The relation between tinea pedis and the internal environment of footwear has not been scientifically proven. This study aimed to determine whether the internal environment of footwear affects the incidence of tinea pedis and tinea unguium. This cross‐sectional, observatory study involved 420 outpatients who were categorized into non‐tinea, tinea pedis or tinea unguium groups based on mycological analysis. External climatic conditions, and temperature, humidity and dew points inside the patients’ footwear were recorded. Univariate and multivariate analyses were used to determine independent risk factors for tinea pedis and tinea unguium. A significant correlation was found between high temperature/high humidity and dew point of the internal environment of the footwear and the season. Furthermore, those who wore footwear with internal environments characterized by high temperature, high humidity, high‐temperature/high‐humidity and high dew point values had a significantly higher incidence of tinea pedis. The internal dew point correlated with the incidence of tinea pedis, whereas the external temperature correlated with the incidence of tinea unguium. The internal humidity and dew point of footwear as well as the frequency with which footwear with a high‐temperature/high‐humidity internal environment were worn was significantly higher in men than in women. In conclusion, the internal environment of footwear is a risk factor for tinea pedis, and this environment is affected by the season. Moreover, the frequency of tinea pedis among men is related to the internal environment of footwear. The dew point is an appropriate index for evaluating temperature and humidity in relation to tinea pedis. For many years, epidemiological studies and clinical experience have indicated that a relationship exists between footwear and tinea pedis (TP).Several risk factors have been reported for TP and tinea unguium (TU).The internal environment of footwear is determined by physical factors of the footwear , human physical factors , socks and environmental factors outside the footwear .In this observational study, 420 outpatients who wore footwear and who presented for examination at the Sasagawa Dermatological Clinic  between 16 May 2011 and 28 November 2014 were enrolled.Based on clinical assessment, subjects with fungal foot disease were classified into TP only, TU only and both (TP only and TU only) (three‐group classification). Subjects were also classified into TP (TP only and both) and TU (TU only and both) in a two‐group classification. For this study, fungal foot disease was considered as including TP only, TU only, or both TP and TU. In addition, the study cohort was divided into three age groups: group I, less than 30 years; group II, 30 years or more and less than 60 years; and group III, 60 years or more. Patient footwear was categorized as follows: (i) natural leather; (ii) synthetic leather; (iii) sneakers; (iv) cloth footwear; (v) sandals; (vi) slippers; and (vii) boots.Clinical assessments included follow‐up examinations, completion of a medical questionnaire and mycological analysis of samples collected from the infected sites. The toenails and feet were examined, and information about the symptoms or characteristics of TU or TP were recorded. Demographic data such as sex, age and employment were also recorded.Skin and toenail scraping smears were collected from patients diagnosed with TP and TU and submitted to mycological testing. Samples were placed on slides and examined with direct microscopy after addition of 15% potassium hydroxide in 40% dimethylsulfoxide solution, using an optical binocular microscope .Temperature, humidity and dew point inside the footwear of all patients were measured using an automatic temperature and humidity data logger monitor . The loggers were positioned on the dorsal side of the feet between the third and fourth toes. Humidity in the fourth interdigital space was also measured in 10 male subjects.Data were recorded while subjects were wearing their footwear, once each minute for a total of 15 min. All measurements were taken while the patients were wearing socks to avoid direct contact with the skin. Patients remained at rest in a seated position for 15 min before measurements were made. Subjects remained at rest in a seated position for at least an additional 15 min after commencement of measurements. Dew points were calculated automatically using software in the logger and were based on temperature and humidity values. A high‐temperature/high‐humidity environment inside the footwear was defined as a temperature of 32°C or more and humidity of 80% or more.External temperature and relative humidity measurements were obtained from climate data records for the Osaka region compiled by the Ministry of Land, Infrastructure, Transport and Tourism, and the Japan Meteorological Agency. In accordance with the designations used by the Japan Meteorological Agency, spring was defined as March to May, summer as June to August, fall as September to November, and winter as December to February. Fall and summer were collectively referred to as the warm season and winter and spring as the cold season.All statistical analyses were performed using IBM SPSS Statistics 22.0 software . Data are presented as mean ± standard deviation. Different tests were used for each analysis. The optimum cut‐off point was determined by the receiver–operator curve (ROC) analysis that separates TP and non‐TP. Details of the tests used are described in This study was conducted in accordance with the ethical guidelines for epidemiological studies designated by the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology after receiving approval from the Institutional Review Board of The Japanese Association for the Promotion of State‐of‐the‐Art in Medicine. All patients  provided written informed consent.Overall, 420 participants  were enrolled in this study. In terms of age demographics, 44.5% of subjects were in the working age group . Among tP < 0.01). The percentage of men with TP only was significantly higher than that of women with TP only (P < 0.05). The prevalence of fungal foot disease was significantly higher in men than in women (P < 0.05). There was no sex‐based difference in the incidence of TU. The subjects were mainly office workers in the working age group, and the incidence of TP was 39.1%. For TU, there was no difference in the incidence between the two sexes.The incidence of TP was significantly higher in men than in women . Furthermore, the mean temperature inside the footwear changed with the season, which was 29.9°C ± 3.4°C in spring, 32.6°C ± 1.5°C in summer, 31.5°C ± 2.6°C in fall and 26.5°C ± 4.1°C in winter. When the four seasons were grouped into two temperature extremes, the mean temperature inside the footwear was significantly higher (P < 0.001) in fall and summer  than in spring and winter . The humidity inside the footwear was also significantly higher (P < 0.001) in the warm season (76.7% ± 9.8%) than in the cold season (69.6% ± 10.2%). A similar trend was found for the dew point   than during the cold season . These results show that the local climate affects the internal environment of the footwear.A significant correlation was found between the internal environment of the footwear and the external environment  . The numThere were significant differences in temperature, humidity and dew point values among the seven types of footwear. Cloth footwear had the highest temperature, humidity and dew point values  and was therefore prone to mustiness . SandalsP < 0.01; Table The temperature, humidity and dew point values of closed footwear  were significantly higher than those of open footwear . The dew point was also higher among the footwear worn by men (26.5°C ± 4.3°C) than by women . The types of footwear most often worn by office workers were synthetic leather (32.7%) and natural leather (12.9%). The types of footwear often worn by men were sneakers (16.8%), synthetic leather (14.2%) and natural leather (10.0%), whereas those worn by women were synthetic leather (20.3%), sneakers (13.5%) and natural leather (9%).Overall, the footwear with a high‐temperature/high‐humidity environment were more commonly worn by men (29.5%) than by women .Average humidity in footwear is 73.84% ± 10.19% . The humidity was significantly higher in men than in women (P < 0.001), humidity  and dew point .The footwear of those with TP registered significantly higher temperature  and internal dew point , humidity , dew point  and high‐temperature/high‐humidity . For TU, temperature was a significant factor  and dew point of 24.56°C  for TP only, and humidity of 74.94%  and dew point of 23.14°C  for fungal foot disease.Previous epidemiological and clinical studies have indicated a relationship between TP and footwear. However, it has not been scientifically proven that the internal environment of footwear and primary climatological factors have an effect on TP risk. To the best of my knowledge, this study is the first to measure the internal environment of footwear and the external environment, as well as assess how they relate to TP and TU incidences. In the present study, measurements were made of the internal footwear environment in the patients’ everyday life setting. These measurements were made during patient hospital visits and associations with TP and TU infections were determined. The results indicate that TP incidence is strongly affected by the internal environment of the footwear, that a significant correlation was found between footwear's internal environment and the season. Moreover, high‐temperature/high‐humidity footwear environments with a high dew point showed a significantly higher prevalence of TP.The footwear's internal environment was more conducive for TP in men than in women.The findings showed that the dew point is a useful indicator of a footwear's internal environment that easily becomes stuffy and is favorable for TP.Although many epidemiological surveys and clinical experiences show a correlation of TP incidence with seasonal changes,Typically, a region's climate has an influence on the footwear's internal temperature.The results presented herein demonstrate a significant correlation between high‐temperature/high‐humidity and high dew point of the footwear's internal environment and the season .Interestingly, 42.3% of TP patients wore footwear that likely have a high‐temperature/high‐humidity internal environment during summer.Many studies have reported the relationship between the footwear's internal environment and footwear type.The type of shoes  is related to TP;Many studies have reported the relationship between sex and TP. These include studies reporting that TP occurs more frequently in men,Trichophyton penetration into the stratum corneum of a host. In vitro studies on invasion and proliferation of Trichophyton rubrum and Trichophyton mentagrophytes, which are major pathogens causing tinea in the stratum corneum, show that both fungi enter the stratum corneum within a day at two different humidity conditions (in an incubator at 35°C: 90% humidity and 100% humidity). The invasion rate of the dermatophytes was slower at 80% humidity,T. rubrum and T. mentagrophytes infiltration was absent at 85% humidity or less, and humidity needed to be at least 90% for dermatophytes to infiltrate and proliferate in the stratum corneum.T. mentagrophytes were able to penetrate the stratum corneum in cases of skin injury even at 70% humidity.Whether temperature or humidity is a critical requirement for dermatophyte infection is currently under debate. However, no studies have elucidated the role of the footwear's internal environment in Further, my results show that the optimal cut‐off point for discriminating between the risk of tinea pedis and non‐tinea pedis is 75% humidity for both patients with TP only and fungal foot disease; humidity and dew point can be assumed to be even higher in the interdigital area and areas close to the skin surface of the foot. Indeed, the average humidity of the fourth interdigital area in the summer was 80%, average maximum humidity was 84%, maximum humidity was 91% and average dew point was 31°C. A humid environment is important for the development of tinea infections;This study has several limitations. First, the study was conducted in a single institution. Second, the research was performed with arbitrary footwear (footwear worn at the visit) and the effect of changing the footwear by the same patients on different occasions was not examined. Finally, the conditions including sex, age, shoe type and experimental environment in this study are also not uniform, as they would be in a controlled experimental study, which is important to completely understand the relationship between footwear type and TP and TU incidences. Thus, a multi‐institutional study with a large sample size should be conducted to verify the results from this study. Verification of the results in countries with climate and lifestyle habits different from those in Japan is also necessary.In conclusion, the internal environment of footwear is a risk factor for TP and TU. The findings confirmed that the footwear's internal environment is affected by the season. Moreover, frequency of TP among men is related to the interior environment of footwear. The dew point is an appropriate index for evaluating temperature and humidity environments in relation to TP. Although this study does not contribute directly to clinical practise, it may enable dermatologists to advise patients on how to wear and maintain footwear, rather than limiting consultations to simply prescribing topical and internal agents. Consequently, dermatologists may play an important role in TP treatment and prevention.None declared.Methods S1. Submission methods.Figure S1. Internal temperature, humidity and dew point of the footwear during cold and warm seasons.Table S1. Demographic and clinical characteristics.Table S2. Tinea unguium (TU) risk factor analysis.Table S3. Fungal foot disease risk factor analysis.Click here for additional data file.


