Effect of Isoscopoletin on Cytokine Expression in HaCaT Keratinocytes and RBL-2H3 Basophils: Preliminary Study.

Isoscopoletin is a compound derived from various plants traditionally used for the treatment of skin diseases. However, there have been no reported therapeutic effects of isoscopoletin on atopic dermatitis (AD). AD is a chronic inflammatory skin disease, and commonly used treatments have side effects; thus, there is a need to identify potential natural candidate substances. In this study, we aimed to investigate whether isoscopoletin regulates the inflammatory mediators associated with AD in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin treated RBL-2H3 cells. We determined the influence of isoscopoletin on cell viability through an MTT assay and investigated the production of inflammatory mediators using ELISA and RT-qPCR. Moreover, we analyzed the transcription factors that regulate inflammatory mediators using Western blots and ICC. The results showed that isoscopoletin did not affect cell viability below 40 µM in either HaCaT or RBL-2H3 cells. Isoscopoletin suppressed the production of TARC/CCL17, MDC/CCL22, MCP-1/CCL2, IL-8/CXCL8, and IL-1ß in TNF-α/IFN-γ-treated HaCaT cells and IL-4 in PMA/ionomycin-treated RBL-2H3 cells. Furthermore, in TNF-α/IFN-γ-treated HaCaT cells, the phosphorylation of signaling pathways, including MAPK, NF-κB, STAT, and AKT/PKB, increased but was decreased by isoscopoletin. In PMA/ionomycin-treated RBL-2H3 cells, the activation of signaling pathways including PKC, MAPK, and AP-1 increased but was decreased by isoscopoletin. In summary, isoscopoletin reduced the production of inflammatory mediators by regulating upstream transcription factors in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin-treated RBL-2H3 cells. Therefore, we suggest that isoscopoletin has the potential for a therapeutic effect, particularly in skin inflammatory diseases such as AD, by targeting keratinocytes and basophils.

Aberrant function of the salience network related to maltreatment experiences during thought-action fusion.

Childhood maltreatment (CM) causes early deviations in cognitive and affective processes, leading to future adaptation failures and psychopathology. Specifically, CM has been linked to cognitive distortions, and recent studies have focused on the impact of CM on the higher level of metacognitive beliefs. However, only a few studies have revealed the neural mechanisms underlying the association between altered metacognition and CM. Therefore, this functional magnetic resonance imaging (fMRI) study investigated the neural correlates of thought-action fusion (TAF) tendency and CM experiences. Overall, 40 young and healthy adults (21 men) participated in this study and underwent fMRI during the TAF task as well as psychological evaluation for CM, TAF tendency, anxiety, and depressive symptoms. During the TAF task, they were asked to read negative (Neg) or neutral (Neu) statements about neutral or close people (CP). Notably, significant activations were found in regions such as the bilateral anterior insula, dorsal anterior cingulate cortex (dACC), caudate, thalamus, medial prefrontal cortex, precuneus, and right amygdala in the NegCp > NeuCP contrast. Furthermore, anterior insula and dACC activities were significantly correlated with total scores of CM experiences and TAF. Exaggerated TAF tendency in persons with CM experiences was associated with increased response of the anterior insula and dACC, which are two core hubs of the salience network. Our results therefore seem to suggest insights for a better understanding of the neural mechanisms underlying metacognitive beliefs related to CM experiences.

Coherent spore dispersion via drop-leaf interaction.

The dispersion of plant pathogens, such as rust spores, is responsible for more than 20% of global crop yield loss annually. However, the release mechanism of pathogens from flexible plant surfaces into the canopy is not well understood. In this study, we investigated the interplay between leaf elasticity and rainfall, revealing how a flexible leaf structure can generate a lateral flow stream, with embedded coherent structures that enhance transport. We first modeled the linear coupling between drop momentum, leaf vibration, and the stream flux from leaf surfaces. With Lagrangian diagnostics, we further mapped out the nested coherent structures around the fluttering profile, providing a dynamical description for local spore delivery. We hope the mechanistic details extracted here can facilitate the construction of physically informed analytical models for local crop disease management.

Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study.

BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

Aromadendrin inhibits PMA-induced cytokine formation/NF-κB activation in A549 cells and ovalbumin-induced bronchial inflammation in mice.

Hyperproduction of immune cell-derived inflammatory molecules and recruitment of immune cells promote the development of allergic asthma (AA). Aromadendrin (ARO) has various biological properties including anti-inflammatory effects. In this study, we evaluated the ameliorative effects of ARO on the development of AA in vitro and in vivo. Phorbol 12-myristate 13-acetate (PMA, 100 nM) was used to induce inflammation in A549 airway epithelial cells. The cohesion of A549 and eosinophil EOL-1 cells was studied. Ovalbumin (30 or 60 µg)/Alum (3 mg) mixture was adapted for AA induction in mice. ARO (5 or 10 mg/kg, p. o.) was administered to mice to investigate its ameliorative effect on AA development. Enzyme-linked immunosorbent assay, western blotting, and hematoxylin and eosin/periodic acid Schiff staining were performed to study the ameliorative effect of ARO on bronchial inflammation. In PMA-stimulated A549 cells, the upregulation of cytokines (interleukin [IL]-1ß/IL-6/tumor necrosis factor alpha [TNF-α]/monocyte chemoattractant protein [MCP]-1]) and nuclear factor kappa B (NF-κB) activation was effectively reduced by ARO pretreatment. ARO suppressed the adhesion of A549 cells and eosinophils. In ovalbumin-induced AA mice, the levels of cells, such as eosinophils, Th2 cytokines, MCP-1 in bronchoalveolar lavage fluid, IgE in serum, and inducible nitric oxide synthase/cyclooxygenase-2 expression in the lung tissue were upregulated, which were all suppressed by ARO. In addition, the increase in cell inflow and mucus formation in the lungs of AA mice was reversed by ARO as per histological analysis. ARO also modulated NF-κB activation in the lungs of AA mice. Overall, the anti-inflammatory properties of ARO in vitro/in vivo studies of AA were notable. Thus, ARO has a modulatory effect on bronchial inflammation and may be a potential adjuvant for AA treatment.

Return to Sports Activity After Reverse Total Shoulder Arthroplasty.

Background: There are little published data on return to sports (RTS) after reverse total shoulder arthroplasty (RTSA). Purpose: To (1) determine the rate and timing of RTS after RTSA in an Asian population, (2) analyze predictive factors for RTS, and (3) determine the relationship between RTS after RTSA and clinical/radiological outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: A retrospective review was performed on consecutive patients with diagnosis of irreparable rotator cuff tear (RCT), cuff tear arthropathy (CTA), or degenerative osteoarthritis who underwent RTSA between May 2017 and May 2020. Included were patients who played sports preoperatively in ≤3 years and had ≥2-year follow-up. Patients were divided into 2 groups based on responses to a telephone survey about RTS after RTSA: those who returned to sports (group A) and those who did not (group B). Patient characteristics, pre- and postoperative clinical features and functional scores, and radiologic outcomes (acromial fracture, scapular notching, heterotopic ossification, and loosening of humeral and glenoid component) were compared between the groups. Results: Of 59 eligible patients, 44 patients (28 in group A, 16 in group B) were included. The RTS rate after RTSA was 63.6%, and the mean RTS time was 9.1 months (range, 3-36 months). There was a significant group difference in body mass index (BMI) (group A, 24.3 ± 2.1; group B, 27.1 ± 4.4; P = .01) and preoperative diagnosis (CTA/irreparable RCT/degenerative osteoarthritis diagnoses: group A, 13/12/3; group B, 3/6/7; P = .03). Patients in group A showed significantly higher forward flexion (P = .03) and higher Simple Shoulder Test score (P = .02) than group B at final clinical follow-up. No significant difference in radiological outcomes was found between the groups. Conclusion: Patients with a low BMI and those diagnosed with CTA or irreparable RCT were found to have better RTS rates after undergoing RTSA, and forward flexion and Simple Shoulder Test scores at final follow-up were significantly higher in the RTS group, with no significant differences in complications.

