On-demand drug delivery bioelectronics through a water-processable low dimensional highly conductive MXene layer.

On-demand drug delivery holds great promise to optimize pharmaceutical efficacy while minimizing the side effects. However, existing on-demand drug delivery systems often require complicated manufacturing processes that preclude their wide implementation of a broad range of drugs. In this work, we demonstrate the introduction of MXene-coated microneedles (MNs) into bioelectronics for digitally controllable gate-valve drug delivery. MXenes, featuring high electronic conductivity, excellent biocompatibility, and solution processibility, enable low-cost scalability for printable bioelectronics. In an electrolytic state (e.g., body fluid), the coated MXene is oxidized and desorbed due to redox reactions caused by electrical bias, allowing the underlying drug to be controllably released. The MXene-incorporated drug delivery system not only demonstrates excellent biocompatibility and operational stability, but also features low-cost construction and sustainable usage. Besides, these MXene-coated MNs allow both on-demand transformation and local-region customization, further increasing the structural versatility and capability of multidrug delivery systems.

Missense Variant c.3301C>T (p.R1101W) in von Willebrand Factor A Sequence in a Patient with Recessive Dystrophic Epidermolysis Bullosa Pruriginosa with Compound Heterozygous COL7A1 Variants.

Dystrophic epidermolysis bullosa (DEB) pruriginosa is a rare subtype of DEB characterized by multiple, violaceous, and severe pruritic lichenified nodules along with blisters. Here, we report the case of a Korean male who, since the age of 3 years, had multiple pruritic nodules with blisters on both lower extremities. Genetic testing is required to diagnose DEB pruriginosa because its clinical and histologic features are inconclusive. We identified compound heterozygous COL7A1 variants of c.5797C>T (p.R1933*) and c.3301C>T (p.R1101W) in the patient, leading to a diagnosis of recessive DEB pruriginosa. Among the variants identified, c.3301C>T is a novel missense variant that has not been reported previously. This variant is in exon 26, which encodes von Willebrand factor A (vWFA) in collagen type VII. vWFA is known to preserve normal dermal structures by interacting with dermal collagens and basement membranes. Considering that this variant contradicts the general concept that autosomal dominant inheritance is more common and that variants typically occur in the triple helical collagenous domain of COL7A1 in DEB pruriginosa, we focus on the rarity of this case and the possible pathogenic role of the c.3301C>T (p.R1101W) variant.

Refractory Bullous Pemphigoid Successfully Treated with Reslizumab: A Possible Novel Therapeutic Modality.

Bullous pemphigoid (BP) is a chronic, autoimmune blistering disease that has concerning morbidity and mortality rates. Recently, several studies have focused on eosinophils due to their significant role in the pathogenesis of BP, considering that they are ubiquitous in the serum, tissue, and blister fluids of patients with BP. With this context, precision therapy that targets mediators of eosinophil activity could be a possible novel therapeutic strategy. Interleukin (IL)-5 is crucial for B-cell maturation, which consequently results in immunoglobulin production, and promotes eosinophil differentiation, proliferation, and activation. To our best knowledge, reslizumab has not yet been reported to treat BP. Herein, we report a case of steroid- and omalizumab-resistant BP treated successfully using reslizumab. Our data suggest that IL-5 could be a novel specific biologic target within the entire immunopathogenesis of BP, and reslizumab would be a novel therapeutic modality.

Amorphous Fluorinated Acrylate Polymer Dielectrics for Flexible Transistors and Logic Gates with High Operational Stability.

Fluorinated amorphous polymeric gate-insulating materials for organic thin-film transistors (OTFTs) not only form hydrophobic surfaces but also significantly reduce traps at the interface between the organic semiconductor and gate insulator. Therefore, these polymeric materials can enhance the OTFT's operation stability. In this study, we synthesized a new polymeric insulating material series composed of acrylate and fluorinated functional groups (with different ratios) named MBHCa-F and used them as gate insulators for OTFTs and in other applications. The insulating features of the MBHCa-F polymers, including surface energy, surface atomic content properties, dielectric constant, and leakage current, were clearly analyzed with respect to the content of the fluorinated functional groups. At higher fluorine-based functional group content, the polymeric series exhibited higher fluorine-based contents at the surface and superior electrical properties, such as field-effect mobility and driving stability, at OTFTs. Therefore, we believe that this study provides a substantial method for synthesizing polymeric insulating materials to enhance the operational stability and electrical performance of OTFTs.

