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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.

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree ( Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of M. alba fruit resulted in the isolation and identification of six phytosterols ( 1 - 6 ). Their structures were determined as 7-ketositosterol ( 1 ), stigmast-4-en-3β-ol-6-one ( 2 ), (3β,6α)-stigmast-4-ene-3,6-diol ( 3 ), stigmast-4-ene-3β,6β-diol ( 4 ), 7β-hydroxysitosterol 3-O-β-d-glucoside ( 5 ), and 7α-hydroxysitosterol 3-O-β-d-glucoside ( 6 ) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound 1 displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound 1 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 1 significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound 1 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol ( 1 ) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.

A free-standing catalyst electrode for the urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) in a urea electrolysis cell was synthesized by electroplating a Ni-Fe alloy onto carbon felt, followed by phosphidation (P-NiFe@CF). The prepared P-NiFe@CF catalyst consisted of Ni 5 P 4 , NiP 2 , and FeP with 3D flower-like P-NiFe architecture on CF. P-NiFe@CF exhibited excellent electrocatalytic activity for the UOR (demanding only 1.39 V (vs. RHE) to achieve 200 mA cm -2 ), and for the HER with a low overpotential of 0.023 V (vs. RHE) at 10 mA cm -2 , indicating its feasibility as a bifunctional catalyst electrode for urea electrolysis. A urea electrolysis cell with P-NiFe@CF as both the free-standing anode and cathode generated a current density of 10 mA cm -2 at a cell potential of 1.37 V (vs. RHE), which is considerably lower than that of water electrolysis, and also lower than previously reported values. The results indicate that the P-NiFe@CF catalyst electrodes can be used as free-standing bifunctional electrodes for urea electrolyzers., (© 2021. The Author(s).)

The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic β-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced insulin secretion in response to high glucose levels with no toxic effects on INS-1 cells. The effect of schisandrin C was superior to that of gliclazide (positive control), a drug commonly used to treat type 2 diabetes (T2D). In addition, western blot analysis showed that the expression of associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), phosphatidylinositol 3-kinase (PI3K), Akt, and insulin receptor substrate-2 (IRS-2), was increased in INS-1 cells after treatment with schisandrin C. In addition, insulin secretion effect of schisandrin C were enhanced by the Bay K 8644 (L-type Ca 2+ channel agonist) and glibenclamide (K + channel blocker), were abolished by the nifedipine (L-type Ca 2+ channel blocker) and diazoxide (K + channel activator). Moreover, schisandrin C enhanced glucose uptake with no toxic effects on C2C12 cells. Western blot analysis showed that the expression of associated proteins, including insulin receptor substrate-1 (IRS-1), AMP-activated protein kinase (AMPK), PI3K, Akt, glucose transporter type 4 (GLUT-4), was increased in C2C12 cells after treatment with schisandrin C. Schisandrin C may improve hyperglycemia by enhancing insulin secretion in pancreatic β-cells and improving glucose uptake into skeletal muscle cells. Our findings may provide evidence that schisandrin C may be beneficial in devising novel anti-T2D strategies.

A highly electroactive Ni-based catalyst for urea oxidation is prepared by a sol-gel method with bubbling of gel mixture. It is observed that the conditions for the gel formation strongly affect the morphology and electrochemical properties of the catalyst materials. As synthesized Ni-catalysts are characterized by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The Ni-based catalyst prepared at optimum conditions in the scope of this study exhibits the urea oxidation activity of 570 mA mg -1 (at 0.54 V). In a single urea/hydrogen peroxide fuel cell test, the Ni-catalyst provides maximum power densities of 19.6 and 36.4 mW cm -2 at 30 and 70 °C, respectively. Additionally, the cell catalyst shows a stable voltage for 3 days. Thus, this work suggests that a novel Ni-based catalyst derived from a facile method can be used for urea oxidation and as an efficient anode material for urea fuel cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Highly porous self-assembled nanostructured Ni@C and NiO@C were synthesized via calcination of a Ni-based metal-organic framework. The morphology, structure, and composition of as synthesized Ni@C and NiO@C were characterized by SEM, FIB-SEM, TEM, and XRD. The electro-catalytic activity of the Ni@C and NiO@C catalysts towards urea oxidation was investigated using cyclic voltammetry. It was found that the Ni@C had a higher residual carbon content and a higher specific surface area than NiO@C, thus exhibiting an enhanced electrochemical performance for urea oxidation. A direct urea fuel cell with Ni@C as an anode catalyst featured an excellent maximum power density of 13.8 mW cm -2 with 0.33 M urea solution in 1 M KOH as fuel and humidified air as oxidant at 50 °C, additionally showing excellent stability during continuous 20-h operation. Thus, this work showed that the highly porous carbon-supported Ni catalysts derived from Ni-based metal-organic framework can be used for urea oxidation and as an efficient anode material for urea fuel cells.

