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BACKGROUND: Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis. METHODS: The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored. RESULTS: Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests. CONCLUSION: Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Toxinas Botulínicas Tipo A , Hiperidrose , Axila , Toxinas Botulínicas Tipo A/efeitos adversos , Humanos , Hiperidrose/diagnóstico , Hiperidrose/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/ß-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/ß-catenin signaling pathway, including Lef1 and ß-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1ß, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/ß-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.
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Folículo Piloso/efeitos dos fármacos , Privilégio Imunológico/efeitos dos fármacos , Inibidores de Janus Quinases/farmacologia , Pirazóis/farmacologia , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/imunologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/imunologia , Humanos , Interferon gama/imunologia , Masculino , Camundongos Endogâmicos C57BL , Nitrilas , Pirimidinas , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Keloid is a representative chronic fibroproliferative condition that occurs after tissue injury. Emerging evidence showed that activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pro-inflammatory response in injured tissues. However, the role of NLRP3 inflammasome in keloid progression remains unclear. Notch signaling, which activates NLRP3 inflammasome, is known to contribute to scar formation in keloid, but the cause of enhanced Notch signaling in keloid is not clear. We sought to investigate whether autophagy regulates Notch1 signaling in keloid fibroblasts and determine whether Notch1 signaling might regulate NLRP3 inflammasomes and myofibroblast differentiation. An in vitro model of keloid was established by culturing primary keloid fibroblasts from patients. Expression levels of Notch1, NLRP3 inflammasome proteins, pro-inflammatory cytokines, and myofibroblast markers in keloid fibroblasts were examined and compared with those in normal fibroblasts. Autophagy known to mediate Notch1 degradation was also monitored in fibroblasts. Small interfering RNA (siRNA) targeting Notch1 was used to transfect keloid fibroblasts to further examine the role of Notch signaling in NLRP3 inflammasome activation. Expression levels of Notch1 and NLRP3 inflammasome in keloid fibroblasts increased compared to those in normal fibroblasts. Such increases were accompanied by increased LC3 levels and reduced autophagic flux. Notch1 silencing in keloid fibroblasts by siRNA transfection significantly suppressed increased levels of overall NLRP3 inflammasome complex proteins, NF-kB, and α-smooth muscle actin. Autophagy induction by rapamycin treatment in keloid fibroblasts effectively suppressed expression levels of Notch1 and NLRP3 inflammasome proteins. Decreased autophagy activity in keloid can result in Notch1-mediated myofibroblast activation and NLRP3 inflammasome signaling activation which is critical for chronic inflammation. Collectively, these results identify Notch1 as a novel activator of NLRP3 inflammasome signaling leading to chronic tissue damage and myofibroblast differentiation in keloid progression.
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Autofagia , Fibroblastos/patologia , Inflamassomos/metabolismo , Inflamação/patologia , Queloide/complicações , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor Notch1/metabolismo , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Fibroblastos/imunologia , Fibroblastos/metabolismo , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Pessoa de Meia-Idade , Miofibroblastos/imunologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Transdução de Sinais , Adulto JovemRESUMO
Porous carbonaceous anode materials have received considerable attention as an alternative anode material, however, there is a critical bottleneck as it suffers from a large irreversible specific capacity loss over several initial cycles owing to undesired surface reactions. In order to suppress undesired surface reactions of porous carbonaceous anode material, here, we suggest a simple and convenient two-step surface modification approach that allows the embedding of an amide functional group on the surface of a porous carbonaceous anode, which effectively improves the surface stability. In this approach, the porous carbonaceous anode material is firstly activated by means of strong acid treatment comprising a combination of H2 SO4 and HNO3 , and it is subjected to further modification by means of an amide coupling reaction. Our additional systematic analyses confirm that the acid functional group effectively transforms into the amide functional group. The resulting amide-functionalized porous carbon exhibits an improved electrochemical performance: the initial discharge specific capacity is greatly reduced to less than 2,620â mA h g-1 and charge specific capacity is well still remained, indicating stabling cycling performance of the cell.