R2 = 0.080–0.921), TICs (Cohen’s  κ = 0.175–0.396) and NTICs (κ = 0.004–0.505). Such diversity may impact on the reliability and reproducibility of PD-L1 IHC assays as a predictor of response to immune checkpoint inhibitors.Programmed cell death ligand-1 immunohistochemical detection (PD-L1 IHC) is a putative predictor of response to PD-1/PD-L1-targeted checkpoint inhibitors. However, there is no gold standard assay in hepatocellular carcinoma (HCC). We evaluated 5 PD-L1 IHC assay platforms  in 100 HCCs reporting PD-L1 expression in malignant (M) and tumour-infiltrating immune cells (TICs) and non-tumorous cirrhotic tissues (NTICs). We found substantial inter-assay heterogeneity in detecting PD-L1 expression in M ( Therapeutic reversal of immune exhaustion with anti-PD-1/programmed cell death ligand-1 (PD-L1)-targeted therapies induces responses in only 20% of patients with HCC.2 However, its utility in HCC remains controversial. Albeit its expanding clinical use, the predictive role of PD-L1 IHC status is limited by analytical variability, a factor that can be potentially controlled by standardisation of PD-L1 protein detection techniques in clinical samples. Compelling evidence in non-small-cell lung cancer (NSCLC) and melanoma suggests significant inter-assay heterogeneity in comparative studies of PD-L1 IHC tests due to geographical heterogeneity in PD-L1 expression, antibody used and interpretation.4 While considerable research efforts are underway to harmonise PD-L1 IHC assays in other solid tumours,5 the performance of the various PD-L1 IHC assays available is unknown in HCC. As a result, no recommendation can be made for an optimal PD-L1 IHC test in HCC, a tumour where PD-L1 expression predicts for adverse prognosis, but whose predictive role in defining an increased likelihood of response to ICPI remains unclear.6 To address this issue, in Blueprint-HCC we performed a quantitative comparison of five antibody clones used for PD-L1 IHC testing in landmark trials of ICPI.PD-L1 expression by immunohistochemistry (IHC) enriches for response to immune checkpoint inhibitors (ICPIs) in selected tumours.n = 41), the academic Liver Unit in Birmingham  and Novara  following ethical approval (Ref. 17/YH/0015). Patients were treated between 2001 and 2016 and clinicopathologic features are presented in Table We constructed tissue microarrays (TMAs) using a multi-centre repository of 100 archival HCC specimens from three tertiary referral centres including Imperial College London . Analysis was performed using PRISM . Pearson’s correlation coefficient and Cohen’s κ were utilised to evaluate the inter-assay agreement in defining the heterogeneity of PD-L1 expression.3PD-L1 expression was scored in M samples as the percentage of immune-positive cells (1% cut-off) multiplied by chromogenic intensity (ranked from 0 to 3) to derive a semi-quantitative H-score.Tumoral PD-L1 expression was lowest for E1L3N , followed by SP263 , 22c3 , 28-8  and SP142  Fig. . In totaR2 = 0.921) and lowest between SP263/28-8 (R2 = 0.080)  Fig. . Low lev80) Fig. . We comp80) Fig. . Cohen’sCC Table .Table 1I8 Compared to other tumours, however, the level of inter-assay heterogeneity observed in HCC samples appears even more substantial. Unlike melanoma and NSCLC, HCC is unique for the presence of an immune cell-rich cirrhotic microenvironment, which adds a further layer of complexity to the classification of PD-L1 status. To address spatial and cellular heterogeneity in PD-L1 immunolabelling, we ensured representation of multiple cores from the centre, periphery of HCC and the cirrhotic microenvironment. With this approach, we were able to discover substantial heterogeneity in PD-L1 immunolabelling of immune cell infiltrates, which was maximal for NTIC (Cohen’s κ range 0.004–0.505) compared to TIC (0.175–0.396). This is not the first report to suggest the relevance of spatial variance as a determinant of PD-L1 IHC status in malignancy, a finding that might explain the suboptimal linkage between PD-L1 expression and response to PD-1/PD-L1-targeting ICPI. Despite the potential for underestimation in determining PD-L1 status due to the focal nature of protein expression in malignant and immune cells, the use of serial TMA sections might have facilitated a more standardised and less subjective evaluation of cancer specimens as shown in previous studies.9 Moreover, in the clinic, the issue of sampling bias is unavoidable as PD-L1 status requires evaluation in biopsy samples, where the quantity of tissue is limited and not dissimilar to that available in a standard TMA section.In Blueprint-HCC we document significant inter-assay variability in tumoral and stromal immunolabelling across the principal antibody clones utilised for PD-L1 IHC testing in clinical trials and routine practice. Our observation mirrors the results generated in melanoma and NSCLC, where a number of companion diagnostic assays have evolved in parallel with the clinical development of PD-1/PD-L1-targeting ICPI.Methodologically, the PD-L1 IHC results reported here have been generated using standardised antigen retrieval, immunostaining and scoring techniques, in an attempt to mitigate potential sources of bias. Importantly, there were no qualitative differences in the staining pattern produced by any of the tested antibodies, all of which reproduced the specific staining patterns in the tested samples comparable with those of appropriate positive control reactions.10Based on our findings, the heterogeneity of PD-L1 IHC assays does not appear dependent on the portion of the PD-L1 protein recognised by the tested antibody. When considering immunostaining in M cores, we did not observe significant differences between the antibodies targeting the extracellular  versus the intracellular domain , a finding of clinical importance due to the existence of diverse splicing variants of PD-L1 with uncertain biologic significance, which might have been differentially captured by each antibody.To conclude, in the Blueprint-HCC study we have shown significant heterogeneity in the performance of PD-L1 IHC assays in HCC. Whether depending on target epitope diversity, differential assay specificity or antibody affinity, our study highlights inter-assay variation to be a critical component of the reliability and reproducibility of PD-L1 expression as a predictive correlate of response to immunotherapy. None of the patients identified in this study have received ICPI treatment for HCC; therefore, we cannot infer a relationship between PD-L1 IHC heterogeneity and response to immunotherapy. Prospective studies evaluating the diverse PD-L1 IHC assays in patient cohorts with adequate linkage with outcomes from PD-1/PD-L1 ICPI treatment are urgently warranted to clarify the clinical meaning of such variation and facilitate patient selection for immunotherapy.Supplementary ResultsSupplementary Materials and Methods


A comparison of the structure and sensitivity of humidity sensors prepared from graphene (G)-PEDOT: PSS ) composite material on flexible and solid substrates is performed. Upon an increase in humidity, the G: PEDOT: PSS composite films ensure a response (a linear increase in resistance versus humidity) up to 220% without restrictions typical of sensors fabricated from PEDOT: PSS. It was found that the response of the examined sensors depends not only on the composition of the layer and on its thickness but, also, on the substrate used. The capability of flexible substrates to absorb the liquid component of the ink used to print the sensors markedly alters the structure of the film, making it more porous; as a result, the response to moisture increases. However, in the case of using paper, a hysteresis of resistance occurs during an increase or decrease of humidity; that hysteresis is associated with the capability of such substrates to absorb moisture and transfer it to the sensing layer of the sensor. A study of the properties of G: PEDOT: PSS films and test device structures under deformation showed that when the G: PEDOT: PSS films or structures are bent to a bending radius of 3 mm (1.5% strain), the properties of those films and structures remain unchanged. This result makes the composite humidity sensors based on G: PEDOT: PSS films promising devices for use in flexible and printed electronics. In recent years, graphene-based gas or vapor sensors have attracted much attention due to their unique sensing performance, room-temperature operating conditions, a variety of feasible designs, and tremendous application perspectives. Over the past few decades, the rapid development of graphene-based sensors for various applications has been observed. Humidity measurement is one of the most significant issues in the fields of medical diagnostics, environmental protection, industrial manufacture, agriculture, etc. Graphene demonstrates great potential for application in resistive humidity sensors . The sen3 or Fe2O3 nanoparticles [One of the organic polymers, poly  doped with poly (styrene sulfonate) (PEDOT: PSS), is a material most often used in humidity-sensor applications . PEDOT: articles ,12, graparticles . The useParticular interest in humidity sensors based on graphene and PEDOT: PSS is due to the possibility of using those materials in flexible, stretchable, and wearable electronics as well as in the printing technology for creating device structures based on such sensors. For an instant, printed PEDOT: PSS electrodes showed good flexibility in several types of flexibility tests, including outer/inner bending, twisting, and stretching . The higIn the present study, we examined the properties of films prepared from