We previously reported that human cytomegalovirus (HCMV) 86 kDa immediate-early 2 gene product (IE86) promotes proteasome-dependent degradation of STING. In the present study, we determined the specific residues of IE86 responsible for STING degradation using a STING-firefly luciferase fusion protein expression system for quantitative meas-urement of STING protein levels. IE86 amino acids (aa) 136-289 were sufficient to promote STING degradation and further induced down-regulation of 2'3'-cyclic GMP-AMP (cGAMP)-mediated IFN-β promoter activation. Interestingly, transactivation domains (TAD) of the IE86 protein located at the N- and C-termini were required for down-regulation of Toll/interleukin-1 receptor (TIR) domain-containing adaptor-inducing interferon β (IFN-β) (TRIF)-mediated IFN-β-and p65/RelA-induced NF-κB-dependent promoter activation while amino acids (aa) 136-289 had no significant effects. Our collective data suggest that the IE86 protein utilizes the aa 136-289 region to promote STING degradation and inhibit the cGAS-STING pathway.

Anion exchange membrane fuel cells (AEMFCs) have captivated vast interest due to non-platinum group metal catalysts and fuel flexibility. One of the major shortcomings of AEMFCs, however, is the lack of a stable and high anion conducting membrane. This study introduces a new strategy for fabrication of high conducting anion exchange membrane (AEM) using a hybrid nanocomposite of graphene oxide (GO), cellulose, and poly(phenylene oxide) (PPO), which are functionalized with 1,4-diazabicyclo[2.2.2]octane. The compositional ratio of GO/cellulose/PPO was optimized with respect to ionic conductivity, water uptake, swelling ratio, and mechanical properties. The membrane at GO/cellulose/PPO weight ratio of 1/1/100 displayed an impressive hydroxyl conductivity of ∼114 mS/cm at 25 °C and ∼215 mS/cm at 80 °C, which is considerably higher than the highest value reported. Further, the hybrid composite membranes were mechanically stable even when operating at high temperature (80 °C). The result indicates that the introduction of quaternized GO and cellulose into a polymer matrix is a promising approach for designing high performance AEMs.

Graphene aerogel-supported manganese ferrite (Mn x Fe 3-x O 4 /GAs) and reduced-graphene oxide/manganese ferrite composite (MnFe 2 O 4 /rGO) were synthesized and studied as cathode catalysts for oxygen reduction reactions in urea/O 2 fuel cells. MnFe 2 O 4 /GAs exhibited a 3D framework with a continuous macroporous structure. Among the investigated Fe/Mn ratios, the more positive oxygen reduction onset potential was observed with Fe/Mn=2/1. The half-wave potential of MnFe 2 O 4 /GAs was considerably more positive than that of MnFe 2 O 4 /rGO and comparable with that of Pt/C, while the stability of MnFe 2 O 4 /GAs significantly higher than that of Pt/C. The best urea/O 2 fuel cell performance was also observed with the MnFe 2 O 4 /GAs. The MnFe 2 O 4 /GAs exhibited an OCV of 0.713 V and a maximum power density of 1.7 mW cm -2 at 60 °C. Thus, this work shows that 3D structured graphene aerogel-supported MnFe 2 O 4 catalysts can be used as an efficient cathode material for alkaline fuel cells., Competing Interests: The authors declare no conflict of interest.

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans worldwide. Although hepatitis E is self-limiting without chronic infection development, HEV infection often leads to severe liver diseases causing high mortality in pregnant women in addition to chronic hepatitis and cirrhosis in immunosuppressed patients. In this study, we investigated the effect of a Liriope platyphylla ethanol extract (LPE) on HEV replication. Interestingly, LPE suppressed replication of the genotype 3 HEV replicon. Sequential solvent fractionation revealed that the ethyl acetate (EA) fraction of LPE exerts the most potent inhibitory effects. With the aid of activity-guided fractionation and multi-step column chromatography, spicatoside A was subsequently isolated in the EA fraction of LPE and specifically shown to exert inhibitory effects on replication of the genotype 3 HEV replicon. In addition, spicatoside A interfered with replication of the HEV genotype 3 strain 47832c and expression of HEV ORF2 capsid proteins. Our findings clearly support the potential utility of spicatoside A as an effective anti-HEV agent.