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This study examined the effects of language differences between Korean and English on the performance of natural language processing in the classification task of identifying inpatient falls from unstructured nursing notes.
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Aprendizado Profundo , Humanos , Acidentes por Quedas/prevenção & controle , Pacientes Internados , Registros Eletrônicos de Saúde , Idioma , Processamento de Linguagem NaturalRESUMO
BACKGROUND: After stroke, gait training is a key component of rehabilitation, and most individuals use a variety of walking aids depending on their physical condition and environment. OBJECTIVE: This study aimed to investigate the potential effect of a one-arm motorized gait device for gait assist of chronic hemiplegic stroke survivors through comparison with traditional gait devices (parallel bar and hemi-walker). METHODS: This study was conducted on 14 chronic hemiplegic stroke survivors. The participants were asked to walk under three conditions using different gait devices, and their gait parameters during walking were collected and analyzed. The first condition involved walking on parallel bars; second condition, walking using hemi-walkers; and third condition, walking using one-arm motorized gait devices. With the use of a gait analysis system, the spatio-temporal gait parameters in each condition were collected, such as gait velocity, cadence, step length, stride length, single support time, and double support time. RESULTS: In the results by repeated-measures ANOVA or the Friedman test, a significant difference was found in the gait parameters among all three conditions (p< 0.05). The post-hoc test showed a significant change in the spatio-temporal gait parameters (especially, velocity, cadence and affected side single and double support time) when one-arm motorized gait device were used compared with parallel bars and hemi-walkers (p< 0.05). CONCLUSION: The results of this study suggest that one-arm motorized gait devices developed for hemiplegic stroke survivors may be more effective potentially than parallel bars and hemi-walkers in gait assistance of chronic hemiplegic stroke survivors.
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Transtornos Neurológicos da Marcha , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Hemiplegia/reabilitação , Marcha , Acidente Vascular Cerebral/complicações , Caminhada , Sobreviventes , Transtornos Neurológicos da Marcha/reabilitaçãoRESUMO
BACKGROUD: Accurate estimation of post-mortem interval (PMI) is crucial in forensic investigations. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable within the cell nucleus despite post-mortem changes. OBJECTIVE: We assessed three target genes (miR-122, miR-133a, and miR-206) for PMI estimation using 72 healthy adult male BALB/c mice exposed to two different temperatures (4 and 21â) at nine different time points over 10 days. METHODS: Initially, the stability of the two reference genes (RNU6B and 5 srRNA) was evaluated using gene stability analysis tools (Delta Ct, Best Keeper, and Genorm) to select the optimal reference gene. RNU6B was found to be the most stable endogenous control. Subsequently, the expression patterns of miR-122, miR-133a, and miR-206 were analyzed within a 10-day PMI period using the heart, skeletal muscle, liver, and brain tissues. RESULTS: At 4â, miR-122 levels significantly decreased on days 8 and 10 in all tissues, with only the liver showing significant changes at 21â. MiR-133a decreased over time in the heart, muscles, and brain, showing a dramatic decrease on days 8 and 10 in the heart and muscles at both temperatures. Although miR-206 levels decreased over time in muscles and liver at 4 â, these increased in the brain at 21 â, with no expression changes in other organs. CONCLUSION: In summary, miR-122, miR-133a, and miR-206 are potential PMI markers in heart and skeletal muscle tissues.
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Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.
