Effect of universal adhesive pretreatments on the bond strength durability of conventional and adhesive resin cements to zirconia ceramic.

PURPOSE: This study aimed to evaluate the effect of pretreatment of three different universal adhesives (Single Bond Universal [SBU], All-Bond Universal [ABU], and Prime&Bond universal [PBU]) on the bonding durability of an adhesive (Panavia F 2.0, PF) and a conventional (Duo-Link, DL) resin cements to air-abraded zirconia. MATERIALS AND METHODS: Rectangular-shaped zirconia specimens were prepared. The chemical composition and surface energy parameters of the materials were studied by Fourier transform infrared spectroscopy and contact angle measurement, respectively. To evaluate resin bonding to the zirconia, all the bonding specimens were immersed in water for 24 h and the specimens to be aged were additionally thermocycled 10000 times before the shear bond strength (SBS) test. RESULTS: The materials showed different surface energy parameters, including the degree of hydrophilicity/hydrophobicity. While the DL/CON (no pretreatment) showed the lowest SBS and a significant decrease in the value after thermocycling (P < .001), the PF/CON obtained a higher SBS value than the DL/CON (P < .001) and no decrease even after thermocycling (P = .839). When the universal adhesives were used with DL, their SBS values were higher than the CON (P < .05), but the trend was adhesive-specific. In conjunction with PF, the PF/SBU produced the highest SBS followed by the PF/ABU (P = .002), showing no significant decrease after thermocycling (P > .05). The initial SBS of the PF/PBU was similar to the PF/CON (P = .999), but the value decreased after thermocycling (P < .001). CONCLUSION: The universal adhesive pretreatment did not necessarily show a synergistic effect on the bonding performance of an adhesive resin cement, whereas the pretreatment was beneficial to bond strength and durability of a conventional resin cement.

Current Status of the Zebrafish Euthanasia and Humane Endpoint in the Republic of Korea and Guideline Suggestion from Nationwide Expert Elicitation: A Model for Other Countries.

Since its introduction as a model organism in the 1980s, the use of zebrafish (Danio rerio) in research has expanded worldwide. Despite its now widespread use in research, guidelines to safeguard the ethical treatment of zebrafish, particularly with regard to euthanasia and humane endpoint practices, remain inadequate. One well-recognized example is the use of excess tricaine methanesulfonate (MS-222) as a means to euthanize zebrafish, regardless of life stage. In this study, through nationwide expert elicitation, we provide a detailed account of zebrafish research practices within the Republic of Korea and the challenges of implementing appropriate methods for euthanasia as a humane endpoint, with many opting for hypothermic shock. We report a local expert consensus for establishing national guidelines to improve zebrafish welfare and good research practice. Suggestions and recommendations for national guidelines were offered. Taken together, our findings raise awareness broadly among zebrafish research practitioners in the field, offer an accurate account of the welfare and treatment of zebrafish in research within the Republic of Korea, and advocate for the development and implementation of national guidelines. As such, our study is useful as a model to adopt the expert elicitation approach to investigate, quantify, and address welfare concerns in zebrafish research, and to establish best practice guidelines.

Identification and Biological Evaluation of a Potent and Selective JAK1 Inhibitor for the Treatment of Pulmonary Fibrosis.

Janus kinase 1 (JAK1) plays a pivotal role in regulating inflammation and fibrosis via the JAK/STAT signaling pathway, making it a promising target for associated diseases. In this study, we explored the modification of an N-methyl 1H-pyrrolo[2,3-b]pyridine-5-carboxylate core, leading to the identification of 4-(((2S,4S)-1-(4-trifluoromethyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (36b) as a highly potent and selective JAK1 inhibitor. Compound 36b exhibited an impressive IC50 value of 0.044 nM for JAK1 and demonstrated remarkable selectivity of 382-fold, 210-fold, and 1325-fold specificity over JAK2, JAK3, and TYK2, respectively. The kinase panel assays further confirmed its specificity, and cell-based experiments established its efficacy in inhibiting JAK1-STAT phosphorylation in human L-132 or SK-MES-1 cells. Pharmacokinetic studies revealed that compound 36b boasts an oral bioavailability exceeding 36%. In a bleomycin-induced fibrosis mouse model, compound 36b significantly reduced STAT3 phosphorylation, resulting in improvement in body weight and reduced collagen deposition, all achieved without significant side effects.

Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model.

PURPOSE: Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. MATERIALS AND METHODS: Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm² using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm². Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. RESULTS: A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC. CONCLUSION: Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.

Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia.

Asymmetric small interfering RNAs (asiRNAs) that mediate RNA interference have been investigated for therapeutic use in various tissues, including skin tissue. Androgenetic alopecia (AGA) is caused by a combination of genetic factors, resulting in sensitivity to dihydrotestosterone (DHT), which binds to the androgen receptor (AR) to mediate a series of biomolecular changes leading to hair loss. This study aimed to evaluate the therapeutic potential of a cell-penetrating, AR-targeting asiRNA (cp-asiAR) for AGA treatment, which was designed to silence the AR gene. AGA mouse models were developed by stimulation with DHT, and ex vivo human scalp tissues were also used for analysis. Cp-asiAR-mediated changes in mRNA expression and protein levels of AR were assessed along with the examination of phenotypic improvements in mouse model of AGA. We also assessed downstream signaling associated with AR in primary human dermal papilla (DP) cells. Several cp-asiARs were screened for selecting the optimal sequence of AR using cell lines in vitro. A cholesterol-conjugated, chemically modified cp-asiAR candidate was optimized under passive uptake conditions in vitro. Intradermal cp-asiAR injection efficiently reduced mRNA and protein levels corresponding to AR in mouse models. Moreover, cp-asiAR injection promoted hair growth in mouse models with DHT-induced AGA. In ex vivo human hair follicle culture, the proportion of telogen hair decreased, and the mean hair bulb diameter increased in the cp-asiAR-treated group. In isolated primary human DP cells, AR expression was effectively downregulated by cp-asiAR. Furthermore, cp-asiAR attenuated DHT-mediated increases in interleukin-6, transforming growth factor-ß1, and dickkopf-1 levels. No significant toxicity was observed in DP cells after cp-asiAR treatment. Cp-asiAR treatment showed effective downregulation of AR expression and prevention of DHT-mediated alterations in the hair cycle and hair diameter, indicating its potential as a novel therapeutic option for AGA.

Pudendal Nerve Terminal Motor Latency Compared by Anorectal Manometry Diagnosing Fecal Incontinence: A Retrospective Study.

OBJECTIVE: The aim of the study was to compare the clinical value of pudendal nerve terminal motor latency in fecal incontinence patients with that of another diagnostic test-anorectal manometry. DESIGN: This study used a cross-sectional design. Medical records of fecal incontinence patients who underwent pudendal nerve terminal motor latency and anorectal manometry testing were reviewed. Greater than 2.4 ms of pudendal nerve terminal motor latency was determined to be abnormal. Anorectal manometry was performed using a station pull-through technique. Mean resting anal pressure, maximal resting anal pressure, mean squeezing anal pressure, and maximal squeezing anal pressure were investigated. For normal and abnormal pudendal nerve terminal motor latency groups, comparative analyses were performed on anorectal manometry results. RESULTS: A total of 31 patients were included. Thirteen patients showed normal pudendal nerve terminal motor latency. For anorectal manometry results, there was no significant difference between normal and abnormal pudendal nerve terminal motor latency groups. Fourteen patients had diabetes mellitus. Subgroup analysis of the 14 diabetic patients showed no significant difference between normal and abnormal pudendal nerve terminal motor latency groups. For 17 nondiabetic patients, there was a significant difference between the groups with positive correlations with mean/maximal resting anal pressures. CONCLUSIONS: Pudendal nerve terminal motor latency significantly correlates with anorectal manometry in fecal incontinence only in nondiabetic patients.