Ni-based catalysts have been considered as an efficient anode material for urea fuel cells due to the low cost and high activity in alkaline media. Herein, we demonstrate that Ni-Co bimetallic nanoparticles decorated carbon nanotube aerogels as catalysts for urea oxidation reaction (UOR) can be synthesized by a polyol reduction and sol-gel method. The morphology, structure, and composition of the Ni-Co/MWCNT aerogels were characterized by scanning electron microscopy and X-Ray diffraction. The electro-catalytic activity of the Ni-Co/MWCNT aerogels towards UOR was investigated using cyclic voltammetry. It was found that the Co-doping at 25% (Co/Ni) significantly increased the oxidation peak current and reduced the overpotential of the UOR. Furthermore, the MWCNT aerogel support also remarkably enhanced electro-catalytic activity by providing a high surface area and fast mass transport for the UOR owing to the porous 3D network structures with uniform distribution of Ni-Co nanoparticles. Urea/O 2 fuel cell with Ni-Co/MWCNT aerogel as anode material exhibited an excellent performance with maximum power density of 17.5 mWcm -2 with an open circuit voltage of 0.9 V. Thus, this work showed that the highly porous three-dimensional Ni-Co/MWCNT aerogel catalysts can be used for urea oxidation and as an efficient anode material for urea fuel cells.

Hepatitis E virus (HEV) is an etiological agent of acute hepatitis E, a self-limiting disease prevalent in developing countries. HEV can cause fulminant hepatic failure with high mortality rates in pregnant women, and genotype 3 is reported to trigger chronic hepatitis in immunocompromised individuals worldwide. Screening of plant extracts for compounds with potential anti-HEV effects led to the identification of a 70% ethanol extract of Lysimachia mauritiana (LME) that interferes with replication of the swine HEV genotype 3 replicon. Furthermore, LME significantly inhibited replication of HEV genotype 3 and expression of HEV ORF2 in infected cells without exerting cytotoxic effects. Collectively, our findings demonstrate the potential utility of LME in the development of novel antiviral drugs against HEV infection.

Various drug-eluting stents (DESs) have been developed to prevent restenosis after stent implantation. However, DES still needs to improve the drug-in-polymer coating stability and control of drug release for effective clinical treatment. In this study, the cobalt-chromium (CoCr) alloy surface was coated with biodegradable poly(D,L-lactide) (PDLLA) and sirolimus (SRL) mixed with hydrophilic Pluronic F127 additive by using ultrasonic spray coating system in order to achieve a stable coating surface and control SRL release. The degradation of PDLLA/SRL coating was studied under physiological solution. It was found that adding F127 reduced the degradation of PDLLA and improved the coating stability during 60days. The effects of organic solvent such as chloroform and tetrahydrofuran (THF) on the coating uniformity were also examined. It was revealed that THF produced a very smooth and uniform coating compared to chloroform. The patterns of in vitro drug release according to the type of organic solvent and hydrophilic additive proposed the possibility of controllable drug release design in DES. It was found that using F127 the drug release was sustained regardless of the organic solvent used. In addition, THF was able to get faster and controlled release profile when compared to chloroform. The structure of SRL molecules in different organic solvents was investigated using ultra-small angle neutron scattering. Furthermore, the structure of SRL is concentration-dependent in chloroform with tight nature under high concentration, but concentration-independent in THF. These results strongly demonstrated that coating stability and drug release patterns can be changed by physicochemical properties of various parameters such as organic solvents, additive, and coating strategy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Rapid re-endothelialization of damaged vessel lining efficiently prevents restenosis and thrombosis and restores original vascular functions. In this study, we designed a novel metallic stent with a heparin-modified surface and used different methods, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and divinyl sulfone (DVS), to load growth factors. First we loaded heparin into a dopamine-conjugated hyaluronic acid (HA) coating to serve as a growth factor reservoir. In a second step, we took advantage of the heparin-binding domain of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to gain advanced re-endothelialization capabilities. We demonstrated that DVS technique offered higher amount of growth factor loading. In vitro assessment also showed better capillary-like structure formation and localized gap junctions when DVS coating was employed. This study suggested that growth factor loaded stent modified by HA and heparin provided the advantage to rapid and tight restoration of endothelium., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt-chromium (Co-Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co-Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co-Cr, but fails after 7weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Biocompatibility, sensing, and self-actuation are very important features for a therapeutic biomedical microrobot. As a new concept for tumor theragnosis, this paper proposes a monocyte-based microrobots, which are combining the phagocytosis and engulfment activities containing human acute monocytic leukemia cell line (THP-1) with various sized polystyrene microbeads are engulfed instead of a therapeutic drug. For the validation of the blood vessel barrier-penetrating activity of the monocyte-based microrobot, we fabricate a new cell migration assay with monolayer-cultured endothelial cell (HUVEC), similar with the blood vessels. We perform the penetrating chemotactic motility of the monocyte-based microrobot using various types of the chemo-attractants, such as monocyte chemotactic protein (MCP)-1, human breast cancer cell lines (MCF7)-cell lysates, and -contained alginate spheroids. The monocyte-based microrobot show chemotactic transmigrating motilities similar with what an actual monocyte does. This new paradigm of a monocyte-based microrobot having various useful properties such as biocompatibility, sensing, and self-actuation can become the basis of a biomedical microrobot using monocytes for diagnosis and therapy of various diseases., (© 2014 Wiley Periodicals, Inc.)

