emerged in the north of the map in ofF2 enhancement appeared at 12:30 LT in One case of the LSTID occurring on 24 November 2010 is shown in ofF2 values recorded by the 99 observation points. The disturbances of several periods are clearly displayed. They lasted for more than 10 h with periods of 3.9 h in ofF2 values is displayed in the second row of The latitude and longitude dependences of the two cases of ionospheric oscillations are drawn in the top two rows of mhF2). The variations of the plasma frequency at the heights from 190 to 230 km with 10 km step are presented in the fourth row of mhF2, respectively. We connect the wave peaks and troughs at different heights and find that the wave phase velocities are downward. The echoes of an ionosonde are reflected below mhF2, so the solid circles in ofF2 curves recorded by the digisondes in Beijing, Mohe and Yakutsk are shown in the bottom row of To further study the characteristics of the two LSTIDs, the observations of the three digisondes at different latitudes are analyzed. The third row of We develop four criteria to accurately recognize the LSTIDs from other ionospheric disturbances: (1) The amplitude of the enhancement or depletion exceeds the diurnal average by at least 5%. (2) At least 60% of the ionospheric observation points of the ionosonde network as well as the Beijing digisonde have recorded the same periodic disturbance. (3) The duration of the wave peak and trough exceeds 30 min. (4) More than two circles of the disturbances are recorded. In the magnetically quiet days from 1 September 2009 to 21 August 2011, 157 cases of the LSTIDs from the north have been recorded by the OI ionosonde network. The total occurrence rate of the quiet-time LSTIDs is 26.39%, which is defined as a fraction of the days the quiet-time LSTIDs were observed against the total number of magnetically quiet days. The four seasons in North China are defined as spring (March–April), summer (May–August), autumn (September–October), and Winter (November–February). The occurrence number and occurrence rate of the quiet-time LSTIDs in four seasons are presented in The occurrence rates of the LSTIDs varying with local time in different months are shown in Two-year azimuth variations of the mid-latitude LSTIDs are presented as the blue dots in Almost all the case studies of the LSTIDs focus on the disturbances associated with storms  propagating equatorward e.g., ,58,59). ,59. 58,5Aside from the GPS network, the dense OI ionosonde network offers another possibility to continuously observe the horizontal propagation of TIDs by both day and night. It is an economical solution using multi-input and multi-output technology. The inversion parameters of the network can present the propagation characteristics of the oscillations on a horizontal plane through the peak plasma density variations at each observation point. Based on the observations of the OI ionosonde network in North China and the digisondes in Beijing, Mohe and Yakutsk, a statistical study of the quiet-time LSTIDs was conducted. An interesting phenomenon of the mid-latitude LSTIDs of quasi-3-h period has been reported. It highlights the observation particularity of the OI ionosonde network, and the long-term observations of this network will deepen our understanding of the atmosphere–ionosphere coupling as well as the influence of momentum from polar regions on the middle and low latitudes.


The use of nanotechnologies is important to reduce environmental health problems in Iran, so the present study was conducted to determine the effectiveness of nanotechnologies in environmental health. This is a cross-sectional descriptive study for 11-year periods (2008–2018) on all articles published in three specialized journals of environmental health with emphasis on the use of nanotechnologies in various fields of environmental health .In this study, 774 articles related to 114 issues of 3 specialized environmental health journals were reviewed. A review of 774 articles showed that 80 articles (10.3%) were published in the field of nanotechnologies. Out of 80 articles published in the field of nanotechnology, 66 articles (82.5%) were published on the subject of water, 9 articles (11.3%) on wastewater and 5 articles (6.2%) on air pollution. Subject review of articles showed that articles using carbon nanotubes to remove natural organic pollutants, surfactants, hydroxybenzenes, phenol, dimethyl phthalates, use of titanium dioxide nanoparticles, iron-magnesium nanoparticles for wastewater treatment, Silver nanoparticles were used to remove air pollution. The results showed that published articles on nanotechnology in the field of environmental health were few. Nanotechnology has emerged from the convergence of the physical sciences, chemistry and biology and is the foundation of convergent technologies  was conducted for 11-year periods 2008–2018) among all articles published in three specialized journals of environmental health. Inclusion criteria for this study included the name of environmental health in the title of the journal, having at least four issues per year and publishing articles for at least three consecutive years. According to the inclusion criteria, three Persian language journals were reviewed: Iranian Journal of Health and Environment (IJHE), Journal of Environmental Health Engineering (JEHE), Journal of Research in Environmental Health (JREH). After visiting the site of the journals, the abstract and then the full text of the articles were reviewed. Articles focusing on the use of nanotechnologies in each of the topics of environmental health  were included in the study. Data collection was done through a researcher-made checklist. To prepare the checklist, scientometric method was used, which is a new method for identifying scientific topics and sub-disciplines in different fields  was related to Iranian Journal of Health and Environment. The highest number of articles related to the 2 years 2015 and 2016, respectively, 112 articles (14.4%) and 111 articles (14.3%) and the lowest number of articles related to the year 2008 with a frequency of 16 articles (1.2%).A review of 774 articles published by journals showed that 80 articles 10.3%) were published in the field of nanotechnology, with the highest number of articles in this field in 2015 with 15 articles. Out of 80 articles published in the field of nanotechnology, 66 articles (82.5%) were published about water pollution, 9 articles (11.3%) about waste water and 5 articles (6.2%) about air pollution  is also one of the strengths of this study.One of the limitations of this study is the lack of review of other environmental health articles in other medical journals.