Optimizing the Aspect Ratio of Nanopatterned Mesoporous TiO2 Thin-Film Layer to Improve Energy Conversion Efficiency of Perovskite Solar Cells.

The energy conversion efficiency (ECE) (η), current density (Jsc), open-circuit voltage (Voc), and fill factor (ff) of perovskite solar cells were studied by using the transmittance of a nanopatterned mesoporous TiO2 (mp-TiO2) thin-film layer. To improve the ECE of perovskite solar cells, a mp-TiO2 thin-film layer was prepared to be used as an electron transport layer (ETL) via the nanoimprinting method for nanopatterning, which was controlled by the aspect ratio. The nanopatterned mp-TiO2 thin-film layer had a uniform and well-designed structure, and the diameter of nanopatterning was 280 nm. The aspect ratio was controlled at the depths of 75, 97, 127, and 167 nm, and the perovskite solar cell was fabricated with different depths. The ECE of the perovskite solar cells with the nanopatterned mp-TiO2 thin-film layer was 14.50%, 15.30%, 15.83%, or 14.24%, which is higher than that of a non-nanopatterned mp-TiO2 thin-film layer (14.07%). The enhancement of ECE was attributed to the transmittance of the nanopatterned mp-TiO2 thin-film layer that is due to the improvement of the electron generation. As a result, better electron generation affected the electron density, and Jsc increased the Voc, and ff of perovskite solar cells.

Detection of sarcopenic obesity and prediction of long-term survival in patients with gastric cancer using preoperative computed tomography and machine learning.

BACKGROUND: Previous studies evaluating the prognostic value of computed tomography (CT)-derived body composition data have included few patients. Thus, we assessed the prevalence and prognostic value of sarcopenic obesity in a large population of gastric cancer patients using preoperative CT, as nutritional status is a predictor of long-term survival after gastric cancer surgery. METHODS: Preoperative CT images were analyzed for 840 gastric cancer patients who underwent gastrectomy between March 2009 and June 2018. Machine learning algorithms were used to automatically detect the third lumbar (L3) vertebral level and segment the body composition. Visceral fat area and skeletal muscle index at L3 were determined and used to classify patients into obesity, sarcopenia, or sarcopenic obesity groups. RESULTS: Out of 840 patients (mean age = 60.4 years; 526 [62.6%] men), 534 (63.5%) had visceral obesity, 119 (14.2%) had sarcopenia, and 48 (5.7%) patients had sarcopenic obesity. Patients with sarcopenic obesity had a poorer prognosis than those without sarcopenia (hazard ratio [HR] = 3.325; 95% confidence interval [CI] = 1.698-6.508). Multivariate analysis identified sarcopenic obesity as an independent risk factor for increased mortality (HR = 2.608; 95% CI = 1.313-5.179). Other risk factors were greater extent of gastrectomy (HR = 1.928; 95% CI = 1.260-2.950), lower prognostic nutritional index (HR = 0.934; 95% CI = 0.901-0.969), higher neutrophil count (HR = 1.101; 95% CI = 1.031-1.176), lymph node metastasis (HR = 6.291; 95% CI = 3.498-11.314), and R1/2 resection (HR = 4.817; 95% CI = 1.518-9.179). CONCLUSION: Body composition analysis automated by machine learning predicted long-term survival in patients with gastric cancer.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

The synergistic effect of focused ultrasound and biophotonics to overcome the barrier of light transmittance in biological tissue.

Optical technology is a tool to diagnose and treat human diseases. Shallow penetration depth caused by the high optical scattering nature of biological tissues is a significant obstacle to utilizing light in the biomedical field. In this paper, light transmission enhancement in the rat brain induced by focused ultrasound (FUS) was observed and the cause of observed enhancement was analyzed. Both air bubbles and mechanical deformation generated by FUS were cited as the cause. The Monte Carlo simulation was performed to investigate effects on transmission by air bubbles and finite element method was also used to describe mechanical deformation induced by motions of acoustic particles. As a result, it was found that the mechanical deformation was more suitable to describe the transmission change according to the FUS pulse observed in the experiment.