Current developments of eco-friendly organic field-effect transistors: from molecular engineering of organic semiconductors to greener device processing.

Replacing environmentally damaging toxic halogenated/aromatic hydrocarbon organic solvents commonly used in solution-processed organic field-effect transistors with more sustainable green solvents has in recent years become a subject of various studies. In the current review, we summarize the properties of solvents used to process organic semiconductors and relate these properties to the toxicities of the solvents. And then, the research efforts to avoid using toxic organic solvents are reviewed, in particular the efforts involving molecular engineering of organic semiconductors achieved by introducing solubilizing side chains or substituents into the backbone and with synthetic strategies to asymmetrically deform the structure of the organic semiconductors and random copolymerization, as well as efforts involving the use of miniemulsion-based nanoparticles to process organic semiconductors.

Comparison of cyclosporine and systemic corticosteroid for treating drug reaction with eosinophilia and systemic symptoms syndrome: A retrospective 20-year single-centre study in South Korea.

BACKGROUND/OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening hypersensitive disorder. Cyclosporine has been indicated for adverse cutaneous drug eruptions. However, studies evaluating its clinical effectiveness in DRESS syndrome have been rare. This study aimed to evaluate the clinical efficacy of cyclosporine in DRESS syndrome compared to that of systemic corticosteroids. METHODS: In the cyclosporine group, oral cyclosporine was administered twice a day for a total of 2-3 mg/kg/day for 1 week, and subsequently reduced to 1-1.5 mg/kg/day for extended treatment. In the corticosteroid group, intravenous or oral methylprednisolone was administered at 1-1.5 mg/kg/day for 1 week, with variable tapering plans. Laboratory changes before and after treatment, hospitalized days, treatment periods, and time to normalization from clinical manifestations in each group were statistically evaluated. Adverse effects of these regimens were observed during the entire treatment period. RESULTS: Eighty patients were enrolled in this retrospective study. The cyclosporine and corticosteroid group had 27 and 53 patients, respectively. Total leucocyte and eosinophil counts, liver enzymes, and C-reactive proteins were significantly decreased after treatment in both groups. There were no statistically significant differences observed in hospitalized days, treatment period, and time to normalization from clinical manifestations between the two groups. The corticosteroid group experienced relatively more adverse effects than the cyclosporine group. CONCLUSIONS: Cyclosporine was discovered to be clinically effective in DRESS syndrome and this study suggests that cyclosporine could be a feasible primary therapeutic option for DRESS syndrome.

A postulated model for photoimmunopathogenesis of chronic actinic dermatitis around adaptive immunity, including Th17 cells, Tregs, TRMs, cytotoxic T cells, and/or common-γ chain receptor+ cells.

BACKGROUND/PURPOSE: The pathogenesis of chronic actinic dermatitis (CAD) is more complicated than other photodermatoses. However, the relationship between the clinical severity of CAD and the offending photocontact or contact allergens or both, and the correlations of CAD immunopathogenesis with the immunoregulatory molecules involved in adaptive immunity are yet to be investigated. METHODS: We performed phototesting with broad-spectrum ultraviolet (UV) B, UVA, and visible light to establish the presence of photosensitivity in 121 patients with CAD, together with photopatch and contact patch testing. Nine patients with CAD were selected according to their clinical severity score for CAD (CSS-CAD), and triple direct immunofluorescence analysis was performed with paraffin-embedded skin biopsy samples. RESULTS: As CSS-CAD was closely correlated with the multiplicity of photo(contact) allergens, particularly photoallergens, three or more photoallergens were detected in the severe CAD group (52.5%); less in the moderate group (32.8%); and only one in the mild group (14.8%; P = .025). In the groups showing greater severity of disease, the absolute numbers of IFN-γ+ , IL-17+ , CD4+, CD8+, common-γ chain receptor (common-γCR)+ , and CD69+ tissue-resident memory cells increased on average; there was also an increase in the CD4+/CD8+ cell ratio, with the more severely affected groups. However, the levels of TNF-α+ and FoxP3+ regulatory T (Treg) cells and the mean IL-17/IFN-γ cell ratio decreased in the more severely affected CSS-CAD subgroups. CONCLUSIONS: Based on the clinical analysis and immunopathogenic results, avoidance of excessive sun exposure, and topical and systemic blocking agents for photo(contact) allergens are recommended. Additionally, conventional immunomodulators and emerging agents including JAK-STAT inhibitors may be administered for CAD treatment in the future.