the G: PEDOT: PSS composite versus the composition of the material and as dependent on the solid and flexible substrates used. A composition ensuring the maximum sensitivity of the film to water adsorption was identified. It was found that the use of flexible substrates, due to their capability to quickly absorb the liquid components of the solution, leads to a more porous structure of the films, thus making the response of such a humidity sensor increase substantially. An analysis of the properties of such films under deformation proved the films show promise for use in flexible electronics.2/Si wafers, Kapton polyimide films, polyethylene terephthalate (PET) with additional hydrophilic adhesion layer on the surface, and ordinary paper were used as the substrates.A graphene suspension with a graphene content of ~1 mg/ml was used as the starting material in the present study. The suspension was obtained by electrochemical exfoliation of highly oriented pyrolytic graphite, followed by the sonication, centrifugation, and filtration of obtained particles on a track membrane with a pore diameter of 1.2 μm . The sec2/Si substrates. In the case of PEDOT: PSS films, the removal of part of the substrate has allowed us to obtain an image of a free film. Raman spectra of the films are shown in AFM images of the surface of the films obtained using a suspension of graphene and PEDOT: PSS, and AFM images of the surface of the C1a1 and C1c structures with one and the same film composition yet printed on different substrates are shown in The response of the structures with different compositions observed on the humidity change to 90% is shown in 2/Si substrates, the C1a2 structure with a minimum film thickness of 300 nm exhibited a maximum response of 27%–60%, and at a film thickness of 3.5 μm, and that response dropped to 15%–35%. In the case of relatively thick G: PEDOT: PSS composite films formed on paper (6.5 to 7.5 μm thick), the film thickness was no longer an obstacle for reaching a pronounced response due to the porosity of the film formed on paper. Moreover, a decrease in film thickness to 3 μm led to a decrease in response to 72%.No less important parameters for the response to moisture is the film thickness. Among the structures fabricated on SiOIn general, it should be noted that the rate of change of the resistance is determined, first of all, by the inertia of the measurement chamber. The inset in r at the substrate thickness t = 100 μm and film thickness d amounts to =t+d)/2r or compressive (negative) strains could be generated. The strain estimated from the bending radius (t+d)/2r . On a ch(t+d)/2r ,20. In t(t+d)/2r ,22,23,24The obtained experimental results can be summarized as follows. (a) The content of the composite was identified at which the response of the sensor to humidity was maximum. This is a composite in which a suspension of graphene and PEDOT: PSS is in a proportion of 1:(1–2). It is shown that the response of the system is unambiguous, the resistance increases by increasing the humidity up to 95%. Film recovery occurs on the same time scales in the entire range of humidity. Estimations of the 1:1 G: PEDOT: PSS film weight content after drying of printed layer gives the value of 10% addition of PEDOT: PSS to graphene and 5% in the case of 1:2. In our paper  we have (b) The use of flexible substrates capable of absorbing the liquid ink component permits the formation of sensor elements with high porosity. As a result, the relatively large thickness of such films does not lead to a loss of layer sensitivity.2/Si substrate a maximum sensor response was observed for the thinnest film.(c) As it could be expected, in the case of using a rigid SiOThe used G: PEDOT: PSS composites and test structures possess properties promising for the use of such humidity sensors in flexible and printed electronics: When the structures are bent to a bending radius of 3 mm (1.5% deformation), their properties remain almost unchanged. A pronounced reduction of the scatter of resistance values was obtained for zigzag-shaped test structures.The bending-induced effects in flexible electronics have emerged as a relatively new experimental and theoretical research area. The optimum device design for flexible electronics requires a comprehensive understanding and accurate modeling of strain-induced effects in sensor devices . The shaThe properties of graphene: PEDOT: PSS composite films are compared as a material for resistive humidity sensors for moisture range 30%–95% fabricated on flexible and rigid substrates. It is shown that the resistance increases almost linearly depending on the environmental humidity. The composite films G: PEDOT: PSS provide the maximum response (increase in resistance) up to 220% for film content 1:(1–2) (10–5 weight % of PEDOT: PSS in graphene film) when exposed to a humid environment without the restrictions typical of humidity sensors prepared from PEDOT: PSS (80% RH). It is found that the response of the sensor depends not only on the composition of the layer but, also, on its thickness, film structure, and substrate used. Formation of the porous film, for instance, due to the capability of flexible substrates to absorb the liquid component of the ink, used to print the sensing layer, leads to increase the response to humidity. However, in the case of using paper as a substrate, a hysteresis occurs in the resistance value under a two-sided variation of humidity. This hysteresis is associated with the capability of such substrates to absorb water. The measurements of the resistivity of G: PEDOT: PSS films under bending deformation showed that down to a bending radius of 3 mm (1.5% deformation), the resistance of the structures remained almost unchanged. Moreover, the transition from strips to zigzag structures reduces the scatter of resistance values observed during multiple measurements. The response of the test device structures also remained almost unchanged for a tensile bending radius from 3 cm to 3 mm. Thus, used composite material and humidity sensors prepared from it are highly promising for use in flexible and printed electronics.


To evaluate the effectiveness and safety of Qingpeng ointment on eczema-associated pruritus. This single center randomized double-blinded placebo-controlled trial enrolled 60 patients with nonexudative eczema, who were randomized at 1:1 ratio to the Qingpeng ointment and placebo control groups (n=30 in each group). The investigational and control ointment were applied on lesions twice daily for two weeks. Visual analogue scale (VAS) and pruritus symptom scores were used to assess pruritus severity, frequency, and duration. Eczema lesions were evaluated by eczema area and severity index (EASI) and lesion morphology scores. Subjects were evaluated after the first treatment and at the end of the first and second week. P < 0.05). The scores of pruritus severity, frequency, and duration were significantly lower in the Qingpeng ointment group than in the control group at the end of week 1 and week 2 of the study . The scores of lesion morphology at the end of week 1 of the study were not significantly different between the two groups, but the Qingpeng ointment group showed significantly lower score than the placebo control group at the end of week 2 of the study. No adverse event was observed in the study. The average age and disease duration were 50.1±13.5 years and 30.9±16.0 weeks, respectively. Baseline EASI and VAS scores were similar between the two groups. VAS scores of the Qingpeng ointment group were significantly lower than those of the placebo control group at 10 minutes and 30 minutes after the first treatment and the first and second week follow-up (all Qingpeng ointment can effectively alleviate pruritus and reduce skin lesions in patients with nonexudative eczema. The antipruritic effects occurred early and at a greater magnitude than the effects on lesion attenuation. Eczema, as a common skin disease, is characterized by a complex etiology and apparent pruritus. The clinical manifestation of eczema is diverse, and eczema lesions can develop in the whole body and are usually symmetric and exudative . PrurituThe neurophysiological mechanism of pruritus remains unclear. Recent studies have confirmed the contributions of various factors to pruritus, such as factors that induce pruritus, specific receptors to the factors, afferent nerve fibers, and the specific regions of the central nervous system where scratch reflex occurs , 6. KeraKeratinocytes express multiple receptors that are specifically associated with pruritus, such as histamine receptor, neuropeptide receptor, neurological factor receptor, cannabinoid receptor, protease activated receptor-2, and transient receptor potential vanilloid subtype 1 , 10. His Oxytropis falcata Bunge, Rheum lhasaense, Aconitum pendulum Busch, Chebulae Fructus (without the kernel), Fructus Terminaliae Billericae, Phyllanthus emblica Linn, Benzoin, Tinospora sinensis (Lour.) Merr., and artificial musk. The main chemical components of Oxytropis falcata Bunge are flavonoids, alkaloids, and steroids. The roots, rhizomes, and the whole plant of Oxytropis falcata Bunge can be used as herb medicine. The herb has anti-inflammatory, analgesic, wound-healing, hemostatic, and anti-itching effects. The 3-acetate aconitine from Aconitum pendulum Busch can inhibit some early symptoms of inflammation, such as capillary hyperpermeability, exudation, edema, and leukocytosis. The main chemical component of Chebulae Fructus, Fructus Terminaliae Billericae, and Phyllanthus emblica Linn is tannin. Galloyl-containing tannin can block or reduce the release of inflammatory