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Corresponding to marine environmental regulations is important in shipbuilding and marine industries. The application of lightweight composite materials on ships is an effective approach to reducing the emission of greenhouse gases. The mechanical fastening method is a good candidate to assemble composites and conventional metals. The joint geometric and environmental effects are two important factors in mechanically fastened ship and marine structures. In this study, we evaluated the W/D (hole diameter to width ratio) and environmental effects on the bearing strength and failure mode of a mechanically fastened non-crimp fabric (NCF) composite material. To consider the effect of joint geometry, wherein hole diameters of 5, 6, 8, and 10 mm were machined. Further, by selecting three environmental conditions (UV, saltwater and low temperature), we evaluated environmental effects on bearing strength and failure modes of NCF composite specimens. The bearing strength increased as W/D decreased, and the bearing strength of the specimen exposed to low temperature and UV environments increased, while that of the specimen exposed to saltwater remained the same. From the failure mode analysis, the specimen that was exposed to salt fog showed the same failure mode as the unaged specimen. It was observed that the changes in the transition section and new failure mode in the xenon arc and low-temperature specimens.

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[ d ]thiazole scaffold, we explored phenolic compounds 1 - 15 with 2-phenylbenzo[ d ]oxazole, which is isosterically related to 2-phenylbenzo[ d ]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3 , 8 , and 13 , featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC 50 value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3 , 8 , and 13 , while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[ d ]oxazole is a promising candidate for tyrosinase inhibition.

Piezoelectric composites, which consist of piezoelectric materials and polymers, are widely employed in various applications such as underwater sonar transducers and medical diagnostic ultrasonic transducers. Acoustic transducers based on piezoelectric composites can have high sensitivity with broad bandwidth. In recent studies, it is demonstrated that 2-2 composites based on single crystals provide further increased sensitivity and wide bandwidth. In order to utilize a 2-2 composite in acoustic sensors, it is required to demonstrate the full material coefficients of the 2-2 composite. In this study, we investigated an analytic solution for determining equivalent material coefficients of a 2-2 composite. Impedance spectrums of the single-phase resonators with equivalent material coefficients and 2-2 composite resonators were compared by the finite element method in order to verify the analytic solutions. Furthermore, the equivalent material coefficients derived from the analytic solution were also verified by comparing the measured and the simulated impedance spectrums. The difference in resonance and anti-resonance frequencies between the measured and simulated impedance spectrums was around 0.5% and 1.2%. By utilizing the analytic solutions in this study, it is possible to accurately derive full equivalent material coefficients of a 2-2 composite, which are essential for the development of acoustic sensors.

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1 - 8 were prepared as potential tyrosinase inhibitors. Four analogs ( 1 - 3 and 5 ) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1 , 3 , and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1 , 3 , and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.

We report a fusedly deposited frequency-selective composite (FD-FSCs), fabricated with a dual-nozzle 3D printer using a conductive carbon black (CB) polylactic acid (PLA) composite filament and a pure PLA polymer filament. The square frequency-selective pattern was constructed by the conductive CB/PLA nanocomposite, and the apertures of the pattern were filled with the pure dielectric PLA material, which allows the FD-FSC to maintain one single plane, even under bending, and also affects the resonating frequency due to the characteristic impedance of PLA ( ε r ' ≈ 2.0). The number of the deposition layer and the printing direction were observed to affect electrical conductivity, complex permittivity, and the frequency selectivity of the FD-FSCs. In addition, the FD-FSCs designed for an X-band showed partial transmission around the resonant frequency and was observed to, quite uniformly, transmit microwaves in the decibel level of -2.17~-2.83 dB in the whole X-band, unlike a metallic frequency selective surface with full transmission at the resonance frequency. FD-FSCs embedded radar absorbing structure (RAS) demonstrates an excellent microwave absorption and a wide effective bandwidth. At a thickness of 4.3 mm, the 10 dB bandwidth covered the entire X-band (8.2~12.4 GHz) range of 4.2 GHz. Therefore, the proposed FD-FSCs fabricated by dual-nozzle 3D printing can be an impedance modifier to expand the design space and the application of radar absorbing materials and structures.

Appendicitis is a prevalent surgical emergency. Although appendectomy has traditionally been the go-to treatment, recent studies suggest antibiotics can be equally effective for uncomplicated cases. However, evidence is scant regarding patients with hematologic disorders. This study delves into the surgical risks tied to appendicitis in patients with underlying hematologic conditions. A retrospective analysis was carried out on patients diagnosed with appendicitis and hematologic disorders from January 2000 to June 2021. Patients were pinpointed using ICD-10 diagnostic codes, and surgical procedures were identified based on the hospital's surgical fee codes. Hematologic conditions were sorted into risk levels, and patient treatments were scrutinized. Among the 131 initially identified patients, 89 were included in the study. Out of these, 75 underwent surgical procedures, while 14 received non-surgical treatments. The surgical group displayed better preoperative laboratory outcomes. Clinical characteristics, hematologic disease risk, and severity of appendicitis appeared not to be related to surgical complications. Patients without surgical complications showed improvement in preoperative absolute neutrophil count (ANC) and platelet counts. Lower preoperative ANCs and platelet counts were associated with extended hospital stays. For patients with hematologic disorders diagnosed with appendicitis, thorough preoperative laboratory evaluations followed by minimally invasive appendectomy appear to be a safe route without heightening the risk of severe complications compared to non-surgical management.