Molecular Engineering of Printed Semiconducting Blends to Develop Organic Integrated Circuits: Crystallization, Charge Transport, and Device Application Analyses.

Solution-based printing has contributed to the facile deposition of various types of materials, including the building blocks of printed electronics. In particular, solution-processable organic semiconductors (OSCs) are regarded as one of the most fascinating candidates for the fabrication of printed electronics. Herein, we report electrohydrodynamic (EHD) jet-printed p- and n-type OSCs, namely 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-PEN) and 6,13-bis((triisopropylsilyl)ethynyl)-5,7,12,14-tetraazapentacene (TIPS-TAP), and their use as single-OSC layers and as OSC mixed p-n layers to fabricate solution-processed p-, n-, and ambipolar-type organic field-effect transistors (OFETs). Use of the dragging mode of EHD jet printing, a process driven under a low electrostatic field with a short nozzle-to-substrate distance, was found to provide favorable conditions for growth of TIPS-PEN and TIPS-TAP crystals. In this way, the similar molecular structures of TIPS-PEN and TIPS-TAP yielded a homogeneous solid solution and showed ambipolar transport properties in OFETs. Therefore, the combination of single- and mixed-OSC layers enabled the preparation of various charge-transported devices from unit to integrated devices (NOT, NAND, NOR, and multivalued logic). Therefore, this fabrication technology can be useful for assisting in the production of OSC layers for practical applications in the near future.

Electrohydrodynamic-Jet-Printed Phthalimide-Derived Conjugated Polymers for Organic Field-Effect Transistors and Logic Gates.

A π-conjugated polymer semiconductor, PBDTTTffPI, was synthesized for use as an organic semiconductor suitable for electrohydrodynamic (EHD) jet printing technology. Bulky alkylation of the polymer gave PBDTTTffPI good solubility in several organic solvents. EHD jet printing using PBDTTTffPI ink produced direct patterns of polymer semiconductors while maintaining smooth surface morphologies and crystal structures similar to those of spin-coated PBDTTTffPI films. EHD-jet-printed PBDTTTffPI was appropriate for use as a semiconductor layer in organic field-effect transistors (OFETs) and logic gates. OFETs that used EHD-jet-printed PBDTTTffPI had better electrical characteristics than devices that used spin-coated semiconductor films. When a dielectric material (Al2O3) with a high dielectric constant was introduced, the jet-printed PBDTTTffPI operated well at low voltages. Integrated devices such as inverters, NAND gates, and NOR gates were fabricated by printing PBDTTTffPI patterns and showed good switching behaviors. Therefore, the use of printable PBDTTTffPI provides an advance toward fabrication of practical integrated arrays in next-generation devices.

Mass-Synthesized Solution-Processable Polyimide Gate Dielectrics for Electrically Stable Operating OFETs and Integrated Circuits.

Polyimides (PIs) are widely utilized polymeric materials for high-temperature plastics, adhesives, dielectrics, nonlinear optical materials, flexible hard-coating films, and substrates for flexible electronics. PIs can be facilely mass-produced through factory methods, so the industrial application value is limitless. Herein, we synthesized a typical poly(amic acid) (PAA) precursor-based solution through an industrialized reactor for mass production and applied the prepared solution to form thin films of PI using thermal imidization. The deposited PI thin films were successfully applied as gate dielectrics for organic field-effect transistors (OFETs). The PI layers showed suitable characteristics for dielectrics, such as a smooth surface, low leakage current density, uniform dielectric constant (k) values regardless of frequency, and compatibility with organic semiconductors. Utilizing this PI layer, we were able to fabricate electrically stable operated OFETs, which exhibited a threshold voltage shift lower than 1 V under bias-stress conditions and a field-effect mobility of 4.29 cm2 V-1 s-1. Moreover, integrated logic gates were manufactured using these well-operated OFETs and displayed suitable operation behavior.

Electrohydrodynamic-Jet-Printed Cinnamate-Fluorinated Cross-Linked Polymeric Dielectrics for Flexible and Electrically Stable Operating Organic Thin-Film Transistors and Integrated Devices.