Heightened but Inefficient Thought-Action Fusion in Obsessive-Compulsive Disorder: New Insight From a Multiple Trial Version of the Classic Thought-Action Fusion Experiment.

OBJECTIVE: Thought-action fusion (TAF), which is a tendency to make the relationship between one's thoughts and external consequences, is a dysfunctional belief linked to obsessive-compulsive disorder (OCD). While the TAF is commonly evaluated using the Thought-Action Fusion Scale (TAFS), it cannot fully reflect the actual experience of experimentally evoked TAF. In the present study, we applied a multiple-trial version of the classic TAF experiment and evaluate two variables, reaction time (RT) and emotional intensity (EI). METHODS: Ninety-three patients with OCD and 45 healthy controls (HCs) were recruited. The participants were asked to read the name of a close or neutral person embedded in different positive (PS) or negative (NS) TAF statements. During the experiments, RT and EI were gathered. RESULTS: The OCD patients presented with longer RT and lower EI in the NS condition than HCs. In each group, the HCs showed a significant relationship between RT in the NS condition and TAFS scores, whereas the patients did not, although they had higher TAFS scores than the HCs. In contrast, the patients showed a trend toward a correlation between RT in the NS condition and guilt. CONCLUSION: These findings may indicate our multiple-trial version of the classical TAF showed reliable results of the two new variables, especially RT, in the task and allow to newly identify paradoxical patterns in which the TAFS scores are high but actual performance is impaired, that is, the inefficient activation of TAF in OCD.

Quercetin Attenuates the Production of Pro-Inflammatory Cytokines in H292 Human Lung Epithelial Cells Infected with Pseudomonas aeruginosa by Modulating ExoS Production.

The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of an experiment on inhibitors with regard to ExoS secretion, we developed a sandwich-type enzyme-linked immunosorbent assay (ELISA) system. Quercetin was selected because it has a prominent ExoS inhibition effect and also is known to have anti-inflammatory and antioxidant effects on mammalian cells. In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10 and 20 µM of quercetin. Also, popB, popD, pscF, and pcrV which are composed of the T3SS needle, are reduced by quercetin at the mRNA level. We also confirmed the inhibitory effect of quercetin on cytokines (IL-6, IL-1ß, and IL-18) in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR) and ELISA. Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the inflammatory disease caused by P. aeruginosa infection.

Relationship between Chronic Rhinosinusitis and the Incidence of Head and Neck Cancer: A National Population-Based Study.

We analyzed the relationship between chronic rhinosinusitis (CRS) and the incidence of head and neck cancers (HNCs) in a Korean adult population. This retrospective cohort study included data from the Korean National Health Insurance Service database. Adjustments were made to minimize risk variables for sex, age, diabetes, hypertension, dyslipidemia, and rhinitis between the two groups. The primary endpoint was newly diagnosed HNC between January 2009 and December 2018. Among 1,337,120 subjects in the Korean National Health Insurance Service database, data from 324,774 diagnosed with CRS (CRS group) and 649,548 control subjects (control group) were selected. Patients with CRS exhibited a statistically significant greater risk for nasal cavity/paranasal sinus cancer, hypopharynx/larynx cancer, and thyroid cancer compared with the control group. In the CRS group, the adjusted hazard ratios for nasal cavity/paranasal sinus cancer were 1.809 (95% confidence interval (CI) 1.085-3.016), 1.343 (95% CI 1.031-1.748) for hypopharynx and larynx cancer, and 1.116 (95% CI 1.063-1.173) for thyroid cancer. CRS was associated with a higher incidence of HNCs. Therefore, physicians should carefully consider the possibility of HNC progression and implement therapeutic strategies to minimize the impact of these diseases.

Connectome-based predictive models using resting-state fMRI for studying brain aging.