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Cóclea , Dexametasona , Perda Auditiva , Hidrogéis , Derivados da Hipromelose , Injeção Intratimpânica , Nanopartículas , Dexametasona/química , Dexametasona/administração & dosagem , Animais , Derivados da Hipromelose/química , Hidrogéis/química , Nanopartículas/química , Camundongos , Cóclea/efeitos dos fármacos , Cóclea/patologia , Perda Auditiva/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Liberação Controlada de Fármacos , Masculino , Sistemas de Liberação de Medicamentos/métodosRESUMO
In this paper, we present a new reset tree-based scheme to protect cryptographic hardware against optical fault injection attacks. As one of the most powerful invasive attacks on cryptographic hardware, optical fault attacks cause semiconductors to misbehave by injecting high-energy light into a decapped integrated circuit. The contaminated result from the affected chip is then used to reveal secret information, such as a key, from the cryptographic hardware. Since the advent of such attacks, various countermeasures have been proposed. Although most of these countermeasures are strong, there is still the possibility of attack. In this paper, we present a novel optical fault detection scheme that utilizes the buffers on a circuit's reset signal tree as a fault detection sensor. To evaluate our proposal, we model radiation-induced currents into circuit components and perform a SPICE simulation. The proposed scheme is expected to be used as a supplemental security tool.
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Finding relations between genes and diseases is essential in developing a clinical diagnosis, treatment, and drug design for diseases. One successful approach for mining the literature is the document-based relation extraction method. Despite recent advances in document-level extraction of entity-entity, there remains a difficulty in understanding the relations between distant words in a document. To overcome the above limitations, we propose an AI-based text-mining model that learns the document-level relations between genes and diseases using an attention mechanism. Furthermore, we show that including a direct edge (DE) and indirect edges between genetic targets and diseases when training improves the model's performance. Such relation edges can be visualized as graphs, enhancing the interpretability of the model. For the performance, we achieved an F1-score of 0.875, outperforming state-of-the-art document-level extraction models. In summary, the SCREENER identifies biological connections between target genes and diseases with superior performance by leveraging direct and indirect target-disease relations. Furthermore, we developed a web service platform named SCREENER (Streamlined CollaboRativE lEarning of NEr and Re), which extracts the gene-disease relations from the biomedical literature in real-time. We believe this interactive platform will be useful for users to uncover unknown gene-disease relations in the world of fast-paced literature publications, with sufficient interpretation supported by graph visualizations. The interactive website is available at: https://ican.standigm.com.
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Práticas Interdisciplinares , Mineração de Dados/métodosRESUMO
Individuals with end-stage kidney disease (ESKD) on dialysis are at a high risk of developing foot ulcerations and undergoing subsequent lower extremity amputation (LEA), which can exert significant impacts on their quality of life and contribute to rising healthcare costs. We aimed to identify risk factors associated with LEA in patients with ESKD to predict LEA progression and eventually prevent it. We used 18 years (2002-2019) of data from the Korean National Health Insurance Service (KNHIS). Data were collected from patients with ESKD who underwent renal replacement therapy (RRT) and had no history of amputation caused by trauma or toxins. The risk factors were compared between patients with or without LEA. We collected data from 220,838 patients newly diagnosed with ESKD, including 6348 in the LEA group and 214,490 in the non-LEA group. The total incidence of LEA was 2.9%. Older age, male gender, lower income, non-metropolitan residence, diabetes mellitus, dialysis treatment (compared to kidney transplantation), microvascular disease, peripheral vascular disease, endovascular procedure, and endovascular operation were associated with an increased risk of LEA. Thus, individuals with ESKD who are at a higher risk for LEA should be closely monitored, and kidney transplantation should be considered as a preventative measure.
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Perovskite quantum dots (PQDs) have been considered promising and effective photovoltaic absorber due to their superior optoelectronic properties and inherent material merits combining perovskites and QDs. However, they exhibit low moisture stability at room humidity (20-30%) owing to many surface defect sites generated by inefficient ligand exchange process. These surface traps must be re-passivated to improve both charge transport ability and moisture stability. To address this issue, PQD-organic semiconductor hybrid solar cells with suitable electrical properties and functional groups might dramatically improve the charge extraction and defect passivation. Conventional organic semiconductors are typically low-dimensional (1D and 2D) and prone to excessive self-aggregation, which limits chemical interaction with PQDs. In this work, we designed a new 3D star-shaped semiconducting material (Star-TrCN) to enhance the compatibility with PQDs. The robust bonding with Star-TrCN and PQDs is demonstrated by theoretical modeling and experimental validation. The Star-TrCN-PQD hybrid films show improved cubic-phase stability of CsPbI3-PQDs via reduced surface trap states and suppressed moisture penetration. As a result, the resultant devices not only achieve remarkable device stability over 1000 h at 20-30% relative humidity, but also boost power conversion efficiency up to 16.0% via forming a cascade energy band structure.