factors and thus attenuate inflammation. The main chemical components of Chebulae Fructus are tannin and polyphenols. The water extracts of Chebulae Fructus can terminate the free radical cascade and have strong antiallergic and antioxidant effects. Extracts from the leave of Phyllanthus emblica Linn can inhibit the bacteria, Staphylococcus aureus, Escherichia coli, and Candida albicans in vitro, and thus can block the allergic reactions caused by those bacteria [Multiple recent articles have shown that the traditional Tibetan herb medicine, Qingpeng ointment, can treat dermatitis and eczema effectively –16. Howebacteria , 16. Polbacteria –17. Studhttp://www.chictr.org.cn/enIndex.aspx and the trial identification number is ChiCTR1800016190.This was a single center, randomized, double-blind, placebo-controlled study. The study protocol was approved by the Institutional Review Board of Beijing Friendship Hospital . All participants signed the informed consent form. The trial has been registered at May 17th 2018. The trial was registered at All patients, who were diagnosed with nonexudative eczema in the Department of Dermatology of Beijing Friendship Hospital from May 2018 to September 2018, were screened. Inclusion criteria were age was 18-75 years; clinical symptoms met the diagnostic criteria for nonexudative eczema [Computer-generated random number was used to allocate participants into the test and control groups at 1:1 ratio. A study nurse, who was blinded to the group allocation, assigned the participants to the testing or placebo control group using the random numbers. Both participants and investigators were blinded to the group allocation.The investigational drug was Qingpeng ointment provided by Tibet Qizheng Tibetan Medicine Co., Ltd. (Batch number 170901). The placebo control was sham ointment, which is the nonmedicine component of Qingpeng ointment. The sham ointment was also provided by Tibet Qizheng Tibetan Medicine Co., Ltd. According to the fingertip unit , QingpenThe effectiveness of the drug on pruritus and skin lesions was evaluated. The patients were followed up at the end of the first and second weeks of the study. VAS score for pruritus and pruritus symptom scores were evaluated before the treatment and at the first and second week follow-up visits . VAS scoEfficacy index = (EASI before treatment - EASI after treatment)/EASI before treatment × 100%. Complete cure was defined as efficacy index ≥ 90%. Significant improvement was defined as 60% ≤ efficacy index < 89%. Moderate improvement was defined as 20% ≤ efficacy index < 59%. No improvement was defined as efficacy index < 20% . EffectiAdverse reactions were recorded by inquiring the subject and observation during the follow-up visits.α = 0.05. Power (1-β) was 80%. In our preliminary studies, we found the effective rate of two-week treatment was 76.7% and 39.5% in Qingpeng ointment group and control group, respectively. The ratio between the two groups was 1:1. The sample size was 30 in each group based on the normal approximation method.The significant level  t-test and repeated measures analysis of variance were used for intragroup comparison of continuous variables. Categorical variables are presented as rates. Intragroup comparison of categorical variables was analyzed by χ2 test. Multivariate analysis of variance was used for intergroup comparison. P < 0.05 was considered statistically significant.The statistical software SPSS 16.0 was used for data analysis. Continuous variables are presented as mean ± standard deviation (SD). PairwiseParticipant flow diagram is presented in P < 0.001). The placebo control group also showed a significant reduction in the VAS score 10 minutes after the first treatment compared with the score before treatment, but did not decrease further at 30 minutes after the first treatment. Intergroup comparison demonstrated that VAS scores of the Qingpeng ointment group were significantly lower than those of the placebo control group at 10 minutes  and 30 minutes  after the first treatment. In addition, VAS scores of the Qingpeng ointment group at the one-week and two-week follow-up visits were also significantly lower than those of the placebo control group (All P < 0.0001). These data suggest that Qingpeng ointment may attenuate eczema-pruritus effectively.The VAS scores before and after treatment are displayed in  P < 0.05). However, the placebo control group showed no such reductions. Intergroup comparison revealed that the total score and scores of pruritus severity, frequency, and duration were similar in the two groups before the treatment whereas were significantly lower in the Qingpeng ointment group than in the control group at the end of week 1 and week 2 of the study . The scores of lesion morphology before the treatment and at the end of week 1 of the study were not significantly different between the two groups, but the Qingpeng ointment group showed significantly lower score than the placebo control group at the end of week 2 of the study (P = 0.011). These results indicate that Qingpeng ointment-mediated attenuation in pruritus may occur earlier than the drug-mediated reduction in skin lesions.The scores of pruritus symptoms and lesion morphology before and after treatment are presented in For the Qingpeng ointment group, the percentage of EASI at the end of week 1 and week 2 relative to the EASI before the treatment was 64.22% and 29.75%, respectively; the percentage of VAS score relative to the baseline score was 46.06% and 28.63%, respectively. For the placebo control group, the EASI% was 78.72% and 65.96%, respectively, and the VAS score% was 98.61% and 82.71%, respectively. The extent of reduction in EASI and VAS score in the Qingpeng ointment group was greater than that in the placebo control group . These rP < 0.0001). The effective rate of the Qingpeng ointment group was 43.33% and 76.67% at the end of week 1 and week 2 of the study, respectively (The EASIs at week 0 and week 1 were similar in the two groups . At the ectively . The effNo adverse event was observed in the study.The current study found that Qingpeng ointment significantly reduced pruritus severity, frequency, duration, and lesion severity. Qingpeng ointment-mediated attenuation in pruritus occurred earlier than the reduction in lesions because the significant reduction in VAS score of pruritus occurred one week earlier than the significant reduction in EASI. These results suggest that Qingpeng ointment can inhibit eczema-associated pruritus without relying on the reduction in lesions. The effective rates of 43.33% at the end of week 1 and 76.67% at the end of week 2 of the study are consistent with the results of previous studies –16. No aThe molecular and cellular mechanism underlying the beneficial effects of Qingpeng ointment may be associated with the drug-mediated inhibition of the signal transduction pathway involved in pruritus development. Furthermore, vacuum homogenizing emulsification technology, super Micro-grinding technology, and unique oil-in-water cream form was used to manufacture Qingpeng ointment. Thus, the ointment can moisturize the skin. Compared with other traditional Tibetan medicine ointment, Qingpeng ointment can more effectively moisturize the skin and facilitate the drug absorption. The matrix of Qingpeng ointment consists of liquid paraffin, glycerin, water, and other moisturizing ingredients. Moisturizing the skin can improve skin barrier function by reducing KLK7 expression and thus effectively alleviate pruritus .The current study showed that in the placebo control group, the VAS score of pruritus reduced significantly 5 minutes after the first administration of the sham ointment, suggesting the sham ointment also relieves pruritus at the first administration. The possible reason for this transient antipruritic effect from the sham ointment may be related to the cooling effects caused by evaporation of the water component of the ointment. This cooling effect might transiently mask the itching sensation. Thus, the VAS score of the placebo control group rose to the baseline levels at the end of the first week of the study. In contrast, VAS score of the Qingpeng ointment group reduced further at 10 and 30 minutes after the first treatment and remained at low levels during the study. The VAS score of Qingpeng ointment group reduced significantly at the end of the first week of the study, indicating a significant relieve of pruritus at the end of the first week, but lesion reduction occurred later. The lesion score reduced significantly at the end of the second week of the study and so did the EASI. Therefore, we believe that Qingpeng ointment may rapidly alleviate pruritus first and then reduce skin lesions by inhibiting inflammation and improving skin barrier function. Oxytropis falcata Bunge and anti-inflammatory and antiallergic ingredients from Chebulae Fructus, Fructus Terminaliae Billericae, and musk.The current study showed that the magnitude of reduction in the VAS score was greater than that in the EASI, which suggests that the drug-mediated alleviation of pruritus had a greater magnitude than the effects of the drug on lesion reduction and that Qingpeng ointment can inhibit pruritus without depending on lesion reduction. Qingpeng ointment contains antipruritic ingredients fromThe limitations of this study include a relatively small sample size and short follow-up time. Long-term follow-up is required to determine the long-term efficacy and the effects of Qingpeng ointment on eczema recurrence. The molecular and cellular mechanism underlying the benefit of Qingpeng ointment remains to be further investigated.