Radical gastrectomy is essential for gastric cancer treatment. While guidelines advise dissecting at least 16 lymph nodes, some research suggests over 30 nodes might be beneficial. This study assessed ICG-guided robotic gastrectomy's effectiveness in thorough lymph node dissection. We analyzed data from 393 stage II or III gastric cancer patients treated at Seoul St. Mary's Hospital from 2016-2022. Patients were categorized into conventional laparoscopy (G1, n = 288), ICG-guided laparoscopy (G2, n = 61), and ICG-guided robotic surgery (G3, n = 44). Among 391 patients, 308 (78.4%) achieved proper lymphadenectomy. The ICG-robotic group (G3) showed the highest success rate at 90.9%. ICG-guided robotic surgery was a significant predictor for achieving proper lymphadenectomy, with an odds ratio of 3.151. In conclusion, ICG-robotic gastrectomy improves lymphadenectomy outcomes in selected gastric cancer cases, indicating a promising surgical approach for the future.

Perfluorohexane sulfonate (PFHxS) is a widely detected replacement for legacy long-chain perfluoroalkyl substances (PFAS) in the environment and human blood samples. Its potential toxicity led to its recent classification as a globally regulated persistent organic pollutant. Although animal studies have shown a positive association between PFHxS levels and hepatic steatosis and hepatocellular hypertrophy, the link with liver toxicity, including end-stage liver cancer, remains inconclusive. In this study, we examined the effects of PFHxS on the proliferation of Hep3B (human hepatocellular carcinoma) and SK-Hep1 (human liver sinusoidal endothelial cells). Cells were exposed to different PFHxS concentrations for 24-48 h to assess viability and 12-14 days to measure colony formation. The viability of both cell lines increased at PFHxS concentrations <200 μM, decreased at >400 μM, and was highest at 50 μM. Colony formation increased at <300 μM and decreased at 500 μM PFHxS. Consistent with the effect on cell proliferation, PFHxS increased the expression of proliferating cell nuclear antigen (PCNA) and cell-cycle molecules (CDK2, CDK4, cyclin E, and cyclin D1). In summary, PFHxS exhibited a biphasic effect on liver cell proliferation, promoting survival and proliferation at lower concentrations and being cytotoxic at higher concentrations. This suggests that PFHxS, especially at lower concentrations, might be associated with HCC development and progression.

Tannic acid (TA) can be used as an additive to improve the properties of hydrogels, but it acts as a radical scavenger, which hinders radical polymerization. In this study, we successfully and easily synthesized a TA-incorporated 2-acrylamido-2-methylpropanesulfonic acid (AMPS) hydrogel using an electron beam (E-beam) in a one-pot process at room temperature. TA successfully grafted onto AMPS polymer chains under E-beam irradiation, but higher TA content reduced grafting efficiency and prevented hydrogel formation. Peel strength of the AMPS hydrogel increased proportionally with TA, but cohesive failure and substrate residue occurred above 1.25 phm (parts per 100 g of AMPS) TA. Tensile strength peaked at 0.25 phm TA but decreased below the control value at 1.25 phm. Tensile elongation exceeded 2000% with TA addition. Peel strength varied significantly with substrate type. The wood substrate had the highest peel strength value of 150 N/m, while pork skin had a low value of 11.5 N/m. However, the addition of TA increased the peel strength by over 300%. The ionic conductivity of the AMPS/TA hydrogel increased from 0.9 S/m to 1.52 S/m with TA content, while the swelling ratio decreased by 50% upon TA addition and increased slightly thereafter., Competing Interests: The authors declare no conflict of interest.

Ionic wind, which is generated by a corona discharge, is a promising field that offers significant advantages by directly converting electrical energy into kinetic energy. Because of the electrical characteristics of ionic wind, most studies aiming to improve the performance of ionic wind generators have focused on modifying the geometry of electrode configurations. A mesh-type electrode is one of the electrodes used as a collecting electrode in an ionic wind generator. Using a mesh electrode results in decreased momentum of the ionic wind and increased pressure drop due to frictional loss of the flow. In this study, to minimize the reduction in momentum, a mesh electrode with a central hole was proposed and investigated. Experiments were conducted with the configuration of a needle and mesh with the central hole. These experiments analyzed the effect of the central hole diameter and the distance between the needle and the mesh electrodes on the electrical and physical characteristics of the ionic wind. The addition of the central hole led to a higher average velocity and lower current, thus resulting in increased energy conversion efficiency. The presented configuration offers a simple geometry without electrical and physical interference from complex configurations, and it is considered to have the potential to improve energy conversion efficiency and optimize ionic wind flow.

