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This study describes the fabrication and characteristics of microneedle array electrodes (MAEs) using Bismuth–Indium–Tin (Bi–In–Sn) alloys. The MAEs consist of 57 pyramid-shaped needles measuring 340 μm wide and 800 μm high. The fabrication process involved micromolding the alloys in a vacuum environment. Physical tests demonstrated that Bi–In–Sn MAEs have good mechanical strength, indicating their suitability for successful skin penetration. The electrode–skin interface impedance test confirmed that Bi–In–Sn MAEs successfully penetrated the skin. Impedance measurements revealed the importance of insulating the microneedle electrodes for optimal electrical performance, and a UV-curable Polyurethane Acrylate coating was applied to enhance insulation. Electrocardiogram measurements using the Bi–In–Sn MAEs demonstrated performance comparable to that of traditional Ag/AgCl electrodes, which shows promise for accurate data collection. Overall, the study demonstrates successful, minimally-invasive skin insertion, improved electrical insulation, and potential applications of Bi–In–Sn microneedle array. These findings contribute to advancements in microneedle technology for biomedical applications. [ABSTRACT FROM AUTHOR]

A wound evolves with variable pHs depending on the healing stage, and the maintenance of mild acidic condition can help healing by deterring the formation of a biofilm. Herein, a dual‐layer wound dressing with an acid‐responsive zeolitic imidazolate framework–8 (ZIF‐8) layer and an acid‐modulating layer is designed to control the acid‐dependent release of therapeutic agents for the improved healing process. The outer dressing layer is coated with curcumin‐incorporated ZIF‐8, where curcumin and zinc ions are released upon dissociation of ZIF‐8 in an acidic condition. The inner layer, a pH modulator, is fabricated by electrospinning polyvinylpyrrolidone with addition of acetic acid. In vitro release test shows that the outer layer dressing attains a considerably higher release of curcumin and Zn2+ under an acidic condition. Combined with the inner acidic layer, the dual layer dressing exhibits facilitated release of effective agents regardless of environmental pHs, attributed to the proper pH modulation to about 6.5. The anti‐oxidant activity of curcumin and antibacterial activity of Zn2+ are confirmed. The study highlights the novel proof‐of‐concept design of active wound dressing demonstrating the dual functions of pH regulation and the stimulus‐responsive drug delivery. [ABSTRACT FROM AUTHOR]

Dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by self-DNA contributes to interferonopathy and promotes autoimmune diseases. To identify potential suppressors of STING-induced type I interferon (IFN) induction, ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-ß promoter activation. Notably, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1- or IRF3-induced, IFN-ß promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-ß promoter activation were identified as ester alkaloids isolated from the genus, Cephalotaxus, homoharringtonine and harringtonine. Furthermore, these two compounds inhibited 2’3’-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity. [ABSTRACT FROM AUTHOR]

Kaempferol, a natural flavonoid abundantly found in plants, is known to have pharmacological properties, such as anti-inflammatory and anti-cancer effects. In this study, we investigated the antiviral effects of kaempferol against a varicella-zoster virus (VZV) clinical isolate in vitro. We found that kaempferol significantly inhibited VZV replication without exhibiting cytotoxicity. Kaempferol exerted its antiviral effect at a similar stage of the VZV life cycle as acyclovir, which inhibits VZV DNA replication. Taken together, our results suggest that kaempferol inhibits VZV infection by blocking the DNA replication stage in the viral life cycle. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection is commonly reported in countries of Northeast Asia including China, Japan and South Korea. The majority of the SFTS patients are elderly and the average fatality rate is more than 10%. A rapid and sensitive diagnostic method to monitor and prevent SFTSV transmission remains an urgent clinical challenge. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections with the reaction time of 50 min from blood plasma without cross-reactivity to other viruses, supporting its application for rapid and sensitive diagnosis of SFTS. Author summary: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by Dabie bandavirus, also known as SFTSV, and reported in countries of Northeast Asia including China, Japan and South Korea. The average fatality rate is more than 10% and reported to increase with age. Currently, no vaccines or targeted treatments for SFTS are available and only symptomatic therapy is offered. Thus, SFTSV diagnosis at early stages is critical for successful therapeutic outcomes. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections under isothermal conditions with the reaction time of 50 min from blood plasma. [ABSTRACT FROM AUTHOR]

• A microfluidic device integrated with arrays of microelectrode was developed to continuously produce cell-free VZV. • Multiple constricted channels and microelectrode arrays were designed to generate a high electrolysis efficiency. • The integrated microfluidic platform accomplished a production yield of 1.4 – 2.1×104 PFU mL–1 of cell-free VZV. • Rapid and high-throughput production of the high-titer cell-free viruses was obtained with relatively low voltage input. Varicella-zoster virus (VZV), the causative agent of varicella and herpes zoster, is highly cell-associated and spreads via cell-to-cell contact in tissue culture. The lack of cell-free VZV hampers studies on VZV biology as well as antiviral and vaccine development. In the present study, a poly(methylmethacrylate) microfluidic device integrated with arrays of microelectrode was fabricated to continuously electrolyse VZV-infected cells to produce cell-free viruses. By designing multiple constrictions and microelectrode arrays, a high electric field is focused on the constricted region of the microchannel to disrupt large numbers of virus-infected cells with high-throughput on a microfluidic platform. Plaque assay and scanning electron microscopy were conducted to quantify and characterize cell-free VZV produced using the microfluidic continuous-flow electrical cell lysis device. The process of microfluidic electrical cell lysis followed by subsequent filtration and virus concentration process yielded a 1.4–2.1 × 104 plaque-forming units (PFUs) per mL of cell-free VZV from 7.0 × 106 VZV-infected human foreskin fibroblasts (HFF) cells. The high electric field formed inside a microfluidic channel combined with the continuous-flow of virus-infected cells within the microchannel enabled the rapid and efficient production of high-titer cell-free virus in large quantities with relatively low input of the voltage. [ABSTRACT FROM AUTHOR]

We previously reported that the ethyl acetate (EtOAc) fraction of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) inhibits varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) replication in vitro. PGG (1,2,3,4,6-penta-O-galloyl-ß-D-glucose) is a major chemical constituent of the EtOAc fraction of ESE that inhibits VZV but not HCMV replication. In this study, we comprehensively screened the chemical compounds identified in the EtOAc fraction of ESE for potential antiviral properties. Among the examined compounds, quercetin and isoquercitrin displayed potent antiviral activities against both VZV and HCMV with no significant cytotoxic effects. Both compounds strongly suppressed the expression of VZV and HCMV immediate–early (IE) genes. Our collective results indicated that, in addition to PGG, quercetin and isoquercitrin are bioactive compounds in the EtOAc fraction of ESE that effectively inhibit human herpesvirus replication. [ABSTRACT FROM AUTHOR]