Herein, printable polymer series containing different portions of cinnamate and perfluorinated phenyl functionalities, namely, polyperfluorostyrene-co-poly(vinylbenzyl cinnamates) (PFS-co-PVBCi (x:y)) copolymers, were synthesized and applied as gate dielectrics for organic thin-film transistors (OTFTs). The polymeric dielectrics were successfully printed via electrostatic force-assisted dispensing mode of electrohydrodynamic jet printing. The dielectric characteristics of the printed polymers, such as surface energy, dielectric constant, leakage current, atomic depth profiles, and deposited semiconducting layer characteristics, were clearly identified. In particular, the difference in driving stability of OTFTs according to the type of polymer was analyzed in detail and a possible mechanism was proposed. Results suggested that PFS-co-PVBCi (3:7) led to optimized consequences, yielding an almost negligible Vth shift under continuous bias stress. Through this, we successfully implemented flexible OTFT and logic devices using printed PFS-co-PVBCi (3:7) dielectrics with stable operation properties. Therefore, we believe that this study will facilitate the printing and synthesis of polymer dielectrics to produce printed and flexible OTFTs.

The OsERF115/AP2EREBP110 Transcription Factor Is Involved in the Multiple Stress Tolerance to Heat and Drought in Rice Plants.

The AP2/EREBP family transcription factors play important roles in a wide range of stress tolerance and hormone signaling. In this study, a heat-inducible rice ERF gene was isolated and functionally characterized. The OsERF115/AP2EREBP110 was categorized to Group-IIIc of the rice AP2/EREBP family and strongly induced by heat and drought treatment. The OsERF115/AP2EREBP110 protein targeted to nuclei and suppressed the ABA-induced transcriptional activation of Rab16A promoter in rice protoplasts. Overexpression of OsERF115/AP2EREBP110 enhanced thermotolerance of seeds and vegetative growth stage plants. The OsERF115/AP2EREBP110 overexpressing (OE) plants exhibited higher proline level and increased expression of a proline biosynthesis P5CS1 gene. Phenotyping of water use dynamics of the individual plant indicates that the OsERF115/AP2EREBP110-OE plant exhibited better water saving traits under heat and drought combined stress. Our combined results suggest the potential use of OsERF115/AP2EREBP110 as a candidate gene for genetic engineering approaches to develop heat and drought stress-tolerant crops.

Strategy for Selective Printing of Gate Insulators Customized for Practical Application in Organic Integrated Devices.

Direct drawing techniques have contributed to the ease of patterning soft electronic materials, which are the building blocks of analog and digital integrated circuits. In parallel with the printing of semiconductors and electrodes, selective deposition of gate insulators (GI) is an equally important factor in simplifying the fabrication of integrated devices, such as NAND and NOR gates, and memory devices. This study demonstrates the fabrication of six types of printed GI layers (high/low-k polymer and organic-inorganic hybrid material), which are utilized as GIs in organic field-effect transistors (OFETs), using the electrostatic-force-assisted dispensing printing technique. The selective printing of GIs on the gate electrodes enables us to develop practical integrated devices that go beyond unit OFET devices, exhibiting robust switching performances, non-destructive operations, and high gain values. Moreover, the flexible integrated devices fabricated using this technique exhibit excellent operational behavior. Therefore, this facile fabrication technique can pave a new path for the production of practical integrated device arrays for next-generation devices.

Direct Patterned Zinc-Tin-Oxide for Solution-Processed Thin-Film Transistors and Complementary Inverter through Electrohydrodynamic Jet Printing.

The solution-processed deposition of metal-oxide semiconducting materials enables the fabrication of large-area and low-cost electronic devices by using printing technologies. Additionally, the simple patterning process of these types of materials become an important issue, as it can simplify the cost and process of fabricating electronics such as thin-film transistors (TFTs). In this study, using the electrohydrodynamic (EHD) jet printing technique, we fabricated directly patterned zinc-tin-oxide (ZTO) semiconductors as the active layers of TFTs. The straight lines of ZTO semiconductors were successfully drawn using a highly soluble and homogeneous solution that comprises zinc acrylate and tin-chloride precursors. Besides, we found the optimum condition for the fabrication of ZTO oxide layers by analyzing the thermal effect in processing. Using the optimized condition, the resulting devices exhibited satisfactory TFT characteristics with conventional electrodes and conducting materials. Furthermore, these metal-oxide TFTs were successfully applied to complementary inverter with conventional p-type organic semiconductor-based TFT, showing high quality of voltage transfer characteristics. Thus, these printed ZTO TFT results demonstrated that solution processable metal-oxide transistors are promising for the realization of a more sustainable and printable next-generation industrial technology.