Changes in the brain with age can provide useful information regarding an individual's chronological age. studies have suggested that functional connectomes identified via resting-state functional magnetic resonance imaging (fMRI) could be a powerful feature for predicting an individual's age. We applied connectome-based predictive modeling (CPM) to investigate individual chronological age predictions via resting-state fMRI using open-source datasets. The significant feature for age prediction was confirmed in 168 subjects from the Southwest University Adult Lifespan Dataset. The higher contributing nodes for age production included a positive connection from the left inferior parietal sulcus and a negative connection from the right middle temporal sulcus. On the network scale, the subcortical-cerebellum network was the dominant network for age prediction. The generalizability of CPM, which was constructed using the identified features, was verified by applying this model to independent datasets that were randomly selected from the Autism Brain Imaging Data Exchange I and the Open Access Series of Imaging Studies 3. CPM via resting-state fMRI is a potential robust predictor for determining an individual's chronological age from changes in the brain.

Alterations of Power Spectral Density in Salience Network during Thought-action Fusion Induction Paradigm in Obsessive-compulsive Disorder.

Objective: Recent studies highlighted the triple-network model which illustrated the interactions among three large-scale networks including salience network (SN). The functional magnetic resonance imaging used in this study was designed to investigate the characteristics of three large-scale networks associated with the thought-action fusion (TAF) in patients with obsessive-compulsive disorder (OCD) using power spectral density (PSD) analysis. Methods: This study included 32 OCD patients and 38 age-matched healthy controls (HC). The TAF task was modified from the experiment of Rassin. PSD from time courses in large-scale networks of each subject was measured to compare between the groups for both TAF and resting state. Results: In SN, OCD reported lower power in the low-frequency domain of SN compared to HC using the two-sample t test during the TAF task (t = -2.395, p = 0.019) but not in the resting state. The PSD in the low-frequency domain of the SN had a significant negative correlation with state score in the guilty inventory (r = -0.361, p = 0.042) in OCD patients. Conclusion: This study suggests that OCD patients showed reduced SN power which can be prominent in a certain situation, such as TAF. In addition, the PSD alterations in SN cause difficulty in processing ambiguous emotional cues in social situations, and the difficulty can be connected with a negative feeling (e.g., guilt).

Dirac-source diode with sub-unity ideality factor.

An increase in power consumption necessitates a low-power circuit technology to extend Moore's law. Low-power transistors, such as tunnel field-effect transistors (TFETs), negative-capacitance field-effect transistors (NC-FETs), and Dirac-source field-effect transistors (DS-FETs), have been realised to break the thermionic limit of the subthreshold swing (SS). However, a low-power rectifier, able to overcome the thermionic limit of an ideality factor (η) of 1 at room temperature, has not been proposed yet. In this study, we have realised a DS diode based on graphene/MoS2/graphite van der Waals heterostructures, which exhibits a steep-slope characteristic curve, by exploiting the linear density of states (DOSs) of graphene. For the developed DS diode, we obtained η < 1 for more than four decades of drain current (ηave_4dec < 1) with a minimum value of 0.8, and a rectifying ratio exceeding 108. The realisation of a DS diode represents an additional step towards the development of low-power electronic circuits.

Purpurin suppresses atopic dermatitis via TNF-α/IFN-γ-induced inflammation in HaCaT cells.

OBJECTIVE: We investigated whether purpurin inhibits various pathways of inflammation leading to atopic dermatitis. INTRODUCTION: 1,2,4-Trihydroxyanthraquinone, commonly called purpurin, is an anthraquinone that is a naturally occurring red/yellow dye. Purpurin is a highly antioxidative anthraquinone and previous studies have reported antibacterial, anti-tumor, and anti-oxidation activities in cells and animals. However, the skin inflammatory inhibition activity mechanism study of purpurin has not been elucidated in vitro. METHODS: In this study, we investigated the anti-inflammatory activity of purpurin in HaCaT (human keratinocyte) cell lines stimulated with a mixture of tumor necrosis factor-alpha (TNF-α)/Interferon-gamma (IFN-γ). The inhibitory effect of Purpurin on cytokines (IL-6, IL-8, and IL-1ß) and chemokine (TARC, MDC, and RANTES) was confirmed by ELISA and RT-qPCR. We investigated each signaling pathway and the action of inhibitors through western blots. RESULTS: The expression levels of cytokines and chemokines were dose-dependently suppressed by purpurin treatment in TNF-α/IFN-γ-induced HaCaT cells from ELISA and real-time PCR. Purpurin also inhibited protein kinase B (AKT), mitogen-activated protein kinase (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) activation in TNF-α/IFN-γ-stimulated HaCaT cells. Additionally, there was a synergistic effect when purpurin and inhibitor were applied together, and inflammation was dramatically reduced. CONCLUSION: Therefore, these results demonstrate that purpurin exhibits anti-inflammatory and anti-atopic dermatitis activity in HaCaT cells.

Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea.

OBJECTIVE: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. METHODS: OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). RESULTS: 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. CONCLUSIONS: The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Time-saving synthetic magnetic resonance imaging protocols for pediatric neuroimaging: impact of echo train length and bandwidth on image quality.

BACKGROUND: Synthetic MRI is a time-efficient imaging technique that provides both quantitative MRI and contrast-weighted images simultaneously. However, a rather long single scan time can be challenging for children. OBJECTIVE: To evaluate the clinical feasibility of time-saving synthetic MRI protocols adjusted for echo train length and receiver bandwidth in pediatric neuroimaging based on image quality assessment and quantitative data analysis. MATERIALS AND METHODS: In total, we included 33 children ages 1.6-17.4 years who underwent synthetic MRI using three sets of echo train length and receiver bandwidth combinations (echo train length [E]12-bandwidth [B in KHz]22, E16-B22 and E16-B83) at 3 T. The image quality and lesion conspicuity of synthetic contrast-weighted images were compared between the suggested protocol (E12-B22) and adjusted protocols (E16-B22 and E16-B83). We also compared tissue values (T1, T2, proton-density values) and brain volumetry. RESULTS: For the E16-B83 combination, image quality was sufficient except for 15.2% of T1-W and 3% of T2-W fluid-attenuated inversion recovery (FLAIR) images, with remarkable scan time reduction (up to 35%). The E16-B22 combination demonstrated a comparable image quality to E12-B22 (P>0.05) with a scan time reduction of up to 8%. There were no significant differences in lesion conspicuity among the three protocols (P>0.05). Tissue value measurements and brain tissue volumes obtained with the E12-B22 protocol and adjusted protocols showed excellent agreement and strong correlations except for gray matter volume and non-white matter/gray matter/cerebrospinal fluid volume in E12-B22 vs. E16-B83. CONCLUSION: The adjusted synthetic protocols produced image quality sufficient or comparable to that of the suggested protocol while maintaining lesion conspicuity with reduced scan time. The quantitative values were generally consistent with the suggested MRI-protocol-derived values, which supports the clinical application of adjusted protocols in pediatric neuroimaging.

Polyethylenimine-Coated Ultrasmall Holmium Oxide Nanoparticles: Synthesis, Characterization, Cytotoxicities, and Water Proton Spin Relaxivities.

Water proton spin relaxivities, colloidal stability, and biocompatibility of nanoparticle magnetic resonance imaging (MRI) contrast agents depend on surface-coating ligands. In this study, hydrophilic and biocompatible polyethylenimines (PEIs) of different sizes (Mn = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho2O3) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho2O3 nanoparticles, with an average particle diameter of 2.05 and 1.90 nm, respectively, demonstrated low cellular cytotoxicities, good colloidal stability, and appreciable transverse water proton spin relaxivities (r2) of 13.1 and 9.9 s-1mM-1, respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r1) (i.e., 0.1 s-1mM-1) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R1) and transverse (R2) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T2 MRI contrast agents in vitro.

Enhanced Tumor Imaging Using Glucosamine-Conjugated Polyacrylic Acid-Coated Ultrasmall Gadolinium Oxide Nanoparticles in Magnetic Resonance Imaging.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (davg = 1.76 nm). Higher positive (brighter or T1) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T1 MRI contrast agents in tumor imaging via GlcN effects.