Recently, humidity sensors have been investigated extensively due to their broad applications in chip fabrication, health care, agriculture, amongst others. We propose a capacitive humidity sensor with a shielding electrode under the interdigitated electrode (SIDE) based on polyimide (PI). Thanks to the shielding electrode, this humidity sensor combines the high sensitivity of parallel plate capacitive sensors and the fast response of interdigitated electrode capacitive sensors. We use COMSOL Multiphysics to design and optimize the SIDE structure. The experimental data show very good agreement with the simulation. The sensitivity of the SIDE sensor is 0.0063% ± 0.0002% RH. Its response/recovery time is 20 s/22 s. The maximum capacitance drift under different relative humidity is 1.28% RH. In addition to daily applications, such as air conditioners and humidifiers, humidity sensors are widely used in industrial process control, medical science, food production, agriculture, and meteorological monitoring ,6,7,8,9.Electronic humidity sensors can be divided into resistive and capacitive . ResistiVarious materials can be used as humidity sensing materials, such as electrolyte , ceramicCapacitive humidity sensors have two basic structures: parallel plate (PP) capacitance a and intIn PP sensors, the upper plate is perforated by an array of holes or parallel stripes to allow water molecules from the air to reach the sensing material underneath. Since the sensing area of the PP capacitor is sandwiched between two parallel plates, the change in the relative dielectric constant of the sensing material in the PP sensors affects the overall capacitance change. Unlike PP sensors, IDE sensors usually only affect the change in the upper capacitance of the IDEs, which makes them less sensitive than PP sensors. However, the exposed sensing area of the PP sensors is smaller than for IDE sensors, which causes a slower response than for IDEs.The IDEs are fabricated on an inert solid or flexible substrate as parallel comb electrodes that overlap each other ,33. IDE It is clear that there are advantages and disadvantages of these two types of sensors. There has been a significant effort to improve the sensor structures. For example, Zhao et al. used RIE (Reactive Ion Etching) and ICP (Inductively Couple Plasma) to etch sensing materials between parallel plates of the sensors to obtain a larger contact area with the tested environment to reduce response time from 35 s to 25 s , but thiInspired by combining the advantages of PP and IDE structures, this paper proposes a novel IDE humidity sensor with a shielding electrode under the IDEs, namely, SIDE. On the SIDE, the capacitance of the lower half of the IDEs is shielded by an additional electrode underneath the IDEs, which effectively raises the relative capacitance change as it becomes exposed to moisture. Thus, a SIDE humidity sensor combines the high sensitivity of PP sensors and the fast response (20 s) as the IDE ones.In this work, we first verified the feasibility of the SIDE structure in the simulation software. Secondly, the thickness of the sensing layer with different electrode gaps and the dielectric thickness between the shielding electrode and the IDEs were optimized regarding the sensitivity and response speed. The SIDE sensor with optimized parameters was fabricated. The sensitivity, response time, recovery time, and stability of the sensor were measured.COMSOL Multiphysics®  is applied to simulate the SIDE and IDE structure. 0) of SIDE and IDE under different relative dielectric constant of PI representing the humidity conditions. C0 is the total capacitance when the relative dielectric constant of the sensing layer is 2.9. ΔC is the capacitance difference between any other relative dielectric constant of PI and 2.9. It can be seen that under the same conditions, ΔC/C0 of the SIDE structure, is about 4 times bigger than that of the IDE structure, which implies that the SIDE will have much higher sensitivity than IDE with the same parameters.max/C0 is also simulated by COMSOL Multiphysics® . We define that ΔCmax/C0 equals to ΔC/C0 with the relative dielectric constant of PI at 2.9 (C0) and 3.7 (Cmax), which indicates the sensitivity of the sensor.The effect of the thickness of the sensing film on ΔCmax/C0 increases as the thickness of the sensing film increases, but flattens at higher thickness. To optimize the sensing film thickness, two facts should be taken into account. On the one hand, it is clear that when the sensing film thickness is equal to the gap between the IDEs  A 2.5 µm-thick negative photoresist is patterned. (b) An e-beam-evaporated Ti/Au layer is deposited and selectively removed by a lift-off process to form the bottom shielding electrode. (c) A layer of 1 µm silicon dioxide is deposited by PECVD . (d) IDEs are fabricated on the silicon dioxide by the same sequence of lithography, e-beam evaporation, and lift-off. (e) A 5 µm-thick PI is spin-coated. Subsequently, the device is baked at 120 °C for 1 h, 180 °C for 1 h, and 250 °C for 6 h to cure the sensing layer. The completed sensor and cross-section of the SIDE structure under scanning electron microscope (SEM) are shown in The setup for the humidity measurement is shown in Cx can be directly measured using the circuit shown in pn . Cx is the sensing capacitance proportional to the humidity. Cp1 and Cp2 are the capacitances between the shielding electrode and the IDEs. Cf is the fixed capacitance of the IC chip. U1 and U2 are the potentials before the humidity sensor and after the IC chip that both can be measured. Therefore, Cx can be calculated using Equation (1).The capacitance above the shielding electrode Before the test, each device is placed in an oven at 100 °C for 10 min to get rid of the effect of the previous measurement.1 − C0, C0 is the capacitance measured at the RH, which is 23.7% ± 0.8%, and C1 is the capacitance measured when the RH is 73.0% ± 0.8%. Δ(% RH) is the difference between the relative humidity values when measuring C1 and C0.The sensitivity (S) can be expressed as Equation (2):The response and recovery dynamics are among the most important characteristics for evaluating the performance of humidity sensors. The response time for RH increase and the recovery time for RH decrease are usually defined for a sensor as the time taken to reach 90% of its total capacitance variation. The response and recovery curves are measured by exposing the SIDE sensor to alternate levels of humidity between 2.0% ± 0.8% and 77.0% ± 0.8% RH.In order to evaluate the functioning of the humidity sensor over long periods of time, we measured the sensor’s capacitance over the duration of 20 h at 25 °C with relative humidity levels of 25.7% ± 0.8%, 34.4% ± 0.8%, 45.0% ± 0.8%, 57.0% ± 0.8%, and 73.5% ± 0.8% RH.R2 of 0.996 and 0.991, respectively. The slopes of the line, i.e., S of SIDE and IDE are 0.0063 and 0.001,65, respectively. Taking the uncertainty of HC2-S into consideration, the S of SIDE and IDE are 0.0063 ± 0.0002 and 0.001,65 ± 0.000,05, respectively. Hence, the sensitivity of the SIDE structure is 3.82 times bigger than that of the IDE. These results show the significant improvement of sensitivity brought by the shielding electrode, that minimizes the large constant capacitance of the substrate. Indeed, whatever substrate the IDE is built on, the relative dielectric constant of the substrate is larger  or close to  the relative dielectric constant of PI (2.9–3.7). The experimental result and simulation data verify the effects of the shielding electrode and shows high agreement as well. It is clear that our proposed SIDE structure can provide an effective way to measure relative humidity more sensitively and accurately. Another advantage of the shielding electrode is that it can effectively suppress the external electromagnetic interference and reduce the noise in the measurement process.A sensitivity test is carried out on the SIDE and IDE structure. max is the maximum measured capacitance after the sensor is exposed to different RH atmosphere, and Cmean is the average capacitance of all recorded values at a certain relative humidity, C0 is the capacitance measured when the RH is 23.7% ± 0.8%. The maximum drift value (D) obtained from In summary, we propose a novel shielded interdigitated electrode structure for humidity sensing. We perform a comprehensive simulation of this structure to optimize the parameters for the sensor fabrication. In simulation and actual testing, we find that the sensitivity of the SIDE structure is much higher than that of the IDE structure because of the effect of the shielding electrode on the capacitance change rate. Since the surface structure of the SIDE structure is still the same as IDE, the SIDE sensor combines the high sensitivity of the parallel plate sensors and fast response of the IDE sensors. The sensitivity of SIDE is 0.0063% ± 0.0002% RH, and the response/recovery time is 20 s/22 s. The stability of the SIDE sensor was also characterized. The maximum drift value under different relative humidity is 1.28% RH. Meanwhile, since the basic operating principle of many capacitive sensors is the same, the SIDE structure can even be applied to capacitive gas sensors, such as volatile organic compound (VOC) sensors which are used to monitor toxic gases. This shows that SIDE can replace IDE in various sensors that are more sensitive to the accuracy and response speed.