Discovery and Biological Evaluation of N-Methyl-pyrrolo[2,3-b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors.

Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Analysis of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamide as a JAK1-selective scaffold, and the synthesis of various methyl amide derivatives provided 4-((cis-1-(4-chlorobenzyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (31g) as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of 31g (38a) exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of 31g on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-ß-induced hepatic stellate cells (HSCs). Specifically, 31g significantly inhibited TGF-ß-induced migration of HSCs at 0.25 µM in wound-healing assays.

Effect of Au Nanoparticles and Scattering Layer in Dye-Sensitized Solar Cells Based on Freestanding TiO2 Nanotube Arrays.

The development of high efficiency dye-sensitized solar cells (DSSCs) has received tremendous attention. Many researchers have introduced new materials for use in DSSCs to achieve high efficiency. In this study, the change in power conversion efficiency (PCE) of DSSCs was investigated by introducing two types of materials-Au nanoparticles (Au NPs) and a scattering layer. A DSSC fabricated without neither Au NPs nor a scattering layer achieved a PCE of 5.85%. The PCE of a DSSC based on freestanding TiO2 nanotube arrays (f-TNTAs) with Au NPs was 6.50% due to better electron generation because the plasmonic absorption band of Au NPs is 530 nm, which matches the dye absorbance. Thus, more electrons were generated at 530 nm, which affected the PCE of the DSSC. The PCE of DSSCs based on f-TNTAs with a scattering layer was 6.61% due to better light harvesting by scattering. The scattering layer reflects all wavelengths of light that improve the light harvesting in the active layer in DSSCs. Finally, the PCE of DSSCs based on the f-TNTAs with Au NPs and a scattering layer was 7.12% due to the synergy of better electron generation and light harvesting by plasmonics and scattering. The application of Au NPs and a scattering layer is a promising research area for DSSCs as they can increase the electron generation and light harvesting ability.

Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.

Photoacoustic imaging to localize indeterminate pulmonary nodules: A preclinical study.

PURPOSE: Diagnosis and resection of indeterminate pulmonary nodules (IPNs) is a growing challenge with increased utilization of chest computed tomography. Photoacoustic (PA) -guided surgical resection with local injection of indocyanine green (ICG) may have utility for IPNs that are suspicious for lung cancer. This preclinical study explores the potential of PA imaging (PAI) to detect ICG-labeled tumors. MATERIALS AND METHODS: ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice. RESULTS: Intracellular ICG fluorescence was detected in H460 cells co-incubated with ICG in vitro. The concentration dependence of the PA signal was logarithmic, and PA signal decline was exponential with increasing tissue depth. The PA signal of 2 mg/mL ICG was still detectable at a depth of 22 mm in chicken breast. The PA signal from ICG mixed with agar was detectable 48 hours post injection into subcutaneous tissue and subcutaneous H460 tumors in nude mice. Similar features of PA signals from ICG-agar in mice lung were obtained. CONCLUSION: The results from this preclinical study suggests that PAI of injected ICG-agar may be beneficial for identifying deeply located tumors. These features may be valuable for IPNs.

Changes in Gait Parameters and Gait Variability in Young Adults during a Cognitive Task while Slope and Flat Walking.