Piezoelectric composites, which consist of a piezoelectric material and a polymer, have been extensively studied for the applications of underwater sonar sensors and medical diagnostic ultrasonic transducers. Acoustic sensors utilizing piezoelectric composites can have a high sensitivity and wide bandwidth because of their high piezoelectric coefficient and low acoustic impedance compared to single-phase piezoelectric materials. In this study, a thickness-mode driving hydrophone utilizing a 2-2 piezoelectric single crystal composite was examined. From the theoretical and numerical analysis, material properties that determine the bandwidth and sensitivity of the thickness-mode piezoelectric plate were derived, and the voltage sensitivity of piezoelectric plates with various configurations was compared. It was shown that the 2-2 composite with [011] poled single crystals and epoxy polymers can provide high sensitivity and wide bandwidth when used for hydrophones with a thickness resonance mode. The hydrophone element was designed and fabricated to have a thickness mode at a frequency around 220 kHz by attaching a composite plate of quarter-wavelength thickness to a hard baffle. The fabricated hydrophone demonstrated an open circuit voltage sensitivity of more than -180 dB re 1 V/μPa at the resonance frequency and a -3 dB bandwidth of more than 55 kHz. The theoretical and experimental studies show that the 2-2 single crystal composite can have a high sensitivity and wide bandwidth compared to other configurations of piezoelectric elements when they are used for thickness-mode hydrophones.

In this study, two thin rectangular PVDFs were installed in the form of a cantilever on a FTEH (funnel-type energy harvester), and a CTEH (cymbal-type energy harvester) was fabricated in a form coupled to the upper part of the support. As a result of measuring the energy harvesting sensitivity according to the installation direction of the CTEH, a high voltage was measured in the structure installed on top of the support across all flow velocity conditions. A composite structure PVDF energy harvester combining CTEH and FTEH was fabricated and the amount of power generated was measured. As a result of measuring the open-circuit voltage of the PVDF energy harvester device with a composite structure to which the optimum resistance of CTEH of 241 kΩ and the optimum resistance of FTEH of 1474 kΩ were applied at a flow rate of 0.25 m/s, the output voltage compared to the RMS average value was 7 to 8.5 times higher for FTEH than for CTEH. When the flow rate was 0.5 m/s, the electrical energy charged for 500 s was measured as 2.0 μWs to 2.5 μWs, and when the flow speed was 0.75 m/s, it reached 2.5 μWs when charged for 300 s, generating the same amount when the flow rate increased by 50%. The time to do it was reduced by 66.7%.

Underwater detection is accomplished using an underwater ultrasonic sensor, sound navigation and ranging (SONAR). Stealth to avoid detection by SONAR plays a major role in modern underwater warfare. In this study, we propose a smart skin that avoids detection by SONAR via controlling the signal reflected from an unmanned underwater vehicle (UUV). The smart skin is a multilayer transducer composed of an acoustic window, a double-layer receiver, and a single-layer transmitter. It separates the incident signal from the reflected signal from outside through the time-delay separation method and cancels the reflected wave from the phase-shifted transmission sound. The characteristics of the receiving and transmitting sensors were analyzed using a finite element analysis. Three types of devices were compared in the design of the sensors. Polyvinylidene fluoride (PVDF), which had little effect on the transmitted sound, was selected as the receiving sensor. A stacked piezoelectric transducer with high sensitivity compared to a cymbal transducer was used as the transmitter. The active reflection control system was modeled and verified using 2D 360° reflection experiments. The stealth effect that could be achieved by applying a smart skin to a UUV was presented through an active reflection-control omnidirectional reflection model.

Polyvinylidene fluoride (PVDF) is an emerging method for energy harvesting by fluid motion with superior flexibility. However, the PVDF energy harvester, which has a high internal impedance and generates a low voltage, has a large power transmission loss. To overcome this problem, we propose an impedance-coupled voltage-boosting circuit (IC-VBC) that reduces the impedance of the PVDF energy harvester and boosts the voltage. SPICE simulation results show that IC-VBC reduces the impedance of the PVDF energy harvester from 4.3 MΩ to 320 kΩ and increases the output voltage by 2.52 times. We successfully charged lithium-ion batteries using the PVDF energy harvester and IC-VBC with low-speed wind power generation.

A vector hydrophone is an underwater acoustic sensor that can detect the direction of a sound source. Wide-band characteristics and high sensitivity enhance the performance of underwater surveillance systems in complex environments. A vector hydrophone comprising a triaxial piezoelectric accelerometer and spherical hydrophone was fabricated and tested in the air and underwater. The vector hydrophone was designed to exceed the quantitative figures of merit (i.e., receiving voltage sensitivity and bandwidth) of commercially available hydrophones. Accelerometer performance was enhanced by placing a pair of piezoelectric single crystals on each axis and modifying the seismic mass material. The receiving voltage sensitivity of the omnidirectional hydrophone was approximately −160 dB relative to 1 V/μPa with the amplifier in water; the sensitivity of the accelerometer exceeded 300 mV/g in air and −215 dB relative to 1 V/μPa underwater over the frequency range of interest. The receiving directivity of the vector hydrophone was validated underwater, which confirmed that it could detect the direction of a sound source., Competing Interests: The authors declare no conflict of interest.

Layered double hydroxides (LDHs) with two-dimensional nanostructure are inorganic materials that have attractive advantages such as biocompatibility, facile preparation, and high drug loading capacity for therapeutic bioapplications. Since the intercalation chemistry of DNA molecules into the LDH materials were reported, various LDH nanohybrids have been developed for biomedical drug delivery system. For these reasons, LDHs hybridized with numerous therapeutic agents have a significant role in cancer imaging and therapy with targeting functions. In this review, we summarized the recent advances in the preparation of LDH nanohybrids for cancer therapeutic strategies including gene therapy, chemotherapy, immunotherapy, and combination therapy.

NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies.

Patients with high-risk non-metastatic renal cell carcinoma (RCC) are at risk of metastatic relapse following nephrectomy. Cabozantinib (CZ), a potent multitarget tyrosine kinase inhibitor, interferes with angiogenesis and immunosuppression associated with surgery-induced metastasis. Here, we explored the therapeutic potential of CZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CZ-PLGA-NPs) as an adjuvant strategy for targeting post-nephrectomy metastasis. A clinically relevant subline recapitulating post-nephrectomy lung metastasis of high-risk human RCC, namely Renca-SRLu5-Luc, was established through in vivo serial selection of luciferase-expressing murine RCC Renca-Luc cells. CZ was encapsulated into PLGA-NPs via the conventional single emulsion technique. The multifaceted preclinical antimetastatic efficacy of CZ-PLGA-NPs was assessed in Renca-SRLu5-Luc cells. CZ-PLGA-NPs with a smooth surface displayed desirable physicochemical properties, good CZ encapsulation efficiency, as well as controlled and sustained CZ release. CZ-PLGA-NPs exhibited remarkable dose-dependent toxicity against Renca-SRLu5-Luc cells by inducing G2/M cell cycle arrest and apoptosis. CZ-PLGA-NPs attenuated in vitro colony formation, migration, and invasion by abrogating AKT and ERK1/2 activation. An intravenous injection of CZ-PLGA-NPs markedly reduced lung metastatic burden and prolonged lifespan with favorable safety in the Renca-SRLu5-Luc experimental lung metastasis model. The novel CZ-PLGA-NPs system with multifaceted antimetastatic effects and alleviating off-target toxicity potential is a promising adjunctive agent for patients with surgically resected high-risk RCC.

Free space optical (FSO) communication can support various unmanned aerial vehicles' (UAVs) applications that require large capacity data transmission. In order to perform FSO communication between two terminals, it is essential to employ a pointing, acquisition, and tracking (PAT) system with an efficient and optimal performance. We report on the development of a common optical-path-based FSO communication system, tailored for applications in UAVs. The proposed system is equipped with a quadrant photodiode (QPD)-based PAT system without an additional beacon beam subsystem. The presented approach reduced the structural complexity and improved the tracking efficiency for the same size, weight, and power (SWaP). To achieve a robust FSO link in a dynamic UAV environment, the observability and controllability were obtained based on the linearized control according to the incident beam size on the QPD, which was verified by optical simulation and experiments. As a result, the QPD-based PAT system for implementing FSO links demonstrated an up to 4.25 times faster tracking performance. Moreover, the FSO link experimentally confirmed the 1.25 Gbps full-duplex error-free communication at a 50 m distance.

Ligustrum lucidum Aiton is a flowering plant of the Oleaceae family, and its fruits have been traditionally used for skin nourishment and the treatment of skin diseases. However, the anti-inflammatory constituents for skin disease are not well-characterized. Phytochemical investigation of L. lucidum fruits resulted in the isolation of a new secoiridoid, secoligulene ( 1 ), together with ( E )-3-(1-oxobut-2-en-2-yl)pentanedioic acid ( 2 ) and trans -( E )-3-(1-oxobut-2-en-2-yl)glutaric acid ( 3 ). Secoligulene ( 1 ) displayed the potent inhibitory effect on NO production with an IC 50 value of 12.0 μg/mL. Secoligulene ( 1 ) also downregulated mRNA transcriptional levels of pro-inflammatory cytokines such as IL-1 α, IL-1β, IL-6 and COX-2 in LPS-stimulated RAW264.7 cells. Further investigation showed that secoligulene ( 1 ) inhibited the phosphorylation of IκB and JNK activated by LPS. In addition, secoligulene ( 1 ) downregulated the expression of chemokines such as CXCL8 and CCL20 in the TNF-α/IL-17/IFN-γ induced HaCaT psoriasis model. Taken together, these findings support the beneficial effects of L. lucidum and its constituents on inflammation-related skin diseases and can be further developed as therapeutic treatments for related diseases., Competing Interests: The authors declare no conflict of interest.

In this study, ionic conductive hydrogels were prepared with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS). Acrylic acid (AA), acrylamide (AAm), and 2-hydroxyethyl acrylate (HEA) were used as comonomers to complement the adhesion properties and ion conductivity of AMPS hydrogels. Hydrogels were prepared by irradiating a 20 kGy dose of E-beam to the aqueous monomer solution. With the E-beam irradiation, the polymer chain growth and network formation simultaneously proceeded to form a three-dimensional network. The preferred reaction was determined by the type of comonomer, and the structure of the hydrogel was changed accordingly. When AA or AAm was used as a comonomer, polymer growth and crosslinking proceeded together, so a hydrogel with increased peel strength and tensile strength could be prepared. In particular, in the case of AA, it was possible to prepare a hydrogel with improved adhesion without sacrificing ionic conductivity. When the molar ratio of AA to AMPS was 3.18, the 90° peel strength of AMPS hydrogel increased from 171 to 428 g f /25 mm, and ionic conductivity slightly decreased, from 0.93 to 0.84 S/m. By copolymerisation with HEA, polymer growth was preferred compared with chain crosslinking, and a hydrogel with lower peel strength, swelling ratio, and ionic conductivity than the pristine AMPS hydrogel was obtained.