Direct Printing of Asymmetric Electrodes for Improving Charge Injection/Extraction in Organic Electronics.

Engineering the energy levels of organic conducting materials can be useful for developing high-performance organic field-effect transistors (OFETs), whose electrodes must be well controlled to facilitate easy charge carrier transport from the source to drain through an active channel. However, symmetric source and drain electrodes that have the same energy levels are inevitably unfavorable for either charge injection or charge extraction. In this study, asymmetric source and drain electrodes are simply prepared using the electrohydrodynamic (EHD)-jet printing technique after the careful work function engineering of organic conducting material composites. Two types of additives effectively tune the energy levels of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate-based composites. These solutions are alternately patterned using the EHD-jet printing process, where the use of an electric field makes fine jet control that enables to directly print asymmetric electrodes. The asymmetric combination of EHD-printed electrodes helps in obtaining advanced charge transport properties in p-type and n-type OFETs, as well as their organic complementary inverters. This strategy is believed to provide useful guidelines for the facile patterning of asymmetric electrodes, enabling the desirable properties of charge injection and extraction to be achieved in organic electronic devices.

Facile Photo-cross-linking System for Polymeric Gate Dielectric Materials toward Solution-Processed Organic Field-Effect Transistors: Role of a Cross-linker in Various Polymer Types.

Energy-efficient solution-processed organic field-effect transistors (OFETs) are highly sought after in the low-cost printing industry as well as for the manufacture of flexible and other next-generation devices. The fabrication of such electronic devices requires high-functioning insulating materials that are chemically and mechanically robust to avoid lowering insulating properties during the device fabrication process or utilization of devices. In this study, we report a facile, fluorinated, UV-assisted cross-linker series using a fluorophenyl azide (FPA), which reacts with the C-H groups of a conventional polymer. This demonstrates the application of the cross-linked films in OFET gate dielectrics. The effects of the cross-linkable chemical structure of the FPA series on the cross-linking chemistry, photopatternability, and dielectric properties of the resulting films are investigated for low/high-k or amorphous/crystalline polymeric gate dielectric materials. The characteristics of insulating layers and behavior of OFETs containing these cross-linked gate dielectrics (for example, leakage current density (J), hysteresis, and charge trap density) depend on the polymer type. Furthermore, an organic-based complementary inverter and various printable OFETs with excellent electrical characteristics are successfully fabricated. Thus, these reported cross-linkers that enable the solution process and patterning of well-developed conventional polymer dielectric materials are promising for the realization of a more sustainable next-generation industrial technology for flexible and printable devices.

Optimization of Hydroxypropyl Methylcellulose and Dextrin in Development of Dried Nanosuspension for Poorly Water-Soluble Drug.

The purpose of this study is to identify the effects of a stabilizer and matrix former in the development of a celecoxib dried nanosuspension (DNS) for high dissolution rate and drug loading. Tween 80 and Hydroxypropyl Methylcellulose (HPMC) were used as stabilizers in the bead-milling process and dextrin was used as the matrix former in the spray-drying. Various nanosuspensions (NS) were prepared by varying the ratio of HPMC and dextrin, and the physicochemical properties of each formulation were evaluated for particle size, morphology, drug loading, crystallinity, redispersibility, physical stability and dissolution rate. HPMC efficiently stabilized the NS system and reduced the particle size of NS. The mean particle size of the NS with 0.5% HPMC (w/v) was the smallest (248 nm) of all formulations. Dextrin has been shown to inhibit the increase of particle size efficiently, which is known to occur frequently when NS is being solidified. As the dextrin increased in DNS, the dissolution rates of reconstituted NS were significantly improved. However, it was confirmed that more than the necessary amount of dextrin in DNS reduced the dissolution and drug loading. The dissolution of celecoxib in DNS prepared at the ratio (drug:dextrin, 1:2.5) was almost the highest. The dissolution of optimal formulation was 95.8% at 120 min, which was 2.0-fold higher than that of NS dried without dextrin. In conclusion, these results suggest that the formulation based on Tween 80, HPMC and dextrin may be an effective option for DNS to enhance its in vitro dissolution and in vivo oral absorption.