Ultra-high exfoliation in water of a nanosized graphite (HSAG) was obtained thanks to the synergy between a graphene layer edge functionalized with hydroxy groups and a polymer such as chitosan (CS). The edge functionalization of graphene layers was performed with a serinol derivative containing a pyrrole ring, serinol pyrrole (SP). The adduct between CS and HSAG functionalized with SP was formed simply with a mortar and pestle, then preparing water dispersions stable for months in the presence of acetic acid. Simple casting of such dispersions on a glass support led to carbon papers. Aerogels were prepared through the freeze-dry procedure. Exfoliation was observed in both these families of composites and ultra-high exfoliation was documented in aerogels swollen in water. Carbon papers and aerogels were stable for months in solvents in a wide range of solubility parameter and in a pretty wide range of pH. By considering that a moderately functionalized nanographite was straightforwardly exfoliated in water in the presence of one of the most abundant biobased polymers, the obtained results pave the way for the simple and sustainable preparation of graphene-based nanocomposites. HSAG–SP/CS adducts were characterized by wide angle X-ray diffraction (WAXD), scanning and transmission electron microscopy , Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. Thermal stability of the composites was studied by thermogravimetric analysis (TGA) and their direct electrical conductivity with the four-point probe method.  According to the nomenclature for graphene and graphene related materials -linked 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose. This polymer was selected as it can be easily obtained (through deacetylation) from chitin, the second most abundant natural biopolymer in the world. Moreover, chitosan can be dissolved in acidic water and a polycation is formed. A working hypothesis was that the exfoliation of the graphitic aggregates could be favored by the interaction between a polycation, such as chitosan treated with acetic acid, and the aromatic layers. In the scientific literature, the covalent functionalization of graphene sheets with chitosan has been reported r, where x and y are fractions of repeating units with free amine and acetylated amine, respectively. The chitosan used in this work has a deacetylation degree of 30%, and therefore x = 0.3 and y = 0.7. It appears that the atomic ratios measured for both HSAG–SP/CS aerogel and paper are very similar to the ones calculated for pure chitosan. Considering that XPS analyses probe only the outer layer of a sample (maximum ca. 100 Å), these results suggest that CS is at the surface of both the aerogel and carbon paper and covers HSAG–SP.XPS analyses were performed on HSAG–SP and on HSAG–SP/CS 1:1 aerogel and paper. For all samples, wide scan spectra, reported in N-acetylglucosamine rings; ii) C3, C4 and C5 in the glucosamine segment and in the N-acetylglucosamine segment; iii) C1 atoms in both segments; iv) C7 in the N-acetylglucosamine unit. Taking into account this classification, the relative amount of the C1s components for the chitosan used in this work  are 35.1%, 44.8%, 14.9% and 5.2%, respectively. These values are very close to the signal area obtained for each C1s contribution for both HSAG–SP/CS aerogel and paper  reflections that indicate the order in the direction orthogonal to structural layers: (002) at 26.6°, which corresponds to an interlayer distance of 0.338 nm, and (004) at 54.3°. The in-plane order is proven by the (100) and (110) reflections at 42.5° and 77.6°, respectively. By using (002) reflection and applying the Scherrer equation (Equation (1)), the out of plane correlation length (D┴) was calculated and about 29 stacked layers were estimated. The two reflections at 10.0° and 19.9° as 2θ angles demonstrate the CS crystallinity a. The paIn the pattern of HSAG–SP/CS 1:1 carbon paper c, the  reflection was observed in the latter sample but not in the composite with 20% by mass of HSAG–SP (1:4 HSAG–SP/CS). Such finding can be attributed to the pronounced exfoliation of HSAG but could also be due to its low relative amount (20% by mass). Water was added to the aerogel with 50% HSAG–SP  are shown in −3. The walls of the cavity are of chitosan, in the presence or in the absence of HSAG–SP, which is in most cases present in large aggregates. A continuous filler network is visible in some areas. This structure accounts for the electrical conductivity of the aerogel, discussed below in the text. Aerogels exhibit a spongy like structure. The highly porous structure is confirmed by the low density, equal to 0.026 g cmThe four-point probe method was used to measure the electrical conductivity of HSAG–SP/CS aerogels . Table 25 μS/cm). A critical value of HSAG–SP/CS ratio exists for having values of electrical conductivity in line with those reported in the literature for carbon papers and aerogels. HSAG–SP/CS 1:1 aerogel shows conductivity compared to the paper with the same HSAG–SP/CS ratio. By increasing the quantity of graphite (4:1 aerogel) conductivity, as expected, increases , n-hexane (b) and DMF (c), as shown in Resistance of HSAG–SP/CS aerogels and carbon papers to solvents was preliminarily investigated. Vials containing specimens of the HSAG–SP/CS 1:1 sample were kept for two months in H3COOH, NaHCO3 and KOH to modulate pH values. The stability of HSAG–SP/CS aerogels in a water solution having different pH was investigated, using substances such as HCl, CHThis paper reports a novel and simple approach to achieve ultra-high exfoliation of graphitic aggregates: An adduct between edge functionalized graphene layers and cationic chitosan was formed in water and subjected to mild sonication. Few-layer graphene was obtained, and the structure of the layers was not appreciably perturbed. In previous reports it was shown that the sonication in water of either the same graphitic material (HSAG), edge functionalized with the same pyrrole compound , or of aCarbon papers and aerogels based on graphene layers and containing high amounts (up to 50% by mass) graphitic material were successfully prepared. Moreover, only few of the graphene layers were stacked or their exfoliation was so extensive that the X-ray pattern of the aerogel swollen in water did not reveal the typical (002) reflection of graphitic aggregates. The procedure here reported for obtaining few-layer graphene and highly exfoliated graphene in polymer matrices is sustainable in many aspects. A polymer, such as chitosan, was used. An HSAG–SP adduct was prepared with a high yield and thus almost no wastes , with the help of only thermal energy. HSAG–SP was mixed with chitosan in water, in the presence of only acetic acid, obtaining stable suspensions. Carbon papers and aerogels were obtained by simple casting and lyophilization of HSAG–SP/CS suspensions, respectively. Moreover, the nanocomposites were shown to have interesting properties: They were electrically conductive and stable for months with unaltered properties if stored in different solvents and at different pH.


Graphene, as the earliest discovered two-dimensional (2D) material, possesses excellently physical and chemical properties. Vast synthetic strategies, including chemical vapor deposition, mechanical exfoliation, and chemical reduction, are proposed. In this paper, a method to synthesize multilayer graphene in a semi-opened environment is presented by introducing arc-discharge plasma technology. Compared with previous technologies, the toxic gases and hazardous chemical components are not generated in the whole process. The synthesized carbon materials were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction, and Raman spectra technologies. The paper offers an idea to synthesize multilayer graphene in a semi-opened environment, which is a development to produce graphene with arc-discharge plasma. Since the graphene was isolated in 2004 by A.K. Geim and K.S. Novoselov via the ‘Scotch tape’ method , researc2SO4) and potassium permanganate (KMnO4) were used. In addition, mechanical exfoliation of highly oriented pyrolytic graphite (HOPG) is a method that is suited to use in laboratory investigations due to its low yield [2 plate. This method depends on the quality of graphene. If the quality of graphene is good, the transformation process is not complex. Among these synthetic strategies, mechanical exfoliation gives the best graphene to date. Graphene synthesis by the epitaxial growth method is non-uniform in thickness and the chemical reduction introduces functionalized organic groups into this 2D structure. Nowadays, some new technologies, such as roll-to-roll technology [After a slow start, there has been a rapid increase of the amount of research on graphene in recent years . For exaow yield ,17. Moreow yield . Chemicaow yield ,20,21. Fow yield ’ or otheow yield ,24—introow yield  indicateow yield  reportedchnology , have be60) was firstly synthesized using the direct current (DC) arc-discharge method by Kratschmer and Huffman with a high yield [2) and helium (He) with an optimized current (about 150 A) in a closed water-cooling stainless steel chamber. Chen et al. [2) and buffer gases at 400 Torr in a relatively short time (about 20 min). This proves that the arc-discharge method has the potential to quickly synthesize graphene. However, to our knowledge, a strictly experimental environment, such as whole ambient pressure, is needed in the synthetic process by arc-discharge plasma and the mechanism has seldom been discussed.In 1990, fullerene , atomic force microscopy (AFM), Raman spectroscopy, and X-ray diffraction (XRD), respectively. The synthesized mechanism was further discussed depending on the dynamics of thermal plasma.Graphene was directly synthesized without catalysts using two different sizes of graphite rods as carbon sources by arc-discharge plasma in a semi-opened environment. The graphite rods used in the experiment of 99.99%. A six-millimeter-diameter graphite rod in a length of 10 mm was employed as the cathode and the anode was also a 10 cm long graphite rod but in a diameter of 10 mm as shown in As shown in 2 F20, FEI, operated at 200 kV). The thickness of the synthesized material was measured accurately in the tapping mode of an atomic force microscopy .Raman spectroscopy  is one of the effective characterization methods to identify the product. The excited wavelength was 532 nm. A laser beam was focused through a micro-scope objective with a high numerical aperture (100×) and NA was set as 0.9. The incident laser power was 1 mW to prevent the pristine sample from being modified. X-ray diffraction (XRD) was measured by a D8 Focus  with monochromatized Cu/Kα radiation (λ = 1.5418 Å). The tube voltage and current were 40 kV and 40 mA, respectively. To further determine the product, transmission electron microscopy  and electron diffraction images were used to get the information of topological and layer number of the product , which is derived from inelastic scattering of two phonons, and the G peak (~1580 cm−1), which is related to the ordered in-plane sp2 carbon structure, can be used to distinguish the number of graphene layer  [−1, only a resonant one can modify the Raman cross section. After the scattering process, the excited electron would be scattered back due to the phonon or a defect, and finally, a new photon is emitted [−1 (a little bit less than 2700 cm−1). With the increase of the graphene layers (from a monolayer to multilayers), the 2D peak upshifted [1 and 2D2 peaks), is not symmetrical and the 2D peak