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No effective therapeutic strategies have been developed against food allergies. Immunomodulation during early infant period could prevent the development of food allergies. We investigated the preventive effects of human hematopoietic mesenchymal stem cells (hHMSCs) in mice with ovalbumin (OVA)-induced food allergy. BALB/c mice with OVA-induced food allergy were divided into 3 groups, and each group was treated with hHMSCs or hHMSC culture medium (hHMSC-CM) or saline. Ear thickness, allergy score, rectal temperature, and diarrhea occurrence were checked. Total IgE, OVA-specific IgE, and mucosal mast cell protease-1 (mMCP-1) were measured by ELISA. Other allergic parameters were analyzed using histology specimens, RT-PCR, and flow cytometry. Treatment with hHMSCs or hHMSC-CM significantly suppressed the frequency of anaphylactic response and rectal temperature decline, reduced diarrhea, total IgE, OVA-specific IgE, and mMCP-1. While the treatment decreased the level of Th2 cytokines, it enhanced IL-10 and TGF-ß1 mRNA. Exposure to hHMSC or hHMSC-CM did not generate regulatory T cells, but reduced mast cells. The immunomodulatory effect on the Th2 cytokines was greater in hHMSC-CM than in hHMSCs. hHMSC treatment may be a promising preventive intervention against food allergy. Further studies are needed to elucidate the key substances released from hHMSC to induce immune tolerance.
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Colorectal perineuriomas are benign mucosal-based mesenchymal tumors composed of perineurial cells and show serrated or hyperplastic crypts in epithelium on histopathological evaluation. Most perineuriomas are usually presented as sessile polyps and often as subepithelial tumors. In this case, colonoscopy revealed a rectal subepithelial tumor (measuring approximately 7 mm) with yellowish- colored normal mucosa. A rectal neuroendocrine tumor was suspected, and cap-assisted endoscopic mucosal resection was performed. Histopathological examination of the resected specimen revealed bland spindle cells showing immunopositivity for CD34. The patient was finally diagnosed with rectal perineurioma.
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Ressecção Endoscópica de Mucosa , Neoplasias de Bainha Neural , Tumores Neuroendócrinos , Neoplasias Retais , Colonoscopia , Humanos , Neoplasias de Bainha Neural/diagnóstico , Neoplasias de Bainha Neural/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgiaRESUMO
Perovskite solar cells (PSCs), which have surprisingly emerged in recent years, are now aiming at commercialization. Rapid, low-temperature, and continuous fabrication processes that can produce high-efficiency PSCs with a reduced fabrication cost and shortened energy payback time are important challenges on the way to commercialization. Herein, we report a reactive ion etching (RIE) method, which is an ultrafast room-temperature technique, to fabricate mesoporous TiO2 (mp-TiO2) as an electron transport layer for high-efficiency PSCs. Replacing the conventional high-temperature annealing process by RIE reduces the total processing time for fabricating 20 PSCs by 40%. Additionally, the RIE-processed mp-TiO2 exhibits enhanced electron extraction, whereupon the optimized RIE-mp-TiO2-based PSC exhibits a power conversion efficiency (PCE) of 19.60% without J-V hysteresis, when the devices were optimized with a TiCl4 surface treatment process. Finally, a flexible PSC employing RIE-mp-TiO2 is demonstrated with 17.29% PCE. Considering that the RIE process has been actively used in the semiconductor industry, including for the fabrication of silicon photovoltaic modules, the process developed in this work could be easily applied toward faster, simpler, and cheaper manufacturing of PSC modules.