Sirolimus (SRL) release from the biodegradable poly(l-lactic-co-glycolic acid) (PLGA) matrix was investigated for the application of drug-eluting stents (DES). In particular, this study focused on whether various organic solvents affect the interaction between SRL and PLGA and the formation of microstructures during ultrasonic coating. The SRL-loaded PLGA coated by tetrahydrofuran or acetone showed a significant initial burst, whereas that from acetonitrile was constantly released during a period of 21 days. On the basis of these results, the interactions at the molecular level of SRL with the polymer matrix were estimated according to various organic solvents. Although the topographies of the coated surface were obviously different, the correlation between surface roughness and SRL release was very poor. Irrespective of organic solvents, FT-IR data showed significantly weak SRL-PLGA interactions. From the result of wide-angle X-ray diffraction, it was confirmed that SRL was dispersed in an amorphous state in the polymer matrix after ultrasonic coating. The glass-transition temperature was also influenced by organic solvents, resulting in a plasticizing effect. The particle size of SRL appeared to determine the release profile from the PLGA matrix, which was the combination of diffusion and polymer degradation at an SRL size of more than 800 nm and the Fickian release at that of less than 300 nm. Therefore, organic solvents can lead to a heterogeneous microstructure in the SRL-loaded PLGA matrix, which is at or near the surface, consisting of aggregated drug- and polymer-rich regions. It is expected that the drug release can be controlled by physicochemical properties of organic solvents, and this study can be used effectively for localized drug release in biomedical devices such as drug-eluting stents.

During the balloon expansion of several commercially available drug-eluting stents, various types of defects in the polymer layer have been observed. The aim of this study is to prevent these defects by increasing the interfacial adhesion between the metal substrate and the drug-in-polymer matrix using poly(caprolactone) (PCL) brushes onto a cobalt-chromium (Co-Cr or CC) alloy surface. The chemical modification of the Co-Cr surface was accomplished by grafting ricinoleic acid (RA) onto the metal substrate followed by surface-initiated ring opening polymerization of ε-caprolactone. The unmodified, RA-grafted (CC-RA), and PCL-grafted Co-Cr substrates (CC-RA-PCL3D and CC-RA-PCL6D) were characterized by various surface analyses. Poly(d,l-lactide) containing sirolimus was spray coated onto the unmodified and modified substrates. The adhesion property of the polymer coating on the PCL-grafted surfaces was improved compared to those of other samples. Among all of the drug-in-polymer coated samples, both CC-RA-PCL3D and CC-RA-PCL6D exhibited a stabilized drug release profile over 49 days. It was also revealed that CC-RA-PCL6D showed the slowest drug release of all the samples. On the basis of these results, the proposed nanocoupling method has shown not only improved adhesion of the drug-in-polymer matrix to the Co-Cr substrate but also controlled drug release.

A systematic review, covering fabrication of nanoscale patterns by laser interference lithography (LIL) and their applications for optical devices is provided. LIL is a patterning method. It is a simple, quick process over a large area without using a mask. LIL is a powerful technique for the definition of large-area, nanometer-scale, periodically patterned structures. Patterns are recorded in a light-sensitive medium that responds nonlinearly to the intensity distribution associated with the interference of two or more coherent beams of light. The photoresist patterns produced with LIL are the platform for further fabrication of nanostructures and growth of functional materials used as the building blocks for devices. Demonstration of optical and photonic devices by LIL is reviewed such as directed nanophotonics and surface plasmon resonance (SPR) or large area membrane reflectors and anti-reflectors. Perspective on future directions for LIL and emerging applications in other fields are presented.

A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber., (© 2013 Wiley Periodicals, Inc.)