exceeded 2700 cm−1 [2D/IG intensity ratio being less than 0.5. The ID/IG intensity ratio is an assessment method of the defect level. Compared with the cathode, the ID/IG ratio in the anode is greater than 0.7, thus showing more defects. The samples for Raman spectroscopy analysis were sonicated in ethyl alcohol for 10 min and then the solution was dropped on an SiOion rule . Such a or few-) . For the emitted . As show emitted . The inspshifted . For gra700 cm−1 ,36. The 700 cm−1 . It can To further identify the materials synthesized in the cathode and anode, the TEM and electron diffraction images were employed. The samples were first sonicated in dimethyl formamide (DMF) for 2 h, and then centrifuged. After that, the supernatant liquid was dropped on the micro-grid and dried by an infrared lamp. The information of the graphite and synthesized materials were detected by TEM as shown in D/IG ratio in the anode. To identify the composition of the material synthesized in the anode, XRD was employed. We found a slight peak around 44.6° in Compared with the material synthesized in the cathode, the product deposited on the anode possessed a high defect as mentioned above. The synthesized products in the cathode and anode were sonicated in the ethyl alcohol, respectively. Then, they were dropped on the mica surface for the AFM test to obtain the AFM images and the thickness information. The AFM testing of material collected from the original graphite rod was also detected. It can be seen that from the AFM image a,b that C and Fe are the carbon atom, iU is the foreign energy, Arc represents the changing condition, and +C and +Fe are the carbon ion and iron ion, respectively.Now, the growth mechanism of graphene in the arc-discharge plasma condition is discussed. The growth pattern for synthesizing graphene without substrate is shown in D/IG ratio (Raman spectrum) of the anode is high with a graphitic structure. Moreover, the synthesized mechanism was further discussed depending on the dynamics of the thermal plasma. When the gas between the cathode and anode was triggered and arc-discharge occurred, individual carbon atoms should evaporate from both the anode and cathode and then re-nucleate in the structure of a regular hexagon. In summary, we provided a method to synthesize multilayer graphene in a semi-opened environment by introducing arc-plasma technology.Multilayer graphene was successfully synthesized in the cathode in a semi-opened environment by introducing arc-discharge plasma. The synthesized material deposited on the cathode and anode was characterized and analyzed by Raman spectrum, TEM, XRD, and AFM. These results show that the graphene in a few layers was synthesized. Compared with the synthesized material in the cathode, the product in the anode showed a different structure. As we can see in the TEM images, the products deposited on the anode possess many black dots in the thin film, which is the reason why the I


Bulk heterojunction (BHJ) structures offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Fabrication methods for the current organic or inorganic BHJ structures invariably create interface mismatch and low doping issues. To overcome such issues, we devised an innovative approach, founded on novel inorganic material system that ensued from single-step electrodeposited copper-indium-selenide compounds. Surface analytical microscopies and spectroscopies reveal unusual phenomena, electro-optical properties and quantum effects. They support the formation of highly-ordered, sharp, abrupt 3-dimensional nanoscale pn BHJs that facilitate efficient charge carrier separation and transport, and essentially perform the same functions as crystalline planar pn junctions. This approach offers a low-cost processing platform to create nanocrystalline films, with the attributes necessary for efficient BHJ operation. It allows roll-to-roll processing of flexible devices in simple thin-film form factor.Semiconductor  Inorganic semiconductors offer superior carrier mobilities, light absorption/emission, and photo/thermal stability relative to organics. Conventional planar pn junction semiconductor devices require high quality, large mono or polycrystals. Their growth by expensive and technically complicated processes is generally incompatible with large-area processing for flexible PV and LED devices. Newer device structures, using bulk heterojunctions (BHJ) offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Current fabrication methods for organic, inorganic or hybrid BHJ structures use two-step process: (i) separate synthesis two types of materials followed by (ii) physical mixing, layering or dispersing nanocrystals in an organic matrix11. Such processing invariably leads to incompatible intra-device interfaces, mismatched shapes and orientations; voids and insulation due to the ligands2. Organic BHJ solar cells are limited by extremely low free carrier concentrations, low mobilities and short lifetime, although ~10% efficiency has been reported7. Inorganic BHJs use colloidal nanocrystals that are difficult to dope and thus, also constrained by extremely low free carrier concentrations12. This work introduces unique nanocrystalline material systems, and discloses a generally accessible, very low-cost method to create high quality, truly nanoscale pn junctions with all the necessary properties for efficient BHJ operation.Semiconductor g) copper-indium-selenide (CISe) films of ordered defect chalcopyrite (ODC) compounds15. Very low ΔH creates self-stabilized CISe-ODC materials16. We exploited this thermodynamic advantage to devise a single-step electrodeposition (SSE) method to synthesize these materials. SSE allows controlling the film composition to produce homogeneous CISe ODC stoichiometries and is therefore, amenable for large area production17.The new device and process concepts draw upon the recent R&D advancements on wide bandgap  vs. capacitance (C) and 1/C2 were obtained with electrolyte impedance spectroscopy, Fig. vs. Ag/AgCl) and doping density (ND) > 1020/cm3 in the measured range. Low trapping defect density was inferred from admittance analysis of the data. It showed minimal frequency dependence of defects even when measured at 300°K. The electronic properties are similar to those for evaporated CuSe (CIGS) with higher carrier densities, lower trapping defect densities, shallower gap states and better cell performance relative to the selenized CIGS(S)18. The results imply that the intrinsic defects in the nano-CISe film are shallow and evenly distributed within the nano-grains and that most of these grains are uniformly and intrinsically doped (1020/cm3 ≡ one doping site per nm3); this can avoid degeneracy as well as contribute free carriers. The free carriers can reduce recombination, increase current and thus, enhance performance.The Mott-Schottky plots of bias  arises from p-CISe grains and the boundaries between light and dark areas evidently correspond to pn junctions. The CISe film is most likely completely depleted because the minority carrier diffusion length of CISe would be larger than the grain size, i.e. all the minority carriers would be swept across the nano pn junctions. As a result, the currents going through the p-grains come from hole-conduction only; this can be orders of magnitude slower than electron-conduction, because the heavier holes move slower, Fig. pn junctions with neutralized electrical charges. The opposite but equivalent conditions prevail for p-type grains under positive DC bias of 1 V, where the boundaries between light and dark areas also correspond to nano pn junctions in the film and these nano junctions are similarly depleted. In both cases, because there are few or no minority carriers to recombine in the p-grain or n-grain, recombination loss would be minimized for devices, such as solar cells.AFM topology and tunnelling current mapping of a CISe film provides direct evidence for the formation of adjacent pn BHJ nanostructure in the CISe film. The secondary electron topography in Fig. pn junctions. It clearly demonstrates a 3-dimensional network of nano pn junctions in the CISe film. The EBIC signal is strongest in the spaces between the large grains, which most likely comprise agglomerates of smaller grains with the same type of conductivity. The opposite EBIC contrast is observed when the current is measured from the other side of the junction and the polarity of the EBIC amplifier is switched, Fig. pn junctions and that the signal response is not related to topology.Electron beam induced current (EBIC) mapping provides clear evidence for the formation of p-CISe and n-CISe phases are abrupt and the pn junctions are of very high quality. Such nano pn homojunctions create an electrical potential gradient, ∇U, at the interface between the grains. The short distance to the nano pn interface enables fast separation of electron and hole carriers. The continuous generation of separated electrons and holes contributes to the high carrier density; it creates and maintains a chemical potential gradient, ∇μ, which drives the transport of electrons and holes separately along the p-CISe and n-CISe phases. Note that standard bilayer planar pn junctions mostly utilize the ∇U effectively, while exitonic BHJ devices mostly utilize the ∇μ19. Unlike either of such device configurations, the CISe BHJ has the potential to effectively utilize both of the fundamental driving forces, i.e. ∇U ≈ ∇μ.The very sharp contrast in both EBIC and AFM data indicates that the interfaces between the 2SO3 (pH 3) electrolyte. Two sharp onsets clearly indicate the presence of more than one compound. The onset values of 980 nm and 1160 nm correspond to the bandgaps of CuInSe2 and CuIn3Se5, Table Figure 20. The EER spectrum shows band edge of the CuIn3Se5 compound at 1.26 eV, which is an exciton-related emission. This bandgap was also associated with a very low broadening parameter, Γ of 42 meV, suggesting excellent crystal quality. The analysis revealed two more bandgaps of 1.14 eV and 1.06 eV, also with relatively low Γ values. The sharp EER peaks for electron transitions and the low Γ values indicate high degree of structural and compositional order and well crystallized chalcopyrite structure. Normally, only single crystal CISe or co-evaporated CIGS films show similar sharp peaks with very low Γ (17–30 meV) values22. In contrast, conventional electrodeposited CuInSe2 films do not show the three levels; their EER spectra show high Γ values (100–400 meV), indicating structural imperfections or sphalerite structure24.Figure 2Se3.5.The bandgaps of 1.26 eV and 1.06 eV closely correspond to theoretically derived values in Table 2 and CuIn3Se5 compounds, Table 2Se3.516, Table 2 and CuIn3Se5 compounds. The band diagram in Fig. pn junctions that leads to the separation of minority carriers across pn junctions .The two bandgaps derived from the EER spectrum of Fig. p-CISe and n-CISe nanocrystals are absorbers, the entire BHJ structure actively contributes to current generation. A number of photocurrent measurements indicate a propensity for the CISe BHJ film to generate high photocurrent (unpublished), comparable to that for large-grained CIGS25. Furthermore, high open circuit potential is also attainable if the BHJ device comprises appropriately band-aligned contact electrodes, Fig. Fp) and electrons (EFn), creating the device open circuit potential, VOC. To maximize the VOC, the difference in the work functions of the contact electrodes should be larger than the difference between the quasi Fermi levels. Heavily doped p+ or n+ contacts can