This study investigates the effects of a cognitive task while walking on a slope or a flat surface on gait parameters and gait variability in young adults. The participants consisted of thirty healthy young subjects. They were instructed to walk on a slope or on a flat surface while performing or not performing a cognitive task, which involved speaking a four-syllable word in reverse. A wearable inertia measurement unit (IMU) system was used to measure spatiotemporal parameters and gait variability. Flat gait (FG) while performing the cognitive task (FGC) and uphill gait (UG) while performing the cognitive task (UGC) significantly altered stride times, gait speeds, and cadence as compared with FG and UG, respectively. Downhill gait (DG) while performing the cognitive task (DGC) caused no significant difference as compared with DG. Gait variability comparisons showed no significant difference between UGC and UG or between FGC and FG, respectively. On the other hand, variabilities of stride times and gait speeds were significantly greater for DGC than DG. FGC and UGC induce natural changes in spatiotemporal gait parameters that enable the cognitive task to be performed safely. DGC should be regarded as high complexity tasks involving greater gait variability to reduce fall risk.

Au-Nanoparticle-Embedded Open-Ended Freestanding TiO2 Nanotube Arrays in Dye-Sensitized Solar Cells for Better Electron Generation and Electron Transport.

Freestanding TiO2 nanotube arrays (TNTAs) were prepared by an electrochemical method, and dye-sensitized solar cells (DSSCs) were fabricated with the open-ended freestanding TNTAs incorporated with Au nanoparticles (NPs). Open-ended freestanding TNTAs were prepared by etching the barrier layer of closed-ended freestanding TNTAs using an ion milling method, and Au NPs were incorporated into the channel of the open-ended freestanding TNTAs by an electrodeposition method. The Au-NP-embedded open-ended freestanding TNTAs were applied to DSSCs to improve the energy conversion efficiency (ECE) by better electron generation and electron transport. The ECE of DSSCs based on the closed-ended freestanding TNTAs with Au NPs increased to 6.116% from 5.502% for DSSCs based on the closed-ended freestanding TNTAs without Au NPs, an enhancement of 11.16% because of better electron generation by the plasmonic and charging effects of the Au NPs. However, the ECE of DSSCs based on the closed-ended freestanding TNTAs incorporated with Au NPs for 40 s decreased from 6.116 to 5.336% because aggregation of the Au NPs led to a decrease in the open-circuit voltage (V oc) and fill factor. For enhanced ECE of DSSCs, the barrier layer of closed-ended freestanding TNTAs was etched by an ion milling method for 0, 30, 60, or 90 min to provide "open-ended freestanding TNTAs". Then, Au NPs were incorporated into the open-ended freestanding TNTAs. After the barrier layer was completely removed by the ion milling method for 90 min, the ECE of the DSSCs reached 7.120% because the electron transport and electrolyte diffusion were improved by the elimination of the barrier layer of the freestanding TNTAs.

Au-Embedded and Carbon-Doped Freestanding TiO2 Nanotube Arrays in Dye-Sensitized Solar Cells for Better Energy Conversion Efficiency.

Dye-sensitized solar cells (DSSCs) are fabricated with freestanding TiO2 nanotube arrays (TNTAs) which are incorporated with Au nanoparticles (NPs) and carbon materials via electrodeposition and chemical vapor deposition (CVD) method to create a plasmonic effect and better electron transport that will enhance their energy conversion efficiency (ECE). The ECE of DSSCs based on the freestanding TNTAs is 5.87%. The ECE of DSSCs, based on the freestanding TNTAs with Au NPs or carbon materials, is 6.57% or 6.59%, respectively, and the final results of DSSCs according to the freestanding TNTAs with Au NPs and carbon materials is increased from 5.87% to 7.24%, which is an enhancement of 23.34% owing to plasmonic effect and better electron transport. Au NPs are incorporated into the channel of freestanding TNTAs and are characterized by CS-corrected-field emission transmission electron microscope (Cs-FE-TEM) and elemental mapping. Carbon materials are also well-incorporated in the channel of freestanding TNTAs and are analyzed by Raman spectroscopy.

Selection of lethal genes for ingestion RNA interference against western flower thrips, Frankliniella occidentalis, via leaf disc-mediated dsRNA delivery.