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For commercialization of perovskite solar cells (PSCs), it is important to substitute the alternative electrode for Au to decrease the unit cost. From the early stage, Ag exhibits a potential to be a good counter electrode in PSCs; however, there is an abnormal s-shaped J-V curve with the Ag electrode, and it is recovered as time passes. The perception of the aging-induced recovery process and refutation of the raised stability issues are required for commercial application of Ag electrodes. Herein, we compared the aging effect of PSCs with Ag and Au electrodes and found that only devices with Ag electrodes have a dramatical aging-induced recovery process. We observed the change of photoelectronic properties only in the devices with Ag electrodes as time passes, which mainly contributes to recovery of the s-shaped J-V curve. We verified the work function change of an aged Ag electrode and its mechanism by photoelectron spectroscopy analysis. By comparing the light stability under 1 sun intensity illumination, we can assure the practical stability of Ag electrodes in case of being encapsulated. This work suggests the profound understanding of the aging-induced recovery process of PSCs and the possibility of commercial application of Ag electrodes.
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Electron selective layers are important to the efficiency, stability and hysteresis of perovskite solar cells. Photo-annealing is a low-cost, roll-to-roll-compatible process that can be applied to the post-treatment fabrication of sol-gel based metal oxide layers. Here, we fabricate an amorphous titanium oxide electron selective layer at a low temperature in a dry atmosphere using a UV light annealing system and compare it with a thermal annealing process. Active oxygen species are created by using UV light to promote hydrolysis and condense the TiO2 precursor, which removes organic ligands effectively. The photo-annealed TiO2-based perovskite solar cell has a power conversion efficiency of 19.37% without hysteresis.
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Photovoltaic technologies based on perovskite absorber materials have led this optoelectronic field into a brand-new horizon. However, the present antisolvents used in the one-step spin-coating method always encounter problems with the very narrow process window. Herein, anisole is introduced into the one-step spin-coating method, and the technology is developed to fabricate perovskite thin films with ultrawide processing window with a dimethylformamide (DMF):dimethyl sulfoxide (DMSO) ratio varying from 6:4 to 9:1 in the precursor solution, anisole dripping time ranging from 5 to 25 s, and an antisolvent volume varying from 0.1 to 0.9 mL. Perovskite thin films as large as 100 cm2 are successfully fabricated using this method. Maximum photoelectric conversion efficiencies of 19.76% for small-area (0.14 cm2 ) and 17.39% for large-area (1.08 cm2 ) perovskite solar cell devices are obtained. It is also found that there are intermolecular hydrogen-bonding forces between anisole and DMF/DMSO that play critical roles in the wide process window. These results provide a deeper understanding of the crystallizing procedure of perovskite during the one-step spin-coating process.
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Silver nanowire-based flexible transparent electrodes have critical problem, in spite of their excellent electrical and optical properties, that the electrical conductance and transparency degrade within several days in air because of oxidation of silver. To prevent the degradation of the silver nanowire, we encapsulated Ag-NWs with thin TiO2 barrier. Bar-coated silver nanowires on flexible polymer substrate were laminated at 120 °C, followed by atomic layer deposition of TiO2 nanoshell. With 20 nm of TiO2 nanoshells on silver nanowires, the transparent electrode keeps its electrical and optical properties over 2 months. Moreover, the TiO2-encapsulated silver nanowire-based transparent electrodes exhibit excellent bending durability.
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We fabricated a mesoporous perovskite solar cell with a â¼14% conversion efficiency, and we investigated its beneficial grain boundary properties of the perovskite solar cells through the use of scanning probe microscopy. The CH3NH3Pb(I0.88,Br0.12)3 showed a significant potential barrier bending at the grain boundary and induced passivation. The potential difference value in the x = 0.00 sample is â¼50 mV, and the distribution of the positive potential is lower than that of the x = 0.12 sample. We also investigated the polarization and hysteretic properties of the perovskite thin films by measuring the local piezoresponse. Specifically, the charged grain boundaries play a beneficial role in electron-hole depairing and in suppressing recombination in order to realize high-efficiency perovskite solar cells.