Esophagojejunal anastomosis (EJA) complications after total gastrectomy are related to significant morbidity and mortality. The aim of this study was to evaluate the association between arterial calcifications and EJA complications such as leak and stricture for gastric cancer. Between January 2014 and October 2019, 30 patients with EJA complications after total gastrectomy were enrolled and matched to 30 patients without complications through retrospective data review. Arterial calcification grade on preoperative computed tomography (CT) was reported in the abdominal aorta and superior mesenteric artery (SMA) as “absent”, “minor”, or “major”, and in the jejunal vascular arcade (JVA) and left inferior phrenic artery (LIPA) as “absent” or “present”. A Chi-square test was used to compare the variables between the two groups. p-Value < 0.050 was considered statistically significant. Among 30 patients, the numbers of patients with leak and stricture were 23 and seven, respectively. Aortic calcifications were not associated with EJA complications regardless of their grade (p = 0.440). Only major SMA calcifications were associated with EJA complications, as they were present in five patients (16.7%) in the complication group and absent in the non-complication group (p = 0.020). Major SMA calcifications were more related to anastomotic stricture than leak. Three (13.0%) out of 23 patients with leak and two (28.6%) out of seven with stricture had major SMA calcifications (p = 0.028). No calcifications were detected in the JVA or LIPA in any of the 60 patients. Major SMA calcifications were found to be associated with EJA complications, especially in stricture.

Experimental and numerical analysis of the drop-on-demand inkjet was conducted to determine the jetting characteristics and meniscus motion under the control of the ink supply pressure. A single transparent nozzle inkjet head driven by a piezoelectric actuator was used to eject droplets. To control ink supply pressure, the pressure of the air in the reservoir was regulated by a dual valve pressure controller. The inkjet performance and the motion of the meniscus were evaluated by visualization and numerical simulation. A two-dimensional axisymmetric numerical simulation with the dynamic mesh method was performed to simulate the inkjet dynamics, including the actual deformation of the piezoelectric actuator. Numerical simulation showed good agreement with the experimental results of droplet velocity and volume with an accuracy of 87.1%. Both the experimental and simulation results showed that the drop volume and velocity were linearly proportional to the voltage change. For the specific voltages, an analysis of the effect of the ink supply pressure control was conducted. At the maximum negative pressure, -3 kPa, the average velocity reductions were 0.558 and 0.392 m/s in the experiment and simulation, respectively, which were 18.7 and 11.6% less than those of the uncontrolled case of 0 kPa. Therefore, the simulation environment capable of simulating the entire inkjet dynamics, including meniscus movement regarded to be successfully established. The average volume reductions were 18.7 and 6.97 pL for the experiment and simulation, respectively, which were 21.7 and 9.17% less than those of the uncontrolled case. In the results of the meniscus motion simulation, the damping of the residual vibration agreed well with the experimental results according to the ink supply pressure change. Reducing the ink supply pressure reduced the speed and volume, improved the damping of residual vibrations, and suppressed satellite drops. Decreasing ink supply pressure can be expected to improve the stability and productivity of inkjet printing.

For the purpose of stably supplying electric power to the underwater wireless sensor, the energy harvesting technology in which a voltage is obtained by generating displacement in a piezoelectric material using flow-induced vibration is one of the most attractive research fields. The funnel type energy harvester (FTEH) with PVDF proposed in this study is an energy harvester in which the inlet has a larger cross-sectional area than the outlet and a spiral structure is inserted to generate a vortex flow at the inlet. Based on numerical analysis, when PVDF with L = 100 mm and t = 1 mm was used, the electric power of 39 μW was generated at flow velocity of 0.25 m/s. In experiment the average RMS voltage of FTEH increased by 0.0209 V when the flow velocity increased by 1 m/s. When measured at 0.25 m/s flow velocity for 25 s, it was shown that voltage doubler rectifier (VDR) generated a voltage of 133.4 mV, 2.25 times larger than that of full bridge rectifier (FBR), and the energy charged in the capacitor was 44.3 nJ, 14% higher in VDR than that of the FBR. In addition, the VDR can deliver power of 17.75 μW for 1 kΩ load. It is shown that if the voltage generated by the FTEH using the flow velocity is stored using the VDR electric circuit, it will greatly contribute to the stable power supply of the underwater wireless sensor.

This paper presents a control technique for reducing the reflection of acoustic signals for the plane array of multilayer acoustic absorbers underwater. In order to achieve this, a plane array of multilayer acoustic absorbers is proposed to attenuate low-frequency noise, with each unit consisting of a piezoelectric transducer, two layers of polyvinylidene fluorides and three layers of the acoustic window. Time-delay separation is used to find the incident and reflected acoustic signals to achieve reflected sound reduction. Experimental comparison of the attenuation rate of the reflected acoustic signal when performing passive and active controls is considered to verify the effectiveness of the time-delay separation technique applied plane array absorbers. Experiments on the plane array of smart skin absorbers confirmed that the reduction of reflected acoustic signals makes it suitable for a wide range of underwater applications.