The western flower thrips, Frankliniella occidentalis, is a major pest that damages a wide variety of crops and vegetables. Following extensive use of insecticides, it has developed high levels of resistance to almost all groups of insecticides due to its high reproduction rate and short generation time. Therefore, an alternative pest control strategy, such as RNA interference (RNAi)-based control, is essential. To establish an ingestion RNAi-based control, a total of 57 genes involved in various biological processes were selected, and their double-stranded RNAs (dsRNA) were delivered to an insecticide-susceptible strain of F. occidentalis via the leaf disc-feeding method using a bioassay chamber optimized by 3D printing. The mortality of dsRNA-ingested thrips was examined every 24 h until 120 h post-treatment. Of the 57 genes screened, dsRNAs of the Toll-like receptor 6, apolipophorin, coatomer protein subunit epsilon and sorting and assembly machinery component were most lethal when ingested by thrips. The dsRNA-fed thrips showed substantially reduced transcription levels of target genes, demonstrating that the observed mortality was likely due to RNAi. When these genes were tested for ingestion RNAi against an insecticide-resistant strain of F. occidentalis, bioassay results were similar. In conclusion, this study provides the first evidence that ingestion RNAi can be lethal to F. occidentalis, a mesophyll sucking pest, and further suggests that transgenic plants expressing hairpin RNA of these essential genes can be employed to control insecticide-resistant thrips.

A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model.

Sutaehwan (STH) has been used in Korean medicine for the treatment of abortus habitualis such as fetal restlessness in the uterus. Previously, we reported that a modified formulation of STH, Sutaehwan-Gami, has phytoestrogen-like properties in an ovariectomized menopausal rat model. However, the therapeutic effects of STH and the precise mechanisms by which STH affects various menopausal symptoms remain poorly understood. The current study was designed to explore the effects of a modified form of STH on menopausal anxiety, depression and heart hypertrophy and its mechanisms in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal mouse models. VCD-induced menopausal model mice were fed a modified form of STH, which contained water extract of 3 herbs (called STH_KP17001) at a dose of 100 or 300 mg/kg/d or as a positive control, estradiol at a dose of 0.2 mg/kg/d with standard mouse pellets for 13 weeks. The results show that STH_KP17001 significantly restored the VCD-induced weight reduction of uterine and ovary through the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in the uterus and ovary. Moreover, STH_KP17001 showed slight proliferative effects and estrogen receptor α phosphorylation in MCF-7 cells. Treatment with STH_KP17001 reversed VCD-induced anxiety and depression through AMP-activated protein kinase (AMPK) activation and brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex, while improving heart hypertrophy through inactivation of inhibitor of kappaB α (IκBα) in the heart. The results indicate that STH_KP17001 improves menopause-induced anxiety, depression and heart hypertrophy, implying its protective role for the management of menopausal symptoms.

Differential expression of acetylcholinesterase 1 in response to various stress factors in honey bee workers.

The honey bee acetylcholinesterase 1 (AmAChE1) has been suggested to be related to stress response as judged from its elevated expression level under brood rearing-suppressed conditions. To further investigate the involvement of AmAChE1 expression in the stress response and its physiological functions, we analyzed altered expression profiles of AmAChE1 induced by diverse stress factors. In addition, transcription profiles of several heat shock protein (Hsp) genes (hsps) and the vitellogenin (Vg) gene (vg) known as general stress markers were investigated as positive references. Among the tested stress conditions, AmAChE1 expression was induced under the brood rearing-suppressed, crowding and heat shock conditions. The hsps, particularly hsp70 and hsp90, responded to seven of nine stress conditions tested, confirming that hsp expression profiles can serve as a general stress marker. Taken together, AmAChE1 expression is not suitable for using as a stress marker due to its limited response. Nevertheless, AmAChE1 expression appears to be connected, at least in part, to heat shock response and other pathways. Considering that AmAChE1 likely regulates the ACh titer particularly in non-neuronal tissues, thereby modulating the signal cascades mediated by mAChR, the AmAChE1 expression profile under different conditions likely provides important information on its physiological roles in honey bees.