move the conduction band (CB) and valence band (VB) edges to create large band offsets. Alternately, electron blocking (EBL) & hole blocking (HBL) layers may be inserted as shown, to maximize the fill-factor.Because both Cu, VSe) and acceptor (VCu) defects27. In nanocrystalline state, the individual grains can only have either p- or n- type doping, but both types can co-exist in different grains, as is observed for CISe. Based on this understanding, we can predict that other II-VI chalcogenides could also form nanocrystalline pn BHJ with high doping density. This work, thus, presents a general, very low-cost platform technology to create high quality nanostructured pn BHJ material systems for high performance devices.Semiconductor behaviour is related to its fundamental properties. CISe-ODCs are unique because they form a series of stable compounds with bandgaps ranging from 1.06–1.34 eV that are intrinsically doped by shallow donor , 1.26 eV (CB), and 1.31 eV, 1.37 eV .Photoluminescence (PL) spectra for the CISe film in Fig. 2: 1.00 eV (CB →VCu or InCu →VB), 0.93 eV (InCu →VCu) and 0.88 eV (VSe →VCu). The broadening parameters (Γ) for EER spectra in Fig. pn BHJ nanostructures29; or above bandgap luminesce from accumulated high densities of electrons in quantum confined regions30. The spatially separated electrons and holes should exhibit long carrier lifetimes after the laser light absorption. Indeed, this specific CISe film was found to exhibit unusually long charge carrier lifetime. Substantially unequal electron paths in n-CISe within the CISe layer could lead to accumulation of high densities of electrons in some regions. The laser could pump and up-convert the electrons to energies well above bandgap, moving them to a different location along the n-CISe path. The electrons can then recombine with holes radiatively to luminesce above the bandgap. The quantum mechanical interactions of high density electrons and laser are expected to be quantized in energy and probably create the multiplet splitting with the discrete 30 mV spacing, displayed in the PL spectrum. In a solar cell, low energy (below bandgap) photons can also pump the accumulated electrons into above bandgap energy, which are essentially up-converted. The resulting broadening of the photon spectral range can significantly improve device efficiency. It is unlikely that the large PL emission peak would originate from the presence of a highly Cu-deficient phase since there is no other manifestation of this phase nor does it explain the dramatic high energy PL emission.With a 540 nm long pass filter, the PL response extends over a wide range of energies, 0.7–2.2 eV; it also indicates free carrier-to-shallow defect transitions, such as those from known shallow defects within the 1.06 eV bandgap of CuInSepn-CISe BHJ can tolerate very wide composition variation, i.e. various CISe film compositions essentially give the same PL spectra of Fig. Both the EER and PL results could be attributed to energy transitions from crystal-field splitting and the spin-orbit coupling. Such phenomena are generally observed for large crystals under cryogenic conditions. The fact that the spectra are well-resolved even at 300°K is remarkable, and attests to the high and unique quality of our SSE-made nanocrystals. Usually, very pure and high-quality crystals or artificially created quantum well structures show such band-to-band transitions and non-linear absorption, and that too under cryogenic conditions. Moreover, the electronic nanostructure of 2 and CuIn3Se5 compounds and a third phase, e.g. (CuInSe2 + CuIn3Se5). The two types of grains arise from the specific SSE process parameter. The CISe film grows in steps that are controlled by the kinetics of several chemical and electrochemical reactions, leading to successive formation of CuSe → CuInSe2 → CuIn3Se5 compounds32. So, depending on the overall film composition, the components and defects organize into two or more compounds, each with distinct ODC stoichiometry. The EER data confirms that the SSE/anneal steps create naturally ordered CISe nanocrystals. AFM and EBIC offer unmistakable evidence that the film comprises CISe nanostructures of mixed p-CISe and n-CISe grains. The grain interface forms pn homojunction and possibly a stable CuInSe2 + CuIn3Se5 molecular complex.The correlation of the surface microscopy and spectral data provide valuable insights into the extraordinary characteristics of SSE-made CISe film. Both EER and EQE spectra affirm the presence of CuInSep- or n-doped nanocrystals; the random mixing of the p-CISe and n-CISe grains leads to the formation of interpenetrated and interconnected p- and n-network. The similar morphology and electronic nanostructure of the CISe-ODC compounds ensures that such a network will form, even when the p:n ratio is off by a wide margin and the individual grains have irregular shapes. The annealing step ensures that the grains grow into each other until the space between them is filled. So the grains have highly desirable matching interfaces that enable efficient BHJ operation. Significantly, this finding solves a major hurdle for creating inorganic pn BHJs. It avoids the need to separately synthesize nanocrystals and/or physically mix two types of materials to create BHJs, as in colloidal nanocrystals.The results thus imply that the CISe film comprises randomly mixed 12. Nanocrystalline CISe films are very different from colloidal nanocrystals because they exhibit high doping densities and tend to form pn junctions. This unique attribute of CISe nanocrystals contributes to its ordered nanoscale morphology. It avoids phase-separated domains formed in conventional BHJs, which tend to impede the interconnections needed for efficient transport of free carriers. The data supports the formation of nano-architectured pn BHJs that are highly ordered, sharp and abrupt. They enable fast, efficient spatial separation and transport of electrons and holes. Such processes would minimize recombination losses in solar cells, greatly relaxing the stringent requirement for large crystals in devices. In other words, the high quality 3-D pn BHJ can perform the same solar cell functions as 2-D planar pn junction, equally well.In general, nanocrystals tend to be perfect and are difficult to dope by extrinsic impurities31. This outcome could have strong implications for accessing a wider spectral range to maximize device efficiency. Also, since the PL emissions cover most of the visible range, the nanostructured CISe film can also function as a good LED. Note that the ‘universal’ n-cathode/pn-CISe/p-anode device structure may be used either in solar cells or LEDs. LED structure is essentially the inverse of a solar cell. The 3D nanostructured pn BHJ layer is isotropic at the µm scale and current can flow through it from either direction. Thus, similar manufacturing processes can fabricate LEDs or solar cells. In theory, solar cell and LED have the same requirements for material quality and properties.The dramatic shift in PL emission to high energies observed for CISe films may offer an alternative type of up-conversion mechanismpn BHJ material systems. Contrary to common perception about electrodeposited films, well-crystalized CISe nanocrystals could be used directly in solar cells or LEDs if the device is appropriately configured to take advantage of their special properties. With the incorporation of finely band-aligned contact electrode materials, the CISe BHJ film can be transformed into high performance flexible devices. The method is amenable to atmospheric, solution-based roll-to-roll manufacturing of solar cells or LEDs in a thin-film form factor. The new phenomena revealed in this work offer significant opportunity for fundamental breakthroughs in basic materials science, as well as novel applications.The above results validate a valuable advance in semiconductor processing. They disclose a generally accessible, very low-cost SSE method to create high quality, nanocrystalline 2 and CuIn3Se5 compounds in roughly 1:1 ratio. The electrolyte comprised Cu2+, In3+ and Se4+ ions in 0.1 M KCl. The [Cu]:[In]:[Se] metals concentration was generally maintained at 1:4:2 ratio and the solution temperature was between 50–60 °C. Most films were deposited at constant potential between −0.51± 0.01 V, using Pine Instruments potentiostat on ~5 cm2 exposed area of back-insulated Mo or stainless-steel foil. X-ray fluorescence analysis (XRF) with Spectro Midex provided the film composition and thickness. The films were briefly annealed in the 200–350 °C range in ambient atmosphere, using a combination of conventional furnace and RTP. Furnace annealing was done at 350 °C for up to 20 min and RTP was done with an IR lamp (650 W) at 90% with 2–3 sec pulses, repeated 10–15 times. The thermal processing requirements vary for different substrates, 17. The annealing was minimized in order to retain the structural order and integrity generated by the SSE process.Thin film CISe samples were prepared by SSE in a standard single compartment 3-electrode cell, comprising an Ag/AgCl (+0.222 vs NHE) reference electrode (RE) and Pt or graphite counter electrode (CE). The films were deposited from a single electrolyte by varying deposition parameters to control the composition of the CISe film to produce CuInSep-type and n-type grains in the film. The AFM topological and nanoelectrical micrographs were obtained with Bruker Dimensional Icon and SCM-PIT probe on a 1 µm area of CISe sample. The dark lift mode was used to eliminate the laser effects because the electron-hole pairs generated in the pn junction device with laser illumination can significantly affect the minority carrier concentration, and hence the Fermi energy level and the width of the depletion region. KPFM measured the work function difference of tip/CISe sample. The measurements were done on 1 µm area of the CISe sample, using PFNQE-AL probe under AC bias of 5 V and lift height of 100 nm.Tunnelling AFM measurements used bias polarity effects to identify pn junctions.The EBIC maps were obtained using Ephemeron Labs quantitative EBIC imaging system designed for nano-electronic materials. The electron beam of an SEM was scanned across the foil/CISe/ITO device surface to generate electron–hole pairs; they separate by drift due to the electric field, causing current flow. A picoammeter detects electronic activity variations due to the presence of 2 to the electrolyte held in a 3-electrode cell provided with 2 quartz windows, Fig. 2SO3 (pH 3) electrolyte, a good hole-scavenger was used to form an electrolytic junction with the CISe sample, Fig. 20. The EER responses were phase sensitively detected at room temperature temperature (non-cryogenic) and the spectrum was analysed by fitting of the experimentally obtained spectrum to the third derivative functional form. The transition energy and the broadening parameters were obtained from equation R/R is the relative reflectivity change, E is photon energy of the probe beam, j is the number of spectral function to be fitted, Egj is the critical point energy, Γj, Cj, and θj are the broadening parameter (≡ measure of disorder), amplitude, and phase angle, respectively; mj corresponds to a band-to-band transition and is assumed to be 2.5.Electrochemical characterization was performed on masked CISe samples, exposing an area of 0.25 cmThe PL spectra were obtained using Horiba’s Micros setup with a 532 nm laser excitation at room temperature. Long pass filters were used to block the short-wave light below 540 nm or 830 nm for the spectra at respective wavelengths.