Experiments and finite element simulations for multiple impact were performed on GLARE 5-2/1 and aluminum 2024-T3. Experiments were conducted on aluminum 2024-T3 and GLARE 5-2/1 at diverse impact energies to produce BVID (barely visible impact damage) and CVID (clearly visible impact damage). The finite element model was developed for multiple impact analysis using ABAQUS software and was confirmed by comparing the finite element analysis outcomes with experimental results. The two- and three-dimensional failure criteria model was applied to predict multiple impact behavior such as load-time history, maximum deflection-impact energy history, and damage progression. In addition, a user subroutine VUMAT was created to represent a three-dimensional progressive failure and was linked with ABAQUS. FEM results showed good agreement with experimental data.

Extracellular vesicles (EVs) have recently been isolated from different plants. Plant-derived EVs have been proposed as potent therapeutics and drug-delivery nanoplatforms for delivering biomolecules, including proteins, RNAs, DNAs, and lipids. Herein, Petasites japonicus -derived EVs (PJ-EVs) were isolated through a series of centrifugation steps and characterized using dynamic light scattering and transmission electron microscopy. Immunomodulatory effects of PJ-EVs were assessed using dendritic cells (DCs). PJ-EVs exhibited a spherical morphology with an average size of 122.6 nm. They induced the maturation of DCs via an increase in the expression of surface molecules (CD80, CD86, MHC-I, and MHC-II), production of Th1-polarizing cytokines (TNF-α and IL-12p70), and antigen-presenting ability; however, they reduced the antigen-uptake ability. Furthermore, maturation of DCs induced by PJ-EVs was dependent on the activation and phosphorylation of MAPK and NF-κB signal pathways. Notably, PJ-EV-treated DCs strongly induced the proliferation and differentiation of naïve T cells toward Th1-type T cells and cytotoxic CD8 + T cells along with robust secretion of IFN-γ and IL-2. In conclusion, our study indicates that PJ-EVs can be potent immunostimulatory candidates with an ability of strongly inducing the maturation of DCs.

Outdated-waste-carbon-fiber-reinforced olefin composites (oCFOCs) were fabricated with easily disposable polyolefin resins, polypropylene (PP), high-density polyethylene (HDPE), and low-density polyethylene (LDPE), by compressive molding using a hot press. The flexural and impact strengths of the oCFOCs from each respective resin type and oCF content, ranging from 35 to 70 wt.%, were increased by the aging treatment (120 °C and 95% humidity under a pressure of 0.8 MPa) until an aging time of three days, due to improved resin impregnation. For the oCFOC with PP, the hydrogen bond between PP and developed C-O groups due to the aging treatment and the existing silane layer of oCF is considered to assist cohesion between the resin and oCF. In particular, PP and 45 wt.% oCF content were the most effective conditions for improving the oCFOCs' mechanical properties, in addition to endowing the oCFOCs with good moldability and dimensional stability. Our results demonstrate that durable recycled composites can be manufactured using oCF and PP.

Techniques for reducing the reflection of acoustic signals have recently been actively studied. Most methods for reducing acoustic signals were studied using the normal-incidence wave reduction technique. Although the technique of canceling an object from the normal incidence wave is essential, research on reducing acoustic signals according to the angle of incidence is required for practical applications. In this study, we designed, fabricated, and experimented with an active reflection controller that can reduce acoustic signals according to the angle of incidence. The controller consists of a transmitter on one layer, a receiver sensor on two layers, and an acoustic window on three layers. To reduce the reflected signal, a combination of the time delay and phase was applied to the controller to minimize the acoustic signal by up to -23 dB at an angle of 10°. A controller array simulation was performed based on the results of a controlled experiment. In conclusion, our proposed controller can reduce acoustic signals according to the angle of incidence, which makes it suitable for many applications.

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.

The purpose of this study was to investigate the effect of the aliphatic moiety in the sulfonated poly(arylene ether sulfone) (SPAES) backbone. A new monomer (4,4'-dihydroxy-1,6-diphenoxyhexane) was synthesized and polymerized with other monomers to obtain partially alkylated SPAESs. According to differential scanning calorimetry analysis, the glass transition temperature (T g ) of these polymers ranged from 85 to 90 °C, which is 100 °C lower than that of the fully aromatic SPAES. Due to the low T g values obtained for the partially alkylated SPAESs, it was possible to prepare a hydrocarbon electrolyte membrane-based membrane electrode assembly (MEA) with Nafion ® binder in the electrode through the use of a decal transfer method, which is the most commercially suitable system to obtain an MEA of proton exchange membrane fuel cells (PEMFCs). A single cell prepared using this partially alkylated SPAES as an electrolyte membrane exhibited a peak power density of 539 mW cm -2 .

The siderophore-antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli , Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa . Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae , and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae , while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa . Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli , K. pneumoniae .

Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1.

In this paper, we present a sensing device with the optical temperature sensors-based quad receiver (Quad-RX) module and a security module. In addition, in order to prevent cyberattacks on critical national infrastructures and key facilities, we implemented symmetric-key and secure hash algorithm-based hardware security modules in the key elements of the sensing device. A preliminary test was conducted prior to a field trial to verify the performance of the developed sensing device. The accuracy and stability of the sensing device were then verified for 1 month in a field test at facilities for energy storage systems and photovoltaic converters in sewage treatment plants.