Methyl p­hydroxycinnamate exerts anti­inflammatory effects in mouse models of lipopolysaccharide­induced ARDS.

Methyl p­hydroxycinnamate (MH), an esterified derivative of p­Coumaric acid exerts anti­inflammatory effects on lipopolysaccharide (LPS)­stimulated RAW264.7 macrophages. Based on these effects, the present study investigated the protective role of MH in a mouse model of LPS­induced acute respiratory distress syndrome (ARDS). The results demonstrated that administration of LPS (5 mg/kg intranasally) markedly increased the neutrophil/macrophage numbers and levels of inflammatory molecules (TNF­α, IL­6, IL­1ß and reactive oxygen species) in the bronchoalveolar lavage fluid (BALF) of mice. On histological examination, the presence of inflammatory cells was observed in the lungs of mice administered LPS. LPS also notably upregulated the secretion of monocyte chemoattractant protein­1 and protein content in BALF as well as expression of inducible nitric oxide synthase in the lungs of mice; it also caused activation of p38 mitogen­activated protein kinase (MAPK) and NF­κB signaling. However, MH treatment significantly suppressed LPS­induced upregulation of inflammatory cell recruitment, inflammatory molecule levels and p38MAPK/NF­κB activation, and also led to upregulation of heme oxygenase­1 (HO­1) expression in the lungs of mice. In addition, the ability of MH to induce HO­1 expression was confirmed in RAW264.7 macrophages. Taken together, the findings of the present study indicated that MH may exert protective effects against airway inflammation in ARDS mice by inhibiting inflammatory cell recruitment and the production of inflammatory molecules.

Impact of fractional amplitude of low-frequency fluctuations in motor- and sensory-related brain networks on spinal cord injury severity.

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p < .05). Higher fALFF values were observed in the putamen and thalamus, and were negatively associated with motor and sensory function (p < .05). In conclusion, alterations in the neural activity of the motor- and sensory-related networks of the brain were observed in complete-SCI and incomplete-SCI patients. Moreover, plastic changes in these brain regions were associated with motor and sensory function.

QTL mapping for Fusarium wilt resistance based on the whole-genome resequencing and their association with functional genes in Raphanus sativus.

KEY MESSAGE: Two major QTL associated with resistance to Fusarium wilt (FW) were identified using whole-genome resequencing. Sequence variations and gene expression level differences suggest that TIR-NBS and LRR-RLK are candidate genes associated with FW-resistance. Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. raphani is an important disease in radish, leading to severe decrease in yield and quality. YR4 as a novel genetic source to resistant to FW was confirmed through screening with five pathogen isolates. We have generated F2 and F2:3 populations segregated with FW resistance using YR4 and YR18 inbred lines. The disease symptom was evaluated in F2:3 population (n = 180) in three independent studies over two years. We identified 4 QTL including the two major QTL (FoRsR7.159A and FoRsR9.359A). FoRsR7.159A and FoRsR9.359A were detected in three replicated experiments. FoRsR7.159A was delimited to the 2.18-Mb physical interval on chromosome R07, with a high LOD value (5.17-12.84) and explained phenotypic variation (9.34%-27.97%). The FoRsR9.359A represented relatively low LOD value (3.38-4.52) and explained phenotypic variation (6.24%-8.82%). On the basis of the re-sequencing data for the parental lines, we identified five putative resistance-related genes and 13 unknown genes with sequence variations at the gene and protein levels. A semi-quantitative RT-PCR analysis revealed that Rs382940 (TIR-NBS) and Rs382200 (RLK) were expressed only in 'YR4' from 0 to 6 days after the inoculation. Moreover, Rs382950 (TIR-NBS-LRR) was more highly expressed in 'YR4' from 3 to 6 days after the inoculation. These three genes might be important for FW-resistance in radish. We identified several markers based on these potential candidate genes. The marker set should be useful for breeding system to introduce the FW resistance loci from 'YR4' to improve tolerance to FW.