Polystyrene-based polymers with variable molecular weights are prepared by radical polymerization of styrene. Polystyrene is grafted with bromo-alkyl chains of different lengths through Friedel-Crafts acylation and quaternized to afford a series of hydroxide-ion-conducting ionomers for the catalyst binder for the membrane electrode assembly in anion-exchange membrane fuel cells (AEMFCs). Structural analyses reveal that the molecular weight of the polystyrene backbone ranges from 10,000 to 63,000 g mol -1 , while the ion exchange capacity of quaternary-ammonium-group-bearing ionomers ranges from 1.44 to 1.74 mmol g -1 . The performance of AEMFCs constructed using the prepared electrode ionomers is affected by several ionomer properties, and a maximal power density of 407 mW cm -2 and a durability exceeding that of a reference cell with a commercially available ionomer are achieved under optimal conditions. Thus, the developed approach is concluded to be well suited for the fabrication of next-generation electrode ionomers for high-performance AEMFCs.

Bombyx batryticatus , a protein-rich edible insect, is widely used as a traditional medicine in China. Several pharmacological studies have reported the anticancer activity of B. batryticatus extracts; however, the capacity of B. batryticatus extracts as immune potentiators for increasing the efficacy of cancer immunotherapy is still unverified. In the present study, we investigated the immunomodulatory role of B. batryticatus protein-rich extract (BBPE) in bone marrow-derived dendritic cells (BMDCs) and DC vaccine-immunized mice. BBPE-treated BMDCs displayed characteristics of mature immune status, including high expression of surface molecules (CD80, CD86, major histocompatibility complex (MHC)-I, and MHC-II), increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-12p70), enhanced antigen-presenting ability, and reduced endocytosis. BBPE-treated BMDCs promoted naive CD4 + and CD8 + T-cell proliferation and activation. Furthermore, BBPE/ovalbumin (OVA)-pulsed DC-immunized mice showed a stronger OVA-specific multifunctional T-cell response in CD4 + and CD8 + T cells and a stronger Th1 antibody response than mice receiving differently treated DCs, which showed the enhanced protective effect against tumor growth in E.G7 tumor-bearing mice. Our data demonstrate that BBPE can be a novel immune potentiator for a DC-based vaccine in anticancer therapy.

To improve the heat resistance of acrylic-based pressure-sensitive adhesive (PSA), silicone-block-containing acrylic PSAs (SPSAs) were synthesized using a polydimethylsiloxane (PDMS)-based macro-azo-initiator (MAI). To evaluate the heat resistance of the PSA films, the probe tack and 90° peel strength were measured at different temperatures. The acrylic PSA showed that its tack curves changed from balanced debonding at 25 °C to cohesive debonding at 50 °C and exhibited a sharp decrease. However, in the case of SPSA containing 20 wt% MAI (MAI20), the balanced debonding was maintained at 75 °C, and its tack value hardly changed with temperature. As the MAI content increased, the peel strength at 25 °C decreased due to the microphase separation between PDMS- and acryl-blocks in SPSA, but the shear adhesion failure temperature (SAFT) increased almost linearly from 41.3 to 122.8 °C. Unlike stainless steel substrate, SPSA showed improved peel strength on a polypropylene substrate due to its low surface energy caused by PDMS block. Owing to the addition of 20 wt% silicone-urethane dimethacrylate oligomer and 200 mJ/cm 2 UV irradiation dose, MAI20 showed significantly increased 90° peel strength at 25 °C (548.3 vs. 322.4 gf/25 mm for pristine MAI20). Its heat resistance under shear stress assessed by shear adhesion failure test (SAFT) exhibited raising in failure temperature to 177.3 °C when compared to non-irradiated sample.

This study analyzed the characteristics of a small reciprocating pump with a cantilever valve driven by a piezo actuator. Three types of valves were fabricated to investigate the effect of the valve stiffness on the pump performance and to measure the variation in the flow rate according to the frequency. The flow rate increased with the driving frequency until a certain frequency was reached, and then it started to decrease. The rise in the pressure of the pump was found to increase as the stiffness decreased. The pump performance could be clearly distinguished according to the stiffness of the valve. The observation of the valve movements revealed that the valve opening time did not change regardless of the operating frequency, but it changed with the valve stiffness. The delay in time for the outlet valve increased significantly with an increase in the frequency. It seems that the overlap of the opening time of the inlet valve and the outlet valve plays an important role in pump performance. Therefore, it is advisable to use different designs for the inlet and outlet valves, where the shape and stiffness of the valve are adjusted.

The formation of a thin 2D perovskite layer on the surface of 3D perovskite films has become a popular strategy for obtaining a high-efficiency perovskite solar cell (PSC) with an ensured device stability. In this review paper, various experimental methods used for growth of the 2D layer are introduced with the resulting film properties. Furthermore, a variety of organic cation sources for the 2D layer, ranging from alkyl to phenyl ammonium, are explored to investigate their impact on the device stability and photovoltaic performance.

Src Homology 2 (SH2) domains arose within metazoan signaling pathways and are involved in protein regulation of multiple pleiotropic cascades. In signal transducer and activator of transcription (STAT) proteins, SH2 domain interactions are critical for molecular activation and nuclear accumulation of phosphorylated STAT dimers to drive transcription. Sequencing analysis of patient samples has revealed the SH2 domain as a hotspot in the mutational landscape of STAT proteins although the functional impact for the vast majority of these mutations remains poorly characterized. Despite several well resolved structures for SH2 domain-containing proteins, structural data regarding the distinctive STAT-type SH2 domain is limited. Here, we review the unique features of STAT-type SH2 domains in the context of all currently reported STAT3 and STAT5 SH2 domain clinical mutations. The genetic volatility of specific regions in the SH2 domain can result in either activating or deactivating mutations at the same site in the domain, underscoring the delicate evolutionary balance of wild type STAT structural motifs in maintaining precise levels of cellular activity. Understanding the molecular and biophysical impact of these disease-associated mutations can uncover convergent mechanisms of action for mutations localized within the STAT SH2 domain to facilitate the development of targeted therapeutic interventions.

Taraxacum officinale has been consumed as a folk remedy due to its diverse physiological activities. This study aimed to investigate the antioxidative potential of T. officinale water extract (TOWE) and ethanol extract (TOEE) against oxidative stress and compare their molecular mechanism via the induction of heme oxygenase-1 (HO-1) in RAW 264.7 cells. The antioxidative activity was evaluated through the radical scavenging assay, the cytoprotection assay against oxidative damage, and Western blot analysis. Both extracts dose-dependently induced HO-1 expression without any cytotoxicity in accordance with the activation of a transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOWE induced HO-1 expression through the phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and c-Jun NH 2 -terminal kinase (JNK), while TOEE activated HO-1 by PI3K/Akt phosphorylation. In order to identify the antioxidative potential by HO-1 induction, oxidative damage-caused cell death by tert-butyl hydroperoxide (t-BHP) was significantly attenuated by both extracts. Their antioxidative potential was confirmed by HO-1 selective inducer and inhibitor, cobalt protoporphyrin (CoPP), and tin protoporphyrin (SnPP), respectively. These results indicate that TOWE and TOEE potently alleviated oxidative damage via the induction of Nrf2/MAPK/PI3K mediated HO-1 induction in RAW 264.7 cells.

Heat dissipation has become an important issue due to the miniaturization of various electronic devices. Various methods such as spray and nozzle coolers, heat sinks and so on are used for heat dissipation. However, the emergence of ferrofluids drastically improves the operating characteristics of electromagnetic systems and devices. A ferrofluid is a suspension containing 10-nm magnetic particles in a colloidal solution. This material exhibits paramagnetic behavior and is sensitive to magnetic field and temperature. In this study, heat transfer characteristics of ferrofluids in a rotating eccentric cylinder were investigated using the commercial code, COMSOL Multiphysics. Numerical results of the local Nusselt number, magnetophoretic force and velocity distributions were obtained from various eccentricities of the cylinder, and the results were graphically depicted with various flow conditions.

Seed size is one of the most important traits determining the yield of cereal crops. Many studies have been performed to uncover the mechanism of seed development. However, much remains to be understood, especially at the molecular level, although several genes involved in seed size have been identified. Here, we show that rice Grain Width 2 (GW2), a RING-type E3 ubiquitin ligase, can control seed development by catalyzing the ubiquitination of expansin-like 1 (EXPLA1), a cell wall-loosening protein that increases cell growth. Microscopic examination revealed that a GW2 mutant had a chalky endosperm due to the presence of loosely packed, spherical starch granules, although the grain shape was normal. Yeast two-hybrid and in vitro pull-down assays showed a strong interaction between GW2 and EXPLA1. In vitro ubiquitination analysis demonstrated that EXPLA1 was ubiquitinated by GW2 at lysine 279 (K279). GW2 and EXPLA1 colocalized to the nucleus when expressed simultaneously. These results suggest that GW2 negatively regulates seed size by targeting EXPLA1 for degradation through its E3 ubiquitin ligase activity.

Nitrate reductases (NRs) catalyze the first step in the reduction of nitrate to ammonium. NR activity is regulated by sumoylation through the E3 ligase activity of AtSIZ1. However, it is not clear how NRs interact with AtSIZ1 in the cell, or how nitrogen sources affect NR levels and their cellular localization. Here, we show that the subcellular localization of NRs is modulated by the E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 and that NR protein levels are regulated by nitrogen sources. Transient expression analysis of GFP fusion proteins in onion epidermal cells showed that the NRs NIA1 and NIA2 localize to the cytoplasmic membrane, and that AtSIZ1 localizes to the nucleoplasm, including nuclear bodies, when expressed separately, whereas NRs and AtSIZ1 localize to the nucleus when co-expressed. Nitrate did not affect the subcellular localization of the NRs, but it caused AtSIZ1 to move from the nucleus to the cytoplasm. NRs were not detected in ammonium-treated cells, whereas the localization of AtSIZ1 was not altered by ammonium treatment. NR protein levels increased in response to nitrate but decreased in response to ammonium. In addition, NR protein levels increased in response to a 26S proteasome inhibitor and in cop1-4 and DN-COP1-overexpressing transgenic plants. NR protein degradation occurred later in cop1-4 than in the wild-type, although the NR proteins did not interact with COP1. Therefore, AtSIZ1 controls nuclear localization of NR proteins, and ammonium negatively regulates their levels. The function and stability of NR proteins might be post-translationally modulated by ubiquitination., Competing Interests: The authors declare no conflicts of interest.

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases.